Prefrontal cortex dysfunction mediates deficits in working memory and prepotent responding in schizophrenia

Perlstein, William M.; Dixit, Neha; Carter, Cameron S.; Noll, Douglas C.; Cohen, Jonathan D.

doi:10.1016/s0006-3223(02)01675-x

Cited by 254 publications

(197 citation statements)

References 56 publications

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“…This result gives support to the recent findings of Perlstein et al (2001Perlstein et al ( , 2003 who identified with separate tasks of WM and inhibitory control that participants with schizophrenia had particular difficulty under conditions of either high WM or prepotency demands. As the experimental demands increased and patient's performance began to suffer, a smaller increase in activation of the right DLPFC region was identified using fMRI, suggesting an insufficient ability to increase top-down control.…”

Section: Implications and Conclusionsupporting

confidence: 88%

Beyond common resources: the cortical basis for resolving task interference

2004

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Recent studies have suggested that declining inhibitory control observed during simultaneous increases in working memory (WM) demands may be due to sharing common neural resources, although it is relatively unclear how these processes are successfully combined at a neural level. Event-related functional MRI was used to examine task performance that required inhibition of varying numbers of items held in WM. Common activation regions for WM and inhibition were observed and this functional overlap may constitute the cortical basis for task interference. However, maintaining successful inhibitory control under increasing WM demands tended not to increase activation in these overlapping regions as might be expected if these common areas reflect common resources essential for task performance. Instead, increased activation was observed predominantly in unique, inhibition-specific regions including dorsolateral prefrontal cortex. The finding that successfully maintaining weaker stimulus -response relationships in the face of competition from stronger, prepotent responses requires greater activity in these regions reveals the means by which the brain resolves task interference and supports theories of how top-down attentional control is implemented. D

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Section: Implications and Conclusionsupporting

confidence: 88%

Beyond common resources: the cortical basis for resolving task interference

2004

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“…Task demands with a stronger PFC-dependence have also revealed gamma deficits in schizophrenia patients, including impaired frontal gamma power (measured by magnetoencephalography) during mental arithmetic performance (Kissler et al, 2000) and an inability to mount increased delay-period gamma power in response to increasing working memory load during the N-Back (Basar-Eroglu et al, 2007). Our research group has reported that schizophrenia patients exhibit impaired frontal induced gamma power during preparatory cognitive control processes (Cho et al, 2006), suggesting a physiological mechanism to link impaired BOLD responses in the DLPFC with impaired cognitive control (Barch et al, 2001;Holmes et al, 2005;MacDonald and Carter, 2003;MacDonald et al, 2005;Perlstein et al, 2003;Snitz et al, 2005;Yoon et al, 2008).…”

Section: Introductionmentioning

confidence: 84%

Gamma Oscillatory Power is Impaired During Cognitive Control Independent of Medication Status in First-Episode Schizophrenia

Minzenberg

Firl

Yoon

et al. 2010

Neuropsychopharmacol

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Schizophrenia is characterized by impaired cognitive control associated with prefrontal cortex dysfunction, but the underlying pathophysioloical mechanisms remain unknown. Higher cognitive processes are associated with cortical oscillations in the gamma range, which are also impaired in chronic schizophrenia. We tested whether cognitive control-related gamma deficits are observed in firstepisode patients, and whether they are associated with antipsychotic medication exposure. Fifty-three first-episode schizophrenia patients (21 without antipsychotic medication treatment) and 29 healthy control subjects underwent electroencephalography (EEG) during performance of a preparatory cognitive control task (preparing to overcome prepotency or POP task). The first-episode schizophrenia patient group was impaired (relative to the control group) on task performance and on delay-period gamma power at each of the three subgroups of frontal electrodes. The unmedicated patient subgroup was similarly impaired compared with controls, and was not different on these measures compared with the medicated patient subgroup. In contrast, delay-period theta power was not impaired in the full patient group nor in the unmedicated patient subgroup. Impaired cognitive control-related gamma cortical oscillatory activity is present at the first psychotic episode in schizophrenia, and is independent of medication status. This suggests that altered local circuit function supporting high-frequency oscillatory activity in prefrontal cortex ensembles may serve as the pathophysiological substrate of cognitive control deficits in schizophrenia.

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“…The DLPFC comprises part of the anterior attentional system that serves to focus attention (1), and dysfunction within that region has been demonstrated in functional neuroimaging studies of schizophrenia patients performing sustained attention tasks (42,43). Therefore, a functional disturbance of dorsolateral prefrontal cortex might alone cause both deficits in sustained attention and in the ability to voluntarily suppress prepotent behavioral responses.…”

Section: Decreased Attention Fixation and Inhibitory Deficit In Schizmentioning

confidence: 99%

Reduced Attentional Engagement Contributes to Deficits in Prefrontal Inhibitory Control in Schizophrenia

Reilly

Harris

Khine

et al. 2008

Biological Psychiatry

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BACKGROUND-Problems with the voluntary control of behavior, such as those leading to increased antisaccade errors, are accepted as evidence of prefrontal dysfunction in schizophrenia. We previously reported that speeded prosaccade responses, i.e. shorter response latencies for automatic shifts of attention to visual targets, were associated with higher antisaccade error rates in schizophrenia. This suggests that dysregulation of automatic attentional processes may contribute to disturbances in prefrontally-mediated control of voluntary behavior.

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Prefrontal cortex dysfunction mediates deficits in working memory and prepotent responding in schizophrenia

Cited by 254 publications

References 56 publications

Beyond common resources: the cortical basis for resolving task interference

Beyond common resources: the cortical basis for resolving task interference

Gamma Oscillatory Power is Impaired During Cognitive Control Independent of Medication Status in First-Episode Schizophrenia

Reduced Attentional Engagement Contributes to Deficits in Prefrontal Inhibitory Control in Schizophrenia

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