Biomedical subjects

M E Shenton

Publications and source records attributed to M E Shenton.

At least 37 records · Page 2Linked to original sources

PubMed2000

Verbal and nonverbal neuropsychological test performance in subjects with schizotypal personality disorder.

OBJECTIVE: The authors contrasted verbal and nonverbal measures of attention and memory in patients with DSM-IV-defined schizotypal personality disorder in order to expand on their previous findings of verbal learning deficits in these patients and to understand better the neuropsychological profile of schizotypal personality disorder. METHOD: Cognitive test performance was examined in 16 right-handed men who met diagnostic criteria for schizotypal personality disorder and 16 matched male comparison subjects. Neuropsychological measures included verbal and nonverbal tests of persistence, supraspan learning, and short- and long-term memory retention. Neuropsychological profiles were constructed by standardizing test scores based on the means and standard deviations of the comparison subject group. RESULTS: Subjects with schizotypal personality disorder showed a mild to moderate general reduction in performance on all measures. Verbal measures of persistence, short-term retention, and learning were more severely impaired than their nonverbal analogs. Performance on measures of memory retention was independent of modality. CONCLUSIONS: The results are consistent with previous reports that have suggested a mild, general decrement in cognitive performance and proportionately greater involvement of the left hemisphere in patients with schizotypal personality disorder. The findings provide further support for a specific deficit in the early processing stages of verbal learning.

Adult↗

PubMed2000

Event-related potentials elicited during a context-free homograph task in normal versus schizophrenic subjects.

Thought disorder in schizophrenia may involve abnormal semantic activation or faulty working memory maintenance. Event-related potentials (ERPs) were recorded while sentences reading "THE NOUN WAS ADJECTIVE/VERB" were presented to 34 schizophrenic and 34 control subjects. Some nouns were homographs with dominant and subordinate meanings. Their sentence ending presented information crucial for interpretation (e.g., The bank was [closed, steep]). Greatest N400 activity to subordinate homograph-meaning sentence endings in schizophrenia would reflect a semantic bias to strong associates. N400 to all endings would reflect faulty verbal working memory maintenance. Schizophrenic subjects showed N400 activity to all endings, suggesting problems in contextual maintenance independent of content, but slightly greater N400 activity to subordinate endings that correlated with the severity of psychosis. Future research should help determine whether a semantic activation bias in schizophrenia toward strong associates is reflected in ERP activity or whether this effect is overshadowed by faulty verbal working memory maintenance of context.

Adult↗

PubMed1999

Schizotypal personality disorder and MRI abnormalities of temporal lobe gray matter.

BACKGROUND: Structural MRI data indicate schizophrenics have reduced left-sided temporal lobe gray matter volumes, especially in the superior temporal gyrus (STG) and medial temporal lobe. Our data further suggest a specificity to schizophrenia spectrum disorders of STG volume reduction. Interpretation of research studies involving schizophrenics may be complicated by the effects of exposure to neuroleptics and chronic illness. Sharing the same genetic diathesis of schizophrenics, subjects with schizotypal personality disorder (SPD) offer a unique opportunity to evaluate commonalities between schizophrenia and SPD, particularly as SPD subjects are characterized by cognitive and perceptual distortions, an inability to tolerate close friendships, and odd behavior, but they are not psychotic and so have generally not been prescribed neuroleptics nor hospitalized. Evaluation of brain structure in SPD may thus offer insight into the "endophenotype" common to both disorders. In addition, differences between groups may suggest which are the brain structures of schizophrenics that contribute to the development of psychosis. METHODS: To test the hypothesis of whether SPD subjects might show similar STG abnormalities, STG and medial temporal lobe regions of interest (ROI) were manually drawn on high resolution coronal MRI 1.5 mm thick slices. Images were derived from 16 right-handed male SPD subjects, without regard to family history, and 14 healthy, right-handed, comparison males who did not differ from the SPD group on parental socio-economic status, age, or verbal IQ. RESULTS: As predicted, SPD subjects showed a reduction in left STG gray matter volume compared with age and gender matched comparison subjects. SPD subjects also showed reduced parahippocampal left/right asymmetry and a high degree of disordered thinking. Comparisons with chronic schizophrenics previously studied by us showed the SPD group had a similarity of left STG gray matter volume reduction, but fewer medial temporal lobe abnormalities. CONCLUSIONS: These abnormalities strengthen the hypothesis of a temporal lobe abnormality in SPD, and the similarity of STG findings in schizophrenia and SPD suggest that STG abnormalities may be part of the spectrum "endophenotype." It is also possible that presence of medial temporal lobe abnormalities may help to differentiate who will develop schizophrenia and who will develop the less severe schizophrenia spectrum disorder, SPD.

Adult↗

PubMed1999

MRI anatomy of schizophrenia.

Structural magnetic resonance imaging (MRI) data have provided much evidence in support of our current view that schizophrenia is a brain disorder with altered brain structure, and consequently involving more than a simple disturbance in neurotransmission. This review surveys 118 peer-reviewed studies with control group from 1987 to May 1998. Most studies (81%) do not find abnormalities of whole brain/intracranial contents, while lateral ventricle enlargement is reported in 77%, and third ventricle enlargement in 67%. The temporal lobe was the brain parenchymal region with the most consistently documented abnormalities. Volume decreases were found in 62% of 37 studies of whole temporal lobe, and in 81% of 16 studies of the superior temporal gyrus (and in 100% with gray matter separately evaluated). Fully 77% of the 30 studies of the medial temporal lobe reported volume reduction in one or more of its constituent structures (hippocampus, amygdala, parahippocampal gyrus). Despite evidence for frontal lobe functional abnormalities, structural MRI investigations less consistently found abnormalities, with 55% describing volume reduction. It may be that frontal lobe volume changes are small, and near the threshold for MRI detection. The parietal and occipital lobes were much less studied; about half of the studies showed positive findings. Most studies of cortical gray matter (86%) found volume reductions were not diffuse, but more pronounced in certain areas. About two thirds of the studies of subcortical structures of thalamus, corpus callosum and basal ganglia (which tend to increase volume with typical neuroleptics), show positive findings, as do almost all (91%) studies of cavum septi pellucidi (CSP). Most data were consistent with a developmental model, but growing evidence was compatible also with progressive, neurodegenerative features, suggesting a "two-hit" model of schizophrenia, for which a cellular hypothesis is discussed. The relationship of clinical symptoms to MRI findings is reviewed, as is the growing evidence suggesting structural abnormalities differ in affective (bipolar) psychosis and schizophrenia.

Brain↗

PubMed1999

P300 topography differs in schizophrenia and manic psychosis.

BACKGROUND: Overall and left temporal scalp area reductions of P300 have been demonstrated in schizophrenia. P300 amplitude and topography in psychotic affective disorder, a crucial comparison in assessing the specificity of P300 abnormalities to schizophrenia, are not well studied. METHODS: P300 was recorded from 35 schizophrenic, 20 psychotic manic, and 30 control subjects. All were right-handed men. RESULTS: P300 was reduced in both psychotic groups relative to control subjects. Anteroposterior P300 topography differed between patient groups, with schizophrenic subjects showing posterior reduction and bipolar subjects showing anterior reduction. Schizophrenic subjects showed an abnormal asymmetry, with smaller P300 over the left temporal scalp site than the right. Both bipolar and control subjects showed a left greater than right asymmetry. CONCLUSIONS: Widespread auditory P300 reductions were present in schizophrenia and bipolar disorder with psychosis, but subtle topographic differences were present in the two diseases. Although unequivocal knowledge of neural generators cannot be derived from topography alone, differences in topography imply different generator configurations. Based on previous studies, the posterior P300 reductions in schizophrenia may reflect abnormalities of a generator located in the left superior temporal gyrus. The frontal reductions in bipolar psychosis may reflect abnormalities in a hypothetical frontal generator, consonant with reports of altered frontal lobe function in mania.

Adolescent↗

PubMed1999

Gamma frequency-range abnormalities to auditory stimulation in schizophrenia.

BACKGROUND: Basic science studies at the neuronal systems level have indicated that gamma-range (30-50 Hz) neural synchronization may be a key mechanism of information processing in neural networks, reflecting integration of various features of an object. Furthermore, gamma-range synchronization is thought to depend on the glutamatergically mediated interplay between excitatory projection neurons and inhibitory neurons utilizing gamma-aminobutyric acid (GABA), which postmortem studies suggest may be abnormal in schizophrenia. We therefore tested whether auditory neural networks in patients with schizophrenia could support gamma-range synchronization. METHODS: Synchronization of the electroencephalogram (EEG) to different rates (20-40 Hz) of auditory stimulation was recorded from 15 patients with schizophrenia and 15 sex-, age-, and handedness-matched control subjects. The EEG power at each stimulation frequency was compared between groups. The time course of the phase relationship between each stimulus and EEG peak was also evaluated for gamma-range (40 Hz) stimulation. RESULTS: Schizophrenic patients showed reduced EEG power at 40 Hz, but not at lower frequencies of stimulation. In addition, schizophrenic patients showed delayed onset of phase synchronization and delayed desynchronization to the click train. CONCLUSIONS: These data provide new information on selective deficits in early-stage sensory processing in schizophrenia, a failure to support the entrainment of intrinsic gamma-frequency oscillators. The reduced EEG power at 40 Hz in schizophrenic patients may reflect a dysfunction of the recurrent inhibitory drive on auditory neural networks.

Acoustic Stimulation↗

PubMed1999

Left planum temporale volume reduction in schizophrenia.

BACKGROUND: The planum temporale, located on the posterior and superior surface of the temporal lobe, is a brain region thought to be a biological substrate of language and possibly implicated in the pathophysiology of schizophrenia. To investigate further the role of planum temporale abnormalities in schizophrenia, we measured gray matter volume underlying the planum temporale from high spatial resolution magnetic resonance imaging techniques. METHODS: Sixteen male patients with chronic schizophrenia and 16 control subjects were matched for age, sex, handedness, and parental socioeconomic status. Magnetic resonance imaging images were obtained from a 1.5-T magnet. RESULTS: Gray matter volume was significantly reduced in the left planum temporale (28.2%) in schizophrenic patients compared with normal controls. Schizophrenic patients showed a reversal of the left greater than right planum temporale asymmetry found in normal controls. Heschl's gyrus (primary auditory cortex) showed no differences between the left and right sides in either group. Of note, the Suspiciousness/Persecution subscale score of the Positive and Negative Syndrome Scale was associated with reduced left planum temporale volume in schizophrenic patients. CONCLUSIONS: Patients with schizophrenia have reduced left planum temporale gray matter and a reversal of planum temporale asymmetry, which may underlie an impairment in language processing and symptoms of suspiciousness or persecution characteristic of schizophrenia.

Adult↗

PubMed1999

AnatomyBrowser: A novel approach to visualization and integration of medical information.

In this article, we present a novel technique for visualization of three-dimensional (3D) surface models, as well as its implementation in a system called AnatomyBrowser. Using our approach, visualization of 3D surface models is performed in two separate steps: a pre-rendering step, in which the models are rendered and saved in a special format, and an actual display step, in which the final result of rendering is generated using information from the prerendering step. Whereas prerendering requires high-end graphics hardware, the final image generation and display can be implemented efficiently in software. Moreover, our current implementation of AnatomyBrowser interface uses the Java programming language and can therefore be readily run on a wide range of systems, including low-end computers with no special graphics hardware. In addition to visualization of 3D models and 2D slices, AnatomyBrowser provides a rich set of annotation and cross-referencing capabilities. We demonstrate several possible applications for AnatomyBrowser, including interactive anatomy atlases, surgery planning, and assistance in segmentation.

Anatomy↗

PubMed1999

Cognitive dysfunction in schizophrenia: unifying basic research and clinical aspects.

Seeking to unite psychological and biological approaches, this paper links cognitive and cellular hypotheses and data about thought and language abnormalities in schizophrenia. The common thread, it is proposed, is a dysregulated suppression of associations (at the behavioral and functional neural systems level), paralleled by abnormalities of inhibition at the cellular and molecular level, and by an abnormal anatomical substrate (reduced MRI gray matter volume) in areas subserving language. At the level of behavioral experiments and connectionist modeling, data suggest an abnormal semantic network connectivity (strength of associations) in schizophrenia, but not an abnormality of network size (number of associates). This connectivity abnormality is likely to be a preferential processing of the dominant (strongest) association, with the neglect of preceding contextual information. At the level of functional neural systems, the N400 event-related potential amplitude is used to index the extent of "search" for a semantic match to a word. In a short stimulus-onset-asynchrony condition, both schizophrenic and schizotypal personality disorder subjects showed, compared with controls, a reduced N400 amplitude to the target words that were related to cues, e.g. cat-dog, a result compatible with behavioral data. Other N400 data strongly and directly suggest that schizophrenics do not efficiently utilize context.

Brain↗

PubMed1999

Identification of neural circuits underlying P300 abnormalities in schizophrenia.

Event-related potentials (ERPs) provide a noninvasive method to evaluate neural activation and cognitive processes in schizophrenia. The pathophysiological significance of these findings would be greatly enhanced if scalp-recorded ERP abnormalities could be related to specific neural circuits and/or regions of the brain. Using quantitative approaches in which scalp-recorded ERP components are correlated with underlying neuroanatomy in schizophrenia, we focused on biophysical and statistical procedures (partial least squares) to relate the auditory P300 component to anatomic measures obtained from quantitative magnetic resonance imaging. These findings are consistent with other evidence that temporal lobe structures contribute to the generation of the scalp-recorded P300 component and that P300 amplitude asymmetry over temporal recording sites on the scalp may reflect anatomic asymmetries in the volume of the superior temporal gyrus in schizophrenia.

Brain Mapping↗

PubMed1999

Superior temporal gyrus volume abnormalities and thought disorder in left-handed schizophrenic men.

OBJECTIVE: Studies of schizophrenia have not clearly defined handedness as a differentiating variable. Moreover, the relationship between thought disorder and anatomical anomalies has not been studied extensively in left-handed schizophrenic men. The twofold purpose of this study was to investigate gray matter volumes in the superior temporal gyrus of the temporal lobe (left and right hemispheres) in left-handed schizophrenic men and left-handed comparison men, in order to determine whether thought disorder in the left-handed schizophrenic men correlated with tissue volume abnormalities. METHOD: Left-handed male patients (N = 8) with DSM-III-R diagnoses of schizophrenia were compared with left-handed comparison men (N = 10) matched for age, socioeconomic status, and IQ. Magnetic resonance imaging (MRI) with a 1.5-T magnet was used to obtain scans, which consisted of contiguous 1.5-mm slices of the whole brain. MRI analyses (as previously defined by the authors) included the anterior, posterior, and total superior temporal gyrus in both the left and right hemispheres. RESULTS: There were three significant findings regarding the left-handed schizophrenic men: 1) bilaterally smaller gray matter volumes in the posterior superior temporal gyrus (16% smaller on the right, 15% smaller on the left); 2) a smaller volume on the right side of the total superior temporal gyrus; and 3) a positive correlation between thought disorder and tissue volume in the right anterior superior temporal gyrus. CONCLUSIONS: These results suggest that expression of brain pathology differs between left-handed and right-handed schizophrenic men and that the pathology is related to cognitive disturbance.

Cognition Disorders↗

PubMed1999

Electrophysiological correlates of language processing in schizotypal personality disorder.

OBJECTIVE: This study examined whether the electrophysiological correlates of language processing found previously to be abnormal in schizophrenia are also abnormal in schizotypal individuals. The authors used the N400 component to evaluate language dysfunction in schizotypal individuals. METHOD: Event-related potentials were recorded in 16 comparison subjects and 17 schizotypal individuals (who met full DSM-III-R criteria) to sentences presented both visually and aurally; half of the sentences ended with an expected word completion (congruent condition), and the other half ended with an unexpected word completion (incongruent condition). RESULTS: In the congruent condition, the N400 amplitude was more negative in individuals with schizotypal personality disorder than in comparison subjects in both the visual and auditory modalities. In addition, in the visual modality, the N400 latency was prolonged in the individuals with schizotypal personality disorder. CONCLUSIONS: The N400 was found to be abnormal in the individuals with schizotypal personality disorder relative to comparison subjects. The abnormality was similar to the abnormality the authors' laboratory reported earlier in schizophrenic subjects, in which the N400 amplitude was found to be more negative in both congruent and incongruent sentence completions. The N400 abnormality is consistent with the inefficient use of context.

Adult↗

PubMed1999

Subgenual cingulate cortex volume in first-episode psychosis.

OBJECTIVE: Gray matter volume and glucose utilization have been reported to be reduced in the left subgenual cingulate of subjects with familial bipolar or unipolar depression. It is unclear whether these findings are secondary to recurrent illness or are part of a familial/genetic syndrome. The authors' goal was to clarify these findings. METHOD: Volumetric analyses were performed by using magnetic resonance imaging in 41 patients experiencing their first episode of affective disorder or schizophrenia and in 20 normal comparison subjects. RESULTS: The left subgenual cingulate volume of the patients with affective disorder who had a family history of affective disorder was smaller than that of patients with affective disorder with no family history of the illness and the normal comparison subjects. Patients with schizophrenia did not differ from comparison subjects in left subgenual cingulate volume. CONCLUSIONS: Left subgenual cingulate abnormalities are present at first hospitalization for psychotic affective disorder in patients who have a family history of affective disorder.

Adult↗

PubMed1999

Quantitative volumetric MRI study of the cerebellum and vermis in schizophrenia: clinical and cognitive correlates.

OBJECTIVE: Recent evidence suggests that the cerebellum may play a role in higher cognitive functions and, therefore, may play an important role in schizophrenia. METHOD: The authors used magnetic resonance imaging to measure cerebellum and vermis volume in 15 patients with schizophrenia and 15 normal comparison subjects. RESULTS: They found that 1) vermis volume was greater in patients with schizophrenia than in normal subjects, 2) greater vermis white matter volume in the patients with schizophrenia significantly correlated with severity of positive symptoms and thought disorder and with impairment in verbal logical memory, and 3) patients with schizophrenia showed a trend for more cerebellar hemispheric volume asymmetry (left greater than right). CONCLUSIONS: These data suggest that an abnormality in the vermis may contribute to the pathophysiology of schizophrenia.

Cerebellum↗

PubMed1998

High-density recording and topographic analysis of the auditory oddball event-related potential in patients with schizophrenia.

BACKGROUND: Prior research has shown reductions of the N1, N2, and P300 auditory event-related potential (ERP) components in schizophrenic patients. Most studies have shown a greater P300 reduction in left versus right temporal leads in schizophrenic patients. These studies were done with sparse electrode arrays, covering restricted areas of the head, thus providing an incomplete representation of the topographic field distribution. METHODS: We used a 64-channel montage to acquire auditory oddball ERPs from 24 schizophrenic patients and 24 controls subjects. The N1, P2, N2, P300, and N2 difference (N2d) amplitudes and latencies were tested for group and laterality differences. Component topographies were mapped onto a three-dimensional head model to display the group differences. RESULTS: The schizophrenic group showed reduction of the N1 component, perhaps reflecting reduced arousal or vigilance, but no N1 topographic difference. An N2d was not apparent in the schizophrenic patients, perhaps reflecting severe disruption in neural systems of stimulus categorization. In the patients, the P300 was smaller over the left temporal lobe sites than the right. CONCLUSIONS: The increased ERP spatial sampling allowed a more complete representation of the dipolar nature of the P300, which showed field contours consistent with neural sources in the posterior superior temporal plane.

Adult↗

PubMed1998

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.

Adult↗

PubMed1998

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.

Adult↗

PubMed1998

First-episode schizophrenic psychosis differs from first-episode affective psychosis and controls in P300 amplitude over left temporal lobe.

BACKGROUND: Schizophrenia is associated with central (sagittal) midline reductions of the P300 cognitive event-related potential and topographic asymmetry of P300, with reduced left temporal voltage. This P300 asymmetry is, in turn, linked to tissue volume asymmetry in the posterior superior temporal gyrus. However, it is unknown whether P300 asymmetry is specific to schizophrenia and whether central and lateral P300 abnormalities are due to chronic morbidity, neuroleptic medication, and/or hospitalization, or whether they are present at the onset of illness. METHODS: P300 was recorded in first-episode schizophrenia, first-episode affective psychosis, and control subjects (n = 14 per group). Subjects silently counted rare (15%) target tones (1.5 kHz) among trains of standard tones (1.0 kHz). Averages were constructed from brain responses to target tones. RESULTS: Peak amplitude of P300 and integrated voltage over 300 to 400 milliseconds were significantly different between first-episode schizophrenics and controls over the posterior sagittal midline of the head. First-episode schizophrenics displayed smaller amplitudes over the left temporal lobe than first-episode affective psychotics and controls, but the groups showed no differences over the right temporal lobe. CONCLUSIONS: Left-sided P300 abnormality in first-episode schizophrenia relative to first-episode affective psychosis and controls suggests that P300 asymmetry is specific to schizophrenic psychosis and present at initial hospitalization. This P300 asymmetry suggests left temporal lobe dysfunction at the onset of schizophrenia.

Adolescent↗