Prefrontal cortex and schizophrenia. A quantitative magnetic resonance imaging study.

OBJECTIVE: To measure prefrontal cortical volume in a group of schizophrenic subjects who presented with mainly positive symptoms and who were previously shown to have volume reductions in left temporal lobe structures. METHOD: Fourteen men with chronic schizophrenia and 15 male control subjects were matched for age, IQ, handedness, and parental socioeconomic status. Magnetic resonance images were obtained by means of a 1.5-T magnet, and contiguous 1.5-mm slices of the entire brain were obtained. RESULTS: No significant differences were found between schizophrenic and control subjects in mean values for prefrontal white or gray matter on either the right or the left side. However, within the schizophrenic group, there was evidence of a relationship between the volumes of left prefrontal gray matter and left temporal lobe structures that was not present in the control group. CONCLUSIONS: At least in this group of schizophrenic subjects with mainly positive symptoms, temporal lobe abnormalities can exist in conjunction with no gross volumetric abnormalities of the prefrontal cortex.

Abnormalities of auditory event-related potentials in schizophrenia prior to treatment.

BACKGROUND: P300 amplitude reduction is a consistent finding in schizophrenic patients, but it is unclear if this abnormality predates neuroleptic treatment or is present at onset of illness. METHODS: Auditory event-related potentials (ERPs), during a standard oddball paradigm, were recorded from 45 neuroleptic-naive schizophrenics, 56 drug-free, previously treated schizophrenics, and 73 healthy normal controls. Forty-seven of the schizophrenic subjects had their first episode within the past year. RESULTS: N200 amplitude did not differ among groups. P300 amplitude was significantly smaller in both neuroleptic-naive and previously treated schizophrenic groups compared to the control groups. There were no significant differences between the two schizophrenic groups in P300 amplitude. N200 and P300 latency were prolonged in previously treated schizophrenics compared to neuroleptic-naive schizophrenics and normal controls. CONCLUSIONS: The present study suggests that ERP abnormalities, especially P300 amplitude reduction, are already present prior to the administration of neuroleptic medication in the earliest stage of schizophrenia.

Magnetic resonance imaging study of hippocampal volume in chronic, combat-related posttraumatic stress disorder.

This study used quantitative volumetric magnetic resonance imaging techniques to explore the neuroanatomic correlates of chronic, combat-related posttraumatic stress disorder (PTSD) in seven Vietnam veterans with PTSD compared with seven nonPTSD combat veterans and eight normal nonveterans. Both left and right hippocampi were significantly smaller in the PTSD subjects compared to the Combat Control and Normal subjects, even after adjusting for age, whole brain volume, and lifetime alcohol consumption. There were no statistically significant group differences in intracranial cavity, whole brain, ventricles, ventricle:brain ratio, or amygdala. Subarachnoidal cerebrospinal fluid was increased in both veteran groups. Our finding of decreased hippocampal volume in PTSD subjects is consistent with results of other investigations which utilized only trauma-unexposed control groups. Hippocampal volume was directly correlated with combat exposure, which suggests that traumatic stress may damage the hippocampus. Alternatively, smaller hippocampi volume may be a pre-existing risk factor for combat exposure and/or the development of PTSD upon combat exposure.

Volumetric evaluation of the thalamus in schizophrenic male patients using magnetic resonance imaging.

BACKGROUND: The thalamus, an important subcortical brain region connecting limbic and prefrontal cortices, has a significant role in sensory and cortical processing. Although inconsistently, previous studies have demonstrated neuroanatomical abnormalities in the thalamus of schizophrenic patients. METHODS: This structural magnetic resonance imaging study, based on segmentation of contiguous coronal 1.5-mm images, compared thalamic brain volumes of 15 chronic, male schizophrenic patients with 15 normal controls matched on age, sex, handedness, and parental socioeconomic status. RESULTS: There were no significant differences between patients and controls in thalamic volumes, right or left, adjusted for total brain volume; however, there were significantly different correlations of thalamic volumes with prefrontal white matter and lateral ventricles among patients, but not among controls. Thalamic volumes among patients were also significantly correlated with bizarre behavior, hallucinations, and thought disorder. CONCLUSIONS: Findings suggest that connectivity between thalamic nuclei and prefrontal cortical areas are abnormal in chronic male schizophrenic patients. In addition, ventricular enlargement may be, in part, due to subtle reduction in thalamic volume and/or in volume of thalamocortical and corticothalamic fibers secondary to thalamic abnormalities. Finally, correlations with positive symptomatology underscore the role of the thalamus in gating or filtering of sensory information and coordination of cortical processing.

A neuropsychological analysis of schizophrenic thought disorder.

We examined the relationship of schizophrenic thought disorder, as measured by the Thought Disorder Index (TDI), with (1) neuropsychological measures of verbal memory, abstraction, executive function, visual memory, and working memory; and (2) quantitative MRI measures of prefrontal and basal ganglia structures. TDI scores correlated strongly with tests of verbal memory, abstraction and executive functions, modestly with tests of working memory, but did not correlate with scores on tests of visual memory. Neither TDI scores nor their neuropsychological correlates were associated with frontal or basal ganglia magnetic resonance imaging (MRI) measures, with the exception of the measures of working memory that demonstrated a modest relationship with frontal and basal ganglia structures. These findings suggest that schizophrenic thought disorder may be strongly related to neuropsychological impairments in verbal memory, abstraction and executive functions, and modestly related to problems with working memory in this sample of patients.

Temporal lobe sulco-gyral pattern anomalies in schizophrenia: an in vivo MR three-dimensional surface rendering study.

Neuroanatomical and histological findings from post-mortem brains, as well as in vivo findings from magnetic resonance imaging (MRI) studies, suggest the presence of morphologic temporal lobe abnormalities in schizophrenia. To determine whether or not sulco-gyral pattern abnormalities in the temporal lobe could be detected in vivo, we applied computerized surface rendering techniques to MR data sets in order to make both qualitative and quantitative analyses of three-dimensional reconstructions of the temporal and frontal cortex in 15 schizophrenic patients and 15 normal controls. The qualitative analysis, based on a visual classification of the temporal lobe sulco-gyral pattern by 4 raters blind to diagnosis, showed that in schizophrenics there was a more vertical orientation to the sulci in the left temporal lobe, with an interrupted course of sulci due to gyri coursing across the sulci. Normal controls, in contrast, showed a more horizontal orientation with no interruptions. These findings were supported by the quantitative analysis, where more sulcal lines, representing an interrupted course of sulci, were observed in the temporal lobes (more pronounced on the left) in schizophrenics than in normal controls. These data suggest that some of the abnormalities observed in schizophrenia may have their origin in alterations occurring during the course of neurodevelopment when the sulco-gyral pattern is determined.

Caudate, putamen, and globus pallidus volume in schizophrenia: a quantitative MRI study.

Basal ganglia structures have been reported to be abnormal in schizophrenia. However, while component structures of the basal ganglia are functionally differentiated, there have been no evaluations of their separate magnetic resonance imaging (MRI) volumes with small voxel (1.5 mm3) spoiled gradient-recalled acquisition in steady state techniques and multi-plane assessments. We examined MRI scans from 15 male, right-handed, neuroleptic-medicated schizophrenic patients and 15 age-, handedness-, and gender-matched normal volunteers. Compared with normal subjects, schizophrenic patients showed enlarged volumes: 14.2% for total basal ganglia, 27.4% for globus pallidus, 15.9% for putamen, and 9.5% for caudate. Increased volumes, especially of the caudate, were associated with poorer neuropsychological test performance on finger tapping and Hebb's Recurring Digits. These findings indicate abnormalities throughout all basal ganglia structures in at least a subgroup of schizophrenic patients.

Deviate P200 and P300 in non-patient college students with high scores on the schizophrenia scale of the Minnesota Multiphasic Personality Inventory (MMPI).

Event-related potentials (ERPs) were examined in 16 college students who had high scores on the Schizophrenia Scale of the MMPI (HSS) but were without a hereditary disposition for major psychiatric disorders. 32 sex- and age-matched college students were used as controls. Subjects whose T scores were higher than 70 were designated the HSS subjects. ERPs were recorded during an auditory oddball task. Although neither the P300 latencies nor the P200 latencies differed between the two subject groups, the amplitudes of P300 to rare stimuli and P200 to frequent stimuli were lower in the HSS subjects than in the controls. These results suggest that deficits, both in the P300-related cognitive function to rare relevant stimuli, as well as matching and/or the comparison process for irrelevant frequent stimuli, may be present in HSS subjects. The HSS subjects, especially those with a combination of P300 and P200 deficits, even though without a hereditary diathesis for schizophrenia, may constitute one type of high-risk group.

Auditory ERPs to non-target stimuli in schizophrenia: relationship to probability, task-demands, and target ERPs.

The effects of task demands and stimulus probability on the N1 and P2 components of the auditory event-related potential (ERP) to non-target stimuli were investigated in normal and medicated schizophrenic subjects. Subjects either read a book while tones were presented, or counted the rare (low probability) tones in an auditory oddball paradigm. The mismatch negativity to rare tones in the reading condition was present, and did not differ between groups. N1 amplitude was smaller in schizophrenic patients in all conditions. When subjects counted the rare tones, the amplitude and latency of P2 increased. This task-related effect on P2 was much greater in control than in schizophrenic subjects. Difference ERPs were used to better characterize the effect of task demands by subtracting the ERP in the reading condition from the ERP in the counting condition. The difference ERP consisted of a negative deflection at 182 ms, and a positive deflection at 276 ms, which were both reduced in schizophrenic subjects. N2 and P3 amplitude to target stimuli were reduced in patients as well, but these abnormalities were uncorrelated with N1 and P2 abnormalities to non-target stimuli. Despite automatic registration of stimulus mismatch, and normal processing speed, patients showed deficient task-related modulation of processing to both non-target and target stimuli. Reduction of N1 amplitude in schizophrenia occurs regardless of task demands, and may reflect a chronic, early-stage disturbance in information processing.

[Cognitive impairment in schizophrenic patients on event-related potentials component P300].

There have been many reports on the Event-Related Potentials (ERPs) abnormalities, especially P300 amplitudes reduction, in schizophrenic patients. However the relationships between P300 abnormalities and schizophrenic subtypes have not been clarified. This study aims to investigate the relationships in a relatively large number of drug free schizophrenics. Seventy three unmedicated schizophrenic patients (45 males, 28 females) who met the DSM-III-R criteria for schizophrenia were tested. Twenty seven of the schizophrenics were paranoid type according to the DSM-III-R, 23 were undifferentiated, 19 were disorganized, 2 catatonic and 2 residual. Seventy three healthy controls were age and gender matched to the patient group. All the ERPs were recorded during auditory odd ball task. Stimuli consists of 2 kHz and 1 kHz tone bursts, and the respective probabilities of the rare and frequent stimuli were 0.2 and 0.8. They were presented random order. The duration of each stimulus was 90 msec with rise and fall times of 10 msec, and the intensity was approximately 70 dB SPL for all the stimuli. The inter-stimulus intervals were 1.7 +/- 0.1 seconds. The subjects were instructed to count the numbers of rare tones. The scalp EEGs were recorded from Ag-AgCl electrodes at 16 sites that referred to linked earlobes. P300 amplitudes reduction [F (1,144) = 39.33, p < 0.001] and P300 latencies prolongation [F (1,144) = 12.41, p < 0.001] were found in schizophrenic group as a whole. Lower amplitude of P300 was observed at both right and left temporal sites in the subjects with undifferentiated type and disorganized type. Although in the subjects with paranoid type, the reduction was recognized at left temporal region, reduced amplitude was not seen at right temporal site. While no relationships between P300 amplitudes, the score of BPRS and SAPS were detected, in the patient with paranoid type, significant negative correlation between P300 amplitudes and SANS total scores was observed (r = -0.425, p = 0.03) at Pz site. These results were discussed with respect to cognitive impairment of schizophrenia.

The N400 component of event-related potentials in schizophrenic patients: a preliminary study.

ERPs were recorded during a word recognition task to investigate cognitive dysfunction in schizophrenia. Thirteen medicated schizophrenics and 26 normal controls were tested. In each trial a pair of stimuli, S1 (a word) and S2 (a word or a non-word), were presented. The subjects were required to discriminate between a word and a non-word for S2 (lexical decision task). In a related (R) condition, S2 was the antonym of S1 (e.g., brother-sister); in an unrelated (U) condition, S1 and S2 were semantically unrelated (e.g., brother-drive); in the non-word (N) condition, S2 was a non-word (e.g., brother-grofe). The ERPs for S2 were analyzed, and the contextual effects on the ERPs for S2 observed for both the patients and controls. For both groups, in the U and N conditions S2 elicited a large negative-trending deflection (N370). In contrast, in the R condition it elicited only a small negative-trending notch. There was no difference in the amplitude of N370 between the groups, but its latency was more prolonged or its wave shape more extended for the schizophrenics than for the controls. The N400 amplitude is concluded to remain unchanged in schizophrenics.

ERPs in schizophrenic patients during word recognition task and reaction times.

Event-related brain potentials (ERPs) were recorded in 28 schizophrenic patients and 26 healthy controls during a word recognition task. In each trial, stimuli consisting of S1 (word) and S2 (word or non-word) were presented. The subjects were required to indicate whether S2 was a word or a non-word by pressing buttons. For both groups, a clear N370 was elicited by S2 which were non-word or semantically unrelated to its S1. The N370 amplitude did not differ between the groups. The schizophrenics responded more slowly than the controls, and the latencies of P200 and N370 were longer for patients than for controls. However, these latencies did not differ between the groups when their reaction times were matched.

Abnormalities of auditory event-related potentials in students with schizotypal personality disorder.

Biological, phenomenological and cognitive similarities are known to exist between schizophrenia and schizotypal personality disorder (SPD). This study examined whether, and to what extent, abnormalities in event-related potentials (ERPs) already extensively reported in schizophrenia can also be observed in persons psychometrically identified with SPD. Event-related potentials were examined in nine SPD subjects and nine controls recruited from among 1693 college students, using the Schizotypal Personality Questionnaire (SPQ) and the Structured Clinical Interview for DSM-III-R (SCID I and II). Event-related potentials were recorded during an auditory oddball task. Smaller P300 amplitude and prolonged P300 latency were found in SPD subjects as compared with controls. Our findings indicate that such individuals do have deficits in information processing similar to that found in schizophrenia. We can conclude that P300 abnormalities may not be specific for SPD but that abnormalities shown in SPD are possibly a vulnerability marker for developing schizophrenia.

Deviate N200 component of event-related potentials in shuchaku-seikaku, a premorbid personality of depression.

Twenty-one healthy subjects with Shuchaku-Seikaku (SS), a premorbid personality of depression, and 44 control subjects were tested for event-related potentials using the auditory odd ball paradigm. A higher percent of the N200 component was evoked by frequent task-irrelevant stimuli in the Shuchaku-Seikaku (81.0%) subjects than in the controls (45.5%). The mean amplitudes in the 50-100 ms latency range for task-relevant rare stimuli were smaller; whereas, the amplitudes in the 100-200 ms range for task-irrelevant frequent stimuli and the amplitudes in the 200-260 ms range for both stimuli were larger (shifted to negative direction) in the SS subjects than in the controls. The evidence suggests that the fully automatic detection process, which is assumed to be correlated with mismatch negativity, is hypoactivated and that a contrarily controlled or conscious mismatch process, which may be N2b, is hyperactivated in SS.

A topographic study of ERPs elicited by visual feature discrimination.

The functional properties and topographic distribution of event-related potential (ERP) components elicited by visual discrimination of orientation, spatial frequency, spatial location, and color were investigated. ERPs were recorded from 28 electrode sites from 16 adult subjects. Five ERP components were measured: N1 (peak latency = 160 ms), P2 (250 ms), anterior N2 (260 ms), posterior N2 (280 ms), and P3 (400 ms). N1 and P2 were more negative when a stimulus was a target, showing the selection negativity effect. Feature-specific effects on component amplitude or topography varied by component. N1 and P2 were sensitive to stimulus orientation and location. Anterior or posterior N2 was sensitive to orientation, spatial frequency, and location. P3 varied with orientation, but not with other stimulus features. Cross-task comparisons of ERPs to vertical line segments in the color, orientation, and location discrimination tasks indicated that P2 and N2, but not N1 and P3, were sensitive to changes in task-demand. These data provide topographic evidence that ERP components in the 160-400 ms time domain can be differentiated on the basis to processing of specific visual features, and reflect neurophysiologically distinct visual pathways in the human cortex.

Abnormalities of the left temporal lobe and thought disorder in schizophrenia. A quantitative magnetic resonance imaging study.

BACKGROUND: Data from postmortem, CT, and magnetic resonance imaging (MRI) studies indicate that patients with schizophrenia may have anatomical abnormalities of the left temporal lobe, but it is unclear whether these abnormalities are related to the thought disorder characteristic of schizophrenia. METHODS: We used new MRI neuroimaging techniques to derive (without knowledge of the diagnosis) volume measurements and three-dimensional reconstructions of temporal-lobe structures in vivo in 15 right-handed men with chronic schizophrenia and 15 matched controls. RESULTS: As compared with the controls, the patients had significant reductions in the volume of gray matter in the left anterior hippocampus-amygdala (by 19 percent [95 percent confidence interval, 3 to 36 percent]), the left parahippocampal gyrus (by 13 percent [95 percent confidence interval, 3 to 23 percent], vs. 8 percent on the right), and the left superior temporal gyrus (by 15 percent [95 percent confidence interval, 5 to 25 percent]). The volume of the left posterior superior temporal gyrus correlated with the score on the thought-disorder index in the 13 patients evaluated (r = -0.81, P = 0.001). None of these regional volume decreases was accompanied by a decrease in the volume of the overall brain or temporal lobe. The volume of gray matter in a control region (the superior frontal gyrus) was essentially the same in the patients and controls. CONCLUSIONS: Schizophrenia involves localized reductions in the gray matter of the left temporal lobe. The degree of thought disorder is related to the size of the reduction in volume of the left posterior superior temporal gyrus.

Electrical source analysis of auditory ERPs in medial temporal lobe amnestic syndrome.

Auditory event-related potential (ERP) components have been anatomically linked to temporal lobe structures and functionally related to attentional and memory processes. We recorded auditory ERPs using an "oddball" paradigm from two patients with amnestic syndromes secondary to medial temporal lobe encephalitic infections. The oddball paradigm elicits the exogenous N1 and P2 components, and the endogenous N2 and P3 components. Electrical source analysis was used to test for alterations in source strength and orientation in these patients compared to control subjects. Symmetric dipoles placed in the temporal lobe region were used to measure ERP component activity. In the patient with a lesion confined to the left, medial temporal lobe, including the posterior hippocampus, dipole orientation was displaced anteriorally. In the patient with lesions to the anterior medial temporal lobe, temporal poles, and orbital frontal cortex, the negative components of the ERP (N1 and N2) were reduced in the right hemisphere, accompanied by disturbed orientation. These findings are consistent with other evidence that the different components of the auditory ERP can be dissociated on the basis of lesion effects, and that the antero-posterior extent of encephalitic lesions may play an important role in modulating ERP abnormalities.