Conjoint left asymmetry of auditory P300 voltage and MRI volume of posterior superior temporal gyrus in schizophrenia: a quantitative evaluation.
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Acoustic Stimulation↗
Biomedical subjects
M E Shenton
Publications and source records attributed to M E Shenton.
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.
Adult↗
Neural circuits in schizophrenia.
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Functional Laterality↗
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.
Acoustic Stimulation↗
The N2 event-related potential reflects attention deficit in schizophrenia.
Schizophrenia involves deficits in detection and filtering of irrelevant stimuli. The N2 event-related potential (ERP), most likely reflecting classification of deviant stimuli, remains largely unstudied in this group. Recently, we reported that N2 amplitude correlated highly with reduced neocortical and medial temporal lobe volumes in schizophrenics. However, little is known about the functional properties of N2 in schizophrenics. To that end, the latency and amplitude of N2 were assessed in schizophrenic and control subjects to differently pitched tones. Subjects pressed a button in response to low probability (p = .15) target tones interspersed among high probability standard tones. Tones were either NEAR (1.4 kHz standard, 1.5 kHz target) or FAR (1 kHz standard, 1.5 kHz target) in pitch. N2 was measured from difference waveforms, subtracting ERPs on a simple reaction time task (target p = 1.0) from those of the detection task. Schizophrenics performed the detection task nearly as well as controls in the FAR condition, and more poorly in the NEAR condition. Schizophrenics displayed virtually no N2 amplitudes in either condition. The results are interpreted as electrophysiological signs of disturbance in stimulus classification and attention processes in schizophrenia directly related to pathology of N2 neural generators, independent of sensory or detectability problems.
Adult↗
Premorbid adjustment in schizophrenia: implications for psychosocial and ventricular pathology.
Premorbid adjustment in schizophrenia is thought important (1) as a predictor of current pathology and course, and (2) as a psychosocial expression of brain pathology preceding psychosis. Its valid and reliable measurement, however, pose a major challenge. To address this issue we interviewed 12 chronic male schizophrenic veterans and their first degree relatives, plus 12 age and social class of origin matched normal controls and their relatives, using the Cannon-Spoor et al. Premorbid Adjustment Scale (PAS), for which we developed our own semi-structured interview. Objective data from school records were also obtained. Schizophrenic's PAS scores were significantly poorer, irrespective of whether PAS scores were based on information from subjects, first degree relatives or from 'combined sources'. PAS scores were worse at all developmental epochs, with a marked divergence beginning in late adolescence. Worse premorbid adjustment in schizophrenia was also highly correlated with current clinical state, more current negative symptoms, less independent living and longer duration of hospitalization. Additionally, worse premorbid adjustment in schizophrenia was associated with larger Magnetic Resonance (MR) Ventricular Brain Ratio (VBR) in an exploratory analysis using a subset of these patients. Premorbid adjustment, rigorously measured, is poorer in schizophrenics than in normal controls and correlates with psychosocial and ventricular pathology in schizophrenia.
Adult↗
Auditory P300 abnormalities and left posterior superior temporal gyrus volume reduction in schizophrenia.
Abnormalities in the auditory P300 event-related potential are one of the most robust findings in schizophrenia. To investigate the brain source(s) of this major functional abnormality, we combined P300 recordings with the use of a new generation of magnetic resonance imaging (MRI) technology to examine specific temporal lobe gray matter regions of interest in schizophrenics and normal controls. In schizophrenics, gray matter volume reductions in the left posterior superior temporal gyrus (STG), which includes Heschl's gyrus and the planum temporale, were highly and specifically associated with both P300 amplitude reduction and left < right topographic asymmetry. In contrast, left hippocampus and parahippocampal gyrus gray matter volume reductions, although present in schizophrenics, were not associated with any P300 abnormalities. There were also no statistically significant correlations between P300 amplitude at any of the central or left-sided electrode sites or any of the MRI-defined volumes of gray matter regions of interest in the right temporal lobe, superior frontal gyrus, or cingulate gyrus; additional work will thus be required to determine the role of these regions, if any, in P300 generation, along with the role of other brain areas not examined in the present study. These initial data appear most compatible with a model that postulates a major role for bilateral STG sources in P300 generation: The strongly asymmetric STG volume reduction (left < < right STG volume) found in many schizophrenic subjects produces asymmetric P300 amplitudes (left < < right) at lateral electrode sites, where the influence of the abnormal region is most easily detected.
Adult↗
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.
Acoustic Stimulation↗
Neuropsychological correlates of MRI temporal lobe abnormalities in schizophrenia.
OBJECTIVE: The authors evaluated the neuropsychological correlates of temporal lobe abnormalities in schizophrenic patients. METHOD: Fifteen schizophrenic patients underwent assessment of memory, by the Wechsler Memory Scale--Revised, and abstraction/categorization, by the similarities subtest of the Wechsler Adult Intelligence Scale--Revised and the Wisconsin Card Sorting Test. Neuropsychological tests of motor and constructional functions were used as control tasks. The patients also underwent magnetic resonance imaging (MRI) studies in which new neuroimaging techniques were used to derive measurements of volume and three-dimensional surface renderings of temporal lobe structures. RESULTS: Spearman rank-order correlations indicated significant associations between poor scores on tests of verbal memory, abstraction, and categorization and reduced volume in temporal lobe structures, including the parahippocampal gyrus and posterior superior temporal gyrus (left and right). By contrast, performance on tests of visual memory and on control tasks was not correlated with MRI temporal lobe abnormalities. CONCLUSIONS: These findings suggest a significant but modest relation between reduced volume in specific temporal lobe regions and neuropsychological deficits in abstraction, categorization, and verbal memory, all of which may reflect a dysfunctional semantic system in schizophrenia.
Adult↗
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.
Adult↗
Attentional cues in chronic schizophrenia: abnormal disengagement of attention.
Posner's (1980) reaction time (RT) paradigm was used to examine the engagement and disengagement operations of visual selective attention in patients with schizophrenia. In the 1st experiment, 14 medicated, chronic schizophrenic subjects (diagnosed by criteria of the Diagnostic and Statistical Manual of Mental Disorders; American Psychiatric Association, 1987) and 15 age-matched normal control subjects made a speeded response to a target preceded by a valid, an invalid, or no cue. Control subjects showed the expected advantage and disadvantage in RT for valid and invalid cues, which suggests intact engagement and disengagement operations. For schizophrenic patients, valid cues also enhanced RT, but invalid cues did not slow RT. Similar results were found in the 2nd experiment. The failure of unpredictable, invalid cues to inhibit RT in chronic schizophrenia may be related to an abnormality in the disengagement operation of selective attention.
Adult↗
Is there P300 asymmetry in schizophrenia?
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Analysis of Variance↗
Application of automated MRI volumetric measurement techniques to the ventricular system in schizophrenics and normal controls.
As an initial approach to computer-automated segmentation of cerebral spinal fluid (CSF) vs. brain parenchyma in MR scans, and the transformation of these data sets into volumetric information and 3D display, we examined the ventricular system in a sample of ten chronic schizophrenics with primarily positive symptoms and 12 normal subjects. While no significant differences were noted between groups on volumetric measures of ventricular brain ratio or lateral ventricle size, normals showed a pattern of left greater than right lateral ventricular volume asymmetry not present in the schizophrenics. Within the schizophrenic group, departure from the normal left greater than right pattern was highly correlated with thought disorder.
Adult↗
Preservation of P300 event-related potential topographic asymmetries in schizophrenia with use of either linked-ear or nose reference sites.
Previous studies of the auditory P300 event-related potential (ERP) from our laboratory have reported a left- greater than right-sided attenuation in medicated chronic schizophrenics compared with normal controls. A possible confound in these studies has been the use of the linked-ear reference (LER), which has been criticized on the grounds that it might either induce or suppress topographic asymmetries. To test the effects of LER on P300 asymmetries in schizophrenia, we recorded ERPs with both LER and a nose reference (NR) in a group of 20 chronic medicated schizophrenics and in group of 20 age-matched normal controls. We here report: (1) confirmation of our previous P300 findings of left temporal scalp region deficit using both LER and NR with a 28-electrode montage; this feature was prominent in the wave form associated with the target stimulus, without the use of the wave form subtractions of our previous studies; (2) no statistically significant topographic differences between the LER and NR for either the schizophrenic or normal subjects; and (3) better performance of the LER in differentiating schizophrenics versus normal controls, due to lower wave form variability. We conclude that the LER is preferable for studies using subject groups and methodology similar to the present study.
Adult↗
Correlations between abnormal auditory P300 topography and positive symptoms in schizophrenia: a preliminary report.
P300 component amplitude in the left temporal scalp region, shown in three previous studies to differentiate normals from schizophrenics, was found to be significantly correlated with the Thought Disorder Index (TDI) and the Scale for the Assessment of Positive Symptoms (SAPS). These correlations occurred primarily in the P300 waveform derived from the Goodin paradigm. These findings suggest a brain processing disturbance in positive symptom schizophrenia that may be reflected by electrophysiological abnormalities detectable in the temporal scalp region.
Adult↗
Thought disorder in the relatives of psychotic patients.
Using the Holzman-Johnston Thought Disorder Index, thought disorder was examined in the first-degree relatives of schizophrenic, manic, and schizoaffective patients. In all three groups, there was a tendency for probands with higher thought disorder to have first-degree relatives with higher thought disorder. Furthermore, the quality of thought disorder in the groups of relatives was similar to that in the groups of probands, although it was clear that the relatives of schizoaffective-manic patients showed the highest amount of thought disorder, which was not found in the proband sample. Although based on a small sample, these findings suggest that amount and type of thought disorder differ not only among medicated patient groups but also among their unmedicated relatives.
Bipolar Disorder↗
Clinical correlations of auditory P200 topography and left temporo-central deficits in schizophrenia: a preliminary study.
A number of studies using nontopographic analyses have reported an amplitude decrement of the auditory P200 component in schizophrenics compared to normal controls. Here we report a topographic analysis of the auditory P200 (204-272 ms; peak to baseline) in chronic medicated schizophrenics (N = 11) and normal controls (N = 18) and the correlation between this measure and clinical symptoms in schizophrenia. Exploratory T-statistic mapping (SPM) and "protected" Hotelling's T-squared contrasts of integrated voltages over the entire scalp showed that schizophrenics' P200 component had diminished amplitude in the left temporo-central region. Furthermore, P200 amplitude in the same scalp region during the experimental condition of counting infrequent tones was highly correlated with negative symptoms in the schizophrenic group.
Adult↗
Two syndromes of schizophrenic psychopathology associated with left vs. right temporal deficits in P300 amplitude. Four case reports.
In four schizophrenic patients, we examined the relationship between clinical course, including neuroleptic response, and the following biological and psychological measures: topography of the auditory P300 event-related potential, computerized tomography (CT), Andreasen's positive and negative symptom scales, the Thought Disorder Index, and a neuropsychological test battery. Two previous studies in our laboratory had shown that schizophrenic patients were differentiated from a matched normal control group by a left temporal scalp region deficit in P300 topography. This present report compares two schizophrenic patients with the typical left temporal P300 topography deficit with two schizophrenic patients with a right temporal P300 topography deficit. The two right temporal deficit patients had more positive symptoms, more thought disorder, more severely impaired functioning, earlier age of onset, poorer response to neuroleptic medications, more diffuse cognitive deficits on a neuropsychological testing battery, and poorer premorbid history than the two left temporal deficit patients. There was some evidence for the presence of more CT abnormalities suggestive of frontal lobe pathology in the right temporal deficit patients.
Adolescent↗