Hiroshi Shigeto

Altered white matter fractional anisotropy and social impairment in children with autism spectrum disorder.

Individuals with autism spectrum disorder (ASD) have severe difficulties in social interaction and communication, as well as restricted and/or stereotyped patterns of behavior. Previous studies have suggested that abnormal neural connectivity might be associated with higher information processing dysfunction involving social impairment. However, the white matter structure in ASD is poorly understood. To explore this, we conducted a voxel-based, whole-brain diffusion tensor imaging (DTI) analysis to determine fractional anisotropy (FA), λ(1), λ(2) and λ(3) in high-functioning children with ASD compared with age-, gender-, and handedness-matched healthy control participants. We then investigated whether DTI parameters were associated with behaviorally measured social function. We found that FA and λ(1) were significantly lower in the ASD group than in the control group in the white matter around left dorsolateral prefrontal cortex (DLPFC), posterior superior temporal sulcus/temporo-parietal junction, right temporal pole, amygdala, superior longitudinal fasciculus, occipitofrontal fasciculus, mid- and left anterior corpus callosum, and mid- and right anterior cingulate cortex. The FA value in the left DLPFC was negatively correlated with the degree of social impairment in children with ASD. Higher λ(1) values were observed in the cerebellar vermis lobules in the ASD group. The white matter alterations in children with ASD were around cortical regions that play important roles in social cognition and information integration. These DTI results and their relationship to social impairment add to evidence of cerebral and cerebellar white matter structural abnormalities in ASD.

Comparison of magnetoencephalography, functional MRI, and motor evoked potentials in the localization of the sensory-motor cortex.

To clarify the topographical relationship between peri-Rolandic lesions and the central sulcus, we carried out presurgical functional mapping by using magnetoencephalography (MEG), functional magnetic resonance imaging (f-MRI), and motor evoked potentials (MEPs) on 5 patients. The sensory cortex was identified by somatosensory evoked magnetic fields using MEG (magnetic source imaging (MSI)). The motor area of the hand region was identified using f-MRI, during a hand squeezing task. In addition, transcranial magnetic stimulation localized the hand motor area on the scalp, which was mapped onto the MRI. In all cases, the sensory cortex was easily identified by MSI and the results of MSI correlated well with the findings obtained by the intraoperative recording of somatosensory evoked potentials. In contrast, the motor cortex could not be localized by f-MRI due to either the activated signal of the large cortical vein or the lack of any functional activation in the area of peri-lesional edema. MEPs were also unable to localize the entire motor strip. Therefore, at present, MSI is considered to be the most reliable method to localize peri-Rolandic lesions [corrected].

Functional network of the basal ganglia and cerebellar motor loops in vivo: Different activation patterns between self-initiated and externally triggered movements

The basal ganglia and cerebellar loops are known to participate differently in self-initiated (SI) and externally triggered (ET) movements. However, no previous neuroimaging studies have illustrated functional organization of these loops in vivo. Here, we aimed to functionally visualize these loops during motor execution using functional magnetic resonance imaging (fMRI) with structural equation modeling (SEM). Twelve normal subjects (24-29 years old) were scanned while performing five different frequencies of sequential left finger movements using either SI or ET movements. Random effect analysis combined with a parametric approach revealed a significant positive linear dependence of cerebral activation upon movement rate in the right Put, GPi, VL, SMC and SMA during SI tasks. During ET tasks, significant positive linear relationships were found in the right SMC, VPL, left CB and DN, whereas tendency for linear relationships was seen in the right PMv. SEM further showed significant interactions within the right basal ganglia-thalamo-motor loop during SI tasks. In contrast, there were significant interactions within the entire right cerebral hemisphere-left cerebellar loop involving CB, DN, VPL, PMv and SMC during ET tasks. Therefore, our modeling approach enabled identification of different contributions of the motor loops of basal ganglia and cerebellum to SI and ET tasks during motor execution.

Visual evoked cortical magnetic responses to checkerboard pattern reversal stimulation: A study on the neural generators of N75, P100 and N145

In an attempt to elucidate the neural generators of pattern reversal visual evoked potentials (PR-VEPs), we measured the visual evoked magnetic fields (PR-VEFs) using a 37-channel magnetoencephalography in six healthy young adults. A half-field checkerboard pattern was phase-reversed at a rate of 1 Hz to stimulate the right or left visual half-field, thus yielding 12 PR-VEFs in total from the six subjects. The simultaneously recorded scalp PR-VEPs showed three distinct components of N75, P100 and N145. Three corresponding components were also identified in the PR-VEFs with similar peak latencies (N75m, P100m and N145m). P100m and N145m were clearly identified in all 12 PR-VEFs, whereas N75m was observed in only nine of 12 PR-VEFs. The equivalent current dipoles (ECDs) of N75m, P100m and N145m were located closely to each other in the occipital cortex around the calcarine fissure contralateral to the stimulated visual field, when they were overlaid on the MRI. The reliability of dipole estimation was highest in P100m, followed by N145m while N75m showed the least reliability. The direction of the current flow of ECDs of N75m and N145m was from the medial to the lateral in the occipital cortex when viewed in a coronal section, whereas that for P100m was toward the medial. The ECD location of P100m changed according to the retinotopic organization when the upper or lower quadrant of the visual field was stimulated, with the ECDs being located in the lower or upper part, respectively, of the visual cortex. Our results therefore indicate that the neural origins of N75m, P100m and N145m of PR-VEFs are in the primary visual cortex on the contralateral side of the stimulated visual half-field, while the three components are physiologically distinct.

Feasibility and limitations of magnetoencephalographic detection of epileptic discharges: Simultaneous recording of magnetic fields and electrocorticography

Abstract Magnetoencephalography (MEG) is considered clinically useful in localizing the epileptogenic focus in partial epilepsy. However, the relationship between the extent of the brain involved in paroxysmal activities and the magnetic field changes at the scalp has not been fully clarified. Furthermore, whether paroxysmal activities generated in deep brain structures such as the hippocampus can be detected magnetically is uncertain. Eight patients with temporal lobe epilepsy and two with extratemporal lobe epilepsy underwent chronic recording from subdural electrodes. Magnetic and electrocorticographic discharges representing epileptic activity were recorded simultaneously. MEG recorded magnetic field changes originating from paroxysmal activity in the superiolateral cerebral cortex when the amplitudes of the electrical paroxysmal activities exceeded 100 µ V and extended over more than 3 cm2 of cortical surface. MEG failed to record paroxysmal activity localized to the medial temporal lobe. MEG is often useful in identifying a spike focus in the superiolateral aspects of the cerebral hemisphere, but not discharges arising from the medial temporal lobe. Rapid decay of the magnetic field is likely to be the reason for this limited sensitivity to medial discharges. [Neurol Res 2002; 24: 531-536]

Differential interaction of somatosensory inputs in the human primary sensory cortex: a magnetoencephalographic study

OBJECTIVE Somatosensory evoked magnetic fields (SEFs) were recorded to investigate the interaction of the somatosensory inputs using the modality of electrical finger stimulation in 6 normal subjects. METHODS Electrical stimuli were given to the index (II), middle (III) or little (V) fingers individually, and also to pairs of either the II and III simultaneously, or the II and V simultaneously. The interaction ratio (IR) was calculated as the ratio of the SEF amplitude by simultaneous two-finger stimulation to the arithmetically summed SEF amplitudes of two individual-finger stimulations. RESULTS SEFs showed 3 major components: N22m, P30m and P60m. The N22m and P60m revealed a clear somatotopic organization in the primary sensory cortex (S1) in the sequence of II, III and V, while the P30m showed a cluster with medial location compared with N22m and P60m in S1. The N22m had a significantly greater IR in II and III stimulation compared to that in II and V stimulation. The P60m also showed a similar trend in the IR but was greater than that of N22m. In contrast, the IR in P30m showed no such tendency. CONCLUSION The interaction of S1 was most influenced when adjacent receptive fields were activated in the modality of electrical finger stimulation. Our results were consistent with the concept that the Brodmanns areas in S1 which produce the 3 components of the SEFs have different functional organization.

Age-related alterations of the functional interactions within the basal ganglia and cerebellar motor loops in vivo

Aging may alter the motor functions of the basal ganglia and cerebellum; however, no previous neuroimaging study has investigated the effect of aging on the functional connectivity of the motor loops involving these structures. Recently, using fMRI with a parametric approach and structural equation modeling (SEM), we demonstrated a significant functional interaction within the basal ganglia-thalamo-motor (BGTM) loop during self-initiated (SI) finger movement in young normal subjects, whereas cerebro-cerebellar (CC) loop was mainly involved during externally triggered (ET) movement. We applied this method to 12 normal aged subjects (53-72 years old) in order to study the effect of age on BGTM and CC loops. Compared with the functional connectivity seen in young subjects, SEM showed decreased connectivity in BGTM loops during SI task, decreased interaction in the CC loop during ET task, and increased connectivity within motor cortices and between hemispheres during both types of tasks. These results suggest an age-related decline of cortico-subcortical connectivity with increased interactions between motor cortices. Aging effects on SI and ET movements are probably caused by functional alterations within BGTM and CC loops.

Oscillatory gamma synchronization binds the primary and secondary somatosensory areas in humans

Induced gamma activity has a key role in the temporal binding of distributed cortico-cortical processing. To elucidate the neural synchronization in the early-stage somatosensory processing, we studied the functional connectivity between the primary and secondary somatosensory cortices (SI and SII) in healthy subjects using magnetoencephalography (MEG) with excellent spatiotemporal resolution. First, somatosensory-evoked magnetic fields were recorded to determine the locations of each cortical activity. Then we analyzed the phase-locking values (PLVs) of the induced gamma activity to assess neural synchrony within the somatosensory cortical network. We also assessed PLVs in patients with multiple sclerosis (MS) to validate our PLV analysis in evaluating the inter-areal functional connectivity, which can often be impaired in MS. The PLVs of the induced gamma activity were calculated for each pair of unaveraged MEG signals that represented the activities of the contralateral SI and bilateral SII areas. Analysis of PLVs between the SI and SII areas showed significantly increased PLVs for gamma-band activities, starting at an early post-stimulus stage in normal controls, whereas this increase in PLVs was apparently diminished in MS. The PLV analysis provided evidence for early-latency, gamma-band neuronal synchronization between the SI and SII areas in normal controls. Our study first demonstrates the gamma-band synchrony in the early-stage human somatosensory processing.

Prenatal freeze lesioning produces epileptogenic focal cortical dysplasia

Purpose: Focal cortical dysplasia (FCD) is thought to be an important cause of intractable epilepsy. However, its epileptogenicity remains unclear. Therefore, we created a novel rat model by freeze lesioning during the late embryonic stage to verify whether FCD influences seizure activities.

d-Cycloserine for the treatment of ataxia in spinocerebellar degeneration

We studied the effects of D-cycloserine, a partial NMDA receptor allosteric agonist, on ataxia in patients with spinocerebellar degeneration. Fifteen Japanese ataxic patients enrolled in a 14-day single-blind trial of D-cycloserine (daily oral dose of 50 mg) following a 14-day single-blind placebo phase. At the end of the D-cycloserine administration, there was a significant reduction in the posture, gait and total score of the international cooperative ataxia rating scale and in the time for walking and speech tasks. D-Cycloserine was well-tolerated and no adverse effect was observed. D-Cycloserine may have therapeutic efficacy for spinocerebellar ataxia.