Shorter Cortical Silent Period Research Articles

The Effect of Epilepsy and Antiepileptic Drugs on Cortical Motor Excitability in Patients With Temporal Lobe Epilepsy.

Transcranial magnetic stimulation (TMS) has been used to assess cortical disinhibition/excitation with epilepsy and determine the degree of patients' response to antiepileptic drugs (AEDs). However, the results of studies are variable and conflicting. We assessed cortical motor excitability in adults with temporal lobe epilepsy (TLE). The TMS parameters used for assessment were: resting (RMT) and active (AMT) motor thresholds, cortical silent period (CSP), and central motor conduction time (CMCT). This study included 40 adults (males, 22; females, 18) with TLE with impaired awareness or to bilateral tonic clonic seizures (mean age, 32.50 ± 3.38 years; duration of illness, 6.15 ± 2.02 years) and on treatment with AEDs (valproate, 15; carbamazepine, 15; levetiracetam, 10]. The majority (62.5%) were seizure-free for ≥1 year on AEDs before TMS testing. All had normal brain magnetic resonance imaging except two, who had mesial temporal sclerosis. Comparing the entire patients with controls, patients had significantly bihemispheric higher RMT and AMT particularly over the epileptic hemisphere and shorter CSP and CMCT in the epileptic hemisphere. Shorter CSP and CMCT were observed in patients on valproate or carbamazepine and those who were uncontrolled on medications but not with levetiracetam. Significant correlations were identified between RMT and AMT (P = 0.01) and between CSP and CMCT (P = 0.001). We conclude that chronic TLE had increased cortical disinhibition in the epileptic hemisphere which can spread outside the epileptogenic zone despite the apparent control on AEDs. The TMS studies using CSP and CMCT may help future prediction of pharmacoresistance and, therefore, the need of combined AEDs with multiple mechanisms of action.

Walking Training Enhances Corticospinal Excitability in Progressive Multiple Sclerosis—A Pilot Study

Background: Inflammatory lesions and neurodegeneration lead to motor, cognitive, and sensory impairments in people with multiple sclerosis (MS). Accumulation of disability is at least partially due to diminished capacity for neuroplasticity within the central nervous system. Aerobic exercise is a potentially important intervention to enhance neuroplasticity since it causes upregulation of neurotrophins and enhances corticospinal excitability, which can be probed using single-pulse transcranial magnetic stimulation (TMS). Whether people with progressive MS who have accumulated substantial disability could benefit from walking rehabilitative training to enhance neuroplasticity is not known.Objective: We aimed to determine whether 10 weeks of task-specific walking training would affect corticospinal excitability over time (pre, post, and 3-month follow-up) among people with progressive MS who required walking aids.Results: Eight people with progressive MS (seven female; 29–74 years old) with an Expanded Disability Status Scale of 6–6.5 underwent harness-supported treadmill walking training in a temperature controlled room at 16°C (10 weeks; three times/week; 40 min at 40–65% heart rate reserve). After training, there was significantly higher corticospinal excitability in both brain hemispheres, reductions in TMS active motor thresholds, and increases in motor-evoked potential amplitudes and slope of the recruitment curve (REC). Decreased intracortical inhibition (shorter cortical silent period) after training was noted in the hemisphere corresponding to the stronger hand only. These effects were not sustained at follow-up. There was a significant relationship between increases in corticospinal excitability (REC, area under the curve) in the hemisphere corresponding to the stronger hand and lessening of both intensity and impact of fatigue on activities of daily living (Fatigue Severity Scale and Modified Fatigue Impact Scale, respectively).Conclusion: Our pilot results support that vigorous treadmill training can potentially improve neuroplastic potential and mitigate symptoms of the disease even among people who have accumulated substantial disability due to MS.

Exercise-Induced Brain Excitability Changes in Progressive Multiple Sclerosis: A Pilot Study.

Even a single bout of aerobic exercise (AE) enhances corticospinal excitability (CSE), a biomarker of neuroplasticity. Because neurodegeneration limits capacity for neuroplasticity, it is not clear whether AE would induce CSE changes in people with progressive multiple sclerosis (MS). People with progressive MS (n = 10) requiring ambulatory assistive devices completed a graded maximal exercise test. Dual-energy x-ray absorptiometry was used to quantify body fat and lean mass. Before and following one 40-minute AE session using body weight-supported (<10% support) treadmill at moderate intensity, CSE was measured using transcranial magnetic stimulation. Variables included resting and active motor thresholds, motor evoked potential (MEP) amplitudes, recruitment curves, and length of the cortical silent period (CSP). Aerobic exercise reduced inhibition (shorter CSP) and increased excitation (increased MEP amplitude) only in the hemisphere corresponding to the stronger hand. Controlling for age, higher fitness and lower body fat significantly predicted exercise-induced reduction in resting motor threshold (ΔR = +0.458, P = 0.046) and CSP (ΔR = +0.568, P = 0.030), respectively. Despite high levels of disability, capacity for exercise-induced neuroplasticity was retained among people with progressive MS. The hemisphere contralateral to the weaker hand was resistant to exercise-induced CSE changes, suggesting less neuroplastic potential. Lower fitness and higher body fat were associated with diminished exercise-induced CSE benefits, suggesting that therapists should consider interventions aimed at improving fitness and combating sedentarism to ultimately enhance the benefits of exercise on the brain.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A302).

Could neurophysiological measures help in understanding alexithymia in multiple sclerosis?

Objectives Patients with multiple sclerosis (MS) could have deficits in emotional processing. Among the latter, alexithymia could affect up to 53% of this population [2] ; it is a multicomponent personality construct that entails an operative thinking and difficulties in understanding and analyzing one's own feelings. Previous transcranial magnetic stimulation (TMS) studies have suggested aberrant interhemispheric transfer and GABAergic transmission behind alexithymia [3] , but none was performed in the context of MS. Methods Right-handed MS patients were enrolled if they had no contraindications to TMS. The Toronto Alexithymia Scale (TAS) classified patients as alexithymic (score > 55) and non-alexithymic. Socio-demographic, clinical and neuropsychological data were collected. The following TMS measures were obtained [1] : resting motor threshold, interhemispheric inhibition (interstimuli interval: 8, 10 and 12 ms) and cortical silent period (CSP). The statistical analysis consisted of group comparison (alexithymic versus non-alexithymic) of socio-demographic, clinical and neuropsychological measures and correlation analysis (corrections with False Discovery Rate approach) between TAS scores and TMS measures. Results Twenty-two patients completed the study (n = 10 alexithymic and n = 12 non-alexithymic). Patients did not significantly differ with regard to socio-demographic, clinical or neuropsychological data. A significantly shorter CSP duration was observed among alexithymic patients (mean: 84.34 ± 49.73) compared to their non-alexithymic counterparts (mean: 159.33 ± 76.96).

P019 Ipsilesional and contralesional cortical silent period in pediatric stroke: Preliminary reports

Question The cortical silent period (CSP) is a transient supression of electromyographic (EMG) activity in a pre-activated muscle after a transcranial magnetic stimulation (TMS) pulse. CSP duration reflects intracortical inhibitory mechanisms. Prolonged lesional and shortened non-lesional CSP durations have been associated with poor functional recovery after adult stroke. However, there are few reports regarding CSP duration in children. Our aims is to characterize ipsilesional and contralesional CSP duration in pediatric stroke. Methods Eight children with congenital hemiparesis due to stroke (4 male, age = 11.75 ± 3.26 years) participated. Surface bipolar electrodes were placed over the affected and non-affected first dorsal interosseous (FDI) muscles. TMS single-pulses were delivered using a Magstin 200 stimulator connected to a 70-mm figure of eight coil over the primary motor cortex, bilaterally. Resting motor threshold (RMT) was determined for the FDI. CSP was assessed at 120% RMT during 20% of FDI maximal voluntary contraction. Results Three children presented without an ipsilesional MEP. Ipsilesional RMT average was 64.8% of maximum stimulator output (MSO) (SD = 9.3; range = 53–75) and 56.7% of MSO (SD = 11.6; range = 38–71) for the contralesional hemisphere. Ipsilesional CSP duration was analyzable in one child, x ¯ = 170.5 ms (SD = 11.4; range = 155.5–196.1) and contralesional CSP duration was found in all 8 children, x ¯ = 118.0 ms (SD = 47.3; range = 62.8–174.9) (Fig. 1 Download : Download high-res image (250KB) Download : Download full-size image ). Conclusion Absence of ipsilesional MEPs has been reported in pediatric hemiparesis and could reflect a persistent or enlarged ipsilateral corticospinal tract projections after stroke. Ipsilesional CSP data was largely unanalyzable (no noticeable CSP) with challenges surrounding the ability of the children to sustain paretic FDI contraction, poor motor control (Fig. 2A) and hand spasticity (Fig. 2B Download : Download high-res image (200KB) Download : Download full-size image ). Reports in typically developing children present with shorter CSP duration (25.5–53.8 ms) than adults (150–300 ms). Our results are similar to previous study with pediatric hemiparesis which showed longer CSP duration in ipsilesional and contralesional hemisphere (Mackey et al., 2014). Longer CSP duration could be related to increased activity of inhibitory interneurons in the motor cortex after a perinatal stroke.

The role of transcranial magnetic stimulation in evaluation of motor cortex excitability in Rett syndrome.

Rett syndrome (RTT) is a frequent neurodevelopmental disorder confirmed by clinical criteria and supported by the methyl-CpG-binding protein 2 gene (MECP2) mutation. A short central motor conduction time (CMCT) was reported in transcranial magnetic stimulation (TMS) studies performed in RTT. This was attributed to hyperexcitability of the motor cortex and/or spinal motor neurons, but was not studied further. We performed TMS in RTT to evaluate motor cortex excitability by determining the cortical motor threshold (CMT) and motor cortex inhibition by the cortical silent period (CSP) besides measuring CMCT. Single-pulse TMS was performed in 17 Rett patients, diagnosed by clinical criteria and MECP2 mutation testing, and the same number of healthy controls. The outcome measures were compared between RTT groups with different antiepileptic drugs (AED) and those with and without the MECP2 mutation. CMCT was shorter, but we found elevated CMT and shorter CSP, which suggests decreased excitatory and inhibitory motor cortical function. The outcome was independent of AED and the presence or absence of the MECP2 mutation. Decreased excitatory and inhibitory motor cortical function could explain the short CMCT, with higher stimulus intensities needed to excite pyramidal neurons.

67. Neural response to transcranial magnetic stimulation in adult thyroid hormone resistance

Thyroid hormone resistance describes a rare syndrome in which the thyroid hormone levels are elevated, but the thyroid stimulating hormone level is not suppressed. The importance of thyroid hormones in brain normal function is corroborated by the frequent association of thyroid dysfunctions with neurological and psychiatric symptoms. In this study, we investigated whether adult thyroid hormone resistance affects cortical excitability and modulates inhibitory and excitatory intracortical circuitries. Cortical excitability was probed with transcranial magnetic stimulation in 6 patients with thyroid hormone resistance, 10 patients affected by hypothyroidism, and 10 age-matched healthy controls. We tested motor thresholds, motor evoked potential recruitment curve, cortical silent period, intracortical inhibition, and intracortical facilitation. Patients with thyroid hormone resistance showed decreased steepness of the motor evoked potential recruitment curves. These changes were paralleled by shorter cortical silent period and increased intracortical inhibition. In conclusion, thyroid hormones may influence cortical excitability and cortical inhibitory circuits in adults.

Cortical Damage and Disability in Multiple Sclerosis: Relation to Intracortical Inhibition and Facilitation.

Multimodal research combining biomarkers of intracortical activity and cortical damage could shed light on pathophysiological and adaptive neural processes related to the clinical severity of neurological conditions such as multiple sclerosis (MS). Among people with relapsing-remitting and progressive forms of MS, we assessed the extent to which transcranial magnetic stimulation (TMS)-based biomarkers of excitatory and inhibitory cortical activity are related to cortical damage and clinical impairment. Participants included 18 healthy individuals and 36 people with MS who had a relapsing-remitting or progressive clinical course. Using TMS, intracortical facilitation (ICF), short-interval intracortical inhibition (SICI), long-interval intracortical inhibition (LICI), and cortical silent period (CSP) were obtained. Cortical volume and cortical magnetization transfer ratio (MTR) were quantified. Disability was assessed with Multiple Sclerosis Functional Composite (MSFC). Lower mean MTR within the cerebral cortex correlated with shorter CSP among MS participants with a progressive, but not a relapsing-remitting, clinical course. Within the cortical hand knob region targeted with TMS, lower MTR was correlated with lower SICI only among individuals with relapsing-remitting MS. Longer CSP, higher ICF, lower cortical MTR, and sex were all independent significant predictors of poor upper extremity motor performance, while only cortical MTR was a significant independent predictor of total MSFC score among people with MS. Cortical damage and cortical activity (both inhibitory and excitatory) may contribute to the severity of motor disability experienced by people with MS. When interpreting TMS-based outcomes, cortical integrity, clinical course, and symptom type should be considered.

Biomarkers in a Taurine Trial for Succinic Semialdehyde Dehydrogenase Deficiency.

We tested the hypothesis that patients with succinic semialdehyde dehydrogenase (SSADH) deficiency on taurine would have decreased cortical excitability as measured by transcranial magnetic stimulation (TMS) and improved cognition, due to taurine's partial GABA(A and B) receptor agonist effects and rescue in the null mouse model from status epilepticus and premature lethality. Biomarkers including neuropsychological testing, TMS, and CSF metabolites were studied in a cohort of patients on and off three months' taurine treatment. Seven patients (5M/2F; age range 12-33 years) were enrolled in this open-label crossover study. Baseline average full-scale IQ (FSIQ) was 44.1 (range 34-55). Of six who returned at 6-month follow-up, five completed cognitive testing (3M/2F) on therapy; average FSIQ = 43.4 (range 33-51). CSF biomarkers (n = 4 subjects) revealed elevation in taurine levels but no change in free or total GABA. Baseline cortical excitability measured with TMS agreed with previous findings in this population, with a short cortical silent period and lack of long-interval intracortical inhibition. Patients on taurine showed a decrease in cortical silent period and short-interval intracortical inhibition compared to their off taurine study. TMS demonstrated decreased inhibition in patients on taurine, in contrast to the study hypothesis, but consistent with its failure to produce clinical or cognitive improvement. TMS may be a useful biomarker for therapy in pediatric neurotransmitter disorders.

Cortical disinhibition in diabetic patients with neuropathic pain

Motor cortex disinhibition has a role in the mechanism of neuropathic pain. The duration of the cortical silent period (CSP) is used as a measure of excitability in cortical inhibitory circuits. We investigated cortical disinhibition in diabetic patients with and without neuropathic pain. We studied diabetic patients with (n = 20) and without (n = 50) neuropathic pain, and control subjects (n = 30). Transcranial magnetic stimulation (TMS) was performed on the right hemisphere at rest, and surface electromyography was recorded from the left first dorsal interosseous muscle for evaluation of motor evoked potential (MEP) latency and amplitude. CSP was recorded from the left FDI, and TMS was then delivered while the subject was performing a voluntary contraction. We showed a low resting motor threshold, a short CSP duration, and a low CSP duration/MEP amplitude ratio in patients with neuropathic pain (P < 0.0001, P < 0.0001, P < 0.0001). Our findings demonstrate that diabetic patients with neuropathic pain have a cortical disinhibition.

The Relationship Between Cortical Inhibition, Antipsychotic Treatment, and the Symptoms of Schizophrenia

Cortical inhibition (CI) deficits assessed by transcranial magnetic stimulation paradigms, short-interval cortical inhibition (SICI), and cortical silent period (CSP) have been demonstrated in schizophrenia (SCZ) patients. Antipsychotic treatments can modify CI and improve clinical symptoms, suggesting a neurophysiological link between the two. Previous studies have demonstrated that clozapine is associated with prolongation in CSP, a gamma-hydroxybutyric acid (GABA)(B)-mediated phenomenon. Furthermore, SICI deficits were associated with psychotic symptom severity, suggesting alternation in GABA(A)-mediated neurotransmission. Such differential association patterns between clinical symptoms and CI deficits and their relationship to antipsychotic treatment thus might provide insights to the pathophysiology of schizophrenia. CI was assessed in 78 SCZ patients and 38 healthy subjects. Clinical symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS). Subjects were grouped according to antipsychotic medication status: unmedicated (n = 7), clozapine (n = 19), olanzapine/quetiapine (n = 32), and risperidone/typical antipsychotics (n = 20). Relative to control subjects, patients receiving clozapine had longer CSP and reduced SICI, whereas patients receiving other antipsychotics and unmedicated patients had shorter CSP. Across all subjects with SCZ, CSP was inversely associated with negative symptoms, and SICI was inversely associated with positive symptoms. These results confirm that unmedicated SCZ patients have CI deficits and that clozapine treatment is associated with potentiation of GABA(B)-inhibitory neurotransmission and reduced GABA(A) inhibitory neurotransmission. Also, the differential associations among SICI, CSP, and clinical symptom dimensions suggest that GABA(A)- and GABA(B)-mediated CI might have different roles in the pathophysiology of symptoms of schizophrenia.

Reduced plastic brain responses in schizophrenia: a transcranial magnetic stimulation study

Background: Abnormalities in brain plasticity, possibly related to abnormal cortical inhibition (CI), have been proposed to underlie the pathophysiology of schizophrenia. Transcranial magnetic stimulation (TMS) provides a dynamic method for non-invasive study of plastic processes in the human brain. We aimed to determine whether patients with schizophrenia would exhibit an abnormal response to repetitive TMS (rTMS) applied to the motor cortex and whether this would relate to deficient cortical inhibition. Methods: Measures of motor cortical excitability and cortical inhibition were made before and after a single 15-min train of 1-Hz rTMS applied to the motor cortex in medicated and unmedicated patients with schizophrenia as well as healthy controls. Results: All three groups had equal motor cortical excitability prior to rTMS, although both patient groups had a shorter cortical silent period (CSP) and less cortical inhibition than the control group. Cortical excitability, as assessed by motor threshold levels, did not reduce in both medicated and unmedicated patients in response to rTMS as was seen in the control group. Significant differences were also seen between the groups in response to the rTMS for motor-evoked potential (MEP) size and cortical silent period duration. Conclusions: Both medicated and medication free patients with schizophrenia demonstrated reduced brain responses to rTMS and deficits in cortical inhibition.

Asymmetry of cortical excitability revealed by transcranial stimulation in a patient with focal motor epilepsy and cortical myoclonus

Motor cortex excitability was analyzed with transcranial stimulation in a patient with motor focal epilepsy and cortical myoclonus originating from the right motor cortex. The motor threshold to single transcranial magnetic shocks, but not to electric stimuli, was higher in the epileptic motor cortex than the normal left motor cortex. Single magnetic shocks elicited a short cortical silent period (50 ms) in the epileptic motor cortex. Paired magnetic stimuli also showed reduced cortico-cortical inhibition. These findings reveal an asymmetry in cortical excitability presumably due to impaired inhibition in the epileptic motor cortex