Biomedical subjects

J E McDowell

Publications and source records attributed to J E McDowell.

12 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

Prefrontal, parietal, and temporal cortex networks underlie decision-making in the presence of uncertainty.

Decision-making in the presence of uncertainty, i.e., selecting a sequence of responses in an uncertain environment according to a self-generated plan of action, is a complex activity that involves both cognitive and noncognitive processes. Using functional magnetic resonance imaging, the neural substrates of decision-making in the presence of uncertainty are examined. Normal control subjects show a significant activation of a frontoparietal and limbic neural system during a two-choice prediction task relative to a two-choice response task. The most prevalent response strategy during the two-choice prediction task was "win-stay/lose-shift," where subjects will repeat the previous response if it successfully predicted the stimulus and switch to the alternative response otherwise. Increased frequency of responses that are consistent with this strategy is associated with activation in the superior temporal gyrus. In comparison, increased frequency of response inconsistent with win-stay/lose-shift is associated with parietal cortex activation. These results support the hypothesis that subjects use a frontoparietal neural system to establish a contingency based decision-making strategy even in the presence of random reinforcement.

Adult↗

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.

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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↗

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↗

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

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.

Adult↗

PubMed1995

Abnormality of smooth pursuit eye movement initiation: specificity to the schizophrenia spectrum?

Schizophrenia patients have a deficiency of smooth pursuit eye movement initiation. We addressed whether this deficit is specifically related to a predisposition for schizophrenia. Thirty-two relatives of schizophrenia patients, eight schizotypals, 13 psychiatric comparison, and 33 nonpsychiatric subjects were assessed on smooth pursuit initiation. The nonpsychiatric subjects had significantly higher eye accelerations than did subjects in the other three groups, who did not significantly differ. The relatives were subdivided into three groups: (a) those with a schizophrenia spectrum disorder (n = 4) performed similarly to the schizotypals; (b) those with a major depression history (n = 7) were similar to the psychiatric comparison subjects; and (c) those with no psychiatric history differed from the nonpsychiatric subjects only on 30 degrees/s targets. There was also a significant relationship between offspring and parent eye accelerations to 30 degrees/s targets (r = .476). These results suggest that pursuit initiation deficits may be associated with a nonspecific, genetically transmitted neurological abnormality among schizophrenia spectrum disorder subjects.

Adult↗

PubMed1994

Smooth pursuit in schizophrenia: abnormalities of open- and closed-loop responses.

A sample of 29 schizophrenia patients and 27 nonpsychiatric subjects were tested on measures of open- and closed-loop smooth-pursuit performance. Rashbass step-ramps were used to measure pursuit latency and open-loop gain. Regular ramps were used to calculate frequency and amplitude of both catch-up saccades and square-wave jerks, frequency of anticipatory saccades, and steady-state gain. Schizophrenia patients demonstrated lower open-loop gain than did nonpsychiatric subjects, an effect that was accentuated at faster target velocities. They also showed reduced steady-state gain, but only to 30 degrees/s right-moving targets. There was no evidence of saccadic abnormalities during smooth pursuit among the schizophrenia patients. These patients generated fewer square-wave jerks than did nonpsychiatric subjects for 10 degrees /s left-moving targets. These results suggest an abnormality of smooth-pursuit initiation among patients with schizophrenia.

Adult↗

PubMed1994

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.

Adult↗

PubMedDate not supplied

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 schizophrenia's essential neuropathology.

Brain Mapping↗