Yung-Yang Lin

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.

Functional characterization of human second somatosensory cortex by magnetoencephalography.

Magnetoencephalographic (MEG) recordings allow noninvasive monitoring of simultaneously active brain areas with reasonable spatial and excellent temporal resolution. Whole-scalp neuromagnetic recordings show activation of contralateral primary (SI) and bilateral second (SII) somatosensory cortices to unilateral median nerve stimulation. Recent MEG studies on healthy and diseased human subjects have shown some functional characteristics of SII cortex. Besides tactile input, the SII cortex also responds to nociceptive afferents. The SII activation is differentially modulated by isometric muscle contraction of various body parts. Lesions in the SII cortex may disturb the self-perception of body scheme. Moreover, the SI and SII cortices may be sequentially activated within one hemisphere, but the SII cortex may also receive direct peripheral input on the ipsilateral side.

Differential effects of muscle contraction from various body parts on neuromagnetic somatosensory responses.

We studied eight healthy subjects with a whole-scalp 306-channel neuromagnetometer to explore the effect of motor activity from different body parts on somatosensory responses to left median nerve stimulation. The stimuli produced clear tactile sensation without any motor movement. In the rest condition, the subject had no task. During contraction conditions, the subject had to maintain submaximal isometric contraction in masseter, left deltoid, left thenar, or left tibialis muscles. Short-latency responses from the primary somatosensory cortex did not change during contraction. Responses from both the right (contralateral) and left second somatosensory cortices (SII) were significantly enhanced during contraction of the left thenar muscles. Responses from the left SII were significantly enhanced also during contraction of the left deltoid muscles, but they were decreased during contraction of the masseter and left tibialis anterior muscles. This study implies that SII activation is modulated by motor activity and that the effect depends on the topographical proximity of the stimulated and contracted body parts.

Magnetoencephalographic yield of interictal spikes in temporal lobe epilepsy: Comparison with scalp EEG recordings

To compare magnetoencephalography (MEG) with scalp electroencephalography (EEG) in the detection of interictal spikes in temporal lobe epilepsy (TLE), we simultaneously recorded MEG and scalp EEG with a whole-scalp neuromagnetometer in 46 TLE patients. We visually searched interictal spikes on MEG and EEG channels and classified them into three types according to their presentation on MEG alone (M-spikes), EEG alone (E-spikes), or concomitantly on both modalities (M/E-spikes). The M-spikes and M/E-spikes were localized with MEG equivalent current dipole modeling. We analyzed the relative contribution of MEG and EEG in the overall yield of spike detection and also compared M-spikes with M/E-spikes in terms of dipole locations and strengths. During the 30- to 40-min MEG recordings, interictal spikes were obtained in 36 (78.3%) of the 46 patients. Among the 36 patients, most spikes were M/E-spikes (68.3%), some were M-spikes (22.1%), and some were E-spikes (9.7%). In comparison with EEG, MEG gave better spike yield in patients with lateral TLE. Sources of M/E- and M-spikes were situated in the same anatomical regions, whereas the average dipole strength was larger for M/E- than M-spikes. In conclusion, some interictal spikes appeared selectively on either MEG or EEG channels in TLE patients although more spikes were simultaneously identified on both modalities. Thus, simultaneous MEG and EEG recordings help to enhance spike detection. Identification of M-spikes would offer important localization of irritative foci, especially in patients with lateral TLE.

Sustained visual cortex hyperexcitability in migraine with persistent visual aura.

Persistent aura without infarction, a rare migraine disorder, is defined by aura symptoms that persist for >1 week without radiological evidence of cerebral infarction. To unveil its pathophysiological mechanisms, this study used magnetoencephalography to characterize the visual cortex excitability in persistent aura by comparison with episodic and chronic migraine. We recruited six patients with persistent visual aura, 39 patients with episodic migraine [12 in ictal phase; 27 in interictal phase (with aura, n = 9; without aura, n = 18)], 18 patients with chronic migraine and 24 healthy controls. Five sequential blocks of 50 neuromagnetic prominent 100 ms responses were obtained, and the dynamic change in visual cortex excitability was evaluated by the percentage changes of individual mean prominent 100 ms amplitudes at blocks 2-5 compared with block 1, with a significant increase indicating potentiation. We found that in patients with persistent aura, there was significant potentiation during ictal periods (P = 0.009 and 0.006 at blocks 2 and 5, respectively), and the excitability change was inversely correlated with the duration of aura persistence (correlation coefficient -0.812, P = 0.050, block 2). The interictal recordings (n = 3) also showed potentiation. In terms of the other migraine spectrum disorders, persistent aura differed from episodic migraine in the presence of ictal potentiation. Persistent aura further differed from chronic migraine in the absence of interictal potentiation in chronic migraine. There was a higher percentage change of response amplitude at the end of stimulation (block 5) in persistent aura (43.3 ± 11.7) than in chronic migraine (-7.6 ± 5.5, P = 0.006) and ictal recordings of episodic migraine (-4.9 ± 9.6, P = 0.020). Normal control subjects had no significant response changes. This magnetoencephalographic study showed that the visual cortex in patients with persistent visual aura maintains a steady-state hyperexcitability without significant dynamic modulation. The excitability characteristic supports persistent visual aura as a nosological entity in migraine spectrum disorders and suggests a pathophysiological link to sustained excitatory effects possibly related to reverberating cortical spreading depression.

Theta oscillation during auditory change detection: An MEG study

To study the phase and power characteristics of brain oscillations during the preattentive detection of auditory deviance, we recorded magnetoencephalographic responses in 10 healthy subjects with an oddball paradigm. As the subject was watching a silent movie, standard tones (1000-Hz frequency, 100-ms duration) and their duration deviants (50-ms duration, probability of 15%) were randomly delivered binaurally. In addition to localizing the magnetic counterpart of mismatch negativity (MMNm) with equivalent current dipole modeling, we also measured the phase-locking value (PLV) and power change of the oscillatory responses to standard and deviant stimuli by employing the Morlet wavelet-based analysis. The MMNm signals peaking at 150-200ms after the onset of deviant were localized in bilateral temporal regions with larger amplitudes in the right hemisphere. Then 50ms after the onset of either standard or deviant stimuli, we observed an increase of PLV and power of theta and alpha oscillations in bilateral temporal regions. PLVs of theta and alpha activities to deviant stimuli were significantly larger in the right than left hemisphere (P<0.001). Compared with standard stimuli, deviants elicited a larger theta PLV (P<0.001) at 150-300ms and a larger theta power change (P<0.05) at 50-300ms for the responses in the right temporal region. In addition, a prominent theta phase-locking of deviant-elicited responses was found in the right frontal area at 110-250ms (P<0.01). Our current data suggest that a pronounced phase and power modulation on sound-elicited theta oscillations might characterize the change detection processing in the temporo-frontal network as reflected by the mismatch negativity.

Persistent ictal-like visual cortical excitability in chronic migraine

&NA; Episodic migraine (EM) may evolve into the more disabling chronic migraine (CM, monthly migraine days ⩾ 8 and headache days ⩾ 15) with unknown mechanism. Aiming to elucidate the pathophysiology of CM and its relationship with EM, this study characterized the visual cortical responses in CM and EM. Neuromagnetic visual‐evoked responses to left‐hemifield checkerboard reversals were obtained in patients with EM (interictal or ictal states), CM (interictal) and age‐matched controls. For each subject, the 1500 evoked responses were sequentially divided into 30 blocks and percentage changes of P100m amplitude in blocks 2, 9, 16, 23, and 30 compared to the first block were computed to assess habituation. At the end of visual stimulation (block 30), P100m amplitude was decreased (habituated) in the controls (n = 32) (35.2 ± 2.6 nAm vs. 41.9 ± 2.7, p = 0.005) but increased (potentiated) in the interictal state of EM (n = 29) (39.7 ± 3.8 vs. 33.5 ± 3.0, p = 0.007). In CM (n = 25), P100m was habituated (46.5 ± 2.9 vs. 51.6 ± 3.7, p = 0.013) but higher at the initial block than in those of the interictal state of EM (p = 0.001). These CM features also characterized the P100m in the ictal state of EM (n = 9). There was no difference of P100m between CM and ictal state of EM. In conclusion, patients with CM demonstrate a persistent ictal‐like excitability pattern of the visual cortex between migraine attacks which may implicate central inhibitory dysfunction.

Ictal Speech Manifestations in Temporal Lobe Epilepsy: A Video‐EEG Study

Summary: To evaluate ictal speech manifestations in complex partial seizures (CPS), we reviewed videotapes of 68 consecutive patients who underwent anterior temporal lobectomy (ATL) for treatment of intractable epilepsy in Taiwan. In all, 261 CPS were collected from their video‐EEG (VEEG) recordings. Cerebral speech dominance was determined by intracarotid injection of sodium amobarbital (Wada test) in all cases. Ictal speech manifestations, classified as verbalization or vocalization, occurred in 32 patients (47.1%) with 96 seizures (36.8%). Ictal verbalization occurred in 10 patients (14.7%). Ictal vocalization was observed in 28 patients (41.2%); including 6 patients who also had ictal verbalization. Thirty‐six patients (52.9%) had no seizure with ictal speech manifestations. Ictal verbalization had significant lateralization value: 90% of patients with this manifestation had seizure focus in the nondominant temporal lobe (p = 0.049). Seizures of patients with ictal vocalization were not more likely to arise from either temporal lobe. We also observed bilingual patients who exclusively spoke in their mother tongue (Taiwanese) rather than the acquired language (Mandarin) in 72.2% of seizures with verbalization. This finding is significant and contrary to a commonly held notion that the acquired language is used in seizures associated with speech behaviors.

Altered gray matter volume in the frontal pain modulation network in patients with cluster headache

&NA; Reduced gray matter volume was found in frontal pain‐modulation areas in patients with cluster headache, suggesting the involvement of insufficient pain‐modulating capacity in this disorder. &NA; Previous functional imaging studies in episodic cluster headache (CH) patients revealed altered brain metabolism concentrated on the central descending pain control system. However, it remains unclear whether changes in brain metabolism during the “in bout” period are due to structural changes and whether these structural changes vary between the “in bout” and “out of bout” periods. To quantify brain structural changes in CH patients, the regional gray matter volume (GMV) was compared among 49 episodic CH patients during the “in bout” period and 49 age‐ and sex‐matched controls. Twelve patients were rescanned during the “out of bout” period to evaluate the changes, if any, between these 2 periods. Compared with healthy controls, CH patients showed significant “in bout” GMV reductions in the bilateral middle frontal, left superior, and medial frontal gyri. Compared to “out of bout” scans, the “in bout” scans revealed significant GMV increases in the left anterior cingulate, insula, and fusiform gyrus. Additionally, compared to healthy controls, the “out of bout” scans revealed a trend of GMV reduction in the left middle frontal gyrus. These affected regions primarily belong to frontal pain modulation areas, and thus these GMV changes may reflect insufficient pain‐modulating capacity in the frontal areas of CH patients.

Oscillatory interaction between human motor cortex and trunk muscles during isometric contraction.

We investigated oscillatory interaction between magnetoencephalographic signals of the human motor cortex and surface electromyogram from the paraspinal (PS) and abdominal (ABD) muscles. The results were compared with data obtained during contraction of the first dorsal interosseus (FDI) and tibialis anterior (TA) muscles. Significant coherence at 15-35 Hz was observed for both PS and ABD muscles in all subjects but the coherence was weak compared with that for FDI and TA. The cortical sources for both the PS and the ABD coherences were located in the motor cortex between the source areas for the FDI and TA coherences, thereby agreeing with the classical trunk area of the motor homunculus previously determined by invasive studies. The sources were strictly contralateral for PS but bilateral for ABD contractions. Our results indicate that during isometric contractions descending motor commands are modulated by cortical oscillations for both limb and trunk muscles, although the modulation is weaker and may be bilateral for trunk muscles.