Shozo Tobimatsu

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.

Steady-state vibration somatosensory evoked potentials : physiological characteristics and tuning function

OBJECTIVE The steady-state somatosensory evoked potentials (S-SEPs) to vibratory stimulation were recorded to characterize their physiological properties. METHODS Vibratory stimuli were applied to the right palmar surface in 10 normal subjects. A total of 200 responses were recorded from electrodes at 2 cm posterior to C3, Cz and C4 and 2 cm anterior to C3. All responses were Fourier analyzed and the amplitudes of the first (1F) and second (2F) harmonic components were thus obtained. The effects of modulation frequency (5-30 Hz) and stimulus intensity (0.001-0.1 Newton (N)) on S-SEPs were studied. RESULTS The amplitudes of 1F and 2F were greatest at the electrode 2 cm posterior to C3, 1F being predominant. The mean 1F amplitudes as a function of modulation frequency showed a bimodal distribution with a trough at 14 Hz and a peak at 21 Hz. The mean 1F amplitudes showed a linear increase of up to 0.05 N and thereafter reached a plateau against the logarithmic stimulus intensity axis. CONCLUSION Vibratory S-SEPs may originate from the primary somatosensory cortex and provide information on the fast-adapting mechanoreceptive afferents. The temporal resonance at 21 Hz places the somatosensory system between the visual and auditory systems.

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.

Simian lentiviral vector-mediated retinal gene transfer of pigment epithelium-derived factor protects retinal degeneration and electrical defect in Royal College of Surgeons rats

Retinitis pigmentosa (RP) is a heterogenous group of inherited retinal diseases resulting in adult blindness caused by mutations of various genes. Although it is difficult to cure the blindness that results from these diseases, delaying the disease progression may be of great benefit, since the majority of RP diseases are seen in middle age or later. To test a gene therapy strategy for RP using a neurotrophic factor gene, we assessed the effect of simian lentivirus (SIV)-mediated subretinal gene transfer of pigment epithelium-derived factor (PEDF), a potent neurotrophic factor, during the disease progression in Royal College of Surgeons (RCS) rats, a well-accepted animal model of RP. Regional gene transfer via SIV into the peripheral subretinal space at the nasal hemisphere was performed in all animals to monitor site-specific transgene expression as well as the therapeutic effect in each retina. Gene transfer of lacZ and PEDF was observed in the regional pigment epithelium corresponding to the regional gene transfer. Histologically, PEDF gene transfer significantly protected the loss of photoreceptor cells (PCs) corresponding to the regions of the gene transfer, compared to those of control groups during the course of the experiment. The antiapoptotic effect of PEDF on PCs is likely to be a related mechanism, because a significant reduction of terminal dUTP-nicked end labeling-positive PC numbers was found in PEDF-treated eyes compared to those of the control group (P<0.05). PEDF-treated eyes also retained a significant sensitivity to light flash during the experimental course. These findings clearly show that neuroprotective gene therapy using PEDF can protect retinal degeneration and functional defects in individuals with RP.

The interaction of the somatosensory evoked potentials to simultaneous finger stimuli in the human central nervous system. A study using direct recordings

In order to investigate the interaction of sensory electrophysiologic fields arising from the adjacent second (II) and third (III) fingers and the distant second and fifth (V) fingers, direct recordings of somatosensory evoked potentials (SEPs) were performed from the sensory and motor cortices, the sensory thalamic nucleus (nucleus ventralis caudalis, VC) and the cuneate nucleus in humans during neurosurgical operations. Electrical stimulation was given to the II, III or V fingers individually, and also to pairs of either the II and III fingers or the II and V fingers simultaneously. The interaction ratio (IR) was devised as the ratio of amplitude attenuation caused by the simultaneous stimulation to two fingers compared with the amplitude of the arithmetically summed SEPs to the individual stimulation of two fingers. The IRs were calculated on N20 and P25 from the sensory cortex, P22 from the motor cortex, P17thal from the VC, and N16cune and P35cune from the cuneate nucleus. With both stimulations to the II and III fingers and the II and V fingers, P25 showed the greatest IR, followed by P22, then by P17thal, with N16cune exhibited the smallest IR. N20 and P35cune showed similar IRs and significantly greater IRs with II and III finger stimulation compared with II and V finger stimulation. These results thus indicate that the interaction of somatosensory impulses occurs in several structures along the sensory pathway in CNS, including the cuneate nucleus, the sensory thalamic nucleus, as well as sensory and motor cortices, with the greatest IRs in the cerebral cortices and the weakest ones in the brain-stem.(ABSTRACT TRUNCATED AT 250 WORDS)

Parvocellular and magnocellular contributions to visual evoked potentials in humans: stimulation with chromatic and achromatic gratings and apparent motion

Psychophysical evidence suggests that two major parallel pathways, the parvocellular (P) and the magnocellular (M) pathways, exist in humans. We herein report that responses specific to the P and M systems can be recorded in human visual evoked potentials (VEPs) by using the appropriate stimuli. The onset of isoluminant chromatic (red-green) and high contrast achromatic sinusoidal gratings were used for stimulating the P-system. A chromatic stimulation evoked a characteristic negative wave (N1) with peak latencies around 120 msec. The amplitude showed an inverse U-shaped function as a function of spatial frequency with a peak at 2 c/deg. In contrast, VEPs to achromatic (black-white) gratings showed different spatial frequency characteristics with a peak at 5.3 c/deg. By varying the luminous intensity ratio between the red and green gratings, N1 was found to reach a maximum during isoluminant stimulation. An apparent motion display was used for stimulating the M-system. The speed of alternation (i.e., the interstimulus interval (ISI)) was varied to record both the transient and steady-state VEPs. Transient VEPs showed triphasic waves with the major positive peak (P1) at around 120 ms. Steady-state VEPs were quasi-sinusoidal waveforms, depending on the ISI, and were quite stable across all subjects. There was a also high correlation between the motion threshold and the VEP amplitude. The above observations indicate that characteristic potentials may distinguish between these two parallel visual systems in humans. Thus, the combined use of isoluminant color and high contrast achromatic gratings and an apparent motion display is considered to be useful for evaluating both systems electrophysiologically.

Acute myelitis with hyperIgEaemia and mite antigen specific IgE: atopic myelitis

An occurrence of acute localised myelitis was recently seen in four adult patients with atopic dermatitis who had hyperIgEaemia and mite antigen specific IgE. The total and mite antigen specific IgE was therefore studied in serum samples from 19 consecutive patients with acute localised myelitis of unknown aetiology, 56 patients with clinically definite multiple sclerosis, and 40 healthy controls. The total IgE concentration was significantly higher in acute localised myelitis (median=360 U/ml) than in multiple sclerosis (median=52 U/ml, p<0.0001) and the controls (median=85 U/ml, p=0.0002). The specific IgE to Dermatophagoides pteronyssinus was found more often in patients with acute localised myelitis (95%) than in patients with multiple sclerosis (34%, p<0.0001) and the controls (35%, p<0.0001) and the specific IgE to Dermatophagoides farinae was similar (acute localised myelitis 79%, multiple sclerosis 29% (p<0.0001), controls 30%, (p=0.0003). Atopic dermatitis coexisted more commonly in patients with acute localised myelitis (37%) than in patients with multiple sclerosis (0%, p<0.0001) and the controls (7.5%, p=0.0089). Therefore, acute localised myelitis with hyperIgEaemia, in which atopy to mite antigens seems to exist, may be a distinct subtype of allergic myelitis—that is, atopic myelitis.

Functional mapping of the sensorimotor cortex: combined use of magnetoencephalography, functional MRI, and motor evoked potentials

Combined use of magnetoencephalography (MEG), functional magnetic resonance imaging (f-MRI), and motor evoked potentials (MEPs) was carried out on one patient in an attempt to localise precisely a structural lesion to the central sulcus. A small cyst in the right frontoparietal region was thought to be the cause of generalised seizures in an otherwise asymptomatic woman. First the primary sensory cortex was identified with magnetic source imaging (MSI) of somatosensory evoked magnetic fields using MEG and MRI. Second, the motor area of the hand was identified using f-MRI during handsqueezing. Then transcranial magnetic stimulation localised the hand motor area on the scalp, which was mapped onto the MRI. There was a good agreement between MSI, f-MRI and MEP as to the location of the sensorimotor cortex and its relationship to the lesion. Multimodality mapping techniques may thus prove useful in the precise localisation of cortical lesions, and in the preoperative determination of the best treatment for peri-rolandic lesions.

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.