Toshio Sato

Electric Dipole Tracing in the Brain by Means of the Boundary Element Method and Its Accuracy

A method of localizing an electrical dipole in the brain from the scalp potential distribution has been developed with the aid of the boundary element method, in which a real geometry of the head is exactly taken into account and homogeneous electrical conductivity is assumed. Accuracy of the method was evaluated through animal experiments with a cat in which a current dipole was artificially generated in the brain. Deviation of the estimated dipole location from the true one was not random, but rather systematic (probably due to in-homogeneous conductivity distribution). It is numerically found that cavities in the skull disturb the inverse solution especially when the dipole is oriented toward the cavities. In vivo tests of the method were also done for primary somatosensory evoked potentials as a response to median nerve stimulation of a cat and myoclonic EEG. Although the homogeneous approximation was made, it does not change the significance of the results obtained by the present method.

Study of the association between the serotonin transporter gene regulatory region polymorphism and personality traits in a Japanese population

Recently a relationship between serotonin transporter transcriptional control region (5-HTTLPR) polymorphism and anxiety related personality traits in Caucasians was reported. We performed PCR of DNAs from the blood for determining the 5-HTTLPR genotypes of 191 Japanese subjects, which were medical staff and students, and obtained Revised NEO Personality Inventory (NEO-PI-R) and the Temperament and Character Inventory (TCI) in 144 subjects. The association was analyzed by one-way ANOVA. The present study demonstrated that allelic frequency of 5-HTTLPR (s allele frequency was 0.785) in our subjects was considerably different from that in Caucasians. No significant differences were found in the anxiety-related personality traits among genotypes, while cooperativeness in TCI showed a significant difference among genotypes. The property of 5-HTTLPR may not be reflected directory on the personality inventories.

The synchronization between brain areas under motor inhibition process in humans estimated by event-related EEG coherence.

To investigate the functional connection of brain areas under motor inhibition, the event-related coherence (ERCoh) of the electroencephalogram (EEG) was calculated for 10 subjects who were asked to perform a visual discrimination (GO/NO-GO) task. The subjects were instructed to push (GO) or not to push (NO-GO) a micro-switch according to different visual stimuli. Twenty-one-channel scalp EEGs were recorded and the surface Laplacians were calculated at F3, F4, C3, C4, P3 and P4 using the source derivation method. The time-courses of the inter- and intra-hemispheric coherence were calculated using the fast Fourier transform for each condition (GO or NO-GO), and were compared statistically between the two conditions. The results suggest that the ERCoh under the NO-GO condition consisted of two components; alpha band synchronization between bilateral frontal areas and theta band synchronization among bilateral frontal, central and parietal areas. It is likely that the former is related directly to the decision not to move, and the latter is related to the motor inhibition process.

Fyn Is Required for Haloperidol-induced Catalepsy in Mice

Fyn-mediated tyrosine phosphorylation of N-methyl-d-aspartate (NMDA) receptor subunits has been implicated in various brain functions, including ethanol tolerance, learning, and seizure susceptibility. In this study, we explored the role of Fyn in haloperidol-induced catalepsy, an animal model of the extrapyramidal side effects of antipsychotics. Haloperidol induced catalepsy and muscle rigidity in the control mice, but these responses were significantly reduced in Fyn-deficient mice. Expression of the striatal dopamine D2 receptor, the main site of haloperidol action, did not differ between the two genotypes. Fyn activation and enhanced tyrosine phosphorylation of the NMDA receptor NR2B subunit, as measured by Western blotting, were induced after haloperidol injection of the control mice, but both responses were significantly reduced in Fyn-deficient mice. Dopamine D2 receptor blockade was shown to increase both NR2B phosphorylation and the NMDA-induced calcium responses in control cultured striatal neurons but not in Fyn-deficient neurons. Based on these findings, we proposed a new molecular mechanism underlying haloperidol-induced catalepsy, in which the dopamine D2 receptor antagonist induces striatal Fyn activation and the subsequent tyrosine phosphorylation of NR2B alters striatal neuronal activity, thereby inducing the behavioral changes that are manifested as a cataleptic response.

EVENT-RELATED DYNAMICS OF THE GAMMA-BAND OSCILLATION IN THE HUMAN BRAIN : INFORMATION PROCESSING DURING A GO/NOGO HAND MOVEMENT TASK

To investigate the gamma band activity relating to the discrimination process and motor behavior in the human brain, the event-related dynamics of the EEG spectrum was calculated during the visual GO/NOGO hand movement task and a control task (the visual element of the GO/NOGO task only) in eight subjects. The subjects were instructed to push (GO) or not to push (NOGO) a microswitch according to different visual stimuli and 21-channel scalp EEGs were recorded. The time courses of the power spectra after the stimuli were calculated using the fast Fourier transform for each condition (GO, NOGO and the control task), and were compared statistically between the conditions. The results suggested that a high gamma band oscillation, occurring at the frontal and left parieto-occipital areas at around 90 ms after the stimuli, relates to the discrimination process. Under the GO condition, this oscillation continued until 140 ms, and a subsequent oscillation occurred over the motor areas at around 200 ms, which seemed to be related to the motor action. On the other hand, under the NOGO condition, a low gamma band oscillation occurred in the central area at around 230 ms, which seemed to be related to the inhibition process.

Decreased Regional Cerebral Metabolic Rate for Glucose in Systemic Lupus erythematosus Patients with Psychiatric Symptoms

To determine brain functional abnormality in systemic lupus erythematosus (SLE) patients with psychiatric symptoms, we evaluated 12 active SLE patients with or without psychiatric symptoms by means of [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography (PET), magnetic resonance imaging and neuropsychological testing. Patients with psychiatric symptoms showed significantly poorer performance in tests which subserved attentional function. The PET study revealed that the psychiatric patients had significantly decreased regional cerebral metabolic rates for glucose in the prefrontal, inferior parietal and anterior cingulate regions. Prefrontal, inferior parietal and anterior cingulate dysfunction may be related to attentional deficits that are involved in various psychiatric symptoms in SLE. PET is an invaluable tool to reveal such brain functional abnormality seen in SLE patients with psychiatric symptoms.

Effects of MRI abnormalities on WAIS-R performance in solvent abusers.

Objective ‐ To clarify how chronic solvent abuse affects cognitive function using magnetic resonance imaging as an index of brain damage. Material and methods ‐ A total of 25 chronic solvent abusers underwent magnetic resonance imaging with quantitative neurometry and Wechsler Adult Intelligence Scales revised. Results ‐ The abusers with white matter change (n=10) showed significantly (P < 0.05) lower performance IQ, especially in Digit Symbol subtest (P<0.01). Also, the severity of pontine atrophy was significantly correlated with PIQ (r=0.60, P<0.01). Conclusions ‐ These data indicate that solvent abuse causes the decline in the test performance reflecting cognitive and fine motor dysfunction and that white matter changes and pontine atrophy may have some roles in this decline.

Regional cerebral blood flow abnormalities in chronic solvent abusers.

This study aimed to reveal regional abnormalities of cerebral blood flow (CBF) and their relation to amotivational syndrome which causes poor social prognosis in solvent abusers. Sixteen chronic solvent abusers (12 males and four females) along with five normal subjects underwent single photon emission computed tomography with N‐isopropyl‐p[123I]iodoamphetamine. The patients received a clinical evaluation with the Scale for the Assessment of Negative Symptoms. Using a semiquantitative method (normalized by the parietal cortex count), patients showed a statistically significant decrease in regional cerebral blood flow (rCBF) in the bilateral prefrontal cortices (P < 0.01). In addition, the severity of hypoperfusion in the bilateral prefrontal cortices was related to the degree of severity of the avolition–apathy scale on SANS (left; P < 0.05, right; P < 0.01) even after excluding the effect of antipsychotics. These results suggest that rCBF abnormalities, especially in the prefrontal cortex, develop in chronic solvent abusers, and that this frontal hypoperfusion may be a biological basis of amotivational syndrome.

The time course of interhemispheric EEG coherence during a GO/NO-GO task in humans

Event-related coherence of the EEG was calculated for 10 subjects performing a visual discrimination GO/NO-GO task. The subjects were instructed to push (GO) or not to push (NO-GO) a button according to visual stimuli. Twenty-one-channel scalp EEGs were recorded and the surface Laplacian was calculated using the source derivation method. The time courses of the coherence between F3 and F4, C3 and C4, and P3 and P4 were calculated using the fast Fourier transform for each task and were compared between conditions. Statistical analysis showed that coherence in the NO-GO condition became significantly higher than that in the GO condition between F3 and F4. The synchronization between bilateral dorsolateral frontal areas might therefore play an important role in the motor inhibition process.

N-glycosylation at noncanonical Asn-X-Cys sequences in plant cells

The vesicular transport pathway in plant cells is often used for higher accumulation of recombinant proteins. In the endoplasmic reticulum, which acts as a gateway to the vesicular transport pathway, N-glycosylation occurs on specific Asn residues. This N-glycosylation in recombinant proteins must be carefully regulated as it can impact their enzymatic activity, half lives in serum when injected, structural stability, etc. In eukaryotic cells, including plant cells, N-glycans were found to be attached to Asn residues in Asn-X-Ser/Thr (X ≠ Pro) sequences. However, recently, N-glycosylations at noncanonical Asn-X-Cys sequences have been found in mammals and yeast. Our laboratory has discovered that N-glycans are attached to Asn residues at Asn-Thr-Cys sequences of double-repeated B subunit of Shiga toxin 2e produced in plant cells, the first reported case of N-glycosylation at a noncanonical Asn-X-Cys sequence in plant cells.