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Practice-induced visual perceptual learning is thought to reflect the plasticity of sensory brain regions. The hypothesis that changes in early visual areas may depend on top-down modulation from higher level brain regions by attentional mechanisms is still debated. We used a causal approach by repetitive transcranial magnetic stimulation (rTMS) to evaluate the role of primary visual cortex (V1) and posterior parietal cortex (PPC) in visual perceptual learning. Twelve healthy volunteers performed a forced-choice orientation discrimination task of gabor patches (consisting of 500 trials in five blocks) without any intervention or immediately after a conditioning inhibitory 1-Hz rTMS protocol delivered over the V1, the right PPC, and the vertex (control area), in four different days. Conditioning inhibition by 1-Hz rTMS over the V1 produced an overall worsening of the performance accuracy but no effect in the learning rate, as measured by the slope of the learning curve. The learning rate was lower after right PPC inhibition compared to the other conditions, when evaluated during the first two blocks (200 trials) where occurred most of the learning. These preliminary findings suggest that higher level brain regions may be involved in the mechanisms underlying perceptual learning.

Epileptic conditions are characterized by an altered balance between excitatory and inhibitory influences at the cortical level. Transcranial magnetic stimulation (TMS) provides a noninvasive evaluation of separate excitatory and inhibitory functions of the cerebral cortex. In addition, repetitive TMS (rTMS) can modulate the excitability of cortical networks. We review the different ways that TMS has been used to investigate pathophysiological mechanisms and effects of antiepileptic drugs in patients with epilepsy and epileptic myoclonus. The safety of different TMS techniques is discussed too. Finally, we discuss the therapeutic prospects of rTMS in this field.

Objectives : To investigate the reorganization of somatosensory and motor cortex in congenital brain injury. Methods : We recorded motor evoked potentials (MEPs) following transcranial magnetic stimulation (TMS) and somatosensory evoked potentials (SEPs) in a 41 year old man with severe congenital right hemiparesis but only mild proprioceptive impairment. Brain magnetic resonance imaging showed a large porencephalic cavitation in the left hemisphere mainly involving the frontal and parietal lobes. Results : TMS showed fast-conducting projections from the undamaged primary motor cortex to both hands, whereas MEPs were not elicited from the damaged hemisphere. Left median nerve stimulation evoked normal short-latency SEPs in the contralateral undamaged somatosensory cortex. Right median nerve stimulation did not evoke any SEP in the contralateral damaged hemisphere, but a middle-latency SEP (positive–negative–positive, 39–44–48ms) in the ipsilateral undamaged hemisphere, with a fronto-central scalp distribution. Conclusions : Our data show that somatosensory function of the affected arm is preserved, most likely through slow-conducting non-lemniscal connections between the affected arm and ipsilateral non-primary somatosensory cortex. In contrast, motor function was poor despite fast-conducting ipsilateral cortico-motoneuronal output from the primary motor cortex of the undamaged hemisphere to the affected arm. This suggests that different forms of reorganization operate in congenital brain injury and that fast-conducting connections between primary cortex areas and ipsilateral spinal cord are not sufficient for preservation or recovery of function.

Objectives : Prolongation of the cortical silent period (CSP) following transcranial magnetic stimulation has been reported in patients with partial epilepsy involving the primary motor cortex (M1). This study aimed to investigate the relationship between the expected intraindividual variations in risk factors for seizures and CSP duration. Methods : We studied a 59-year-old woman with a rolandic meningioma and simple motor partial seizures and a 71-year-old woman with a parietal/occipital meningioma and complex partial seizures. Both patients had seizure as their initial symptom with complete postsurgical remission. Repeated pre- and postoperative CSP recordings were made from both first dorsal interosseous muscles. We compared the results to those obtained in 13 normals. Results : In the patient with simple motor partial seizures, the CSP was significantly prolonged in preoperative recordings and 3 weeks after surgery. This CSP lengthening partly subsided 3 months after surgery. Finally, the CSP was normal 6, 8, and 18 months after surgery. In the patient with complex partial seizures, no CSP change was observed. Conclusions : In our patient with a rolandic meningioma, CSP prolongation was observed when the risk of seizure relapse was supposed to be higher (preoperative and early postoperative periods). This supports the view that CSP changes reflect compensatory mechanisms in M1 epilepsy.

Neurophysiological studies suggest that reading sheet music facilitates sensorimotor cortex in musicians. The aim of the present study was twofold: to evaluate (1) whether in piano players, reading notes in the bass clef (usually played with the left hand) and in the treble clef (usually played with the right hand) selectively enhances right and left M1 excitability, respectively (inter-hemispheric effect); and (2) whether reading notes played with the thumb or with the little finger selectively modulate the excitability of the abductor pollicis brevis (APB) and abductor digitorum minimi (ADM) muscles, respectively (intra-hemispheric effect). Seven pianists participated to the study. Single pulse TMS was applied to either M1 while subjects alternatively read the bass or the treble clef of five sheets music without any movements. As a baseline condition TMS was delivered during the observation of a blank pentagram. When subjects read the treble clef, the excitability of the left M1 was significantly higher compared to that recorded in the right M1. No significant differences emerged during reading of the bass clef. Moreover, motor-evoked potentials were higher in the ADM muscle regardless the note. These preliminary data support the view that music reading may induce specific inter-hemispheric modulation of the motor cortex excitability.

Deficient voluntary control of behaviour and impulsivity are key aspects of impulse control disorders. The objective of the present study was to evaluate the relationship between behavioural measures of impulsivity and awareness of voluntary action. Seventy-four healthy volunteers completed the Barratt Impulsiveness Scale (BIS), a questionnaire used to measure impulsive personality traits, and a go/no-go task. Moreover, all participants performed a task in which, using the Libet’s clock, they were requested to report the time of a self-initiated movement (M-judgment) or the time they first felt intention to move (W-judgment). A positive relationship between W-judgment and impulsivity measures emerged. Namely, high scores in the attentional and motor impulsivity subscales of BIS and in the number of inhibitory failure responses in the go/no-go task, were related to a low difference between the W-judgment and the actual movement (i.e. the awareness of intention to move was closer to the voluntary movement execution). In contrast no relationship emerged with M-judgment. Findings suggest that impulsivity may be related to a delayed awareness of voluntary action. We hypothesize that in impulse control disorders the interval between conscious intention and actual movement could be insufficient to allow a conscious ‘veto’ of the impending action.

The cortical silent period (CSP) following transcranial magnetic stimulation reflects GABAB-mediated inhibition in the primary motor cortex (M1), and could contribute to understand the pathophysiological substrates of epilepsies. Increased CSP duration has been reported in idiopathic generalized epilepsy (IGE) and in partial epilepsy (PE) involving the M1, although other studies yielded discordant findings. In this meta-analysis we systematically assessed the consistency of CSP changes in untreated epileptic patients. We searched for controlled studies evaluating the CSP in drug-naive or drug-free patients with IGE or PE. The mean difference between CSP duration obtained in patients and controls was calculated. Fourteen studies (267 patients and 234 controls) were included. A significant mean difference was found, with longer CSP in patients than in controls. The difference was still greater if IGE patients only were analyzed. CSP modifications did not depend from differences in motor threshold between patients and controls. Meta-analysis confirms CSP modifications in epilepsies, with enhancement of this cortical inhibitory measure in most IGE patients. This provides a rationale for investigations aiming to verify the hypotheses that increased CSP reflects compensatory neural phenomena counteracting transition from the interictal to ictal state, and that CSP variability reflects the pathophysiological heterogeneity of epileptic syndromes.

Background In a patient with post-traumatic vegetative state (VS), a non-significant trend toward neurobehavioral gains has been reported after the application of a patterned rTMS protocol over the right dorsolateral prefrontal cortex ( Louise-Bender Pape et al., 2009 ). Recently, in a patient with minimal conscious state, Piccione et al., 2011 reported an arousal with transient increase of meaningful behaviours and EEG changes after 20-Hz rTMS over the primary motor cortex (M1). This has raised interest in the scientific community but has also had disproportionate resonance in mass media and strong expectations among the patients’ families. Objective To evaluate the effect of a non-invasive brain stimulation protocol with high-frequency rTMS in VS by a randomised, double blind, sham-controlled trial with a cross-over design. Methods Eleven patients classified as being in a VS (9 post-anoxic, 2 post-traumatic) were included in the study. Twenty-Hertz rTMS or sham stimulation were applied to the left M1 for 5 consecutive days. Daily sessions consisted of 10 min stimulation (1000 pulses) at an intensity of 60% maximum stimulator output. Primary outcome measures were changes in the JFK Coma Recovery Scale-Revised (CRS-R) scale total score and Clinical Global Impression (CGI) scale. Evaluations were performed at baseline, after the first day of treatment, immediately after the end of the 5-days treatment, and 1 week and 1 month later. Results Slight changes observed in the CRS-R and CGI scores did not significantly differ between real or sham stimulation conditions. In addition, no concordance was seen between CGI changes observed by clinician and patient’s relatives. Conclusion Findings did not provide evidence of therapeutic effect of rTMS in VS, at least with conventional coils and current safety parameters.

The aim of this study was twofold: first, to evaluate the efficacy of a short physical therapy program on freezing of gait (FoG) in Parkinson’s disease (PD) and second, to test whether tDCS may potentiate the effect of rehabilitation. Nine PD patients with mild FoG attended 5 consecutive daily sessions (45–60 min) of physical therapy focused to learn strategies for overcoming FoG. Patients were randomized to receive sham or real anodal tDCS (2 mA, 20 min) of the leg motor cortex before each session. Kinematic variables were recorded at baseline, one (T1) and six (T2) weeks after intervention. An overall significant improvement of number of strides and time to turn during a standardized walking test was observed at T1 and T2 compared to the baseline. A trend towards a larger effect on these measures (T1 and T2 vs baseline) was seen in the 4 patients receiving real tDCS compared to the five subjects receiving sham stimulation. Preliminary data may support the efficacy of this short physical therapy intervention in PD patients with mild FOG. Completion of the study is necessary to interpret the current non-significant trend towards a potentiation of this effect by anodal tDCS.

Perceptual events occur in multiple sensory modalities. Recent neuroimaging data challenge the traditional models arguing for sensory integration to occur in higher-order association cortices and support the hypothesis of a multisensory interplay at low-level sensory-specific cortex. We used an on-line interference approach by rTMS to investigate the role of the left lateral occipital cortex (LOC) in audio-visual (AV) object recognition process. Fifteen healthy volunteers performed a visual identification task of degraded pictures (living and non-living) presented alone (V) or simultaneously to coherent (c-AV) or non-coherent (nc-AV) sounds. Focal 10-Hz rTMS at an intensity of 100% resting motor threshold was delivered simultaneously to the picture (500 ms). Two blocks of 60 pictures were randomly displayed in two different experimental conditions: rTMS of the left LOC and over Cz (cortical control area). Accuracy and reaction time of identification were analyzed. rTMS of the left LOC produced a worsening of the accuracy compared to rTMS over Cz specifically in the c-AV condition. Interestingly, the effect was significant for stimuli belonging to the living semantic category. These data support the view that audiovisual interaction effect may occur at early stage of recognition processing.

We used transcranial alternating current stimulation (tACS) to modulate brain oscillations during spontaneous motor tempo and sensorimotor synchronization tasks to evaluate the effect of specific frequencies on motor performance. Six healthy subjects performed self-paced finger movements and auditory-paced finger tapping (synchronization–continuation task) with isochronous rhythmic sequences of 500 and 1500 ms interstimulus intervals (ISI). During each task, tACS was delivered to the left M1 (“reference” electrode on Pz) at an intensity of 1 mA in 5 randomized conditions: 5, 10, 20, 40 Hz, and sham. Baseline recordings (without tACS) were performed before and after each experimental session. In synchronization task with sequences of ISI 500 ms, 20 Hz tACS modified anticipatory mechanisms as revealed by a reduction of the negative mean asynchrony between the onset of the auditory cue and the motor response. However, this effect did not reach statistical significance due to the small sample. No effect emergent in the other conditions. We hypothesize that the reduction of the negative mean asynchrony may reflect a slowing of the motor output. These preliminary data are in line with previous studies in literature reporting specific effects of tACS at beta frequency on motor functions and cortical excitability.

In carotid endarterectomy (CEA), EEG and somatosensory evoked potentials (SEPs) are the most commonly used monitoring techniques to prevent perioperative stroke. However, which of these methods is the most appropriate is not definitely established. Here we evaluated retrospectively simultaneous EEG and SEP recordings. Our CEA series was analyzed backward to identify 30 patients requiring carotid shunt. Shunting was performed in 7.1% of 420 consecutive CEA over a 20-month period. All CEAs were continuously monitored by multi-channel EEG and SEPs before, during and 20 min following carotid cross-clamping. The most reliable SEP criterion for shunting was marked amplitude reduction or disappearance of cortical components (N20, P25), usually associated or preceded by a unilateral or bilateral suppression of EEG activity. Three of the shunted patients had minor postoperative neurological deficits. Amongst the 390 non-shunted patients, 1 had a postoperative ischemic stroke and 1 one had a cerebral hemorrhage. Findings confirm that SEPs are less sensitive but more specific than EEG for the detection of cerebral ischemia in CEA. The number of shunting and major ischemic events in non-shunted patients associated to simultaneous EEG and SEP monitoring was lower than those commonly reported in the literature of CEA.

Transcranial magnetic stimulation (TMS) and neuroimaging studies suggest a functional link between the emotion-related brain areas and the motor system. It is not well understood, however, whether the motor cortex activity is modulated by specific emotions experienced during music listening. In 23 healthy volunteers, we recorded the motor evoked potentials (MEP) following TMS to investigate the corticospinal excitability while subjects listened to music pieces evoking different emotions (happiness, sadness, fear, and displeasure), an emotionally neutral piece, and a control stimulus (musical scale). Quality and intensity of emotions were previously rated in an additional group of 30 healthy subjects. Fear-related music significantly increased the MEP size compared to the neutral piece and the control stimulus. This effect was not seen with music inducing other emotional experiences and was not related to changes in autonomic variables (respiration rate, heart rate). Current data indicate that also in a musical context, the excitability of the corticomotoneuronal system is related to the emotion expressed by the listened piece.

Objective Time processing in the millisecond-to-minute range is reflected by Event-Related Potentials (ERPs), but the neural circuits of timing remains controversial. In the present study we investigated the role of different cortical areas in the processing of basic temporal information using an interference approach with repetitive transcranial magnetic stimulation (rTMS) and ERPs as indices of timing mechanisms. Methods Nine healthy volunteers performed a temporal discrimination task in which they had to decide whether the time interval between two tones was shorter (800 ms), equal to, or longer (1200 ms) than a previously listened standard interval (1000 ms) and press different buttons accordingly. The task was performed at the baseline and immediately after a 15-min-long train of focal 1-Hz rTMS delivered to supplementary motor area, right posterior parietal cortex, right superior temporal gyrus, or Oz (control area). Accuracy and reaction times and ERPs during (contingent negative variation, CNV) and after the end of the comparison interval were analyzed. Results At the baseline, CNV was modulated by the interval duration and the analysis of the ERP evoked after the end of the comparison interval showed that the amplitude of the positive peak emerging approximately after 200 ms was higher for ‘Long’ compared to ‘Short’ intervals, whereas amplitude for ‘Equal’ was intermediate. RTMS interference had no significant effect on behavioural performance or ERP components. Conclusion These data may suggest that these cortical areas are less crucially involved than other brain regions (e.g. sub-cortical or cerebellar areas) in the neural mechanisms processing basic temporal information like interval duration.