Taira Uehara

Minimum norm estimates in MEG can delineate the onset of interictal epileptic discharges: A comparison with ECoG findings

The analysis of epileptic discharges in magnetoencephalography with minimum norm estimates (MNE) is expected to provide more precise localization of epileptic discharges compared with electroencephalographic estimations. However, the clinical feasibility of MNE remains unclear. In this study, we aimed to elucidate the onset and propagation patterns of interictal spikes using MNE. Seven patients with intractable epilepsy whose epileptogenicity was assumed to exist in the convexity of the cerebral cortex were studied. For MNE and electrocorticography (ECoG), we characterized the propagation patterns of interictal epileptic discharges according to the area in which they originated and where they extended; we then examined whether the propagation patterns observed in MNE were identified by ECoG. We also examined the relationship between the positions of spikes estimated by the equivalent current dipole (ECD) method and MNE. Among the seven patients, nine propagation patterns of epileptic discharges were observed by MNE, all of which were also identified by ECoG. In seven patterns, the epileptic activity propagated around the initial portion. However, in two patterns, the center of activities moved according to propagation with maintained activity of the initial portion. The locations of spikes identified by the ECD method were within the areas estimated by MNE when the epileptic activity propagated. However, the ECD method failed to detect onset activities identified by MNE in three of nine patterns. Thus, MNE is more useful as a means of presurgical evaluation for epilepsy than the ECD method because it can delineate the onset of epileptic activities as shown in ECoG.

Thymoma-Associated Progressive Encephalomyelitis with Rigidity and Myoclonus Successfully Treated with Thymectomy and Intravenous Immunoglobulin

cle spasms were frequently experienced. Her neck, trunk and extremities showed rigido-spasticity. Painful spasms were easily elicited by auditory, visual and tactile stimuli. Reflex myoclonus was also observed. Hyper-reflexia was seen in 4 limbs and pathological reflexes were bilaterally positive. Sensation was normal. Blood cell counts and serum chemistry revealed no abnormalities. The anti-glutamic acid decarboxylase (GAD) antibody level was 9,020 U/ml in serum and 109 U/ml in cerebrospinal fluid (normal 1.5). Anti-acetylcholine receptor antibody was positive at a titer of 11.9 nmol/l (normal 0.2). Serum anti-amphiphysin antibody was negative. Cerebrospinal fluid analysis showed no abnormality. Head and spinal cord MRI was normal. There was no slowing in electroencephalography. Nerve conduction study was normal. There was no decrease in compound muscle action po tential on repetitive stimulation of the median nerve. Needle electromyography revealed continuous contraction of both agonist and antagonist muscles in the extremities ( fig. 1 A). Thoracic CT depicted the presence of thymoma in the anterior mediastinum ( fig. 1 B).

Age-related changes across the primary and secondary somatosensory areas: An analysis of neuromagnetic oscillatory activities

OBJECTIVE Age-related changes are well documented in the primary somatosensory cortex (SI). Based on previous somatosensory evoked potential studies, the amplitude of N20 typically increases with age probably due to cortical disinhibition. However, less is known about age-related change in the secondary somatosensory cortex (SII). The current study quantified age-related changes across SI and SII mainly based on oscillatory activity indices measured with magnetoencephalography. METHODS We recorded somatosensory evoked magnetic fields (SEFs) to right median nerve stimulation in healthy young and old subjects and assessed major SEF components. Then, we evaluated the phase-locking factor (PLF) for local field synchrony on neural oscillations and the weighted phase-lag index (wPLI) for cortico-cortical synchrony between SI and SII. RESULTS PLF was significantly increased in SI along with the increased amplitude of N20m in the old subjects. PLF was also increased in SII associated with a shortened peak latency of SEFs. wPLI analysis revealed the increased coherent activity between SI and SII. CONCLUSIONS Our results suggest that the functional coupling between SI and SII is influenced by the cortical disinhibition due to normal aging. SIGNIFICANCE We provide the first electrophysiological evidence for age-related changes in oscillatory neural activities across the somatosensory areas.

Multiphasic acute disseminated encephalomyelitis associated with atypical rubella virus infection

We report the first case of an occurrence of multiphasic acute disseminated encephalomyelitis (ADEM) associated with atypical rubella virus infection with no rash and long-term increased titers of serum anti-rubella IgM in a 17-year-old male who had no history of rubella vaccination. He suffered from at least six clinical exacerbations with disseminated hyperintense lesions on FLAIR MR images during the course of 18 months. Repeated methylprednisolone pulse therapy and intravenous immunoglobulin therapy resolved the exacerbations. In patients with multiphasic ADEM of unknown etiology, clinicians should also consider the possibility of preceding infection with rubella virus.

Modular organization of intrinsic brain networks: A graph theoretical analysis of resting-state fMRI

Recently, modular organization of intrinsic brain networks has been revealed by the graph theoretical analysis of resting-state functional MRI (rs-fMRI). In this paper, we introduce the concept of the graph theoretical analysis and modular organization. Then, we present the results of our analysis. In the graph theoretical analysis, intrinsic brain networks measured by rs-fMRI are modeled as the graphs (nodes linked by edges). Then, a module is defined as a group of highly inter-connected nodes which have relatively sparse connections to nodes in other modules. Recently, effective module detection methods have been proposed, and applied to rs-fMRI. In our study, rs-fMRI data were collected from 18 healthy young participants, and we detected the modules from a group level graph with fine spatial resolution. As a result, we found 6 dominant modules (default-mode, fronto-parietal, cingulo-opercular, sensorimotor, visual, and auditory). These modules were also detected when another module detection method was applied. Then, nodes were classified according to their roles based on their intra-module and inter-module connections. We found that majority of brain regions were classified as peripheral nodes which mostly connect with nodes within their modules. Interestingly, fronto-parietal module which consists of transmodal higher-order brain regions had more connector nodes (connecting with other modules) than unimodal visual and sensorimotor modules. This suggested that modular organization in intrinsic brain networks can reflect functional properties of brain systems.

A case of multiple system atrophy-parkinsonian type with stuttering- and palilalia-like dysfluencies and putaminal atrophy

Both developmental and acquired stuttering are related to the function of the basal ganglia-thalamocortical loop, which includes the putamen. Here, we present a case of stuttering- and palilalia-like dysfluencies that manifested as an early symptom of multiple system atrophy-parkinsonian type (MSA-P) and bilateral atrophy of the putamen. The patient was a 72-year-old man with no history of developmental stuttering who presented with a stutter for consultation with our otorhinolaryngology department. The patient was diagnosed with MSA-P based on parkinsonism, autonomic dysfunction, and bilateral putaminal atrophy revealed by T2-weighted magnetic resonance imaging. Treatment with levodopa improved both the motor functional deficits related to MSA-P and stuttering-like dysfluencies while reading; however, the palilalia-like dysfluencies were much less responsive to levodopa therapy. The patient died of aspiration pneumonia two years after his first consultation at our hospital. In conclusion, adult-onset stuttering- and palilalia-like dysfluencies warrant careful examination of the basal ganglia-thalamocortical loop, and especially the putamen, using neuroimaging techniques. Acquired stuttering may be related to deficits in dopaminergic function.

Neuromagnetic changes of the somatosensory information processing in normal aging

Age-related electrophysiological changes in the primary somatosensory cortex (SI) are well known. There is evidence that the amplitude of the N20 component of median nerve somatosensory evoked potentials typically increases with age, probably because of cortical disinhibition. The secondary somatosensory cortex (SII) receives dual input from the SI and the thalamus. We quantified age-related changes both in SI and SII using magnetoencephalography (MEG). We recorded somatosensory evoked magnetic fields (SEFs) to median nerve stimulation in 15 young adults (aged 22-36 years, mean age 29.0±4.1) and 15 older adults (aged 52-67 years, mean age 61.9±5.4), and analysed major SEF components in SI and SII. The amplitude and equivalent current dipole (ECD) strength of the N20m were significantly increased in the older adults, consistent with the well-known electrophysiological change for cortical disinhibition in SI. The latency of N20m showed a trend for increase in older subjects, possibly reflecting slowing of conduction velocity in the peripheral nerves. In contrast, SII response (response peak at around 80-120 ms) showed a different change in aging. Latencies of the contralateral SII responses showed a trend for shortening in the older adults. There were no significant age-related changes for the amplitudes and ECD strengths. Thus, SI and SII are differently affected by aging. The shortening of the SII latency suggests age-related plastic-adaptive change in SII, which is mediated by the direct thalamocortical pathway.

Hyperexcitability restricted to the lower limb motor system in a patient with stiff-leg syndrome

We report a 29-year-old man who presented with a 2-year history of progressive stiffness and painful spasms limited to the bilateral lower limbs, exaggerated by auditory and tactile stimuli. His deep tendon reflexes were slightly increased in both lower extremities. His plantar response was flexor. His serum and cerebrospinal fluid were negative for anti-glutamic acid decarboxylase antibodies. Electromyography of antagonist muscle pairs in his distal lower limbs revealed a failure of reciprocal inhibition. We used transcranial magnetic stimulation with a paired-pulse paradigm, delivered to the cortical area of the upper and lower limbs, and revealed significantly enhanced facilitation only in the area of his lower limbs, but not that representing his upper limbs. His symptoms were improved substantially by 20mg/day of oral diazepam. To our knowledge this is the first report of a patient with hyperexcitability limited to the lower limb motor system in a patient with stiff-leg syndrome.

Altered neural synchronization to pure tone stimulation in patients with mesial temporal lobe epilepsy: An MEG study

OBJECTIVE Our previous study of monaural auditory evoked magnetic fields (AEFs) demonstrated that hippocampal sclerosis significantly modulated auditory processing in patients with mesial temporal lobe epilepsy (mTLE). However, the small sample size (n = 17) and focus on the M100 response were insufficient to elucidate the lateralization of the epileptic focus. Therefore, we increased the number of patients with mTLE (n = 39) to examine whether neural synchronization induced by monaural pure tone stimulation provides useful diagnostic information about epileptic foci in patients with unilateral mTLE. METHODS Twenty-five patients with left mTLE, 14 patients with right mTLE, and 32 healthy controls (HCs) were recruited. Auditory stimuli of 500-Hz tone burst were monaurally presented to subjects. The AEF data were analyzed with source estimation of M100 responses in bilateral auditory cortices (ACs). Neural synchronization within ACs and between ACs was evaluated with phase-locking factor (PLF) and phase-locking value (PLV), respectively. Linear discriminant analysis was performed for diagnosis and lateralization of epileptic focus. RESULTS The M100 amplitude revealed that patients with right mTLE exhibited smaller M100 amplitude than patients with left mTLE and HCs. Interestingly, PLF was able to differentiate the groups with mTLE, with decreased PLFs in the alpha band observed in patients with right mTLE compared with those (PLFs) in patients with left mTLE. Right hemispheric predominance was confirmed in both HCs and patients with left mTLE while patients with right mTLE showed a lack of right hemispheric predominance. Functional connectivity between bilateral ACs (PLV) was reduced in both patients with right and left mTLE compared with that of HCs. The accuracy of diagnosis and lateralization was 80%-90%. CONCLUSION Auditory cortex subnormal function was more pronounced in patients with right mTLE compared with that in patients with left mTLE as well as HCs. Monaural AEFs can be used to reveal the pathophysiology of mTLE. Overall, our results indicate that altered neural synchronization may provide useful information about possible functional deterioration in patients with unilateral mTLE.

T159. Hemispheric difference in temporal perception between 40- and 80-Hz auditory steady-state responses: MEG and ECoG studies

Introduction Auditory steady-state responses (ASSRs) underlie the temporal integration of the auditory cortex (AC). However, the hemispheric asymmetry of the temporal integration has not yet been systematically studied because most of studies adopted binaural stimulation to record ASSRs. Although 40-Hz ASSRs are considered as a potential biomarker for various psychiatric diseases, physiological implications of 80-Hz ASSRs have not been well understood due to their weak EEG responses. Currently, 80-Hz oscillations are reported to be brain stem origin. Thus, we studied the functional difference between 40-Hz and 80-Hz ASSRs with monaural presentation measured by MEG and ECoG in order to clarify the hemispheric lateralization of temporal integration. Methods MEGs were recorded from 14 healthy subjects (aged 20–46 years). The trains of clicks for 40 Hz or 80 Hz with 500 ms duration were presented 200 times monaurally with inter-train interval of 500 ms. ASSRs consisted of transient onset and offset responses intermixed with induced oscillations. The amplitudes and peak latencies of transient responses were analyzed after applying 5 to 30 Hz bandpass filter. In contrast, the induced oscillations were time-frequency analyzed in the frequency range of 40 Hz (35–45 Hz) and 80 Hz (75–85 Hz). Then, they were evaluated by the phase locking factor. In four patients with localization-related epilepsy who underwent ECoG, ASSRs were recorded to elucidate the neural sources of 80-Hz oscillations. Results Both the onset and offset responses were well delineated in the 80-Hz condition compared with those of 40 Hz. The onset responses were recorded in the bilateral ACs without asymmetry while the offset responses were significantly larger in the right AC by left ear stimulation. 40-Hz oscillations were induced mainly in the contralateral AC in the 40-Hz condition, while 80 Hz oscillations showed right hemispheric predominance in the 80-Hz condition irrespective of the stimulated ear. In ECoG recordings, the 80-Hz stimulation revealed clear 80 Hz oscillations in the bilateral ACs. Conclusion The offset responses by 80-Hz stimulation were clearly obtained in the right AC. The 80-Hz oscillations showed the right hemispheric predominance while those of 40-Hz were recorded mainly in the contralateral AC. The discrimination among single sounds is an important part of the perceptual process. The auditory perception to 80-Hz (12.5 ms) stimulation is considered as “continuous sound”, while that to 40-Hz (25 ms) stimulation as “periodic sound”. Our findings suggest that the former is processed in the right AC whereas the latter in the contralateral AC. Our results are consistent with behavioral studies that separation time of 20–30 ms is required to distinguish sequences of auditory events and that the inflection point of amplitude modulation detection is about 50 Hz. Our findings also endorse use of 80-Hz ASSRs for the basic and clinical researches in temporal perception.