Physiological dysfunction of dorsolateral prefrontal cortex in schizophrenia
01 Jan 1985-Vol. 44, Iss: 5
TL;DR: DLPFC dysfunction in schizophrenia is linked to pathophysiology of a regionally specific neural system rather than to global cortical dysfunction, and that this pathophysology is most apparent under prefrontally specific cognitive demand.
About: The article was published on 1985-01-01 and is currently open access. It has received 535 citations till now. The article focuses on the topics: Dorsolateral prefrontal cortex & Consumer neuroscience.
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TL;DR: These data indicate that N-methyl-D-aspartate antagonists produce a broad range of symptoms, behaviors, and cognitive deficits that resemble aspects of endogenous psychoses, particularly schizophrenia and dissociative states.
Abstract: Background: To characterize further behavioral, cognitive, neuroendocrine, and physiological effects of subanesthetic doses of ketamine hydrochloride in healthy human subjects. Ketamine, a phencyclidine hydrochloride derivative, is a dissociative anesthetic and a noncompetitive antagonist of the N -methyl-D-aspartate subtype of excitatory amino acid receptor. Methods: Nineteen healthy subjects recruited by advertisements from the community participated in this randomized, double-blind, placebo-controlled study. Subjects completed three test days involving the 40-minute intravenous administration of placebo, ketamine hydrochloride (0.1 mg/kg), or ketamine hydrochloride (0.5 mg/kg). Behaviors associated with the positive and negative symptoms of schizophrenia were assessed by using the Brief Psychiatric Rating Scale. Changes in perception and behaviors associated with dissociative states were assessed by the Perceptual Aberration Subscale of the Wisconsin Psychosis Proneness Scale and the Clinician-Administered Dissociative States Scale. Cognitive function was assessed by using the (1) Mini-Mental State Examination; (2) tests sensitive to frontal cortical dysfunction, including a continuous performance vigilance task, a verbal fluency task, and the Wisconsin Card Sorting Test; and (3) tests of immediate and delayed recall. Plasma levels of cortisol, prolactin, homovanillic acid, and 3-methoxy-4-hydroxyphenethyleneglycol were measured. Results: Ketamine (1) produced behaviors similar to the positive and negative symptoms of schizophrenia; (2) elicited alterations in perception; (3) impaired performance on tests of vigilance, verbal fluency, and the Wisconsin Card Sorting Test; (4) evoked symptoms similar to dissociative states; and (5) preferentially disrupted delayed word recall, sparing immediate recall and postdistraction recall. Ketamine had no significant effect on the Mini-Mental State Examination at the doses studied. Ketamine also had no effect on plasma 3-methoxy-4hydroxyphenethyleneglycol levels, although it blunted a test day decline in plasma homovanillic acid levels at the higher dose. It also dose dependently increased plasma cortisol and prolactin levels. Ketamine produced small dose-dependent increases in blood pressure. Conclusions: These data indicate that N -methyl-Daspartate antagonists produce a broad range of symptoms, behaviors, and cognitive deficits that resemble aspects of endogenous psychoses, particularly schizophrenia and dissociative states.
3,166 citations
TL;DR: It was found that PCP-induced psychotomimetic effects are associated with submicromolar serum concentrations of PCP and the findings suggest that endogenous dysfunction of NMDA receptor-mediated neurotransmission might contribute to the pathogenesis of schizophrenia.
Abstract: Objective: Phencyclidine (PCP, “angel dust”) induces a psychotomimetic state that closely resembles schizophrenia. As opposed to amphetamine-induced psychosis, PCP-induced psychosis incorporates both positive (e.g., hallucinations, paranoia) and negative (e.g., emotional withdrawal, motor retardation) schizophrenic symptoms. PCP-induced psychosis also uniquely incorporates the formal thought disorder and neuropsychological deficits associated with schizophrenia. The purpose of the present paper is to review recent advances in the study of the molecular mechanisms of PCP action and to describe their implications for the understanding ofschizophrenic pathophysiology. Methoc�: Twenty-five papers were identified that described the clinicaldose and serum and CSF levelsat which PCP induces its psychotomimetic effects. The dose range ofPCP-induced effects were compared to the dose range at which PCP interacts with specific molecular targets and affects neurotransmission. Results: It was found that PCP-induced psychotomimetic effects are associated with submicromolar serum concentrations of PCP. At these concentrations PCP interacts selectively with a specific binding site (PCP receptor) that is associated with the N-methyl-D-aspartate (NMDA)-type excitatory amino acid receptor. Occupation ofits receptor by PCP induces noncompetitive inhibition of NMDA receptor-mediated neurotransmission. Other NMDA antagonists such as the dissociative anesthetic ketamine induce PCP-like neurobehavioral effects in proportion to their potency in binding to the PCP receptor and inducing NMDA receptor inhibition. Conclusions: These findings suggestthat endogenous dysfunction ofNMDA receptor-mediated neurotransmission might contribute to the pathogenesis of schizophrenia. The relative implications of the PCP and amphetamine models ofschizophrenia are discussedin relationship to the diagnosis and etiology of schizophrenia. (Am J Psychiatry1991;148:1301-1308)
2,883 citations
TL;DR: It now appears that at the level of the putamen such inputs remain segregated within the "motor" circuit, and it is difficult to imagine how such functional specificity could be maintained in the absence of strict topographic specificity within the sequential projections that comprise these two circuits.
Abstract: The central theme of the "segregated circuits" hypothesis is that structural convergence and functional integration occurs within, rather than between, each of the identified circuits Admittedly, the anatomical evidence upon which this scheme is based remains incomplete The hypothesis continues to be predicated largely on comparisons of anterograde and retrograde labeling studies carried out in different sets of animals Only in the case of the "motor" circuit has evidence for the continuity of the loop been demonstrated directly in individual subjects; for the other circuits, such continuity is inferred from comparisons of data on different components of each circuit obtained in separate experiments Because of the marked compression of pathways leading from cortex through basal ganglia to thalamus, comparisons of projection topography across experimental subjects may be hazardous Definitive tests of the hypothesis of maintained segregation await additional double- and multiple-label tract-tracing experiments wherein the continuity of one circuit, or the segregation of adjacent circuits, can be examined directly in individual subjects It is worthy of note, however, that the few studies to date that have employed this methodology have generated results consistent with the segregated circuits hypothesis Moreover, single cell recordings in behaving animals have shown striking preservation of functional specificity at the level of individual neurons throughout the "motor" and "oculomotor" circuits It is difficult to imagine how such functional specificity could be maintained in the absence of strict topographic specificity within the sequential projections that comprise these two circuits This is not to say, however, that we expect the internal structure of functional channels (eg, the "arm" channel within the "motor" circuit) to have cable-like, point-to-point topography When the grain of analysis is sufficiently fine, anatomical studies have shown repeatedly that the terminal fields of internuclear projections (eg, to striatum, pallidum, nigra, thalamus, etc) often appear patchy and highly divergent, suggesting that neighboring groups of projection cells tend to influence interdigitating clusters of postsynaptic neurons While more intricate and complex than simple point-to-point topography, however, this type arrangement should also be capable of maintaining functional specificity As discussed briefly above, it is not yet clear to what extent the inputs to the "motor" circuit from the different precentral motor fields (eg, MC, SMA, APA) are integrated in their passage through the circuit It now appears that at the level of the putamen such inputs remain segregated(ABSTRACT TRUNCATED AT 400 WORDS)
2,659 citations
TL;DR: The results indicate that schizophrenia is characterized by a broadly based cognitive impairment, with varying degrees of deficit in all ability domains measured by standard clinical tests.
Abstract: The neurocognitive literature on test performance in schizophrenia is reviewed quantitatively. The authors report 22 mean effect sizes from 204 studies to index schizophrenia versus control differences in global and selective verbal memory, nonverbal memory, bilateral and unilateral motor performance, visual and auditory attention, general intelligence, spatial ability, executive function, language, and interhemispheric tactile-transfer test performance. Moderate to large raw effect sizes (d > .60) were obtained for all 22 neurocognitive test variables, and none of the associated confidence intervals included zero. The results indicate that schizophrenia is characterized by a broadly based cognitive impairment, with varying degrees of deficit in all ability domains measured by standard clinical tests.
2,372 citations
TL;DR: Although the dorsolateral PFC is but one critical structure in a network of anterior and posterior “attention control” areas, it does have a unique executiveattention role in actively maintaining access to stimulus representations and goals in interference-rich contexts.
Abstract: We provide an “executive-attention” framework for organizing the cognitive neuroscience research on the constructs of working-memory capacity (WMC), general fluid intelligence, and prefrontal cortex (PFC) function. Rather than provide a novel theory of PFC function, we synthesize a wealth of singlecell, brain-imaging, and neuropsychological research through the lens of our theory of normal individual differences in WMC and attention control (Engle, Kane, & Tuholski, 1999; Engle, Tuholski, Laughlin, & Conway, 1999). Our critical review confirms the prevalent view that dorsolateral PFC circuitry is critical to executive-attention functions. Moreover, although the dorsolateral PFC is but one critical structure in a network of anterior and posterior “attention control” areas, it does have a unique executiveattention role in actively maintaining access to stimulus representations and goals in interference-rich contexts. Our review suggests the utility of an executive-attention framework for guiding future research on both PFC function and cognitive control.
2,075 citations
References
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Book•
01 Jan 1998
TL;DR: The item-banked version of Raven's APM delivers a set of 23 matrices randomly selected from a recommend RAVEN'S Standard Progressive Matrices (SPM). Manual.
Abstract: The item-banked version of Raven's APM delivers a set of 23 matrices randomly selected from a recommend RAVEN'S Standard Progressive Matrices (SPM). Manual. Additionally, research suggests a strong degree of equivalence. engineering students in South Africa on Raven's Standard. Progressive averaged a Raven's Standard Progressive Matrices (SPM) score of 37 out of 60. By the (1990). Manual for Raven's Progressive Matrices and Vocabulary Scales. Emotional Intelligence, and Raven Standard Progressive Matrices Test Plus were intelligence and the Standard Progressive Matrices to assess cognitive intelligence. The emotional quotient inventory (eq-i): technical manual.
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