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S F Faux

Publications and source records attributed to S F Faux.

At least 19 recordsLinked to original sources

Increased rate of P300 latency prolongation with age in schizophrenia. Electrophysiological evidence for a neurodegenerative process.

BACKGROUND: The latency of the P300 event-related potential is prolonged in disorders associated with neural damage and degeneration and also becomes prolonged in the course of neural changes that accompany aging. We tested whether the rate of P300 latency increase with age was greater in male schizophrenic patients than in normal subjects because a steeper slope in schizophrenia would suggest a progressive neurodegenerative process. We also evaluated a subset of these subjects for changes in brain volumes as determined by magnetic resonance imaging. METHOD: The P300 component was elicited during an auditory "oddball" paradigm and was recorded from 47 male patients with chronic schizophrenia whose mean age at onset was 22.4 years and from 47 age-, handedness-, and gender-matched control subjects. The relation of P300 latency and amplitude to age within each group was evaluated using correlation and regression analyses. Brain volumes determined via magnetic resonance imaging were evaluated by quantitative volumetric analyses of images acquired with three-dimensional Fourier transform and double echo-spin echo-pulse sequences. RESULTS: The slope of P300 latency on age was steeper for schizophrenic patients than for normal control subjects at midline frontal and central electrode sites. The slope of N100 latency did not differ, implying that the P300 differences were not likely to be due to peripheral hearing loss or damage affecting the initial stages of neural processing. Posterior superior temporal gyrus gray matter volume determined via magnetic resonance imaging significantly diminished with age on the left side in patients with schizophrenia but not on the right side or in controls; these slopes were not, however, statistically significantly different from each other. CONCLUSIONS: These findings provide preliminary evidence that male patients with chronic schizophrenia experience a neurodegenerative process that becomes evident in adulthood and is reflected by the rate of change of P300 latency with age. Whether this process is due to the primary effects of schizophrenia or is secondary to factors associated with schizophrenia's chronic course and treatment remains a question for future investigation.

Acoustic Stimulation

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

Parametric manipulations of auditory stimuli differentially affect P3 amplitude in schizophrenics and controls.

Schizophrenics show P3 amplitude reduction and topographic asymmetries. It is unclear whether the underlying cause of these deficits is primarily functional or structural. This study examined the effect of stimulus discriminability and task instruction on behavioral performance and P3 in schizophrenics and normal control subjects. Stimulus discriminability was manipulated by varying the overall loudness and pitch disparity of the two tones in an auditory oddball paradigm. Instructions emphasized either speed or accuracy of response. Instructions had no significant effects on reaction time, perceptual sensitivity, response bias, or P3. With increased discriminability, however, both groups improved in mean reaction time to targets and perceptual sensitivity. In controls, P3 became earlier and larger with increased stimulus discriminability and was consistently larger over left temporal areas than over right temporal areas. In schizophrenics, P3 latency was related to stimulus discriminability, but amplitude was not; P3 amplitude did not increase with improvement of perceptual sensitivity and reaction time. Unlike normal controls, schizophrenics had a P3 asymmetry at temporal sites, with reduced left-sided voltages. The results are not consistent with a primarily functional cause of P3 aberrations in schizophrenia and are compatible with the hypothesis that P3 amplitude deficits in schizophrenia are related to underlying pathophysiology of temporal lobe generator sites.

Acoustic Stimulation

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

ERP abnormalities during semantic processing in schizophrenia.

To examine the neurophysiological and cognitive characteristics of thought disturbance in schizophrenic patients, we examined the amplitude, latency, and topography of a specific event-related brain potential (ERP), the N400, which is elicited by semantically incongruent words and phrases. Twelve chronic schizophrenic patients and twelve age-matched control subjects read sentences presented visually that had either semantically correct (e.g., 'People pray in their local church') or incorrect endings (e.g., 'Every Sunday morning people pray in their local nest'). Relative to normal controls, schizophrenic patients had significantly reduced N400 amplitude and increased latency to semantically anomalous endings. Additionally, a late positive component which follows the N400 was significantly reduced in amplitude in schizophrenic patients. However, patients and controls did not differ significantly in terms of the topographical distribution of either the N400 or its late positive potential, examined at 28 electrode sites. Thus, N400 topography in schizophrenic patients was not accompanied by the asymmetry which frequently characterizes the well known auditory P300 disturbance in schizophrenic patients. We concluded that these findings may reflect a profound disturbance in attentional processes in chronic schizophrenia.

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

Neuroleptics improve sustained attention in schizophrenia. A study using signal detection theory.

To test the hypothesis that antipsychotic drugs improve attentional processes in schizophrenia, we used a computer-controlled, perceptually degraded continuous performance test (CPT), based on signal detection theory. CPT stimuli were degraded (blurred) to reduce discriminability so that signal detection analysis could be used to distinguish specific attentional processes, as measured by A', from nonspecific factors, as measured by B". Thirteen medicated and 12 neuroleptic-withdrawn schizophrenics visually monitored digits to detect a target under perceptually undegraded and degraded conditions. The principal result was that the neuroleptic-withdrawn patients showed a significant decline in the attention-specific measure of A' over time on task only for the degraded targets, independent of changes in the nonspecific index of B". These results demonstrate that neuroleptic withdrawal may compromise specific attentional processes, namely the ability to sustain attention, as measured by a precise performance task which controlled for nonspecific factors.

Adult

Analysis of scalp voltage asymmetries using Hotelling's T2 methodology.

Topographic mapping procedures are becoming increasingly popular, and scalp voltage asymmetries are a measure of specific interest. Standard statistical techniques in the field to detect voltage asymmetries, "significance probability mapping (SPM)" and repeated-measures analysis of variance (ANOVA) have statistical assumptions which are not in accord with electrophysiological data, and which therefore may lead to serious statistical errors. These limitations and a superior method using multivariate analysis are discussed. This paper provides a sample data set, for illustration of specific computational steps, and to provide an empirical example and reference for the theoretical discussion.

Brain Mapping

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

CT abnormalities in schizophrenia. A preliminary study of their correlations with P300/P200 electrophysiological features and positive/negative symptoms.

Computed tomographic scans were scored blindly for the size of cerebrospinal fluid spaces in a group of nine medicated schizophrenics and a group of nine age-matched normal volunteers without psychiatric or medical problems. Overall, ten of the 18 computed tomography (CT) features measured were significantly enlarged in the schizophrenic group. These abnormal CT features were then correlated with electrophysiological and clinical measurements performed on the schizophrenic patients. Left sylvian fissure enlargement, thought to reflect temporal lobe tissue loss, was highly correlated with a left temporal scalp region feature of the auditory P300 measure (T3 electrode) that differentiated schizophrenics and normals, and both the left sylvian fissure enlargement and the P300 measure were highly correlated with positive symptoms (total score on the Scale for the Assessment of Positive Symptoms). Frontal superficial (cortical) sulcal enlargement was prominent in the schizophrenic group and was highly correlated with another electrophysiological measure, auditory P200, at left central scalp locations. There was no significant correlation between left sylvian fissure and frontal sulcal enlargement within the schizophrenic group, and intercorrelations between CT variables in the schizophrenic group were, in general, less significant than in the control group. Although we should be cautious about generalizability because of the small number of patients, these data are compatible with the hypothesis that different subgroups of schizophrenic pathological features are characterized by different CT, electrophysiological, and clinical presentations.

Adult

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

P300 in schizophrenia: confirmation and statistical validation of temporal region deficit in P300 topography.

Comparison of normal and medicated schizophrenic groups on the auditory P300 component of the event-related potential confirmed our earlier finding of a left temporal deficit in P300 amplitude in schizophrenia. A difference in P300 topography between groups was evident in both color mapping and in grand-averaged waveforms, which was statistically validated by the presence of a group-by-scalp region interaction (p less than 0.05). The left temporal area in schizophrenics was denoted as the region of greatest deficit and of maximal statistical separation (p less than 0.05) relative to normals by t statistic mapping (SPM), Hotelling's T-squared "protected" contrasts of individual scalp regions, and the relative ratio of left scalp amplitudes to right scalp amplitudes. The left temporal scalp region yielding maximal group separation in the previous study also statistically separated the schizophrenic group from the normal group. This feature correctly differentiated 9 of 11 schizophrenics and 7 of 9 controls. These findings are compatible with other histological, metabolic, and electrophysiological studies suggesting temporal lobe abnormality in schizophrenia.

Adult

Differentiation of schizophrenics and normal controls is enhanced by the Goodin subtraction procedure.

The P300 event-related potential as calculated by the Goodin subtraction procedure (P300g) combines attentive and inattentive condition waveforms in order to isolate components specifically related to target stimulus processing. The waveform was compared with the more commonly employed unsubtracted P300 waveform associated with attended infrequent stimuli (P300ia). The P300g produced the largest overall schizophrenic and control group differences in mean integrated amplitude compared with the P300ia. A group by scalp region interaction in the P300g, indicative of group topographic alterations, was also noted which was not present in the unsubtracted P300ia. Furthermore, the P300g pinpointed the single best scalp region (left temporal) for maximal group separation. This temporal asymmetry was found to originate in the inattentive condition waveforms, indicating a possible abnormality in "nonvoluntary" processing. We conclude that combining attentive and inattentive condition waveforms to form the P300g enhanced clinically relevant group differences between schizophrenics and normals compared with the P300ia.

Acoustic Stimulation