Shin-Ichi Niwa

Attention deficits assessed by continuous performance test and span of apprehension test in Japanese schizophrenic patients

To examine whether attention deficits in the Continuous Performance Test (CPT) and in the Span of Apprehension Test (SPAN) are observed in Japanese schizophrenics, 49 chronic medicated schizophrenics and 43 normal controls were administered the UCLA version of CPT and SPAN. To investigate whether each measure of the CPT and the SPAN is independently correlated to symptoms, a hierarchical multiple regression was conducted with the attentional measures and age as independent variables and with the conceptual disorganization scores on the Brief Psychiatric Rating Scale (BPRS) as a dependent variable in schizophrenic subjects. Decreased performance on the CPT and SPAN measures was observed in the Japanese patients. This indicates that the CPT and the SPAN can detect the attention deficits of schizophrenics in Japan as well as Europe and the US. The SPAN scores in the present study were lower than in previous studies. This may be due to a lower level of familiarity of Japanese subjects with the Roman alphabet. Each measure of the CPT and the SPAN was significantly correlated with the conceptual disorganization scores after controlling for the other measure and age. We concluded that each deficit in sustained attention and processing capacity was independently related to formal thought disorder in schizophrenia.

Correlations of event-related potentials with schizophrenic deficits in information processing and hemispheric dysfunction

In order to obtain further insight into hemispheric dysfunction in schizophrenics, two experiments were conducted employing event-related potential (ERP) recording during dichotic detection tasks as well as syllable discrimination tasks. Results concerning ERPs derived from the T3 and T4 regions are reported. Based on results in the two experiments, it is concluded that schizophrenics display a dysfunction of the left hemisphere, as well as a dysfunction in the ingration mechanism of both hemispheres. It is also speculated that the left-hemisphere dysfunction in schizophrenics is particularly correlated with positive psychotic symptoms.

Verbal memory disturbances in left temporal lobe epileptics

The relationship between laterality of paroxysmal discharges and characteristics of disturbances in memory functioning was investigated in temporal lobe epileptics. Subjects consisted of 22 temporal lobe epileptic patients, in whom the foci of the paroxysmal discharges were localized to one side of the temporal regions. The left focus group consisted of 10 patients; the right focus group, 12. Subjects were required to recognize verbal material presented to one hemisphere by means of a tachistoscope. The left focus group alone failed to demonstrate a right visual field superiority in these tasks. It was concluded that the left focus group specifically demonstrate disturbances in verbal memory functioning, particularly when stimuli were presented to the left hemisphere. Paroxysmal discharges seemed to interfere with normal memory functioning in the region where the foci of these discharges were found.

Behavioral and P3 amplitude enhancement in schizophrenia following feedback training

In order to clarify the remediability of behavioral and electrophysiological abnormalities in schizophrenia, hit rate, reaction time, and P3 amplitude from auditory event-related potentials were evaluated before and after feedback training of a task in 14 schizophrenics and 12 age-matched normal controls. Although mean changes in the three indices due to the training were nonsignificant in both schizophrenic and normal control groups as a whole, the changes in hit rate and reaction time correlated significantly with the P3 amplitude change in the schizophrenic (r = 0.60 and -0.58, respectively) but not in the normal control group. The P3 amplitude change also correlated with the P3 amplitude before the training only in the schizophrenic group (r = -0.68), suggesting that the training was more effective for the schizophrenic patients with marked P3 amplitude reduction. The observed P3 amplitude increase due to training may represent an electrophysiological correlate of a remediable aspect of behavioral deficits in schizophrenics, which may underlie the effectiveness of nonpharmacological treatments.

Effects of repeated methamphetamine administration on dopamine D1 receptor, D2 receptor and adenylate cyclase type V mRNA levels in the rat striatum.

Dopamine D1 receptor (D1R), D2 receptor (D2R) and adenylate cyclase type V (AC5) mRNAs in the rat dorsal striatum (CPu) and ventral striatum (Acb) were measured by in situ hybridization histochemistry (ISHH) after repeated methamphetamine (MAP) administration. MAP (4 mg/kg) or an equivalent volume of saline was administered intraperitoneally once daily for 10 days to male Wistar rats. After 7 days of abstinence, behavioral experiment with MAP-challenge revealed that a significant behavioral sensitization was achieved in MAP-treated animals. The animals were sacrificed 7 days after the last injection and brain sections were analyzed by ISHH using 35S-labeled antisense oligonucleotide probes. We found that D1R mRNA levels in the CPu were significantly increased (124% of control, P < 0.01). In contrast, repeated MAP-treatment did not significantly affect the expression of D1R mRNA in Acb or mRNA for D2R or AC5. It was concluded that MAP-induced behavioral sensitization is accompanied by increased D1R mRNA levels in CPu.

Distributions of the Nd and P300 in a normal sample

To obtain objective criteria for assessing the attentional and cognitive functioning of psychiatric populations, we attempted to standardize values of two components in Event-Related Potentials (ERPs), namely the attention-related negative potential (Nd) and the P300, in normal populations. The study consisted of 100 healthy volunteers (50 females, 50 males) who were given the task of making dichotic syllable discriminations requiring key-press responses. Their ages ranged between 18 and 59 years (mean +/- S.D., 32.3 +/- 11.3 years). Nd was found to be maximum in the Fz region, P300 being maximum in the Pz region. The means and standard deviations of Nd and P300 areas in their maximum regions were 554.1 +/- 307.8 microV ms and 2148.5 +/- 1248.5 microV ms, respectively. The transformation plot for symmetry indicated the suitable power of transformation to be 1/2 for both Nd and P300 distributions. After being transformed into square-root values, the distribution patterns of Nd and P300 areas were examined. When the lower limit of normal values was tentatively assigned to mean -2 S.D. using square-root transformed data for both Nd and P300, 97% of the subjects were found to display values above the lower normal limit for Nd, and 98% for the P300. Neither, Nd nor P300 areas correlated with age, while P300 latencies displayed a weak positive correlation with age. Females displayed relatively larger values than males for Nd and P300 areas and P300-peak amplitudes. However, the differences between females and males were not statistically significant. Females and males showed nearly equal P300-peak latencies.

Effects of repeated administration of methamphetamine on P3-like potentials in rats

Effects of repeated administration of methamphetamine (MAP) on a component of the cortical event-related potential (ERP), P3-like potential which corresponds to the human P3b, were examined in rats performing an active discrimination task. Rats were trained to press a bar within 1200 ms after cessation of a target tone (1000 Hz) lasting for 800 ms, and to withhold an overt response to the standard tone (2000 Hz). The rats were given intracranial electrical stimulation to the medial forebrain bundle as a reward, only when they correctly responded to the target tone. ERPs before drug administration were recorded after the correct response ratio exceeded 85%. Thereafter, a daily dose of 4 mg/kg of MAP, or the same volume of saline in another group, was administered intraperitoneally 15 times. ERPs were recorded again 7-10 days after the last injection. In the rats which received MAP the amplitude of the P3-like potential decreased with no change in its latency, while the response latency of bar-pressing and the correct response ratio were not altered significantly. These results suggest some changes in catecholaminergic transmission induced by repeated MAP-administration affect a P3 generation mechanism. MAP-treated rats may be useful as an animal model to investigate neural mechanisms of MAP-psychosis and schizophrenia.

FRACTAL PROPERTY OF EYE MOVEMENTS IN SCHIZOPHRENIA

Abstract. On the basis of a temporal model of animal behavior we conducted temporal analysis of eye movements in schizophrenic subjects (n=10) and normal controls (n=10). We found a fractal property in schizophrenic subjects, the fixation time of eye movement during reading ambiguous and difficult sentences showing a clear inverse power law distribution. An exponential distribution of a nonfractal nature was found in normal controls.

Social cue perception in Japanese schizophrenic patients

Although abnormal social cue perception in schizophrenia is thought to be a factor in impairing the acquisition of social skills, there have been no studies on social cue perception in Japanese schizophrenics. In order to clarify the characteristics of social cue perception in Japanese schizophrenic patients, 46 schizophrenics and 41 normal controls were presented 12 videotaped vignettes of interpersonal situations, and then they were asked true-false questions about the interaction viewed. Additionally, schizophrenics were administered the Bech version of the Brief Psychiatric Rating Scale. The results showed that the schizophrenic group showed a poorer performance on the cue recognition task than the normal group, and in particular, schizophrenics exhibiting false alarm errors were seen more often than schizophrenics exhibiting omission errors. This suggests that false recognition of information that does not actually exist in social situation is an important characteristic of social cue perception in schizophrenic patients. The false alarm rates on the cue recognition task in schizophrenics were related to the severity of positive-thought disorder, but not to that of negative symptoms. There was no significant relationship between the omission error rates and the two symptom scores in schizophrenics. Faulty cue recognition and positive-thought disorder may be due to a common factor.

Diagnostic reliability and significance of irregular beta patterns

Abstract: We designated EEGs with marked and irregular beta waves in basic patterns as “irregular beta patterns” on the basis that these patterns are related with particular symptoms such as dysphoria, irritability and autonomic symptoms and they implicate choice of therapeutic agents. Because of good response to antiepileptic agents in patients with “irregular beta patterns” along with EEG characteristics, we hypothesized that the prevalence of “irregular beta patterns” is higher in epileptics than in other psychiatric patients. In the present study, we tested this hypothesis, investigating actual frequencies of these patterns among different diagnostic categories for all patients whose EEG were recorded in all the first‐visit patients to the Outpatient Clinic, Deparmtent of Neuropsychiatry of the Tokyo University Hospital during one year period of 1986. Before starting this investigation, we checked the interrater reliability for these patterns. Therefore, two studies are reported here. In Study 1, five raters judged 98 EEG recordings blindly (43 epileptics and 55 healthy subjects). As a result, the generalized Kappa of 0.473 was obtained, indicating our agreement level was moderate or fair. This result lends support to our contention that irregular beta patterns are reliably judged. In Study 2, we judged the EEG recordings (137 schizophrenics, 62 affective disorders, 43 epileptics and 55 healthy controls) and calculated the prevalence rate of “irregular beta patterns” among the diagnostic categories. The results show that the prevalence rates of “irregular beta patterns” among psychiatric disorders and normal controls were 13% (18/137) in schizophrenics, 11% (7/62) in affective disorders, 14% (6/43) in epileptics and 4% (2/55) in healthy controls. These rates did not differ significantly among the three disorders. Thus, our hypothesis was not supported. The clinical significance of these patterns is discussed.