Brett A. Clementz

Saccadic system functioning among schizophrenia patients and their first-degree biological relatives

In Study 1, 30 schizophrenia Ss and 27 nonpsychiatric comparison Ss were presented with a fixation task, a visually guided reflexive saccade (prosaccade) task, a predictive tracking task (0.4-Hz square wave), and an antisaccade task. The 2 groups did not differ on either the fixation or prosaccade tasks. Schizophrenia Ss had an increased number of errors on the antisaccade task and had decreased rightward visually guided saccade amplitudes during the predictive tracking task. In Study 2, 13 psychiatric comparison Ss and 32 first-degree biological relatives of the schizophrenia Ss were compared with the schizophrenia Ss and a larger and older sample of nonpsychiatric Ss (n = 33) on the predictive tracking and antisaccade tasks. The groups did not differ on predictive saccadic tracking. The schizophrenia Ss and their first-degree biological relatives made more errors on the antisaccade task than both the nonpsychiatric and psychiatric comparison groups (who did not significantly differ). Results are consistent with the notion that dysfunction of dorsolateral prefrontal cortex, caudate nucleus, or both is related to liability for schizophrenia.

P50 suppression among schizophrenia and normal comparison subjects : a methodological analysis

The present report investigated the relationship between P50 suppression and habituation among 20 schizophrenia and 20 normal comparison subjects. Subjects were presented with clicks delivered over headphones in a S1-S2 paradigm (clicks were separated by 500 msec; average intertrial interval was 8 sec). There were 60 total trials; the data were analyzed separately for the first and second 30 trials. The groups did not differ either on the number of usable trials or on the morphology of their P50 responses. Consistent with previous reports, schizophrenia patients demonstrated deficient P50 suppression. The overall suppression effect was not due to a group difference on S1 P50 amplitudes, but was associated with schizophrenia patients having smaller S1-S2 P50 amplitude difference scores than normal comparison subjects. Furthermore, the suppression effect appears to be more pronounced during the first than during the second block of trials. Thus, it may be important to evaluate changes in P50 responses over time among schizophrenia and normal comparison subjects.

Clinical and biological concomitants of resting state EEG power abnormalities in schizophrenia

BACKGROUND This study investigated the clinical and biological concomitants of electroencephalogram power abnormalities in schizophrenia. METHODS We examined the power characteristics of resting electroencephalograms in 112 schizophrenic patients. Also collected were measures of psychotic symptomatology, brain morphology, ocular motor functioning, electrodermal activity, and nailfold plexus visibility. Seventy-eight nonschizophrenic psychosis patients (e.g., mood disorder patients with psychosis) and 107 nonpsychiatric control subjects were included for comparison. RESULTS Schizophrenic patients whose electroencephalograms were characterized by augmented low-frequency power and diminished alpha-band power had more negative symptoms, larger third ventricles, larger frontal horns of the lateral ventricles, increased cortical sulci widths, and greater ocular motor dysfunction compared with schizophrenic patients without these electroencephalogram characteristics. In nonschizophrenic psychosis patients, augmented low-frequency and diminished alpha-band powers failed to be associated with any clinical or biological indices. CONCLUSIONS Results suggest that clinical and biological concomitants of low-frequency and alpha-band power abnormalities in schizophrenia are unique, perhaps indicating the presence of thalamic and frontal lobe dysfunction.

Multiple site evaluation of P50 suppression among schizophrenia and normal comparison subjects

Normally, when two brief, non-startling auditory stimuli are presented 500 ms apart, with long (e.g., 10 s) interpair intervals, the positive potential occurring approx. 50 ms after the first stimulus (P50) is relatively large, and the P50 to the second stimulus is smaller. In schizophrenia patients, however, the P50 to the second stimulus is larger than normal. In this study, 36 schizophrenia and 36 normal comparison subjects were tested in a two-click paradigm. Data were recorded from six electrode locations (F3, Fz, F4, C3, Cz, C4). The results support the hypothesis that schizophrenia patients have poor P50 suppression that is not an artifact of differential P50 wave morphology or differences in the number of usable trials between groups. In addition, the vertex location alone (Cz) was equal to, if not better than, any combination of sites for differentiating between groups. These results support the use of the Cz site alone in most investigations of P50 suppression deficits among schizophrenia spectrum patients. Further work investigating the neuropathological correlates of poor P50 suppression among schizophrenia patients by recording from multiple electrode locations, however, could be helpful.

Linkage of a composite inhibitory phenotype to a chromosome 22q locus in eight Utah families

Eight Utah multigenerational families, each with three to six cases of schizophrenia, were phenotyped with two specific measures of inhibitory neurophysiological functioning, P50 auditory sensory gating (P50), and antisaccade ocular motor performance (AS). A genomewide linkage analysis was performed to screen for loci underlying a qualitative phenotype combining the P50 and AS measures. For this composite inhibitory phenotype, the strongest evidence for linkage was to the D22s315 marker on chromosome 22q (lod score = 3.55, theta = 0) under an autosomal dominant model. Simulation analyses indicate that this 3.55 lod score is unlikely to represent a false positive result. Lod scores were 2.0 or greater for markers flanking D22s315. A nonparametric linkage (NPL) analysis of the chromosome 22 data showed evidence for allele sharing over the broad region surrounding D22s315 with a maximum NPL score of 3.83 (p = .002) for all pedigrees combined.

Eye tracking dysfunction in schizophrenia: characterization of component eye movement abnormalities, diagnostic specificity, and the role of attention.

To characterize oculomotor components and diagnostic specificity of eye tracking abnormalities in schizophrenia, we examined a large consecutively admitted series of psychotic patients and matched controls. The most common abnormality in schizophrenic patients was low gain (slow) pursuit eye movements (47% of cases). Pursuit and saccadic eye movement abnormalities were no more severe in schizophrenic Ss than in those with affective psychoses, except that high rates of catch-up saccades were unique to schizophrenic Ss (17% of cases). These findings indicate that impaired pursuit eye movements are a major cause of eye tracking impairments in schizophrenia, that tracking dysfunctions commonly occur in affective psychoses, and that markedly high rates of catch-up saccades during eye tracking may be specific to schizophrenia.

Psychophysiological measures of (dis)inhibition as liability indicators for schizophrenia

Two psychophysiological measures, poor suppression of midlatency auditory-evoked responses in a paired stimulus paradigm and ocular motor abnormalities, may index genetic liability for schizophrenia. An important feature of these measures is that both patients and their nonpsychotic relatives exhibit basically the same performance. These measures may be successful endophenotypes for schizophrenia because they assess poor response inhibition associated with dysfunction of dorsolateral prefrontal cortex circuitry. Data bearing on this hypothesis are reviewed, and it is posited that assessment of the auditory-evoked gamma band response and saccade measures of inhibitory abilities are the most valid behavioral measures of schizophrenias neuropathological correlates. The extant data suggest that psychophysiological studies of schizophrenia can provide consistent and theoretically meaningful information for localizing neuropathology and for assessing the genetics of this complex disorder.

Behavioral and brain imaging studies of saccadic performance in schizophrenia

Data are reviewed from a series of saccadic studies demonstrating that schizophrenia subjects have normal performance on some types, and abnormal performance on other types, of tasks. Normal refixation saccade characteristics and BOLD signal change among schizophrenia subjects suggest that basic saccade generating circuitry is functionally intact among these subjects. Schizophrenia patients and their relatives, however, demonstrate difficulty with saccadic inhibition, a function ostensibly mediated by DLPFC circuitry. We review additional evidence for saccadic inhibition being associated with prefrontal circuitry provided by EEG and fMRI data. Minimum norm analysis of EEG data suggests that dipolar activity preceding correct antisaccades occurred preferentially in prefrontal cortex. Furthermore, there is an indication from the fMRI data that prefrontal activity may be increased in normal, but not in schizophrenia, subjects during antisaccade tasks. These data suggest that a research program relying on multiple functional imaging technologies may be helpful for furthering our understanding of schizophrenias essential neuropathology.

Ocular-Motor Delayed-Response Task Performance among Schizophrenia Patients

Twenty schizophrenia patients and 20 nonpsychiatric subjects were presented with an ocular-motor delayed-response task. Schizophrenia patients generated fewer memory-guided saccades which were characterized by increased latency and decreased gain relative to the nonpsychiatric subjects. In addition, the patients generated an increased frequency of reflexive (made to the initial cue) and anticipatory (made during the delay period) errors. The results are most consistent with hypothesized pathology of prefrontal cortex among schizophrenia patients.

Ocular motor delayed-response task performance among patients with schizophrenia and their biological relatives

Schizophrenia patients and their relatives have saccadic abnormalities characterized by problems inhibiting a response. The dorsolateral prefrontal cortex and its associated circuitry ostensibly mediate inhibition and support correct delayed response performance. In this context, two components of delayed response task performance are of interest: memory saccade metrics and error saccades made during the delay. To evaluate these variables, an ocular motor delayed response task was presented to 23 schizophrenia patients, 25 of their first-degree biological relatives, and 19 normal subjects. The measure that best differentiated groups was an increased frequency of error saccades generated during the delay by schizophrenia subjects and relatives. Decreased memory saccade gain also characterized patients and relatives. The similar pattern of results demonstrated by the patients with schizophrenia and their relatives suggests that performance on ocular motor delayed response tasks, either alone or in combination with other saccadic variables, may provide useful information about neural substrates associated with a liability for developing schizophrenia.