Influence of the supplementary motor area on primary motor cortex excitability during movements triggered by neutral or emotionally unpleasant visual cues.

The stronger anatomo-functional connections of the supplementary motor area (SMA), as compared with premotor area (PM), with regions of the limbic system, suggest that SMA could play a role in the control of movements triggered by visual stimuli with emotional content. We addressed this issue by analysing the modifications of the excitability of the primary motor area (M1) in a group of seven healthy subjects, studied with transcranial magnetic stimulation (TMS), after conditioning TMS of SMA, during emotional and non-emotional visually cued movements. Conditioning TMS of the PM or of contralateral primary motor cortex (cM1) were tested as control conditions. Single-pulse TMS over the left M1 was randomly intermingled with paired TMS, in which a conditioning stimulation of the left SMA, left PM or right M1 preceded test stimulation over the left M1. The subjects carried out movements in response to computerised visual cues (neutral pictures and pictures with negative emotional content). The amplitudes of motor-evoked potentials (MEPs) recorded from the right first dorsal interosseous muscle after paired TMS were measured and compared with those obtained after single-pulse TMS of the left M1 under the various experimental conditions. Conditioning TMS of the SMA in the paired-pulse paradigm selectively enhanced MEP amplitudes in the visual-emotional triggered movement condition, compared with single-pulse TMS of M1 alone or with paired TMS during presentation of neutral visual cues. On the other hand, conditioning TMS of the PM or cM1 did not differentially influence MEP amplitudes under visual-emotional triggered movement conditions. This pattern of effects was related to the intensity of the conditioning TMS over the SMA, being most evident with intensities ranging from 110% to 80% of motor threshold. These results suggest that the SMA in humans could interface the limbic and the motor systems in the transformation of emotional experiences into motor actions.

Effects of motor imagery on motor cortical output topography in Parkinson's disease.

BACKGROUND: The motor impairment in Parkinson's disease (PD) could partly reflect a failure to activate processes of motor imagery. OBJECTIVE: To verify any selective changes of motor output during motor imagery, lateralized to the hemisphere contralateral to the clinically affected side of hemiparkinsonian patients. METHODS: Transcranial magnetic stimulation (TMS) was used to map the cortical representations of the contralateral abductor digiti minimi muscle (ADM) during rest, contraction, and motor imagery in a group of patients with hemi-PD and in a group of healthy volunteers. Seven patients with hemi-PD and seven healthy subjects were examined. Focal TMS was applied over a grid of 20 scalp positions on each hemiscalp. Maps were characterized by area (number of excitable positions), volume (the sum of motor evoked potential amplitudes at all scalp positions), and center of gravity (a map position representing an amplitude-weighted calculation of the excitable area). RESULTS: In healthy control subjects, the area of cortical representation of ADM was symmetrically increased in both hemispheres by mental simulation of movement and real muscle contraction. In patients with hemi-PD, there was a hemispheric asymmetry in the area of cortical representation elicited by motor imagery. The area was reduced in the clinically affected hemisphere. The volume of cortical representation was increased under all conditions and in both hemispheres in patients with PD. However, largely because the volume was so high at rest in patients, the increment in volume associated with contraction was smaller than in control subjects. CONCLUSION: This study demonstrates the presence of a tonic hyperactivation of motor cortical circuitry in PD in conjunction with an abnormality of either motor imagery or the process by which motor imagery engages the sensorimotor cortices in the clinically affected hemisphere.

Paired transcranial magnetic stimulation protocols reveal a pattern of inhibition and facilitation in the human parietal cortex.

Intracortical inhibition (ICI) and facilitation (ICF) of the human motor cortex can be induced by paired transcranial magnetic stimulation (TMS). Although demonstrated in experimental animals, the existence of intracortical inhibitory and excitatory circuits in parietal sensory cortex has not been documented in humans. The aim of this study was to investigate the effects of paired TMS of the parietal cortex on contralateral tactile perception. Fifteen healthy subjects were involved in a task of discrimination of electrical stimuli delivered at near-threshold intensity of sensory perception over the left thumb. Paired TMS was delivered with a focal coil on the right posterior parietal lobe after various delays from the presentation of finger stimuli. The effects of different interstimulus intervals (ISI: 1, 3, 5, 7, 10 and 15 1 1 Bms1B) between the conditioning and the test TMS stimulus on tactile perception were studied. The conditioning stimulus intensity was set at 70 % of motor threshold, while test TMS intensity was 130 % of motor threshold. Single pulse suprathreshold TMS interfered with the perception of finger stimuli, while subthreshold stimuli such as the 'conditioning' stimuli had no effect on sensory perception. Paired TMS differentially influenced the performance depending on the ISI. At an ISI of 1 1 1 Bms1B, paired TMS stimuli induced a significant worsening of the performance compared with single pulse TMS; at an ISI of 5 1 1 Bms1B, paired TMS stimuli induced a significant facilitation of the performance compared with single pulse TMS, restoring baseline performance levels. These results suggest that paired TMS can reveal a selective pattern of ICI and ICF in the human parietal cortex.

Time-dependent activation of parieto-frontal networks for directing attention to tactile space. A study with paired transcranial magnetic stimulation pulses in right-brain-damaged patients with extinction.

Tactile extinction has been interpreted as an attentional disorder, closely related to hemineglect, due to hyperactivation of the unaffected hemisphere, resulting in an ipsilesional attentional bias. Paired transcranial magnetic stimulation (TMS) techniques, with a subthreshold conditioning stimulus (CS) followed at various interstimulus intervals (ISIs) by a suprathreshold test stimulus (TS), are useful for investigating intracortical inhibition and facilitation in the human motor cortex. In the present work, we investigated the effects of paired TMS over the posterior parietal and frontal cortex of the unaffected hemisphere in a group of eight right-brain-damaged patients with tactile extinction who were carrying out a bimanual tactile discrimination task. The aim of the study was to verify if paired TMS could induce selective inhibition or facilitation of the unaffected hemisphere depending on the ISI, resulting, respectively, in an improvement and a worsening of contralesional extinction. In addition, we wanted to investigate if the effects of parietal and frontal TMS on contralesional extinction appeared at different intervals, suggesting time-dependent activation in the cortical network for the processing of tactile spatial information. Paired TMS stimuli with a CS and a TS, separated by two ISIs of 1 and 10 ms, were applied over the left parietal and frontal cortex after various intervals from the presentation of bimanual cutaneous stimuli. Single-test parietal TMS stimuli improved the patients' performance, whereas paired TMS had distinct effects depending on the ISI: at ISI = 1 ms the improvement in extinction was greater than that induced by single-pulse TMS; at ISI = 10 ms we observed worsening of extinction, with complete reversal of the effects of single-pulse TMS. Compared with TMS delivered over the frontal cortex, parietal TMS improved the extinction rate in a time window that began earlier. These findings shed further light on the mechanism of tactile extinction, suggesting relative hyperexcitability of the parieto-frontal network in the unaffected hemisphere, which is amenable to study and modulation by paired TMS pulses. In addition, the results show time-dependent processing of tactile spatial information in the parietal and frontal cortices, with a bimodal distribution of activity, at least in the attentional network of the unaffected hemisphere.

Neurophysiological follow-up of motor cortical output in stroke patients.

BACKGROUND AND PURPOSE: Transcranial magnetic stimulation (TMS) has been employed in following up a population of 20 stroke patients in a post-acute, apparently stabilized stage. Neurophysiological and clinical data were recorded in 5 different recording sessions, from the beginning of a neuro-rehabilitation treatment (T0, at about 5 weeks from the ictal event.), followed up for about 4 months (T4), with the purpose to study any modification of the cortical motor output in the course of a neuro-rehabilitation treatment. METHODS: Motor evoked potentials (MEPs) were simultaneously recorded from 10 muscles of both upper limbs (affected and not-affected); meanwhile, clinical and functional scores were gathered. Spinal responsiveness was investigated via H-reflex and F-wave recordings. RESULTS: We describe a pattern of improving changes still taking place four months after the stroke, even if the maximal amelioration burden was concentrated between T0 and T1 and T1 and T2 recording sessions (T0/admission to T2/42 days from T0=about 80 days from stroke occurrence). In particular, the excitability threshold (ETh) was progressively decreasing in the affected hemisphere (AH; P<0.001 between T0 and T4), while MEPs amplitude and latency tended toward normality, more in the resting state than during voluntary contraction. Slopes of neurophysiological and clinical data evolution were taken and trends of amelioration described. CONCLUSIONS: These findings suggest that rearrangements of motor cortical neural circuitries are still operating after several months from an acute vascular monohemispheric insult, coupled with a clinical improvement in disability and neurological scores. The steepest part of the slopes were evident in the first 80 days, suggesting that this period is the one in which plastic changes of cortical motor areas are mainly active.

Intracortical excitatory and inhibitory phenomena to paired transcranial magnetic stimulation in healthy human subjects: differences between the right and left hemisphere.

Intracortical inhibition (ICI) and facilitation (ICF) to paired magnetic stimuli reflect the activation of interneuronal circuits within the motor cortex. Intersubjects physiological variability of these phenomena, partly limits the usefulness of such method. Therefore, interhemispheric ICI/ICF differences might represent a more sensitive and less variable neurophysiological parameter to test the motor cortex excitability. Motor evoked potentials from the hand muscles were recorded in ten healthy subjects in a paired-pulse paradigm. Interstimulus intervals (ISIs) from 1 to 50 ms were used. The time course of ICI and ICF in the two hemispheres is consistent with minimal interhemispheric asymmetries. The interhemispheric differences of ICI and ICF could be a valuable neurophysiological marker for the diagnosis, prognosis and follow-up of neurological diseases characterized by monohemispheric damage and lateralized motor deficits.

Transcranial magnetic stimulation reveals an interhemispheric asymmetry of cortical inhibition in focal epilepsy.

Transcranial magnetic stimulation (TCS) was applied to both hemispheres of 16 patients affected by criptogenic focal epilepsy to evaluate the interhemispheric symmetry of the motor cortex excitability. The amplitude of the motor evoked potentials (MEPs) and the duration of the post-MEP silent period (SP) were measured at threshold (THR) and at increasing TCS stimulation intensities. The THR was significantly higher in patients than in 16 age-matched control subjects (p < 0.01). No interhemispheric differences were found in MEP amplitude. In controls, the correlation between SP duration and increasing TCS stimulus intensity was linear with a symmetrical progression of the SP duration over the two hemispheres. In patients this linear SP progression was lacking on the 'epileptic' hemisphere: the SP duration did not increase following TCS > 40% above THR, indicating abnormal interhemispheric asymmetry. This finding suggests a selective dysfunction of inhibition in the epileptic hemisphere as signaled by an abnormal SP duration in response to progressively higher TCS intensities.

Neurophysiological evaluation of tactile space perception deficits through transcranial magnetic stimulation.

We describe a procedure useful to investigate the contralateral space perception deficits frequently encountered in patients with unilateral right brain damage. In particular, we focused on the phenomenon of extinction, i.e., the failure to perceive a contralesional stimulus only when a symmetrical contralateral stimulus is simultaneously applied. Fifteen right brain- and 15 left brain-damaged patients were examined. Somatosensory perception was evaluated by using a dedicated electronic device able to provide electrical stimuli of variable intensity to digits of one or both hands. The electrical stimulator was able to trigger a magnetic brain stimulator connected with a focal figure of eight coil. Threshold electrical stimuli were delivered to one or both hands of the patients, who were asked to indicate whether they perceived the stimulus (i) and to localise it (them). The electrical stimulator was connected with a magnetic stimulator with an interstimulus interval (ISI) of 40 msec (electrical stimulation preceding the transcranial one). Focal threshold transcranial magnetic stimulation (TMS) was applied to frontal and parietal scalp sites of the unaffected hemisphere. At each interpulse interval we found that TMS of the unaffected hemisphere was associated to a decrease in the level of contralesional extinction. Our method demonstrates that a basic deficit underlying neglect and extinction of contralateral space in unilaterally brain damaged patients is the interhemispheric imbalance between the two hemispheres in directing contralateral attention. A transient interference with the function of the unaffected hemisphere can improve these deficits, suggesting a possible application of TMS in the daily clinical practice for speeding up recovery from neglect.

Interhemispheric asymmetries in the perception of unimanual and bimanual cutaneous stimuli. A study using transcranial magnetic stimulation.

Previous studies have shown that transcranial magnetic stimulation (TMS) of the sensorimotor cortex can induce a suppression of cutaneous perception from the fingers of the contralateral hand. In this work, 17 normal subjects were submitted to focal TMS of frontal and parietal scalp sites of each hemisphere. TMS was delivered at two interstimulus intervals (20 and 40 ms) following a cutaneous electrical stimulation of the first, third and fifth digits of either hand or both hands near the subjective threshold of perception. The aim of our study was to investigate whether TMS could detect an asymmetrical hemispheric specialization in the sensory perception of unimanual and bimanual, ipsilateral and contralateral sensory stimuli. At each interpulse interval, the right parietal cortex was significantly more sensitive to TMS interference with stimulus detection for both contralateral and ipsilateral stimuli compared with the left parietal cortex. These effects were mainly evident during bimanual discrimination tasks. Our results are indicative of an interhemispheric difference in the detection of cutaneous sensation, showing right hemispheric prevalence in the perception of contralateral as well as of ipsilateral stimuli. They provide neurophysiological support in normal humans to the clinical evidence which indicates that right hemisphere lesions can indeed produce deficits in the perception of ipsilateral sensory stimuli.

Left frontal transcranial magnetic stimulation reduces contralesional extinction in patients with unilateral right brain damage.

It has been demonstrated previously that transcranial magnetic stimulation (TMS) of the sensorimotor cortex can induce transient suppression of the perception of cutaneous near-threshold stimuli from fingers of the contralateral hand in normal individuals. One explanation accounting for deficits in the exploration of contralateral space following a unilateral hemispheric lesion refers to a loss of the normal interhemispheric balance, with a resultant hyperactivation of the unaffected hemisphere due to the release of reciprocal inhibition by the affected one. In order to verify this hypothesis, we investigated the effects of a TMS-induced transient dysfunction of the normal hemisphere upon contralateral tactile extinctions in two groups: (i) 14 right brain-damaged patients and (ii) 14 left brain-damaged control patients. Single-pulse TMS was delivered to frontal and parietal scalp sites of the unaffected hemisphere after an interval of 40 ms from an electrical unimanual or bimanual digit stimulation. In right brain-damaged patients, left frontal TMS significantly reduced the rate of contralateral extinctions compared with controls. After left parietal TMS, the number of extinctions was comparable to the baseline. This pattern of increased sensitivity to cutaneous stimulation ipsilateral to TMS was not observed in left brain-damaged control patients. In this group, right hemisphere TMS did not significantly alter the recognition of bimanual stimuli delivered to the space contralateral to the lesion. The suggestion is made that extinctions produced by right brain damage may be dependent on a breakdown in the balance of hemispheric rivalry in directing spatial attention to contralateral hemispace, so that the unaffected hemisphere generates an unopposed orienting response to the side of the lesion. The mechanisms whereby the left frontal TMS transiently ameliorates these deficits may involve stimulus-induced removal of a left frontal-right parietal transcallosal inhibitory flow, although interactions at subcortical levels cannot be excluded.

A method to monitor motor cortical excitability in human stroke through motor evoked potentials.

We describe a procedure aimed to analyse Motor Evoked Potentials (MEPs) interhemispheric differences in motor excitability in a monohemispheric subacute stroke population. This protocol has specifically been oriented to scan for any differences in MEPs amplitude at rest and during contractions from a hand muscle, Abductor Digiti Minimi (ADM), after focal Transcranial Magnetic Stimulation (TMS) in both Affected (AH) and Unaffected (UH) Hemispheres. Stroke patients can be included in the protocol if they have suffered acute stroke during the two to four month period to the admission in our rehabilitation hospital. The purpose of this protocol is to establish whether any clear pattern of interhemispheric responsiveness exists and/or to define any possible correlation between MEPs and clinical data. Disability and neurological scores are evaluated to allow a numerical comparison with electrophysiological data. Two recording sessions are planned: the first when the selected patient is admitted (T1) and the second after 8 weeks (T2). Such a period has been arbitrarily chosen because it represents a reliable time after the first recording in order to observe clinical amelioration if present. Criteria for reproducibility of experimental conditions are illustrated.

Follow-up of interhemispheric differences of motor evoked potentials from the 'affected' and 'unaffected' hemispheres in human stroke.

We analysed motor-evoked potentials (MEPs) from the hand muscles during focal transcranial magnetic stimulation (TCS) in both the affected (AH) and the unaffected (UH) hemispheres of 17 monohemispheric stroke patients followed-up in subacute stage. Recording sessions were performed at 2 (T1 session) and 4 (T2 session) months from acute stroke. Clinical and functional scores were evaluated. An age-sex matched group of 20 healthy subjects have been referenced. In T1, relaxed MEPs from AH were smaller than UH (p<0.001) and normals (p<0.001). In T2, an increase of AH relaxed-MEPs amplitude was observed, combined with an improvement of clinical and functional scores (p<0.001). On the other hand, the amplitude of contracted MEPs from the AH in T1 was larger than in the normal group. This parameter decreased toward normal limits in T2, provided that the amplitude of the MEPs from the AH improved, while it further increased when TCS of the AH continued to fail in eliciting MEPs. This phenomenon was statistically combined with clinical improvement of disability and neurological scores. Recovery of the excitability AH threshold with progressive 'balancing' of the UH hyperresponsiveness represents a good prognostic parameter for clinical outcome of hand motor function.

Hand motor cortical area reorganization in stroke: a study with fMRI, MEG and TCS maps.

The anatomical and functional correlates of the hand sensorimotor areas was investigated in a stroke patient with a malacic lesion in the left fronto-parieto-temporal cortex. The patient presented hemiplegia and motor aphasia 12 months earlier, followed by an excellent motor recovery. Transcranial magnetic stimulation mapping, functional magnetic resonance and magnetoencephalography were used as methods of functional imaging and all yielded consistent results. In particular, an asymmetrical enlargement and posterior shift of the sensorimotor areas localized in the affected hemisphere were found with all three techniques. Aspects related to brain 'plasticity' for functional recovery are discussed.

Age and stage dependency of P300 latency alterations in non-demented Parkinson's disease patients without therapy.

Acoustic P300 was recorded from Fz, Cz and Pz by means of an 'odd-ball' paradigm in 44 non-demented de novo Parkinson's disease patients (PD) or PD patients under treatment withdrawal, and in 31 age-matched normal subjects, to evaluate whether a P300 latency increase was present in PD patients. The influence of age and disease stage on latency was successively verified by subgrouping PD patients according to different age ('young' and 'old') and disease stage ('early' or 'advanced'). PD patient data were compared to data of normal subjects subgrouped into 'young' and 'old' or, to eliminate the age-dependent shift of latency, this latter was adjusted to 60 years in all the examined subjects. A significant increase of latency has been found in Fz and Cz in the 'old' group of PD patients (n = 23) but not in the 'young' group (n = 21) utilising both methods. Moreover, a significant latency increase was also present in Fz and Cz in the group of 'advanced' PD patients (n = 8), but not in the group of 'early' PD patients (n = 36) utilising age-adjusted measurements. When the 'early' PD patient group was divided into 'young' (n = 20) and 'old' (n = 16), the 'early old' group displayed significantly increased latencies in Fz compared with normal subjects. Abnormal P300 latencies were observed, at least in one electrode, by analysing the raw data, in 5.0% of the 'early young', 43.7% of the 'early old' and up to 62.7% of the 'advanced' patients. Fz represented the site in which abnormal P300 latencies were most often observed. Moreover, in the total group of PD patients, the P300 delay was significant only on the frontal (Fz) site when compared with normal subjects. The reported findings were interpreted as if PD produces a sort of 'accelerated effect of age' on the cognitive functions, presumably produced by a mechanism different from that producing motor impairment since no clear correlation could be detected between P300 latency and motor score. The frontal impairment of P300 is in line with previous neuropsychological findings obtained in these patients. Considering that about 30% of PD patients develop dementia during their disease progression, a border-line or abnormal P300 latency observed at disease onset may represent a predictive marker of this evolution.

Interhemispheric differences of hand muscle representation in human motor cortex.

Focal magnetic transcranial stimulation (TCS) is employed for mapping of the motor cortical output to abductor digiti minimi (ADM) muscle. The aim of this study was to evaluate the interhemispheric asymmetries in normals. Motor maps were obtained through motor evoked potentials (MEPs) recordings from ADM muscle in 20 healthy subjects in right and left hemispheres TCS. Measurement of several indexes such as excitability threshold, MEPs amplitude, MEPs latency, and silent period duration did not show differences between the hemispheres. Moreover, no interhemispheric asymmetries were found when the amplitude ratio values were analyzed. The hand motor cortical area, as represented by the number of responsive sites (3.6 vs. 3.5) and the "hot spot" site localization presented a fairly symmetrical organization. Absolute values displayed a relatively wide intersubject variability, while their interhemispheric differences were extremely restricted. This observation can offer a new tool in diagnosing and following up neurological disorders affecting the central motor system, mainly for those concerning monohemispheric lesions.

Mapping of motor cortical reorganization after stroke. A brain stimulation study with focal magnetic pulses.

BACKGROUND AND PURPOSE: Focal transcranial magnetic stimulation (TCS) is used for noninvasive and painless mapping of the somatotopical organization of the motor cortex. TCS mapping of motor cortical output to the abductor digiti minimi (ADM) muscle was followed up in monohemispheric stroke patients by evaluating motor evoked potentials (MEPs). This approach allowed noninvasive investigation of the functional reorganization of hand motor areas. METHODS: Motor maps were constructed for 15 subacute stroke patients about 2 months from the ictus by recording MEPs from the ADM muscle via focal TCS in the affected hemisphere (AH) and unaffected hemisphere (UH) at the beginning of (T1) and after 8 to 10 weeks of neurorehabilitation (T2). Barthel Index and Canadian Neurological Scale scores were evaluated as well. An age-sex matched group of 15 healthy control subjects was enrolled to establish normative data. RESULTS: MEP excitability threshold was significantly higher in the AH of stroke patients than in normal subjects and in the UH (P < .001); excitability threshold was not significantly different between normal subjects and UH. In the AH, MEPs were significantly (P < .001) delayed in latency both in T1 and T2, with a significant decrease of the extenuation of motor output area to the ADM muscle (P < .05) in T1 versus control group and UH. This area was significantly enlarged (P < .05) in T2. Amplitude of MEPs from the AH, both at rest and during voluntary contraction, was significantly lower than normal in T1 (P < .001); it increased in T2 (P < .01) during relaxation but was still smaller than normal during contraction (P < .001). In combination with these findings, an improvement of Barthel Index and Canadian Neurological Scale scores (P < .001) was observed between T1 and T2 (P < .001). Central conduction time was prolonged in stroke patients both in T1 and T2. Changes in the shape of motor maps in the AH during follow-up in T2 were either isolated (therefore increasing the interhemispheric asymmetry) or also were "mirrored" on the UH. CONCLUSIONS: Our neurophysiological data are consistent with the presence of a rearrangement of the motor cortical output area and correlate well with an improvement of motor performances. These findings confirm the existence in adults of a "plasticity" in the central nervous system that is still operating between 2 and 4 months from the acute ictal episode. The observed neurophysiological modifications are significantly correlated with clinical improvement of disability and clinical scores.

SEPs N30 amplitude in Parkinson's disease and in pharmacologically induced rigidity: relationship with the clinical status.

The frontal N30 wave amplitude of somatosensory evoked potentials (SEPs) has been studied in 41 Parkinson's disease (PD) patients (pts) in a basal condition and compared to that of 30 normal subjects; moreover the N30 amplitude and clinical motor score have been evaluated in a subgroup of 30 PD pts before and during apomorphine infusion and in a second subgroup of 22 PD pts also during levodopa chronic therapy. The data show that N30 amplitude is decreased in PD pts in basal condition and increased following both treatments by a percentage proportional to the clinical improvement Analysis by non parametric correlations showed that the increase is well correlated to the clinical score amelioration induced by apomorphine in the more affected side. The best correlation was to rigidity score amelioration in the group of PD pts in medium stage (Hohen and Yahr stage between 2 and 3), suggesting a relationship between the rigidity and N30 amplitude decrease. Non parkinsonian subjects, treated with low (11 aged normal subjects) and high (eight young psychotic pts) doses of antidopaminergic drugs, were studied. N30 amplitude decreases were only found in the group of eight psychotic pts showing clinical extrapyramidal signs, produced by the high dose of drug administered, but not in the group treated with the lower dose not producing extrapyramidal side effects, although this dose was efficacious on different modalities of evoked potentials. We conclude that N30 amplitude decrease in PD reflects the dopaminergic lack paralleled by clinical symptoms. We propose that N30 amplitude variations by dopaminergic agonists may be useful in the clinical evaluation of dopamine related and non related tone alterations.

Post-stroke reorganization of brain motor output to the hand: a 2-4 month follow-up with focal magnetic transcranial stimulation.

Focal transcranial magnetic stimulation (TCS) was employed for the representation of the motor cortex in a population of 18 patients to investigate the functional properties of hand motor areas 2-4 months after a monohemispheric stroke. Eleven sites were stimulated to elicit motor evoked potentials (MEPs) in abductor digiti minimi muscle after TCS of affected (AH) and unaffected (UH) hemispheres; recording sessions were performed at the beginning (T1) and after 8-10 weeks (T2) of neurorehabilitation. Barthel index and Canadian neurological scale scores were evaluated. A group of 20 healthy control subjects was enrolled. In stroke patients the AH was less excitable than normal, combined with a decrease in motor cortical output area (P < 0.05) in T1. In T2, there was an enlargement of the hand motor area on the AH combined with an improvement of clinical scores (P < 0.001). In T1 and T2, the amplitude of MEPs in the AH was reduced (P < 0.001) with a prolongation of central conduction time (P < 0.001) and with a tendency towards improvement in T2; the amplitude of contracted MEPs was larger than normal in the UH in T1. Both in T1 and T2, anomalous 'hot spot' (most excitable) scalp sites, never seen in normals, were often encountered (T2 > T1) on the AH and UH. Interhemispheric differences for topography and latency of MEPs were remarkably affected. Our data are consistent with a rearrangement of the brain motor cortical output between 2 and 4 months following stroke. The amelioration of the neurophysiological parameters was correlated with clinical improvement in disability and neurological scores. This study confirms the existence in adults of brain 'plasticity' still operating between 2 and 4 months from an acute vascular monohemispheric insult.