Appraisal of definition of baseline length for somatosensory evoked magnetic fields.

BACKGROUND: The baseline (BL) segment in the prestimulus period is generally assigned as a reference of evoked activities. However, an experimenter empirically defines its length in each condition. So far, the criterion for the length of a BL segment has not been established. NEW METHOD: We evaluated the effect of the length of the BL segment by recording somatosensory evoked magnetic fields (SEFs) under fixed stimulus onset asynchrony (SOA). For the evaluation of the length of the BL segment in the prestimulus period, five proportions in relation to SOA were used as the BL segment. In addition, we adopted other two types of BL segment which were the single data point measured from the value of stimulus onset (BL0) and the mean value of the whole raw data throughout the recording (DC mean). We investigated the influence of the BL segments on SEFs by utilizing two indicators: normalized N20 m amplitudes and estimated locations of corresponding equivalent current dipoles (ECDs). RESULTS: Both indicators did not show any significant differences, based on the factor of BL segments, in any SOA conditions. COMPARISON WITH EXISTING METHOD: The BL0 had by far the largest variation in the ECD locations.Therefore, utilizing stimulus onset as the BL segment should be avoided. In addition, considering that other BL segments provided comparable values by the two indicators, the DC mean can reasonably be adopted. CONCLUSIONS: We suggest that utilizing the DC mean could be employed as the BL segment.

Appearance of bitemporal periodic EEG activity in the last stage of Gerstmann-Sträussler-Scheinker syndrome (Pro102Leu): A case report.

EEG findings in advanced Gerstmann-Sträussler-Scheinker syndrome (GSS) are shown. A 56-year-old woman developed GSS symptoms and was diagnosed as having GSS with the P102L mutation at age 58. During the early stage, there were no significant EEG findings. Her clinical condition worsened and she developed akinetic mutism at age 62. The patient died of pneumonia at age 65. EEGs were recorded annually from age 61 to 65. Bilateral independent periodic discharges (BIPDs) in both temporal areas appeared at age 64. No clinical seizures were noticed. MEG showed the sharp waves of BIPDs originated independently in each temporal lobe. Other causes of BIPDs were absent.

Role of beta-band resting-state functional connectivity as a predictor of motor learning ability.

It has been suggested that resting-state functional connectivity (rs-FC) between the primary motor area (M1) region of the brain and other brain regions may be a predictor of motor learning, although this suggestion is still controversial. In the work reported here, we investigated the relationship between M1 seed-based rs-FC and motor learning. Fifty-three healthy volunteers undertook random button-press and sequential motor learning tasks. Five-minute resting-state data acquisition was performed between the two tasks. Oscillatory neural activities during the random task and the rest period were measured using magnetoencephalography. M1 seed-based rs-FC was calculated for the alpha and beta bands using amplitude envelope correlation, in which the seed location was defined as an M1 position with peak event-related desynchronization value. The relationship between rs-FC and the performance of motor learning was examined using whole brain correlation analysis. The results showed that beta-band resting-state cross-network connectivity between the sensorimotor network and the core network, particularly the theory of mind network, affected the performance of subsequent motor learning tasks. Good learners could be distinguished from poor learners by the strength of rs-FC between the M1 and the left superior temporal gyrus, a part of the theory of mind network. These results suggest that cross-network connectivity between the sensorimotor network and the theory of mind network can be used as a predictor of motor learning performance.

Localization of Sensorimotor Cortex Using Navigated Transcranial Magnetic Stimulation and Magnetoencephalography.

The mapping of the sensorimotor cortex gives information about the cortical motor and sensory functions. Typical mapping methods are navigated transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG). The differences between these mapping methods are, however, not fully known. TMS center of gravities (CoGs), MEG somatosensory evoked fields (SEFs), corticomuscular coherence (CMC), and corticokinematic coherence (CKC) were mapped in ten healthy adults. TMS mapping was performed for first dorsal interosseous (FDI) and extensor carpi radialis (ECR) muscles. SEFs were induced by tactile stimulation of the index finger. CMC and CKC were determined as the coherence between MEG signals and the electromyography or accelerometer signals, respectively, during voluntary muscle activity. CMC was mapped during the activation of FDI and ECR muscles separately, whereas CKC was measured during the waving of the index finger at a rate of 3-4 Hz. The maximum CMC was found at beta frequency range, whereas maximum CKC was found at the movement frequency. The mean Euclidean distances between different localizations were within 20 mm. The smallest distance was found between TMS FDI and TMS ECR CoGs and longest between CMC FDI and CMC ECR sites. TMS-inferred localizations (CoGs) were less variable across participants than MEG-inferred localizations (CMC, CKC). On average, SEF locations were 8 mm lateral to the TMS CoGs (p < 0.01). No differences between hemispheres were found. Based on the results, TMS appears to be more viable than MEG in locating motor cortical areas.

Modulation of Motor Learning Capacity by Transcranial Alternating Current Stimulation.

Motor function can be modulated by transcranial alternating current stimulation (tACS) in alpha, beta, and high-gamma frequencies. However, few studies have investigated tACS-induced behavioral changes in combination with endogenous oscillatory neural activity in detail. Herein, we investigated the effect of tACS on motor learning capacity and endogenous oscillatory neural activity. Fifty-two healthy volunteers were randomly assigned to four stimulation groups (10 Hz, 20 Hz, 70 Hz, or sham) and performed a visually cued button press motor learning task before and after tACS, which was delivered at the left primary motor area. Oscillatory neural activities during the motor learning task were measured using magnetoencephalography (MEG). Following tACS, the capacity for motor learning was significantly increased for 70 Hz tACS compared to sham stimulation. Oscillation analysis revealed a significant increase in beta-band power after 70-Hz tACS but not in the other stimulation groups. Our finding that capacity for motor learning and endogenous oscillatory beta activity were modulated in parallel after 70-Hz tACS suggests that 70-Hz tACS may increase the motor learning capacity by cross-modulating beta oscillatory activity. Because high gamma and beta oscillatory activity have been shown to reflect the activity of excitatory and inhibitory interneuron, our results may derive from the modulation of excitatory and inhibitory interneurons in M1 by 70-Hz tACS.

Electroclinical and radiological observation of dysfunctional zones in a patient with neurosyphilis.

We report a 33-year-old Japanese man who suffered from repetitive generalized tonic-clonic seizures which were medically intractable. Neurosyphilis was serologically diagnosed in blood and cerebrospinal fluid, and penicillin G (PcG) was consequently effective. The EEG during PcG pre-treatment showed frequent right occipital spikes and right frontocentral slow waves, which disappeared after treatment. During pre-treatment, positron emission tomography with 18-fluorodeoxyglucose and Tc-99m ethyl cysteinate dimer single-photon emission computed tomography revealed occipital hypermetabolism and hyperperfusion ("hot" area) and fronto-temporo-parietal hypometabolism and hypoperfusion ("cool" area) over the right hemisphere. The spike sources of magnetoencephalography during pre-treatment were localized to "hot" areas, and the slow activities were distributed to the fronto-temporo-parietal region, corresponding to "cool" areas. The inflammatory seizure focus and reversible dysfunctional zone associated with neurosyphilis were clearly delineated using these techniques.

Establishing a New Screening System for Mild Cognitive Impairment and Alzheimer's Disease with Mental Rotation Tasks that Evaluate Visuospatial Function.

BACKGROUND: The mental rotation task is well-known for the assessment of visuospatial function; however, it has not been used for screening of dementia patients. OBJECTIVE: The aim of this study was to create a simple screening test for patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) by focusing on non-amnestic symptoms. METHODS: Age-matched healthy controls (age 75.3±6.8), patients with MCI (76.5±5.5), and AD (78.2±5.0) participated in this study. They carried out mental rotation tasks targeting geometric graphics or alphabetical characters with three rotating angles (0°, 90°, and 180°) and indicated the correct answer. Response accuracy and reaction time were recorded along with their eye movements using an eye tracker. To quantify their visual processing strategy, the run count ratio (RC ratio) was calculated by dividing the mean number of fixations in incorrect answers by that in correct answers. RESULTS: AD patients showed lower accuracy and longer reaction time than controls. They also showed a significantly greater number of fixation and smaller saccade amplitude than controls, while fixation duration did not differ significantly. The RC ratio was higher for AD, followed by MCI and control groups. By setting the cut-off value to 0.47 in the 180° rotating angle task, we could differentiate MCI patients from controls with a probability of 80.0%. CONCLUSIONS: We established a new screening system for dementia patients by evaluating visuospatial function. The RC ratio during a mental rotation task is useful for discriminating MCI patients from controls.

The Involvement of Sensory-motor Networks in Reflex Seizure.

Reflex seizures are epileptic events triggered by specific external stimuli, or less commonly, internal mental stimuli. Understanding the characteristics of reflex seizures is important to elucidate the mechanisms underlying network abnormalities in epileptic conditions. This report details a patient with medically intractable reflex seizures provoked by sensory stimuli to the patient's right foot. Single-photon emission computed tomography (SPECT) during the seizure induced by sensory stimulation showed hyperperfusion in broad sensory-motor networks (dorsal column-medial lemniscus pathway, left thalamus, bilateral postcentral gyri and posterior parietal cortices, left supplementary motor area (SMA), and left paracentral lobule) and left caudateputamen. The irritative zones and ictal onset zone were localized to the left medial frontoparietal (SMA, anterior and middle cingulate gyrus, and paracentral lobule) and lateral posterior parietal cortices, as evidenced by amelioration of reflex seizures following intracranial electroencephalography and surgical resection of these areas. The neuroradiological and electrophysiological findings in our case study illustrate that the mechanism of reflex seizures may be associated with hyperexcitability of the broad sensory-motor networks, including the basal ganglia. Disconnection of these networks is necessary to treat reflex seizures.

Load effect on background rhythms during motor execution: A magnetoencephalographic study.

We investigated the effect of load against self-paced movement on cortical involvement for motor execution. Ten right-handed healthy volunteers were requested to perform brisk extension of the right index finger at self-paced intervals exceeding 10s for three load conditions: 0g, 50g and 100g. Movement-related magnetic fields were recorded using an MEG system. The signals were band-pass-filtered through 18-23Hz and rectified before averaging with respect to EMG onset. We analyzed the time course and %change of peak amplitude with reference to the baseline amplitude in event-related desynchronization (ERD) or synchronization (ERS) in each hemisphere. Maximum response was observed around the left somatomotor area for all conditions. ERD did not show any significant difference before the movement onset among the three load conditions. For %change, ERS in the post-movement period was significantly larger for the 100g load condition than for the 0g load condition, and that was significantly greater over the left than over the right hemisphere. These findings indicate that the load has little effect on pre-movement desynchronization, whereas it affects the post-movement synchronization on background rhythms.

Neuromodulatory Role of Revascularization Surgery in Moyamoya Disease.

BACKGROUND: To evaluate the effectiveness of bypass surgery for moyamoya disease, electrocorticography was first evaluated. METHODS: A total of 13 hemispheres in 9 patients with moyamoya disease were included in this study. To record the spectral power of electrocorticography continuously during the bypass procedure, a 4 × 5 subdural electrode grid was placed on the middle frontal gyrus. The changes in spectral power before and after bypass surgery were evaluated and compared with those in a control group. The correlation between changes in spectral power and regional cerebral blood flow was analyzed. RESULTS: The average spectral power ratio of the beta band per total band in moyamoya disease before bypass surgery was lower than that of controls (P = 0.027), and the significance disappeared after bypass surgery (P = 0.800). The spectral power levels of the beta band and gamma band were increased in moyamoya disease after bypass surgery (P < 0.001). Changes in spectral power of the beta band correlated with changes in regional cerebral blood flow (P = 0.002). CONCLUSIONS: The spectral power of the beta band on electrocorticography was focally suppressed in patients with moyamoya disease, and the suppression was reversible by revascularization surgery. Steno-occlusive ischemic changes in moyamoya disease might cause suppression of neurophysiologic activity, and the present results provide insight into the potential neuromodulatory role of revascularization surgery.

Cortico-muscular synchronization by proprioceptive afferents from the tongue muscles during isometric tongue protrusion.

Tongue movements contribute to oral functions including swallowing, vocalizing, and breathing. Fine tongue movements are regulated through efferent and afferent connections between the cortex and tongue. It has been demonstrated that cortico-muscular coherence (CMC) is reflected at two frequency bands during isometric tongue protrusions: the beta (ß) band at 15-35Hz and the low-frequency band at 2-10Hz. The CMC at the ß band (ß-CMC) reflects motor commands from the primary motor cortex (M1) to the tongue muscles through hypoglossal motoneuron pools. However, the generator mechanism of the CMC at the low-frequency band (low-CMC) remains unknown. Here, we evaluated the mechanism of low-CMC during isometric tongue protrusion using magnetoencephalography (MEG). Somatosensory evoked fields (SEFs) were also recorded following electrical tongue stimulation. Significant low-CMC and ß-CMC were observed over both hemispheres for each side of the tongue. Time-domain analysis showed that the MEG signal followed the electromyography signal for low-CMC, which was contrary to the finding that the MEG signal preceded the electromyography signal for ß-CMC. The mean conduction time from the tongue to the cortex was not significantly different between the low-CMC (mean, 80.9ms) and SEFs (mean, 71.1ms). The cortical sources of low-CMC were located significantly posterior (mean, 10.1mm) to the sources of ß-CMC in M1, but were in the same area as tongue SEFs in the primary somatosensory cortex (S1). These results reveal that the low-CMC may be driven by proprioceptive afferents from the tongue muscles to S1, and that the oscillatory interaction was derived from each side of the tongue to both hemispheres. Oscillatory proprioceptive feedback from the tongue muscles may aid in the coordination of sophisticated tongue movements in humans.

[Dramatic seizure reduction with levetiracetam in adult Dravet syndrome: a case report].

A 28 year-old man who had been diagnosed as having Dravet syndrome (DS) since his childhood by a pediatric hospital was referred to our department from the local pediatric clinic. Until then, his seizures were medically intractable, and generalized tonic-clonic convulsions had occurred monthly even when administered enough valproate, zonisamide and clorazepate. After adding levetiracetam (LEV) to his drug regimen at the age of 29, the seizures disappeared for more than one year. LEV was found to be effective in this adult patient as well as in a series of children affected with DS.

Modulation of alpha activity in the parieto-occipital area by distractors during a visuospatial working memory task: a magnetoencephalographic study.

Oscillatory brain activity is known to play an essential role in information processing in working memory. Recent studies have indicated that alpha activity (8-13 Hz) in the parieto-occipital area is strongly modulated in working memory tasks. However, the function of alpha activity in working memory is open to several interpretations, such that alpha activity may be a direct neural correlate of information processing in working memory or may reflect disengagement from information processing in other brain areas. To examine the functional contribution of alpha activity to visuospatial working memory, we introduced visuospatial distractors during a delay period and examined neural activity from the whole brain using magnetoencephalography. The strength of event-related alpha activity was estimated using the temporal spectral evolution (TSE) method. The results were as follows: (1) an increase of alpha activity during the delay period as indicated by elevated TSE curves was observed in parieto-occipital sensors in both the working memory task and a control task that did not require working memory; and (2) an increase of alpha activity during the delay period was not observed when distractors were presented, although TSE curves were constructed only from correct trials. These results indicate that the increase of alpha activity is not directly related to information processing in working memory but rather reflects the disengagement of attention from the visuospatial input.

Contralateral dominance of corticomuscular coherence for both sides of the tongue during human tongue protrusion: an MEG study.

Sophisticated tongue movements contribute to speech and mastication. These movements are regulated by communication between the bilateral cortex and each tongue side. The functional connection between the cortex and tongue was investigated using oscillatory interactions between whole-head magnetoencephalographic (MEG) signals and electromyographic (EMG) signals from both tongue sides during human tongue protrusion compared to thumb data. MEG-EMG coherence was observed at 14-36 Hz and 2-10 Hz over both hemispheres for each tongue side. EMG-EMG coherence between tongue sides was also detected at the same frequency bands. Thumb coherence was detected at 15-33 Hz over the contralateral hemisphere. Tongue coherence at 14-36 Hz was larger over the contralateral vs. ipsilateral hemisphere for both tongue sides. Tongue cortical sources were located in the lower part of the central sulcus and were anterior and inferior to the thumb areas, agreeing with the classical homunculus. Cross-correlogram analysis showed the MEG signal preceded the EMG signal. The cortex-tongue time lag was shorter than the cortex-thumb time lag. The cortex-muscle time lag decreased systematically with distance. These results suggest that during tongue protrusions, descending motor commands are modulated by bilateral cortical oscillations, and each tongue side is dominated by the contralateral hemisphere.

[Selective impairment and a unique recovery of bilateral horizontal gaze and facial palsy in a discrete pontine lesion: a case report].

A 77-year-old woman with bilateral horizontal gaze palsy, right hemifacial weakness and incomplete quadriplegia was transferred to our hospital. Brain magnetic resonance imaging on the first day revealed a slit-like signal deficit of the basilar artery and an abnormal signal area at the dorsal midline portion of the lower pons. Quadriplegia fluctuated in several days after admission, then disappeared finally. In spite of the recovery of quadriplegia, bilateral facial weakness appeared on Day 14 after the onset. Concerning the impairment of extraocular movements, bilateral adduction restored gradually followed by improvement of the right abduction. The clinical course suggested the involvement of bilateral medial longitudinal fasciculus (MLF) and abducens nuclei (or fibers) as the etiology of gaze palsy. Although bilateral MLF sign recovered within 3 weeks, and the abductor palsy of both eyes was persisted in mild degree. As imaging analysis did not always show the causative lesion, which correlated with the rapidly alternating signs in the patient, and careful neurological observation was therefore useful in the management of patients with brainstem dysfunction.

[Late-onset sarcoglycanopathy: a cause of repeated muscle cramps after exertion].

A 61-year-old man in generally good health had a 2-year history of repetitive episodes of muscle cramps, weakness, numbness and muscle pain of the bilateral limbs after exerting himself. During each episode, his serum creatine kinase level became elevated then recovered only after sufficient hydration had been provided. Bilateral thigh MRI showed abnormal muscular signals, and the patient was subsequently diagnosed by muscle biopsy, immunohistochemistry, and mini-multiplex western blotting analysis as having solitary sarcoglycanopathy. Late-onset sarcoglycanopathy has rarely been described. In the present patient, his mild clinical condition, subclinical cardiomyopathy and possible involvement of polyneuropathy are unique features.

Familial Parkinsonism with digenic parkin and PINK1 mutations.

To clarify the genetic correlation between parkin and PINK1, we screened for PINK1 mutations in 175 parkinsonism patients with parkin mutations. We detected two sibling pairs and one sporadic patient carrying both parkin and PINK1 mutations. The age at onset of Parkinsonism of patients with the digenic mutations was lower than that of patients with the same parkin mutation alone. In addition, two of three patients carrying both parkin and PINK1 mutations had schizophrenia. These findings indicate that PINK1 mutation might modify parkin mutation-positive Parkinsonism, and PINK1 mutations might be associated with psychiatric disorders.

[Fulminant strongyloidiasis successfully treated by subcutaneous ivermectin: an autopsy case].

We report a 49-year-old man who was a human T-cell leukemia virus type 1 (HTLV-1) carrier, born in Okinawa prefecture where both strongyloidiasis and HTLV-1 are endemic. He presented with fever, headache and urinary retention. On the basis of CSF examination and MRI findings, his condition was diagnosed as myelitis. He received methylprednisolone pulse therapy. He was transferred to our hospital due to severe paralytic ileus. Strongyloides stercoralis (S. stercoralis) was found in the duodenal stained tissue of a biopsy specimen. Ivermectin applied both orally and through enema were ineffective because of severe ileus and intestinal bleeding. Nine mg (200 microg/kg) of ivermectin solution was administered subcutaneously every other day for five days (total amount 45 mg). The S. stercoralis burden in the stool decreased and paralytic ileus gradually resolved. Three weeks after the resolution of S. stercoralis infection, purulent meningitis developed and acute obstructive hydrocephalus appeared. The hydrocephalus improved by ventricular drainage. Approximately three months after drainage, he died of incidental aspiratory pneumonia. Autopsy showed neither eggs nor larvae of S. stercoralis in the organs. In this case, the fourth reported case in the world, subcutaneous ivermectin injection was dramatically effective. We should consider a diagnosis of strongyloidiasis for any patient from Okinawa prefecture who was an HTLV-1 carrier presenting with unknown origin ileus after treatment of steroid therapy.