Motor Cortex In Patients Research Articles

Excitability of the motor cortex in patients with migraine changes with the time elapsed from the last attack

BackgroundMotor-evoked potentials (MEPs) produced by single-pulse transcranial magnetic stimulation (TMS) of the motor cortex can be an objective measure of cortical excitability. Previously, MEP thresholds were found to be normal, increased, or even reduced in patients with migraine. In the present study, we determined whether the level of cortical excitability changes with the time interval from the last migraine attack, thereby accounting for the inconsistencies in previous reports.MethodsTwenty-six patients with untreated migraine without aura (MO) underwent a MEP study between attacks. Their data were then compared to the MEP data collected from a group of 24 healthy volunteers (HVs). During the experiment, the TMS figure-of-eight coil was positioned over the left motor area. After identifying the resting motor threshold (RMT), we delivered 10 single TMS pulses (rate: 0.1 Hz, intensity: 120% of the RMT) and averaged the resulting MEP amplitudes.ResultsThe mean RMTs and MEP amplitudes were not significantly different between the MO and HV groups. In patients with MO, the RMTs were negatively correlated with the number of days elapsed since the last migraine attack (rho = -0.404, p = 0.04).ConclusionOur results suggest that the threshold for evoking MEPs is influenced by the proximity of an attack; specifically, the threshold is lower when a long time interval has passed after an attack, and is higher (within the range of normative values) when measured close to an attack. These dynamic RMT variations resemble those we reported previously for visual and somatosensory evoked potentials and may represent time-dependent plastic changes in brain excitability in relation to the migraine cycle.

Cervical Spondylotic Myelopathy: Metabolite Changes in the Primary Motor Cortex after Surgery.

Purpose To characterize longitudinal metabolite alterations in the motor cortex of patients with cervical spondylotic myelopathy (CSM) by using proton magnetic resonance (MR) spectroscopy and to evaluate white matter integrity with diffusion-tensor imaging in patients who are recovering neurologic function after decompression surgery. Materials and Methods Informed written consent was obtained for all procedures and the study was approved by Western University's Health Sciences Research Ethics Board. Twenty-eight patients with CSM and 10 healthy control subjects were prospectively recruited and underwent two separate 3-T MR imaging examinations 6 months apart. Patients with CSM underwent surgery after the first examination. N-acetylaspartate (NAA), an indicator of neuronal mitochondrial function, normalized to creatine (Cr) levels were measured from the motor cortex contralateral to the greater functional deficit side in the patient group and on both sides in the control group. Fractional anisotropy and mean diffusivity were measured by means of diffusion-tensor imaging in the white matter adjacent to the motor and sensory cortices of the hand and the entire cerebral white matter. Clinical data were analyzed by using Student t tests. Results In patients with CSM, NAA normalized to Cr (NAA/Cr) levels were significantly lower 6 months after surgery (1.48 ± 0.08; P < .03) compared with preoperative levels (1.73 ± 0.09), despite significant improvement in clinical questionnaire scores. Fractional anisotropy and mean diffusivity were the same (P > .05) between the patient and control groups in all measured regions at all time points. Conclusion NAA/Cr levels decreased in the motor cortex in patients with CSM 6 months after successful surgery. Intact white matter integrity with decreased NAA/Cr levels suggests that mitochondrial metabolic dysfunction persists after surgery. © RSNA, 2016 Online supplemental material is available for this article.

Effects of cerebellar theta-burst stimulation on arm and neck movement kinematics in patients with focal dystonia.

To investigate the cerebellar inhibitory influence on the primary motor cortex in patients with focal dystonia using a cerebellar continuous theta-burst stimulation protocol (cTBS) and to evaluate any relationship with movement abnormalities. Thirteen patients with focal hand dystonia, 13 patients with cervical dystonia and 13 healthy subjects underwent two sessions: (i) cTBS over the cerebellar hemisphere (real cTBS) and (ii) cTBS over the neck muscles (sham cTBS). The effects of cerebellar cTBS were quantified as excitability changes in the contralateral primary motor cortex, as well as possible changes in arm and neck movements in patients. Real cerebellar cTBS reduced the excitability in the contralateral primary motor cortex in healthy subjects and in patients with cervical dystonia, though not in patients with focal hand dystonia. There was no correlation between changes in primary motor cortex excitability and arm and neck movement kinematics in patients. There were no changes in clinical scores or in kinematic measures, after either real or sham cerebellar cTBS in patients. The reduced cerebellar inhibitory modulation of primary motor cortex excitability in focal dystonia may be related to the body areas affected by dystonia as opposed to being a widespread pathophysiological abnormality. The present study yields information on the differential role played by the cerebellum in the pathophysiology of different focal dystonias.

N-acetylaspartate in the motor and sensory cortices following functional recovery after surgery for cervical spondylotic myelopathy.

OBJECTIVE Cervical spondylotic myelopathy (CSM) is the most common cause of reversible spinal cord dysfunction in people over the age of 55 years. Following surgery for symptomatic CSM, patients demonstrate motor improvement early in the postoperative course, whereas sensory improvement can lag behind. The authors of the present study hypothesized that changes in the concentration of N-acetylaspartate (NAA) in the motor and sensory cortices in the brain would emulate the time course of neurological recovery following decompression surgery for CSM. Their aim was to compare and contrast how metabolite levels in the motor and sensory cortices change after surgery to reverse downstream spinal cord compression. METHODS Twenty-four patients with CSM and 8 control subjects were studied using proton MR spectroscopy (1H-MRS) images acquired on a 3.0-T Siemens MRI unit. The 1H-MRS data (TE 135 msec, TR 2000 msec) were acquired to measure absolute levels of NAA from the motor and sensory cortices in the cerebral hemisphere contralateral to the side of greater deficit at baseline in each subject. Data were also acquired at 6 weeks and 6 months following surgery. Control subjects were also evaluated at 6 weeks and 6 months following baseline data acquisition. Neurological function was measured in each subject at all time points using the Neck Disability Index (NDI), modified Japanese Orthopaedic Association (mJOA) questionnaire, and the American Spinal Injury Association (ASIA) neurological classification. RESULTS In the motor cortex of patients, NAA levels decreased significantly (p < 0.05) at 6 weeks and 6 months postsurgery compared with baseline levels. In the sensory cortex of patients, NAA levels decreased significantly (p < 0.05) only at 6 months after surgery compared with baseline and 6-week levels. No significant changes in NAA were found in control subjects. Clinical scores demonstrated significant (p < 0.05) motor recovery by 6 weeks, whereas sensory improvements (p < 0.05) appeared at only 6 months. CONCLUSIONS Findings suggest that metabolite changes in both the motor and sensory cortices mimic the time course of functional motor and sensory recovery in patients with CSM. The temporal course of neurological recovery may be influenced by metabolic changes in respective cortical regions.

Increased cerebellar activation after repetitive transcranial magnetic stimulation over the primary motor cortex in patients with multiple system atrophy.

Previous review reported that the high-frequency repetitive transcranial magnetic stimulation (rTMS) over the primary motor area (M1) of Parkinson's disease (PD) patients could alleviate their symptoms. This study aimed to investigate the effect of rTMS over the left M1 of patients with multiple system atrophy (MSA). Fifteen MSA patients were randomly assigned to receive a 10-session real (EP: group of experimental patients; n=7) or sham (CP: group of control patients; n=8) rTMS stimulation over two weeks. The overall experimental procedure consisted of two functional magnetic resonance imaging (fMRI) sessions, before and after a 10-session rTMS treatment. A complex self-paced sequential tapping task was performed during fMRI scanning. In addition, 18 age and gender matched healthy controls (HC) were enrolled. Subjects from the HC group did not receive any rTMS treatment and they underwent fMRI examination only once. The primary end point was the motor score change of the Unified Multiple System Atrophy Rating Scale (UMSARS-II) measured before and after the 5th and 10th session. Task-related activation was also compared among groups. After active rTMS treatment, only patients of EP group significant improvement in UMSARS-II score. Compared to HC, MSA patients showed significant activation over similar brain areas except for the cerebellum. Increased activation was obtained in the bilateral cerebellum after rTMS treatment in the EP group. On the contrary, no increased activation was identified in the CP group. Our results highlight rTMS over M1 induced motor improvement in MSA patients that may be associated with increased activation in the cerebellum.

The Axon Guidance Protein Semaphorin 3A Is Increased in the Motor Cortex of Patients With Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disorder that leads to progressive paralysis of skeletal muscles and death by respiratory failure. There is increasing evidence that ALS is at least in part an axonopathy and that mechanisms regulating axonal degeneration and regeneration might be pathogenetically relevant. Semaphorin 3A (Sema3A) is an axon guidance protein; it acts as an axon repellent and prevents axonal regeneration. Increased Sema3A expression has been described in a mouse model of ALS in which it may contribute to motor neuron degeneration. This study aimed to investigate Sema3A mRNA and protein expression in human CNS tissues. We assessed Sema3A expression using quantitative real-time PCR, in situ hybridization, and immunohistochemistry in motor cortex and spinal cord tissue of 8 ALS patients and 6 controls. We found a consistent increase of Sema3A expression in the motor cortex of ALS patients by all 3 methods. In situ hybridization further confirmed that Sema3A expression was present in motor neurons. These findings indicate that upregulation of Sema3A may contribute to axonal degeneration and failure of regeneration in ALS patients. The inhibition of Sema3A therefore might be a promising future therapeutic option for patients with this disease.

ID 99 – Functional connectivity study on repetitive transcranial magnetic stimulation for central post-stroke pain

Objective Central post-stroke pain (CPSP) is one of the most refractory chronic pain syndromes. We and others have reported that repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex relieves pain in patients with CPSP. However, the mechanism underlying the pain relief remains unclear. This study aimed to investigate functional connectivity specific to CPSP and functional connectivity alteration associated with pain relief by rTMS. Methods Subjects were 12 patients with CPSP and 12 age-matched healthy controls. Resting-state function MRI (rs-fMRI) was taken before and after 5 Hz-rTMS of the ipsilesional primary motor cortex in patients, meanwhile rs-fMRI was taken once in controls without the rTMS intervention. rs-fMRI data was preprocessed, and second-level analyses of seed-to-voxel connectivity were implemented. Results The functional connectivity related to the ipsilesional primary motor cortex (FC-M1) was larger in patients than in controls. The alteration of FC-M1 after rTMS negatively correlated with pain relief. Conclusions Our findings suggested that alteration of the functional connectivity might be one of the mechanisms underlying pain relief by rTMS in CPSP. Key message rTMS might affect the functional connectivity related to the stimulation site in patients with CPSP.

High-Resolution 7T MR Imaging of the Motor Cortex in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis is a progressive motor neuron disorder that involves degeneration of both upper and lower motor neurons. In patients with amyotrophic lateral sclerosis, pathologic studies and ex vivo high-resolution MR imaging at ultra-high field strength revealed the co-localization of iron and activated microglia distributed in the deep layers of the primary motor cortex. The aims of the study were to measure the cortical thickness and evaluate the distribution of iron-related signal changes in the primary motor cortex of patients with amyotrophic lateral sclerosis as possible in vivo biomarkers of upper motor neuron impairment. Twenty-two patients with definite amyotrophic lateral sclerosis and 14 healthy subjects underwent a high-resolution 2D multiecho gradient-recalled sequence targeted on the primary motor cortex by using a 7T scanner. Image analysis consisted of the visual evaluation and quantitative measurement of signal intensity and cortical thickness of the primary motor cortex in patients and controls. Qualitative and quantitative MR imaging parameters were correlated with electrophysiologic and laboratory data and with clinical scores. Ultra-high field MR imaging revealed atrophy and signal hypointensity in the deep layers of the primary motor cortex of patients with amyotrophic lateral sclerosis with a diagnostic accuracy of 71%. Signal hypointensity of the deep layers of the primary motor cortex correlated with upper motor neuron impairment (r = -0.47; P < .001) and with disease progression rate (r = -0.60; P = .009). The combined high spatial resolution and sensitivity to paramagnetic substances of 7T MR imaging demonstrate in vivo signal changes of the cerebral motor cortex that resemble the distribution of activated microglia within the cortex of patients with amyotrophic lateral sclerosis. Cortical thinning and signal hypointensity of the deep layers of the primary motor cortex could constitute a marker of upper motor neuron impairment in patients with amyotrophic lateral sclerosis.

A Potential Biomarker in Amyotrophic Lateral Sclerosis: Can Assessment of Brain Iron Deposition with SWI and Corticospinal Tract Degeneration with DTI Help?

Iron-mediated oxidative stress plays a pivotal role in the pathogenesis of amyotrophic lateral sclerosis. This study aimed to assess iron deposition qualitatively and quantitatively by using SWI and microstructural changes in the corticospinal tract by using DTI in patients with amyotrophic lateral sclerosis. Seventeen patients with amyotrophic lateral sclerosis and 15 age- and sex-matched controls underwent brain MR imaging with SWI and DTI. SWI was analyzed for both signal-intensity scoring and quantitative estimation of iron deposition in the anterior and posterior banks of the motor and sensory cortices and deep gray nuclei. The diffusion measurements along the corticospinal tract at the level of pons and medulla were obtained by ROI analysis. Patients with amyotrophic lateral sclerosis showed reduced signal-intensity grades in the posterior bank of the motor cortex bilaterally. Quantitative analysis confirmed significantly higher iron content in the posterior bank of the motor cortex in patients with amyotrophic lateral sclerosis. In contrast, no significant differences were noted for the anterior bank of the motor cortex, anterior and posterior banks of the sensory cortex, and deep nuclei. Receiver operating characteristic comparison showed a cutoff of 35μg Fe/g of tissue with an area under the curve of 0.78 (P = .008) for the posterior bank of the motor cortex in discriminating patients with amyotrophic lateral sclerosis from controls. Fractional anisotropy was lower in the pyramidal tracts of patients with amyotrophic lateral sclerosis at the pons and medulla on either side, along with higher directionally averaged mean diffusivity values. The combination of SWI and DTI revealed an area under the curve of 0.784 for differentiating patients with amyotrophic lateral sclerosis from controls. Measurements of motor cortex iron deposition and diffusion tensor parameters of the corticospinal tract may be useful biomarkers for the diagnosis of clinically suspected amyotrophic lateral sclerosis.

No effects of 20 Hz-rTMS of the primary motor cortex in vegetative state: A randomised, sham-controlled study

We assessed the effects of a non-invasive neuromodulatory intervention with repetitive transcranial magnetic stimulation (rTMS) of the motor cortex in patients with vegetative state (VS) by a randomised, sham-controlled study with a cross-over design. Eleven patients classified as being in VS (9 post-anoxic, 2 post-traumatic, time elapsed from the injury 9–85 months) were included in the study. Real or sham 20 Hz rTMS were applied to the left primary motor cortex (M1) for 5 consecutive days. Primary outcome measures were changes in the JFK Coma Recovery Scale-Revised (CRS-R) scale total score and Clinical Global Impression Improvement (CGI-I) scale. Additional measures were EEG changes and impression of the patients' relatives using the CGI-I scale. Evaluations were blindly performed at baseline, after the first day of treatment, immediately after the end of the 5-days treatment, 1 week and 1 month later. Slight changes observed in the CRS-R and CGI-I scores did not significantly differ between real or sham stimulation conditions. EEG was not significantly changed on average, although spots of brain reactivity were occasionally found underneath the stimulation point. Findings did not provide evidence of therapeutic effect of 20 Hz rTMS of the M1 in chronic VS, at least with conventional coils and current safety parameters. Therefore, they might be useful to better allocate human and financial resources in future trials.

Normalization of sensorimotor integration by repetitive transcranial magnetic stimulation in cervical dystonia.

Previous studies indicated that sensorimotor integration and plasticity of the sensorimotor system are impaired in dystonia patients. We investigated motor evoked potential amplitudes and short latency afferent inhibition to examine corticospinal excitability and cortical sensorimotor integration, before and after inhibitory 1Hz repetitive transcranial magnetic stimulation over primary sensory and primary motor cortex in patients with cervical dystonia (n=12). Motor evoked potentials were recorded from the right first dorsal interosseous muscle after application of unconditioned transcranial magnetic test stimuli and after previous conditioning electrical stimulation of the right index finger at short interstimulus intervals of 25, 30 and 40ms. Results were compared to a group of healthy age-matched controls. At baseline, motor evoked potential amplitudes did not differ between groups. Short latency afferent inhibition was reduced in cervical dystonia patients compared to healthy controls. Inhibitory 1Hz sensory cortex repetitive transcranial magnetic stimulation but not motor cortex repetitive transcranial magnetic stimulation increased motor evoked potential amplitudes in cervical dystonia patients. Additionally, both 1Hz repetitive transcranial magnetic stimulation over primary sensory and primary motor cortex normalized short latency afferent inhibition in these patients. In healthy subjects, sensory repetitive transcranial magnetic stimulation had no influence on motor evoked potential amplitudes and short latency afferent inhibition. Plasticity of sensorimotor circuits is altered in cervical dystonia patients.

Comment: Cu-ATSM to treat and image amyotrophic lateral sclerosis.

Diagnostic imaging for amyotrophic lateral sclerosis (ALS) has the potential to alleviate elements of uncertainty associated with the current diagnostic process and to improve probability of successful outcomes from therapeutic clinical trials via earlier enrollment and treatment of participants. Ikawa et al.1 describe outcomes from an assessment of 62Cu-ATSM in patients with ALS using PET. Selective accumulation of the radiotracer in the motor cortex of patients with ALS and its correlation with disease severity supports the use of this compound to image ALS via PET. Although the study involved a limited number of participants (12 ALS and 9 healthy controls), the outcomes are nonetheless encouraging. Increasing radioactive half-life of the tracer by using 64Cu-ATSM (12 hours) instead of 62Cu-ATSM (10 minutes) together with a longer postinjection imaging interval could afford greater sensitivity and thereby better insight to whether Cu-ATSM PET may be used for diagnostic purposes.

Assessment of excitability at the brainstem and cortex in primary headaches with allodynia.

The aims were to assess the excitability of motor cortex and trigeminal structures in patients with primary headaches experiencing allodynia and to investigate the alterations in interictal allodynia and blink reflex excitability after repetitive transcranial magnetic stimulation (rTMS). Patients with strictly lateralized primary headaches were included, and Allodynia Symptom Checklist was used to detect allodynia. Paired transcranial magnetic stimulation and blink reflex recovery studies were performed on both sides. Ten Hertz or sham rTMS was applied on the motor cortex in patients with interictal allodynia. Allodynic symptoms were registered quantitatively, and blink reflex study was repeated after these trials. Seventeen of 34 patients with headache described allodynia. Our findings showed bilateral hyperexcitability of cortical and trigeminal structures in the allodynic group. Interictal allodynia, detected in 13 allodynic patients, improved after rTMS as compared with sham stimulation, and this effect appeared to be more evident in the late period. Bilateral increases in the cortical and trigeminal excitability were shown in patients with allodynia, and rTMS was effective for reducing clinical allodynia. The authors suggest that allodynic condition of the patients should be taken into account in the planning and evaluation of electrophysiological studies, and rTMS may be considered as a treatment alternative for troublesome allodynia.

Effects of High-Frequency Repetitive Transcranial Magnetic Stimulation on Motor Functions in Patients with Subcortical Stroke

Article type: Original Article Background: Motor function impairment occurs in approximately two-thirds of patients with subcortical stroke. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique for modulating cortical excitability. Objectives: The present study was designed for assessing the efficacy of highfrequency rTMS (5 Hz) on ipsilesional primary motor cortex in patients with subcortical stroke. Materials and Methods: Thirty participants who had subcortical stroke in the previous four weeks to four months were enrolled in this randomized double blinded clinical trial. Participants were divided into experimental and control groups and their motor ability of both upper and lower extremities were assessed using Fugl-Meyer assessment of motor recovery after stroke (FMA) before and after intervention. The study intervention rTMS (5 Hz) was administered in six 10-minute sessions on the ipsilesional primary motor cortex in the experimental group and on the vertex in the control group. Results: Mean change in FMA score after rTMS sessions was significantly higher in the experimental group than in the control group (p = 0.00). Mean time interval between the stroke and rTMS intervention had a weak and insignificant (ρ = 0.097; p = 0.61) correlation with changes of FMA score. Conclusions: High-frequency (5 Hz) rTMS effectively improved motor function in patients with subcortical stroke.

P467: Combined neurophysiological and imaging assessment of motor cortical areas in EPM1A patients

s of Poster Presentations / Clinical Neurophysiology 125, Supplement 1 (2014) S1–S339 S173 reviewed. A test was defined as successful if the patients’ habitual attacks were captured. Results: Ten patients were identified who had a repeat HVT following unsuccessful inpatient video-telemetry. In 4/10 patients repeat HVT captured their habitual episodes (40%). Conclusion: Investigation with repeat HVT captured the habitual attacks in 40% of patients compared to 8% with repeat inpatient VTs. These results suggest that if repeat telemetry is required, HVT is the most successful option to capture habitual attacks. Further work is needed to confirm diagnostic accuracy and utility of HVT considering parameters such as age and nature of disease (epileptic v. non-epileptic attacks). P467 Combined neurophysiological and imaging assessment of motor cortical areas in EPM1A patients E. Visani1, L. Canafoglia1, D. Rossi Sebastiano1, V. Contarino2, L. D’Incerti2, F. Panzica1, S. Franceschetti1 1Fondazione IRCCS Carlo Besta, Neurophysiology, Milan, Italy; 2Fondazione IRCCS Carlo Besta, Neuroradiology, Milan, Italy Question: To assess functional organization of the motor cortex in patients with cortical myoclonus due to Unverricht-Lundborg disease (EPM1A) using multimodal neurophysiologic and imaging approach. Methods: Seven healthy subjects and nine EPM1A patients were enrolled in the study. TMS-based mapping of primary motor cortex of the hand associated to real-time frameless neuronavigation system was performed. fMRI activation maps related to hand motor task was obtained. Cortical thickness (CTH) analysis were applied on T1-weighted 3D images. Results: Bilaterally resting motor threshold was significantly higher and mean amplitude of the motor evoked potentials was significantly lower in the patients with respect to healthy subjects. There were no differences between groups in the extension of the cortical representation of the ABP muscle, but bilaterally the centers of gravity (CoGs) of EPM1A patients (Fig. 1, filled circles) lied posteriorly than that of healthy subjects (Fig. 1, crossed circles). fMRI did not revealed significant differences between groups, although a slightly posterior localization of activated cluster was found in patients (Fig. 2A, red cluster) with respect to healthy subjects (Fig. 2A, blue cluster). CTH analysis revealed significant alterations in both precentral and paracentral areas bilaterally, resulting in a thinning of these areas in EPM1A patients (Fig. 2B).

Poster #M179 REDUCED THETA BAND RESPONSE TO RELEVANCE IN SCHIZOPHRENIA

Objective: The aim of the study was to examine intracortical excitability in cerebellar patients. Methods: Short-latency intracortical inhibition (SICI), long-latency intracortical inhibition (LICI) and intracortical facilitation (ICF) to paired transcranial magnetic stimulation (TMS) were investigated in 8 patients with ‘pure’ cerebellar syndromes and in 14 age-matched normal controls. The conditioning stimulus for short-latency intracortical inhibition and intracortical facilitation was set at 70% of the resting motor threshold (RMT) and preceded the test stimulus (110–120% of the resting motor threshold) by interstimulus intervals (ISIs) of 1–30 ms. For the long-latency intracortical inhibition determinations, the conditioning stimulus was set at 120% of the resting motor threshold and preceded the test stimulus (also 120% of the resting motor threshold) by interstimulus intervals of 30–500 ms. Results: No statistically significant differences were found between patients and controls as regards either short-latency intracortical inhibition or intracortical facilitation. A significant prevalence of long-latency intracortical inhibition was present in cerebellar patients at interstimulus intervals of 200–500 ms (conditioned MEP amplitude=29–41% of test MEP) as compared to controls (71–96% of test MEP). The amplitude of conditioned MEPs was persistently less than 45% of the test MEP in six patients, who were studied at interstimulus intervals up to 1000 ms. Conclusions: Long-latency intracortical inhibition was prevalent and abnormally longer-lasting in patients. Tonic hyperactivation of a subpopulation of GABAergic interneurons in the motor cortex of patients may be the mechanism responsible for this abnormality. Our findings seem to be specific to cerebellar diseases and are the opposite of those found in movement disorders such as dystonia and Parkinson's disease. These data suggest that the cerebellum and the basal ganglia may have opposite influences in tuning the excitability of the motor cortex.

Transcranial direct current stimulation (tDCS) for fatigue in multiple sclerosis

The debilitating fatigue that patients with multiple sclerosis (MS) commonly experience during day-to-day living activities responds poorly to current therapeutic options. Direct currents (DC) delivered through the scalp (transcranial DC stimulation or tDCS) at weak intensities induce changes in motor cortical excitability that persist for almost an hour after current offset and depend on current polarity. tDCS successfully modulates cortical excitability in various clinical disorders but no information is available for MS related fatigue. In this study we aimed to assess fatigue symptom after five consecutive sessions of anodal tDCS applied over the motor cortex in patients with MS. We enrolled 25 patients with MS all of whom experienced fatigue. We delivered anodal and sham tDCS in random order in two separate experimental sessions at least 1 month apart. The stimulating current was delivered for 15 minutes once a day for 5 consecutive days. In each session the Fatigue Impact Scale (FIS) and the Back Depression Inventory (BDI) were administered before the treatment (baseline), immediately after treatment on day five (T1), one week (T2) and three weeks (T3) after the last tDCS session. All patients tolerated tDCS well without adverse events. The fatigue score significantly decreased after anodal tDCS in 65% of the patients (responders). After patients received tDCS for 5 days their FIS scores improved by about 30% and the tDCS-induced benefits persisted at T2 and T3. Our preliminary findings suggest that anodal tDCS applied over the motor cortex, could improve fatigue in most patients with MS.

P 11. Cortical inhibition within motor and frontal regions in alcohol dependence: A TMS–EEG study

Background Preclinical studies suggest that alterations within the frontal cortex play a critical role in the neurophysiology of alcohol dependence. The combination of transcranial magnetic stimulation and electroencephalography (TMS-EEG) allows a direct assessment of cortical excitability and inhibition within the frontal cortex in human subjects. We report the first application of TMS-EEG to measure these indices within the frontal cortices of patients with alcohol dependence. Methods Cortical inhibition was assessed in 12 patients with alcohol dependence and 14 healthy controls through single and paired-pulse transcranial magnetic stimulations (TMS) paradigms delivered to both the frontal and motor cortices. Long interval cortical inhibition (LICI) was used to index inhibition in the frontal cortex. Short intracortical inhibition (SICI) and cortical silent period (CSP) was used to index inhibition, while intracortical facilitation (ICF) measured facilitation, in the motor cortex. Cortical excitability was indexed by the resting motor threshold (RMT) and active motor threshold (AMT). Results The alcohol dependent group demonstrated deficits in LICI across both the left and right dorsolateral prefrontal cortex relative to healthy controls. The alcohol dependent group also exhibited reduced RMT and AMT. In terms of motor cortex inhibition, there were no significant differences in SICI, ICF or CSP, although increased intra-trial-variability in SICI was observed in the alcohol dependent group. Conclusions The current study provides the first direct evidence of reduced cortical inhibition that is specific to the frontal cortex of patients with alcohol dependence. Our study also revealed evidence of altered cortical excitability in the motor cortex of patients with alcohol dependence; however, the utility of using the motor cortex to index cortical alterations related to alcohol dependence remains unclear. Although these findings are preliminary, they provide critical neurophysiological evidence of disrupted cortical excitability within the frontal cortex of alcohol dependent patients.

An Imbalance Between Excitatory and Inhibitory Neurotransmitters in Amyotrophic Lateral Sclerosis Revealed by Use of 3-T Proton Magnetic Resonance Spectroscopy

A lack of neuroinhibitory function may result in unopposed excitotoxic neuronal damage in amyotrophic lateral sclerosis (ALS). To determine whether there are reductions in γ-aminobutyric acid (GABA) levels and elevations in glutamate-glutamine (Glx) levels in selected brain regions of patients with ALS by use of proton magnetic resonance spectroscopy. Case-control study using short echo time and GABA-edited proton magnetic resonance spectroscopy at 3 T with regions of interest in the left motor cortex, left subcortical white matter, and pons; data analyzed using logistic regression, t tests, and Pearson correlations; and post hoc analyses performed to investigate differences between riluzole-naive and riluzole-treated patients with ALS. Tertiary referral center. Twenty-nine patients with ALS and 30 age- and sex-matched healthy controls. Fifteen patients were taking 50 mg of riluzole twice a day as part of their routine clinical care for ALS. Levels of GABA, Glx, choline (a marker of cell membrane turnover), creatine (a marker of energy metabolism), myo-inositol (a marker of glial cells), and N-acetylaspartate (a marker of neuronal integrity). Patients with ALS had significantly lower levels of GABA in the motor cortex than did healthy controls (P < .01). Patients with ALS also had significantly lower levels of N-acetylaspartate in the motor cortex (P < .01), subcortical white matter (P < .05), and pons (P < .01) and higher levels of myo-inositol in the motor cortex (P < .001) and subcortical white matter (P < .01) than did healthy controls. Riluzole-naive patients with ALS had higher levels of Glx than did riluzole-treated patients with ALS (P < .05 for pons and motor cortex) and healthy controls (P < .05 for pons and motor cortex). Riluzole-naive patients with ALS had higher levels of creatine in the motor cortex (P < .001 for both comparisons) and subcortical white matter (P ≤ .05 for both comparisons) than did riluzole-treated patients with ALS and healthy controls. Riluzole-naive patients with ALS had higher levels of N-acetylaspartate in the motor cortex than did riluzole-treated patients with ALS (P < .01). There are reduced levels of GABA in the motor cortex of patients with ALS. There are elevated levels of Glx in riluzole-naive patients with ALS compared with riluzole-treated patients with ALS and healthy controls. These results point to an imbalance between excitatory and inhibitory neurotransmitters as being important in the pathogenesis of ALS and an antiglutamatergic basis for the effects of riluzole, although additional research efforts are needed.

Reduced postmovement cortical inhibition in patients with paroxysmal kinesigenic dyskinesia

To characterize movement-related neural oscillatory activity and to clarify its neurophysiologic role in paroxysmal kinesigenic dyskinesia (PKD). We recorded neuromagnetic event-related desynchronization (ERD) and event-related synchronization (ERS) activities in response to a self-paced finger-lifting task in 16 patients with PKD and 17 healthy controls. The amplitude of α-ERD was comparable between the healthy controls and patients with PKD, whereas either the contralateral or ipsilateral β-ERS was decreased. The peak latency of contralateral β-ERS was delayed in patients with PKD. Patients with less frequent dyskinetic attacks demonstrated a larger ipsilateral β-ERS. Moreover, some patients with PKD revealed a lesser degree of contralateral preponderance of β-ERS generation. The present data imply a decreased postmovement inhibition of motor cortex in patients with PKD, and the inhibitory function in the contralateral hemisphere is more affected than that in the ipsilateral hemisphere.