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Prefronto-cortical dopamine D1 receptor sensitivity can critically influence working memory maintenance during delayed response tasks.

ABSTRACT: The dopamine (DA) hypothesis of cognitive deficits suggests that too low or too high extracellular DA concentration in the prefrontal cortex (PFC) can severely impair the working memory (WM) maintenance during delay period. Thus, there exists only an optimal range of DA where the sustained-firing activity, the neural correlate of WM maintenance, in the cortex possesses optimal firing frequency as well as robustness against noisy distractions. Empirical evidences demonstrate changes even in the D1 receptor (D1R)-sensitivity to extracellular DA, collectively manifested through D1R density and DA-binding affinity, in the PFC under neuropsychiatric conditions such as ageing and schizophrenia. However, the impact of alterations in the cortical D1R-sensitivity on WM maintenance has yet remained poorly addressed. Using a quantitative neural mass model of the prefronto-mesoprefrontal system, the present study reveals that higher D1R-sensitivity may not only effectuate shrunk optimal DA range but also shift of the range to lower concentrations. Moreover, higher sensitivity may significantly reduce the WM-robustness even within the optimal DA range and exacerbates the decline at abnormal DA levels. These findings project important clinical implications, such as dosage precision and variability of DA-correcting drugs across patients, and failure in acquiring healthy WM maintenance even under drug-controlled normal cortical DA levels.

SUBMITTER: Reneaux M

PROVIDER: S-EPMC5973564 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Prefronto-cortical dopamine D1 receptor sensitivity can critically influence working memory maintenance during delayed response tasks.

Reneaux Melissa M Gupta Rahul R

PloS one 20180529 5

The dopamine (DA) hypothesis of cognitive deficits suggests that too low or too high extracellular DA concentration in the prefrontal cortex (PFC) can severely impair the working memory (WM) maintenance during delay period. Thus, there exists only an optimal range of DA where the sustained-firing activity, the neural correlate of WM maintenance, in the cortex possesses optimal firing frequency as well as robustness against noisy distractions. Empirical evidences demonstrate changes even in the D ...[more]

PMID: 29813109

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Project description:The Working Memory model of human memory, first introduced by Baddeley and Hitch (1974), has been one of the most influential psychological constructs in cognitive psychology and human neuroscience. However the neuronal correlates of core components of this model have yet to be fully elucidated. Here we present data from two studies where human temporal cortical single neuron activity was recorded during tasks differentially affecting the maintenance component of verbal working memory. In Study One we vary the presence or absence of distracting items for the entire period of memory storage. In Study Two we vary the duration of storage so that distractors filled all, or only one-third of the time the memory was stored. Extracellular single neuron recordings were obtained from 36 subjects undergoing awake temporal lobe resections for epilepsy, 25 in Study one, 11 in Study two. Recordings were obtained from a total of 166 lateral temporal cortex neurons during performance of one of these two tasks, 86 study one, 80 study two. Significant changes in activity with distractor manipulation were present in 74 of these neurons (45%), 38 Study one, 36 Study two. In 48 (65%) of those there was increased activity during the period when distracting items were absent, 26 Study One, 22 Study Two. The magnitude of this increase was greater for Study One, 47.6%, than Study Two, 8.1%, paralleling the reduction in memory errors in the absence of distracters, for Study One of 70.3%, Study Two 26.3% These findings establish that human lateral temporal cortex is part of the neural system for working memory, with activity during maintenance of that memory that parallels performance, suggesting it represents active rehearsal. In 31 of these neurons (65%) this activity was an extension of that during working memory encoding that differed significantly from the neural processes recorded during overt and silent language tasks without a recent memory component, 17 Study one, 14 Study two. Contrary to the Baddeley model, that activity during verbal working memory maintenance often represented activity specific to working memory rather than speech or language.

Dataset Information

Prefronto-cortical dopamine D1 receptor sensitivity can critically influence working memory maintenance during delayed response tasks.

Publications

Prefronto-cortical dopamine D1 receptor sensitivity can critically influence working memory maintenance during delayed response tasks.

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