Excitability In Patients Research Articles

Gait Training—Induced Change in Corticomotor Excitability in Patients With Chronic Stroke

Background. Numerous studies have reported the effects of gait training on motor performance after stroke. However, there is limited information on treatment-induced changes in corticomotor excitability. Objectives. The purpose of the study was to investigate the effects of additional gait training on motor performance and corticomotor excitability and to demonstrate the relationship between motor improvement and corticomotor excitability change in patients with chronic stroke. Methods. Fourteen patients were randomly assigned to the experimental or control group. Participants in both groups participated in general physical therapy. Those in the experimental group received additional body weight− supported treadmill training for 4 weeks. All participants received baseline and posttreatment assessments. The outcome measures included assessment of the Berg Balance Scale (BBS) and gait parameters. Focal transcranial magnetic stimulation was used to measure the motor threshold, map size, and location of the amplitude-weighted center of gravity of the motor map for the tibialis anterior (TA) and abductor hallucis (AH) muscles. Results . After general physical therapy, we noted that the patients showed an improvement only in walking speed and cadence, and there were no significant changes in corticomotor excitability. After additional gait training, participants improved significantly on BBS score, walking speed, and step length. Moreover, the motor threshold for TA decreased significantly in the unaffected hemisphere. The map size for TA was increased in both hemispheres, whereas that for AH was increased only in the affected hemisphere. There were significant differences between the change scores of the groups in terms of walking speed, step length, and motor threshold for TA in the unaffected hemisphere and map size for AH in the affected hemisphere. Additionally, the changes in corticomotor excitability correlated with functional improvement. Conclusions . Additional gait training may improve balance and gait performance and may induce changes in corticomotor excitability.

Motor Cortex Excitability After Vagus Nerve Stimulation in Major Depression

Recent data suggest that inhibitory pathways may be involved in the pathophysiology of depression and in the mode of action of some antidepressant interventions. The aim of the present study was to test whether vagus nerve stimulation (VNS) can affect motor cortex excitability. Measures of motor cortical excitability were probed by using single-pulse and paired-pulse transcranial magnetic stimulation at baseline, after 10 weeks of left VNS, and additionally, in an on-off paradigm in 10 patients with treatment-resistant unipolar depression. Ten weeks of VNS was associated with a selective and pronounced increase in intracortical inhibition, whereas no changes occurred in the on-off paradigm. These results suggest that VNS is capable of changing motor cortical excitability in patients with depression.

Effects of spinal cord stimulation on cortical excitability in patients with chronic neuropathic pain: A pilot study

Background Despite a broad clinical use, the mechanism of action of SCS is poorly understood. Current information suggests that the effects of SCS are mediated by a complex set of interactions at several levels of the nervous system including spinal and supraspinal mechanisms. Aims The study was undertaken to investigate the influence of SCS on distinct parameters of cortical excitability using single- and paired-pulse transcranial magnetic stimulation (TMS). Methods Five patients with chronic neuropathic pain were examined with the SCS stimulator on and off by means of TMS. Pain was assessed using a visual-analogue scale. Electrophysiological and pain parameters of patients during this procedure were compared by means of a linear mixed effect model. Results SCS induced a significant modulation of cortical excitability, especially by influencing the parameter “intracortical facilitation” ( t = −2.657; df = 8; p = 0.029). A significant relationship between this parameter and “perceived pain” could be obtained ( t = −4.798; df = 8; p = 0.002). Conclusions These results suggest that SCS is able to influence neurobiological processes at the supraspinal level and that clinical effects of SCS may be at least in part of cortical origin.

Changes in blink reflex excitability after globus pallidus internus stimulation for dystonia

A pathophysiological feature of dystonia is reduced inhibition at various levels of the nervous system, which may be detected in clinically unaffected body parts. Chronic deep brain stimulation (DBS) of the globus pallidus internus (GPi) has emerged as an effective treatment for primary torsion dystonia (PTD), although its mechanism of action and impact on inhibitory abnormalities in dystonia are unknown. We sought to understand the effect of GPi DBS on brainstem excitability in patients with PTD. We measured the blink reflex from orbicularis oculi in response to paired electrical stimulation of the supraorbital nerve at interstimulus intervals of 500 and 1,000 milliseconds in 10 patients with PTD before and at intervals of 1, 3, and 6 months after bilateral GPi DBS and in 10 healthy subjects. Patients were clinically evaluated using the Burke-Fahn-Marsden dystonia rating scale. We found R2 inhibition was significantly decreased in PTD patients compared with control subjects and progressively increased after GPi DBS, which correlated with clinical improvement in dystonia. We conclude that GPi DBS for PTD results in functional reorganization of the nervous system, which includes a long-term increase in brainstem inhibition.

Cabergoline reverses cortical hyperexcitability in patients with restless legs syndrome

To reverse the profile of abnormal intracortical excitability in patients with restless legs syndrome (RLS) by administering the dopaminergic agonist cabergoline. The effects of this drug on motor cortex excitability were examined with a range of transcranial magnetic stimulation (TMS) protocols before and after administration of cabergoline over a period of 4 weeks in 14 patients with RLS and in 15 healthy volunteers. Measures of cortical excitability included central motor conduction time; resting and active motor threshold to TMS; duration of the cortical silent period; short latency intracortical inhibition (SICI) and intracortical facilitation using a paired-pulse TMS technique. Short latency intracortical inhibition was significantly reduced in RLS patients compared with the controls and this abnormal profile was reversed by treatment with cabergoline; the other TMS parameters did not differ significantly from the controls and remained unaffected after treatment with cabergoline. Cabergoline had no effect on cortical excitability of the normal subjects. As dopaminergic drugs are known to increase SICI, our findings suggest that RLS may be caused by a central nervous system dopaminergic dysfunction. This study demonstrates that the cortical hyperexcitability of RLS is reversed by cabergoline, and provides physiological evidence that this dopamine agonist may be a potentially efficacious option for the treatment of RLS.

Homeostatic effects of plasma valproate levels on corticospinal excitability changes induced by 1 Hz rTMS in patients with juvenile myoclonic epilepsy

Objective The preliminary results of noninvasive brain stimulation for epilepsy treatment have been encouraging, but mixed. Two important factors may contribute to this heterogeneity: the altered brain physiology of patients with epilepsy and the variable presence of antiepileptic drugs. Therefore, we aimed to study the effects of 1 Hz rTMS on corticospinal excitability in patients with juvenile myoclonic epilepsy (JME) in two different conditions: low- or high-plasma valproate levels. Methods Fifteen patients with JME and 12 age-matched healthy subjects participated in this study. Corticospinal excitability before and after 1 Hz rTMS was assessed in JME patients with low- and high-plasma valproate levels; and these results were compared with those in healthy subjects. Results In patients with chronic use of valproate and low-plasma concentrations, 1 Hz rTMS had a similar significant inhibitory effect on corticospinal excitability as in healthy subjects. However, in the same patients when the serum valproate concentration was high, 1 Hz rTMS increased the corticospinal excitability significantly. In addition, there was a significant positive correlation between plasma valproate levels and the motor threshold changes after 1 Hz rTMS. Conclusions Our findings can be accounted for by mechanisms of homeostatic plasticity and illustrate the dependency of the modulatory effects of rTMS on the physiologic state of the targeted brain cortex. Significance The therapeutic use of rTMS in epilepsy should take into consideration the interaction between rTMS and drugs that change cortical excitability.

Sacral Nerve Stimulation Reduces Corticoanal Excitability in Patients With Faecal Incontinence

Sacral Nerve Stimulation Reduces Corticoanal Excitability in Patients With Faecal Incontinence

Altered response to rTMS in patients with Alzheimer's disease

Objective In this study, we tested the excitability of cortical motor areas in patients with Alzheimer's disease. Because repetitive transcranial magnetic stimulation (rTMS) modulates cortical excitability, possibly by inducing a short-term increase in synaptic efficacy, we used rTMS to investigate motor cortex excitability in patients with Alzheimer's disease. Methods We tested the changes in the size and threshold of motor evoked potential (MEP) and cortical silent period (CSP) duration evoked by focal rTMS delivered in 10 trains of 10 stimuli at 5 Hz frequency and 120% rMth intensity in a group of patients with Alzheimer's disease, and age-matched controls. In a further session, rTMS was also delivered at 1 Hz frequency (trains of 10 stimuli, 120% rMth). Results Whereas in control subjects, 5 Hz-rTMS elicited normal MEPs that progressively increased in size during the train, in patients, it elicited MEPs that decreased in size. The increase in the duration of the CSP was similar in patients and healthy controls. One hertz rTMS left the MEP amplitude unchanged in patients and healthy controls. Conclusions The lack of MEP facilitation reflects an altered response to 5 Hz-rTMS in patients with Alzheimer's disease. Significance Our rTMS findings strongly suggest an altered cortical plasticity in excitatory circuits within motor cortex in patients with Alzheimer's disease.

Effects of sleep deprivation on cortical excitability in patients affected by juvenile myoclonic epilepsy: a combined transcranial magnetic stimulation and EEG study

Objective: To investigate the effect of sleep deprivation on corticospinal excitability in patients affected by juvenile myoclonic epilepsy (JME) using different transcranial magnetic stimulation (TMS) parameters. Methods: Ten patients with...

Corticospinal Excitability in Patients With Chronic Low Back Pain

This study was designed to investigate corticospinal excitability of lumbar muscles using transcranial magnetic stimulation (TMS) in patients with chronic low back pain and correlate this with self-rated measures of disability and pain. Twenty-four patients with chronic low back pain and 11 healthy control subjects were used in this study. TMS was delivered through an angled double-cone coil, with its cross-over on the vertex and a posterior-to-anterior current flow in the brain. Electromyographic (EMG) recordings were made from erector spinae (ES) muscles at the fourth lumbar level. Motor cortical excitability was assessed using motor threshold (MTh) for motor evoked potentials (MEPs) and threshold for silent period (SP) during facilitation of the back muscles. Latency, duration, and area of MEPs and SPs were also measured. The latency, duration, and size of MEPs and SPs did not differ between the left and right ES muscles in either the patients or the control subjects and also did not differ between the patients and the control subjects. However, there was a significantly higher MTh and threshold for the SP in the patients as compared with the control subjects; the full significance of this requires further investigation. Interestingly, there was a positive correlation between the self-rated measure of disability (the Oswestry Disability Index score) and both the MTh and the threshold for the SP in the patients. There was also a positive correlation between the self-rated index of back pain and the threshold for the SP in the patients. This finding of an association between clinical and neurophysiologic measures reinforces the need for further research to establish the clinical relevance of these rises in MTh and SP threshold. In summary, this study has revealed that corticospinal excitability, driving ES muscles close to the site of pain, is lowered in patients with chronic low back pain.

Repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex and cortical excitability in patients with major depressive disorder

Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex is a relatively non-invasive technique with putative therapeutic effects in major depression. However, the exact neurophysiological basis of these effects needs further clarification. Therefore, we studied the impact of ten daily sessions of left, dorsolateral prefrontal rTMS on motor cortical excitability, as revealed by transcranial magnetic stimulation-elicited motor-evoked potentials in 30 patients. As compared to the non-responders, responders (33%) showed changes in parameters pointing towards a reduced cortical excitability. These results suggest that repetitive transcranial magnetic stimulation of the dorsolateral, prefrontal cortex may have inhibitory effects on motor cortical neuronal excitability in patients with major depressive disorder. Furthermore, measurement of motor cortical excitability may be a useful tool for investigating and monitoring inhibitory brain effects of antidepressant stimulation techniques like rTMS.

Corticospinal excitability during motor imagery of a simple tonic finger movement in patients with writer's cramp

Motor imagery (MI) is the mental rehearsal of a motor act without overt movement. Using transcranial magnetic stimulation (TMS), we tested the effect of MI on corticospinal excitability in patients with writer's cramp. In 10 patients with writer's cramp and 10 healthy controls, we applied focal TMS over each primary motor area and recorded motor evoked potentials (MEPs) from contralateral hand and arm muscles while participants imagined a tonic abduction of the index finger contralateral to the stimulated hemisphere. In healthy controls and patients, the MEP amplitude in the relaxed first dorsal interosseus muscle (FDI) showed a muscle-specific increase during MI; however, the increase was less pronounced in patients than in healthy controls. In addition, in patients but not in controls, the MEP amplitude also increased in hand and forearm muscles not involved in the imagined movement. This abnormal spread of facilitation was observed in the affected and unaffected upper limb. MI of simple hand movements is less efficient and less focussed in patients with writer's cramp than it is in normal subjects.

Sacral nerve stimulation reduces corticoanal excitability in patients with faecal incontinence

Sacral nerve stimulation (SNS) can produce symptomatic relief in patients with faecal incontinence. Moreover, peripheral nerve stimulation has been shown to affect brain function. The aim of this study was to determine whether SNS might produce important changes in cortical activity linked to improved continence. In an experimental study, ten women with intractable faecal incontinence (mean age 51.3 years) were serially mapped with transcranial magnetic stimulation before and immediately after 14 days of temporary SNS (15 Hz, pulse width 210 micros), and then 2 weeks later. Anal sphincter electromyographic responses were recorded to cortical stimulation of multiple points over a scalp grid covering the bilateral medial cortex. Continence scores, anorectal manometry and rectal sensitivity data were also collected. SNS improved global symptom scores in the majority of patients; mean(s.e.m.) continence scores fell from 16.9(1.6) to 10.6(1.8) (P = 0.042). Cortical mapping showed a consistent decrease in corticoanal representation and overall excitability immediately after SNS compared with baseline (mean(s.e.m.) 38,083(13,669) versus 42,507(13,297) microV s; P = 0.017), which was reversed 2 weeks after SNS wire removal. SNS produces symptom benefit in patients with faecal incontinence that is associated with a reversible reduction in corticoanal excitability. SNS therefore drives dynamic brain changes that may play a functional role in influencing anal continence.

Cortical Inhibition Is Reduced in Chronic and Episodic Migraine and Demonstrates a Spectrum of Illness

The pathophysiological relationship between episodic migraine and chronic migraine is not fully understood. We aimed to examine transcranial magnetic stimulation (TMS) indices of cortical excitability in patients with episodic migraine (EM) and probable chronic migraine (PCM), and matched controls. Cortical excitability was assessed at baseline with two well-established methods: phosphene thresholds (PT) and magnetic suppression of perceptual accuracy (MSPA) profiles. Five EM patients, five PCM patients, and five normal controls participated in the main study. In addition, two patients were reassessed after 30 days of treatment with topiramate. Both PT and MPSA measures were consistent in indicating a continuum of excitability across the three groups: PCM patients had the highest excitability, followed by EM, then controls. In the two treated patients MPSA profiles appeared to normalize at a 100 mg dosage. Patients with PCM appear to be characterized by very high cortical excitability. This may contribute to their greatly increased attack frequency. TMS-based methods will be important for future research examining the evolution of chronic migraine from episodic migraine over time.

Lack of Effect of Botulinum Toxin on Cortical Excitability in Patients With Cranial Dystonia

The aim of this study was to verify whether botulinum toxin (BTX)-induced clinical improvement of cranial dystonia is associated with changes in the cortical silent period (SP), a measure of cortical excitability. By transcranial magnetic stimulation (TMS), high-intensity stimuli were delivered with a round coil centered at the vertex during a maximal muscle contraction of the orbicularis oculi. Motor evoked potentials (MEPs) and SPs were obtained from surface electrodes placed over the orbicularis oculi muscle before and 2 to 3 weeks after BTX-A injection into the affected muscles in 10 patients with cranial dystonia and 8 age-matched control subjects. BTX injection improved blepharospasm in all patients. Facial muscle SPs were significantly shorter in patients than in control subjects and did not significantly change after treatment, at the time of maximal clinical improvement. We conclude that the clinical improvement induced by BTX in patients with cranial dystonia is largely symptomatic. It does not appear to result from modulation of abnormal aspects of intracortical excitability, although these may play a role in craniofacial dystonia.

OPL159 Assessment of the effects of sleep deprivation on cortical excitability in patients with new onset seizures using transcranial magnetic stimulation

OPL159 Assessment of the effects of sleep deprivation on cortical excitability in patients with new onset seizures using transcranial magnetic stimulation

Pallidotomy effect on the cortical excitability in patients with severe Parkinson's disease

Surgical lesions in the medial pallidum have been shown to ameliorate motor deficits in patients with Parkinson's disease (PD). It is believed that interruption of the pallidothalamocortical projections to the motor cortex is required for the satisfactory results. In this report, we adopt cortico-cortical inhibition as the tool to assess the pallidotomy effect on cortical excitability in PD. Interstimulus interval between 1 and 15 msec were investigated. The average peak-to-peak amplitude was measured and calculated at each delay. A total of 8 patients (M:F = 4:4) 54.9 years of age (SD = 9.6) and 10 controls were recruited for the study. In the controls, the inhibitory phenomenon was observed from the 1-msec to the 4-msec delay points and the maximal inhibition was at the 3-msec delay point (33.69% +/- 6.50% of the control response). Mild facilitation was noticed since the 5-msec delay point and thereafter. In patients before operation, a similar trend of inhibition was also observed in the initial 4 msec with the maximal inhibition also at the 3-msec delay point (64.66 +/- 6.77% of the control response). In the postoperative group, the short interstimulus interval inhibition can no longer be observed and the conditioned response was 95.06 +/- 23.68% of the control at the 3-msec delay point. The suppression was gone at and after the 7-msec delay point. Results of repeated-measures analysis of variance show a significant difference among the controls and PD patients before and 3 months after pallidotomy (F = 3.40, P = 0.05). Post hoc examination revealed a significant difference between the controls and PD patients 3 months after pallidotomy at the 3-msec delay point (P = 0.004). However, no correlation was observed between the 3-msec inhibition and the Unified Parkinson's Disease Rating Scale Motor score or the dyskinesia score. The results suggest that pallidotomy can modulate the cortical inhibitory circuitry in patients with PD.

A “new-old” way of thinking about brain disorder, cerebral excitability – the fundamental property of nervous tissue

Cerebral excitability is normally distributed, and pubertal age is a distinguishing factor. The final developmental event in CNS comprising selective pruning of excitatory synapses coincides with puberty. With early puberty, excess excitation and synaptic density, we have photic susceptibility, paroxysmal EEGs, disturbed circadian rhythms, paroxysmal disorders treated with drugs lowering excitation. Manic-depressive psychosis accords with this. Migraine with paroxysmal EEG, photophobia, hemianopsia, scintillating scotomas, excess excitation in the visual system, benefits from lowering excitation. With late puberty, attenuated CNS, we have disorders in need of raising excitation to avoid breakdown of circuitry, insufficient fill-in mechanism, silent spots, subjectively experienced only – objectively verifiable psychosis: i.e., schizophrenia treated with convulsant neuroleptics. By affecting pubertal age, we affect the distribution of excitation and of post-pubertal brain disorders in accordance with their level of excitation. Excitation is equally important in chronic disorders: l'dopa adversity in Parkinsonism could be due to further lowering of excitation in patients with a deficiency, a schizophrenia-like psychosis develops. Given unavoidable adversity of anti-psychotics, and a marked rise in suicide in schizophrenic and manic-depressive since their introduction, we want to prevent the occurrence of disorders at the extremes, whether very early or late puberty. DHA normalises excitability at all levels of excitation. An adequate daily intake of DHA, before puberty as well as after, might probably reduce or eliminate a development of psychopathology. Lithium is a robust neurotropic agent, and lithiation of the drinking water could be a way of reducing suicide, homicide, violent behaviour, and drug abuse.

Repetitive transcranial magnetic stimulation reveals abnormal plastic response to premotor cortex stimulation in schizophrenia

Schizophrenia may be characterized by abnormal plastic modulation in cortical neuronal circuits. Activation of premotor cortex using repetitive transcranial magnetic stimulation (rTMS) produces suppression of cortical excitability in primary motor cortex. We hypothesized that premotor rTMS would cause less suppression of motor cortical excitability in patients with schizophrenia than in control subjects. Twelve patients diagnosed with schizophrenia and twelve healthy control subjects underwent subthreshold rTMS to the premotor area in a 15-min conditioning train. Measurements of primary motor cortical excitability (motor evoked potential; MEP), the resting motor threshold (RMT), and cortical inhibition (CI) were taken before and after the rTMS. There was no difference in RMT between groups at baseline, although the patient group had less CI than the control group at baseline. Following rTMS, the change in both MEP size and RMT between groups was significant. After rTMS, MEP size was suppressed in the control group and increased in the patient group, whereas RMT increased in the normal control group and decreased in the patient group. Patients with schizophrenia demonstrate abnormal brain responses to rTMS applied to the premotor cortex that appear to relate to reduced motor cortical inhibition.

Effect of electroconvulsive therapy on cortical excitability in patients with major depression: a transcranial magnetic stimulation study

Objective The antidepressant action of electro-convulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) may be related to their ability to modulate cortical excitability. The aim of this study was to investigate changes in cortical excitability following ECT in patients with major depression (MD) and to compare therapeutic efficacy of ECT combined with rTMS to that of ECT alone. Methods Twenty-two patients with MD were assigned to receive ECT and right prefrontal 1 Hz rTMS ( n=12) or ECT with sham rTMS ( n=10). ECT was given twice weekly and rTMS was applied on the remaining 4 days, throughout 3 weeks. The resting motor threshold (rMT) and motor evoked potential (MEP)/M-wave area ratio were evaluated before and 6 h after the first, third and sixth ECT session. The active motor threshold (aMT), intra-cortical inhibition (ICI) and intra-cortical facilitation (ICF) were measured at baseline and 24 h after the last ECT. Results There were no significant differences in the degree of clinical improvement and measures of cortical excitability in the ECT+active rTMS group as compared to the ECT+sham rTMS group. Marked clinical improvement observed in 19 out of the 22 patients was associated with a significant increase of the MEP/M-wave area ratio, decrease of the aMT and reduction of the ICI in the left hemisphere. Conclusions The antidepressant effect of ECT was associated with an enhancement of left hemispheric excitability. rTMS did not add to the beneficial effect of ECT. However, the small sample size and the robust effect of ECT might have obscured a potential therapeutic effect of rTMS. Significance Measures of cortical excitability may provide insight to our understanding of the mechanism of action of ECT and might be useful for the assessment of treatment response.