Emotional processing in RRMS patients: Dissociation between behavioural and neurophysiological response.

BACKGROUNG: Multiple sclerosis (MS) results in a broad range of symptoms, including motor, visual, cognitive, and neuropsychiatric deficits. Some studies, considering affective facial expressions to study emotion processing, demonstrated emotion recognition difficulties in MS patients. OBJECTIVE: We investigated the impact of MS on the emotional-behaviour rating and neurophysiological response (Event Related Potentials-ERP) through a battery of affective visual stimuli selected from the International Affective Picture System (IAPS). METHODS: Twenty patients with diagnosis of Relapsing Remitting MS (RRMS) and 20 Healthy Controls (HC) matched by age, gender and education were enrolled. Each of them, after a neuropsychological assessment, were asked to evaluate arousal and valence of affective visual stimuli. RESULTS: Our results showed higher P300 amplitudes in RRMS patients than HC group for pleasant and unpleasant images. Moreover, RRMS patients showed lower Reaction Time (RT) respect HC in valence rating. No other effect did emerge between groups. CONCLUSION: Our study shows early compensatory cerebral mechanisms in RRMS patients throughout emotional information processing, particularly for unpleasant and pleasant stimuli. We hypothesize that this compensatory cerebral mechanism reduces the behavioural dissimilarity between patients and HC.

Cognitive Impairment in Relapsing-Remitting Multiple Sclerosis Patients with Very Mild Clinical Disability.

Cognitive dysfunction affects 40-65% of multiple sclerosis (MS) patients and can occur in the early stages of the disease. This study aimed to explore cognitive functions by means of the Italian version of the minimal assessment of cognitive function in MS (MACFIMS) in relapsing-remitting MS (RRMS) patients with very mild clinical disability to identify the primarily involved cognitive functions. Ninety-two consecutive RRMS patients with Expanded Disability Status Scale (EDSS) scores ≤ 2.5 and forty-two healthy controls (HC) were investigated. Our results show that 51.1% of MS patients have cognitive dysfunction compared to HC. An impairment of verbal and visual memory, working memory, and executive functions was found in the RRMS group. After subgrouping RRMS by EDSS, group 1 (EDSS ≤ 1.5) showed involvement of verbal memory and executive functions; moreover, group 2 (2 ≤ EDSS ≤ 2.5) patients were also impaired in information processing speed and visual memory. Our results show that utilizing a comprehensive neuropsychological assessment, approximately half of MS patients with very mild physical disability exhibit cognitive impairment with a primary involvement of prefrontal cognitive functions. Detecting impairment of executive functions at an early clinical stage of disease could be useful to promptly enroll MS patients in targeted rehabilitation.

Functional and structural balances of homologous sensorimotor regions in multiple sclerosis fatigue.

Fatigue in multiple sclerosis (MS) is a highly disabling symptom. Among the central mechanisms behind it, an involvement of sensorimotor networks is clearly evident from structural and functional studies. We aimed at assessing whether functional/structural balances of homologous sensorimotor regions-known to be crucial for sensorimotor networks effectiveness-decrease with MS fatigue increase. Functional connectivity measures at rest and during a simple motor task (weak handgrip of either the right or left hand) were derived from primary sensorimotor areas electroencephalographic recordings in 27 mildly disabled MS patients. Structural MRI-derived inter-hemispheric asymmetries included the cortical thickness of Rolandic regions and the volume of thalami. Fatigue symptoms increased together with the functional inter-hemispheric imbalance of sensorimotor homologous areas activities at rest and during movement, in absence of any appreciable parenchymal asymmetries. This finding supports the development of compensative interventions that may revert these neuronal activity imbalances to relieve fatigue in MS.

Oral fingolimod reduces glutamate-mediated intracortical excitability in relapsing-remitting multiple sclerosis.

OBJECTIVE: Fingolimod is an effective disease modifying therapy for multiple sclerosis (MS). Beyond its main action on peripheral lymphocytes, several noteworthy side effects have been demonstrated in vitro, among which modulation of neural excitability. Our aim was to explore cortical excitability in vivo in patients treated with fingolimod 0.5mg/day. METHODS: Paired-pulse TMS was applied on the left primary motor cortex in 13 patients affected by relapsing-remitting MS, the day before the first dose of fingolimod (T0) and 60days later (T1). Resting motor threshold, baseline motor evoked potentials, short interval intracortical inhibition (at 1, 3, 5ms) and intracortical facilitation (at 7, 9, 11 and 13ms) were estimated at T0 and T1. RESULTS: Intracortical facilitation was reduced at T1, without any changes in short interval intracortical inhibition. CONCLUSIONS: Fingolimod selectively reduced intracortical facilitation, which is mainly mediated by glutamate. SIGNIFICANCE: This is the first in vivo confirmation of the effects of fingolimod on glutamatergic drive in treated humans. Our results suggest a novel neuromodulatory activity of fingolimod with potential effect on glutamate-mediated excitotoxicity in vivo, as already seen in animal models.

Inter-hemispheric functional connectivity changes with corpus callosum morphology in multiple sclerosis.

Multiple sclerosis (MS) affects myelin sheaths within the central nervous system, concurring to cause brain atrophy and neurodegeneration as well as gradual functional disconnections. To explore early signs of altered connectivity in MS from a structural and functional perspective, the morphology of corpus callosum (CC) was correlated with a dynamic inter-hemispheric connectivity index. Twenty mildly disabled patients affected by a relapsing-remitting (RR) form of MS (EDSS⩽3.5) and 15 healthy subjects underwent structural MRI to measure CC thickness over 100 sections and electroencephalography to assess a spectral coherence index between primary regions devoted to hand control, at rest and during an isometric handgrip. In patients, an overall CC atrophy was associated with increased lesion load. A less efficacious inter-hemispheric coherence (IHCoh) during movement was associated with CC atrophy in sections interconnecting homologous primary motor areas (anterior mid-body). In healthy controls, less efficacious IHCoh at rest was associated with a thinner CC splenium. Our data suggest that in mildly disabled RR-MS patients a covert impairment may be detected in the correlation between the structural (CC thickness) and functional (IHCoh) measures of homologous networks, whereas these two counterparts do not yet differ individually from controls.

Functional and molecular evidence of myelin- and neuroprotection by thyroid hormone administration in experimental allergic encephalomyelitis.

AIMS: Recent data in mouse and rat demyelination models indicate that administration of thyroid hormone (TH) has a positive effect on the demyelination/remyelination balance. As axonal pathology has been recognized as an early neuropathological event in multiple sclerosis, and remyelination is considered a pre-eminent neuroprotective strategy, in this study we investigated whether TH administration improves nerve impulse propagation and protects axons. METHODS: We followed up the somatosensory evoked potentials (SEPs) in triiodothyronine (T3)-treated and untreated experimental allergic encephalomyelitis (EAE) Dark-Agouti female rats during the electrical stimulation of the tail nerve. T3 treatment started on the 10th day post immunization (DPI) and a pulse administration was continued until the end of the study (33 DPI). SEPs were recorded at baseline (8 DPI) and the day after each hormone/ vehicle administration. RESULTS: T3 treatment was associated with better outcome of clinical and neurophysiological parameters. SEPs latencies of the two groups behaved differently, being briefer and closer to control values (=faster impulse propagation) in T3-treated animals. The effect was evident on 24 DPI. In the same groups of animals, we also investigated axonal proteins, showing that T3 administration normalizes neurofilament immunoreactivity in the fasciculus gracilis and tau hyperphosphorylation in the lumbar spinal cord of EAE animals. No sign of plasma hyperthyroidism was found; moreover, the dysregulation of TH nuclear receptor expression observed in the spinal cord of EAE animals was corrected by T3 treatment. CONCLUSIONS: T3 supplementation results in myelin sheath protection, nerve conduction preservation and axon protection in this animal model of multiple sclerosis.

High frequency repetitive transcranial magnetic stimulation decreases cerebral vasomotor reactivity.

OBJECTIVE: Repetitive Transcranial Magnetic Stimulation (rTMS) has been recently employed as a therapeutic strategy for stroke, although its effects on cerebral hemodynamics has been poorly investigated. This study aims to examine the impact of high frequency rTMS on cerebral vasomotor reactivity (VMR). METHODS: Twenty-nine healthy subjects were randomly assigned to real (19) or sham 17-Hz rTMS, applied on primary motor cortex (M1) of the dominant hemisphere. All subjects underwent Transcranial Doppler of the middle cerebral arteries to evaluate mean flow velocity and VMR before (T(0)) and within 10 min (T(1)) following rTMS. Four subjects underwent further VMR evaluations at 2 (T(2)), 5 (T(3)) and 24 h (T(4)) after rTMS. As a control condition, 10 subjects underwent real (5) or sham rTMS on calcarine cortex. In addition, five acute stroke patients underwent five daily rTMS sessions on the affected hemisphere mimicking a therapeutic trial. RESULTS: Following real rTMS on M1 (p=0.002) and calcarine cortex (p<0.001) VMR decreased with respect to T(0) in both hemispheres, while no change was observed after sham rTMS (p>0.6). VMR tended to remain lower than T(0) until T(3.) Cerebral VMR decreased independently of the stimulated side also in the patients' group. CONCLUSIONS: High frequency rTMS reduces cerebral VMR, possibly as a secondary effect on autonomic control of cerebral hemodynamics. SIGNIFICANCE: The effect of rTMS on cerebral hemodynamics should be carefully considered before proceeding toward a therapeutic application in stroke patients.

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.

Are autonomic signals influencing cortico-spinal motor excitability? A study with transcranial magnetic stimulation.

In order to investigate the role of visceral afferent inputs flowing along autonomic fibers on corticospinal tract excitability, the variability of Motor Evoked Potentials (MEPs), elicited by Transcranial Magnetic Stimulation (TMS), was analysed during simultaneous monitoring of electrocardiogram (EKG) phases, breathing phases and sudomotor skin responses (SSRs) in a group of 10 healthy subjects. A cascade of at least 60 consecutive magnetic stimuli, with an interstimulus interval randomly varying between 20 and 40 s, was acquired. At the end of the recording session, the subject was asked to make at random five not consecutive self-paced forced inspirations. TMS was carried out at an intensity 10% above motor threshold excitability via a circular coil placed over the motor area of the right hemisphere. MEPs were recorded from the contralateral abductor digiti minimi muscle (ADM). Sudomotor Skin Responses (SSRs) were recorded on both hand palms. MEPs latency and amplitude did not show significant correlation with any of the EKG and respiratory phases. During forced inspiration, a significant latency shortening was found. TMS elicited SSRs, whose amplitudes were not correlated with MEP parameters. During forced inspiration a significant SSR amplitude increment, not correlated with MEP latency shortening, was also observed. These results assign a minor if any role to the considered autonomic parameters in modulating corticospinal motor excitability.

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.

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.

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.

Effect of paired transcranial magnetic stimulation on the cortical silent period.

OBJECTIVE: To investigate the behaviour of silent period (SP) during paired magnetic cortical stimulation. BACKGROUND: Paired cortical magnetic stimulation is known to inhibit or facilitate motor evoked potentials (MEPs), but no attention has been paid to its effect on SP. METHODS: SP was measured in the contracted first dorsal interosseus muscle after paired cortical stimuli at given interstimulus intervals (ISIs) in eight healthy subjects. Test stimulus intensity was fixed at 110% of resting threshold (RT), while three levels of conditioning stimulus intensities at 40%, 65% and 90% RT were separately employed. We also examined the effect of progressively increasing the test stimulus intensity (120-150 RT) on SP while maintaining stable conditioning stimulus intensity. RESULTS: 65% RT conditioning stimulus shortened the SP at 1-3 ms ISIs with MEP size reduction, and prolonged the SP at 15-20 ms ISIs without affecting MEP size. 90% RT conditioning stimulus showed only SP prolongation, while 40% RT showed only SP shortening at 1 ms ISI. The SP shortening at 2 ms ISI was the most evident with 120% RT test stimulus, but without correlation with the MEP size. The SP prolongation at 15 ms ISI was maximal with 110% RT test stimulus and then almost abolished with 150% RT. The SP shortening at short intervals might be due not only to spinal but also to suprasegmental mechanisms, conceivably mediating cortical excitatory drive to the corticospinal tract. The SP prolongation at intermediate intervals might be due to activation of slowly conducting, intra- or sub-cortical polysynaptic pathways exerting a facilitatory drive on the cortical inhibitory interneurons.

Modulation of intracortical excitability for different muscles in the upper extremity: paired magnetic stimulation study with focal versus non-focal coils.

OBJECTIVE: Intracortical excitability was studied for 4 muscles in the upper extremity by paired transcranial magnetic stimulation on the motor cortex, using focal and non-focal coils. METHODS: Surface EMG responses of two hand and two forearm muscles were simultaneously recorded in 13 healthy subjects, after delivering paired stimuli at interstimulus intervals (ISIs) of 1-50 ms using circular and figure-of-8 (focal) coils. The intensities of conditioning and test stimuli were submotor and supramotor thresholds, respectively. RESULTS: Paired stimulation using a circular coil showed constant inhibition at 2 ms ISI for all muscles, but not at 5 ms ISI, and induced facilitation at 10 ms ISI. The results using a focal coil were similar to those with a circular coil at all ISIs except at 5 ms ISI, where the former showed inhibition. At 20 and 30 ms ISIs, there was interindividual variability for both coils, some subjects showing inhibition and others facilitation. CONCLUSIONS: The difference of the inhibition at 5 ms ISI between using circular and focal coils could be attributed to the cortical mechanism. The inhibitory effect at 2 ms ISI, consistently observed for the 4 muscles with both types of coil, could be easily applied to assess the inhibitory intracortical function in patients with neurological diseases.

Neurophysiology of sensorimotor integration in Parkinson's disease.

Parkinson's disease (PD) is a major neurologic disorder that distinctively and selectively affects movement and--by extension--the motor system. A large body of evidence has been accumulated over the years showing that movement disorders of PD are also due to sensory disturbances that affect sensorimotor integration. The aim of this review is to discuss the possible contribution of neurophysiologic techniques in evaluating the functionality of sensorimotor integration mechanisms in PD. Somatosensory evoked potentials (SEPs) are an appropriate functional approach for the evaluation of sensory processes in the human brain. SEPs from the frontal scalp sites are considered markers of the functionality of a cortico-subcortico-cortical loop that includes the basal ganglia as well as the premotor and supplementary motor areas. Over the years, it has been demonstrated that PD patients--especially in the early stages of the disease--show a severely depressed frontal responsiveness to sensory stimuli as tested via SEPs. The transient recovery of frontal SEP amplitude after apomorphine, a potent dopamine agonist drug, is a good and specific predictor of the clinical response of PD patients to L-dopa therapy.