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Biomedical subjects

B A Clementz

Publications and source records attributed to B A Clementz.

At least 19 recordsLinked to original sources
PubMed2000

Normal P50 suppression in schizophrenia patients treated with atypical antipsychotic medications.

OBJECTIVE: Patients with schizophrenia have deficits in attention, cognition, and information processing. Measures such as P50 suppression are used to study cognitive and attentional dysfunction among these patients. P50 suppression is an operational measure of sensory gating that can be assessed by averaging electroencephalographic responses to multiple pairs of auditory clicks separated by 500 msec. Normally, the P50 response to the second click is smaller than the response to the first click. Many studies have demonstrated that schizophrenia patients have deficient P50 suppression, meaning that the difference between the first and second clicks is not as large as normal. Atypical antipsychotic medications may have superior clinical efficacy for negative symptoms and cognitive deficits. It is important, therefore, to evaluate the effects of atypical antipsychotic medications on measures such as P50 suppression. METHOD: P50 suppression of 13 patients with schizophrenia receiving clinically effective doses of clozapine, olanzapine, or risperidone (classified as atypical antipsychotic medications) was compared to that of 13 patients receiving conventional antipsychotic medications. RESULTS: The patient groups did not differ on clinical or demographic measures. The patients receiving atypical antipsychotic medications had normal-range P50 suppression (mean=72%). In contrast, the patients receiving typical antipsychotic medications had dramatically lower P50 suppression (mean=27%). CONCLUSIONS: The results support the hypothesis that patients treated with atypical antipsychotic medications have normal P50 measures of sensory gating. Longitudinal within-subjects studies are warranted to clarify the mechanisms mediating this effect.

Acoustic Stimulation↗
PubMed1999

Hemispheric differences on auditory evoked response suppression in schizophrenia.

Using binaural stimuli, schizophrenia subjects have worse auditory evoked response (AER) suppression than normals in a paired-click paradigm. In this study we investigated hemispheric differences in AER suppression between groups using monaural and binaural stimulus presentation. Auditory evoked responses from 12 schizophrenia and 12 normal subjects were recorded with a 148-channel whole-head biomagnetometer. One hundred and twenty pairs of clicks were presented in three counterbalanced blocks (left, right, binaural). With monaural stimuli, patients had worse M100 suppression than normals in ipsilateral (effect size -2.13) but not in contralateral hemisphere (effect size -0.43). The groups did not differ on gamma band response suppression. Overall, the best group separations were obtained with binaural stimulus presentation on M100 suppression (effect size -4.14).

Acoustic Stimulation↗
PubMed1999

Measuring liability for schizophrenia using optimized antisaccade stimulus parameters.

The ability to identify unaffected gene carriers within families may be crucial to the success of schizophrenia genetics studies. Data collected from three family samples (N = 365) demonstrated that poor antisaccade performance is an exceptionally promising indicator of liability for schizophrenia. A particular antisaccade task version provides large separations (5-6 sigma) between proband and normal groups. Poor antisaccade performance alone correctly identified 70% of patients in California, Utah, and Micronesia schizophrenia samples. Twenty-five to 50% of these patients' nonpsychotic first-degree relatives also had poor antisaccade performance, yielding risk ratios around 20:1 for simplex and 50:1 for multiplex schizophrenia families. Poor antisaccade performance is associated with dorsolateral prefrontal cortex pathology, suggesting that dysfunction of this circuitry also may predispose individuals to developing this disease.

Adult↗
PubMed1999

Saccadic performance characteristics and the behavioural neurology of Tourette's syndrome.

OBJECTIVE: To better understand the neuropathological correlates of Tourette's syndrome (TS), measures of saccadic eye movement performance were examined among patients with TS. METHODS: A case-control design was used. Twenty one patients with DSM-IV TS (mean age 40.6 years (SD 11.0); 38% female) mainly recruited from UCSD Psychiatry Services, and a community based sample of 21 normal subjects (mean age 34.6 years (SD 13.4); 43% women) participated in this study. Participants were administered ocular motor tasks assessing visual fixation, and the generation of prosaccades, predictive saccades, and antisaccades. Saccadic reaction time, amplitude, duration, and mean and peak velocity were computed. Intrusive saccades during visual fixation and the proportion of correct antisaccade responses were also evaluated. RESULTS: The groups had similar visual fixation performance. Whereas patients with TS generated prosaccades with normal reaction times and amplitudes, their saccade durations were shorter and their mean velocities were higher than in normal subjects. During a prosaccade gap task, patients with TS exhibited an increased proportion of anticipatory saccades (RTs<90). The proportion of "express" saccades (90<RTs<135) did not differ between groups. Patients with TS had fewer correct antisaccade responses than did normal subjects, an effect accounted for by 19% of the patients. Antisaccade reaction times among patients with TS were increased during an overlap version of the task. CONCLUSION: These findings suggest that TS mildly affects the ocular motor control circuitry associated with saccade inhibition.

Adolescent↗
PubMed1998

Failure of dominant left-hemispheric activation to right-ear stimulation in schizophrenia.

Schizophrenia is associated with an absence of the lateralizations that typify the human brain. Previous evidence emphasized structural changes, particularly reduced asymmetry in extension and surface of the planum temporale, although gross structural deviations occur only in a minority of patients. The present study describes an absence of lateralization on a robust functional measure that characterized schizophrenia patients: healthy subjects but not schizophrenics displayed a contralateral left-hemispheric dominance of the auditory evoked magnetic field to right-ear auditory stimulation. Absence of contralateral dominance in response to auditory stimuli among schizophrenia patients may indicate a failure to establish unequivocal left-hemispheric dominance of the phonological loop as hypothesized by Crow.

Acoustic Stimulation↗
PubMed1998

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.

Adult↗
PubMed1998

Fixation stability among schizophrenia patients.

Twenty-four schizophrenia and 26 normal subjects were presented targets for fixation at +/-17.5 degrees and 0 degrees of visual angle. The manner in which stimuli were presented allowed us to evaluate for the presence of gaze-evoked and rebound drifts, and for frequency of saccades at both eccentric and central fixation. Schizophrenia patients and normal subjects had remarkably similar performance regardless of stimulus condition. These results suggest that the gaze-holding apparatus is functioning normally among schizophrenia patients, a finding that is not easily attributable to either medication effects and/or low statistical power. These data are another indication that schizophrenia patients have specific, not general, abnormalities of ocular motor control.

Adult↗
PubMed1998

Poor P50 suppression among schizophrenia patients and their first-degree biological relatives.

OBJECTIVE: This study's goal was to replicate the finding that family members of schizophrenia patients show poor P50 suppression during a paired-click auditory evoked response paradigm. METHOD: The paired-click paradigm was used to test 44 schizophrenia patients, 60 of their clinically unaffected first-degree relatives, and 45 normal subjects. Two clicks (83 dB[A] over a 60-dB[A] white noise background) separated by 500 msec were presented 60 times to all subjects. P50 responses to the first and second clicks were selected from the digitally filtered data by using standard methods and the Cz recording site. RESULTS: The schizophrenia patients had smaller P50 responses to click 1 than either their relatives or the normal subjects; the patients and their relatives, who did not significantly differ, had larger P50 responses to click 2 than the normal subjects. Schizophrenia patients had worse P50 suppression than either their family members or the normal subjects; the patients' family members had worse P50 suppression than the normal subjects. CONCLUSIONS: Family members of schizophrenia patients have worse P50 suppression than normal subjects. To the authors' knowledge, this is the first demonstration independent of the group associated with the University of Colorado that schizophrenia patients' family members have poor P50 suppression. This result is intrinsically important, perhaps especially because a recent report suggests genetic linkage of poor P50 suppression to the cholinergic receptor's alpha7 nicotinic subunit.

Acoustic Stimulation↗
PubMed1998

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 schizophrenia's 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.

Evoked Potentials, Auditory↗
PubMed1997

The gamma band response may account for poor P50 suppression in schizophrenia.

The relationship between gamma band response (GBR) and P50 suppression was investigated among 10 DSM-IV schizophrenia patients and 10 normal comparison subjects using neuromagnetic and electrical recordings. In a paired-click paradigm, the neuromagnetic GBR and M100 suppression data improved schizophrenia-normal group separations over the typical electrical, vertex-recorded P50 suppression measure. The neuromagnetic GBR was also superior to the magnetic equivalent of P50 (M50) for discriminating schizophrenia and normal subjects. Our data are consistent with the hypothesis that P50 may be a subcomponent of the GBR, and that P50 suppression may be a proxy for GBR suppression. Measurement of the GBR should be given consideration as another, and perhaps better, means for evaluating auditory-evoked response abnormalities among schizophrenia patients.

Adult↗
PubMed1997

Season of birth and electroencephalogram power abnormalities in schizophrenia.

To determine the association between season of birth and electroencephalogram (EEG) power abnormalities in schizophrenia, this study examined the resting EEGs of 28 winter-born and 81 nonwinter-born schizophrenia patients. Eighteen winter-born and 58 nonwinter-born nonschizophrenic psychosis patients (e.g., bipolar disorder patients with psychotic features), and 97 normal subjects were also studied. Compared to normal subjects, nonwinter-born schizophrenia patients had augmented low-frequency power and diminished alpha band power, but winter-born schizophrenia patients failed to have any EEG power abnormalities. Nonwinter-born nonschizophrenic psychosis patients had the same low-frequency and alpha band power abnormalities as nonwinter-born schizophrenia patients. The winter-born non-schizophrenic psychosis group failed to show any EEG power abnormalities. The results of this study indicate that in psychosis the functional characteristics of the brain vary depending on the season in which a person is born. Low-frequency and alpha band EEG power abnormalities may help distinguish psychosis stemming from a seasonally varying pathogen from psychosis of other etiologies.

Bipolar Disorder↗
PubMed1997

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.

Arousal↗
PubMed1997

The effect of fixation condition manipulations on antisaccade performance in schizophrenia: studies of diagnostic specificity.

This series of studies evaluated (1) hypotheses that poor antisaccade performance is attributable to confounding variables (e.g., visual attention deficits, incomplete understanding of task demands) and (2) the specificity of poor antisaccade performance to schizophrenia. In addition to self-correcting errors before being cued to do so, schizophrenia patients also showed the expected saccadic reaction time changes to fixation condition manipulations: decreased latencies for gap and increased latencies for overlap trials. These data suggest that schizophrenia patients are adequately engaged in and understand the antisaccade task. Schizophrenia patients made fewer correct antisaccade responses than other psychiatric patients (obsessive-compulsive and bipolar disorder) and normal subjects. The first-degree relatives of schizophrenia patients also generated a decreased proportion of correct antisaccade responses compared with normal subjects. For schizophrenia patients who performed below the range of normal subjects, 26% of their relatives also performed below the normal range. Conversely, patients who performed normally did not have a single poor-performing relative. These data suggest that increased antisaccade error rates may index a liability for schizophrenia within a subset of families.

Adult↗
PubMed1997

Characteristics of open- and closed-loop smooth pursuit responses among obsessive-compulsive disorder, schizophrenia, and nonpsychiatric individuals.

Twenty obsessive-compulsive disorder patients and comparison samples of 20 schizophrenia and 20 nonpsychiatric individuals were presented with (a) a step-ramp task designed to measure smooth pursuit initiation and (b) a regular ramp task designed to measure steady-state tracking performance. Obsessive-compulsive disorder and non-psychiatric individuals had statistically similar pursuit reaction time and average eye accelerations during the open-loop interval. They also had similar closed-loop performance. Schizophrenia patients, however, had delayed pursuit reaction times and reduced eye acceleration during the last 60 ms of the open-loop interval. These findings suggest that brain regions supporting smooth pursuit performance are unimpaired among obsessive-compulsive disorder patients. Furthermore, the deficits found in the schizophrenia patients replicate and extend the results of previous smooth pursuit studies.

Adult↗
PubMed1996

The ability to produce express saccades as a function of gap interval among schizophrenia patients.

The ability to produce "express saccades" is associated with adequate functioning of saccadic burst cells in the superior colliculus. Saccadic burst cells appear to be under the inhibitory control of both the collicular and the dorsolateral frontal fixation systems. Twenty schizophrenia patients and 20 nonpsychiatric subjects were presented a saccade task that included five different gap intervals (0, 100, 200, 300, and 400 ms) between fixation point offset and peripheral target onset (at +/-4 degrees). All subjects generated the highest frequency of express saccades in trials with a gap interval of 200 ms. Schizophrenia patients had an increased frequency of express saccades across gap intervals, especially for targets presented in the right visual field. The groups did not differ in the percentages of anticipatory saccades or saccadic amplitudes. These results suggest that schizophrenia patients' saccadic burst cells in the superior colliculus are functioning adequately, but may be consistent with dysfunction of dorsolateral frontal cortex and/or its interconnecting subcortical circuitry.

Humans↗
PubMed1996

Timing and amplitude of saccades during predictive saccadic tracking in schizophrenia.

Schizophrenia patients have ocular motor abnormalities. It has been hypothesized that these abnormalities are associated with frontal eye field pathology. If so, schizophrenia patients should have difficulties decreasing saccadic reaction times in response to predictably moving targets. To evaluate the frontal eye field hypothesis, 25 schizophrenic and 26 nonpsychiatric subjects completed predictive saccadic tracking tasks. The groups demonstrated equivalent decreases in saccadic reaction times over consecutive trials. Schizophrenia patients, however, had faster reaction times and shorter amplitude saccades than nonpsychiatric subjects. The shorter amplitude saccades were made regardless of reaction time, perhaps an antipsychotic medication effect. The reaction time results are unlikely to be an effect of treatment with antipsychotic medication and are inconsistent with the hypothesis that schizophrenia patients have frontal eye field pathology.

Adult↗
PubMed1996

Saccades to moving targets in schizophrenia: evidence for normal posterior cortex functioning.

People diagnosed with schizophrenia have abnormalities of smooth pursuit eye movement initiation that could be attributable to dysfunction of posterior cortical areas and/or the smooth pursuit regions of frontal cortex. To evaluate whether schizophrenia patients' pursuit initiation performance is most consistent with pre- or postrolandic neuropathology, 25 schizophrenia patients and 25 nonpsychiatric individuals were presented step-ramp stimuli moving either away from or toward the fovea. Schizophrenia and nonpsychiatric individuals did not differ on position error of saccades to moving targets, suggesting that the schizophrenia patients did not have general difficulty with motion perception. During the initial 100 ms of smooth pursuit, however, schizophrenia patients had significantly slower eye velocities than did nonpsychiatric individuals. These results suggest that schizophrenia patients' smooth pursuit abnormalities are not associated with neuropathology of posterior cortical areas.

Adult↗