Biomedical subjects

B A Clementz

Publications and source records attributed to B A Clementz.

At least 19 recordsLinked to original sources

PubMed2001

Timing and magnitude of frontal activity differentiates refixation and anti-saccade performance.

EEG data were recorded while 10 subjects generated refixation saccades towards a visual target and antisaccades away from a visual cue. Theoretically, the same basic neural circuitry supports refixation and correct anti-saccade performances, with additional activity in primarily dorsolateral prefrontal cortex circuitry supporting antisaccade-associated inhibitory processes. Analyses demonstrated that sensory registration of visual stimuli is similar for refixation and anti-saccade conditions. Increased frontal brain activity at 5 and 15 Hz was observed preceding correct antisaccades when compared to refixation saccades. These analyses provide specific information suggesting that 160-60 ms before saccade generation is the critical period for response inhibition.

Adult↗

PubMed2001

Multichannel electroencephalographic assessment of auditory evoked response suppression in schizophrenia.

Reduced auditory evoked response (AER) suppression in a paired-stimulus paradigm (where suppression equals the difference between S1 and S2 amplitudes divided by S1 amplitude) may index genetic liability for schizophrenia. The present report is a multiple-channel electroencephalographic (EEG) study of AER suppression among 20 normal and 20 schizophrenia subjects. The typical paired-stimulus paradigm was used to evoke time-locked AERs. AER responses were scored at P50 and N100 in the time domain using both single (Cz) and multichannel data (after reduction using principal components analysis, PCA), and were scored for information in the gamma (20-50 Hz) and low-frequency (1-20 Hz) ranges using multichannel information (also after PCA). The time domain analyses demonstrated that schizophrenia patients differ from normal in amplitude of response to the first, but not to the second, stimulus for both P50 and N100. The frequency domain data demonstrated that schizophrenia patients differed from normal on amplitude of the low-frequency response (LFR) to the first, but not to the second, stimulus. The groups did not differ significantly on amplitudes of the gamma-band responses. Group separations were largest for the multichannel N100 and LFR data, with the LFR demonstrating a modestly better risk ratio for differentiating schizophrenia from normal subjects. The present results suggest two novel differences from previous AER suppression studies: (1) S1 amplitudes largely determine differences between normal and schizophrenia groups on AER suppression, and (2) frequency domain analyses may provide important complimentary information when studying AERs in schizophrenia.

Acoustic Stimulation↗

PubMed2001

Response to the first stimulus determines reduced auditory evoked response suppression in schizophrenia: single trials analysis using MEG.

OBJECTIVE: Reduced auditory evoked response (AER) suppression in a paired-stimulus paradigm may index genetic liability for schizophrenia. In most published studies of AER suppression, scores are based on data averaged over numerous stimulus presentations and recorded from few channels. It is unclear whether averaged data are equally representative of single trial responses in normal and schizophrenia subjects. In the present report, we used 148 channel magnetoencephalography to investigate grand-average and single trial responses on AER suppression. METHODS: The typical paired-stimulus paradigm was used to evoke time-locked AERs from 20 normal and 20 schizophrenia patients. Gamma band response (GBR) and low frequency response (LFR) characteristics were measured on grand-averaged and single trial data. Generalized eigenvalue decomposition was used to reduce the multiple channel information to a vector that accounted for the most AER variance for the GBR and LFR. RESULTS: Group performances on grand-average and single trials were similar. A remarkable difference, which replicates previous studies, was that schizophrenia subjects had smaller LFR amplitudes in response to the first stimulus than normal. CONCLUSIONS: These findings are inconsistent with the "poor suppression" theory often used to explain schizophrenia-normal group differences when using the paired-stimulus paradigm.

Acoustic Stimulation↗

PubMed2001

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.

Adult↗

PubMed2001

Saccadic inhibition among schizotypal personality disorder subjects.

Schizotypal personality disorder (SPD) is theoretically part of the schizophrenia spectrum both clinically and neurobiologically. A liability for developing schizophrenia may be associated with dysfunction of dorsolateral prefrontal cortex (DLPFC) and its cortical and/or subcortical circuitry. If so, abnormalities on tasks associated with DLPFC functioning among SPD subjects would support the thesis that SPD is neurobiologically related to schizophrenia. Antisaccade and ocular motor delayed response performance, both of which are ostensibly supported by DLPFC circuitry, were assessed among 29 SPD, 17 schizophrenia, and 25 normal subjects. Generally, the SPD subjects' performance was more similar to normal than to schizophrenia groups. There was evidence, however, for inhibition abnormalities in a subgroup of SPD subjects. Antisaccade performance identified more SPD subjects as "abnormal" than delayed response measures.

Adult↗

PubMed2000

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.

Adolescent↗

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↗