Wan-Yu Hsu

Effects of Repetitive Transcranial Magnetic Stimulation on Motor Functions in Patients With Stroke: A Meta-Analysis

Background and Purpose— The purpose of this study was to perform a meta-analysis of studies that investigated the effects of repetitive transcranial magnetic stimulation (rTMS) on upper limb motor function in patients with stroke. Methods— We searched for randomized controlled trials published between January 1990 and October 2011 in PubMed, Medline, Cochrane, and CINAHL using the following key words: stroke, cerebrovascular accident, and repetitive transcranial magnetic stimulation. The mean effect size and a 95% CI were estimated for the motor outcome and motor threshold using fixed and random effect models. Results— Eighteen of the 34 candidate articles were included in this analysis. The selected studies involved a total of 392 patients. A significant effect size of 0.55 was found for motor outcome (95% CI, 0.37–0.72). Further subgroup analyses demonstrated more prominent effects for subcortical stroke (mean effect size, 0.73; 95% CI, 0.44–1.02) or studies applying low-frequency rTMS (mean effect size, 0.69; 95% CI, 0.42–0.95). Only 4 patients of the 18 articles included in this analysis reported adverse effects from rTMS. Conclusions— rTMS has a positive effect on motor recovery in patients with stroke, especially for those with subcortical stroke. Low-frequency rTMS over the unaffected hemisphere may be more beneficial than high-frequency rTMS over the affected hemisphere. Recent limited data suggest that intermittent theta-burst stimulation over the affected hemisphere might be a useful intervention. Further well-designed studies in a larger population are required to better elucidate the differential roles of various rTMS protocols in stroke treatment.

Effects of noninvasive brain stimulation on cognitive function in healthy aging and Alzheimer's disease: a systematic review and meta-analysis

The study aimed to evaluate the effects of noninvasive brain stimulation on cognitive function in healthy older adults and patients with Alzheimers disease. A comprehensive literature search was performed on noninvasive stimulation studies published from January 1990 to November 2014 in Pubmed and Web of Science. Fourteen articles with a total of 331 participants were identified as studies with healthy older adults, and the mean effect size and 95% confidence interval were estimated. A significant effect size of 0.42 was found for the cognitive outcome. Further subgroup analyses demonstrated more prominent effects for studies delivering the stimulation before the execution of the task and studies applying multiple sessions of stimulation. To assess the effects of stimulation on Alzheimers disease patients, 11 studies with a total of 200 patients were included in the analysis. A significant effect size of 1.35 was found for the cognitive outcomes. Subgroup analyses indicated more pronounced effects for studies applying the stimulation during the execution of the task compared with studies delivering the stimulation before the execution of the task. Noninvasive brain stimulation has a positive effect on cognitive function in physiological and pathological aging.

Antiepileptic effects of low frequency repetitive transcranial magnetic stimulation: A meta-analysis

PURPOSE To evaluate the antiepileptic efficacy of low frequency repetitive transcranial magnetic stimulation (rTMS) in medically intractable epilepsy. METHODS A comprehensive literature search was performed on articles published from 1990 to 2010 in Medline, Pubmed, CINAHL, and Cochrane using the following keywords: epilepsy, seizure, transcranial magnetic stimulation, repetitive transcranial magnetic stimulation. Two reviewers assessed article eligibility and extracted the data independently. For outcome measures, effect size and 95% confidence interval (CI) were calculated for seizure frequency, spike number, duration of epileptiform abnormalities (EAs), and resting motor threshold (RMT) by using fixed and random effect models. RESULTS Eleven articles were identified, with a total of 164 participants. Based on seizure frequency, a significant effect size was found (effect size: 0.34, with a 95% CI at 0.10-0.57). Considering between-study heterogeneity, we conducted a second meta-analysis, and the underlying etiology was considered important for the treatment effect. Cortical dysplasia or neocortical epilepsy showed an effect size of 0.71, with a 95% CI at 0.30-1.12. In contrast, other epileptic disorders showed an effect size of 0.22. CONCLUSION Low frequency rTMS has a favorable effect on seizure reduction, particularly evident in patients with neocortical epilepsy or cortical dysplasia.

Inadequate inhibition of redundant auditory inputs in Alzheimer's disease: An MEG study

This study aimed to characterize the cortical deficits in processing auditory inputs in patients with Alzheimers disease (AD). The magnetic counterparts of P50 (M50) and mismatch negativity (MMNm) during a passive oddball paradigm were analyzed with equivalent current dipole modeling. The results showed larger cortical activation of standard-evoked M50 in AD patients compared to young and elderly controls. In contrast, smaller amplitudes and longer peak latencies were found in the MMNm of the elderly and AD patients compared with young adults. The MMNm latency was longer in AD patients than in elderly controls. A Spearman correlation test showed an inverse correlation between the cortical strengths of M50 and MMNm in the right hemisphere. In conclusion, age-related changes in the M50 and MMNm components, which may reflect deficits in central auditory processing, are discussed, along with the possibility that increased M50 responses are related to decreased inhibition of redundant inputs in mild AD.

Effects of physiological aging on mismatch negativity: A meta-analysis

Mismatch negativity (MMN) is a promising window on how the functional integrity of auditory sensory memory and change discrimination is modulated by age and relevant clinical conditions. However, the effects of aging on MMN have remained somewhat elusive, particularly at short interstimulus intervals (ISIs). We performed a meta-analysis of peer-reviewed MMN studies that had targeted both young and elderly adults to estimate the mean effect size. Nine studies, consisting of 29 individual investigations, were included and the final total study population consisted of 182 young and 165 elderly subjects. The effects of different deviant types and duration of ISIs on the effect size were assessed. The overall mean effect size was 0.63 (95% CI at 0.43-0.82). The effect sizes for long ISI (>2s, effect size 0.68, 95% CI at 0.31-1.06) and short ISI (<2s, effect size 0.61, 95% CI at 0.39-0.84) were both considered moderate. A further analysis showed a prominent aging-related decrease in MMN responses to duration and frequency changes at short ISIs. It was also interesting to note that the effect size was about 25% larger for duration deviant condition compared to the frequency deviant condition. In conclusion, a reduced MMN response to duration and frequency deviants is a robust feature among the aged adults, which suggests that there has been a decline in the functional integrity of central auditory processing in this population.

Differential cerebral reactivity to shortest and longer tones: Neuromagnetic and behavioral evidence

Detecting a change in sound duration is important in language processing. The cerebral reactivity to a duration deviant in oddball paradigm has been reflected as a mismatch negativity (MMN). This study aimed to see cerebral responses to several duration-varying sounds presented with equal probability. Magnetoencephalographic (MEG) and behavior responses to equi-probable sounds (25-50-75-100-125 ms or 50-75-100-125-150 ms tones) were recorded in 10 healthy adult volunteers. By subtracting the average of the responses to 4 longer tones from the response to the shortest tone, a clear deflection peaking at 100-200 ms from stimulus onset was identified. This activity was called as sub-standard MMNm, and its amplitude tended to increase with the increment of duration deviance within a stimulation paradigm. The source of sub-standard MMNm was localized in superior temporal area, with 5-6 mm more anterior to the generator of N100m response. Behavioral tests also showed best performance in the recognition of the shortest tone than longer tones. In conclusion, the preferential response to the shortest tone in an equiprobable paradigm suggests an asymmetrical processing in the auditory cortex for duration-varying sounds.

Altered inhibitory modulation of somatosensory cortices in paroxysmal kinesigenic dyskinesia.

The objective of this study was to clarify the excitability profiles of the somatosensory cortices in patients with paroxysmal kinesigenic dyskinesia.

Widespread inter-ictal excitability changes in patients with temporal lobe epilepsy: A TMS/MEG study.

PURPOSE Transcranial magnetic stimulation (TMS) has been used to elucidate the altered balance between excitatory and inhibitory circuits in the motor cortex in epilepsy; however, TMS could not well assess excitability changes beyond the motor cortex. This study aimed to address the spatial profile of cortical excitability changes in patients with temporal lobe epilepsy (TLE) by using TMS and magnetoencephalography (MEG). METHODS Eighteen patients with TLE and 18 healthy control subjects were recruited. Resting motor threshold (RMT) and intracortical inhibition (ICI) were measured to reflect motor cortical excitability by using TMS. A whole-head MEG was applied to record auditory and somatosensory evoked responses to paired-pulse stimuli. A paired-pulse inhibition (PPI) ratio, defined as the amplitude ratio between responses to the second and the first stimuli, was used to assess the auditory and somatosensory cortical excitability. A high PPI ratio suggests an increase in cortical excitability, while a low ratio indicates a decrease in excitability. RESULTS Compared to control subjects, TLE patients exhibited increased RMT in motor cortex and higher PPI ratios for auditory P50m and somatosensory P35m responses. Notably, patients with a lower seizure frequency tended to exhibit a higher RMT or a lower P35m PPI ratio. CONCLUSIONS Present data suggest that the cortical excitability alteration in focal epilepsy is widely distributed beyond the epileptic focus and the profiles of excitability change correlate with clinical severity in terms of seizure frequency. Combined MEG and TMS studies provide new insight into the inter-ictal cortical excitability profiles in patients with epilepsy.

Reduced postmovement cortical inhibition in patients with paroxysmal kinesigenic dyskinesia

Objective: To characterize movement-related neural oscillatory activity and to clarify its neurophysiologic role in paroxysmal kinesigenic dyskinesia (PKD). Methods: 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. Results: 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. Conclusions: 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.

Abnormal Somatosensory Synchronization in Patients With Paroxysmal Kinesigenic Dyskinesia: A Magnetoencephalographic Study:

Paroxysmal kinesigenic dyskinesia (PKD) is a rare group of hyperkinetic movement disorders characterized by brief attacks of choreoathetosis or dystonia. To clarify the alterations of the functional connectivity within the somatosensory network in PKD patients, magnetoencephalographic (MEG) responses to paired median-nerve electrical stimulation were recorded in 10 PKD patients treated by carbamazepine or oxcarbamazepine and 22 age-matched controls. In patients, MEG recordings were obtained during drug-on and -off periods. Source-based functional connectivity analysis was performed between contralateral primary (cSI) and secondary (cSII), and ipsilateral secondary (iSII) somatosensory areas. During drug-off periods, patients with PKD demonstrated decreased cSI-iSII and increased cSII-iSII somatosensory connectivity at theta band. Drug-on periods lowered the functional connectivity in cSI-cSII at alpha and beta bands and in cSII-iSII at theta band compared with the drug-off periods. We suggest that altered theta functional connectivity in cSI-iSII and cSII-iSII could be the neurophysiological signatures in PKD.