Aberrant brain activation following motor skill learning in schizophrenic patients as shown by functional magnetic resonance imaging.

BACKGROUND: Motor skill learning may be impaired in schizophrenia. While functional brain imaging studies have shown reduced activation during motor task performance in schizophrenic patients, brain activity changes with motor skill learning in these patients have not been studied by functional imaging. METHODS: A sequential complex motor task involving the right hand was performed by nine medicated schizophrenic patients and 10 age-matched healthy controls. Functional magnetic resonance images were obtained using a gradient echo, echoplanar imaging (EPI) pulse sequence before and after 1 week of training in performing the task. RESULTS: Bilaterally, patients showed significantly less blood oxygenation level-dependent (BOLD) signal response in the premotor area (PMA) before beginning motor training than controls. BOLD signal response increased in the left PMA of schizophrenic patients after 1 week of motor training; in contrast, the signal decreased in the left PMA of control subjects. Training effects concerning the number of finger movement sequences achieved did not differ between groups. Daily neuroleptic dose did not significantly affect changes with training in BOLD signal response in the PMA. CONCLUSIONS: These preliminary results suggest that schizophrenic patients have dysfunction of neural networks in areas including the PMA that are involved in executing a complex motor task. In terms of brain activity, motor learning may be less efficient or slower in the patients than in healthy subjects.

Haloperidol improves membrane phospholipid abnormalities in temporal lobes of schizophrenic patients.

Using 31P magnetic resonance spectroscopy, we examined changes in the levels of phosphorus metabolites in the temporal lobes of 13 schizophrenic patients before and 12 weeks after initiating haloperidol treatment. Spectra were obtained from a volume of interest positioned in each temporal lobe. Findings were compared with those in 13 age- and gender-matched healthy subjects. Prior to treatment the patients showed higher levels of phosphodiesters (PDE) in both temporal lobes than healthy subjects. Haloperidol administration significantly reduced the excess of PDE in the left temporal lobe, although the PDE concentration remained somewhat higher bilaterally than in controls. Treatment was associated with a decline in the total symptom score according to the Brief Psychiatric Rating Scale and the score for positive symptoms showed a relatively high correlation with reduction in PDE level in the left temporal lobe. These preliminary results suggest that haloperidol may partially normalize disturbed metabolism or abnormalities in components of membrane phospholipids in the left temporal lobe of untreated schizophrenic patients, paralleling symptom alleviation.

Changes in levels of phosphorus metabolites in temporal lobes of drug-naive schizophrenic patients.

OBJECTIVE: The authors examined phospholipids and high-energy phosphorus metabolism in the temporal lobes of drug-naive schizophrenic patients. METHOD: In vivo 31P magnetic resonance spectroscopy was performed on 17 first-episode, drug-naive schizophrenic patients and 17 age- and gender-matched healthy subjects. RESULTS: Patients showed higher levels of phosphodiesters and lower levels of phosphomonoesters than the comparison group. Phosphocreatine levels were increased in the left temporal lobes of patients. CONCLUSIONS: The results suggest disturbed membrane phospholipid metabolism in both temporal lobes and decreased energy demands in the left temporal lobes of drug-naive schizophrenic patients.

P300 event-related potentials in probable dissociative generalized amnesia.

1. To investigate whether abnormalities in objective neurophysiologic measures are observable in patients with probable dissociative generalized amnesia, the P300 and N100 event-related potentials were evaluated in six such patients in both acute stage and after recovery from amnesia. Findings were compared with those in 12 age- and gender-matched healthy subjects. 2. While latencies did not differ from those of control subjects, P300 amplitudes in acute-stage recordings were lower than those in controls. Repeated recordings in the patients showed a significant increase in P300 amplitude after recovery from amnesia. 3. Amplitude and latency of N100 did not differ between the patient and control groups, nor changed significantly after retrieval of memory. 4. These findings suggest that some unknown biological and/or psychologic mechanisms that cause retrograde autobiographic amnesia may impair cognitive function as reflected in an objective neurophysiologic measure such as the P300.

Subtype-associated metabolite differences in the temporal lobe in schizophrenia detected by proton magnetic resonance spectroscopy.

Brain imaging studies have indicated that the medial temporal lobe functions aberrantly in schizophrenic patients. Both diagnostic subtype and gender may affect functional and morphologic abnormalities in this region. We investigated subtype- and gender-associated differences in metabolites in the left medial temporal lobe in 40 medicated schizophrenic patients by proton magnetic resonance spectroscopy and compared findings with those in 40 healthy control subjects. Peaks corresponding to N-acetylaspartate (NAA), choline-containing compounds (Cho), creatine-phosphocreatine (Cr), and inositol were measured. Schizophrenic patients showed a decrease in the NAA/Cr ratio in the left medial temporal lobe, and patients with the disorganized subtype of illness showed significantly lower NAA/Cr and Cho/Cr ratios than those with paranoid schizophrenia. The NAA/Cr ratio in patients with the undifferentiated subtype also was significantly lower than in the paranoid subtype. No significant associations were observed between metabolite ratios and clinical symptom scores, age at onset of illness, or gender. These findings suggest that patients with the disorganized and undifferentiated subtypes have greater impairments in neuronal integrity or function in the left medial temporal lobe than patients with other subtypes of schizophrenia.

Hippocampal volume asymmetry and age at illness onset in males with schizophrenia.

To determine whether there are disturbances of hippocampal volume asymmetry in schizophrenic patients, we obtained contiguous, 1-mm-thick magnetic resonance images in 28 males with chronic schizophrenia and in 28 age-matched healthy males. The schizophrenic patients showed a bilateral reduction in volume of the hippocampal formation (HF; left 7.0%; right 8.7%). This reduction was significantly associated with the severity of disorganization syndrome (P < 0.0005). A significant asymmetry in the HF volume was found in the control subjects (P = 0.006), but not in the patients (P = 0.40). There was a significant positive correlation between the asymmetry index and the patient's age at the onset of schizophrenia (r = 0.46, P = 0.01). Results indicate that a disturbance in the normal asymmetry of the HF may be a characteristic in schizophrenia, particularly in patients with an early onset of the illness.

Proton magnetic resonance spectroscopy of basal ganglia in chronic schizophrenia.

Proton spectra in the regions of the right and left basal ganglia were studied in 14 medicated patients with chronic schizophrenia using proton magnetic resonance spectroscopy (1H MRS). Ratios of N-acetyl-aspartate (NAA) to choline-containing compounds (Cho) were significantly reduced in the bilateral basal ganglia regions compared to normal subjects. The relative level of Cho was increased in the left basal ganglia region in comparison to normal subjects. This finding suggests the presence of disturbances in phospholipid metabolism in the basal ganglia. The level of NAA was decreased in the bilateral basal ganglia regions, which may indicate neuronal dysfunction. The 1H MRS study demonstrated dysfunctions in the basal ganglia regions in medicated patients with chronic schizophrenia.

Cavum septum pellucidum in schizophrenia: a magnetic resonance imaging study.

In order to determine if cavum septum pellucidum (CSP) is more prevalent in schizophrenic patients, we studied 72 Japanese patients who fulfilled the DSM-III-R criteria for schizophrenia and 41 normal controls. Sagittal, 1 mm thick magnetic resonance imaging slices of the entire cranium were obtained using a gradient-echo pulse sequence, and coronal and axial images were reconstructed for assessment. A CSP was observed in 34 patients (47.2%) and in 16 controls (38.0%). Although the CSP appeared to be more prevalent in schizophrenic patients, this difference was not statistically significant. However, schizophrenic patients with a history of long-term institutionalization had a higher incidence of CSP compared with patients who had not been admitted to hospital for more than 3 years (68.2 vs 38.0%). These results suggest that the CSP may be a pathophysiology that characterizes schizophrenic patients with poor prognoses.

Phosphorus magnetic resonance spectroscopy in schizophrenia: correlation between membrane phospholipid metabolism in the temporal lobe and positive symptoms.

1. To determine any correlations between phosphorus metabolites in the temporal lobes and clinical symptoms in schizophrenic patients, the authors performed 31phosphorus magnetic resonance spectroscopy in 31 medicated patients and age- and sex- matched normal subjects. 2. Schizophrenic patients demonstrated an increased level of phosphodiesters (PDE) in the temporal lobes bilaterally and a decreased level of beta-adenosine triphosphate (beta-ATP) in the left temporal lobe. 3. A significant positive correlation was observed between the level of PDE in the left temporal lobe and the score of positive symptoms on the Brief Psychiatric Rating Scale. 4. These results suggest that altered membrane phospholipid metabolism in the left temporal lobe is associated with neuroleptic-resistant positive symptoms in schizophrenic patients.

Proton magnetic resonance spectroscopy of the left medial temporal and frontal lobes in chronic schizophrenia: preliminary report.

Proton magnetic resonance spectroscopy (MRS) was performed in 30 medicated schizophrenic patients and 30 normal subjects. Two groups, each containing 15 schizophrenic patients and 15 age-and sex-matched normal subjects, received MRS examinations for different volumes of interest, either the frontal lobe or the medial temporal lobe. Schizophrenic patients showed a decrease in the ratios of N-acetylaspartate (NAA)/choline-containing compounds (Cho) and NAA/creatine-phosphocreatine (Cr). The patients also showed an increase in the ratio of Cho/Cr in the left medial temporal lobe but not in the left frontal lobe. The age at onset of illness correlated positively with the ratios of NAA/Cho and NAA/Cr in the medial temporal lobe. No significant correlation was observed between the ratios of NAA/Cho, NAA/Cr, or Cho/Cr in the left medial temporal and frontal lobes and clinical symptomatology as assessed by the Scale for the Assessment of Negative Symptoms and the Positive and Negative Syndrome Scale.

Shortening of the hippocampal formation in first-episode schizophrenic patients.

Shortening of hippocampal formation (HF) in chronic schizophrenic patients have been demonstrated in our previous study. The purpose of the present study is to test if shortening of the HF occurs in schizophrenic patients suffering their initial psychotic episode. We performed contiguous, 1 mm thick, magnetic resonance imaging scans in 20 first-episode schizophrenic patients, 21 chronic schizophrenic patients, and 25 healthy subjects. Both groups of schizophrenic patients demonstrated significant shortening of the HF compared with normal controls (first-episode schizophrenia, 5.3%; chronic schizophrenia, 8.0%). However, the HF length was not significantly different between the first-episode and chronic schizophrenic patients. No significant correlation was seen between the HF length and the duration of illness in chronic schizophrenic patients. These results suggest that the HF shortening observed in schizophrenic patients may be genetic and/or developmental in origin.

Correlation of third ventricular enlargement and EEG slow wave activity in schizophrenic patients.

Twenty-eight schizophrenic patients and 22 normal control subjects underwent magnetic resonance imaging (MRI) and topographic electroencephalography (EEG) in a study attempting to correlate morphological and electrophysiological findings. Schizophrenic patients had larger anterior horns of the lateral ventricles and third ventricles than normal control subjects. Schizophrenic patients showed more delta wave activity in the right parietooccipital region than normal control subjects. Alpha 2 wave activity was reduced in the entire region in schizophrenic patients. In schizophrenic patients, a significant positive correlation was seen between the area of the third ventricle and delta wave activity in the right occipital region. These results suggest that schizophrenic patients may have a dysfunction of diencephalic structures associated with morphological abnormality.

Developing of EEG print and its preliminary technical application.

In this report, we discuss a method called "EEG print" to represent EEG contrast mapping in time and frequency domains simultaneously. A bank of bandpass FIR (Finite Impulse Response) digital filters is used to obtain EEG prints. EEG prints were taken from four areas (F3, F4, O1 and O2) of EEG when healthy subjects were at rest with their eyes closed. The pattern of the prints was classified into four types: alpha type, beta type, alpha + beta type and complex type. It was found that EEG prints may vary from person-to-person but they usually do not vary much between the four areas for a given person. The method is further modified to obtain "differential EEG prints" to investigate whether meaningful higher frequency EEG components exist. Differentiation of EEG resulted in marked intensification of the fast waves, using 0.14 Hz as the critical point. In differential EEG print with higher order differentiation, amplification in the high frequency components increase their frequency. As a result, it is possible to observe variations in the high frequency components, which are otherwise not detectable in the usual EEG print. EEG print can be used for representing the function of the brain. Using the method for classification of EEG print patterns, described in this paper, we can clarify not only the characteristics of the normal brain but also the pathophysiology of mentally-ill patients.

31P magnetic resonance spectroscopy of the medial temporal lobe of schizophrenic patients with neuroleptic-resistant marked positive symptoms.

31P magnetic resonance spectroscopy was performed in 16 mediated schizophrenic patients with neuroleptic-resistant marked positive symptoms and in 16 healthy volunteers matched for age and sex in order to determine what changes in phosphorus metabolites are detected in such patients as compared to the controls. The schizophrenic patients showed an increased level of phosphodiesters in the bilateral medial temporal lobes. They also showed a decrease in the level of beta-ATP in the left medial temporal lobe. These findings suggest that schizophrenic patients with prominent positive symptoms refractory to neuroleptics may have a disturbance of bilateral membrane phospholipid and left-sided high-energy phosphate metabolism in the medial temporal lobe.

Brain atrophy and intellectual impairment in tardive dyskinesia.

Fourteen chronic schizophrenic patients with tardive dyskinesia (TD) and 13 without TD were given psychological tests and CT scans. The low density rate (LDR), i.e., the ratio of the X-ray absorption (corresponding nearly to that of cerebrospinal fluid) of a brain lesion to the X-ray absorption of the whole brain, was used as an index of brain atrophy (HN-method). The LDR of the left hemisphere of the TD patients was significantly higher than that of non-TD patients in the basal nucleus and lateral ventricle, and the LDR of the right hemisphere for the TD patients was significantly higher than that of non-TD patients in the basal nucleus. The Hasegawa Dementia Rating Scale (HDRS) and Bender-Gestalt Test (BGT) for the TD patients were significantly lower than those for the non-TD patients. Our study revealed that brain atrophy was greater in TD than in non-TD patients and tended to be more pronounced in the left hemisphere, and that the degree of intellectual impairment was greater in the TD patients than in the non-TD group. The results suggest that schizophrenic brains with TD tend to be more easily damaged than those without TD, that this tendency predominates on the left side, and that intellectual impairment in TD is related to brain atrophy.