Mirta Fiorio | Università di Verona (original) (raw)

Papers by Mirta Fiorio

Experimental Brain Research, 2012

The purpose of the present experiment was to investigate the effects of emotional interference on... more The purpose of the present experiment was to investigate the effects of emotional interference on consolidation of sequential learning. In different sessions, 6 groups of subjects were initially trained on a serial reaction time task (SRTT). To modulate consolidation of the newly learned skill, subjects were exposed, after the training, to 1 of 3 (positive, negative or neutral) different classes of emotional stimuli which consisted of a set of emotional pictures combined with congruent emotional musical pieces or neutral sound. Emotional intervention for each subject group was done in 2 different time intervals (either directly after the training session or 6 h later). After a 72 h post-training interval, each group was retested on the SRTT. Re-test performance was evaluated in terms of response times and accuracy during execution of a target sequence. Emotional intervention did not influence either response times or accuracy of re-testing SRTT target task performance, both variables sensitive to implicit knowledge acquired during SRTT training. However, explicit awareness of sequence knowledge after 72 h was enhanced when negative stimuli had been applied at 0 h after training. These findings suggest that consolidation of explicit aspects of procedural learning may be more responsive toward emotional interference than implicit aspects.

Neurology, Mar 11, 2003

Motor and nonmotor timing functions and cross-modal processing of visual-tactile signals may be l... more Motor and nonmotor timing functions and cross-modal processing of visual-tactile signals may be linked to basal ganglia. These neural structures are thought to be dysfunctional in dystonia. To test whether cross-modal stimulation influences deficits of temporal discrimination in dystonia. Eight patients with generalized dystonia and 10 control subjects were asked to discriminate whether pairs of unimodal (tactile or visual) and cross-modal (visual and tactile) stimuli were simultaneous or sequential and, in the latter case, which stimulus preceded the other. Visual stimuli consisted of red lights and tactile stimuli of non-noxious electrical shocks. Intervals between stimuli in each pair were increased from 0 to 400 msec (in steps of 10 msec). Patients with dystonia recognized the asynchrony between the experimental stimuli and judged correctly which stimulus in a pair came first, at significantly longer intervals than did controls. Moreover, differences in performance between patients and controls were maximal for cross-modal stimuli. The defective performance of patients with dystonia in the cross-modal combinations showed a high positive correlation with the severity of symptoms. Patients with generalized dystonia present with difficulties both in timing functions and in cross-modal processing of visual-tactile stimuli.

Journal of Neurology, Feb 1, 2004

Psychophysical studies show alterations of cross-modal integration and timing processes in patien... more Psychophysical studies show alterations of cross-modal integration and timing processes in patients with generalized and focal hand dystonia. Here we assess the capability of 10 cervical dystonia patients, 5 patients with cervical pain but no dystonia, and 10 healthy controls to determine whether pairs of visual, tactile or visuo-tactile stimuli were simultaneous or sequential (TD threshold) and which stimulus preceded the other (temporal order judgement, TOJ). Visual stimuli consisted of light emitting diodes and tactile stimuli of non-noxious electrical shocks delivered to the hands. Intervals between stimuli were increased from 0 to 400 ms in steps of 10 ms. Cervical dystonia patients had a clear impairment of tactile and visuo-tactile temporal discrimination compared with patients with cervical pain but no dystonia who performed as well as healthy subjects. This suggests that deficits of temporal discrimination in cervical dystonia patients are not due to the possible distracting effect of unpleasant sensations or pain. Comparisons with previous studies show that deficits in cervical dystonia were more severe than in focal hand dystonia and less severe than in generalized dystonia. Thus, impairment of sensory timing may be a marker of disease, which varies along a continuum in the different forms of dystonia.

Frontiers in Behavioral Neuroscience, 2009

Neuropsychologia, 2015

Traditional definitions of focal dystonia point to its motor component, mainly affecting planning... more Traditional definitions of focal dystonia point to its motor component, mainly affecting planning and execution of voluntary movements. However, focal dystonia is tightly linked also to sensory dysfunction. Accurate motor control requires an optimal processing of afferent inputs from different sensory systems, in particular visual and somatosensory (e.g., touch and proprioception). Several experimental studies indicate that sensory-motor integration - the process through which sensory information is used to plan, execute, and monitor movements - is impaired in focal dystonia. The neural degenerations associated with these alterations affect not only the basal ganglia-thalamic-frontal cortex loop, but also the parietal cortex and cerebellum. The present review outlines the experimental studies describing impaired sensory-motor integration in focal dystonia, establishes their relationship with changes in specific neural mechanisms, and provides new insight towards the implementation of novel intervention protocols. Based on the reviewed state-of-the-art evidence, the theoretical framework summarized in the present article will not only result in a better understanding of the pathophysiology of dystonia, but it will also lead to the development of new rehabilitation strategies.

NeuroImage

Our understanding of how genotype determines phenotype in primary dystonia is limited. Familial y... more Our understanding of how genotype determines phenotype in primary dystonia is limited. Familial young-onset primary dystonia is commonly due to the DYT1 gene mutation. A critical question, given the 30% penetrance of clinical symptoms in DYT1 mutation carriers, is why the same genotype leads to differential clinical expression and whether non-DYT1 adult-onset primary dystonia, with and without family history share pathophysiological mechanisms with DYT1 dystonia. This study examines the relationship between dystonic phenotype and the DYT1 gene mutation by monitoring whole-brain structure using voxel-based morphometry. We acquired magnetic resonance imaging data of symptomatic and asymptomatic DYT1 mutation carriers, of non-DYT1 primary dystonia patients, with and without family history and control subjects with normal DYT1 alleles. By crossing the factors genotype and phenotype we demonstrate a significant interaction in terms of brain anatomy confined to the basal ganglia bilateral...

PLOS ONE, 2015

As recently demonstrated, a placebo procedure in motor performance increases force production and... more As recently demonstrated, a placebo procedure in motor performance increases force production and changes the excitability of the corticospinal system, by enhancing the amplitude of the motor evoked potentials (MEP) and reducing the duration of the cortical silent period (CSP). However, it is not clear whether these neurophysiological changes are related to the behavioural outcome (increased force) or to a general effect of expectation. To clarify this, we investigated the nocebo effect, in which the induced expectation decreases force production. Two groups of healthy volunteers (experimental and control) performed a motor task by pressing a piston with the right index finger. To induce a nocebo effect in the experimental group, low frequency transcutaneous electrical nerve stimulation (TENS) was applied over the index finger with instructions of its detrimental effects on force. To condition the subjects, the visual feedback on their force level was surreptitiously reduced after TENS. Results showed that the experimental group reduced the force, felt weaker and expected a worse performance than the control group, who was not suggested about TENS. By applying transcranial magnetic stimulation over the primary motor cortex, we found that while MEP amplitude remained stable throughout the procedure in both groups, the CSP duration was shorter in the experimental group after the nocebo procedure. The CSP reduction resembled previous findings on the placebo effect, suggesting that expectation of change in performance diminishes the inhibitory activation of the primary motor cortex, independently of the behavioural outcome.

Frontiers in Human Neuroscience, 2014

Dystonia has historically been considered a disorder of the basal ganglia, mainly affecting plann... more Dystonia has historically been considered a disorder of the basal ganglia, mainly affecting planning and execution of voluntary movements. This notion comes from the observation that most lesions responsible for secondary dystonia involve the basal ganglia. However, what emerges from recent research is that dystonia is linked to the dysfunction of a complex neural network that comprises basal ganglia-thalamic-frontal cortex, but also the inferior parietal cortex and the cerebellum. While dystonia is clearly a motor problem, it turned out that sensory aspects are also fundamental, especially those related to proprioception. We outline experimental evidence for proprioceptive dysfunction in focal dystonia from intrinsic sensory abnormalities to impaired sensorimotor integration, which is the process by which sensory information is used to plan and execute volitional movements. Particularly, we will focus on proprioceptive aspects of dystonia, including: (i) processing of vibratory input, (ii) temporal discrimination of two passive movements, (iii) multimodal integration of visual-tactile and proprioceptive inputs, and (iv) motor control in the absence of visual feedback. We suggest that these investigations contribute not only to a better understanding of dystonia pathophysiology, but also to develop rehabilitation strategies aimed at facilitating the processing of proprioceptive input.

Frontiers in Behavioral Neuroscience, 2009

Frontiers in Behavioral Neuroscience, 2009

Neuroscience, 2010

Brain mechanisms for action understanding rely on matching the observed actions into the viewer&a... more Brain mechanisms for action understanding rely on matching the observed actions into the viewer's motor system. Health professionals, who treat patients affected by movement disorders as dystonia, frequently see hyperkinetic action patterns characterized by an overflow of muscle co-contractions. To avert an overload of the motor system during observation of those actions, they might need to look at dystonic motor symptoms in a cool, detached way. To investigate whether visual expertise about atypical movement kinematics influences the viewer's motor system, we applied transcranial magnetic stimulation to clinicians and to naive subjects, while they observed handwriting actions performed with two different kinematics: fluent and non-fluent. Crucially, the latter movement pattern was easily recognized by the clinicians as a typical expression of writer's cramp, whereas it was unknown to the naive subjects. Results showed that clinicians had similar corticospinal activation during observation of dystonic and healthy writings, whereas naive subjects were hyper-activated during observation of dystonic movements. Hyper-activation was selective for the muscles directly involved in the dystonic co-contractions and inversely correlated with subjective movement fluency scores, hinting at a fine-tuned association between the breakdown of observed movement fluency and corticospinal activation. These findings suggest that observation of unusual pathological actions differently modulates the viewer's motor system, depending on knowledge, visual expertise, and ability in recognizing suboptimal movement kinematics.

PLoS ONE, 2014

Sensory alterations, a common feature of such movement disorders as Parkinson&amp... more Sensory alterations, a common feature of such movement disorders as Parkinson's disease (PD) and dystonia, could emerge as epiphenomena of basal ganglia dysfunction. Recently, we found a selective reduction of tactile perception (Aristotle's illusion, the illusory doubling sensation of one object when touched with crossed fingers) in the affected hand of patients with focal hand dystonia. This suggests that reduced tactile illusion might be a specific feature of this type of dystonia and could be due to abnormal somatosensory cortical activation. The aim of the current study was to investigate whether Aristotle's illusion is reduced in the affected hand of patients with PD. We tested 15 PD patients, in whom motor symptoms were mainly localised to one side of the body, and 15 healthy controls. Three pairs of fingers were tested in crossed (evoking the illusion) or parallel position (not evoking the illusion). A sphere was placed in the contact point between the two fingers and the blindfolded participants had to say whether they felt one or two stimuli. Stimuli were applied on the affected and less or unaffected side of the PD patients. We found no difference in illusory perception between the PD patients and the controls, nor between the more affected and less/unaffected side, suggesting that Aristotle's illusion is preserved in PD. The retained tactile illusion in PD and its reduction in focal hand dystonia suggest that the basal ganglia, which are dysfunctional in both PD and dystonia, may not be causally involved in this function. Instead, the level of activation between digits in the somatosensory cortex may be more directly involved. Finally, the similar percentage of illusion in the more affected and less or unaffected body sides indicates that the illusory perception is not influenced by the presence or amount of motor symptoms.

In order to obtain further information on the pathophysiology of functional tremor, we assessed t... more In order to obtain further information on the pathophysiology of functional tremor, we assessed tactile discrimination threshold and proprioceptive temporal discrimination motor threshold values in 11 patients with functional tremor, 11 age- and sex-matched patients with essential tremor and 13 healthy controls. Tactile discrimination threshold in both the right and left side was significantly higher in patients with functional tremor than in the other groups. Proprioceptive temporal discrimination threshold for both right and left side was significantly higher in patients with functional and essential tremor than in healthy controls. No significant correlation between discrimination thresholds and duration or severity of tremor was found. Temporal processing of tactile and proprioceptive stimuli is impaired in patients with functional tremor. The mechanisms underlying this impaired somatosensory processing and possible ways to apply these findings clinically merit further research.

Journal of cognitive neuroscience, Jan 16, 2014

It is solidly established that top-down (goal-driven) and bottom-up (stimulus-driven) attention m... more It is solidly established that top-down (goal-driven) and bottom-up (stimulus-driven) attention mechanisms depend on distributed cortical networks, including prefrontal and frontoparietal regions. Instead, it is less clear whether the BG also contribute to one or the other of these mechanisms, or to both. The current study was principally undertaken to clarify this issue. Parkinson's disease (PD), a neurodegenerative disorder primarily affecting the BG, has proven to be an effective model for investigating the contribution of the BG to different brain functions; therefore, we set out to investigate deficits of top-down and bottom-up attention in a selected cohort of PD patients. With this objective in mind, we compared the performance on three computerized tasks of two groups of 12 parkinsonian patients (assessed without any treatment), one otherwise pharmacologically treated and the other also surgically treated, with that of a group of controls. The main behavioral tool for ou...

Journal of Neuroscience, 2014

Despite behavioral evidence showing placebo modulations of motor performance, the neurophysiologi... more Despite behavioral evidence showing placebo modulations of motor performance, the neurophysiological underpinnings of these effects are still unknown. By applying transcranial magnetic stimulation (TMS) over the primary motor cortex, we investigated whether a placebo modulation of force could change the excitability of the corticospinal system. Healthy human volunteers performed a motor task by pressing a piston as strongly as possible with the right index finger. Two experimental groups were instructed that treatment with peripheral low-frequency transcutaneous electrical nerve stimulation (TENS) applied on the first dorsal interosseus would induce force enhancement. One experimental group was conditioned about the effects of TENS with a surreptitious amplification of the visual feedback signaling the force level. The other group, instead, was only verbally influenced, without conditioning. At the end of the instructive placebo procedure, the two experimental groups reached higher levels of force, believed that TENS had been effective and expected to perform better compared with two control groups, who were not influenced about TENS. Moreover, the experimental groups presented enhanced excitability of the corticospinal system in the muscle specifically involved in the task (first dorsal interosseus), as shown by increased amplitude of the motor evoked potentials and decreased duration of the cortical silent period (the latter only in the conditioned group). Crucially, the TMS pulse was delivered when all the subjects exerted the same amount of force, ruling out bottom-up influences. These findings hint at a top-down, cognitive enhancement of corticospinal excitability as a neural signature of placebo modulation of motor performance.

Social Neuroscience, 2013

This study was designed to combine two, otherwise separated, fields of research regarding motor r... more This study was designed to combine two, otherwise separated, fields of research regarding motor resonance and mimicry by adopting a naturalistic mimicry paradigm while probing motor resonance with transcranial magnetic stimulation (TMS). At stake was whether the motor system resonates instantaneously with unobtrusive nonverbal behavior of another person. We measured excitability in the left and right hand while participants viewed sequences of video clips and static images. In the video clips an actor performed several clerical tasks, while either inconspicuously touching his face (face-touching (FT) condition) or not (no face-touching (NFT) condition). We found that excitability was higher in the FT condition than in the NFT and baseline conditions. Furthermore, our data showed a general heightened excitability in the left motor cortex relative to the right. Taken together, the results suggest that observed hand-face gestures--even though outside the primary focus of attention and occurring inconspicuously throughout an ongoing action setting--can cause instantaneous resonant activity in the observer's motor system. It thus supports the idea of motor resonance involvement in mimicry and demonstrates that this can be studied using a naturalistic mimicry paradigm.

PLoS ONE, 2013

Performance of timed motor sequences relies on the cerebellum and basal ganglia, which integrate ... more Performance of timed motor sequences relies on the cerebellum and basal ganglia, which integrate proprioceptive information during the motor task and set internal timing mechanisms. Accordingly, these structures are also involved in other temporal processes, such as the discrimination of the different afferent information in the domain of time. In the present study we tested temporal processing of proprioceptive and tactile stimuli in 20 patients with neurodegenerative cerebellar ataxia and 20 age- and sex-matched healthy subjects. Tactile temporal discrimination threshold was defined as the value at which subjects recognized the two stimuli as asynchronous. Temporal discrimination movement threshold of the first dorsal interosseous and flexor carpi radialis was defined as the shortest interval between two paired electrical stimuli in which the subjects blindfolded perceived two separate index finger abductions and wrist flexions. Both tactile and movement temporal discrimination thresholds were higher in patients with cerebellar ataxia. No correlation was found with disease duration and severity. Our study demonstrates that temporal processing of tactile and proprioceptive stimuli is impaired in patients with cerebellar neurodegeneration and highlights the involvement of cerebellum in temporal processing of somatosensory stimuli of different type.

Neuroscience Letters, 2007

Perception of limb position and motion is abnormal in Parkinson&a... more Perception of limb position and motion is abnormal in Parkinson's disease (PD). Despite the fact that the processing of proprioceptive inputs is inherently temporal, most studies have assessed spatial aspects of proprioception in PD patients. Here, we use a recently described method to test whether deficits also exist in temporal discrimination of proprioceptive inputs. We induced index finger abduction or wrist flexion through percutaneous electrical stimulation of the motor point of the first dorsal interosseous muscle (FDI) or the flexor carpii radialis (FCR), respectively. Twelve patients with unilateral bradykinetic-rigid PD and 12 healthy subjects were asked to report whether pairs of stimuli separated by different time intervals produced single or double index finger abduction movement or wrist flexion. The shortest interval at which subjects reported two separated movements was considered as temporal movement discrimination threshold. Results showed that thresholds were significantly higher in PD patients than in control subjects for both FCR and FDI muscle, thus demonstrating for the first time that temporal proprioceptive processing is altered in PD.

Neuroscience, 2012

Transcranial magnetic stimulation (TMS) studies have shown that the motor system is facilitated w... more Transcranial magnetic stimulation (TMS) studies have shown that the motor system is facilitated when we imagine performing motor actions. However, it is not clear whether the individual's motor system modulates bilaterally and selectively for task parameters, such as movement direction and amplitude. To investigate this issue, we applied single-pulse TMS over the left and right primary motor cortex (M1) of healthy subjects, who had to imagine grasping and rotating a clock hour hand, having a starting position at noon, towards four different times: 2, 5, 7 and 10 o'clock. Rotations could be in clockwise (2 and 5 o'clock) or counter-clockwise (7 and 10 o'clock) directions and could require small (2 and 10 o'clock) or large (5 and 7 o'clock) rotation angle. TMS motor-evoked potentials were recorded for three muscles, and movements were imagined with the right and left hands. Results showed that during motor imagery a mirroring pattern was present between the right and the left motor cortices, showing selective activation of the hand-intrinsic muscles spatially close to the direction of the imagined movement. Overall a higher activation for large and a lower activation for small rotation angle were found, but no selective muscle activity was present within the hand-intrinsic muscles for this parameter. Following these results we propose that during action imagination an internally coded covariance between movement parameters is present with a muscle-specific activation for movement direction. Ó

Experimental Brain Research, 2012

The purpose of the present experiment was to investigate the effects of emotional interference on... more The purpose of the present experiment was to investigate the effects of emotional interference on consolidation of sequential learning. In different sessions, 6 groups of subjects were initially trained on a serial reaction time task (SRTT). To modulate consolidation of the newly learned skill, subjects were exposed, after the training, to 1 of 3 (positive, negative or neutral) different classes of emotional stimuli which consisted of a set of emotional pictures combined with congruent emotional musical pieces or neutral sound. Emotional intervention for each subject group was done in 2 different time intervals (either directly after the training session or 6 h later). After a 72 h post-training interval, each group was retested on the SRTT. Re-test performance was evaluated in terms of response times and accuracy during execution of a target sequence. Emotional intervention did not influence either response times or accuracy of re-testing SRTT target task performance, both variables sensitive to implicit knowledge acquired during SRTT training. However, explicit awareness of sequence knowledge after 72 h was enhanced when negative stimuli had been applied at 0 h after training. These findings suggest that consolidation of explicit aspects of procedural learning may be more responsive toward emotional interference than implicit aspects.

Neurology, Mar 11, 2003

Motor and nonmotor timing functions and cross-modal processing of visual-tactile signals may be l... more Motor and nonmotor timing functions and cross-modal processing of visual-tactile signals may be linked to basal ganglia. These neural structures are thought to be dysfunctional in dystonia. To test whether cross-modal stimulation influences deficits of temporal discrimination in dystonia. Eight patients with generalized dystonia and 10 control subjects were asked to discriminate whether pairs of unimodal (tactile or visual) and cross-modal (visual and tactile) stimuli were simultaneous or sequential and, in the latter case, which stimulus preceded the other. Visual stimuli consisted of red lights and tactile stimuli of non-noxious electrical shocks. Intervals between stimuli in each pair were increased from 0 to 400 msec (in steps of 10 msec). Patients with dystonia recognized the asynchrony between the experimental stimuli and judged correctly which stimulus in a pair came first, at significantly longer intervals than did controls. Moreover, differences in performance between patients and controls were maximal for cross-modal stimuli. The defective performance of patients with dystonia in the cross-modal combinations showed a high positive correlation with the severity of symptoms. Patients with generalized dystonia present with difficulties both in timing functions and in cross-modal processing of visual-tactile stimuli.

Journal of Neurology, Feb 1, 2004

Psychophysical studies show alterations of cross-modal integration and timing processes in patien... more Psychophysical studies show alterations of cross-modal integration and timing processes in patients with generalized and focal hand dystonia. Here we assess the capability of 10 cervical dystonia patients, 5 patients with cervical pain but no dystonia, and 10 healthy controls to determine whether pairs of visual, tactile or visuo-tactile stimuli were simultaneous or sequential (TD threshold) and which stimulus preceded the other (temporal order judgement, TOJ). Visual stimuli consisted of light emitting diodes and tactile stimuli of non-noxious electrical shocks delivered to the hands. Intervals between stimuli were increased from 0 to 400 ms in steps of 10 ms. Cervical dystonia patients had a clear impairment of tactile and visuo-tactile temporal discrimination compared with patients with cervical pain but no dystonia who performed as well as healthy subjects. This suggests that deficits of temporal discrimination in cervical dystonia patients are not due to the possible distracting effect of unpleasant sensations or pain. Comparisons with previous studies show that deficits in cervical dystonia were more severe than in focal hand dystonia and less severe than in generalized dystonia. Thus, impairment of sensory timing may be a marker of disease, which varies along a continuum in the different forms of dystonia.

Frontiers in Behavioral Neuroscience, 2009

Neuropsychologia, 2015

Traditional definitions of focal dystonia point to its motor component, mainly affecting planning... more Traditional definitions of focal dystonia point to its motor component, mainly affecting planning and execution of voluntary movements. However, focal dystonia is tightly linked also to sensory dysfunction. Accurate motor control requires an optimal processing of afferent inputs from different sensory systems, in particular visual and somatosensory (e.g., touch and proprioception). Several experimental studies indicate that sensory-motor integration - the process through which sensory information is used to plan, execute, and monitor movements - is impaired in focal dystonia. The neural degenerations associated with these alterations affect not only the basal ganglia-thalamic-frontal cortex loop, but also the parietal cortex and cerebellum. The present review outlines the experimental studies describing impaired sensory-motor integration in focal dystonia, establishes their relationship with changes in specific neural mechanisms, and provides new insight towards the implementation of novel intervention protocols. Based on the reviewed state-of-the-art evidence, the theoretical framework summarized in the present article will not only result in a better understanding of the pathophysiology of dystonia, but it will also lead to the development of new rehabilitation strategies.

NeuroImage

Our understanding of how genotype determines phenotype in primary dystonia is limited. Familial y... more Our understanding of how genotype determines phenotype in primary dystonia is limited. Familial young-onset primary dystonia is commonly due to the DYT1 gene mutation. A critical question, given the 30% penetrance of clinical symptoms in DYT1 mutation carriers, is why the same genotype leads to differential clinical expression and whether non-DYT1 adult-onset primary dystonia, with and without family history share pathophysiological mechanisms with DYT1 dystonia. This study examines the relationship between dystonic phenotype and the DYT1 gene mutation by monitoring whole-brain structure using voxel-based morphometry. We acquired magnetic resonance imaging data of symptomatic and asymptomatic DYT1 mutation carriers, of non-DYT1 primary dystonia patients, with and without family history and control subjects with normal DYT1 alleles. By crossing the factors genotype and phenotype we demonstrate a significant interaction in terms of brain anatomy confined to the basal ganglia bilateral...

PLOS ONE, 2015

As recently demonstrated, a placebo procedure in motor performance increases force production and... more As recently demonstrated, a placebo procedure in motor performance increases force production and changes the excitability of the corticospinal system, by enhancing the amplitude of the motor evoked potentials (MEP) and reducing the duration of the cortical silent period (CSP). However, it is not clear whether these neurophysiological changes are related to the behavioural outcome (increased force) or to a general effect of expectation. To clarify this, we investigated the nocebo effect, in which the induced expectation decreases force production. Two groups of healthy volunteers (experimental and control) performed a motor task by pressing a piston with the right index finger. To induce a nocebo effect in the experimental group, low frequency transcutaneous electrical nerve stimulation (TENS) was applied over the index finger with instructions of its detrimental effects on force. To condition the subjects, the visual feedback on their force level was surreptitiously reduced after TENS. Results showed that the experimental group reduced the force, felt weaker and expected a worse performance than the control group, who was not suggested about TENS. By applying transcranial magnetic stimulation over the primary motor cortex, we found that while MEP amplitude remained stable throughout the procedure in both groups, the CSP duration was shorter in the experimental group after the nocebo procedure. The CSP reduction resembled previous findings on the placebo effect, suggesting that expectation of change in performance diminishes the inhibitory activation of the primary motor cortex, independently of the behavioural outcome.

Frontiers in Human Neuroscience, 2014

Dystonia has historically been considered a disorder of the basal ganglia, mainly affecting plann... more Dystonia has historically been considered a disorder of the basal ganglia, mainly affecting planning and execution of voluntary movements. This notion comes from the observation that most lesions responsible for secondary dystonia involve the basal ganglia. However, what emerges from recent research is that dystonia is linked to the dysfunction of a complex neural network that comprises basal ganglia-thalamic-frontal cortex, but also the inferior parietal cortex and the cerebellum. While dystonia is clearly a motor problem, it turned out that sensory aspects are also fundamental, especially those related to proprioception. We outline experimental evidence for proprioceptive dysfunction in focal dystonia from intrinsic sensory abnormalities to impaired sensorimotor integration, which is the process by which sensory information is used to plan and execute volitional movements. Particularly, we will focus on proprioceptive aspects of dystonia, including: (i) processing of vibratory input, (ii) temporal discrimination of two passive movements, (iii) multimodal integration of visual-tactile and proprioceptive inputs, and (iv) motor control in the absence of visual feedback. We suggest that these investigations contribute not only to a better understanding of dystonia pathophysiology, but also to develop rehabilitation strategies aimed at facilitating the processing of proprioceptive input.

Frontiers in Behavioral Neuroscience, 2009

Frontiers in Behavioral Neuroscience, 2009

Neuroscience, 2010

Brain mechanisms for action understanding rely on matching the observed actions into the viewer&a... more Brain mechanisms for action understanding rely on matching the observed actions into the viewer's motor system. Health professionals, who treat patients affected by movement disorders as dystonia, frequently see hyperkinetic action patterns characterized by an overflow of muscle co-contractions. To avert an overload of the motor system during observation of those actions, they might need to look at dystonic motor symptoms in a cool, detached way. To investigate whether visual expertise about atypical movement kinematics influences the viewer's motor system, we applied transcranial magnetic stimulation to clinicians and to naive subjects, while they observed handwriting actions performed with two different kinematics: fluent and non-fluent. Crucially, the latter movement pattern was easily recognized by the clinicians as a typical expression of writer's cramp, whereas it was unknown to the naive subjects. Results showed that clinicians had similar corticospinal activation during observation of dystonic and healthy writings, whereas naive subjects were hyper-activated during observation of dystonic movements. Hyper-activation was selective for the muscles directly involved in the dystonic co-contractions and inversely correlated with subjective movement fluency scores, hinting at a fine-tuned association between the breakdown of observed movement fluency and corticospinal activation. These findings suggest that observation of unusual pathological actions differently modulates the viewer's motor system, depending on knowledge, visual expertise, and ability in recognizing suboptimal movement kinematics.

PLoS ONE, 2014

Sensory alterations, a common feature of such movement disorders as Parkinson&amp... more Sensory alterations, a common feature of such movement disorders as Parkinson's disease (PD) and dystonia, could emerge as epiphenomena of basal ganglia dysfunction. Recently, we found a selective reduction of tactile perception (Aristotle's illusion, the illusory doubling sensation of one object when touched with crossed fingers) in the affected hand of patients with focal hand dystonia. This suggests that reduced tactile illusion might be a specific feature of this type of dystonia and could be due to abnormal somatosensory cortical activation. The aim of the current study was to investigate whether Aristotle's illusion is reduced in the affected hand of patients with PD. We tested 15 PD patients, in whom motor symptoms were mainly localised to one side of the body, and 15 healthy controls. Three pairs of fingers were tested in crossed (evoking the illusion) or parallel position (not evoking the illusion). A sphere was placed in the contact point between the two fingers and the blindfolded participants had to say whether they felt one or two stimuli. Stimuli were applied on the affected and less or unaffected side of the PD patients. We found no difference in illusory perception between the PD patients and the controls, nor between the more affected and less/unaffected side, suggesting that Aristotle's illusion is preserved in PD. The retained tactile illusion in PD and its reduction in focal hand dystonia suggest that the basal ganglia, which are dysfunctional in both PD and dystonia, may not be causally involved in this function. Instead, the level of activation between digits in the somatosensory cortex may be more directly involved. Finally, the similar percentage of illusion in the more affected and less or unaffected body sides indicates that the illusory perception is not influenced by the presence or amount of motor symptoms.

In order to obtain further information on the pathophysiology of functional tremor, we assessed t... more In order to obtain further information on the pathophysiology of functional tremor, we assessed tactile discrimination threshold and proprioceptive temporal discrimination motor threshold values in 11 patients with functional tremor, 11 age- and sex-matched patients with essential tremor and 13 healthy controls. Tactile discrimination threshold in both the right and left side was significantly higher in patients with functional tremor than in the other groups. Proprioceptive temporal discrimination threshold for both right and left side was significantly higher in patients with functional and essential tremor than in healthy controls. No significant correlation between discrimination thresholds and duration or severity of tremor was found. Temporal processing of tactile and proprioceptive stimuli is impaired in patients with functional tremor. The mechanisms underlying this impaired somatosensory processing and possible ways to apply these findings clinically merit further research.

Journal of cognitive neuroscience, Jan 16, 2014

It is solidly established that top-down (goal-driven) and bottom-up (stimulus-driven) attention m... more It is solidly established that top-down (goal-driven) and bottom-up (stimulus-driven) attention mechanisms depend on distributed cortical networks, including prefrontal and frontoparietal regions. Instead, it is less clear whether the BG also contribute to one or the other of these mechanisms, or to both. The current study was principally undertaken to clarify this issue. Parkinson's disease (PD), a neurodegenerative disorder primarily affecting the BG, has proven to be an effective model for investigating the contribution of the BG to different brain functions; therefore, we set out to investigate deficits of top-down and bottom-up attention in a selected cohort of PD patients. With this objective in mind, we compared the performance on three computerized tasks of two groups of 12 parkinsonian patients (assessed without any treatment), one otherwise pharmacologically treated and the other also surgically treated, with that of a group of controls. The main behavioral tool for ou...

Journal of Neuroscience, 2014

Despite behavioral evidence showing placebo modulations of motor performance, the neurophysiologi... more Despite behavioral evidence showing placebo modulations of motor performance, the neurophysiological underpinnings of these effects are still unknown. By applying transcranial magnetic stimulation (TMS) over the primary motor cortex, we investigated whether a placebo modulation of force could change the excitability of the corticospinal system. Healthy human volunteers performed a motor task by pressing a piston as strongly as possible with the right index finger. Two experimental groups were instructed that treatment with peripheral low-frequency transcutaneous electrical nerve stimulation (TENS) applied on the first dorsal interosseus would induce force enhancement. One experimental group was conditioned about the effects of TENS with a surreptitious amplification of the visual feedback signaling the force level. The other group, instead, was only verbally influenced, without conditioning. At the end of the instructive placebo procedure, the two experimental groups reached higher levels of force, believed that TENS had been effective and expected to perform better compared with two control groups, who were not influenced about TENS. Moreover, the experimental groups presented enhanced excitability of the corticospinal system in the muscle specifically involved in the task (first dorsal interosseus), as shown by increased amplitude of the motor evoked potentials and decreased duration of the cortical silent period (the latter only in the conditioned group). Crucially, the TMS pulse was delivered when all the subjects exerted the same amount of force, ruling out bottom-up influences. These findings hint at a top-down, cognitive enhancement of corticospinal excitability as a neural signature of placebo modulation of motor performance.

Social Neuroscience, 2013

This study was designed to combine two, otherwise separated, fields of research regarding motor r... more This study was designed to combine two, otherwise separated, fields of research regarding motor resonance and mimicry by adopting a naturalistic mimicry paradigm while probing motor resonance with transcranial magnetic stimulation (TMS). At stake was whether the motor system resonates instantaneously with unobtrusive nonverbal behavior of another person. We measured excitability in the left and right hand while participants viewed sequences of video clips and static images. In the video clips an actor performed several clerical tasks, while either inconspicuously touching his face (face-touching (FT) condition) or not (no face-touching (NFT) condition). We found that excitability was higher in the FT condition than in the NFT and baseline conditions. Furthermore, our data showed a general heightened excitability in the left motor cortex relative to the right. Taken together, the results suggest that observed hand-face gestures--even though outside the primary focus of attention and occurring inconspicuously throughout an ongoing action setting--can cause instantaneous resonant activity in the observer's motor system. It thus supports the idea of motor resonance involvement in mimicry and demonstrates that this can be studied using a naturalistic mimicry paradigm.

PLoS ONE, 2013

Performance of timed motor sequences relies on the cerebellum and basal ganglia, which integrate ... more Performance of timed motor sequences relies on the cerebellum and basal ganglia, which integrate proprioceptive information during the motor task and set internal timing mechanisms. Accordingly, these structures are also involved in other temporal processes, such as the discrimination of the different afferent information in the domain of time. In the present study we tested temporal processing of proprioceptive and tactile stimuli in 20 patients with neurodegenerative cerebellar ataxia and 20 age- and sex-matched healthy subjects. Tactile temporal discrimination threshold was defined as the value at which subjects recognized the two stimuli as asynchronous. Temporal discrimination movement threshold of the first dorsal interosseous and flexor carpi radialis was defined as the shortest interval between two paired electrical stimuli in which the subjects blindfolded perceived two separate index finger abductions and wrist flexions. Both tactile and movement temporal discrimination thresholds were higher in patients with cerebellar ataxia. No correlation was found with disease duration and severity. Our study demonstrates that temporal processing of tactile and proprioceptive stimuli is impaired in patients with cerebellar neurodegeneration and highlights the involvement of cerebellum in temporal processing of somatosensory stimuli of different type.

Neuroscience Letters, 2007

Perception of limb position and motion is abnormal in Parkinson&a... more Perception of limb position and motion is abnormal in Parkinson's disease (PD). Despite the fact that the processing of proprioceptive inputs is inherently temporal, most studies have assessed spatial aspects of proprioception in PD patients. Here, we use a recently described method to test whether deficits also exist in temporal discrimination of proprioceptive inputs. We induced index finger abduction or wrist flexion through percutaneous electrical stimulation of the motor point of the first dorsal interosseous muscle (FDI) or the flexor carpii radialis (FCR), respectively. Twelve patients with unilateral bradykinetic-rigid PD and 12 healthy subjects were asked to report whether pairs of stimuli separated by different time intervals produced single or double index finger abduction movement or wrist flexion. The shortest interval at which subjects reported two separated movements was considered as temporal movement discrimination threshold. Results showed that thresholds were significantly higher in PD patients than in control subjects for both FCR and FDI muscle, thus demonstrating for the first time that temporal proprioceptive processing is altered in PD.

Neuroscience, 2012

Transcranial magnetic stimulation (TMS) studies have shown that the motor system is facilitated w... more Transcranial magnetic stimulation (TMS) studies have shown that the motor system is facilitated when we imagine performing motor actions. However, it is not clear whether the individual's motor system modulates bilaterally and selectively for task parameters, such as movement direction and amplitude. To investigate this issue, we applied single-pulse TMS over the left and right primary motor cortex (M1) of healthy subjects, who had to imagine grasping and rotating a clock hour hand, having a starting position at noon, towards four different times: 2, 5, 7 and 10 o'clock. Rotations could be in clockwise (2 and 5 o'clock) or counter-clockwise (7 and 10 o'clock) directions and could require small (2 and 10 o'clock) or large (5 and 7 o'clock) rotation angle. TMS motor-evoked potentials were recorded for three muscles, and movements were imagined with the right and left hands. Results showed that during motor imagery a mirroring pattern was present between the right and the left motor cortices, showing selective activation of the hand-intrinsic muscles spatially close to the direction of the imagined movement. Overall a higher activation for large and a lower activation for small rotation angle were found, but no selective muscle activity was present within the hand-intrinsic muscles for this parameter. Following these results we propose that during action imagination an internally coded covariance between movement parameters is present with a muscle-specific activation for movement direction. Ó