Viviana Versace

Theta-burst stimulation of the left hemisphere accelerates recovery of hemispatial neglect

Objective: Cortico-cortical circuits originating from the posterior parietal cortex (PPC) of the intact left hemisphere (LH) may become hyperexcitable in patients with hemispatial neglect due to a right hemispheric (RH) stroke. Methods: In the current randomized, double-blind, sham-controlled study, we investigated safety and efficacy of continuous theta-burst stimulation (cTBS) in 10 sessions over 2 weeks applied over the intact PPC of the LH in subacute ischemic stroke patients. Severity of neglect was assessed through the standardized Behavioral Inattention Test (BIT). We also measured, by means of bifocal transcranial magnetic stimulation (TMS), how cTBS modified the excitability of the parieto-frontal functional connections in the intact LH. Results: We found that 2 weeks of cTBS, but not sham cTBS, were effective in improving neglect symptoms as measured by BIT score. BIT scores improved by 16.3% after 2 weeks of cTBS and 22.6% at 1 month follow-up. We also found that hyperexcitability of LH parieto-frontal circuits was reduced following treatment with real but not sham cTBS. Conclusion: These findings suggest that a 2-week course of cTBS over the LH PPC may be a potential effective strategy in accelerating recovery from visuospatial neglect in subacute stroke patients, possibly counteracting the hyperexcitability of LH parieto-frontal circuits. Classification of evidence: This study provides Class III evidence that left posterior parietal cortex theta-burst stimulation improves hemispatial neglect for up to 2 weeks after treatment.

Repetitive transcranial magnetic stimulation of the motor cortex ameliorates spasticity in multiple sclerosis

Objective: To investigate whether repetitive transcranial magnetic stimulation (rTMS) can modify spasticity. Methods: We used high-frequency (5 Hz) and low-frequency (1 Hz) rTMS protocols in 19 remitting patients with relapsing–remitting multiple sclerosis and lower limb spasticity. Results: A single session of 1 Hz rTMS over the leg primary motor cortex increased H/M amplitude ratio of the soleus H reflex, a reliable neurophysiologic measure of stretch reflex. Five hertz rTMS decreased H/M amplitude ratio of the soleus H reflex and increased corticospinal excitability. Single sessions did not induce any effect on spasticity. A significant improvement of lower limb spasticity was observed when rTMS applications were repeated during a 2-week period. Clinical improvement was long-lasting (at least 7 days after the end of treatment) when the patients underwent 5 Hz rTMS treatment during a 2-week protocol. No effect was obtained after a 2-week sham stimulation. Conclusions: Repetitive transcranial magnetic stimulation may improve spasticity in multiple sclerosis.

In vivo definition of parieto-motor connections involved in planning of grasping movements

We combined bifocal transcranial magnetic stimulation (TMS) and diffusion tensor imaging (DTI) tractography to investigate in humans the contribution of connections originating from different parietal areas in planning of different reaching to grasp movements. TMS experiments revealed that in the left hemisphere functional connectivity between the primary motor cortex (M1) and a portion of the angular gyrus (AG) close to the caudal intraparietal sulcus was activated during early preparation of reaching and grasping movements only when the movement was made with a whole hand grasp (WHG) towards objects in contralateral space. In contrast, a different pathway, linking M1 with a part of the supramarginal gyrus (SMG) close to the anterior intraparietal sulcus, was sensitive only to the type of grasp required (precision grasping) but not to the position of the object in space. A triple coil experiment revealed that inactivation of the ventral premotor area (PMv) by continuous theta burst stimulation interfered with some of these interactions. Anatomical DTI tractography revealed that AG and SMG are strongly connected with PMv and with M1 by different bundles of the superior longitudinal fasciculus (SLF). These results demonstrate the existence of segregated parieto-premotor-motor pathways crucial for preparation of different grasping actions and indicate that these may process information relevant to both the position of the object and the hand shape required to use it.

Asymmetry of Parietal Interhemispheric Connections in Humans

Visuospatial abilities are preferentially mediated by the right hemisphere. Although this asymmetry of function is thought to be due to an unbalanced interaction between cerebral hemispheres, the underlying neurophysiological substrate is still largely unknown. Here, using a method of trifocal transcranial magnetic stimulation, we show that the right, but not left, human posterior parietal cortex exerts a strong inhibitory activity over the contralateral homologous area by a short-latency connection. We also clarify, using diffusion-tensor magnetic resonance imaging, that such an interaction is mediated by direct transcallosal projections located in the posterior corpus callosum. We argue that this anatomo-functional network may represent a possible neurophysiological basis for the ongoing functional asymmetry between parietal cortices, and that its damage could contribute to the clinical manifestations of neglect.

Low frequency rTMS of the SMA transiently ameliorates peak-dose LID in Parkinson’s disease

OBJECTIVE To determine whether low-frequency repetitive transcranial magnetic stimulation (rTMS) may modulate l-DOPA-induced dyskinesia (LID) in dyskinetic Parkinsons disease (PD) patients. LID is a severe motor complication in advanced PD patients. The neural mechanisms involved in LID are not clear, and it is apparent that both an excessive decrease in internal pallidus firing and a modification and overactivation of cortical motor and premotor areas are involved in its pathogenesis. METHODS Using low frequency 1Hz repetitive rTMS we investigated whether decrease of excitability of the supplementary motor area (SMA) may result in modification of LID in PD patients. Furthermore we tested whether it was possible to enhance and/or prolong the beneficial effects of the treatment with repeated sessions of stimulation. RESULTS We observed that 1Hz rTMS induced a transient reduction of dyskinesias. A single session of rTMS improved LID, while repeated sessions of stimulation failed to enhance and/or prolong the beneficial effects of the procedure, without causing motor deterioration or other adverse effects. CONCLUSIONS These results suggest that LID may depend on an increased excitability of the SMA. SIGNIFICANCE SMA rTMS is effective in reducing transiently LID, although cannot yet be considered clinically useful.

Long-term effects on cortical excitability and motor recovery induced by repeated muscle vibration in chronic stroke patients.

Background. Muscle vibration modifies corticomotor excitability in healthy subjects and reduces muscle tonus in stroke patients. Objective. This study examined whether repeated muscle vibration (rMV) applied over the flexor carpi radialis (FCR) and biceps brachii (BB) can induce long-lasting changes, using transcranial magnetic stimulation (TMS), in patients with chronic stroke. Methods. Thirty hemiparetic patients who offered at least minimal wrist and elbow isometric voluntary contractions were randomly assigned to either an experimental group, which received rMV in addition to physiotherapy (rMV + PT), or a control group that underwent PT alone. The following parameters of the FCR, BB, and extensor digitorum communis (EDC) were measured through TMS before, and 1 hour, 1 week, and 2 weeks after the end of intervention: resting motor threshold (RMT), map area, map volume, short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF). Muscle tonus and motor function were assessed on the same day as TMS. Results. Pre–post analysis revealed a reduction in RMT and an increase in motor map areas occurred in the vibrated muscles only in the rMV + PT group, with an increase in map volumes of all muscles. Moreover, SICI increased in the flexors and decreased in the extensor. These neurophysiological changes lasted for at least 2 weeks after the end of rMV + PT and paralleled the reduction in spasticity and increase in motor function. A significant correlation was found between the degree of spasticity and the amount of intracortical inhibition. Conclusion. rMV with PT may be used as a nonpharmacological intervention in the neurorehabilitation of mild to moderate hemiparesis.

TMS activation of interhemispheric pathways between the posterior parietal cortex and the contralateral motor cortex

Using a twin coil transcranial magnetic stimulation (tc‐TMS) approach we have previously demonstrated that facilitation may be detected in the primary motor cortex (M1) following stimulation over the ipsilateral caudal intraparietal sulcus (cIPS). Here we tested the interhemispheric interactions between the IPS and the contralateral motor cortex (M1). We found that conditioning the right cIPS facilitated contralateral M1 when the conditioning stimulus had an intensity of 90% resting motor threshold (RMT) but not at 70% or 110% RMT. Facilitation was maximal when the interstimulus interval (ISI) between cIPS and M1 was 6 or 12 ms. These facilitatory effects were mediated by interactions with specific groups of interneurons in the contralateral M1. In fact, short intracortical inhibition (SICI) was reduced following cIPS stimulation. Moreover, additional comparison of facilitation of responses evoked by anterior–posterior versus posterior–anterior stimulation of M1 suggested that facilitation was more effective on early I1/I2 circuits than on I3 circuits. In contrast to these effects, stimulation of anterior IPS (aIPS) at 90% RMT induced inhibition, instead of facilitation, of contralateral M1 at ISIs of 10–12 ms. Finally, we found similar facilitation between left cIPS and right M1 although the conditioning stimuli had to have a higher intensity compared with stimulation of right cIPS (110% instead of 90% RMT). These findings demonstrate that different subregions of the posterior parietal cortex (PPC) in humans exert both facilitatory and inhibitory effects towards the contralateral primary motor cortex. These corticocortical projections could contribute to a variety of motor tasks such as bilateral manual coordination, movement planning in space and grasping.

Effects of motor cortex rTMS on lower urinary tract dysfunction in multiple sclerosis

We tested the effects of 5-Hz rTMS over the motor cortex in multiple sclerosis (MS) subjects complaining of lower urinary tract symptoms either in the filling or voiding phase. Our data show that motor cortex stimulation for five consecutive days over two weeks ameliorates the voiding phase of the micturition cycle, suggesting that enhancing corticospinal tract excitability might be useful to ameliorate detrusor contraction and/or urethral sphincter relaxation in MS patients with bladder dysfunction. Multiple Sclerosis 2007; 13: 269–271. http://msj.sagepub.com

Improvement of choreic movements by 1Hz repetitive transcranial magnetic stimulation in Huntington's disease patients

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Fast increase of motor cortical inhibition following postural changes in healthy subjects.

BACKGROUND AND AIMS Postural reactions are associated with changes in the excitability of the motor system. In the present study we investigated the presence of neurophysiological changes of motor cortical areas targeting muscles of the inferior limbs following treatment with a physiotherapy technique aimed to treat postural dysfunctions by stretching postural muscles, global postural reeducation (GPR). METHODS Twenty healthy subjects were evaluated with paired-transcranial magnetic stimulation (TMS) of the motor cortex and recording of motor evoked potentials (MEPs) from peripheral muscles of the inferior limb before and after two GPR manoeuvres applied in different experiments (1 and 2). RESULTS The effects of GPR were posture- and task-specific: indeed, a GPR manoeuvre applied in standing subjects increased inhibition in cortical areas controlling flexor muscles (Biceps Femoris: p<0.05) while increasing the excitation of cortical areas controlling extensor muscles (Tibialis Anterior: p<0.05). On the other hand, following a GPR manoeuvre applied in subjects in supine position, increased inhibition in cortical areas controlling flexor muscles (Biceps Femoris and Soleus) was not paralleled by excitation of extensor ones (F=12.2; p=0.005). CONCLUSIONS These findings provide a neurophysiological basis to the clinical benefits associated to physiotherapy and suggest potential applications of treatments based on postural changes on motor cortical disorders.