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D S Manoach

Publications and source records attributed to D S Manoach.

16 recordsLinked to original sources
PubMed2005

The use of working memory for task prediction: what benefits accrue from different types of foreknowledge?

The assumption that the deployment of executive processes invariably improves task performance is implicit to cognitive theory. In particular, working memory can be used to retain and update historical information about predictable trial sequences (foreknowledge) so that subjects can anticipate and prepare for the upcoming trial more effectively. We review the effects of different types of foreknowledge on response accuracy and latency, particularly in relation to experiments investigating saccadic eye movements in humans. While it is possible to make all aspects of an impending trial predictable, varying the predictability of different components of the trial independently can reveal which cognitive operations are potentially modifiable by foreknowledge. These operations include stimulus processing, retrieval of task-set rules, and response preparation, among others. The available data suggest that, while response preparation can be completed and the response even executed before the stimulus appears (i.e. anticipation) when the subject possesses complete task-foreknowledge (knowing both the stimulus to appear and the response required), foreknowledge of the task-set alone does not permit advance configuration of the task-set rules. A taxonomy for foreknowledge is proposed, including foreknowledge for timing, stimulus, set, response, and task. Work on differentiating these effects in neurophysiology, neuroimaging, and neuropsychology is still in the early stages.

Animals↗
PubMed2004

Deficient saccadic inhibition in Asperger's disorder and the social-emotional processing disorder.

BACKGROUND: Both Asperger's disorder and the social-emotional processing disorder (SEPD), a form of non-verbal learning disability, are associated with executive function deficits. SEPD has been shown to be associated with deficient saccadic inhibition. OBJECTIVE: To study two executive functions in Asperger's disorder and SEPD, inhibition and task switching, using a single saccadic paradigm. METHODS: 22 control subjects and 27 subjects with developmental social processing disorders-SEPD, Asperger's disorder, or both syndromes-performed random sequences of prosaccades and antisaccades. This design resulted in four trial types, prosaccades and antisaccades, that were either repeated or switched. The design allowed the performance costs of inhibition and task switching to be isolated. RESULTS: Subjects with both Asperger's disorder and SEPD showed deficient inhibition, as indicated by increased antisaccade errors and a disproportionate increase in latency for antisaccades relative to prosaccades. In contrast, task switching error and latency costs were normal and unrelated to the costs of inhibition. CONCLUSIONS: This study replicates the finding of deficient saccadic inhibition in SEPD, extends it to Asperger's disorder, and implicates prefrontal cortex dysfunction in these syndromes. The finding of intact task switching shows that executive function deficits in Asperger's disorder and SEPD are selective and suggests that inhibition and task switching are mediated by distinct neural networks.

Adult↗
PubMed2002

Cognitive slowing in Parkinson's disease resolves after practice.

OBJECTIVE: To assess the effect of dopaminergic repletion on working memory in Parkinson's disease. METHODS: The role of dopaminergic state on working memory in patients with Parkinson's disease was determined using the Sternberg item recognition paradigm, a continuous performance task that dissociates the motor and cognitive components of response time. Ten patients with Parkinson's disease were tested in an "on" state (on dopaminergic drug treatment) and a practical "off" state in two sessions held one week apart in counterbalanced order; 10 controls matched for age and education were studied at the same time points. RESULTS: Patients with Parkinson's disease showed impaired working memory, independent of motor slowing. During session 1, the performance of the patients was worse than the controls, regardless of dopaminergic state. The patients showed a significant improvement in the cognitive component of task performance during the second session, such that they no longer differed from the controls. The performance of the control subjects remained stable over the two sessions. CONCLUSIONS: Working memory performance of patients with Parkinson's disease did not change in association with dopaminergic state; rather, the performance improved over time. The pattern of improvement over time suggests a delay in proceduralising the task, similar to the deficits shown by such patients in procedural learning of other tasks.

Aged↗
PubMed2001

Test-retest reliability of a functional MRI working memory paradigm in normal and schizophrenic subjects.

OBJECTIVE: Repeated functional magnetic resonance imaging (fMRI) studies of schizophrenic subjects may identify brain activity changes in response to interventions. To interpret the findings, however, it is crucial to know the test-retest reliability of the measures used. METHOD: The authors scanned seven normal subjects and seven schizophrenic subjects on two occasions during performance of a working memory task. They quantified the reliability of task performance and brain activation. RESULTS: In both groups, task performance was reliable, and all a priori regions were activated in group-averaged test and retest data. In individual schizophrenic subjects, however, indices of cognitive activation were not reliable across sessions. Normal subjects showed reasonable reliability of activation. CONCLUSIONS: Even given reliable task performance, stable clinical status, and a stable pattern of group-averaged activation, individual subjects showed unreliable brain activation. This suggests that repeated fMRI studies of schizophrenia should control for sources of variation, both artifactual and intrinsic.

Adult↗
PubMed2000

Schizophrenic subjects show aberrant fMRI activation of dorsolateral prefrontal cortex and basal ganglia during working memory performance.

BACKGROUND: Working memory (WM) deficits in schizophrenia have been associated with dorsolateral prefrontal cortex (DLPFC) dysfunction in neuroimaging studies. We previously found increased DLPFC activation in schizophrenic versus normal subjects during WM performance (Manoach et al 1999b). We now have investigated whether schizophrenic subjects recruit different brain regions, particularly the basal ganglia and thalamus, components of frontostriatal circuitry thought to mediate WM. METHODS: We examined regional brain activation in nine normal and nine schizophrenic subjects during WM performance using functional magnetic resonance imaging. Subjects performed a modified version of the Sternberg Item Recognition Paradigm that included a monetary reward for correct responses. We compared high and low WM load conditions to each other and to a non-WM baseline condition. We examined activation in both individual subjects and averaged group data. RESULTS: Relative to normal subjects, schizophrenic subjects exhibited deficient WM performance, at least an equal magnitude of right DLPFC activation, significantly greater left DLPFC activation, and increased spatial heterogeneity of DLPFC activation. Furthermore, only the schizophrenic group activated the basal ganglia and thalamus, even when matched for task performance with the normal group. CONCLUSIONS: Aberrant WM performance and brain activation in schizophrenia may reflect dysfunction of frontostriatal circuitry that subserves WM. Future studies will elucidate the contribution of the anatomical components of this circuitry to WM deficits.

Adult↗
PubMed2000

Perceptual organization in schizophrenia: the processing of symmetrical configurations.

The hypothesis that the perceptual organization dysfunction of patients with poor premorbid schizophrenia is due to a deficit in global visual sensory store processing was tested by assessing their ability to process symmetrical configurations that develop early and have strong prepotent structures. Two same-different judgment tasks in which performance varies as a function of the symmetrical organization and task demands were administered to participants with good and poor premorbid schizophrenia, those with mood disorders, and normal controls. Like the other groups, poor premorbid schizophrenics' latency and error response patterns closely paralled the a priori model of adequate processing. The results support their competence in perceptually processing symmetrical configurations and disconfirm the hypothesis that their input deficiencies represent a general deficiency in all forms of perceptual organization. The implications for specifying their early input dysfunction are discussed.

Adolescent↗
PubMed1999

Schizophrenic subjects activate dorsolateral prefrontal cortex during a working memory task, as measured by fMRI.

BACKGROUND: Neuroimaging studies of schizophrenic subjects performing working memory (WM) tasks have demonstrated a relative hypoactivity of prefrontal cortex compared with normal subjects. METHODS: Using functional magnetic resonance imaging (fMRI), we compared dorsolateral prefrontal cortex (DLPFC) activation in 12 schizophrenic and 10 normal subjects during rewarded performance of a WM task. Subjects performed a modified version of the Sternberg Item Recognition Paradigm (SIRP), a continuous performance, choice reaction time (RT) task that requires WM. We compared a high WM load condition with a nonWM choice RT condition and with a low WM load condition. RESULTS: Schizophrenic subjects performed the tasks better than chance but worse than normal subjects. They showed greater activation than normal subjects in the left DLPFC but did not differ in the right DLPFC or in the control region. In the schizophrenic group, left DLPFC activation was inversely correlated with task performance, as measured by errors. CONCLUSIONS: These findings contrast with previous studies that demonstrated task-related hypofrontality in schizophrenia. Task parameters that may contribute to this difference are discussed. We hypothesize that the performance and activation differences we observed are also manifestations of prefrontal dysfunction in schizophrenia. They reflect inefficient functioning of the neural circuitry involved in WM.

Adult↗
PubMed1997

Deficient antisaccades in the social-emotional processing disorder.

We investigated whether adolescents and adults with the developmental social-emotional processing disorder (SEPD) exhibit deficits in visual attention, as measured by eye movements, when compared with dyslexic and normal control subjects. On the antisaccade task, subjects with SEPD made more errors than either control group and were the only group to show a decrease in performance accuracy compared with prosaccade. This deficit in inhibiting reflexive shifts of attention and gaze suggests that individuals with SEPD have dysfunction of the prefrontal component of the right hemisphere dominant network for spatially directed attention.

Adolescent↗
PubMed1997

Prefrontal cortex fMRI signal changes are correlated with working memory load.

We investigated whether a nonspatial working memory (WM) task would activate dorsolateral prefrontal cortex (DLPFC) and whether activation would be correlated with WM load. Using functional magnetic resonance imaging we measured regional brain signal changes in 12 normal subjects performing a continuous performance, choice reaction time task that requires WM. A high WM load condition was compared with a non-WM choice reaction time control condition (WM effect) and a low WM load condition (load effect). Significant changes in signal intensity occurred in the DLPFC, frontal motor regions and the intraparietal sulcus (IPS) in both comparisons. These findings support the role of DLPFC and IPS in WM and suggest that signal changes in DLPFC correlate with WM load.

Adult↗
PubMed1996

Absence of neglect for mental representations during the intracarotid amobarbital procedure.

BACKGROUND: The unilateral suppression of right-hemisphere electrophysiological activity during the intracarotid amobarbital procedure results in left neglect on visuomotor search tasks. OBJECTIVE: To investigate whether right-hemisphere inactivation during the intracarotid amobarbital procedure also results in left neglect of the mental representation of a remembered scene. DESIGN: Before the intracarotid amobarbital procedure, 16 subjects were asked to draw a room from their homes. Following the right-hemisphere injection, subjects wee tested for the presence of left neglect of extrapersonal space using a Random Letter Cancellation Test. To test for neglect of the mental representation of a remembered scene, they were then asked to report items from the room they had drawn. RESULTS: While 10 of the 16 subjects showed left neglect on the Random Letter Cancellation Test, only one subject showed left neglect of the mental representation. The other 15 subjects recalled approximately equal numbers of items from the left and the right hemispaces. CONCLUSIONS: These results replicate previous findings of left neglect of extra personal space during the intracarotid amobarbital procedure and fail to show concurrent neglect for mental representations. They provide further evidence for the multiplicity and dissociability of the behavioral manifestations of neglect.

Amobarbital↗
PubMed1996

D-cycloserine added to clozapine for patients with schizophrenia.

OBJECTIVE: The effects of D-cycloserine added to clozapine were assessed and compared with previous results for D-cycloserine plus conventional neuroleptics. METHOD: Ten schizophrenic outpatients receiving clozapine entered consecutive 2-week trials of placebo and D-cycloserine at 5, 15, 50, and 250 mg/day. Clinical evaluations were videotaped and scored by a rater blind to the sequence of assessments. RESULTS: There was a significant dose effect of D-cycloserine on scores on the Scale for the Assessment of Negative Symptoms (SANS); the 50-mg dose produced a mean 21% increase in SANS score. The patients had significantly higher baseline serum glutamate concentrations than the patients receiving typical neuroleptics in the previous trial. Baseline glutamate level and change in glycine level significantly correlated with response of negative symptoms to 50-mg D-cycloserine. CONCLUSIONS: The improvement of negative symptoms with D-cycloserine previously observed in patients receiving typical neuroleptics did not occur in patients treated with clozapine.

Adult↗
PubMed1995

Dose-finding trial of D-cycloserine added to neuroleptics for negative symptoms in schizophrenia.

OBJECTIVE: The authors conducted a dose-finding study of D-cycloserine, a partial agonist at the glycine site of the N-methyl-D-aspartate subtype of the glutamate receptor, added to conventional neuroleptics for schizophrenic patients with prominent negative symptoms. METHOD: Nine patients with schizophrenia completed consecutive 2-week trials of placebo and four doses of D-cycloserine. Clinical assessments were videotaped and were scored by a rater who was blind to temporal sequence. RESULTS: D-Cycloserine at a dose of 50 mg/day produced a significant reduction (mean = 21%, SD = 28%) in negative symptoms and significantly improved reaction time as measured by Sternberg's Item Recognition Paradigm, a test mediated in part by prefrontal cortex. CONCLUSIONS: This preliminary evidence suggests that D-cycloserine may improve negative symptoms and cognitive deficits over a narrow dose range when added to conventional antipsychotic agents.

Adult↗
PubMed1994

Handedness is related to formal thought disorder and language dysfunction in schizophrenia.

The handedness of 29 schizophrenics, 42 manic-depressives, and 25 normal controls was examined in relation to formal thought disorder and language dysfunction. Subjects demonstrated hand preference (Preference Index) and also performed four tasks of manual proficiency. On each of the four proficiency tasks a lateral proficiency score was computed to quantify direction and degree of manual superiority and their mean constituted the Lateral Proficiency Index. A Variability Index, consisting of their standard deviation, was also computed. Sinistrality, as measured by the Preference Index, was related to severity of formal thought disorder in male schizophrenics. The Variability Index was significantly related to severity of formal thought disorder and to language dysfunction in the schizophrenic group as a whole. These relations were not demonstrated in the control groups. These findings support the hypothesis that, in schizophrenia, atypical handedness is a marker of left-hemisphere dysfunction that also disrupts language processes, including those implicated in the manifestation of formal thought disorder.

Adult↗
PubMed1994

Right hemisphere learning disability associated with left hemisphere dysfunction: anomalous dominance and development.

Two patients are described with the social emotional processing disorder, a developmental syndrome usually ascribed to right hemisphere dysfunction. In these two patients however, neurological examinations, EEG, and neuroimaging studies were all consistent with left hemisphere dysfunction. Both patients were left handed and had findings suggestive of anomalous dominance for language. It is proposed that early left hemisphere injury may have resulted in functional reorganisation that allowed sparing of language and motor skills but interfered with the development of functions that the right hemisphere normally subserves.

Adult↗