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Carlo Adolfo PORRO

Professore Ordinario presso: Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze sede ex-Sc. Biomediche


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Pubblicazioni

2021 - Different semantic and affective meaning of the words associated to physical and social pain in cancer patients on early palliative/supportive care and in healthy, pain-free individuals [Articolo su rivista]
Borelli, Eleonora; Bigi, Sarah; Potenza, Leonardo; Artioli, Fabrizio; Eliardo, Sonia; Mucciarini, Claudia; Cagossi, Katia; Razzini, Giorgia; Pasqualini, Antonella; Lui, Fausta; Ferlazzo, Fabio; Cruciani, Massimiliano; Bruera, Eduardo; Efficace, Fabio; Luppi, Mario; Cacciari, Cristina; Porro, Carlo Adolfo; Bandieri, Elena
abstract


2020 - Inhibitory Plasticity: From Molecules to Computation and Beyond [Articolo su rivista]
Gandolfi, Daniela; Bigiani, Albertino; Porro, Carlo Adolfo; Mapelli, Jonathan
abstract

Synaptic plasticity is the cellular and molecular counterpart of learning and memory and, since its first discovery, the analysis of the mechanisms underlying long-term changes of synaptic strength has been almost exclusively focused on excitatory connections. Conversely, inhibition was considered as a fixed controller of circuit excitability. Only recently, inhibitory networks were shown to be finely regulated by a wide number of mechanisms residing in their synaptic connections. Here, we review recent findings on the forms of inhibitory plasticity (IP) that have been discovered and characterized in different brain areas. In particular, we focus our attention on the molecular pathways involved in the induction and expression mechanisms leading to changes in synaptic efficacy, and we discuss, from the computational perspective, how IP can contribute to the emergence of functional properties of brain circuits.


2020 - Scattering Compensation for Deep Brain Microscopy: The Long Road to Get Proper Images [Articolo su rivista]
Pozzi, Paolo; Gandolfi, Daniela; Porro, Carlo Adolfo; Bigiani, Albertino; Mapelli, Jonathan
abstract

Multiphoton microscopy is the most widespread method for preclinical brain imaging when sub-micrometer resolution is required. Nonetheless, even in the case of optimal experimental conditions, only a few hundred micrometers under the brain surface can be imaged by multiphoton microscopy. The main limitation preventing the acquisition of images from deep brain structures is the random light scattering which, until recently, was considered an unsurmountable obstacle. When in 2007 a breakthrough work by Vellekoop and Mosk [1] proved it is indeed possible to compensate for random scattering by using high resolution phase modulators, the neuro-photonics community started chasing the dream of a multiphoton microscopy capable of reaching arbitrary depths within the brain. Unfortunately, more than 10 years later, despite a massive improvement of technologies for scattering compensation in terms of speed, performances and reliability, clear images from deep layers of biological tissues are still lacking. In this work, we review recent technological and methodological advances in the field of multiphoton microscopy analyzing the big issue of scattering compensation. We will highlight the limits hampering image acquisition, and we will try to analyze the road scientists must tackle to target one of the most challenging issue in the field of biomedical imaging.


2020 - Voxel sensitivity to kinematic and object-related features during action observation [Poster]
Simonelli, Francesca; Handjaras, Giacomo; Benuzzi, Francesca; Bernardi, Giulio; Leo, Andrea; Duzzi, Davide; Cecchetti, Luca; Nichelli, Paolo F.; Porro, Carlo A.; Pietrini, Pietro; Lui, Fausta; Ricciardi, Emiliano
abstract


2019 - Influence of anxiety and alexithymia on brain activations associated with the perception of others’ pain in autism [Articolo su rivista]
Lassalle, Amandine; Zürcher, Nicole R.; Porro, Carlo A.; Benuzzi, Francesca; Hippolyte, Loyse; Lemonnier, Eric; Åsberg Johnels, Jakob; Hadjikhani, Nouchine
abstract

The circumstances under which empathy is altered in ASD remain unclear, as previous studies did not systematically find differences in brain activation between ASD and controls in empathy-eliciting paradigms, and did not always monitor whether differences were primarily due to ASD “per se”, or to conditions overlapping with ASD, such as alexithymia and anxiety. Here, we collected fMRI data from 47 participants (22 ASD) viewing pictures depicting hands and feet of unknown others in painful, disgusting, or neutral situations. We computed brain activity for painful and disgusting stimuli (vs. neutral) in whole brain and in regions of interest among the brain areas typically activated during the perception of nociceptive stimuli. Group differences in brain activation disappeared when either alexithymia or anxiety – both elevated in the ASD group – were controlled for. Regression analyses indicated that the influence of symptoms was mainly shared between autistic symptomatology, alexithymia and anxiety or driven by unique contributions from alexithymia or anxiety. Our results suggest that affective empathy may be affected in ASD, but that this association is complex. The respective contribution of alexithymia and anxiety to decreased affective empathy of people with ASD may be due to the association of those psychiatric conditions with reduced motor resonance/Theory of Mind.


2019 - Words hurt: common and distinct neural substrates between physical and semantic pain [Poster]
Borelli, Eleonora; Lui, Fausta; Benuzzi, Francesca; Cacciari, Cristina; Porro, Carlo Adolfo
abstract


2019 - “When you’re smiling”: how facial expressions affect visual recognition of emotions [Poster]
BENUZZI, Francesca; BALLOTTA, DANIELA; PORRO, Carlo Adolfo; Nichelli, Paolo F.; LUI, Fausta
abstract

Introduction: Facial expressions can elicit simulation in onlookers, and can thus trigger the subjective experience of the same emotion. Moreover, facial muscles activity occurs automatically during the perception of an emotional facial expression (Dimberg and Thunberg, 1998) and preventing it may interfere with the accuracy of emotion recognition (Ponari et al. 2012). However, whether posing a facial expression can shift the perception of ambiguous expressions, and the possible neural basis of this phenomenon, have not been studied. In the present fMRI study we evaluated the effect of posing a facial expression on the recognition of ambiguous emotional faces. Methods: Twenty-six healthy female subjects (mean age 24 + 5,15 years) took part in the experiment. An fMRI event-related paradigm was used. The volunteers were asked to pose a facial expression (happy -H; disgusted –D; neutral -N) according to an emoticon shown on the screen, then to watch a real face expressing an emotion, finally to indicate whether the emotion perceived was happiness (h) or disgust (d). As stimuli, six different ambiguous emotional faces were used; they were a blend of happy and disgusted faces, built from pictures from the Ekman series (Ekman and Friesen, 1976). Three neutral faces (Ekman and Friesen, 1976) were used as controls. The Interpersonal Reactivity Index (IRI, Albiero et al. 2006) questionnaire for empathy was also administered. Functional data were acquired using a Philips Achieva system at 3T and a gradient-echo echo-planar sequence from 30 axial contiguous slices (TR=2000 ms; 326 volumes x 4 sessions; in-plane matrix= 64x64; voxel size: 3x3x4). fMRI analysis was performed using SPM12 (Wellcome Department of Imaging Neuroscience, London, UK). A double statistical threshold (single-voxel statistics and spatial extent) was used to achieve a combined (i.e., corrected for multiple comparisons) significance level of α < 0.05 (3dClustSim AFNI routine). Results: Behavioural results: Posing a disgusted face increased the percentages of d responses (X2=675,2; p< 0.001; Fig. 1a); whereas posing a happy face increased the h responses (X2=119,3; p< 0.001; Fig. 1a) Functional results: Posing happiness and perceiving disgust with respect to posing happiness and perceiving happiness (Hd vs Hh) activated a widespread functional network comprising several left regions (frontal operculum, insula, SMA, medial frontal gyrus, ACC, and basal ganglia, angular gyrus) as well as the right inferior frontal cortex (Figure 1b top). These areas are known to be involved in the a-modal processing of emotions. Posing a neutral face and perceiving happiness with respect to posing a neutral face and perceiving disgust (Nh vs Nd) activated the right posterior insula (Figure 1b bottom). Finally, in several contrasts we found some clusters of increased activity correlating with scores of some subscales of the IRI questionnaire: in particular, high scores in Empathic Concern correlated with the activity of the precuneus in the Ff vs Fd contrast; Fantasy scores correlated with the activity of the right anterior insula within the Df vs Ff contrast and with posterior cingulate and precuneus in the Dd vs Ff contrast. Conclusions: Perceiving a positive, happy face activated the posterior insula, an area consistently activated by pleasurable touch (Morrison, 2016). Behaviourally, posing an emotion shifts the visual perception of ambiguous expressions towards that same emotion. This effect is modulated by the neural system comprising medial and lateral regions of the prefrontal cortex. We can speculate that a cognitive top-down process from the prefrontal cortex could prevent the sensory-motor simulation elicited by the facial expression in being effective on the recognition of others' facial emotions. References Albiero, P. et al. (2006), Contributo all’adattamento italiano dell’Interpersonal Reactivity Inde


2018 - Assessing denoising strategies to increase signal to noise ratio in spinal cord and in brain cortical and subcortical regions [Articolo su rivista]
Maugeri, L.; Moraschi, M.; Summers, P.; Favilla, S.; Mascali, D.; Cedola, A.; Porro, C. A.; Giove, F.; Fratini, M.
abstract

Functional Magnetic Resonance Imaging (fMRI) based on Blood Oxygenation Level Dependent (BOLD) contrast has become one of the most powerful tools in neuroscience research. On the other hand, fMRI approaches have seen limited use in the study of spinal cord and subcortical brain regions (such as the brainstem and portions of the diencephalon). Indeed obtaining good BOLD signal in these areas still represents a technical and scientific challenge, due to poor control of physiological noise and to a limited overall quality of the functional series. A solution can be found in the combination of optimized experimental procedures at acquisition stage, and well-adapted artifact mitigation procedures in the data processing. In this framework, we studied two different data processing strategies to reduce physiological noise in cortical and subcortical brain regions and in the spinal cord, based on the aCompCor and RETROICOR denoising tools respectively. The study, performed in healthy subjects, was carried out using an ad hoc isometric motor task. We observed an increased signal to noise ratio in the denoised functional time series in the spinal cord and in the subcortical brain region.


2018 - Effect of visual stimuli of pain on empathy brain network in people with and without Autism Spectrum Disorder [Articolo su rivista]
Lassalle, Amandine; Zürcher, Nicole R; Hippolyte, Loyse; Billstedt, Eva; Porro, Carlo A; Benuzzi, Francesca; Solomon, Patricia; Prkachin, Kenneth M; Lemonnier, Eric; Gillberg, Christopher; Åsberg Johnels, Jakob; Hadjikhani, Nouchine
abstract

The extent to which affective empathy is impaired in Autism Spectrum Disorder (ASD) remains unclear, as some—but not all—previous neuroimaging studies investigating empathy for pain in ASD have shown similar activation levels to those of neurotypicals individuals. These inconsistent results could be due to the use of different empathy-eliciting stimuli. While some studies used pictures of faces exhibiting a painful expression, others used pictures of limbs in painful situations. In this study, we used fMRI to compare activation in areas associated with empathy processing (empathy network) for these two types of stimuli in 31 participants (16 with ASD, 15 controls). We found a group difference in the inferior frontal gyrus (IFG) and the thalamus when participants viewed stimuli of limbs in painful situations, but not when they viewed face stimuli with a painful expression. Both groups of participants activated their empathy network more when viewing pictures of limbs in painful situations than when viewing pictures of faces with a painful expression; this increased activation for limbs versus faces was significantly enhanced in controls relative to ASD participants, especially in the secondary somatosensory cortex (SII). Our findings suggest that empathy defect of people with ASD is contingent upon the type of stimuli used, and may be related to the level of Mirror Neuron System involvement, as brain regions showing group differences (IFG, SII) underlie embodiment. We discuss the potential clinical implications of our findings in terms of developing interventions boosting the empathetic abilities of people with ASD.


2018 - Modulation of neural circuits underlying temporal production by facial expressions of pain [Articolo su rivista]
Ballotta, Daniela; Lui, Fausta; Porro, Carlo Adolfo; Nichelli, Paolo Frigio; Benuzzi, Francesca
abstract

According to the Scalar Expectancy Theory, humans are equipped with a biological internal clock, possibly modulated by attention and arousal. Both emotions and pain are arousing and can absorb attentional resources, thus causing distortions of temporal perception. The aims of the present single-event fMRI study were to investigate: a) whether observation of facial expressions of pain interferes with time production; and b) the neural network subserving this kind of temporal distortions. Thirty healthy volunteers took part in the study. Subjects were asked to perform a temporal production task and a concurrent gender discrimination task, while viewing faces of unknown people with either pain-related or neutral expressions. Behavioural data showed temporal underestimation (i.e., longer produced intervals) during implicit pain expression processing; this was accompanied by increased activity of right middle temporal gyrus, a region known to be active during the perception of emotional and painful faces. Psycho-Physiological Interaction analyses showed that: 1) the activity of middle temporal gyrus was positively related to that of areas previously reported to play a role in timing: left primary motor cortex, middle cingulate cortex, supplementary motor area, right anterior insula, inferior frontal gyrus, bilateral cerebellum and basal ganglia; 2) the functional connectivity of supplementary motor area with several frontal regions, anterior cingulate cortex and right angular gyrus was correlated to the produced interval during painful expression processing. Our data support the hypothesis that observing emotional expressions distorts subjective time perception through the interaction of the neural network subserving processing of facial expressions with the brain network involved in timing. Within this frame, middle temporal gyrus appears to be the key region of the interplay between the two neural systems.


2018 - Pain mirrors: Neural correlates of observing self or others' facial expressions of pain [Articolo su rivista]
Benuzzi, Francesca; Lui, Fausta; Ardizzi, Martina; Ambrosecchia, Marianna; Ballotta, Daniela; Righi, Sara; Pagnoni, Giuseppe; Gallese, Vittorio; Porro, Carlo Adolfo
abstract

Facial expressions of pain are able to elicit empathy and adaptive behavioral responses in the observer. An influential theory posits that empathy relies on an affective mirror mechanism, according to which emotion recognition relies upon the internal simulation of motor and interoceptive states triggered by emotional stimuli. We tested this hypothesis comparing representations of self or others' expressions of pain in nineteen young healthy female volunteers by means of functional magnetic resonance imaging (fMRI). We hypothesized that one's own facial expressions are more likely to elicit the internal simulation of emotions, being more strictly related to self. Video-clips of the facial expressions of each volunteer receiving either painful or non-painful mechanical stimulations to their right hand dorsum were recorded and used as stimuli in a 2 × 2 (Self/Other; Pain/No-Pain) within-subject design. During each trial, a 2 s video clip was presented, displaying either the subject's own neutral or painful facial expressions (Self No-Pain, SNP; Self Pain, SP), or the expressions of other unfamiliar volunteers (Others' No-Pain, ONP; Others' Pain, OP), displaying a comparable emotional intensity. Participants were asked to indicate whether each video displayed a pain expression. fMRI signals were higher while viewing Pain than No-Pain stimuli in a large bilateral array of cortical areas including middle and superior temporal, supramarginal, superior mesial and inferior frontal (IFG) gyri, anterior insula (AI), anterior cingulate (ACC), and anterior mid-cingulate (aMCC) cortex, as well as right fusiform gyrus. Bilateral activations were also detected in thalamus and basal ganglia. The Self vs. Other contrast showed signal changes in ACC and aMCC, IFG, AI, and parietal cortex. A significant interaction between Self and Pain [(SP vs. SNP) > (OP vs. ONP)] was found in a pre-defined region of aMCC known to be also active during noxious stimulation. These findings demonstrate that the observation of one's own and others' facial expressions share a largely common neural network, but self-related stimuli induce generally higher activations. In line with our hypothesis, selectively greater activity for self pain-related stimuli was found in aMCC, a medial-wall region critical for pain perception and recognition.


2018 - Placebo Effects on the Neurologic Pain Signature: A Meta-analysis of Individual Participant Functional Magnetic Resonance Imaging Data [Articolo su rivista]
Zunhammer, Matthias; Bingel, Ulrike; Wager, Tor D; Porro, Carlo Adolfo; Lui, Fausta.
abstract

Importance: Placebo effects reduce pain and contribute to clinical analgesia, but after decades of research, it remains unclear whether placebo treatments mainly affect nociceptive processes or other processes associated with pain evaluation. Objective: We conducted a systematic, participant-level meta-analysis to test the effect of placebo treatments on pain-associated functional neuroimaging responses in the neurologic pain signature (NPS), a multivariate brain pattern tracking nociceptive pain. Data Sources: Medline (PubMed) was searched from inception to May 2015; the search was augmented with results from previous meta-analyses and expert recommendations. Study Selection: Eligible studies were original investigations that were published in English in peer-reviewed journals and that involved functional neuroimaging of the human brain with evoked pain delivered under stimulus intensity-matched placebo and control conditions. The authors of all eligible studies were contacted and asked to provide single-participant data. Data Extraction and Synthesis: Data were collected between December 2015 and November 2017 following the Preferred Reporting Items for Systematic Review and Meta-Analyses of individual participant data guidelines. Results were summarized across participants and studies in a random-effects model. Main Outcomes and Measures: The main, a priori outcome was NPS response; pain reports were assessed as a secondary outcome. Results: We obtained data from 20 of 28 identified eligible studies, resulting in a total sample size of 603 healthy individuals. The NPS responses to painful stimulation compared with baseline conditions were positive in 575 participants (95.4%), with a very large effect size (g = 2.30 [95% CI, 1.92 to 2.69]), confirming its sensitivity to nociceptive pain in this sample. Placebo treatments showed significant behavioral outcomes on pain ratings in 17 of 20 studies (85%) and in the combined sample (g = -0.66 [95% CI, -0.80 to -0.53]). However, placebo effects on the NPS response were significant in only 3 of 20 studies (15%) and were very small in the combined sample (g = -0.08 [95% CI, -0.15 to -0.01]). Similarly, analyses restricted to studies with low risk of bias (g = -0.07 [95% CI, -0.15 to 0.00]) indicated very small effects, and analyses of just placebo responders (g = -0.22 [95% CI, -0.34 to -0.11]) indicated small effects, as well. Conclusions and Relevance: Placebo treatments have moderate analgesic effects on pain reports. The very small effects on NPS, a validated measure that tracks levels of nociceptive pain, indicate that placebo treatments affect pain via brain mechanisms largely independent of effects on bottom-up nociceptive processing.


2018 - The psycholinguistic and affective structure of words conveying pain [Articolo su rivista]
Borelli, Eleonora; Crepaldi, Davide; Porro, Carlo Adolfo; Cacciari, Cristina
abstract

Despite the flourishing research on the relationships between affect and language, the characteristics of pain-related words, a specific type of negative words, , have never been systematically investigated from a psycholinguistic and emotional perspective, despite their psychological relevance. This study offers psycholinguistic, affective, and pain-related norms for words expressing physical and social pain. This may provide a useful tool for the selection of stimulus materials in future studies on negative emotions and/or pain. We explored the relationships between psycholinguistic, affective, and pain-related properties of 512 Italian words (nouns, adjectives and verbs) conveying physical and social pain by asking 1020 Italian students to provide ratings of Familiarity, Age of Acquisition, Imageability, Concreteness, Context Availability, Valence, Arousal, Pain-Relatedness, Intensity, and Unpleasantness. We also collected data concerning Length, Written Frequency (Subtlex-IT), N-Size, Orthographic Levenshtein Distance 20, Neighbor Mean Frequency, and Neighbor Maximum Frequency of each word. Interestingly, the words expressing social pain were rated as more negative, arousing, pain-related, and conveying more intense and unpleasant experiences than the words conveying physical pain.


2018 - What is the role of the placebo effect for pain relief in neurorehabilitation? Clinical implications from the Italian consensus conference on pain in neurorehabilitation [Articolo su rivista]
Castelnuovo, Gianluca; Giusti, Emanuele Maria; Manzoni, Gian Mauro; Saviola, Donatella; Gabrielli, Samantha; Lacerenza, Marco; Pietrabissa, Giada; Cattivelli, Roberto; Maria Spatola, Chiara Anna; Rossi, Alessandro; Varallo, Giorgia; Novelli, Margherita; Villa, Valentina; Luzzati, Francesca; Cottini, Andrea; Lai, Carlo; Volpato, Eleonora; Cavalera, Cesare; Pagnini, Francesco; Tesio, Valentina; Castelli, Lorys; Tavola, Mario; Torta, Riccardo; Arreghini, Marco; Zanini, Loredana; Brunani, Amelia; Seitanidis, Ionathan; Ventura, Giuseppe; Capodaglio, Paolo; D'Aniello, Guido Edoardo; Scarpina, Federica; Brioschi, Andrea; Bigoni, Matteo; Priano, Lorenzo; Mauro, Alessandro; Riva, Giuseppe; Di Lernia, Daniele; Repetto, Claudia; Regalia, Camillo; Molinari, Enrico; Notaro, Paolo; Paolucci, Stefano; Sandrini, Giorgio; Simpson, Susan; Wiederhold, Brenda Kay; Gaudio, Santino; Jackson, Jeffrey B.; Tamburin, Stefano; Benedetti, Fabrizio; Agostini, Michela; Alfonsi, Enrico; Aloisi, Anna Maria; Alvisi, Elena; Aprile, Irene; Armando, Michela; Avenali, Micol; Azicnuda, Eva; Barale, Francesco; Bartolo, Michelangelo; Bergamaschi, Roberto; Berlangieri, Mariangela; Berlincioni, Vanna; Berliocchi, Laura; Berra, Eliana; Berto, Giulia; Bonadiman, Silvia; Bonazza, Sara; Bressi, Federica; Brugnera, Annalisa; Brunelli, Stefano; Buzzi, Maria Gabriella; Cacciatori, Carlo; Calvo, Andrea; Cantarella, Cristina; Caraceni, Augusto; Carone, Roberto; Carraro, Elena; Casale, Roberto; Castellazzi, Paola; Castino, Adele; Cerbo, Rosanna; Chiò, Adriano; Ciotti, Cristina; Cisari, Carlo; Coraci, Daniele; Dalla Toffola, Elena; Defazio, Giovanni; De Icco, Roberto; Del Carro, Ubaldo; Dell'Isola, Andrea; De Tanti, Antonio; D'Ippolito, Mariagrazia; Fazzi, Elisa; Ferrari, Adriano; Ferrari, Sergio; Ferraro, Francesco; Formaglio, Fabio; Formisano, Rita; Franzoni, Simone; Gajofatto, Francesca; Gandolfi, Marialuisa; Gardella, Barbara; Geppetti, Pierangelo; Giammò, Alessandro; Gimigliano, Raffaele; Greco, Elena; Ieraci, Valentina; Invernizzi, Marco; Jacopetti, Marco; La Cesa, Silvia; Lobba, Davide; Magrinelli, Francesca; Mandrini, Silvia; Manera, Umberto; Marchettini, Paolo; Marchioni, Enrico; Mariotto, Sara; Martinuzzi, Andrea; Masciullo, Marella; Mezzarobba, Susanna; Miotti, Danilo; Modenese, Angela; Molinari, Marco; Monaco, Salvatore; Morone, Giovanni; Nappi, Rossella; Negrini, Stefano; Pace, Andrea; Padua, Luca; Pagliano, Emanuela; Palmerini, Valerio; Pazzaglia, Costanza; Pecchioli, Cristiano; Picelli, Alessandro; Porro, Carlo Adolfo; Porru, Daniele; Romano, Marcello; Roncari, Laura; Rosa, Riccardo; Saccavini, Marsilio; Sacerdote, Paola; Schenone, Angelo; Schweiger, Vittorio; Scivoletto, Giorgio; Smania, Nicola; Solaro, Claudio; Spallone, Vincenza; Springhetti, Isabella; Tassorelli, Cristina; Tinazzi, Michele; Togni, Rossella; Torre, Monica; Traballesi, Marco; Tramontano, Marco; Truini, Andrea; Tugnoli, Valeria; Turolla, Andrea; Vallies, Gabriella; Verzini, Elisabetta; Vottero, Mario; Zerbinati, Paolo
abstract

Background: It is increasingly acknowledged that the outcomes of medical treatments are influenced by the context of the clinical encounter through the mechanisms of the placebo effect. The phenomenon of placebo analgesia might be exploited to maximize the efficacy of neurorehabilitation treatments. Since its intensity varies across neurological disorders, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCP) summarized the studies on this field to provide guidance on its use. Methods: A review of the existing reviews and meta-analyses was performed to assess the magnitude of the placebo effect in disorders that may undergo neurorehabilitation treatment. The search was performed on Pubmed using placebo, pain, and the names of neurological disorders as keywords. Methodological quality was assessed using a pre-existing checklist. Data about the magnitude of the placebo effect were extracted from the included reviews and were commented in a narrative form. Results: 11 articles were included in this review. Placebo treatments showed weak effects in central neuropathic pain (pain reduction from 0.44 to 0.66 on a 0-10 scale) and moderate effects in postherpetic neuralgia (1.16), in diabetic peripheral neuropathy (1.45), and in pain associated to HIV (1.82). Moderate effects were also found on pain due to fibromyalgia and migraine; only weak short-term effects were found in complex regional pain syndrome. Confounding variables might have influenced these results. Clinical implications: These estimates should be interpreted with caution, but underscore that the placebo effect can be exploited in neurorehabilitation programs. It is not necessary to conceal its use from the patient. Knowledge of placebo mechanisms can be used to shape the doctor-patient relationship, to reduce the use of analgesic drugs and to train the patient to become an active agent of the therapy.


2017 - Voluntary modulation of mental effort investment: An fMRI study [Articolo su rivista]
Khachouf, Omar T.; Chen, Gang; Duzzi, Davide; Porro, Carlo A.; Pagnoni, Giuseppe
abstract

Mental effort is a common phenomenological construct deeply linked to volition and self-control. While it is often assumed that the amount of exertion invested in a task can be voluntarily regulated, the neural bases of such faculty and its behavioural effects are yet insufficiently understood. In this study, we investigated how the instructions to execute a demanding cognitive task either "with maximum exertion" or "as relaxed as possible" affected performance and brain activity. The maximum exertion condition, compared to relaxed execution, was associated with speeded motor responses without an accuracy trade-off, and an amplification of both task-related activations in dorsal frontoparietal and cerebellar regions, and task-related deactivations in default mode network (DMN) areas. Furthermore, the visual cue to engage maximum effort triggered an anticipatory widespread increase of activity in attentional, sensory and executive regions, with its peak in the brain stem reticular activating system. Across individuals, this surge of activity in the brain stem, but also in medial wall cortical regions projecting to the adrenal medulla, positively correlated with increases in heart rate, suggesting that the intention to willfully modulate invested effort involves mechanisms related to catecholaminergic transmission and a suppression of DMN activity in favor of externally-directed attentional processes.


2016 - Brain Activation Patterns Characterizing Different Phases of Motor Action: Execution, Choice and Ideation [Articolo su rivista]
Gardini, Simona; Venneri, Annalena; Mcgeown, William Jonathan; Toraci, Cristian; Nocetti, Luca; Porro, Carlo Adolfo; Caffarra, Paolo
abstract

Motor behaviour is controlled by a large set of interacting neural structures, subserving the different components involved in hierarchical motor processes. Few studies have investigated the neural substrate of higher-order motor ideation, i.e. the mental operation of conceiving a movement. The aim of this functional magnetic resonance imaging study was to segregate the neural structures involved in motor ideation from those involved in movement choice and execution. An index finger movement paradigm was adopted, including three different conditions: performing a pre-specified movement, choosing and executing a movement and ideating a movement of choice. The tasks involved either the right or left hand, in separate runs. Neuroimaging results were obtained by comparing the different experimental conditions and computing conjunction maps of the right and left hands for each contrast. Pre-specified movement execution was supported by bilateral fronto-parietal motor regions, the cerebellum and putamen. Choosing and executing finger movement involved mainly left fronto-temporal areas and the anterior cingulate. Motor ideation activated almost exclusively left hemisphere regions, including the inferior, middle and superior frontal regions, middle temporal and middle occipital gyri. These findings show that motor ideation is controlled by a cortical network mainly involved in abstract thinking, cognitive and motor control, semantic and visual imagery processes.


2016 - Diagnosing and assessing pain in neurorehabilitation: from translational research to the clinical setting. Evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation. [Articolo su rivista]
Porro, Carlo Adolfo; Sandri Ni, Giorgio; Truini, Andrea; Tugnoli, Valeria; Alfonsi, Enrico; Berliocchi, Laura; Cacciatori, Carlo; La Cesa, Silvia; Magri Nelli, Francesca; Sacerdote, Paola; Valeriani, Massimiliano; Tamburin, Stefano
abstract

Pain is very common in neurorehabilitation, where it may be a target for treatment and have a negative effect on rehabilitation procedures and outcomes. Promising preliminary preclinical data support certain therapeutic approaches to pain, but there is a strong need of adequate preclinical models, experimental settings, outcome measures, and biomarkers that are more relevant for pain within the neurorehabilitation field. Data on the diagnosis and assessment of nociceptive and neuropathic pain (NP) are very scanty in neurorehabilitation, but those from other contexts can be adapted and translated to this specific setting. The Italian Consensus Conference on Pain in Neurorehabilitation (ICCPN) has searched and evaluated existing evidence on animal models for the treatment of pain, definition and diagnostic criteria for nociceptive and NP, screening tools and questionnaires, along with diagnostic, clinical and instrumental techniques to distinguish nociceptive from NP and, more generally, to assess pain in the field of neurorehabilitation. The present ICCPN recommendations provide information on the relevance of current preclinical models, and may be helpful in ameliorating pain diagnosis and assessment, which are prerequisites for better application and tailoring of current pharmacological and non-pharmacological treatments. They may also be useful for future studies aimed at filling the gaps in the current knowledge of these topics.


2016 - Psychological considerations in the assessment and treatment of pain in neurorehabilitation and psychological factors predictive of therapeutic response: Evidence and recommendations from the Italian consensus conference on pain in neurorehabilitation [Articolo su rivista]
Castelnuovo, Gianluca; Giusti, Emanuele M.; Manzoni, Gian Mauro; Saviola, Donatella; Gatti, Arianna; Gabrielli, Samantha; Lacerenza, Marco; Pietrabissa, Giada; Cattivelli, Roberto; Spatola, Chiara A. M.; Corti, Stefania; Novelli, Margherita; Villa, Valentina; Cottini, Andrea; Lai, Carlo; Pagnini, Francesco; Castelli, Lorys; Tavola, Mario; Torta, Riccardo; Arreghini, Marco; Zanini, Loredana; Brunani, Amelia; Capodaglio, Paolo; D'Aniello, Guido E.; Scarpina, Federica; Brioschi, Andrea; Priano, Lorenzo; Mauro, Alessandro; Riva, Giuseppe; Repetto, Claudia; Regalia, Camillo; Molinari, Enrico; Notaro, Paolo; Paolucci, Stefano; Sandrini, Giorgio; Simpson, Susan G.; Wiederhold, Brenda; Tamburin, Stefano; Agostini, Michela; Alfonsi, Enrico; Aloisi, Anna Maria; Alvisi, Elena; Aprile, Irene; Armando, Michela; Avenali, Micol; Azicnuda, Eva; Barale, Francesco; Bartolo, Michelangelo; Bergamaschi, Roberto; Berlangieri, Mariangela; Berlincioni, Vanna; Berliocchi, Laura; Berra, Eliana; Berto, Giulia; Bonadiman, Silvia; Bonazza, Sara; Bressi, Federica; Brugnera, Annalisa; Brunelli, Stefano; Buzzi, Maria Gabriella; Cacciatori, Carlo; Calvo, Andrea; Cantarella, Cristina; Caraceni, Augusto; Carone, Roberto; Carraro, Elena; Casale, Roberto; Castellazzi, Paola; Castino, Adele; Cerbo, Rosanna; Chiò, Adriano; Ciotti, Cristina; Cisari, Carlo; Coraci, Daniele; Toffola, Elena Dalla; Defazio, Giovanni; De Icco, Roberto; Del Carro, Ubaldo; Dell'Isola, Andrea; De Tanti, Antonio; D'Ippolito, Mariagrazia; Fazzi, Elisa; Ferrari, Adriano; Ferrari, Sergio; Ferraro, Francesco; Formaglio, Fabio; Formisano, Rita; Franzoni, Simone; Gajofatto, Francesca; Gandolfi, Marialuisa; Gardella, Barbara; Geppetti, Pierangelo; Giammò, Alessandro; Gimigliano, Raffaele; Greco, Elena; Ieraci, Valentina; Invernizzi, Marco; Jacopetti, Marco; La Cesa, Silvia; Lobba, Davide; Magrinelli, Francesca; Mandrini, Silvia; Manera, Umberto; Marchettini, Paolo; Marchioni, Enrico; Mariotto, Sara; Martinuzzi, Andrea; Masciullo, Marella; Mezzarobba, Susanna; Miotti, Danilo; Modenese, Angela; Molinari, Marco; Monaco, Salvatore; Morone, Giovanni; Nappi, Rossella; Negrini, Stefano; Pace, Andrea; Padua, Luca; Pagliano, Emanuela; Palmerini, Valerio; Pazzaglia, Costanza; Pecchioli, Cristiano; Picelli, Alessandro; Porro, Carlo Adolfo; Porru, Daniele; Romano, Marcello; Roncari, Laura; Rosa, Riccardo; Saccavini, Marsilio; Sacerdote, Paola; Schenone, Angelo; Schweiger, Vittorio; Scivoletto, Giorgio; Smania, Nicola; Solaro, Claudio; Spallone, Vincenza; Springhetti, Isabella; Tassorelli, Cristina; Tinazzi, Michele; Togni, Rossella; Torre, Monica; Traballesi, Marco; Tramontano, Marco; Truini, Andrea; Tugnoli, Valeria; Turolla, Andrea; Vallies, Gabriella; Verzini, Elisabetta; Vottero, Mario; Zerbinati, Paolo
abstract

Background: In order to provide effective care to patients suffering from chronic pain secondary to neurological diseases, health professionals must appraise the role of the psychosocial factors in the genesis and maintenance of this condition whilst considering how emotions and cognitions influence the course of treatment. Furthermore, it is important not only to recognize the psychological reactions to pain that are common to the various conditions, but also to evaluate how these syndromes differ with regards to the psychological factors that may be involved. As an extensive evaluation of these factors is still lacking, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCPN) aimed to collate the evidence available across these topics. Objectives: To determine the psychological factors which are associated with or predictive of pain secondary to neurological conditions and to assess the influence of these aspects on the outcome of neurorehabilitation. Methods: Two reviews were performed. In the first, a PUBMED search of the studies assessing the association between psychological factors and pain or the predictive value of these aspects with respect to chronic pain was conducted. The included papers were then rated with regards to their methodological quality and recommendations were made accordingly. In the second study, the same methodology was used to collect the available evidence on the predictive role of psychological factors on the therapeutic response to pain treatments in the setting of neurorehabilitation. Results: The first literature search identified 1170 results and the final database included 189 articles. Factors such as depression, anxiety, pain catastrophizing, coping strategies, and cognitive functions were found to be associated with pain across the various conditions. However, there are differences between chronic musculoskeletal pain, migraine, neuropathy, and conditions associated with complex disability with regards to the psychological aspects that are involved. The second PUBMED search yielded 252 studies, which were all evaluated. Anxiety, depression, pain catastrophizing, coping strategies, and pain beliefs were found to be associated to different degrees with the outcomes of multidisciplinary programs, surgery, physical therapies, and psychological interventions. Finally, sense of presence was found to be related to the effectiveness of virtual reality as a distraction tool. Conclusions: Several psychological factors are associated with pain secondary to neurological conditions and should be acknowledged and addressed in order to effectively treat this condition. These factors also predict the therapeutic response to the neurorehabilitative interventions.


2016 - Psychological treatments and psychotherapies in the neurorehabilitation of pain: Evidences and recommendations from the italian consensus conference on pain in neurorehabilitation [Articolo su rivista]
Castelnuovo, Gianluca; Giusti, Emanuele M.; Manzoni, Gian Mauro; Saviola, Donatella; Gatti, Arianna; Gabrielli, Samantha; Lacerenza, Marco; Pietrabissa, Giada; Cattivelli, Roberto; Spatola, Chiara A. M.; Corti, Stefania; Novelli, Margherita; Villa, Valentina; Cottini, Andrea; Lai, Carlo; Pagnini, Francesco; Castelli, Lorys; Tavola, Mario; Torta, Riccardo; Arreghini, Marco; Zanini, Loredana; Brunani, Amelia; Capodaglio, Paolo; D'Aniello, Guido E.; Scarpina, Federica; Brioschi, Andrea; Priano, Lorenzo; Mauro, Alessandro; Riva, Giuseppe; Repetto, Claudia; Regalia, Camillo; Molinari, Enrico; Notaro, Paolo; Paolucci, Stefano; Sandrini, Giorgio; Simpson, Susan G.; Wiederhold, Brenda; Tamburin, Stefano; Agostini, Michela; Alfonsi, Enrico; Aloisi, Anna Maria; Alvisi, Elena; Aprile, Irene; Armando, Michela; Avenali, Micol; Azicnuda, Eva; Barale, Francesco; Bartolo, Michelangelo; Bergamaschi, Roberto; Berlangieri, Mariangela; Berlincioni, Vanna; Berliocchi, Laura; Berra, Eliana; Berto, Giulia; Bonadiman, Silvia; Bonazza, Sara; Bressi, Federica; Brugnera, Annalisa; Brunelli, Stefano; Buzzi, Maria Gabriella; Cacciatori, Carlo; Calvo, Andrea; Cantarella, Cristina; Caraceni, Augusto; Carone, Roberto; Carraro, Elena; Casale, Roberto; Castellazzi, Paola; Castino, Adele; Cerbo, Rosanna; Chi�, Adriano; Ciotti, Cristina; Cisari, Carlo; Coraci, Daniele; Toffola, Elena Dalla; Defazio, Giovanni; De Icco, Roberto; Del Carro, Ubaldo; Dell'Isola, Andrea; De Tanti, Antonio; D'Ippolito, Mariagrazia; Fazzi, Elisa; Ferrari, Adriano; Ferrari, Sergio; Ferraro, Francesco; Formaglio, Fabio; Formisano, Rita; Franzoni, Simone; Gajofatto, Francesca; Gandolfi, Marialuisa; Gardella, Barbara; Geppetti, Pierangelo; Giamm�, Alessandro; Gimigliano, Raffaele; Greco, Elena; Ieraci, Valentina; Invernizzi, Marco; Jacopetti, Marco; La Cesa, Silvia; Lobba, Davide; Magrinelli, Francesca; Mandrini, Silvia; Manera, Umberto; Marchettini, Paolo; Marchioni, Enrico; Mariotto, Sara; Martinuzzi, Andrea; Masciullo, Marella; Mezzarobba, Susanna; Miotti, Danilo; Modenese, Angela; Molinari, Marco; Monaco, Salvatore; Morone, Giovanni; Nappi, Rossella; Negrini, Stefano; Pace, Andrea; Padua, Luca; Pagliano, Emanuela; Palmerini, Valerio; Pazzaglia, Costanza; Pecchioli, Cristiano; Picelli, Alessandro; Porro, Carlo Adolfo; Porru, Daniele; Romano, Marcello; Roncari, Laura; Rosa, Riccardo; Saccavini, Marsilio; Sacerdote, Paola; Schenone, Angelo; Schweiger, Vittorio; Scivoletto, Giorgio; Smania, Nicola; Solaro, Claudio; Spallone, Vincenza; Springhetti, Isabella; Tassorelli, Cristina; Tinazzi, Michele; Togni, Rossella; Torre, Monica; Traballesi, Marco; Tramontano, Marco; Truini, Andrea; Tugnoli, Valeria; Turolla, Andrea; Vallies, Gabriella; Verzini, Elisabetta; Vottero, Mario; Zerbinati, Paolo
abstract

Background: It is increasingly recognized that treating pain is crucial for effective care within neurological rehabilitation in the setting of the neurological rehabilitation. The Italian Consensus Conference on Pain in Neurorehabilitation was constituted with the purpose identifying best practices for us in this context. Along with drug therapies and physical interventions, psychological treatments have been proven to be some of the most valuable tools that can be used within a multidisciplinary approach for fostering a reduction in pain intensity. However, there is a need to elucidate what forms of psychotherapy could be effectively matched with the specific pathologies that are typically addressed by neurorehabilitation teams. Objectives: To extensively assess the available evidence which supports the use of psychological therapies for pain reduction in neurological diseases. Methods: A systematic review of the studies evaluating the effect of psychotherapies on pain intensity in neurological disorders was performed through an electronic search using PUBMED, EMBASE, and the Cochrane Database of Systematic Reviews. Based on the level of evidence of the included studies, recommendations were outlined separately for the different conditions. Results: The literature search yielded 2352 results and the final database included 400 articles. The overall strength of the recommendations was medium/low. The different forms of psychological interventions, including Cognitive-Behavioral Therapy, cognitive or behavioral techniques, Mindfulness, hypnosis, Acceptance and Commitment Therapy (ACT), Brief Interpersonal Therapy, virtual reality interventions, various forms of biofeedback and mirror therapy were found to be effective for pain reduction in pathologies such as musculoskeletal pain, fibromyalgia, Complex Regional Pain Syndrome, Central Post-Stroke pain, Phantom Limb Pain, pain secondary to Spinal Cord Injury, multiple sclerosis and other debilitating syndromes, diabetic neuropathy, Medically Unexplained Symptoms, migraine and headache. Conclusions: Psychological interventions and psychotherapies are safe and effective treatments that can be used within an integrated approach for patients undergoing neurological rehabilitation for pain. The different interventions can be specifically selected depending on the disease being treated. A table of evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation is also provided in the final part of the paper.


2014 - Cognitive modulation of pain and predictive coding. Comment on "Facing the experience of pain: a neuropsychological perspective" by Fabbro and Crescentini [Articolo su rivista]
Pagnoni, Giuseppe; Porro, Carlo Adolfo
abstract

A commentary on the article “Facing the experience of pain: A neuropsychological perspective” by Fabbro and Crescentini, where the potential usefulness of adopting a predictive coding approach to understand pain perception is outlined.


2014 - Ranking brain areas encoding the perceived level of pain from fMRI data [Articolo su rivista]
S., Favilla; A., Huber; Pagnoni, Giuseppe; Lui, Fausta; P., Facchina; Cocchi, Marina; Baraldi, Patrizia; Porro, Carlo Adolfo
abstract

Pain perception is thought to emerge from the integrated activity of a distributed brain system, but the relative contribution of the different network nodes is still incompletely understood. In the present functional magnetic resonance imaging (fMRI) study,we aimed to identify themore relevant brain regions to explain the time profile of the perceived pain intensity in healthy volunteers, during noxious chemical stimulation (ascorbic acid injection) of the left hand. To this end, we performed multi-way partial least squares regression of fMRI data from twenty-two a-priori defined brain regions of interest (ROI) in each hemisphere, to build a model that could efficiently reproduce the psychophysical pain profiles in the same individuals; moreover, we applied a novel three-way extension of the variable importance in projection (VIP) method to summarize each ROI contribution to the model. Brain regions showing the highest VIP scores included the bilateral mid-cingulate, anterior and posterior insular, and parietal operculum cortices, the contralateral paracentral lobule, bilateral putamen and ipsilateral medial thalamus.Most of these regions, with the exception of medial thalamus,were also identified by a statistical analysis on mean ROI beta values estimated using the time course of the psychophysical rating as a regressor at the voxel level. Our results provide the first rank-ordering of brain regions involved in coding the perceived level of pain. These findings in amodel of acute prolonged pain confirm and extend previous data, suggesting that a bilateral array of cortical areas and subcortical structures is involved in pain perception


2014 - Spatial extent of pain influences gray matter volume in fibromyalgia patients. [Poster]
Huber, Alexa; Lui, Fausta; Duzzi, Davide; Pagnoni, Giuseppe; Santarcangelo, E. L.; Carli, G.; Porro, Carlo Adolfo
abstract

Aim of Investigation: Fibromyalgia (FS) is a syndrome characterised by chronic widespread pain, whose pathophysiology is still controversial. Previous studies assessing alterations in local gray matter volume (GMV) in FS have obtained somewhat inconsistent results, possibly due to differences in clinical features. Our aim was to assess GMV changes in FS compared to a control group, and their correlations with the severity of clinical aspects, including illness duration, pain intensity and quality, body pain area, number of positive tender points and depression. Methods: Thirty-four women with FS diagnosed by a rheumatologist and 38 healthy women (controls, C) without chronic pain matched for age (FS: range 18-55 ys, mean 44; C: 25-60 ys, mean 45.6), menopausal status, educational level, handedness and caffeine consumption, participated in the study. The control subjects had experienced no pain (N=9) or episodic/recurrent pain without (N=20) or with use of pain killers (N=9) over the past year. Depressive symptoms were assessed using the Center for Epidemiology Studies-Depression Scale (CES-D); the sensory (S), affective (A) and evaluative (E) quality of spontaneous pain were tested using the Italian adaptation of the McGill Pain Questionnaire (Questionario Italiano del Dolore - QUID). Spatial extent of pain was assessed using Margolis body pain area drawings. Pressure pain thresholds were measured by means of an algometer applied to the 18 defining tender points and to 10 additional points to obtain a detailed picture of spatial distribution of allodynia. A high-resolution structural T1-weighted brain scan (360 sagittal slices without gap; isotropic voxel size 0.5mm; FOV 240 x 240 x 180mm; TR 35ms; flip angle 50; TE 5.7ms) was acquired for each subject, using a 3T Philips Achieva MR scanner. GMV was assessed applying voxel-based morphometry Oasis, The Online Abstract Submission System http://www.abstractsonline.com/submit/SubmitPrin... 1 of 3 03/07/2014 01:46 PM International Association for the Study of Pain 1510 H Street NW, Suite 600 Washington, DC 20005-1020 USA Phone: +1-202-524-5300 (VBM) to modulated data in SPM8 using the VBM8 toolbox (voxel-wise critical p < 0.005; cluster size corrected for multiple comparisons using AlphaSim with 10,000 Monte Carlo simulations). Results: Patients showed no significant differences in GMV compared to the total control group. In the patient sample, GMV was negatively correlated with QUID-E score in BA 6 and with the spatial extent of spontaneous pain in the bilateral parahippocampal gyrus (pHG), and it was positively correlated with illness duration in the cerebellum. GMV was independent of pain intensity, tender point count, CES-D, QUID-S and QUID-A score. Reported pain extent ranged from 9-90% of body surface (mean/median: 48%). Patients with below-median pain extent had greater GMV than patients with above-median values in the bilateral pHG and cerebellum, left paracentral lobule (BA 6) and cingulate gyrus (BA 31). GMV values of the controls in these brain areas were intermediate between the two patient groups. Spatial extent of pain was positively correlated with tender point count and with QUID-S and was independent of all other clinical and nuisance variables included in the study. Conclusions: Some, but not all, previous VBM studies have reported reduced GMV in the pHG and in the cingulate cortex in FS (Wood, 2010). Our results point to a possible explanation for these inconsistent findings: depending on how widespread their pain, FS patients may show either reduced or increased GMV in the pHG and cingulate cortex, i.e. they are more different from each other than from the control group. Further research is needed to explore the possible causes of these inter-individual differences within the FS population. Reference: Wood PB. Variations in brain gray matter associated with chronic pain. Curr Rheumatol Rep 2010;12:462-469.


2014 - Structural and functional cerebral correlates of hypnotic suggestibility [Articolo su rivista]
Huber, Alexa; Lui, Fausta; Duzzi, Davide; Pagnoni, Giuseppe; Porro, Carlo Adolfo
abstract

Little is known about the neural bases of hypnotic suggestibility, a cognitive trait referring to the tendency to respond to hypnotic suggestions. In the present magnetic resonance imaging study, we performed regression analyses to assess hypnotic suggestibility-related differences in local gray matter volume, using voxel-based morphometry, and in waking resting state functional connectivity of 10 resting state networks, in 37 healthy women. Hypnotic suggestibility was positively correlated with gray matter volume in portions of the left superior and medial frontal gyri, roughly overlapping with the supplementary and pre-supplementary motor area, and negatively correlated with gray matter volume in the left superior temporal gyrus and insula. In the functional connectivity analysis, hypnotic suggestibility was positively correlated with functional connectivity between medial posterior areas, including bilateral posterior cingulate cortex and precuneus, and both the lateral visual network and the left fronto-parietal network; a positive correlation was also found with functional connectivity between the executive-control network and a right postcentral/parietal area. In contrast, hypnotic suggestibility was negatively correlated with functional connectivity between the right fronto-parietal network and the right lateral thalamus. These findings demonstrate for the first time a correlation between hypnotic suggestibility, the structural features of specific cortical regions, and the functional connectivity during the normal resting state of brain structures involved in imagery and self-monitoring activity.


2014 - The current state-of-the-art of spinal cord imaging: Applications [Articolo su rivista]
C., Wheeler Kingshott; P. W., Stroman; J. M., Schwab; M., Bacon; R., Bosma; J., Brooks; D., Cadotte; T., Carlstedt; O., Ciccarelli; J., Cohen Adad; A., Curt; N., Evangelou; M. G., Fehlings; M., Filippi; B., Kelley; S., Kollias; A., Mackay; Porro, Carlo Adolfo; S., Smith; S. M., Strittmatter; Summers, Paul Eugene; A. J., Thompson; I., Tracey
abstract

A first-ever spinal cord imaging meeting was sponsored by the International Spinal Research Trust and the Wings for Life Foundation with the aim of identifying the current state-of-the-art of spinal cord imaging, the current greatest challenges, and greatest needs for future development. This meeting was attended by a small group of invited experts spanning all aspects of spinal cord imaging from basic research to clinical practice. The greatest current challenges for spinal cord imaging were identified as arising from the imaging environment itself; difficult imaging environment created by the bone surrounding the spinal canal, physiological motion of the cord and adjacent tissues, and small crosssectional dimensions of the spinal cord, exacerbated by metallic implants often present in injured patients. Challenges were also identified as a result of a lack of "critical mass" of researchers taking on the development of spinal cord imaging, affecting both the rate of progress in the field, and the demand for equipment and software to manufacturers to produce the necessary tools. Here we define the current state-of-the-art of spinal cord imaging, discuss the underlying theory and challenges, and present the evidence for the current and potential power of these methods. In two review papers (part I and part II), we propose that the challenges can be overcome with advances in methods, improving availability and effectiveness of methods, and linking existing researchers to create the necessary scientific and clinical network to advance the rate of progress and impact of the research.


2014 - The current state-of-the-art of spinal cord imaging: Methods [Articolo su rivista]
P., Stroman; C., Wheeler Kingshott; M., Bacon; J. M., Schwab; R., Bosma; J., Brooks; D., Cadotte; T., Carlstedt; O., Ciccarelli; J., Cohen Adad; A., Curt; N., Evangelou; M. G., Fehlings; M., Filippi; B., Kelly; S., Kollias; A., Mackay; Porro, Carlo Adolfo; S., Smith; S. M., Strittmatter; Summers, Paul Eugene; I., Tracey
abstract

A first-ever spinal cord imaging meeting was sponsored by the International Spinal Research Trust and the Wings for Life Foundation with the aim of identifying the current state-of-the-art of spinal cord imaging, the current greatest challenges, and greatest needs for future development. This meeting was attended by a small group of invited experts spanning all aspects of spinal cord imaging from basic research to clinical practice. The greatest current challenges for spinal cord imaging were identified as arising from the imaging environment itself; difficult imaging environment created by the bone surrounding the spinal canal, physiological motion of the cord and adjacent tissues, and small cross-sectional dimensions of the spinal cord, exacerbated by metallic implants often present in injured patients. Challenges were also identified as a result of a lack of "critical mass" of researchers taking on the development of spinal cord imaging, affecting both the rate of progress in the field, and the demand for equipment and software to manufacturers to produce the necessary tools. Here we define the current state-of-the-art of spinal cord imaging, discuss the underlying theory and challenges, and present the evidence for the current and potential power of these methods. In two review papers (part I and part II), we propose that the challenges can be overcome with advances in methods, improving availability and effectiveness of methods, and linking existing researchers to create the necessary scientific and clinical network to advance the rate of progress and impact of the research.


2014 - Whole-Body Mapping of Spatial Acuity for Pain and Touch [Articolo su rivista]
Flavia, Mancini; Bauleo, Armando; Jonathan, Cole; Lui, Fausta; Porro, Carlo Adolfo; Patrick, Haggard; Gian Domenico, Iannetti
abstract

Objective: Tactile spatial acuity is routinely tested in neurology to assess the state of the dorsal column system. In contrast, spatial acuity for pain is not assessed, having never been systematically characterized. More than a century after the initial description of tactile acuity across the body, we provide the first systematic whole-body mapping of spatial acuity for pain. Methods: We evaluated the 2-point discrimination thresholds for both nociceptive-selective and tactile stimuli across several skin regions. Thresholds were estimated using pairs of simultaneous stimuli, and also using successive stimuli. Results and interpretation: These two approaches produced convergent results. The fingertip was the area of highest spatial acuity, for both pain and touch. On the glabrous skin of the hand, the gradient of spatial acuity for pain followed that observed for touch. On the hairy skin of the upper limb, spatial acuity for pain and touch followed opposite proximal–distal gradients, consistent with the known innervation density of this body territory. Finally, by testing spatial acuity for pain in a rare participant completely lacking Ab fibers, we demonstrate that spatial acuity for pain does not rely on a functioning system of tactile primary afferents. This study represents the first systematic characterization of spatial acuity for pain across multiple regions of the body surface.


2013 - Activation Likelihood Estimation meta-analysis of brain correlates of placebo analgesia in human experimental pain [Articolo su rivista]
M., Amanzio; F., Benedetti; Porro, Carlo Adolfo; S., Palermo; F., Cauda
abstract

Placebo analgesia (PA) is one of the most studied placebo effects. Brain imaging studies published over the last decade, using either positron emission tomography (PET) or functional magnetic resonance imaging (fMRI), suggest that multiple brain regions may play a pivotal role in this process.However, there continues to be much debate as to which areas consistently contribute to placebo analgesia-related networks. In the present study, we used activation likelihood estimation (ALE) meta-analysis, a state-of-the-art approach, to search for the cortical areas involved in PA in human experimental pain models. Nine fMRI studies and two PET studies investigating cerebral hemodynamic changes were included in the analysis. During expectation of analgesia, activated foci were found in the left anterior cingulate, right precentral, and lateral prefrontal cortex and in the left periaqueductal gray (PAG). During noxious stimulation, placebo-related activations were detected in the anterior cingulate and medial and lateral prefrontal cortices, in the left inferior parietal lobule and postcentral gyrus, anteriorinsula, thalamus, hypothalamus, PAG, and pons; deactivations were found in the left mid- and posterior cingulate cortex, superior temporal and precentral gyri, in the left anterior and right posterior insula, in the claustrum and putamen, and in the right thalamus and caudate body. Our results suggest on one hand that the modulatory cortical networks involved in PA largely overlap those involved in the regulation of emotional processes, on the other that brain nociceptive networks are downregulatedin parallel with behavioral analgesia.


2013 - An algorithm to estimate anatomical connectivity between brain regions using diffusion MRI [Articolo su rivista]
M., Campanella; E., Molinari; Baraldi, Patrizia; Nocetti, Luca; Porro, Carlo Adolfo; D. C., Alexander
abstract

The study of anatomical connectivity is essential for interpreting functional MRI data, and establishing how brain areas are linked together into networks to support higher order functions. Diffusion weighted MR images (DWI) and tractography provide a unique noninvasive tool to explore the connectional architecture of the brain. The identification of anatomical circuits associated with a specific function can be better accomplished by the joint application of diffusion and functional MRI. In this paper, we propose a simple algorithm to identify the set of pathways between two regions of interest. The method is based upon running deterministic tractography from all possible starting positions in the brain, and selecting trajectories that intersect both regions. We compare results from single fibre tractography using diffusion tensor imaging, and multifibre tractography using reduced encoding Persistent Angular Structure (PAS) MRI, on standard DWI datasets from healthy human volunteers. Our results show that, in comparison with single fibre tractography, the multifibre technique reveal additional putative routes of connection. We demonstrate highly consistent results of the proposed technique over a cohort of 16 healthy subjects.


2013 - Comparison of tissue occupancy functional contrasts for 3D turbo-spin-echo acquisition [Poster]
Summers, Paul Eugene; Bauleo, Armando; Cretti, F.; Lui, Fausta; Porro, Carlo Adolfo
abstract

Introduction: Functional vascular occupancy imaging has demonstrated task correlated MR signal changes using inversion recovery (IR) prepared images, where the inversion time (TI) has been chosen to selectively null blood (vascular space occupancy – VASO, (Lu et al., 2003)), grey matter (VASO by tissue suppression – VAST (Wu et al., 2008)), or CSF (VASO-FLAIR (Donahue et al., 2006)). Weakness of these approaches are that functional responses may not be due to volume changes in a single tissue compartment, and that the underlying imaging sequence may be sensitive to other mechanisms (e.g. BOLD) (Donahue et al., 2006). Our purpose was to compare the functional responses from different vascular space occupancy preparations of a short TE turbo-spin echo (TSE) sequence. Methods: Eight healthy subjects were scanned at 3T after providing informed consent. The task consisted of self-paced, left-hand finger tapping. Four variants of vascular occupancy fMRI were tested: VASO (TI = 646ms), VAST (TI = 578ms), VASO-FLAIR (TI = 781ms) and nonInVASO (no inversion pulse VASO), all based on a 3D TSE acquisition (TE/TR 8.4ms/2.4s, 4 shots, time per volume 9.6s, 1.5x1.5x1.5mm, 8 slices, FOV 222x60x12mm, 180° refocusing pulses, ant/post sat bands). Task blocks were 48s long, and each run consisted of 45 volumes, with the sequence order varied between subjects. These scans were centered on the focus of BOLD response in/adjacent to the right hand knob detected with an EPI acquisition (TE/TR 30ms/3s, 3x3x3mm, 42 slices) performed during execution of the same task (30 second blocks, 70 volumes). Whole-brain T2, 3D T1, and nonInVASO images were also obtained. GLM analysis (1.5mm FWHM smoothing, high pass filter cut-off 100s, default gamma-variate hrf, GRF-based voxel-wise corrected p<0.05) was per formed following motion correction and ICA denoising (4 components) using fsl (v 5.0.1). Due to slight rotations during acquisition, only 6 slices were retained for analysis. Results: Despite operator confirmation of task performance, one subject showed minimal BOLD and no significant vascular occupancy responses, and was therefore excluded from analysis. In the other subjects, VASO, VAST and VASO-FLAIR showed nearly identical patterns and locations of activity (Figure 1) and no significant differences in the grey matter (GM), white matter, CSF distribution of activated voxels. The nonInVASO scans showed smaller volumes of activity. GM was the predominant site of response for all scans. VAST yielded the highest % signal changes; VASO yielded the highest z-score followed closely by VASO-FLAIR; and these all had signal changes negatively correlated with the task. The nonInVASO responses correlated positively with the task and were the smallest % signal change and maximum z-scores roughly one-third lower than VASO. Significant oppositely-signed responses (i.e. positive of VASO, VAST and VASO-FLAIR, negative for nonInVASO) were not observed.Conclusions: Our results suggest that VASO, VAST and VASO-FLAIR are sensitive to volume changes in the same tissue compartment. VAST yielded the highest % signal changes due mainly to the smallest baseline signal but this did not result in greater sensitivity to activation as indicated by maximum z-scores. The negative VAST response however, suggests that the inversion was not fully optimized to grey matter but could reflect T2 blurring of white matter signal. VASO was the most sensitive to activation followed closely by VASO-FLAIR. Similarly located activations were seen with nonInVASO, but with smaller spatial extents and lower sensitivity. The implications and operative mechanism for the nonInVASO functional contrast remain to be established. Possible mechanisms include BOLD contrast (through T2 sensitivity or blurring by the long TSE echo train), vascular space occupancy changes coupled with inherent blood-tissue contrast, diff


2013 - Human Parietofrontal Networks Related to Action Observation Detected at Rest [Articolo su rivista]
E., Molinari; Baraldi, Patrizia; M., Campanella; Duzzi, Davide; L., Nocetti; Pagnoni, Giuseppe; Porro, Carlo Adolfo
abstract

Recent data show a broad correspondence between human resting state and task-related brain networks. We performed a functional magnetic resonance imaging (fMRI) study to compare, in the same subjects, the spatial independent component analysis (ICA) maps obtained at rest and during the observation of either reaching/grasping hand actions or matching static pictures. Two parietofrontal networks were identified by ICA from action observation task data. One network, specific to reaching/grasping observation, included portions of the anterior intraparietal cortex and of the dorsal and ventral lateral premotor cortices. A second network included more posterior portions of the parietal lobe, the dorsomedial frontal cortex, and more anterior and ventral parts,respectively, of the dorsal and ventral premotor cortices, extending toward Broca’s area; this network was more generally related to the observation of hand action and static pictures. A good spatial correspondence was found between the 2 observation-related ICA maps and 2 ICA maps identified from resting-state data. The anatomical connectivity among the identified clusters was tested in the same volunteers, using persistent angular structure--MRI and deterministic tractography. These findings extend available knowledge of human parietofrontal circuits and further support the hypothesis of a persistent coherence within functionally relevant networks during rest.


2013 - Hypnotic susceptibility explains differences in resting state functional connectivity [Poster]
Huber, Alexa; Lui, Fausta; Pagnoni, Giuseppe; Duzzi, Davide; Summers, Paul Eugene; Porro, Carlo Adolfo
abstract

Introduction: Hypnotic susceptibility (HS) is a measurable cognitive trait defined as the generalized tendency to respond to hypnotic suggestions [1]. Very little is known about the neural bases of HS [2]. Our aim was to assess HS-related differences in resting state func tional c onnec tivity. Methods: N=35 healthy women (3 ambidextrous, 4 left-handed; age range 19-56 yrs, mean 36.9 yrs) partic ipated in the study. HS was assessed with the Stanford Hypnotic Susc eptibility Sc ale – Form A (SHSS:A), mental absorption with the T ellegen Absorption Sc ale (T AS) and trait anxiety with the State-T rait Anxiety Inventory Form Y (ST AI-Y2). Subjec ts were not in any way pre-selec ted for SHSS sc ore. T o measure spontaneous BOLD signal fluc tuations at rest, two runs of EPI sc ans were ac quired while subjec ts lay in the sc anner relaxed with eyes c losed (for eac h run: 200 volumes; T R 2 s; isometric voxel size 3.6 mm; 35 axial slic es without gap; matrix 80 x 63 voxels; FOV 286 x 229 mm; ac quisition time 7 min), using a 3T Philips Ac hieva MR sc anner. A T 1-weighted brain image (isotropic voxel size 0.5 mm) was ac quired for inter-subjec t alignment. EPI data were analysed using AFNI. Preproc essing inc luded the removal of physiologic al, white matter and hardware related noise using RET ROICOR and ANAT ICOR proc edures, lowpass filtering to remove frequenc ies >0.1 Hz, and 6-mm FWHM spatial smoothing. Seed-based func tional c onnec tivity (FC) was quantified as the z-transformed Pearson c orrelation with the seed signal (average BOLD signal within a sphere of 6mm radius). Seeds were plac ed (a) within key regions of the Default Mode Network (DMN) taken from the literature; (b) in the two areas (anterior c ingulate c ortex – ACC; dorsolateral prefrontal c ortex – DLPFC) desc ribed in Hoeft et al. [2]; and (c ) in 15 seeds ad-hoc plac ed along the c ingulate c ortex in eac h hemisphere. HS-related differenc es in FC were assessed by using SHSS sc ore as a between-subjec ts linear regressor to explain FC z-sc ores. Furthermore, some of the c lusters whic h resulted signific antly c onnec ted with the above mentioned seeds, e.g. orbitofrontal c ortex (OFC), were, in turn, used as seeds (d). Results: SHSS sc ores ranged from 0-10 (mean 3.6). Eighteen subjec ts had low (SHSS<4), 14 medium (SHSS=4-7) and 3 high SHSS sc ores (SHSS>7). SHSS was independent of age, educ ational level, handedness, trait anxiety and mental absorption. SHSS was positively c orrelated with FC (a) of DMN seeds, i.e., the right medial PFC, left posterior c ingulate c ortex (PCC) and left posterior insula with c erebellar foc i, and (b) of Hoeft et al.'s [2] ACC seed with c erebellar regions, and of right DLPFC with left OFC. When foc using on the c ingulate c ortex (c ), SHSS was positively c orrelated with FC of ACC with mid-c ingulate c ortex (MCC), of various seeds in the ACC and MCC with c erebellar foc i, and of MCC with bilateral OFC. SHSS was also positively c orrelated with FC of the OFC foc i (d) with a wide network of regions, inc luding MCC, bilateral DLPFC (see Fig. 1), pre- and postcentral gyri, superior temporal gyri and insula as well as cerebellum and contralateral precuneus (Fig. 2). Conclusions:Among healthy women, individuals with higher HS show higher resting state FC between OFC, DLPFC, cingulate cortex and cerebellum. Further researc h is needed to c onfirm these relationships in men, and to assess their cognitive correlates.


2013 - Hypnotic susceptibility modulates brain activity related to experimental placebo analgesia [Articolo su rivista]
Huber, Alexa; Lui, Fausta; Porro, Carlo Adolfo
abstract

Identifying personality traits and neural signatures that predict placebo responsiveness is important, both on theoretical and practical grounds. In the present functional magnetic resonance imaging (fMRI) study, we performed multiple-regression interaction analysis to investigate whether hypnotic susceptibility (HS), a cognitive trait referring to the responsiveness to suggestions, explains interindividual differences in the neural mechanisms related to conditioned placebo analgesia in healthy volunteers. HS was not related to the overall strength of placebo analgesia. However, we found several HS-related differences in the patterns of fMRI activity and seed-based functional connectivity that accompanied placebo analgesia. Specifically, in subjects with higher HS, the placebo response was related to increased anticipatory activity in a right dorsolateral prefrontal cortex focus, and to reduced functional connectivity of that focus with brain regions related to emotional and evaluative pain processing (anterior mid-cingulate cortex/medial prefrontal cortex); an opposite pattern of fMRI activity and functional connectivity was found in subjects with lower HS. During pain perception, activity in the regions reflecting attention/arousal (bilateral anterior thalamus/left caudate) and self-related processing (left precuneus and bilateral posterior temporal foci) was negatively related to the strength of the analgesic placebo response in subjects with higher HS, but not in subjects with lower HS. These findings highlight HS influences on brain circuits related to the placebo analgesic effects. More generally, they demonstrate that different neural mechanisms can be involved in placebo responsiveness, depending on individual cognitive traits.


2013 - Multi-shot turbo spin-echo for 3D vascular space occupancy imaging [Articolo su rivista]
F. R., Cretti; Summers, Paul Eugene; Porro, Carlo Adolfo
abstract

Vascular space occupancy (VASO) is a magnetic resonance imaging technique sensitive to cerebral blood volume, and is a potential alternative to the blood oxygenation level dependent (BOLD) sensitive technique as a basis for functional mapping of the neurovascular response to a task. Many implementations of VASO have made use of echo-planar imaging strategies that allow rapid acquisition, but risk introducing potentially confounding BOLD effects. Recently, multi-slice and 3D VASO techniques have been implemented to increase the imaging volume beyond the single slice of early reports. These techniques usually rely, however, on advanced scanner software or hardware not yet available in many centers. In the present study, we have implemented a short-echo time, multi-shot 3D Turbo Spin-Echo (TSE) VASO sequence that provided 8-slice coverage on a routine clinical scanner. The proposed VASO sequence was tested in assessing the response of the human motor cortex during a block design finger tapping task in 10 30 healthy subjects. Significant VASO responses, inversely correlated with the task, were found at both individual and group level. The location and extent of VASO responses were in close correspondence to those observed using a conventional BOLD acquisition in the same subjects. Although the spatial coverage and temporal resolution achieved were limited, robust and consistent VASO responses were observed. The use of a susceptibility insensitive volumetric TSE VASO sequence may have advantages in locations where conventional BOLD and echo-planar based VASO imaging is compromised.


2013 - Short echo-time 3D-TSE with and without VASO preparation: functional MRI [Poster]
Summers, Paul Eugene; Bauleo, Armando; Cretti, Fabiola; Lui, Fausta; Porro, Carlo Adolfo
abstract

Purpose: Short echo time (shTE) turbo-spin echo (TSE) pulse sequences are considered very weakly sensitive to blood oxygenation level dependent (BOLD) signal changes, and have been proposed to avoid cancellation of functional responses in blood nulled vascular space occupancy (VASO) fMRI studies where task-related increases in blood volume lead to decreases in signal (1,2). A positive functional contrast in shTE TSE studies has, however, been reported by some authors and attributed to changes in extravascular water distribution termed SEEP (3). Our purpose was to determine whether functional contrast in shTE TSE-based VASO experiments might be contaminated by BOLD or SEEP effects. Methods: A 3D-TSE sequence without (shTE TSE; TE/TR/TDyn 8.5ms/2400ms/9.6s, FOV: 210x52x12mm, Matrix 160x40x8, Refocussing Angle 180deg, Turbo factor 80, echo spacing 8.5ms, 70 dynamics, centre-out sampling) and with blood-nulling (VASO; TI 600ms) was used to acquire image series from the hand sensorimotor area of the cerebral cortex during a block-design finger tapping task (block duration 48s, 9 blocks). The inversion time assumed suppression of longitudinal relaxation during the TSEecho train. For comparison purposes, a BOLD-sensitive gradient-echo EPI series was also obtained (TE/TR/TDyn 35ms/3000ms/3s, FOV: 230x230x120, Matrix 64x64x30, Excitation Flip Angle 90deg, 70 dynamics) with the same task. The finger tapping task was self-paced left-hand finger tapping, and controlled via auditory commands. fMRI time-series were motion-corrected, and an independent component analysis (MELODIC, fsl) used to identify 7 components for denoising prior to a glm (FEAT, fsl) with a single regressor convolved with the default hemodynamic response function. Spatial smoothing was limited to a 1.5mm FWHM. Voxels were considered to show a significant functional response using a p-value < 0.005 with cluster-wise correction for multiple comparisons. We present results from the first 2 subjects who participated in the study. Results: Functional responses were found using both variants of the shTE TSE sequence within the area of BOLD response seen with conventional EPI-based fMRI. The spatial correspondence of responses was striking (Figures 1a and 1b), but having an inverted response when blood-nulling is applied (Figure 1c; bars indicate task blocks). The sequences yielded similar maximum functional contrast to noise ratios of 4.0 and 4.6 (on % signal changes of 0.98% and 3.6%) without and with blood-nulling respectively. Discussion: The inverted functional response when blood-nulling is applied indicates the expected VASO changes. The robust functional contrast in shTE TSE without blood nulling may also be consistent with this effect, but our results are not sufficient to exclude contributions from SEEP, or BOLD that would run counter to the VASO contrast in blood-nulled measurements. The functional contrast to noise ratio in both cases are similar. Nonetheless, the small fractional signal change in the non-nulled case suggests that BOLD and SEEP and inflow effects make only minor contributions. The 3D TSE strategy used here is hampered by limited spatial coverage and low temporal efficiency relative to conventional EPI. Improvements are likely possible however, as we have not made use of parallel imaging techniques, nor pursued extremely long echo trains that may reduce scan time. References: 1. Stroman P, et al. Magnetic Resonance in Medicine 49:433–439 (2003). 2. Cretti F, et al. ESMRMB 2009 187. 3. Poser B, Norris D. Magn Reson Mater Phy (2007) 20:63–67.


2013 - Somatotopy of nociceptive responses in the human spinal cord [Articolo su rivista]
Summers, Paul Eugene; F., Giove; Porro, Carlo Adolfo
abstract

This Letter to the Editor of the journal Pain addresses the study by Nash and colleagues (Pain 2013;154:776-781), reporting fMRI somatotopic responses to noxious stimulations within the human spinal cord. Spinal cord fMRI, although a rapidly expanding field, is still hampered by significant technical shortcomings. This paper is welcome, in that it introduces significant technical novelty. However, more details are needed about the methods followed, in order to grasp the procedures and to assess their actual efficacy. Moreover, the spatial specificity of the responses is not fully supported by the results, both regarding the spinal cord site and side.


2013 - The spatial resolution of the nociceptive system. [Poster]
Bauleo, Armando; Mancini, F.; Lui, Fausta; Porro, Carlo Adolfo; Haggard, P.
abstract

Background and aims: A systematic study of the spatial resolution of the nociceptive system across different body districts is surprisingly lacking, especially considering the recent description of a fovea for pain at the fingertips (Mancini et al Curr Biol 2013). In this psychophysical study we assessed the spatial acuity of ten body regions, using the two-point discrimination (2PD) of Nd:YAP laser pulses that selectively activate Aδ cutaneous afferents. Methods: Using two Nd:YAP lasers we delivered either one or two simultaneous pulses (diameter: 1.3 mm) of identical energy on each of the following body sites: forehead, volar forearm, hand dorsum, hand palm, fingertip, shoulder, lower back, upper thigh, calf, and foot dorsum. The 2PD task consisted in judging whether one or two stimuli were delivered, using ascending and descending staircases of varying spatial distance between the two pulses. Single stimuli were included as catch trials. All stimuli elicited a clear pinprick sensation related to the activation of Aδ afferents. Results: We found a proximal-distal gradient of spatial acuity for nociceptive stimuli, with higher acuity for proximal stimuli, an observation in agreement with innervation density of skin nociceptors and perceptual threshold of Aδ stimuli. Two distal regions (fingertips and palm) represented an exception, and showed maximal spatial acuity (see also Mancini et al., 2013). Conclusions: This study provides the first systematic description of spatial acuity of the nociceptive system across the entire body in healthy participants.


2012 - Alterations in cortical gray matter volume, thickness and surface area in women with fibromyalgia syndrome. [Poster]
Lui, Fausta; Huber, Alexa; Duzzi, Davide; Summers, Paul Eugene; Porro, Carlo Adolfo
abstract

Aim of Investigation: Recent neuroimaging studies using voxel-based morphometry (VBM) demonstrated reductions in brain gray matter (GM) volume in Fibromyalgia (FS), a chronic pain syndrome thought to result from altered central pain processing. Little is known about the relative contribution of the two components of cortical GM volume – thickness and surface area – to these structural alterations. Our aim was to assess alterations in GM morphology (volume, thickness, area) in FS compared to a control group, and to correlate GM morphology with clinical variables of pain, namely duration, intensity (VAS), and tender point count, and with depression score (Center for Epidemiology Studies-Depression Scale). Methods: Twenty-three women with FS and 26 healthy pain-free women matched for age and educational level participated in the study. Pressure pain thresholds were measured with an algometer applied to the 18 defining tender points and to 10 additional points to obtain a total positive tender point count. A high-resolution structural T1-weighted brain scan (360 sagittal slices without gap; isotropic voxel size 0.5mm; FOV 240 x 240 x 180mm; TR 35ms; flip angle 50°; TE 5.7ms) was acquired for each subject, using a 3T Philips Achieva MR scanner. GM volume was assessed applying VBM to modulated data in SPM8 using an individualised DARTEL template for inter-subject alignment. Surface-based measures of cortical thickness and area were obtained using the Freesurfer 4.5.0 software. Both the VBM and Freesurfer data were spatially smoothed using an 8mm FWHM Gaussian kernel. The statistical analysis of the surface-based data was performed both on vertex-wise values and on values averaged within 64 anatomical Regions of Interest (ROIs). Nuisance influences of age, total intracranial volume (TIV), handedness and menopause were removed. Results: Compared to the control group, FS patients showed i) reduced GM volume in the left medial and superior frontal gyrus (BA 6; a trend that became significant after controlling for depression score), ii) reduced surface area in the left pericalcarine cortex, and iii) increased thickness in the left fusiform gyrus and in the right rostral middle frontal cortex. Pain intensity was negatively correlated with thickness in the bilateral paracentral lobule (BA 6); however, brain morphology was correlated neither with pain duration nor with positive tender point count. The only significant age-by-group interaction consisted in the fact that the age-related loss in GM thickness and area in the left lateral occipital cortex was less steep in patients compared to controls, because the patients had lower values already at a younger age. Conclusions: The present results provide further evidence for altered brain morphology in FS, including brain areas in which this had not been previously demonstrated, and show a relationship of specific structural changes with the severity of specific symptoms.


2012 - Psychological and brain structural correlates of responsiveness to analgesia suggestions in patients with fibromialgia syndrome. [Poster]
Huber, Alexa; Lui, Fausta; Duzzi, Davide; Summers, Paul Eugene; Carli, G.; Santarcangelo, E. L.; Porro, Carlo Adolfo
abstract

Aim of Investigation: In healthy people, the effectiveness of analgesia suggestions increases with the individual level of hypnotic susceptibility (HS), a measurable cognitive trait defined as the generalized tendency to respond to hypnotic suggestions. However, chronic pain patients may benefit from analgesia suggestions even when they are low susceptible to hypnosis. Very little is known about the potential brain structural correlates of the responsiveness to analgesia suggestions in chronic pain. Our aim was to assess possible a) psychological and b) gray matter (GM) morphology correlates of inter-individual differences in the patients' behavioural response to an imaginative analgesia suggestion, in women suffering from chronic pain due to fibromyalgia syndrome (FS), using MRI. Methods: Sixty-eight women with FS and 26 healthy women participated in a screening session to fill in questionnaires on depression (CES-D), anxiety (STAI-Y), mental absorption (TAS), imagery ability (BETTS) and (for the patients) on clinical symptoms and pain coping strategies (BPCI). HS was assessed with the Stanford Hypnotic Susceptibility Scale (SHSS:A). A 1.5-min imaginative analgesia suggestion was read once to each patient during normal waking (i.e., without a hypnotic induction) without any prior training. A high-resolution structural T1-weighted brain image (360 sagittal slices without gap; isotropic voxel size 0.5mm; FOV 240 x 240 x 180mm; TR 35ms; flip angle 50°; TE 5.7ms) was acquired for 23 of the patients and all 26 controls, using a 3T Philips Achieva MR scanner. GM volume was assessed applying VBM to modulated data in SPM8, using a tailored DARTEL template for inter-subject alignment. Surface-based measures of cortical thickness and surface area were obtained using the Freesurfer 4.5.0 software. Nuisance influences of age, total intracranial volume, handedness and educational level were removed in the analysis. Results: Patients and controls showed similar HS levels (mean±SD: all patients 4.7±3.0; scanned patients 4.0±3.0; controls: 2.9±2.7). Behavioural data showed that the majority (76%) of patients reported reduction of ongoing pain, either weak-moderate (1-30%; n=20) or strong (>30%; n=32), following the analgesia suggestion reading; a similar proportion was found in patients who underwent scanning. The amount of analgesia was positively correlated with HS (Pearson r=.48), mental absorption (r=.31) and mental avoidance coping (r=.25), and negatively with state anxiety (r=-.41), support-seeking coping (r=-.27) and opioid use; it was independent of all other clinical variables, including pain intensity and duration. While controlling for HS, the amount of analgesia was negatively trend correlated with GM volume in the anterior midbrain/hypothalamus (this cluster missed significance by 11 voxels). In the control sample (but not in the patient sample), higher HS was associated with reduced GM volume in the posterior insula bilaterally. Across the whole scanned group (subjects and patients), HS was associated with reduced cortical thickness in the left medial orbitofrontal cortex. Conclusions: This is the first study to demonstrate a relationship of brain GM anatomical features with HS and the effectiveness of cognitive modulation of clinical pain induced by analgesia suggestions in the waking state. A larger cohort of patients including a higher number of highly hypnotisable individuals is needed to investigate these relationships more thoroughly.


2012 - “To accept or to reject? It depends on who proposes it”. An fMRI study on the Ultimatum Game. [Poster]
Lui, Fausta; Bauleo, Armando; Pesciarelli, Francesca; Duzzi, Davide; Lotto, L; Cacciari, Cristina; Rumiati, R; Porro, Carlo Adolfo
abstract

Introduction: In the Ultimatum Game (UG), a proposer decides in which proportion to split a fixed amount of money (e.g., 10 €) with a responder. Both get their share only if the responder accepts the offer. Despite what would be predicted by expected utility models, typically some offers (most frequently the lowest ones) are rejected, being considered unfair [3]. Brain imaging and TMS studies [2, 4-5, 7] have investigated the brain circuits involved in different aspects of the UG. In the present study, we tested the hypothesis that the identity of the proposers, specifically, their economic status, i) affects acceptance rates; ii) modulates brain activity of the responders in the UG protocol. Methods: Twenty-one healthy right-handed volunteers (all females; mean age 22.8 ± 3.1) took part in this study. During the fMRI scan, each volunteer was asked to play 54 trials (split in 3 runs) of UG. All human proposers were presented as females and could be either A) old-age retirees living on a small pension, or B) well-to-do businesswomen/professionals. Their identity was introduced by a brief description including first name, age and social status (e.g., Maria, 84, with minimum pension). Offers by a computer were the control condition. The amount of money to share was € 10 in each trial, with three types of offers. that we defined as: Unfair (1 or 2 €), Fair (4 or 5 €), Mid-value (3 €). On each trial, participants saw the description of the proposer (8 s), then they were presented with an offer (8 s). Both proposer and offer type were presented in random order. Finally, participants accepted or rejected the offer by pressing a button. Functional imaging was performed on a 3T Philips Achieva scanner. Thirty axial slices were acquired (TR=2000 ms; FOV=240x240 mm; in-plane matrix=80x80; voxel size=3.0x3.0x4.0 mm). Data analysis was carried out using a General Linear Model (GLM) as implemented in SPM5; significance level was set at α < 0.05 corrected for multiple comparisons, as assessed by AlphaSim (http://afni.nimh.nih.gov/afni/doc/manual/AlphaSim). Results: Behavioral data: Acceptance rates were significantly higher for proposer A than for the other proposers, for both Unfair and Mid-value offers (p<0.001), but not for Fair offers. fMRI data: Unfair offers, compared to Fair offers, elicited signal increases in anterior mid-cingulate cortex (aMCC) and right prefrontal cortex (PFC); smaller (subthreshold) clusters were present also in left PFC and, bilaterally, in anterior insula (Fig.1). The contrast Fair vs. Unfair offers did not elicit suprathreshold activity. When we compared proposer B vs A in the trials in which offers were subsequently accepted, we found a significant signal increase in the right insula (Fig. 2). When offers were subsequently rejected, a comparison of proposer A vs B revealed an active cluster in precuneus/posterior cingulate cortex (PCC) (Fig. 3). The opposite contrasts did not reveal any significant cluster. Conclusions: We show here that the economic status of the proposers selectively affects i) acceptance rates, and ii) brain activity; namely, in case of accepted offers, proposer B caused a selective activation in posterior insula. This area is known to have complex functions, among which a role in pain perception and modulation [6] and in attention to negative emotions [8]. This activation might suggest that accepting the offers from proposer B bears some similarity with an unpleasant experience. In case of subsequently rejected offers, proposer A caused a selective activation in precuneus/PCC. This is a very complex region, part of the so-called "default mode network", which is active during the conscious resting state, and inhibited during non-self related tasks [1]. We may hypothesize that rejecting offers from a proposer with whom people could easily empathise, implies a greater focus on first-person perspective, an


2011 - A regularization algorithm for decoding perceptual temporal profiles from fMRI data [Articolo su rivista]
Prato, Marco; Favilla, Stefania; Zanni, Luca; Porro, Carlo Adolfo; Baraldi, Patrizia
abstract

In several biomedical fields, researchers are faced with regression problems that can be stated as Statistical Learning problems. One example is given by decoding brain states from functional magnetic resonance imaging (fMRI) data. Recently, it has been shown that the general Statistical Learning problem can be restated as a linear inverse problem. Hence, new algorithms were proposed to solve this inverse problem in the context of Reproducing Kernel Hilbert Spaces. In this paper, we detail one iterative learning algorithm belonging to this class, called ν-method, and test its effectiveness in a between-subjects regression framework. Specifically, our goal was to predict the perceived pain intensity based on fMRI signals, during an experimental model of acute prolonged noxious stimulation. We found that, using a linear kernel, the psychophysical time profile was well reconstructed, while pain intensity was in some cases significantly over/underestimated. No substantial differences in terms of accuracy were found between the proposed approach and one of the state-of-the-art learning methods, the Support Vector Machines. Nonetheless, adopting the ν-method yielded a significant reduction in computational time, an advantage that became more evident when a relevant feature selection procedure was implemented. The ν-method can be easily extended and included in typical approaches for binary or multiple classification problems, and therefore it seems well-suited to build effective brain activity estimators.


2011 - Functional connectivity of frontal components of the human mirror system: a PPI study. [Poster]
Lui, Fausta; Duzzi, Davide; Ghio, MARTA VIRGINIA; Bauleo, Armando; Porro, Carlo Adolfo
abstract

Introduction Great attention has been paid to the human mirror system (MNS) in recent years (Caspers et al., 2010; Rizzolatti & Sinigaglia 2010); among the peculiarities of the human MNS, the fact that it responds to action observation even in the absence of a target object (Lui et al., 2008). However, so far few studies have dealt with the functional connectivity of the components of this system (Skippers et al., 2007; Hattori et al., 2009; Xu et al., 2009; Emmorey et al., 2010). With the present work, we aimed at revealing patterns of connectivity of ventral premotor cortex/dorsal BA44 (PMv) and Broca area (BA44/45) during the observation of different types of gestures: Symbolic (SY) and Grasping (GR). Methods Twenty healthy right-handed volunteers (8 males, 12 females; mean age 26.6) took part in this study. An event-related paradigm was adopted. A continuous video was presented, showing some common objects (glasses, cup, scissors, etc.) on a table. At intervals, an actor, of whom only the trunk and arms were visible, performed different kinds of hand movements: a) SY: non-object related symbolic actions (OK, hello, etc.); b) GR: grasping of an object. Three runs were carried out for each subject. Six movements for each class were shown in each run, alternated in pseudorandom order; each single movement was presented only once to each volunteer. Functional imaging was performed on a 3T Philips Intera scanner. Twenty-four axial slices were acquired (in-plane matrix: 64x64; TR: 2515 ms; voxel size: 3.75x3.75x4 mm, with a 0.6 mm gap between contiguous slices). Data analysis was carried out using SPM5. After a conventional GLM analysis, we assessed changes in functional connectivity related to the SY and GR observation tasks, by means of two separate PsychoPhysiologic Interaction (PPI) analyses (Friston et al., 1997). Foci in the right PMv and left BA44/45, identified by the conventional GLM analyses, were the seed regions. Group analyses were performed by random-effect models. Results Activity in right PMv during the observation of SY was positively related to activity in bilateral regions in posterior (occipito-temporo-parietal) cortex and cerebellum; during the observation of GR, the pattern was similar, but an additional correlated focus was present in the right inferior and middle frontal gyri, BA44/45/46 (Fig. 1). Activity in left BA44/45 during the observation of SY was positively related to activity in two foci: a larger focus in the left inferior and middle frontal gyri, mainly in BA45/46/47, and a second focus in the medial and superior frontal gyri, BA6/8, also mostly in the left hemisphere (Fig. 2). During the observation of GR, a very different pattern was present, with extensive bilateral clusters in sensorimotor and premotor cortex (mainly BA3/4/6/7 and BA6/8). Conclusions The present data suggest that right PMv and left Broca area are parts of different functional networks, differentially active during the observation of different meaningful arm-hand actions. The PMv connections to a mainly visual network during the observation of symbolic, intransitive movements are probably related to extracting visuo/spatial features of the observed scene; only during observation of grasping, PMv relates to the inferior frontal gyrus. On the other hand, the left Broca area has a specific pattern of connectivity with premotor regions involved in higher-order motor programming during the observation of symbolic gestures. References Caspers, S. et al. (2010), 'ALE meta-analysis of action observation and imitation in the human brain', NeuroImage, vol. 50, pp. 1148-1167. Emmorey, K. et al. (2010), ‘CNS activation and regional connectivity during pantomime observation: no engagement of the mirror neuron system for deaf signers’, Neuroimage vol. 49, pp. 994-1005. Hattori, N. et al. (2009), ‘Discrete parieto-frontal functional connectivity related to graspi


2011 - Semiautomated segmentation of the human spine based on echoplanar images [Articolo su rivista]
G., Giulietti; Summers, Paul Eugene; Ferraro, Diana; Porro, Carlo Adolfo; B., Maraviglia; F., Giove
abstract

The number of functional magnetic resonance imaging (fMRI) studies performed on the human spinal cord (SC) has considerably increased in recent years. The lack of a validated processing pipeline is, however, a significant obstacle to the spread of SC fMRI. One component likely to be involved in any such pipeline is the process of SC masking, analogous to brain extraction in cerebral fMRI. In general, SC masking has been performed manually, with the incumbent costs of being very time consuming and operator dependent.To overcome these drawbacks, we have developed a tailored semiautomatic method for segmenting the echoplanar images (EPI) of human spine that is able to identify the spinal canal and the SC. The method exploits both temporal and spatial features of the EPI series and was tested and optimized on EPI images of cervical spine acquired at 3 T. The dependence of algorithm performance on the degree of EPI image distortion was assessed by computing the displacement warping field that best matched the EPI to the corresponding high-resolution T2 images. Segmentation accuracy was above 80%, a significant improvement over values obtained with similar approaches, but not exploiting temporal information. Geometric distortion was found to explain about 50% of the variance of algorithm classification efficiency.


2010 - A quantitative comparison of BOLD fMRI responses to noxious and innocuous stimuli in the human spinal cord [Articolo su rivista]
Summers, Paul Eugene; Ferraro, Diana; Duzzi, Davide; Lui, Fausta; G. D., Iannetti; Porro, Carlo Adolfo
abstract

Recent studies have shown that functional magnetic resonance imaging (fMRI) can non-invasively assess spinal cord activity. Yet, a quantitative description of nociceptive and non-nociceptive responses in the human spinal cord, compared with random signal fluctuations in resting state data, is still lacking. Here we have investigated the intensity and spatial extent of blood oxygenation level dependent (BOLD) fMRI responses in the cervical spinal cord of healthy volunteers, elicited by stimulation of the hand dorsum (C6-C7 dermatomes). In a block design fMRI paradigm, periods (20 s each) of repetitive noxious (laser heat) or innocuous (brushing) stimulation were alternated with rest. To estimate the level of false positive responses, functional images were acquired during a separate run while subjects were at rest. In a first analysis of averaged peri-stimulus signals from all voxels within each half of the spinal cord, we found bilateral fMRI responses to both stimuli. These responses were significantly larger during noxious than during innocuous stimulation. No significant fMRI signal change was evident over corresponding time periods during the Rest run. In a second, general linear model analysis, we identified a voxel population preferentially responding to noxious stimulation, which extended rostro-caudally over the length (4 cm) of the explored spinal cord region. By contrast, we found no evidence of voxel populations responding uniquely to innocuous stimuli, or showing decreased activity following either kind of somatosensory stimulus. These results provide the first false-positive-controlled comparison of spinal BOLD fMRI responses to noxious and innocuous stimuli in humans, confirming and extending physiological information obtained in other species.


2010 - A regularization algorithm for decoding perceptual profiles [Poster]
Favilla, Stefania; Prato, Marco; Zanni, Luca; Porro, Carlo Adolfo; Baraldi, Patrizia
abstract

In this study we wished to test the feasibility of predicting the perceived pain intensity in healthy volunteers, based on fMRI signals collected during an experimental pain paradigm lasting several minutes. This model of acute prolonged (tonic) pain bears some similarities with clinically relevant conditions, such as prolonged ongoing activity in nociceptors and spontaneous fluctuations of perceived pain intensity over time.To predict individual pain profile, we tested and optimized one methodological approach based on new regularization learning algorithms on this regression problem.


2010 - Functional exploration of the human spinal cord during voluntary movement and somatosensory stimulation [Articolo su rivista]
Summers, Paul Eugene; G. D., Iannetti; Porro, Carlo Adolfo
abstract

Demonstrations of the possibility of obtaining functional information from the spinal cord in humans using fMRI have been growing in number and sophistication, but the technique and the results that it provides are still perceived by the scientific community with a greater degree of scepticism than fMRI investigations of brain function. Here we review the literature on spinal fMRI in humans during voluntary movements and somatosensory stimulation. Particular attention is given to study design, acquisition and statistical analysis of the images, and to the agreement between the obtained results and existing knowledge regarding spinal cord anatomy and physiology.A striking weakness of many spinal fMRI studies is the use of small numbers of subjects and of time-points in the acquired functional image series. In addition, spinal fMRI is characterised by large physiological noise, and the recorded functional responses are poorly characterised. For all these reasons, spinal fMRI experiments risk of having low statistical power, and few spinal fMRI studies have yielded physiologically relevant information.Thus, while available evidence indicates that spinal fMRI is feasible, we are only approaching the stage at which the technique can be considered to have been rigorously established as a viable means of non-invasively investigating spinal cord functioning in humans.


2010 - Neural bases of conditioned placebo analgesia [Articolo su rivista]
Lui, Fausta; Colloca, L.; Duzzi, Davide; Anchisi, Davide; Benedetti, F.; Porro, Carlo Adolfo
abstract

Despite growing interest in the placebo effect, the neural correlates of conditioned analgesia are still incompletely understood. We investigated herein on brain activity during the conditioning and post-conditioning phases of a placebo experimental paradigm, using event-related fMRI in 31 healthy volunteers.Brief laser heat stimuli delivered to one foot (either right or left) were preceded by different visual cues, signalling either painful stimuli alone, or painful stimuli accompanied by a (sham) analgesic procedure.Cues signalling the analgesic procedure were followed by stimuli of lower intensity in the conditioning session, whereas in the test session both cues were followed by painful stimuli of the same intensity. During the first conditioning trials, progressive signal increases over time were found during anticipation of analgesia compared to anticipation of pain, in a medial prefrontal focus centered on medial area BA8, and in bilateral lateral prefrontal foci. These frontal foci were adjacent to, and partially overlapped, those active during anticipation of analgesia in the test session, whose signal changes were related to the magnitudeof the placebo behavioral response, and those active during placebo analgesia. Specifically, a large focus in the right prefrontal cortex showed activity related to analgesia, irrespective of the expected side of stimulation. Analgesia was also related to decreased activity, detectable immediately following noxious stimulation, in parietal, insular and cingulate pain-related clusters. Our findings of dynamic changesin prefrontal areas during placebo conditioning, and of direct placebo effects on cortical nociceptive processing, add new insights into the neural bases of conditioned placebo analgesia.


2009 - Brain networks responsive to aversive visual stimuli in humans [Articolo su rivista]
Benuzzi, Francesca; Lui, Fausta; Duzzi, Davide; Nichelli, Paolo Frigio; Porro, Carlo Adolfo
abstract

The neural mechanisms subserving recognition of noxious stimuli and empathy for pain appear to involve at least in part the corticalregions associated with the processing of pain affect. An important issue concerns the specificity of brain networks associated with observing and representing painful conditions, in comparison with other unpleasant stimuli. Recently, we found both similarities and differences between the brain patterns of activity related to the observation of noxious or disgusting stimuli delivered to one hand or foot. Overlap regions included the perigenual anterior cingulate (pACC), whose activity was related to the perceived unpleasantness. We aimed here atrevealing how pACC functional connectivity changes in relationship to the different experimental conditions, using a psychophysiological interaction model. Activity in pACC during the observation of painful stimuli was specifically and positively related to regions in the right hemisphere, including portions of the prefrontal, midcingulate and insular cortex. On the other hand, positive changes in pACC connectivity during the vision of disgusting stimuli were present in the right basal ganglia. These data suggest that pACC activity is part of different networks involved in the recognition of painful or disgusting stimuli.


2009 - From BOLD-FMRI signals to the prediction of subjective pain perception through a regularization algorithm [Relazione in Atti di Convegno]
Prato, Marco; Favilla, Stefania; Baraldi, Patrizia; Porro, Carlo Adolfo; Zanni, Luca
abstract

Functional magnetic resonance imaging, in particular theBOLD-fMRI technique, plays a dominant role in humanbrain mapping studies, mostly because of its noninvasivenessand relatively high spatio-temporal resolution.The main goal of fMRI data analysis has been to revealthe distributed patterns of brain areas involved in specificfunctions, by applying a variety of statistical methods withmodel-based or data-driven approaches. In the last years,several studies have taken a different approach, where thedirection of analysis is reversed in order to probe whetherfMRI signals can be used to predict perceptual or cognitivestates. In this study we test the feasibility of predicting theperceived pain intensity in healthy volunteers, based on fMRIsignals collected during an experimental pain paradigm lastingseveral minutes. In particular, we introduce a methodologicalapproach based on new regularization learning algorithmsfor regression problems.


2009 - Open your mind to placebo conditioning [Articolo su rivista]
Porro, Carlo Adolfo
abstract

This invited Editorial briefly reviews available evidence about the key role of learning and of prefrontal regions in placebo analgesia. These findings have potentially strong clinical implications, because placebo effects can overlap those of drugs and of other therapeutic approaches.


2009 - Pain Anticipation in the Cingulate Gyrus [Capitolo/Saggio]
Porro, Carlo Adolfo; Lui, Fausta
abstract

Throughout this chapter, we focus mainly on theinvolvement of the cingulate cortex in the anticipationof somatosensory input and specifi cally of pain. Thisissue has important theoretical and clinical implications,given the role of the cingulate cortex in themechanisms of pain and analgesia (see Chapters 14and 15). A specifi c question is that whether anticipationis able to affect the activity of pain-related populationsin the cingulate cortex and in the pain matrix in general.Indeed, it has long been hypothesized (James 1892)that essentially the same brain regions were implicatedboth in the anticipation and in the perception of astimulus; this hypothesis has now been directly testedby electrophysiological and functional imaging studiesin humans and non-human primates. Also, whenappropriate, we will briefl y compare the activity ofthe cingulate cortex during anticipation of painand during anticipation of other aversive or rewardevents. The specifi c goals of this chapter include thefollowing:1 Assess electrophysiological evidence of neurons activeduring pain anticipation in the cingulate cortex.2 Evaluate evidence from functional imaging studiesof activity changes related to somatosensory anticipationin different portions of the cingulate gyrus inhealthy volunteers and in pain patients.3 Appraise the modulation of basal- and stimulusevokedactivity of pain-related populations in thecingulate cortex and in other pain-related areas.4 Consider anticipation of pain and analgesia in termsof the potential underlying mechanisms and cingulatecircuits.


2008 - Does it look painful or disgusting? Ask your parietal and cingulate cortex [Articolo su rivista]
Benuzzi, Francesca; Lui, Fausta; Duzzi, Davide; Nichelli, Paolo Frigio; Porro, Carlo Adolfo
abstract

Looking at still images of body parts in situations that are likely to cause pain has been shown to be associated with activation in some brain areas involved in pain processing. Because pain involves both sensory components and negative affect, it is of interest to explore whether the visually evoked representations of pain and of other negative emotions overlap. By means of event-related functional magnetic resonance imaging, here we compare the brain areas recruited, in female volunteers, by the observation of painful, disgusting, or neutral stimuli delivered to one hand or foot. Several cortical foci were activated by the observation of both painful and disgusting video clips, including portions of the medial prefrontal cortex, anterior, mid-, and posterior cingulate cortex, left posterior insula, and right parietal operculum. Signal changes in perigenual cingulate and left anterior insula were linearly related to the perceived unpleasantness, when the individual differences in susceptibility to aversive stimuli were taken into account. Painful scenes selectively induced activation of left parietal foci, including the parietal operculum, the postcentral gyrus, and adjacent portions of the posterior parietal cortex. In contrast, brain foci specific for disgusting scenes were found in the posterior cingulate cortex. These data show both similarities and differences between the brain patterns of activity related to the observation of noxious or disgusting stimuli. Namely, the parietal cortex appears to be particularly involved in the recognition of noxious environmental stimuli, suggesting that areas involved in sensory aspects of pain are specifically triggered by observing noxious events.


2008 - Experimental designs and brain mapping approaches for studying the placebo analgesic effect [Articolo su rivista]
L., Colloca; F., Benedetti; Porro, Carlo Adolfo
abstract

The placebo effect has intrigued scientists since it was proposed. The debate has now centered on how it works. Significant progress has been made and most of our knowledge about the neurobiological mechanisms comes from the field of pain and analgesia. The appropriateness of the experimental/clinical paradigms is crucial when we want to investigate the mechanisms of the placebo phenomenon. Recently, functional imaging techniques, such as positron emission tomography, magnetic resonance imaging, and electro/magnetoencephalography have also given the opportunity to define the neuroanatomical bases of placebo analgesia. This work systematically reviews the literature that deals with placebo analgesia, emphasizing both the methodological aspects and the neurobiological advances. The understanding of placebo mechanisms is fundamental and necessary to identify ways of accessing and harnessing these mechanisms in clinical practice to the patient’s benefit.


2008 - Neural substrates for observing and imagining non-object-directed actions [Articolo su rivista]
Lui, Fausta; G., Buccino; Duzzi, Davide; Benuzzi, Francesca; G., Crisi; Baraldi, Patrizia; Nichelli, Paolo Frigio; Porro, Carlo Adolfo; G., Rizzolatti
abstract

The present fMRI study was aimed at assessing the cortical areas active when individuals observe non-object-directed actions (mimed, symbolic, and meaningless), and when they imagine performing those same actions. fMRI signal increases in common between action observation and motor imagery were found in the premotor cortex and in a large region of the inferior parietal lobule. While the premotor cortex activation overlapped that previously found during the observation and imagination of object-directed actions, in the parietal lobe the signal increase was not restricted to the intraparietal sulcus region, known to be active during the observation and imagination of object-directed actions, but extended into the supramarginal and angular gyri. When contrasting motor imagery with the observation of non-object-directed actions, signal increases were found in the mesial frontal and cingulate cortices, the supramarginal gyrus, and the inferior frontal gyrus. The opposite contrast showed activation virtually limited to visual areas. In conclusion, the present data define the common circuit for observing and imagining non-object-directed actions. In addition, they show that the representation of non-object-directed actions include parietal regions not found to be involved in coding object-directed actions.


2008 - Physiological noise modelling for spinal functional magnetic resonance imaging studies [Articolo su rivista]
BROOKS J. C., W; Beckmann, C; MILLER K., L; Wise, R; Porro, Carlo Adolfo; Tracey, I; Jenkinson, M.
abstract

Spinal cord functional imaging allows assessment of activity in primary synaptic connections made by sensory neurons relaying information about the state of the body. However, reported human data based on gradient-echo techniques have been largely inconsistent, with no clear patterns of activation emerging. One reason for this variability is the influence of physiological noise, which is typically not corrected for. By acquiring single-slice resting data from the spinal cord with a conventional gradient-echo EPI pulse sequence at TR = 200 ms (critically sampled) and TR = 3 s (under-sampled), we have characterised various sources of physiological noise. In 8 healthy subjects, the presence of physiologically dependent signal was explored using probabilistic independent component analysis (PICA). Based on the insights provided by PICA, we defined a new physiological noise model (PNM) based on retrospective image correction (RETROICOR), which uses independent physiological measurements taken from the subject to model sources of noise. Statistical significance of individual components included in the PNM was assessed by F-tests, which demonstrated that the optimal PNM included cardiac, respiratory, interaction and low-frequency regressors. In a group of 10 healthy subjects, activation data were acquired from the cervical spinal region (T1 to C5) during painful thermal stimulation of the right and left hands. The improvement obtained when using a PNM in estimating spinal cord activation was reflected in a reduction of false-positive activation (active voxels in the CSF space surrounding the cord), when compared to conventional GLM modelling without a PNM.


2008 - Predicting subjective pain perception based on BOLD-fMRI signals: a new machine learning approach [Relazione in Atti di Convegno]
Favilla, Stefania; Prato, Marco; Zanni, Luca; Porro, Carlo Adolfo; Baraldi, Patrizia
abstract

Functional magnetic resonance imaging, in particular the BOLD-fMRI technique, plays a dominant role in human brain mapping studies, mostly because of its non-invasiveness, good spatial and acceptable temporal resolution in comparison with other techniques. The main goal of fMRI data analysis has been to reveal the distributed patterns of brain areas involved in specific functions and their interactions, by applying a variety of univariate or multivariate statistical methods with model-basedor data-driven approaches. In the last few years, a growing number of studies have taken a different approach, where the direction of analysis is reversed in order to probe whether fMRI signals can be used to predict perceptual or cognitive states. In this study we wished to test the feasibility of predicting the perceived pain intensity in healthy volunteers, based on fMRI signals collected during an experimental pain paradigm lasting several minutes. To this end, we tested and optimized one methodological approach based on new regularization learning algorithms on this regression problem.


2008 - Simultaneous acquisition of time-domain fNIRS and fMRI during brain cortex activity [Relazione in Atti di Convegno]
Contini, D.; Torricelli, A.; Pifferi, A.; Spinelli, L.; Cubeddu, R.; Nocetti, L.; Porro, C. A.; Baraldi, P.
abstract

A time-domain fNIRS system was developed for simultaneous acquisition with fMRI. Preliminary results indicate the potentiality of the system. To our knowledge this is the first timedomain fNIRS and fMRI study on human brain. ©2008 Optical Society of America.


2008 - Touch or pain? Spatio-temporal patterns of cortical fMRI activity following brief mechanical stimuli [Articolo su rivista]
Lui, Fausta; Duzzi, Davide; Corradini, Matteo; M., Serafini; Baraldi, Patrizia; Porro, Carlo Adolfo
abstract

Most imaging studies on the human pain system have concentrated so far on the spatial distribution of pain-related activity. In the present study, we investigated similarities and differences between the spatial and temporal patterns of brain activity related to touch vs. pain perception. To this end, we adopted an event-related functional magnetic resonance imaging (fMRI) paradigm allowing us to separately assess the activity related to stimulus anticipation, perception, and coding. The fMRI signal increases following brief mechanical noxious or non-noxious stimulation of the hand dorsum were largely overlapping in the contralateral and ipsilateral hemispheres, including portions of the parietal, insular, frontal and cingulate cortices. Higher activity following noxious stimulation was found in the contralateral mid-anterior insular cortex, in the anterior mid-cingulate cortex (aMCC) and in the adjacent dorso-medial frontal cortex. Significant decreases in fMRI signals following both tactile and painful stimuli were found in perigenual cingulate (pACC)/medial prefrontal cortex (MPF) and in the posterior cingulate/precuneus/paracentral lobule; more intense decreases were found in the pACC/MPF following painful stimuli. fMRI signal increases in the contralateral insula and in aMCC, but not in the parietal cortex, were more prolonged following painful than tactile stimuli. Moreover, a second peak of signal increases (albeit of lower intensity) was found in anterior insula and aMCC during pain intensity rating. These results show specific spatio-temporal patterns of cortical activity related to processing noxious vs. non-noxious mechanical stimuli.


2007 - An ARX model-based approach to trial by trial identification of fMRI-BOLD responses [Articolo su rivista]
Baraldi, Patrizia; Manginelli, Angela; Maieron, Marta; D., Liberati; Porro, Carlo Adolfo
abstract

Being able to estimate the fMRI-BOLD response following a single task or stimulus is certainly of value, since it allows to characterize its relationship to different aspects either of the stimulus, or of the subject's performance. In order to detect and characterize BOLD responses in single trials, we developed and validated a procedure based on an AutoRegressive model with eXogenous Input (ARX). The use of an individual exogenous input for each voxel makes the modeling sensitive enough to reveal differences across regions, avoiding any a priori assumption about the reference signal. The detection of variability across trials is ensured by a suitable choice, for each voxel, of the order of the moving average, which in our implementation determines the relative delay between the recorded and the reference signal. This is a quality useful in finding different time profiles of activation from high temporal resolution fMRI data. The results obtained from simulated fMRI data resulting from synthetic activations in actual noise indicate that such approach allows to evaluate important features of the response, such as the time to onset, and time to peak. Moreover, the results obtained from real high temporal resolution fMRI data acquired at l.5 T during a motor task are consistent with previous knowledge about the responses of different cortical areas in motor programming and execution. The proposed procedure should also prove useful as a pre-processing step in different approaches to the analysis of fMRI data.


2007 - Enhancement of force after action observation. Behavioural and neurophysiological studies [Articolo su rivista]
Porro, Carlo Adolfo; Facchin, P; Fusi, S; Dri, G; Fadiga, L.
abstract

We tested here the hypothesis that observing others’ actions can facilitate basic aspects of motor performance, such as force production, even if subjects are not required to immediately reproduce the observed actions and if they are not aware that observation can form the basis for procedural training. To this end, we compared in healthy volunteers the effects of repeated actual execution (MOV) or observation (OBS) of a simple intransitive movement (abduction of the right index and middle fingers). In a first experiment, we found that both actual and observational training significantly increased the finger abduction force of both hands. In the MOV group, force increases over pre-training values were significantly higher in the trained than in the untrained hand (50% versus 33%), whereas they were similar for the two hands in the OBS group (32% versus 30%). No force change was found in the control, untrained group. In a second experiment, we found that both training conditions significantly increased the isometric force exerted during right index finger abduction, whereas no post-training change in isometric force was found during abduction of the right little finger. Actual performance, imagination and, to a lower extent, observation of fingers movement enhanced the excitability of the corticospinal system targeting the first dorsal interosseus muscle, as tested by transcranial magnetic stimulation; pre- and post-training effects were of similar magnitude.These results show a powerful, specific role of action observation in motor training, likely exerted through premotor areas, which may prove useful in physiological and rehabilitative conditions.


2007 - Functional Responses in the Human Spinal Cord during Willed Motor Actions: Evidence for Side- and Rate-Dependent Activity [Articolo su rivista]
Maieron, Marta; IANNETTI G., D; Bodurka, J; Tracey, I; BANDETTINI P., A; Porro, Carlo Adolfo
abstract

Although the spinal cord is the output station of the central motor system, little is known about the relationships between its functionalactivity and willed movement parameters in humans. We investigated here blood oxygenation level-dependent functional magneticresonance imaging (fMRI) signal changes in the cervical spinal cord during a simple finger-to-thumb opposition task in 13 right-handedvolunteers, using a dedicated array of 16 receive-only surface coils on a 3 Tesla MRI system. In a first experiment, we found significantfMRI signal increases on both sides of the lower cervical spinal cord while subjects performed the motor task at a comfortable pace (0.5Hz) using either hand. Both the spatial extent of movement-related clusters and peak signal increases were significantly higher on the sideof the cord ipsilateral to the moving hand than on the contralateral side. Movement-related activity was consistently larger than signalfluctuations during rest. In a second experiment, we recorded spinal cord responses while the same motor sequence was performed usingthe dominant hand at two different rates (0.5 or 1 Hz). The intensity but not the spatial extent of the response was larger during higherrates, and it was higher on the ipsilateral side of the cord. Notwithstanding the limited spatial resolving power of the adopted technique,the present results clearly indicate that the finger movement-related fMRI signals recorded from the spinal cord have a neural origin andthat as a result of recent technological advances, fMRI can be used to obtain novel and quantitative physiological information on theactivity of spinal circuits


2007 - Neural networks related to observing symbolic and meaningless intransitive hand movements [Relazione in Atti di Convegno]
Lui, Fausta; Duzzi, Davide; Benuzzi, Francesca; M., Serafini; Baraldi, Patrizia; G., Rizzolatti; Porro, Carlo Adolfo
abstract

In spite of the increasing literature on the neural system involved in the observation of biological movements1, few studies so far have dealt with the observation of meaningful hand movements2-4. Furthermore, they yielded partially conflicting results, possibly because of different techniques used, stimuli presented and tasks assigned to the subjects. Methods Twenty healthy right-handed volunteers (8 males, 12 females; mean age 26.6) took part in this study. An event-related paradigm was adopted. A continuous video was presented, showing a table with some common objects (glasses, cup, scissors, etc.). At intervals, an actor, of whom only the trunk and arms were visible, performed different kinds of hand movements: a) symbolic (OK, hello, etc.) (SY); b) meaningless (ML); c) grasping an object; b) simply touching an object. Only data regarding the first two conditions (i.e., intransitive movements) will be presented here. No movement was ever repeated during each experiment. Three runs were carried out for each subject. Six movements for each class were shown in each run, alternated in pseudorandom order. Functional imaging was performed on a 3T Philips Intera scanner. Twenty-four axial slices were acquired (in-plane matrix: 64x64; TR: 2515 ms; voxel size: 3.75x3.75x4 mm, with a 0.6 mm gap between contiguous slices). Data analysis was carried out using SPM5. Multi-subject analyses were performed using a random effect model. In particular, direct comparisons between SY and ML, and between ML and SY, were performed. Results Direct subtraction of SY vs. ML evoked a signal increase mainly in the left hemisphere (Fig. 1, top row) in a fronto-temporal circuit including the middle temporal gyrus/superior temporal sulcus (also on the right), dorsal premotor cortex and inferior frontal gyrus; in addition, activity increased in the dorsomedial prefrontal cortex (Talairach coordinates: x=4, y=48, z=23) and in the head of the left caudate nucleus. The contrast ML vs. SY (Fig. 1, bottom row) evoked increased activity bilaterally in the middle/inferior temporal gyrus; mainly on the right in the superior and inferior parietal lobules; and exclusively on the right in premotor cortex/inferior frontal gyrus. Conclusions The present findings show that observing symbolic actions involves a mainly left fronto-temporal pathway. A focus in the dorsomedial prefrontal cortex specifically active during SY observation could be related to a circuit involved in social interactions5. Observing meaningless movements activates bilateral temporal areas and predominantly right parietal and premotor areas. Some of these latter areas are part of the mirror system1. It appears therefore that mainly the right mirror system is involved in the analysis of the motor aspects of movement, when no semantic content is present. References 1) Rizzolatti and Craighero Annu. Rev. Neurosci. 27:169-192, 2004. 2) Decety et al. Brain 120:1763-1777, 1997. 3) Tanaka et al. Neuroreport 12:1171-1174, 2001. 4) Rumiati et al. J.Cogn.Neurosci. 17:1420-1431, 2005. 5) Iacoboni et al. Neuroimage 21:1167-1173, 2004.


2007 - Parietal cortex involvement in the localization of tactile and noxious mechanical stimuli: A transcranial magnetic stimulation study [Articolo su rivista]
Porro, Carlo Adolfo; M., Martinig; P., Facchin; Maieron, Marta; A. K. P., Jones; L., Fadiga
abstract

The cortical system underlying perceptual ability to localize tactile and noxious cutaneous stimuli in humans is still incompletely understood. We used transcranial magnetic stimulation (TMS) to transiently interfere with the function of the parietal cortex, at different times after the beginning of noxious or non-noxious mechanical stimulation of the hairy skin overlying the dorsal surface of the first metacarpal of the contralateral hand. Peripheral stimuli consisted of rounded (1 mm diameter) or sharp (0.2 mm) metal tips; skin contact lasted on average 242 ms (noxious) and 228 ms (non-noxious). Brief (80 ms, 25 Hz) TMS trains, given at 150 ms after the onset of cutaneous stimulation, significantly impaired subjects' ability in localizing non-nociceptive, tactile input, an effect which was not observed when TMS was applied at 300 ins after cutaneous stimulation. In contrast, brief TMS trains given at 300 ms after the onset of cutaneous Stimulation significantly impaired Subjects' ability in localizing nociceptive input, an effect which was not observed when TMS was applied at 150 ms after cutaneous stimulation. No impairment in stimulus detection was found in comparison with control sham TMS. The timing of parietal TMS interference with the ability to localize tactile and painful stimuli is compatible with known time differences in the arrival of non-noxious and noxious information in the postcentral gyrus. On these grounds, our findings support the existence of overlapping cortical populations in the contralateral parietal lobe, exerting a role in spatial discriminative aspects of touch and mechanically induced pain. (c) 2006 Elsevier B.V. All rights reserved.


2006 - Attributing a meaning to hand movements: an fMRI study [Relazione in Atti di Convegno]
Lui, Fausta; G., Buccino; Duzzi, Davide; Benuzzi, Francesca; Baraldi, Patrizia; Porro, Carlo Adolfo; G., Rizzolatti
abstract

Increasing attention is being paid to functional activations related to body movement inner representations, during either observation or imagery (1,2). So far, however, few studies have dealt with the presence or absence of a meaning in the observed and/or imagined movements (3).MethodsThirteen healthy right-handed volunteers (5 males, 8 females; age 20-31) took part in the study. At the beginning of each trial, a short video was presented, showing different kinds of intransitive hand movements: pantomimes, or symbolic gestures, or nonsense movements. The subjects had either to imagine to perform the same movement they had just seen in the previous video (imagery task); or to observe another movement, different from the previous one (observation task). Four runs, twenty trials each, were carried out for each subject. Functional imaging was performed on a 1.5 Signa GE MR scanner, acquiring 18 contiguous axial slices (TR: 2000 ms; voxel size: 3.75x3.75x6 mm). Data analysis was carried out using the SPM99 package (Wellcome Department of Imaging Neuroscience, London, UK). Multi-subject analyses were performed using a random effect model. In particular, in order to identify patterns of activation related to the attribution of a meaning to movements, we performed a conjunction analysis of the contrasts “pantomimes vs. nonsense” and “symbolic vs. nonsense”, for observation and imagery separately.ResultsDuring the observation of meaningful actions, as compared with meaningless movements, mainly left hemisphere activations (Fig. 1A) were found in the frontal and temporal cortex: namely, in precentral gyrus (BA 6), inferior frontal gyrus (IFG, BA45) and middle frontal gyrus (BA10), and in superior temporal gyrus (BA22); in addition, activity increased in the right middle temporal gyrus and in medial occipital areas bilaterally. During imagery of meaningful vs. meaningless movements, regions of increased signal were in the left IFG (BA45) (Fig 1B), in the right parietal operculum/posterior insula, and in lateral occipital/posterior temporal cortex in both hemispheres.ConclusionsA common region functionally activated during both imagery and observation of meaningful vs. meaningless movements is the left IFG. Actually, a smaller signal increase was present in IFG also for meaningless movements (data not shown). The IFG had been found active in a previous study when observing meaningful upper limb movements with the intention to either recognize or to imitate them (3). The IFG is part of the so-called mirror system, devoted to action understanding and imitation (1). Our results support the hypothesis that the left IFG is specifically involved in attributing a meaning to upper limb movements, during both passive (observation) and active (imagery) inner representations. 1) G. Rizzolatti and L. Craighero Annu.Rev.Neurosci. 2004.2) M. Jeannerod Neuroimage. 14:S103-S109, 2001.3) J. Decety et al. Brain 120:1763-1777, 1997.


2006 - DISCUSSION [Altro]
Porro, C. A.; Rizzolatti, G.; Rumiati, R. I.; Mehler, J.; Tanifuji, M.; Logothetis, N. K.; Scott, S. H.; Krubitzer, L.; Schall, J. D.; Haggard, P.; Diamond, M. E.; Barash, S.; Treves, A.; Hasson, U.
abstract


2006 - Discussion [Altro]
Derdikman, D.; Romo, R.; Brecht, M.; Dehaene, S.; Harris, J. A.; Porro, C. A.; Rizzolatti, G.; Schall, J. D.; Logothetis, N. K.
abstract


2006 - Discussion [Altro]
Logothetis, N. K.; Hasson, U.; Dehaene, S.; Rizzolatti, G.; Diamond, M. E.; Krubitzer, L.; Harris, J. A.; Romo, R.; Brecht, M.; Porro, C. A.
abstract


2006 - Functional activity mapping of brainstem nociceptive networks in animals [Capitolo/Saggio]
Porro, Carlo Adolfo; Lui, Fausta
abstract

In this paper, we review blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies addressing the neural correlates of touch, thermosensation, pain and the mechanisms of their cognitive modulation in healthy human subjects. There is evidence that fMRI signal changes can be elicited in the parietal cortex by stimulation of single mechanoceptive afferent fibers at suprathreshold intensities for conscious perception. Positive linear relationships between the amplitude or the spatial extents of BOLD fMRI signal changes, stimulus intensity and the perceived touch or pain intensity have been described in different brain areas. Some recent fMRI studies addressed the role of cortical areas in somatosensory perception by comparing the time course of cortical activity evoked by different kinds of stimuli with the temporal features of touch, heat or pain perception. Moreover, parametric single-trial functional MRI designs have been adopted in order to disentangle subprocesses within the nociceptive system.Available evidence suggest that studies that combine fMRI with psychophysical methods may provide a valuable approach for understanding complex perceptual mechanisms and top-down modulation of the somatosensory system by cognitive factors specifically related to selective attention and to anticipation. The brain networks underlying somatosensory perception are complex and highly distributed. A deeper understanding of perceptual-related brain mechanisms therefore requires new approaches suited to investigate the spatial and temporal dynamics of activation in different brain regions and their functional interaction.


2006 - General discussion I [Altro]
Treves, A.; Diamond, M. E.; Wolpert, D. M.; Brecht, M.; Derdikman, D.; Scott, S. H.; Romo, R.; Sparks, D. L.; Haggard, P.; Logothetis, N. K.; Schall, J. D.; Rizzolatti, G.; Porro, C. A.; Esteky, H.; Barash, S.
abstract


2006 - General discussion III [Altro]
Tanifuji, M.; Rizzolatti, G.; Tsakiris, M.; Romo, R.; Harris, J. A.; Logothetis, N. K.; Diamond, M. E.; Sparks, D. L.; Schall, J. D.; Rumiati, R. I.; Treves, A.; Derdikman, D.; Wolpert, D. M.; Gold, J. I.; Dehaene, S.; Krubitzer, L.; Porro, C. A.
abstract


2006 - Pain Processing and Modulation in the Cingulate Gyrus [Relazione in Atti di Convegno]
VOGT B., A; Porro, Carlo Adolfo; Faymonville, M. E.
abstract

Cingulate cortex occupies a large part of the medial surface of the brain and has become an important region of interest in acute and chronic pain studies. Although it is among the most frequently activated regions in human functional imaging research, no part of the cingulate gyrus can be referred to as a “pain center” because none has been shown to have mainly pain processing functions. For example, the midcingulate region, which is usually activated during acute noxious stimulation, has primarily skeletomotor functions through the two cingulate motor areas and has been activated in numerous tasks that do not involve noxious stimuli. These include the Stroop and Flanker interference, complex movement, and word generation tasks. The logic of studying pain processing in this context requires a clear statement of the functions of each cingulate region in general brain function followed by an assessment of how these functions are redirected to resolve problems of anticipated or actual pain experiences. Here we consider the structural, connection and functional organization of the cingulate gyrus, its top-down role in anticipation of pain and the application of hypnosis to engage cingulate mediated processing for hypnosedation.


2005 - Analisi di dati fMRI-BOLD a singolo evento: un approccio con reti neurali non supervisionate [Articolo su rivista]
Duzzi, Davide; Manginelli, Angela; Maieron, Marta; Porro, Carlo Adolfo; Baraldi, Patrizia
abstract

Negli studi di risonanza magnetica funzionale (fMRI) cerebrale hanno assunto particolare rilevanza i protocolli di stimolazione basati su singoli eventi. Nel lavoro viene descritta una strategia di analisi di dati fMRI-BOLD, con lo scopo di rilevare il profilo temporale della risposta ad ogni singola stimolazione, nelle diverse aree cerebrali coinvolte. Il metodo si avvale di una fase di pre-elaborazione dei dati finalizzata ad incrementare il basso contrasto segnale-rumore tipico di dati derivanti da un singolo evento e di una fase di classificazione, caratterizzazione e localizzazione delle risposte realizzata implementando una rete neurale basata sull’algoritmo di Kohonen delle mappe auto-organizzanti (SOMs). I risultati, ottenuti sia su immagini fMRI simulate, che su dati reali relativi ad un soggetto umano, mostrano la validita’ di questo approccio guidato dai dati nell’identificazione delle risposte ad una singola stimolazione e ne forniscono i limiti di applicabilita’.


2005 - Cardioventilatory responses during real or imagined walking at low speed [Articolo su rivista]
S., Fusi; D., Cutuli; M. R., Valente; P., Bergonzi; Porro, Carlo Adolfo; P. E., Di Prampero
abstract

There is increasing evidence that motor imagery involves at least in part central processes used in motor control. In order to deepen our understanding on the neural mechanisms underlying vegetative responses to real and imagined exercise, we determined cardioventilatory variables during actual or imagined treadmill walking on flat terrain at speeds of 2, 3.5 or 5 km/h, in a group of 14 healthy volunteers. During actual walking, as expected, a comparable intensity-dependent increase was found in ventilation, oxygen consumption, tidal volume and respiratory rate. Imagined walking led to a significant, albeit small (less than 10%), increase in ventilation and oxygen consumption, and to larger increases (up to 40%) in respiratory rate, which was paralleled by a non significant trend towards a decline of tidal volume. These results confirm and extend previous observations showing that motor imagery is accompanied by centrally induced changes in vegetative responses, and provide evidence for a differential control on respiratory rate and tidal volume.


2004 - Corticospinal excitability during painful self-stimulation in humans: a transcranial magnetic stimulation study [Articolo su rivista]
Fadiga, L.; Craighero, L.; Dri, G.; Facchin, P.; FABBRI DESTRO, M.; Porro, Carlo Adolfo
abstract

We investigated changes in the corticospinal pattern of activity in healthy volunteers during sustained noxious and non-noxious mechanical stimulation of the first hand digit, resulting from active (self-stimulation) or passive (externally-induced) pressing against a sharp or blunted tip. The results indicate that, in order to press a finger onto a noxious stimulus with the same force generated to press onto a non-noxious one, the motor cortex adopts a peculiar strategy in terms of recruitment of motor units. This is reflected by an increase of corticospinal excitability (as revealed by motor potentials evoked by transcranial magnetic stimulation of the contralateral primary motor cortex) and EMG activity of agonist muscles, possibly related to an increase of motor unit synchronization.


2004 - Diurnal changes of tonic nociceptive responses in mice: evidence for a proalgesic role of melatonin [Articolo su rivista]
Perissin, L.; Boccalon, S.; Scaggiante, B.; Petrelli, L.; Ortolani, F.; Porro, Carlo Adolfo
abstract

Diurnal variations in tonic pain reactions have been described in mice tested in Spring, but the underlying mechanisms are still unknown. We tested the potential role of melatonin, a key hormone in the control of neuro-endocrine circadian rhythms. The experiments were performed in male CBA/J mice housed under controlled temperature, humidity, and light (12/12 dark/light cycle) conditions, during the Light (7–10a.m.) or Dark (7–10p.m.) phases of the diurnal cycle. In a first group of experiments, animals were either pretreated with i.p. saline (controls) or with the melatonin receptor antagonist, luzindole (30 mg/kg), before the s.c. injection of a dilute formalin solution into a hindpaw. In control animals, pain-related behavioral reactions (licking and flinching) were higher in the evening (Dark) than in the morning (Light), both during the first (0–10 min) and the second (11–55 min) phase of the response to s.c. formalin. In animals pre-treated with luzindole, no diurnal changes occurred, pain reactions in the Dark being similar to those of the Light Control group. In a second group of experiments, artificial pinealectomy, obtained by exposing animals to continuous light for 48 h, also reduced pain reactions in the evening to levels comparable to those in the morning. Receptor autoradiography showed lower binding availability at spinal cord level in mice sacrificed during the Dark, as expected from the circadian pattern of melatonin secretion. A further significant decrease of melatonin receptor binding was induced by noxious stimulation. These results suggest a proalgesic role of endogenous melatonin in tonic pain.


2004 - Effects of ketamine anesthesia on central nociceptive processing in the rat: a 2-deoxyglucose study. [Articolo su rivista]
Porro, Carlo Adolfo; Cavazzuti, Milena; Giuliani, Daniela; Vellani, Vittorio; Lui, Fausta; Baraldi, Patrizia
abstract

Ketamine is a dissociative anesthetic with complex actions on the CNS. We investigated here the effects of ketamine anesthesia on somatosensory processing in the rat spinal cord, thalamus, and cerebral cortex, using the quantitative 2-deoxyglucose mapping technique. Unanesthetized or ketamine-anesthetized male Sprague-Dawley rats received a s.c. injection of a dilute formaldehyde solution (5%, 0.08 ml) into a forepaw, inducing prolonged noxious afferent input, or an equal volume of isotonic saline as a control stimulus. The 2-deoxyglucose experiments started 30 min after the injection. In the cervical enlargement of the spinal cord, ketamine had no significant effect on glucose metabolic rates in saline-injected animals, whereas it prevented the metabolic increases elicited by prolonged noxious stimulation in unanesthetized animals. At the thalamic level, ketamine increased glucose uptake in both saline- and formalin-injected rats in the lateral posterior, lateral dorsal, medial dorsal, gelatinosus, antero-ventral and antero-medial thalamic nuclei, whereas it decreased metabolic activity in the ventro-basal complex. At the cortical level, the drug increased metabolic activity in both control and formalin groups in the lacunosus-molecularis layer of the dorsal hippocampus, posterior parietal, retrosplenial, cingulate and frontal cortex; significant metabolic decreases were found in the CA1 region of the dorsal hippocampus and in the parietal 1 and 2 cortical areas. In the investigated brain regions, ketamine did not abolish noxious-evoked increases in glucose uptake, which were in fact enhanced in the forelimb cortex and in the lacunosus-molecularis layer of the hippocampus. The dissociation between the spinal and supraspinal effects of ketamine suggests a specific antinociceptive action on spinal circuits, in parallel with complex changes of the activity of brain circuits involved in somatosensory processing. More generally, this study shows that functional imaging techniques are able to quantitatively assess the effects of anesthetic drugs on nociceptive processing at different levels of the neuraxis. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.


2004 - Long-term effects of vaccination on attentional performance [Articolo su rivista]
Nicoletti, Roberto; Porro, Carlo Adolfo; G., Brighetti; Monti, Daniela; Pagnoni, Giuseppe; Guido, Marcello; Rubichi, Sandro; Franceschi, Claudio
abstract

To investigate the possible influence of stimulation of the immune system on cognitive tasks, C healthy volunteers were vaccinated against hepatitis B and tested over a 6 month-period in a simple reaction times and the Stroop task. In general, the Stroop effect demonstrates that both the name and meaning of a word are automatically processed even when voluntary attention is trying hard not to process them. Unlike placebo group, vaccinated subjects showed a persistent lack of the classical Stroop effect. These findings may be explained by a constraint satisfaction model of the Stroop task, assuming a selective weakening of the connection matrix, and suggest that immune-cognitive effects may occur, besides the well known immune-cognitive influences like those elicited by emotional stress.


2004 - Neural circuits involved in the recognition of actions performed by nonconspecifics: An fMRI study [Articolo su rivista]
G., Buccino; Lui, Fausta; N., Canessa; I., Patteri; G., Lagravinese; Benuzzi, Francesca; Porro, Carlo Adolfo; G., Rizzolatti
abstract

Functional magnetic resonance imaging was used to assess the cortical areas active during the observation of mouth actions performed by humans and by individuals belonging to other species (monkey and dog). Two types of actions were presented: biting and oral communicative actions (speech reading, lip-smacking, barking). As a control, static images of the same actions were shown. Observation of biting, regardless of the species of the individual performing the action, determined two activation foci (one rostral and one caudal) in the inferior parietal lobule and an activation of the pars opercularis of the inferior frontal gyrus and the adjacent ventral premotor cortex. The left rostral parietal focus (possibly BA 40) and the left premotor focus were very similar in all three conditions, while the right side foci were stronger during the observation of actions made by conspecifics. The observation of speech reading activated the left pars opercularis of the inferior frontal gyrus, the observation of lip-smacking activated a small focus in the pars opercularis bilaterally, and the observation of barking did not produce any activation in the frontal lobe. Observation of all types of mouth actions induced activation of extrastriate occipital areas. These results suggest that actions made by other individuals may be recognized through different mechanisms. Actions belonging to the motor repertoire of the observer (e.g., biting and speech reading) are mapped on the observer's motor system. Actions that do not belong to this repertoire (e.g., barking) are essentially recognized based on their visual properties. We propose that when the motor representation of the observed action is activated, the observer gains knowledge of the observed action in a “personal” perspective, while this perspective is lacking when there is no motor activation.


2004 - Percept-related activity in the human somatosensory system: functional magnetic resonance imaging studies [Articolo su rivista]
Porro, Carlo Adolfo; Lui, Fausta; P., Facchin; Maieron, Marta; Baraldi, Patrizia
abstract

In this paper, we review blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies addressing the neural correlates of touch, thermosensation, pain and the mechanisms of their cognitive modulation in healthy human subjects. There is evidence that fMRI signal changes can be elicited in the parietal cortex by stimulation of single mechanoceptive afferent fibers at suprathreshold intensities for conscious perception. Positive linear relationships between the amplitude or the spatial extents of BOLD fMRI signal changes, stimulus intensity and the perceived touch or pain intensity have been described in different brain areas. Some recent fMRI studies addressed the role of cortical areas in somatosensory perception by comparing the time course of cortical activity evoked by different kinds of stimuli with the temporal features of touch, heat or pain perception. Moreover, parametric single-trial functional MRI designs have been adopted in order to disentangle subprocesses within the nociceptive system. Available evidence suggest that studies that combine fMRI with psychophysical methods may provide a valuable approach for understanding complex perceptual mechanisms and top-down modulation of the somatosensory system by cognitive factors specifically related to selective attention and to anticipation. The brain networks underlying somatosensory perception are complex and highly distributed. A deeper understanding of perceptual-related brain mechanisms therefore requires new approaches suited to investigate the spatial and temporal dynamics of activation in different brain regions and their functional interaction.


2003 - Functional Imaging Correlates of Pain Perception [Articolo su rivista]
Porro, Carlo Adolfo; Baraldi, Patrizia; P., Facchin; Lui, Fausta; M., Maieron
abstract

Pain is a complex experience characterized by sensory,emotional, and cognitive aspects, which is likely to resultfrom the activity of large populations of central nervoussystem (CNS) cells. A crucial challenge in pain research istherefore to identify how the joint involvement of the differentnociceptive networks, that have been described byanatomical and electrophysiological techniques in experimentalanimals [1], gives rise to pain perception andmodulation.To this end, it is necessary to monitor functional activityof large neuronal arrays, in parallel with psychophysicalself-reports. This has been accomplished in humansusing different kinds of functional imaging techniques,among which positron emission tomography (PET) andfunctional magnetic resonance imaging (fMRI). Theyallow an indirect estimation of neural activity by investigatinglocal metabolic or hemodynamic changes, whichare closely related to the electrical activity of nerve cellsunder physiological circumstances [2]. In many studies, ablock experimental design was adopted: namely, brainactivity was compared among short periods of time (typically60 seconds in PET studies), each characterized bycontinuous (or repeated) innocuous or noxious stimulation.A single perceptual judgement was obtained at theend of each block, thus preventing appreciation of timerelatedchanges in nociceptive activity. Using blockdesigns makes it difficult to discriminate between brainactivity related to differences in the perceived pain intensity,to changes in the level of arousal during noxiousinput, or to anticipation of pain. The fMRI technique hasa better temporal resolution (usually on the order ofseconds) and it is therefore more suitable than PET totrace changes in functional activity of discrete brain areasover time. This can be done using brief stimuli (from hundredsmilliseconds to 2 seconds) in the so-called eventrelatedparadigms [3], using short epochs of 20-30 s, orduring time-varying pain induced by prolonged chemicalstimulation [4].Recent imaging studies have demonstrated the involvementof specific cortical and subcortical systems in differentaspects of the conscious experience of pain (seereview in [5]).


2003 - Functional activity mapping of the mesial hemispheric wall during anticipation of pain [Articolo su rivista]
Porro, Carlo Adolfo; V., Cettolo; M. P., Francescato; Baraldi, Patrizia
abstract

The relative contributions of autonomic arousal and of cognitive processing to cortical activity during anticipation of pain, and the role of changes in thalamic outflow, are still largely unknown. To address these issues, we investigated with functional magnetic resonance imaging (fMRI) the activity of the contralateral mesial hemispheric wall in 56 healthy volunteers while they expected the stimulation of one foot, which could be either painful or innocuous. The waiting period was characterized by emotional arousal, a moderate rise in heart rate, and by increases in mean fMRI signals in the medial thalamus, mid- and posterior cingulate cortex, and in the putative foot area of the primary somatosensory and motor cortex. The same brain regions, excepting posterior cingulate, were also activated by somatosensory stimulation. We identified by cross-correlation analysis a cluster population whose fMRI signal time course was related to the mean heart rate (HR) profile, showing selective changes of activity during the waiting period. Positively correlated clusters were found mainly in sensorimotor areas, mid- and posterior cingulate, and dorsomedial prefrontal cortex. Negatively correlated clusters predominated in the perigenual anterior cingulate and ventromedial prefrontal cortex. HR clusters had different characteristics from, and showed limited spatial overlap with, clusters whose fMRI signals were related to the psychophysical pain intensity profile; however, both cluster populations were affected by anticipation. These findings unravel a complex pattern of brain activity during uncertain anticipation of noxious input, likely related both to changes in the level of arousal and to cognitive modulation of the pain system. (C) 2003 Elsevier Science (USA). All rights reserved.


2003 - Functional imaging and pain: behavior, perception, and modulation [Articolo su rivista]
Porro, Carlo Adolfo
abstract

Time-dependent increases of local metabolic or blood flow rates have been described in spinal cord and brain nociceptive networks during acute and chronic pain states in experimental animals, in parallel with changes of different behavioral endpoints of pain and hyperalgesia. In healthy human volunteers, pain intensity-related hemodynamic changes have been identified in a widespread, bilateral brain system including parietal, insular, cingulate and frontal cortical areas, as well as thalamus, amygdala and midbrain, during different kinds of acute noxious stimulation. Specific patterns of nociceptive activity may characterize hyperalgesic states and some chronic pain conditions. Both animal and human imaging studies suggest that forebrain nociceptive systems are under inhibitory control by endogenous opioids; in humans, acute administration of -opioid receptor agonists blunts noxious heat-evoked activation in several brain areas. Anticipation of pain may in itself induce changes in brain nociceptive networks. Moreover, pain-related increases in cortical activity can be modulated by different cognitive processes, such as hypnotic suggestions, focussing or diverting attention, and placebo. These findings highlight the complexity of the pain system, and begin to disclose the spatio-temporal dynamics of brain networks underlying pain perception and modulation in health and disease.


2003 - Independent time courses of supraspinal nociceptive activity and spinally mediated behavior during tonic pain [Articolo su rivista]
Porro, Carlo Adolfo; Cavazzuti, Milena; Lui, Fausta; Giuliani, Daniela; Pellegrini, Maddalena; Baraldi, Patrizia
abstract

The behavioral response to acute tissue injury is usually characterized by different phases, but the brain mechanisms underlying changes in pain-related behavior over time are still poorly understood. We aimed to analyze time-dependent changes in metabolic activity levels of 49 forebrain structures in the formalin pain model, using the autoradiographic 2-deoxyglucose method in unanesthetized, freely moving rats. We examined rats during the first phase of pain-related reactions ('early' groups), or during the third recovery phase, 60 min later, when the supraspinally mediated behavioral responses were reduced ('late' group). In the early groups, metabolic rates were bilaterally increased over control values in the periaqueductal gray, zona incerta and in several thalamic nuclei (anteroventral, centrolateral, lateral dorsal, parafascicular, posteromedial, submedius, ventromedial, and ventrobasal complex), as well as in the habenulae and in the parietal, cingulate, antero-dorsal insular, and anterior piriform cortex. A contralateral, somatotopically specific activation was found in the putative hindlimb representation area of the somatosensory cortex. In the late group, noxious-induced activation declined in most structures. However, metabolic rates were higher than controls in the periaqueductal gray and zona incerta and in two other structures not previously active: the prerubral area/field of Forel and the arcuate hypothalamic nucleus. These findings provide a time-dependent functional map of nociceptive and anti-nociceptive forebrain circuits during tonic pain. The parallel decrease in licking behavior and forebrain activity, at times when spinally mediated limb flexion responses were still present, suggests that endogenous antinociceptive systems may differently modulate spinal and supraspinal nociceptive networks following acute tissue injury. (C) 2003 International Association for the Study of Pain Published by Elsevier Science B.V. All fights reserved.


2003 - Representation of different trigeminal divisions within the primary and secondary human somatosensory cortex [Articolo su rivista]
Iannetti, G. D.; Porro, Carlo Adolfo; Pantano, P.; Romanelli, P. L.; Galeotti, F.; Cruccu, G.
abstract

Clinical, neurophysiological, and neuroimaging studies have yielded controversial results about the representation of the face in the somatosensory cortex. To clarify this issue we mechanically stimulated the left forehead (ophthalmic trigeminal division, V1) and left lower lip (mandibular trigeminal division, V3) in 14 healthy volunteers during acquisition of whole-brain fMRI images. During V1 and V3 stimulation the fMRI signal in the primary (SI) and secondary (SII) somatosensory cortices in the contralateral hemisphere increased. Within both SI and SII, the foci activated by stimulation of the two trigeminal divisions largely overlapped. In contrast, the ipsilateral representation differed. Whereas V3 stimulation activated the contralateral somatosensory cortex alone, V1 stimulation activated SI and SII bilaterally. These results to some extent contrast with electrophysiological data in monkeys and disclose distinct cortical representations within facial territories in humans. © 2003 Elsevier Science (USA). All rights reserved.


2003 - Tonic pain responses in mice: effects of sex, season, and day time [Articolo su rivista]
Perissin, L.; Facchin, P.; Porro, Carlo Adolfo
abstract

Seasonal and diurnal variations in tonic pain reactions were examined in female and male CBA/J mice maintained in a 12/12 dark/light cycle, at controlled temperature and humidity conditions. Animals were injected into the dorsum of one hindpaw with a dilute (20 mul, 1%) formalin solution. Pain-related behaviors were quantified as the time spent licking the injected paw and the number of flinching episodes. The experiments were performed during the first part of the light phase (Light: from 7 to 10 a.m.) or during the first part of the dark phase of the diurnal cycle (Dark: from 7 to 10 p.m.), in two different periods of the year: Spring (March-June) and Winter (November-January). Considering all data, females showed a slightly enhanced licking response, as well as an increase in the time spent in self-grooming, in comparison with males. In Spring, the licking and flinching responses were higher during the Dark phase than during the Light phase. This held for both sexes and for both phases of the behavioral response to formalin injection. By contrast, no significant diurnal variation in pain reactions was found in Winter. These seasonal and diurnal differences were not due to nonspecific changes in motor behavior, inasmuch as locomotor activity and self-grooming showed a different pattern: during the second phase after formalin, self-grooming was higher in the Light period in the experiments performed in Spring, whereas locomotor activity showed no significant seasonal changes. These results show that the behavioral reactions to prolonged noxious input, integrated both at spinal and supraspinal sites, undergo similar seasonal and diurnal variations in both sexes, strengthening the importance of chronobiological factors in the modulation of nociception.


2002 - Does anticipation of pain affect cortical nociceptive systems? [Articolo su rivista]
Porro, Carlo Adolfo; Baraldi, Patrizia; Pagnoni, Giuseppe; Serafini, M.; Facchin, P.; Maieron, Marta; Nichelli, Paolo Frigio
abstract

Anticipation of pain is a complex state that may influence the perception of subsequent noxious stimuli. We used functional magnetic resonance imaging (fMRI) to study changes of activity of cortical nociceptive networks in healthy volunteers while they expected the somatosensory stimulation of one foot, which might be painful (subcutaneous injection of ascorbic acid) or not. Subjects had no previous experience of the noxious stimulus. Mean fMRI signal intensity increased over baseline values during anticipation and during actual stimulation in the putative foot representation area of the contralateral primary somatosensory cortex (SI). Mean fMRI signals decreased during anticipation in other portions of the contralateral and ipsilateral SI, as well as in the anteroventral cingulate cortex. The activity of cortical clusters whose signal time courses showed positive or negative correlations with the individual psychophysical pain intensity curve was also significantly afected during the waiting period. Positively correlated clusters were found in the contralateral SI and bilaterally in the anterior cingulate, anterior insula, and medial prefrontal cortex. Negatively correlated clusters were found in the anteroventral cingulate bilaterally. In all of these areas, changes during anticipation were of the same sign as those observed during pain but less intense (similar to30-40% as large as peak changes during actual noxious stimulation). These results provide evidence for top-down mechanisms, triggered by anticipation, modulating cortical systems involved in sensory and affective components of pain even in the absence of actual noxious input and suggest that the activity of cortical nociceptive networks may be directly influenced by cognitive factors.


2002 - Human brain language by functional magnetic lexical decision task processing areas identified resonance imaging using a lexical decision task [Articolo su rivista]
CALANDRA BUONAURA, Giovanna; Basso, Gianpaolo; Gorno Tempini, Ml; Serafini, M.; Pagnoni, Giuseppe; Baraldi, Patrizia; Porro, Carlo Adolfo; Nichelli, Paolo Frigio
abstract

The purpose of this study was to validate a functional magnetic resonance imaging (fMRI) paradigm to activate both anterior and posterior language areas while collecting accuracy and reaction time data on subjects' performance. The paradigm was based on alternating graphemic and lexical decision tasks. In line with the classical model of language organisation, based on lesion data, and with the results of previous neuroimaging studies, cortical activation associated with lexical decision-making was strongly lateralised to the left hemisphere and involved a network of regions in the frontal, temporal and parietal lobes. Single subject analysis demonstrated that the activation paradigm we propose is suitable for detecting language processing areas in humans for clinical studies.


2001 - Explicit and incidental facial expression processing: an fMRI study [Articolo su rivista]
Gorno Tempini, Ml; Pradelli, S.; Serafini, M.; Pagnoni, Giuseppe; Baraldi, Patrizia; Porro, Carlo Adolfo; Nicoletti, Roberto; Umita, C.; Nichelli, Paolo Frigio
abstract

Considerable evidence indicates that processing facial expression involves both subcortical (amygdala and basal ganglia) and cortical (occipito-temporal, orbitofrontal, and prefrontal cortex) structures. However, the specificity of these regions for single types of emotions and for the cognitive demands of expression processing, is still unclear. This functional magnetic resonance imaging (fMRI) study investigated the neural correlates of incidental and explicit processing of the emotional content of faces expressing either disgust or happiness. Subjects were examined while they were viewing neutral, disgusted, or happy faces., The incidental task required subjects to decide about face gender, the explicit task to decide about face expression. In the control task subjects were requested to detect a white square in a greyscale mosaic stimulus. Results showed that the left inferior frontal cortex and the bilateral occipito-temporal junction responded equally to all face conditions. Several cortical and subcortical regions were modulated by task type, and by facial expression. Right neostriatum. and left amygdala were activated when subjects made explicit judgements of disgust, bilateral orbitofrontal cortex when they made judgement of happiness, and right frontal and insular cortex when they made judgements about any emotion.


2001 - Pattern of brain activity during mental imagery of eye movements [Abstract in Rivista]
Lui, Fausta; Baraldi, Patrizia; Benuzzi, Francesca; Fonda, Sergio; Maieron, Marta; Serafini, M; Nichelli, Paolo Frigio; Corazza, Ruggero; Porro, Carlo Adolfo
abstract

Previous studies have revealed that imagery of segmental motor events share a common neural substrate with actual motorperformance. The present study is aimed at investigating whether the cortical regions activated during imagined saccades overlap with areas activated during executed voluntary saccades.


2000 - Diurnal variations in tonic pain reactions in mice [Articolo su rivista]
Perissin, L.; Facchin, P.; Porro, Carlo Adolfo
abstract

Diurnal changes in the behavioural reactions to subcutaneous formalin injection (20 mu l, 1%) into the dorsum of an hindpaw were examined in female CBA/J mice aged 70-75 days, maintained in a 12/2 dark/light cycle (light on at 07.00 h; light off at 19.00 h). Mice showed higher pain scores, as expressed by the amount of time spent licking the injected paw and by the number of flinching episodes, when tested under red light at the beginning of the dark phase (19.00-22.00: Dark group) than when tested either under white or red light at the beginning of the light phase of the diurnal cycle (7.00-10.00). The increases in pain reactions at night were found both during the first (0-10 min) and the second (11-55 min) phase of the behavioural response to formalin injection. They were not due to aspecific increases in motor behaviour, since self-grooming actually decreased in the Dark group during the second phase of the response, and the amount of locomotor activity after the injection was similar to, or lower than, that found in mice tested in the morning under white or red light, respectively. In another group of female CBA/J mice tested in the hotplate apparatus (at a temperature of 52 degrees), paw-lick latencies were significantly higher in mice tested at dark during the night, whereas jump (escape) latencies were higher in the morning. These results demonstrate different diurnal variations in the reactions to brief or prolonged noxious stimulation in mice, with greater responses to tonic pain at the onset of the dark phase.


2000 - Ipsilateral involvement of primary motor cortex during motor imagery [Articolo su rivista]
Porro, Carlo Adolfo; Cettolo, V.; Francescato, M. P.; Baraldi, Patrizia
abstract

To investigate whether motor imagery involves ipsilateral cortical regions, we studied haemodynamic changes in portions of the motor cortex of 14 right-handed volunteers during actual motor performance (MP) and kinesthetic motor imagery (MI) of simple sequences of unilateral left or right finger movements, using functional magnetic resonance imaging (fMRI). Increases in mean normalized fMRI signal intensities over values obtained during the control (visual imagery) task were found during both MP and MI in the posterior part of the precentral gyrus and supplementary motor area, both on the contralateral and ipsilateral hemispheres. In the left lateral premotor cortex, fMRI signals were increased during imagery of either left or right finger movements. Ipsilateral cortical clusters displaying fMRI signal changes during both MP and MI were identified by correlation analyses in 10 out of 14 subjects; their extent was larger in the left hemisphere. A larger cortical population involved during both contralateral MP and MI was found in all subjects. The overall spatial extent of both the contralateral and the ipsilateral MP + MI clusters was similar to 90% of the whole cortical volume activated during MP. These results suggest that overlapping neural networks in motor and premotor cortex of the contralateral and ipsilateral hemispheres are involved during imagery and execution of simple motor tasks.


1999 - Bilateral representation of sequential finger movements in human cortical areas [Articolo su rivista]
Baraldi, Patrizia; Porro, Carlo Adolfo; M., Serafini; Pagnoni, Giuseppe; Nichelli, Paolo Frigio; Corazza, Ruggero; C., Murari
abstract

The spatial distribution of cortical neural clusters activated during movement of either hand ('bilateral' population), or only of one hand, was investigated in healthy right-handed volunteers performing a sequential finger opposition task, using echo-planar functional magnetic resonance imaging. 'Bilateral' clusters were found in the mesial premotor, perirolandic and adjacent lateral premotor cortex of the two hemispheres, and in the left superior parietal lobule. In the precentral gyrus, their spatial extent was larger on the left hemisphere. Clusters activated exclusively during contralateral finger movements were equally distributed in the left and right perirolandic cortex. No cluster activated exclusively during ipsilateral finger movements was detected. These findings support a role of the motor/lateral premotor cortex of the dominant hemisphere in bilateral motor control. (C) 1999 Elsevier Science ireland Ltd. All rights reserved.


1999 - CNS pattern of metabolic activity during tonic pain: evidence for modulation by beta-endorphin [Articolo su rivista]
Porro, Carlo Adolfo; Cavazzuti, Milena; Baraldi, Patrizia; Giuliani, Daniela; Ae, Panerai; Corazza, Ruggero
abstract

CNS correlates of acute prolonged pain, and the effects of partial blockade of the central beta-endorphin system, were investigated by the quantitative 2-deoxyglucose technique in unanaesthetized, freely moving rats. Experiments were performed during the second, tonic phase of the behavioural response to a prolonged chemical noxious stimulus (s.c. injection of dilute formalin into a forepaw), or after minor tissue injury (s.c. saline injection). During formalin-induced pain, local glucose utilization rates in the CNS were bilaterally increased in the grey matter of the cervical spinal cord, in spinal white matter tracts and in several supraspinal structures, including portions of the medullary reticular formation, locus coeruleus, lateral parabrachial region, anterior pretectal nucleus, the medial, lateral and posterior thalamic regions, basal ganglia, and the parietal, cingulate, frontal, insular and orbital cortical areas. Pretreatment with anti-beta-endorphin antibodies, injected i.c.v., led to increased metabolism in the tegmental nuclei, locus coeruleus, hypothalamic and thalamic structures, putamen, nucleus accumbens, diagonal band nuclei and dentate gyrus, and in portions of the parietal, cingulate, insular, frontal and orbital cortex. In formalin-injected rats, pretreated with anti-beta-endorphin, behavioural changes indicative of hyperalgesia (increased licking response) were found, which were paralleled by a significant enhancement of functional activity in the anterior pretectal nucleus and in thalamo-cortical systems. A positive correlation was found between the duration of the licking response and metabolic activity of several forebrain regions. These results provide a map of the CNS pattern of metabolic activity during tonic somatic pain, and demonstrate a modulatory role for beta-endorphin in central networks that process somatosensory inputs.


1999 - Functional magnetic resonance imaging as a tool for investigating human cortical motor function [Articolo su rivista]
Porro, Carlo Adolfo; Corazza, Ruggero
abstract

Non-invasive functional magnetic resonance imaging (fMRI) mapping techniques sensitive to the local changes of blood flow, blood volume, and blood oxygenation which accompany neuronal activation have been widely used over the last few years to investigate the functional organization of human cortical motor systems, and specifically of the primary motor cortex. Validation studies have demonstrated a good correspondence between quantitative and topographic aspects of data acquired by fMRI and positron emission tomography. The spatial and temporal resolution, affordable by fMRI has allowed to achieve new important information on the distributed representation of hand movements in multiple functional modules, and on the intensity and spatial extent of neural activation in the contralateral and ipsilateral primary motor cortex in relation to parametric and nonparametric aspects of movement and to the degree of handedness. Neural populations with different functional characteristics have been identified in anatomically defined regions, and the temporal aspects of the activation during voluntary movement tracked in different components of the motor system. Finally, this technique has proved useful to deepen our understanding of the neural basis of motor imagery, demonstrating increased activity in the primary motor cortex during mental representation of sequential finger movements.


1999 - Neural circuits underlying ketamine induced oculomotor behavior in the rat: 2-deoxyglucose studies [Articolo su rivista]
Porro, Carlo Adolfo; Biral, Gp; Benassi, Carlo; Cavazzuti, Milena; Baraldi, Patrizia; Lui, Fausta; Corazza, Ruggero
abstract

Time-related changes in oculomotor function and of metabolic activity patterns in selected brain networks, as assessed by the quantitative 2-deoxyglucose technique, were investigated in Long-Evans rats following intraperitoneal administration of a ketamine anesthetic dose. During ketamine-induced anesthesia a nystagmic-like behavior was present, characterized by unidirectional slow ocular drifts with superimposed paroxystic bursts of quick (saccadic-like) eye movements; all quick movements were executed in the horizontal direction, were strictly confined to an ocular hemifield of vision, and were followed by a backward (centripetal) drift. A metabolic hyperactivity was found in the dorsomedial shoulder region of the frontal cortex, corresponding to the rat saccadic cortical generator area, whereas functional activity levels were decreased in cerebellum and in several brainstem regions, including portions of the reticular formation and medial vestibular nuclei, putatively indicated as the locus of the oculomotor neural integrator. Starting 2 h after drug injection, a gradual recovery of oculomotor function occurred, with the disappearance of slow ocular drifts. However, an almost uninterrupted sequence of individual saccades was still present. Significant metabolic increases were found at this time in the cingulate and frontal cortex, basal ganglia, superior colliculus, paramedian reticular formation and oculomotor nuclei, the cerebellar vermis and paraflocculus. In medial vestibular nuclei, metabolic levels were undistinguishable from controls. These results suggest different concentration-dependent actions of ketamine on cortical and subcortical circuits involved in saccade generation and gaze holding. These effects are likely to be related at least in part to antagonism of N-methyl-D-aspartate receptor-mediated functions.


1998 - Temporal and intensity coding of pain in human cortex [Articolo su rivista]
Porro, Carlo Adolfo; Cettolo, V; Francescato, Mp; Baraldi, Patrizia
abstract

We used a high-resolution functional magnetic resonance imaging (fMRI) technique in healthy right-handed volunteers to demonstrate cortical areas displaying changes of activity significantly related to the time profile of the perceived intensity of experimental somatic pain over the course of several minutes. Twenty-four subjects (ascorbic acid group) received a subcutaneous injection of a dilute ascorbic acid solution into the dorsum of one foot, inducing prolonged burning pain (peak pain intensity on a 0-100 scale: 48 +/- 3, mean +/- SE; duration: 11.9 +/- 0.8 min). fMRI data sets were continuously acquired for similar to 20 min, beginning 5 min before and lasting 15 min after the onset of stimulation, from two sagittal planes on the medial hemispheric wall contralateral to the stimulated site, including the cingulate cortex and the putative foot representation area of the primary somatosensory cortex (SI). Neural clusters whose fMRI signal time courses were positively or negatively correlated (P < 0.0005) with the individual pain intensity curve were identified by cross-correlation statistics in all 24 volunteers. The spatial extent of the identified clusters was linearly related (P < 0.0001) to peak pain intensity. Regional analyses showed that positively correlated clusters were present in the majority of subjects in ST, cingulate, motor, and premotor cortex. Negative correlations were found predominantly in medial parietal, perigenual cingulate, and medial prefrontal regions. To test whether these neural changes were due to aspecific arousal or emotional reactions, related either to anticipation or presence of pain, fMRI experiments were performed with the same protocol in two additional groups of volunteers, subjected either to subcutaneous saline injection (saline: n = 16), inducing mild short-lasting pain (peak pain intensity 23 +/- 4; duration 2.8 +/- 0.6 min) or to nonnoxious mechanical stimulation of the skin (controls: n = 16) at the same body site. Subjects did not know in advance which stimulus would occur. The spatial extent of neural clusters whose signal time courses were positively or negatively correlated with the mean pain intensity curve of subjects injected with ascorbic acid was significantly larger (P < 0.001) in the ascorbic acid group than both saline and controls, suggesting that the observed responses were specifically related to pain intensity and duration. These findings reveal distributed cortical systems, including parietal areas as well as cingulate and frontal regions, involved in dynamic encoding of pain intensity over time, a process of great biological and clinical relevance.


1996 - Functional imaging studies of the pain system in man and animals [Capitolo/Saggio]
Porro, Carlo Adolfo; Cavazzuti, Milena
abstract

ND


1996 - Primary motor and sensory cortex activation during motor performance and motor imagery: A functional magnetic resonance imaging study [Articolo su rivista]
Porro, Carlo Adolfo; Francescato, Mp; Cettolo, V; Diamond, Me; Baraldi, Patrizia; Zuiani, C; Bazzocchi, M; Diprampero, Pe
abstract

The intensity and spatial distribution of functional activation in the left precentral and postcentral gyri during actual motor performance (MP) and mental representation [motor imagery (MI)] of self-paced finger-to-thumb opposition movements of the dominant hand were investigated in fourteen right-handed volunteers by functional magnetic resonance imaging (fMRI) techniques. Significant increases in mean normalized fMRI signal intensities over values obtained during the control (visual imagery) tasks were found in a region including the anterior bank and crown of the central sulcus, the presumed site of the primary motor cortex, during both MP (mean percentage increase, 2.1%) and MI (0.8%). In the anterior portion of the precentral gyrus and the postcentral gyrus, mean functional activity levels were also increased during both conditions (MP, 1.7 and 1.2%; MI, 0.6 and 0.4%, respectively). To locate activated foci during MI, MP, or both conditions, the time course of the signal intensities of pixels lying in the precentral or postcentral gyrus was plotted against single-step or double-step waveforms, where the steps of the waveform corresponded to different tasks. Pixels significantly (r > 0.7) activated during both MP and MI were identified in each region in the majority of subjects; percentage increases in signal intensity during MI were on average 30% as great as increases during MP. The pixels activated during both MP and MI appear to represent a large fraction of the whole population-activated during MP. These results support the hypothesis that MI and MP involve overlapping neural networks in perirolandic cortical areas.


1994 - Reply to B. Linderoth and E. Brodin [Abstract in Rivista]
Porro, C. A.; Aloisi, A. M.; Carli, G.; Cavazzuti, M.; Baraldi, P.
abstract


1993 - 'Mirror pain' in the formalin test: behavioral and 2-deoxyglucose studies [Articolo su rivista]
A. M., Aloisi; Porro, Carlo Adolfo; Cavazzuti, Milena; Baraldi, Patrizia; G., Carli
abstract

Subcutaneous injection of a dilute formaldehyde solution (5 or 10%) into a hind paw induced, in the majority of rats, the appearance of 'mirror pain': licking the contralateral untreated hind paw 10-60 min after injection. Contralateral licking activity was much less frequent than the ipsilaterally directed one, but the overall intensities of the two responses were positively correlated. Qualitatively, the two behaviours were similar. Functional activity levels of the lumbar spinal cord, as revealed by the 2-deoxyglucose (2-DG) technique, were increased bilaterally over the first hour after unilateral hind limb formalin injection in unanesthetized, freely moving rats. The enhancement of the [C-14]2-DG uptake could be detected both in dorsal and ventral horns, as well as in the gray matter surrounding the central canal, and the anterolateral and dorsolateral funiculi. These metabolic changes may reflect an enhancement of the functional activity of both interneuronal pools and units projecting to supraspinal centers, giving rise to a referred contralateral pain.


1993 - Spatial and temporal aspects of spinal cord and brainstem activation in the formalin pain model [Articolo su rivista]
Porro, Carlo Adolfo; Cavazzuti, M.
abstract

ND


1992 - Central changes of beta-endorphin-like immunoreactivity during rat tonic pain differ from those of purified beta-endorphin. [Articolo su rivista]
Facchinetti, Fabio; Tassinari, G.; Porro, Carlo Adolfo; Galetti, A.; Genazzani, Andrea Riccardo
abstract

Several studies have described changes in beta-endorphin-like immunoreactivity (beta-ELI) in the rat brain in response to pain and stress stimuli. In order to ascertain the components of beta-ELI, brain samples of rats experiencing acute prolonged (tonic) pain were evaluated for their beta-ELI and later submitted to a chromatographic purification allowing the measurement of beta-endorphin (beta-EP) and acetyl beta-EP. The chromatographic analysis of both ventromedial hypothalamus (VMH) and periaqueductal grey (PAG) homogenates indicates that beta-ELI is distributed in several fractions including shortened forms of beta-EP and their respective acetylated compounds. Quantitatively, while beta-ELI in formalin-injected animals was increased by 48\% in VMH and 45\% in PAG in respect to controls, the net increase of purified beta-EP was 1100\% and 470\%, respectively, for VMH and PAG. Moreover, the maximal increase of beta-ELI was evident at 120 min, in both tissues. In contrast, the beta-EP peak was reached at 30 min in VMH and at 60 min in PAG. Acetyl beta-EP was unchanged by treatment in both central areas. No correlation of beta-ELI and beta-EP was found in VMH. These data demonstrate that the evaluation of beta-ELI gives a poor estimate of beta-EP changes, due to several components of the endorphin family.


1991 - Brain and Spinal Cord Metabolic Activity during Propofol Anaesthesia [Articolo su rivista]
Cavazzuti, Milena; Porro, Carlo Adolfo; Barbieri, Alberto; G., Galetti
abstract

We have investigated the effects of propofol anaesthesia on the metabolic activity pattern of 35 regions of the rat brain and cervical spinal cord using the 14C-2-deoxyglucose technique. Anaesthesia was produced by an i.v. bolus of the commercial preparation of the drug (8 mg kg-1) and maintained with successive bolus administrations of 6 mg kg-1. Functional activity values (expressed as rates of local utilization of glucose) were reduced in 31 grey matter and two white matter structures in a propofol group relative both to saline-injected and vehicle-injected (aqueous emulsion containing 10% soya bean oil, 1.2% egg phosphatide and 2.25% glycerol) controls. Values from the two control groups did not differ significantly. Propofol-induced depression of metabolic activity was present in central nervous system regions belonging to sensory (auditory, visual and somatosensory), motor and limbic systems, including spinal cord grey matter. Mean percentage decreases ranged from 40% (vestibular nuclei) to 76% (cingulate cortex). Although these values may be slightly overestimated because of the modest increase in PaCo2 in the anaesthetized group, propofol appeared to elicit generalized reduction of central nervous system functional activity.


1991 - Functional activity mapping of the rat brainstem during formalin-induced noxious stimulation [Articolo su rivista]
Porro, Carlo Adolfo; Cavazzuti, Milena; Galetti, A.; Sassatelli, L.
abstract

Functional activity changes in 35 selected structures of the rat brainstem elicited by subcutaneous formalin injection in a forepaw were investigated by the [14C]2-deoxyglucose method in unanesthetized, freely moving animals. Experiments were initiated 2 min ("early" group) or 60 min ("late" group) after the injection. Treatment induced a significant increase of [14C]2-deoxyglucose uptake relative to controls in 17 structures of the "early" group, including portions of the bulbar, pontine and mesencephalic reticular formation, nucleus raphe magnus, median and dorsal raphe nuclei, the ventrolateral and dorsal subdivisions of the periaqueductal gray matter, deep layers of the superior colliculus and the anterior pretectal nucleus. Most changes were bilateral, with the exception of the increases observed in the nucleus reticularis paragigantocellularis and the lateral parabrachial area, which were contralateral, and the one in the mesencephalic reticular formation, which was ipsilateral to the injected paw. In pentobarbital-anesthetized rats a significant difference in metabolic activity values between formalin- and saline-injected animals was only detected at the medullary level. In the "late" unanesthetized formalin group functional activity levels were higher than controls in four structures, including the lateral reticular and paragigantocellular nuclei, contralaterally, and nucleus cuneiformis and ventrolateral periaqueductal gray matter, bilaterally. No between-groups difference was observed in visual or auditory structures. These results provide evidence for activation of several brainstem regions, which are conceivably involved in different sensory, motivational or motor circuits, during the initial phase of formalin-evoked noxious stimulation in unanesthetized animals. Functional changes blunted over time as did pain-related behavior integrated at the supraspinal level, but they persisted in some brainstem regions for which involvement in endogenous antinociceptive systems have been suggested. The mechanisms underlying these time-related changes need to be clarified. © 1991.


1991 - Functional activity mapping of the rat spinal cord during formalin-induced noxious stimulation [Articolo su rivista]
Porro, Carlo Adolfo; Cavazzuti, Milena; Galetti, A.; Sassatelli, L.; Barbieri, G. C.
abstract

The functional activity pattern in the cervical enlargement of the spinal cord (as expressed by changes in local glucose utilization) was investigated by the semi-quantitative [14C]2-deoxyglucose technique 2 min ("early" group) or 60 min ("late" group) after injection of a small amount of dilute formalin (0.06-0.08 ml, 5%) in a forepaw of unanesthetized, freely-moving rats. Control animals were either injected with an equivalent volume of saline or simply handled. In both formalin groups a tonic flexion of the injected limb was present during the experiments, while supraspinal-integrated behavior (such as licking the affected paw) was sharply reduced in the late group. A bilateral increase of metabolic activity indexes, more pronounced on the ipsilateral side, was found in the "early" formalin-injected animals. The highest increase over control values was found in the medial part of the superficial (laminae I-II) region of the ipsilateral dorsal horn. However, the [14C]2-deoxyglucose uptake was found to be elevated over the whole extent of the dorsal horns, as well as in the gray matter surrounding the central canal, anterior horns and ipsilateral dorsolateral funiculus. In a parallel group of experiments performed in pentobarbital-anesthetized rats metabolic increases in the early period after formalin injection were less pronounced; they were only found in the ipsilateral side of the cord. In the "late" formalin group the overall metabolic changes were less conspicuous. They were mainly observed in the side ipsilateral to the injection, the highest increase being found in the deep portion (laminae V-VI) of the dorsal horn. Therefore, the spatial distribution of functional activation elicited during prolonged noxious stimulation in the spinal cord gray matter of unanesthetized rats varies accorcling to time and changes in animal behavior. © 1991.


1989 - The interstitial nucleus of the superior fasciculus, posterior bundle (INSFp) in the guinea pig: another nucleus of the accessory optic system processing the vertical retinal slip signal. [Articolo su rivista]
Benassi, Carlo; Biral, Giampaolo; Lui, Fausta; Porro, Carlo Adolfo; Corazza, Ruggero
abstract

As in rabbit, gerbil, and rat, the guinea pig interstitial nucleus of the superior fasciculus, posterior bundle (INSFp) is a sparse assemblage of neurons scattered among the fibers forming the fasciculus bearing this name. Most of the INSFp neurons are small and are ovoid in shape. Interspersed among these, are a few larger, elongated neurons whose density becomes greater and whose shape becomes fusiform in correspondence to the zone of transition from the superior fasciculus to the ventral part of the medial terminal nucleus (MTN). Like the MTN, the INSFp is activated by retinal-slip signals evoked by whole-field visual patterns moving in the vertical direction, as shown by the increase of 14C-2-deoxyglucose (2DG) uptake into this nucleus. At the same level of luminous flux, neither pattern moving in the horizontal direction nor the same pattern held stationary can elicit increases in the INSFp 2DG assumption. The specificity of the observed increases in metabolic rates in INSFp following vertical whole-field motion suggests that this assemblage of neurons relays visual signals used in the control of vertical optokinetic nystagmus.


1987 - Correspondence between the activation of the nucleus tractus optici and the appearance of optokinetic nystagmus in the albino guinea pig [Articolo su rivista]
Biral, Giampaolo; Benassi, Carlo; Lui, Fausta; Porro, Carlo Adolfo; Cavazzuti, Milena; Corazza, Ruggero
abstract

It is known that albinism is accompanied by several visual disturbances. The anomalous features of the optokinatic eye nystagmus (OKN) found in albino strains of different species have been ascribed to he same visual defects. The occurrence of a clear horizontal OKN in albino Guinea pig led us to investigate activity in the Nucleus of the optic tract (NOT)