Tatsuhide Oga

Low-frequency rTMS over lateral premotor cortex induces lasting changes in regional activation and functional coupling of cortical motor areas

OBJECTIVE To study the effect of 0.9 Hz repetitive transcranial magnetic stimulation (rTMS) of the lateral premotor cortex on neuronal activity in cortical motor areas during simple motor tasks. METHODS In 8 subjects, electroencephalogram (EEG) and electromyogram (EMG) were simultaneously recorded during voluntary contractions of the thumb before and after a 15 min train of 0.9 Hz rTMS over the left lateral premotor cortex at stimulus intensity of 90% of active motor threshold. After-effects on cortical motor activity were assessed by measuring the task-related EEG power and inter-regional coherence changes, and the EEG-EMG coherence (EMGCoh). RESULTS Low-frequency rTMS over the premotor cortex gave rise to (i) a reduction of the task-related power decrease in the alpha and beta bands, (ii) a selective increase in the task-related coherence change among cortical motor areas in the upper alpha band, and (iii) a decrease in the cortico-muscular coherence. These effects lasted about 15 min after the end of rTMS intervention. CONCLUSIONS The attenuated task-related power changes and decreased EMGCoh point to a lasting suppression of voluntary activation of cortical motor areas after rTMS. The present data provide an evidence for a transient reorganization of movement-related neuronal activity in the cortical motor areas after 0.9 Hz rTMS over the premotor cortex. SIGNIFICANCE Low-frequency rTMS changes the regional activation and functional coupling of cortical motor areas as demonstrated by EEG analysis.

Short-term high-frequency transcutaneous electrical nerve stimulation decreases human motor cortex excitability.

Several previous studies have shown that periods of changed sensory input can have after effects on the excitability of the corticospinal system. Here we test whether the parameters of peripheral stimulation conventionally used to treat pain with transcutaneous electrical nerve stimulation (TENS: 90 Hz) also have modulatory effects on the motor system. We measured the amplitude of motor evoked potentials (MEPs) elicited by the focal transcranial magnetic stimulation in the right abductor pollicis brevis and first dorsal interosseous muscles before and after 30 min TENS over the right thenar eminence. In addition, we evaluated tactile and 2-point discrimination thresholds at the same site. TENS transiently reduced MEPs and increased sensory thresholds. This suggests that short-term TENS might have an inhibitory effect on both the sensory and motor systems.

Implicit and explicit processing of kanji and kana words and non-words studied with fMRI

Using functional magnetic resonance imaging (fMRI), we investigated the implicit language processing of kanji and kana words (i.e., hiragana transcriptions of normally written kanji words) and non-words. Twelve right-handed native Japanese speakers performed size judgments for character stimuli (implicit language task for linguistic stimuli), size judgments for scrambled-character stimuli (implicit language task for non-linguistic stimuli), and lexical decisions (explicit language task). The size judgments for scrambled-kanji stimuli and scrambled-kana stimuli produced activations on the bilateral lingual gyri (BA 18), the bilateral occipitotemporal regions (BA 19/37), and the bilateral superior and inferior parietal cortices (BA 7/40). Interestingly, besides these areas, activations of the left inferior frontal region (Brocas area, BA 44/45) and the left posterior inferior temporal cortex (PITC, BA 37), which have been considered as language areas, were additionally activated during size judgment for kanji character stimuli. Size judgment for kana character stimuli also activated Brocas area, the left PITC, and the left supramarginal gyrus (SMG, BA 40). The activations of these language areas were replicated in the lexical decisions for both kanji and kana. These findings suggest that language processing of both kanji and kana scripts is obligatory to literate Japanese subjects. Moreover, comparison between the scrambled kanji and the scrambled kana showed no activation in the language areas, while greater activation in the bilateral fusiform gyri (left-side predominant) was found in kanji vs. kana comparison during the size judgment and the lexical decision. Kana minus kanji activated the left SMG during the size judgment, and Brocas area and the left middle/superior temporal junction during the lexical decision. These results probably reflect that in implicit or explicit reading of kanji words and kana words (i.e., hiragana transcriptions of kanji words), although using largely overlapping cortical regions, there are still some differences. Kanji reading may involve more heavily visual orthographic retrieval and lexical-semantic system through the ventral route, while kana transcriptions of kanji words require phonological recoding to gain semantic access through the dorsal route.

Second somatosensory area (SII) plays a significant role in selective somatosensory attention

In order to explore human cortical areas involved in active attention toward a somatosensory modality, somatosensory evoked cortical magnetic fields were recorded in ten healthy adults with a 122-channel whole-head magnetometer while the subjects performed the selective attention task. Two kinds of stimulus modality, somatosensory and auditory, were presented independently in the same session. For the somatosensory modality, a randomized sequence of strong (P=0.45) and weak (P=0.05) electric stimuli was delivered to the right median nerve at the wrist. For the auditory modality, a randomized sequence of 900-Hz (P=0.45) and 950-Hz (P=0.05) tones was delivered to both ears. Subjects were requested to pay attention to the specified stimulus modality (either somatosensory or auditory) and to count the number of rare stimuli of the attended modality (weak stimuli in the somatosensory or 950-Hz tone in the auditory modality). A total of 12 sessions were performed for each subject, among which the order of attended modality was changed alternately and counterbalanced among subjects. In the data analysis, somatosensory evoked fields for frequent stimuli (strong electric stimuli) were compared between the two conditions; attend somatosensory condition (ATS) and attend auditory condition (non-attend somatosensory condition; NATS). In six out of the ten subjects, somatosensory evoked fields showed attention-related change. The magnitude of the estimated generator source in SII, but not in SI, significantly increased from NATS to ATS while keeping the same locations. Moreover, a simulation study using the estimated sources in SII in NATS supported the enhancement of the activity in the SII rather than participation of additional sources in the selective attention task. These results suggest that the SII plays a main role in selective somatosensory attention.

Short-lasting impairment of tactile perception by 0.9Hz-rTMS of the sensorimotor cortex

To test whether low-frequency repetitive transcranial magnetic stimulation (rTMS) of sensorimotor cortex (SM1) has prolonged effects on somatosensory function, eight subjects were given 900 TMS pulses over the left hand SM1 (0.9Hz, 90% of the resting motor threshold) or at sites 3 cm anterior or posterior to it. Tactile threshold of the right hand was increased for a short duration after rTMS over SM1, but two-point discrimination and median nerve SEPs were unaffected after rTMS at any sites.

Modulation of the Visual Word Retrieval System in Writing: A Functional MRI Study on the Japanese Orthographies

We used functional magnetic resonance imaging (fMRI) to examine whether the act of writing involves different neuro-psychological mechanisms between the two script systems of the Japanese language: kanji (ideogram) and kana (phonogram). The main experiments employed a 2 2 factorial design that comprised writing-to-dictation and visual mental recall for kanji and kana. For both scripts, the actual writing produced a widespread fronto-parietal activation in the left hemisphere. Especially, writing of kanji activated the left posteroinferior temporal cortex (lPITC), whereas that of kana also yielded a trend of activation in the same area. Mental recall for both scripts activated similarly the left parieto-temporal regions including the lPITC. The writing versus mental recall comparison revealed greater activations in the left sensorimotor areas and right cerebellum. The kanji versus kana comparison showed increased responses in the left prefrontal and anterior cingulate areas. Especially, the lPITC showed a significant task-by-script interaction. Two additional control tasks, repetition (REP) and semantic judgment (SJ), activated the bilateral perisylvian areas, but enhanced the lPITC response only weakly. These results suggest that writing of the ideographic and phonographic scripts, although using the largely same cortical regions, each modulates the visual word-retrieval system according to their graphic features. Furthermore, comparisons with two additional tasks indicate that the activity of the lPITC increases especially in expressive language operations regardless of sensory modalities of the input stimulus.

Cortical mechanisms of unilateral voluntary motor inhibition in humans

While motor control is very often a goal-oriented event, little is known about the mechanisms underlying the termination of motor performance. To investigate what type of cortical activation underlies the muscle relaxation required to terminate the act, we performed single- and double-pulse transcranial magnetic stimulation (TMS) studies during voluntary muscle relaxation in nine normal volunteers. Subjects maintained a weak isometric contraction of the right first dorsal interosseous muscle (FDI), and either increased the level of contraction (Contraction), terminated the contraction (Relaxation), or maintained it (No-go) depending on a visual cue. Motor evoked potentials (MEP) and the silent period (SP) were recorded from the FDI during motor activity. To measure intra-cortical inhibition (ICI), we also performed double-pulse TMS, applying subthreshold conditioning stimuli at interstimulus intervals of 2 ms. When single-pulse TMS was given just prior to muscle relaxation (-21 to -70 ms), the MEP was reduced while the SP was unchanged. Intra-cortical inhibition was smaller just prior to the muscle relaxation. Unilateral voluntary muscle relaxation may not be associated with activation of the intracortical inhibitory system, but rather with the possible excitation of the corticospinal system, which can inhibit motoneurons disynaptically. These findings suggest that multiple inhibitory mechanisms act in diverse ways to achieve motor inhibition.

Mirror visual feedback can induce motor learning in patients with callosal disconnection

Mirror therapy using mirror visual feedback (MVF) has been applied to the stroke rehabilitation of hemiparesis. One possible mechanism of mirror therapy is the functional interhemispheric connectivity between sensorimotor areas via corpus callosum. To test this hypothesis, we investigated the MVF-induced motor learning in 2 patients with callosal disconnection. Callosal connection in patients was evaluated by clinical measures and the interhemispheric inhibition (IHI) using transcranial magnetic stimulation. Both patients suffered from somatosensory cognitive disconnection, and one showed the loss of IHI. Motor training with MVF significantly improved the motor behavior of both patients. Extending our previous study, the results of callosal patients suggested that the visual feedback through a mirror might play the crucial important role for the improvement of motor performance, rather than interhemispheric interaction via corpus callosum.

Nausea as a complication of low-frequency repetitive transcranial magnetic stimulation of the posterior fossa

BACKGROUND Transcranial magnetic stimulation (TMS) can non-invasively investigate the function of human brain. However, it can induce a focal pain at the stimulated site on the scalp or seizures when applied with high frequency (>1 Hz). Here we report an induction of nausea as a complication of low-frequency repetitive TMS (rTMS) of the cerebellum. SUBJECTS AND METHODS Eight right-handed normal volunteers underwent low-frequency (0.9 Hz) rTMS of the right cerebellum. The stimulus intensity was set at 90% of the resting motor threshold determined by TMS to motor cortex. RESULTS Nausea lasted as long as 10 min after the end of rTMS without apparent neurological deficit in two subjects. This symptom was replicated when the same protocol was applied on a different day in the same subjects. CONCLUSIONS Low-frequency rTMS of cerebellum is still a safe procedure, but the experimenters should keep in mind the possibility of inducing nausea.

Dominance of ipsilateral corticospinal pathway in congenital mirror movements

Objective: To clarify the mechanism of congenital mirror movements. Design: The triple stimulation technique (TST) and the silent period were used to investigate a patient with congenital mirror movements. The TST was used to calculate the ratio of ipsilateral to contralateral corticospinal tracts from the two hemispheres to the spinal motor neurones. Results: Transcranial magnetic stimulation over unilateral M1 induced larger ipsilateral than contralateral motor evoked potentials on both sides. Only 9% of spinal motor neurones innervating the abductor digitorum minimi were excited by contralateral primary motor cortex (M1) stimulation, while 94% were excited by the ipsilateral M1 stimulation. The silent period was examined during mirror movements and with voluntary contraction of the right first dorsal interosseus mimicking mirror movements. Left M1 stimulation (through the crossed corticospinal tract) did not show any difference in silent period between the two conditions, while right M1 stimulation (through the uncrossed tract) caused a longer silent period during mirror movements than during voluntary contractions. Conclusions: The results suggest that mirror movements may be caused by a strong connection between ipsilateral M1 and the mirror movements conveyed through a dominant ipsilateral corticospinal pathway.