Relation of Prefrontal Cortex Dysfunction to Working Memory and Symptoms in Schizophrenia

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

doi:10.1176/appi.ajp.158.7.1105

Cited by 566 publications

(396 citation statements)

References 52 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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“…There have been suggestions in the literature that, as NMDA antagonists induce psychotic symptoms and the NMDA receptor is involved in memory, the cognitive deficits observed in schizophrenia may be mediated by the NMDA receptor (eg Newcomer and Krystal, 2001). While cognitive impairment in schizophrenia still remains ill-defined, highly tentatively it appears that the profile of cognitive effects of ketamine appears somewhat similar to that observed in schizophrenia and organic psychosis (Perlstein et al, 2001), but differs in impairments to procedural learning and preserved executive functioning. Further research using techniques such as pharmacological functional magnetic resonance imaging may shed light on the similarity between neuroanatomical substrates of NMDA antagonist-induced cognitive impairments and those observed in schizophrenia.…”

Section: Discussionmentioning

confidence: 85%

Acute Effects of Ketamine on Memory Systems and Psychotic Symptoms in Healthy Volunteers

Morgan

Mofeez

Brandner

et al. 2003

Neuropsychopharmacol

239

174

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N-methyl-D-aspartate (NMDA) receptor antagonists have been demonstrated to induce schizophrenia-like symptoms and cognitive impairment in humans. The NMDA receptor has been strongly implicated in memory, but research to date on the effects of NMDA antagonists has examined only some aspects of human memory functions. This study used a double-blind, placebo-controlled, independent groups design with 54 healthy volunteers to examine the effects of infusions of two doses (0.4, 0.8 mg/kg) of the NMDA antagonist ketamine upon the five human memory systems, aspects of executive functioning and schizophrenia-like and dissociative symptoms. Ketamine produced a dose-dependent impairment to episodic and working memory and a slowing of semantic processing. Ketamine also impaired recognition memory and procedural learning. Attention, perceptual priming and executive functioning were not affected following the drug. In addition, ketamine induced schizophrenia-like and dissociative symptoms, which were not correlated with the cognitive measures. These data suggest that, in humans, ketamine produces a selective pattern of impairments to working, episodic, and procedural memory but not to perceptual priming, attention or aspects of executive functioning.

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“…Although there is considerable evidence that patients with schizophrenia fail to activate DLPFC to the degree seen in normal comparison subjects (termed hypofrontality) on a host of working memory or executive tasks including the Wisconsin Card-Sorting Task [Weinberger et al, 1986], the Tower of London [Andreasen et al, 1992], the n-back task [Carter et al, 1998], and verbal fluency [Yurgelun-Todd et al, 1996], more recent studies have stressed that DLPFC activation in patients is linked to performance deficits, with good performance associated with relatively greater DLPFC activity and marked behavioral deficits linked to relatively reduced DLPFC signal [Callicott et al, 2000;Perlstein et al, 2001;Ragland et al, 1998;Ramsey et al, 2002]. Manoach [2003] recently argued that task-related hypofrontality may be secondary to methodological issues or to between-group performance or motivational differences, and suggests that until the exact role of the prefrontal cortex in executive and working memory tasks is delineated, interpretation of reduced DLPFC activity in patients with schizophrenia is confounded.…”

Section: Introductionmentioning

confidence: 99%

Beyond hypofrontality: A quantitative meta‐analysis of functional neuroimaging studies of working memory in schizophrenia

Glahn

Ragland

Abramoff

et al. 2005

Human Brain Mapping

552

393

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Abstract:Although there is considerable evidence that patients with schizophrenia fail to activate the dorsolateral prefrontal cortex (DLPFC) to the degree seen in normal comparison subjects when performing working memory or executive tasks, hypofrontality may be coupled with relatively increased activity in other brain regions. However, most imaging studies of working memory in schizophrenia have focused on DLPFC activity. The goal of this work is to review functional neuroimaging studies that contrasted patients with schizophrenia and healthy comparison subjects during a prototypical working memory task, the n-back paradigm, to highlight areas of hyper-and hypoactivation in schizophrenia. We utilize a quantitative metaanalysis method to review 12 imaging studies where patients with schizophrenia were contrasted with healthy comparison subjects while performing the n-back paradigm. Although we find clear support for hypofrontality, we also document consistently increased activation in anterior cingulate and left frontal pole regions in patients with schizophrenia compared to that in controls. These data suggest that whereas reduced DLPFC activation is reported consistently in patients with schizophrenia relative to healthy subjects, abnormal activation patterns are not restricted to this region, raising questions as to whether the pathophysiological dysfunction in schizophrenia is specific to the DLPFC and about the relationship between impaired performance and aberrant activation patterns. The complex pattern of hyper-and hypoactivation consistently found across studies implies that rather than focusing on DLPFC dysregulation, researchers should consider the entire network of regions involved in a given task when making inferences about the biological mechanisms of schizophrenia. Hum Brain Mapp 25:60 -69, 2005.

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Relation of Prefrontal Cortex Dysfunction to Working Memory and Symptoms in Schizophrenia

Cited by 566 publications

References 52 publications

Beyond common resources: the cortical basis for resolving task interference

Beyond common resources: the cortical basis for resolving task interference

Acute Effects of Ketamine on Memory Systems and Psychotic Symptoms in Healthy Volunteers

Beyond hypofrontality: A quantitative meta‐analysis of functional neuroimaging studies of working memory in schizophrenia

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