Masato Higashima

A quantitative magnetic resonance imaging study of patients with schizophrenia.

SummaryTwenty patients with schizophrenia and ten normal control subjects underwent magnetic resonance imaging of the brain. The volumes of several brain structures were measured using a computer image analysing system. The schizophrenic patients had significantly smaller left parahippocampal volume and larger left temporal horn volume than the control subjects. A larger body of the right lateral ventricle could be estimated in the schizophrenics, but this difference was not significant. In the patient group a non-significant negative corrlation was established between the presence of positive symptoms and the left temporal horn volume. There was no signieficant correlation between the temporal horn and temporal lobe or medial temporal structures. Our results indicate that the left medial temporal structure or left temporal lobe may be involved in schizophrenia and that temporal horn enlargement does not simply represent volume loss of the surrounding tissue.

SPECT analysis of regional cerebral blood flow changes in patients with schizophrenia during the Wisconsin card sorting test

Single photon emission computed tomography (SPECT) images were obtained in 10 right-handed neuroleptic-treated schizophrenic patients and 10 healthy volunteers using Tc-99m-hexamethyl-propylenamine oxime (Tc99m-HMPAO) during performance of the Wisconsin Card Sorting Test (WCST) and at rest. None of the patients showed severe impairment on the WCST. The patient group showed a statistically insignificant trend to incur more unique errors. In both the patient and control groups, the left lateral prefrontal blood flow significantly increased during the WCST, as compared to during resting conditions. Only during the WCST, the patient group showed a significant regional cerebral blood flow (rCBF) decline in the left medial prefrontal cortex, as well as in the right side under both the test and resting conditions. This left medial prefrontal rCBF during the WCST correlated positively with the number of unique errors, although this correlation was statistically insignificant. The right fronto-parietal rCBF was significantly increased in the patient group under both the test and resting conditions. Moreover, in the left hippocampal region, the patient group showed a significant rCBF increase under resting conditions.

P300 and the thought disorder factor extracted by factor-analytic procedures in schizophrenia

BACKGROUND In order to clarify the clinical significance of P300 as a biologic marker that can reflect schizophrenic symptomatology, many previous studies have evaluated the relationship of P300 with the symptoms on the basis of a positive/negative dichotomy, but yielded inconsistent conclusions. Such a dichotomy has been criticized as being too reductionistic. Recently, most studies with factor-analytic procedures have extracted some symptom factors outside this dichotomy. Therefore, it is important to examine associations of P300 with the symptom factors extracted by these statistical analyses. METHODS In the present study, the amplitudes of P300 were measured by using an auditory oddball paradigm for 73 schizophrenics whose psychopathology was assessed with the Positive and Negative Syndrome Scale (PANSS). RESULTS The principal component analysis of the PANSS items revealed five factors labeled the thought disorder, negative, hostile/excitable, delusional/hallucinatory, and depressive factors. The score for the thought disorder factor correlated negatively with the amplitude of P300 recorded at Pz T5, and T6, but that for the other factors did not. CONCLUSIONS These findings suggest that the reduction of P300 amplitudes recorded at the midline parietal and bilateral temporoparietal regions may be one of the electrophysiologic indices representing the thought disorder clinically observed in schizophrenia.

Reduced auditory P300 amplitude, medial temporal volume reduction and psychopathology in schizophrenia

Twenty-five schizophrenic patients diagnosed by DSM-III-R underwent event-related potentials and magnetic resonance imaging scans. Latency and amplitude of P300 waveform were measured using an auditory odd-ball paradigm. Anterior and posterior volumes of the superior temporal gyrus and medial temporal structure were measured from contiguous coronal images using the level of the mammillary body as an anatomical landmark. Principal component analysis of P300 latency and amplitude disclosed two orthogonal independent factors each: overall latency and residual, and amplitudes from posterior and anterior recordings, respectively. Structural volumes consisted of four orthogonally independent factors: left superior temporal volume, anterior medial temporal volume, right superior temporal volume, and posterior medial temporal volume. The factor score of the P300 amplitude from posterior recordings correlated with the factor score of volumetric changes in the anterior medial temporal structures. The present study failed to replicate a previously reported association between auditory P300 amplitude and superior temporal volume. Furthermore, the factor score of the P300 amplitude was correlated with the severity of clinical ratings of attentional impairments and positive thought disorder. These findings demonstrate that the information processing dysfunction of schizophrenia indicated by reduced P300 amplitude is associated with structural abnormality in the medial temporal lobe.

Native EEG and treatment effects in neuroleptic-naïve schizophrenic patients: time and frequency domain approaches.

Time domain analysis of electroencephalography (EEG) can identify subsecond periods of quasi-stable brain states. These so-called microstates assumingly correspond to basic units of cognition and emotion. On the other hand, Global Field Synchronization (GFS) is a frequency domain measure to estimate functional synchronization of brain processes on a global level for each EEG frequency band [Koenig, T., Lehmann, D., Saito, N., Kuginuki, T., Kinoshita, T., Koukkou, M., 2001. Decreased functional connectivity of EEG theta-frequency activity in first-episode, neuroleptic-naive patients with schizophrenia: preliminary results. Schizophr Res. 50, 55-60.]. Using these time and frequency domain analyzes, several previous studies reported shortened microstate duration in specific microstate classes and decreased GFS in theta band in drug naïve schizophrenia compared to controls. The purpose of this study was to investigate changes of these EEG parameters after drug treatment in drug naïve schizophrenia. EEG analysis was performed in 21 drug-naive patients and 21 healthy controls. 14 patients were reevaluated 2-8 weeks (mean 4.3) after the initiation of drug administration. The results extended findings of treatment effect on brain functions in schizophrenia, and imply that shortened duration of specific microstate classes seems a state marker especially in patients with later neuroleptic responsive, while lower theta GFS seems a state-related phenomenon and that higher gamma GFS is a trait like phenomenon.

Quantal analysis of potentiating action of phorbol ester on synaptic transmission in the hippocampus.

The mechanism of the potentiating action of phorbol diacetate on synaptic transmission in the hippocampus was studied by the quantal analysis technique. Thin transverse sections were prepared from guinea pig hippocampus and intracellular potentials were recorded from CA3 neurons. Unitary excitatory postsynaptic potentials (EPSPs) were induced in the impaled neurons by brief glutamate pulses administered to granule cells. The amplitude of the unitary EPSPs fluctuated according to Poisson distribution. From the mean and variance of the amplitude of the unitary EPSPs, the mean quantal content (m) and the mean quantal amplitude (q) were calculated. Before phorbol diacetate administration, the values of m and q were 9.7 +/- 1.4 and 1.1 +/- 0.28 mV (mean +/- S.D.), respectively. Potentiation of synaptic transmission by phorbol diacetate was accompanied by increases in the value of m. The value of q remained unchanged in most neurons and decreased in some. These results indicate that the phorbol ester causes an increase in release of neurotransmitter and thereby potentiates synaptic transmission.

Regional cerenral blood flow in patients with schizophrenia: relevance to symptom structures

Regional cerebral blood flow (rCBF) was measured with technetium-99m hexamethylpropyleneamine oxime single photon emission computed tomography in 38 neuroleptic-treated schizophrenic patients. To improve the validity of the evaluation of symptomatology, we applied findings previously derived in a principal component analysis (PCA) of the Positive and Negative Syndrome Scale. The PCA had disclosed five orthogonal independent symptom structures (i.e., negative, hostile/excited, thought disordered, delusional/hallucinatory, and depressive components), and obtained factor scores for 70 schizophrenic subjects, including the present sample. Stepwise regression analysis elucidated some of the cortical regions in which relative rCBF predicted the severity of symptoms--namely, lateral and orbital prefrontal, lateral temporal, inferior parietal, and medial temporal regions. Findings suggested that symptom structures derived from PCA could prove helpful in elucidating the pathophysiology of neural mechanisms.

Activation of GABAergic function necessary for afterdischarge generation in rat hippocampal slices

Involvement of gamma-aminobutyric acid (GABA)-mediated function in epileptogenesis was studied in rat hippocampal slices, in which repetition of high-frequency electrical stimulation induced afterdischarges (ADs) to create an in vitro model for ictal activity. A GABAA receptor antagonist, bicuculline, fully blocked the ADs. On the other hand, the presence of bicuculline caused single stimuli to evoke short-duration epileptiform bursts, a well-known model for interictal activity. Therefore, we conclude that activation of GABAergic function appears to be necessary for ictal activity, while its dysfunction induces interictal activity, and propose a modification to the simple disinhibition hypothesis for epileptogenesis.

Evaluation and interpretation of symptom structures in patients with schizophrenia

Seventy Japanese DSM‐III‐R schizophrenic patients were assessed for 30 clinical symptoms using the Positive and Negative Syndrome Scale (PANSS) of Kay et al. Principal component analysis was applied to the full item set of this scale and disclosed 5 orthogonal independent symptom groups: negative, hostile/excited, thought‐disordered, delusional/hallucinatory and depressive components. Our results provided further support of the contention that more than 2 (i.e., positive and negative) dimensions are required to account for structures of the schizophrenic symptoms.

Inhibitors of high-affinity uptake augment depolarizations of hippocampal neurons induced by glutamate, kainate and related compounds

SummaryActions of dihydrokainate (DHKA) and 3-hydroxy-DL-aspartate (HAsp), inhibitors of high-affinity uptake for L-glutamate (Glu), were studied in vitro in thin hippocampal slices of the guinea pig. The amplitude of the depolarizations induced by Glu and by L-aspartate (Asp) in CA3 neurons are markedly augmented by DHKA and HAsp. Depolarizations induced by D-homocysteate (DH) were unaffected by the inhibitors. In about half of the neurons, depolarizations induced by L-homocysteate (LH) and by quisqualate (Quis) were slightly augmented by the inhibitors. Fast responses to kainate (KA) were augmented by the inhibitors to a similar extent as were Glu responses whereas slow KA responses were insensitive to HAsp. HAsp was without effect on excitatory postsynaptic potentials elicited by stimulation of granular layer. These findings are in general agreement with the biochemical data on amino acid uptake processes and are also consistent with the slow time-courses of depolarizations induced by DH, LH and Quis. Augmentation of fast KA responses provides strong evidence for the hypothesis that an KA pulse causes a liberation of Glu and/or Asp from the tissue and the liberated amino acid(s) induces the fast KA response in neurons nearby.