Acute effects of lithium on excitability of human motor cortex

ObjectiveLithium has been widely used to treat bipolar affective disorder for over 60 years. Still, its acute effects in human cerebral cortex are poorly understood. This study aimed at investigating the acute effects of lithium on motor cortex excitability as measured by transcranial magnetic stimulation (TMS).MethodsTen healthy young adults participated in a double-blind placebo-controlled randomized crossover study with four sessions, where a single oral dose of lithium carbonate (450 mg, 900 mg, or 1350 mg) or placebo was tested. Focal TMS of the hand area of left motor cortex was used to test resting and active motor thresholds, motor evoked potential input–output curve (MEP IO-curve), slope of the MEP IO-curve and paired-pulse measures of intracortical inhibition and facilitation before, and two and four hours after drug administration.ResultsTwo hours post drug administration, 450 mg of lithium carbonate increased the slope of the MEP IO-curve while 1350 mg tended to decrease it. Lithium had no effect on motor thresholds, or intracortical inhibition or facilitation.ConclusionsThe acute effects of lithium on MEP IO-curve, a marker of corticospinal excitability, are consistent with an inverted U-shaped dose–response relationship.SignificanceFindings are important for our understanding of the therapeutic and toxic effects of lithium on the human central nervous system.     

The effect of modafinil on cortical excitability in patients with narcolepsy: A randomized,placebo-controlled,crossover study

ObjectiveTo investigate the effect of modafinil on cortical excitability in patients with narcolepsy using transcranial magnetic stimulation (TMS).MethodsNineteen drug-naïve narcolepsy patients with cataplexy (10 males, 9 females, and mean age 28.5 years) and 25 age- and sex-matched healthy controls were recruited. In this double-blind, randomized, crossover study, patients and controls received a single dose of 400 mg modafinil or placebo. Modafinil and placebo administrations were separated by a 2-week washout period. TMS parameters, such as resting motor thresholds (RMT), motor-evoked potential (MEP) amplitudes, cortical silent periods (CSP), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF), were measured before and 3 h after administering modafinil or placebo. The differences of TMS parameters were statistically tested between patients and controls and between before and after modafinil or placebo administration.ResultsNarcolepsy patients had significantly increased CSP durations compared to controls (independent t-test, P < 0.05), indicating decreased excitability of cortical networks in human narcolepsy. In patients after modafinil administration, MEP amplitudes, SICI, and ICF increased, and CSP duration shortened significantly, meaning enhanced motor excitability, whereas in controls modafinil did not change TMS parameters significantly. Placebo administration did not affect TMS parameters both in patients or controls.ConclusionsNarcolepsy patients with cataplexy showed decreased cortical excitability than normal healthy controls. Single dose modafinil significantly increased motor excitability in narcolepsy patients but had no effect in healthy controls.     

Behavioural exposure and sleep do not modify corticospinal and intracortical excitability in the human motor system

ObjectiveBehavioural exposure and sleep may bidirectionally modify the excitability of cortical networks including those in the motor cortex. Here we tested whether the excitability of intracortical inhibitory and excitatory networks within the primary motor cortex exhibited changes suggestive of a time of day influence.MethodsShort-interval intracortical inhibition (SICI) and facilitation (ICF), and input–output curves (IO curves) were investigated using transcranial magnetic stimulation (TMS). Recordings were made from the resting right first dorsal interosseous (FDI) muscle in 10 healthy subjects on three occasions: 9 A.M. and 4 P.M. of the same day, and 9 A.M. of the following day.ResultsThere was no significant change in any of the measures across the three assessments.ConclusionsThese findings provide evidence that time of day does not significantly influence corticospinal and intracortical excitability in the primary motor cortex.SignificanceThese results provide no support for the hypothesis that synapses within the motor cortex undergo potentiation due to daytime use and behavioural experiences. Additionally, these findings provide evidence that measurement of motor cortical excitability is not systematically biased by time-of-day dependent variability and thus does not pose a confound in studies assessing corticospinal excitability longitudinally.     

Increased motor cortical excitability after whole-hand electrical stimulation: A TMS study

ObjectiveTo examine the neuromodulatory effect of whole-hand mesh-glove (MG) stimulation on motor cortical pathways, we explored motor cortical excitability before and after suprathreshold whole-hand MG stimulation using transcranial magnetic stimulation (TMS).MethodsTwenty-eight healthy volunteers (14 controls) were studied at baseline, immediately post and 1 h post-MG stimulation for 30 min. Motor thresholds (MTs), motor evoked potentials (MEPs) recruitment curve, short intracortical inhibition (SICI) and intracortical facilitation (ICF) after paired magnetic stimuli were evaluated.ResultsAfter MG stimulation the MTs were significantly reduced and slope of MEP recruitment curve significantly increased; furthermore, the stimulation led to a sustained decrease of SICI and increase of ICF in the contralateral motor cortex. These effects lasted for at least 60 min and were stronger 1 h post-stimulation compared with testing immediately after stimulation. A sham group did not show any differences before and after MG stimulation.ConclusionsWe provide a first demonstration that MG whole-hand stimulation induces increases in motor cortical excitability lasting at least 1 h. Both the strength of the corticospinal projections and the inhibitory and facilitatory intracortical mechanisms are involved. Synaptic modifications such as long-term potentiation mechanisms may underlie this stimulation-induced cortical plasticity changes.SignificancePresent results prove the MG stimulation to be a promising tool in neurorehabilitation.     

Unilateral grip fatigue reduces short interval intracortical inhibition in ipsilateral primary motor cortex

ObjectiveThis study was designed to examine whether exhaustive grip exercise of the left hand affected intracortical excitability in ipsilateral motor cortex.MethodsTen healthy male subjects (aged 21–24 years) participated in experiment 1 in which paired-pulse transcranial magnetic stimulation (TMS) was used to test corticospinal and corticocortical excitability in right (relaxed) first dorsal interosseous (FDI) muscle during the recovery period after exhaustive forceful grip exercise of the left hand. Seven of the same subjects participated in experiment 2, in which the intensity of the test stimulus was adjusted so that the amplitude of motor evoked potential (MEP_TEST) was kept constant throughout the measurement.ResultsIn experiment 1, MEP_TEST was slightly reduced from 5 to 15 min after exercise whilst short interval intracortical inhibition (SICI) at interstimulus interval (ISI) of 2 and 3 ms became less effective. Intracortical facilitation (ICF) was unchanged. In experiment 2 when the MEP_TEST was maintained at a constant size there was again no change in ICF, and the reduction in SICI was still present at the same intervals.ConclusionsWe conclude that unilateral exhaustive grip exercise reduced the excitability of the corticospinal output of the ipsilateral motor cortex whilst simultaneously reducing the excitability of SICI. These results would be compatible with the idea that fatigue increases the tonic level of interhemispheric inhibition from the fatigued to the non-fatigued cortex.SignificanceMuscle fatigue to the point of exhaustion has lasting effects on the excitability of intracortical circuits in the non-exercised hemisphere, perhaps via changes in the tonic levels of activity in transcallosal pathways.     

Modafinil reverses hypoexcitability of the motor cortex in narcoleptic patients: A TMS study

ObjectiveAlthough many animal and human studies have been performed, the exact mechanisms of action whereby modafinil promotes wakefulness are still not completely understood. We aimed to investigate the functional effects of modafinil on motor cortex excitability in patients with narcolepsy by means of transcranial magnetic stimulation (TMS) techniques.MethodsIn a double-blind and placebo-controlled design, 24 drug-naive narcoleptic patients with cataplexy and 20 control subjects were administered modafinil or placebo over a period of 4 weeks. TMS was performed twice during the awake state before and at the end of treatment; measures of cortical excitability included central motor conduction time, resting motor threshold, short latency intracortical inhibition (SICI) and intracortical facilitation to paired-TMS. TMS measures were correlated with the conventional neurophysiological method of Multiple Sleep Latency Test (MSLT) and the subjective Epworth Sleepiness Scale (ESS).ResultsAs previously reported, motor threshold and SICI were significantly increased in patients with narcolepsy; modafinil reversed this cortical hypoexcitability, but only SICI differences reached statistical significance. The Spearman rank correlation analysis revealed the highest correlation between SICI and the MSLT; a positive correlation was also found between SICI and the ESS, as well as between RMT and both measures of daytime sleepiness.ConclusionsThis represents the first report investigating effects of modafinil on cortical excitability in human narcolepsy. Since SICI is thought to be directly related to GABA_A intracortical inhibitory activity, we demonstrated that the dose of modafinil that induces a satisfactory wakefulness-promoting response in narcoleptic patients also causes decrease in GABAergic transmission.     

Carbamazepine reduces short-interval interhemispheric inhibition in healthy humans

ObjectiveWe sought to elucidate the influence of centrally active drugs on interhemispheric inhibition (IHI) between primary motor cortices in healthy humans.MethodsWe therefore studied IHI before and 2 h after intake of a single oral dose of carbamazepine, dextrometorphane, lorazepam, or placebo and compared it with the well known results for short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF). Drugs were tested in separate sessions and in random order.ResultsWhile SICI and ICF were not altered by carbamazepine, IHI was reduced at the interstimulus interval of 8 ms. Dextrometorphane tended to enhance SICI and to reduce ICF and had no effect on IHI. Lorazepam reduced ICF as expected and enhanced IHI at the long intervals of 50 and 80 ms. A moderate trend for interhemispheric facilitation was inconsistently observed at the interval 2 ms and blocked by carbamazepine. In addition, carbamazepine increased the motor threshold.ConclusionsWe conclude that circuits mediating short interstimulus intervals of IHI are susceptible to sodium channel blockade.SignificanceThe results increase our knowledge of interhemispheric transmission.     

Zonisamide decreases cortical excitability in patients with idiopathic generalized epilepsy.

ObjectiveTo evaluate changes in cortical excitability after long-term zonisamide (ZNS) administration.MethodsFifteen drug-naïve idiopathic generalized epilepsy (IGE) patients (8 male, mean age 24.9 years) were enrolled. The transcranial magnetic stimulation (TMS) parameters obtained using two Magstim 200 stimulators were resting motor threshold (RMT), motor evoked potential (MEP) amplitudes, cortical silent period (CSP), intracortical inhibition (ICI), and intracortical facilitation (ICF). TMS parameters were compared before and after ZNS administration.ResultsAll patients were administered ZNS monotherapy (200 mg/day) for 8 weeks. No patient reported seizures during the study period. After ZNS treatment MEP amplitudes were significantly reduced in right (−34.2%) and left hemispheres (−37.0%) (Wilcoxon’s signed rank test after Bonferroni’s correction for multiple comparisons, P < 0.05). Mean RMT, CSP, and ICI/ICF were not changed by ZNS (P > 0.05).ConclusionsThese findings suggest that ZNS decreases cortical excitability in patients with IGE and a MEP amplitude is a useful TMS parameter for evaluating changes in cortical excitability induced by ZNS.SignificanceThe findings in this study are helpful to understand how ZNS affects the excitability of the motor cortex in patients with IGE.     

Functional repetitive transcranial magnetic stimulation increases motor cortex excitability in survivors of stroke

ObjectiveTo determine if repetitive transcranial magnetic stimulation (rTMS) applied to the motor cortex with simultaneous voluntary muscle activation, termed functional-rTMS, will promote greater neuronal excitability changes and neural plasticity than passive-rTMS in survivors of stroke.MethodsEighteen stroke survivors were randomized into functional-rTMS (EMG-triggered rTMS) or passive-rTMS (rTMS only; control) conditions. Measures of short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF), force steadiness (coefficient of variation, CV) at 10% of maximum voluntary contraction, and pinch task muscle activity were assessed before and after rTMS. Functional-rTMS required subjects to exceed a muscle activation threshold to trigger each rTMS train; the passive-rTMS group received rTMS while relaxed.ResultsSignificant interactions (time × condition) were observed in abductor pollicis brevis (APB) SICI, APB ICF, CV of force, and APB muscle activity. Functional-rTMS decreased APB SICI (p < 0.05) and increased ICF (p < 0.05) after stimulation, whereas passive-rTMS decreased APB muscle activity (p < 0.01) and decreased CV of force (p < 0.05). No changes were observed in FDI measures (EMG, ICF, SICI).Conclusion(s)Functional-rTMS increased motor cortex excitability, i.e., less SICI and more ICF for the APB muscle. Passive stimulation significantly reduced APB muscle activity and improved steadiness.SignificanceFunctional-rTMS promoted greater excitability changes and selectively modulated agonist muscle activity.     

Wake up to sleep: The effects of lacosamide on daytime sleepiness in adults with epilepsy

ObjectiveThe objective of the study was to investigate the effects of lacosamide (LCM) on daytime sleepiness ascertained by the Epworth Sleepiness Scale (ESS) in adults with focal epilepsy in a randomized, controlled design.MethodsSubjects taking ≤ 2 AEDs for ≥ 4 weeks underwent polysomnography with EEG followed by the maintenance of wakefulness test (MWT) and completed the ESS and other patient-reported outcomes (PROs) at baseline, LCM 200 mg/day, and LCM 400 mg/day (Visit 4; V4). Primary endpoint was ESS change (V4 to baseline) between LCM and placebo. Noninferiority test on ESS used a one-sided t-test based on a hypothesized difference of 4-point change between groups. Superiority test used a two-sided t-test to investigate the difference in change in PROs and MWT mean sleep latency (MSL) between groups. Fifty-five subjects provided 80% power to show noninferiority of LCM assuming 10% dropout.ResultsFifty-two subjects (mean age: 43.5 ± 13.2 years, 69% female, median monthly seizure frequency: 1 [0, 4.0]) participated. Baseline group characteristics including age, sex, ethnicity, standardized AED dose, seizure frequency, and ESS were similar. Abnormal baseline ESS scores were found in 35% of subjects. Noninferiority test found a ≤ 4-point increase in ESS (mean [95% CI]) in LCM subjects vs. placebo (− 1.2 [− 2.9, 0.53] vs. − 1.1 [− 5.2, 3.0], p = 0.027) at V4. No significant difference in change in PROs, MSL, seizure frequency, or AED standardized dose was observed between groups.SignificanceOur interventional trial found that LCM is not a major contributor to daytime sleepiness based on subjective and objective measures. Inclusion of sleepiness measures in AED trials is warranted given the high prevalence of sleep–wake complaints in people with epilepsy.     

Altered cortical excitability in patients with untreated obstructive sleep apnea syndrome

ObjectiveTo investigate cortical excitability in patients with obstructive sleep apnea syndrome (OSAS) during wakefulness.MethodsThe authors recruited 45 untreated severe OSAS (all males, mean age 47.2 years, mean apnea–hypopnea index = 44.6 h^?1) patients and 44 age-matched healthy male volunteers (mean apnea–hypopnea index = 3.4 h^?1). The TMS parameters measured were resting motor threshold (RMT), motor evoked potential (MEP) amplitude, cortical silent period (CSP), and short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF). These parameters were measured in the morning (9–10 am) more than 2 h after arising and the parameters of patients and controls were compared. The Epworth Sleepiness Scale (ESS) and the Stanford Sleepiness Scale (SSS) were also measured before the TMS study.ResultsOSAS patients had a significantly higher RMT and a longer CSP duration (t-test, p < 0.001) compared to healthy volunteers. No significant difference was observed between MEP amplitudes at any stimulus intensity or between the SICI (2, 3, 5 ms) and ICF (10, 15, 20 ms) values of OSAS patients and healthy volunteers (p > 0.05).ConclusionsThis TMS-based study suggests that untreated severe OSAS patients have imbalanced cortical excitabilities that enhanced inhibition or decreased brain excitability when awake during the day.     

Comparison of lacosamide versus sodium valproate in status epilepticus: A pilot study

PurposeThe purpose of this study was to compare the efficacy and safety of lacosamide (LCM) and sodium valproate (SVA) in lorazepam (LOR)-resistant SE.MethodsPatients with LOR-resistant SE were randomized to intravenous LCM 400mg at the rate of 60 mg/kg/min or SVA 30 mg/kg at the rate of 100 mg/min. The SE severity score (STESS), duration of SE and its etiology, and MRI findings were noted. Primary outcome was seizure cessation for 1 h, and secondary outcomes were 24 h seizure remission, in-hospital death, and severe adverse events (SAE).ResultsSixty-six patients were included, and their median age was 40 (range 18–90) years. Thirty-three patients each received LCM and SVA. Their demographic, clinical, STESS, etiology, and MRI findings were not significantly different. One-hour seizure remission was not significantly different between LCM and SVA groups (66.7% vs 69.7%; P = 0.79). Twenty-four-hour seizure freedom was insignificantly higher in SVA (20, 66.6%) compared with LCM group (15, 45.5%). Death (10 vs 12) and composite side effects (4 vs 6) were also not significantly different in LCM and SVA groups. LCM was associated with hypotension and bradycardia (1 patient), and SVA with liver dysfunction (6).ConclusionIn patients with LOR-resistant SE, both LCM and SVA have comparable efficacy and safety.     

Transcranial alternating current stimulation (tACS) modulates cortical excitability as assessed by TMS-induced phosphene thresholds

ObjectiveRecent developments in transcranial alternating current stimulation (tACS) provide a powerful approach to establish the functional roles of neuronal oscillatory activities in the human brain. Here, we investigated whether tACS can reach and modulate the excitability of the visual cortex in a frequency-dependent manner.MethodsWe measured the cortical excitability of the visual cortex using single pulse transcranial magnetic stimulation (TMS) while delivering tACS to the occipital region at different frequencies (5, 10, 20 and 40 Hz).ResultsWe found that tACS at 20 Hz decreased TMS–phosphene threshold (i.e., increased the excitability of the visual cortex) during the stimulation, whereas other frequencies did not affect TMS–phosphene thresholds.ConclusionsOur findings demonstrate direct interactions of tACS with the visual cortex in a frequency-dependent manner.SignificanceOur present work provides further demonstration of the potential of tACS as a method to selectively modulate the excitability of the visual cortex.     

Reduced plastic brain responses to repetitive transcranial magnetic stimulation in severe obstructive sleep apnea syndrome

ObjectivesAbnormalities in cortical excitability have been proposed to underlie the pathophysiology of various neurocognitive manifestations of obstructive sleep apnea syndrome (OSAS). Transcranial magnetic stimulation (TMS) provides a noninvasive method for study and modulation of cortical excitability in the human brain, and repetitive TMS (rTMS) has been proven useful for neurophysiologic investigation in various neurologic conditions. We aimed to investigate cortical excitability in patients with OSAS during wakefulness and to determine if rTMS would change the abnormal excitability patterns.MethodsMeasures of motor cortical and corticospinal excitability (resting motor threshold [RMT], motor-evoked potential [MEP] amplitude, and cortical silent period [CSP]) were taken before and after a session of 10-Hz rTMS applied to the motor cortex in 13 individuals with untreated severe OSAS (apnea–hypopnea index [AHI] > 30) and 12 age- and sex-matched healthy controls (HC).ResultsOSAS subjects had a significantly higher RMT (P < .003) and a longer CSP duration (P < .002) compared to HC. No difference was observed between MEP values of OSAS subjects and HC (P > .05). In response to rTMS, the HC group had a significant increase in CSP and MEP values from baseline, which were absent in OSAS subjects.ConclusionsIndividuals with OSAS demonstrated increased motor cortex inhibition, which did not respond to 10-Hz rTMS. As rTMS-induced changes in MEP and CSP involve a separate neurotransmitter system (N-methyl-d-aspartate [NMDA] and gamma-aminobutyric acid [GABA], respectively), these findings suggest a widespread alteration in cortical neurophysiology in severe OSAS subjects that requires clarification with further exploration.     

Pharmacodynamic and pharmacokinetic interactions of perampanel and other antiepileptic drugs in a rat amygdala kindling model

PurposeThis study explored the pharmacodynamic and pharmacokinetic effects of combining perampanel (PER) with commonly co-administered AEDs.MethodA strong stimulus intensity (three-fold higher than after-discharge threshold) was used to elicit drug-resistant seizures in a rat amygdala kindling model. Vehicle, low-dose PER (0.75 mg/kg), or high-dose PER (1.5 mg/kg), in combination with vehicle, levetiracetam (LEV) 50 mg/kg, lamotrigine (LAM) 20 mg/kg, carbamazepine (CBZ) 20 mg/kg, or valproic acid (VPA) 200 mg/kg, were administered intraperitoneally to groups of 6–13 rats. Seizure score, electroencephalography (EEG) seizure duration, and motor seizure duration were evaluated, with pharmacodynamic interactions determined by two-way analysis of variance (ANOVA). Motor impairment was evaluated by rotarod test and two-way ANOVA.ResultsHigh-dose PER, but not low-dose PER, LEV, LAM, CBZ, or VPA, reduced EEG seizure duration, motor seizure duration, and seizure score compared with vehicle alone. However, when low-dose PER was administered in combination with LEV, LAM, CBZ, or VPA, seizure severity parameters were reduced compared with the concomitant AEDs alone. These pharmacodynamic interactions were statistically significant in some cases, but the same AED combinations were not associated with statistically significant neurotoxic interactions. Efficacy may have been slightly affected by changes in PER plasma concentrations in the presence of other AEDs:PER plasma concentrations increased with LEV or LAM co-administration, and decreased with CBZ or VPA co-administration.ConclusionOverall, these data support published Phase III data demonstrating the efficacy of PER as adjunctive therapy for the treatment of refractory partial-onset seizures in patients aged ≥12 years.     

Increased cortical excitability after selective REM sleep deprivation in healthy humans: A transcranial magnetic stimulation study

BackgroundREM sleep has antiepileptogenic properties whereas, its loss is known to have a proconvulsive role. However, the mechanisms underlying the proepileptogenic effects of REM sleep deprivation are yet not fully understood. The aim of our study was to evaluate the effects of selective REM sleep deprivation (SRD) on cortical excitability in healthy subjects by means of transcranial magnetic stimulation (TMS).MethodsTen normal subjects underwent three TMS sessions: (1) in baseline condition (BL), (2) after SRD by awakening them at each REM sleep onset and (3) after non-rapid eye movement sleep awakenings (NREM-A) as control for potential non-specific effects of interruptions. The TMS investigation included two protocols: (a) the evaluation of motor evoked potentials (MEPs) and silent period (SP) parameters, recorded in response to single pulse magnetic stimulation; (b) the evaluation of the time course of intracortical motor activity tested with paired-pulse TMS applied at inter-stimulus intervals of 1–10 ms.ResultsAfter SRD the principal finding observed using single pulse TMS was a significant reduction in the duration of SP whereas, a reduction of intracortical inhibition was found, using the paired-pulse TMS. TMS parameters did not show significant changes after NREM-A with respect to BL.ConclusionsSRD may influence cortical excitability with a reduction of inhibitory intracortical mechanisms, thus supporting the proconvulsant role of REM loss.     

Determining optimal rTMS parameters through changes in cortical inhibition

ObjectivesEvidence shows that repetitive transcranial magnetic stimulation (rTMS) changes cortical inhibition (CI) and excitability and that these changes may relate to its therapeutic effects. This study aimed to investigate the effects of differing durations or ‘doses’ of rTMS on cortical inhibition and excitability in healthy subjects.MethodsFour different experiments were conducted: 1 session of 1200 pulses of 1 or 20 Hz active or sham rTMS; 10 sessions of 1 or 20 Hz active or sham rTMS, 1200 pulses/session; 1 session of 3600 pulses of 1 or 20 Hz active or sham rTMS; 1 session of 6000 pulses of 20 Hz active or sham rTMS. Measures of cortical inhibition and excitability included short-interval intracortical inhibition, long interval cortical inhibition, cortical silent period (CSP), motor evoked potential amplitude, resting motor threshold and intracortical facilitation.ResultsOnly 6000 pulses of 20 Hz rTMS lead to a significant lengthening of the CSP and therefore potentiation of CI. There were no changes to excitability measures.ConclusionOnly high frequency rTMS potentiated CI. Longer treatment durations are required to produce such changes.SignificanceStudies investigating the therapeutic effects of rTMS may benefit from extended dosing with increased number of pulses per session. CSP lengthening may be used to guide treatment response.     

Effects of theta burst stimulation on motor cortex excitability in Parkinson's disease

ObjectiveLong-term potentiation (LTP)-like plasticity induced by paired associative stimulation (PAS) is impaired in Parkinson’s disease (PD). Intermittent theta burst stimulation (iTBS) is another rTMS protocol that produces LTP-like effects and increases cortical excitability but its effects are independent of afferent input. The aim of the present study was to examine the effects of iTBS on cortical excitability in PD.MethodsiTBS was applied to the motor cortex in 10 healthy subjects and 12 PD patients ON and OFF dopaminergic medications. Motor evoked potential (MEP) before and for 60 min after iTBS were used to examine the changes in cortical excitability induced by iTBS. Paired-pulse TMS was used to test whether intracortical circuits, including short interval intracortical inhibition, intracortical facilitation, short and long latency afferent inhibition, were modulated by iTBS.ResultsAfter iTBS, the control, PD ON and OFF groups had similar increases in MEP amplitude compared to baseline over the course of 60 min. Changes in intracortical circuits induced by iTBS were also similar for the different groups.ConclusionsiTBS produced similar effects on cortical excitability for PD patients and controls.SignificanceSpike-timing dependent heterosynaptic LTP-like plasticity induced by PAS may be more impaired in PD than frequency dependent homosynaptic LTP-like plasticity induced by iTBS.     

History of exposure to dopaminergic medication does not affect motor cortex plasticity and excitability in Parkinson’s disease

ObjectiveLittle is known whether and how chronic exposure to dopaminergic treatment alters physiological mechanisms in Parkinson’s disease (PD).MethodsTwo clinically similar groups of PD patients, one consisting of drug-naïve patients and another of patients already on chronic dopaminergic medication (when off medication), were compared to each other and to a control group. Plasticity and excitability of the hand primary motor cortex of the more affected side were evaluated using transcranial magnetic stimulation (TMS) techniques.ResultsThere was little difference between two patient groups, and both groups showed similar differences in comparison to controls: decreased facilitatory sensory-motor plasticity (as measured by paired associative stimulation [PAS] protocol), impaired short-interval intracortical inhibition (SICI), and diminished slope of input–output curves at higher TMS intensities. The exception was that 30 min after PAS, intracortical facilitation (ICF) was significantly reduced in drug-naïve patients, whereas it changed much less in other two groups.ConclusionsChronic exposure to dopaminergic drugs does not affect substantially the features of motor cortex excitability and plasticity in PD. There is little interaction between plasticity and excitability features of motor cortex in PD.SignificanceReduced response to facilitatory PAS protocol, reduced SICI, and reduced slope of the input–output curve at higher TMS pulse intensities, seem to be physiological markers for the presence of the pathological disease process in PD. Long term treatment does not seem to change the underlying physiology of the disease.     

Effects of persistent Mal de debarquement syndrome on balance,psychological traits,and motor cortex exctiability

Mal de debarquement syndrome (MdDS) is a poorly characterized and understood disorder of perceived motion. We sought to characterize postural control and the psychological impact of MdDS. Additionally, we explored whether patients with MdDS exhibit altered corticospinal and intracortical excitability. In a case-control study we compared patients with MdDS to age- and sex-matched controls (n = 8/group). Postural stability (σ_r) was quantified from plane phase plots based on center or pressure, and psychological indices of depression, fatigue and kinesiophobia were obtained. Transcranial magnetic stimulation (TMS) was used to assess corticospinal excitability by quantifying the motor evoked potential (MEP) amplitude of the flexor carpi radialis, and intracortical excitability was assessed by quantifying indices of intracortical facilitation (ICF), and short-interval and long-interval intracortical inhibition using a paired-pulse TMS paradigm. The patients with MdDS exhibited greater mean (±standard error of the mean) σ_r during semi-tandem stance (10.9 ± 1.5 compared to 7.1 ± 0.7, p = 0.04), higher levels of kinesiophobia (41.6 ± 2.8 compared to 27.3 ± 2.2), and higher levels of fatigue (27.0 ± 4.1 compared to 48.4 ± 1.0). Patients with MdDS exhibited a higher mean motor threshold (MT) (58.1 ± 2.5 compared to 47.4 ± 2.7% of stimulator output), and larger MEP (13.1 ± 3.1 compared to 5.1 ± 1.2% of maximal compound muscle action potential) but there was no difference in measures of intracortical excitability. These findings suggest that patients with MdDS exhibit impaired postural stability, and high levels of kinesiophobia and fatigue. Additionally, we observed that patients with MdDS exhibit higher MT and large MEP amplitudes, but do not exhibit differences in measures of intracortical excitability, compared to controls. These findings help characterize MdDS, and provide insight into the physiology of MdDS.