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Cools, R, Gibbs SE, Miyakawa A, Jagust W, D’Esposito.  2008.  Working memory capacity predicts dopamine synthesis capacity in the human striatum., 2008 Jan 30. Journal of Neuroscience. 28(5):1208-1212. Abstract2008_cools.pdf

Evidence from psychopharmacological research has revealed that dopamine receptor agents have opposite effects on cognitive function depending on baseline levels of working memory capacity. These contrasting effects have been interpreted to reflect differential baseline levels of dopamine. Here we demonstrate for the first time that working memory capacity as measured by listening span predicts dopamine synthesis capacity in the striatum, indicating that subjects with low working memory capacity have low DA synthesis capacity in the striatum, whereas subjects with high working memory capacity have high DA synthesis capacity in the striatum.

McDowell, S, Whyte J, D’Esposito.  1997.  Working memory impairments in traumatic brain injury: evidence from a dual-task paradigm., 1997 Oct. Neuropsychologia. 35(10):1341-1353. Abstract1997_mcdowell.pdf

Although many individuals with traumatic brain injury (TBI) perform well on standard neuropsychological tests, they often exhibit marked functional difficulties. The functions which are impaired seem to be analogous to the role of the central executive system (CES) in Baddeley’s [Working Memory, 1986, Oxford University Press, New York] widely accepted model of working memory. The purpose of this study was to investigate CES function in individuals with TBI with a dual-task paradigm. We studied 25 non-demented persons who were at various stages in their recovery from severe TBI and compared their performance on a dual-task paradigm to a group of age-matched controls. Our dual-task paradigm measured performance on a simple visual reaction time task both alone (baseline) and during concurrent tasks of articulation or digit span. Subjects were also assessed with other neuropsychological tests of executive function. TBI patients had slower reaction times on the primary task when performed alone (P < 0.05) and greater decrements in performance during dual-task conditions (P < 0.01). They also exhibited significantly greater deficits than control subjects on other measures of executive function. Although correlations between dual-task performance and other executive measures were quite low, principle components analysis suggested that a common factor does exist between these measures. These findings support the conclusion that TBI patients have a working memory impairment that is due to dysfunction of the CES and which may be related to executive function deficits as measured by standard neuropsychological testing.

Logie, RH, D’Esposito.  2007.  Working memory in the brain., 2007 Jan. Cortex. 43(1):1-4. Abstract2007_logie.pdf


Westphal, AJ, Ballard ME, Rodriguez N, Vega TA, D'Esposito M, Kayser AS.  2021.  Working memory, cortical dopamine tone, and frontoparietal brain recruitment in post-traumatic stress disorder: a randomized controlled trial., 2021 Jul 12. Translational psychiatry. 11(1):389. Abstract

Post-traumatic stress disorder (PTSD) leads to impairments in both cognitive and affective functioning. Animal work suggests that chronic stress reduces dopamine tone, and both animal and human studies argue that changes in dopamine tone influence working memory, a core executive function. These findings give rise to the hypothesis that increasing cortical dopamine tone in individuals with greater PTSD symptomatology should improve working memory performance. In this pharmacological functional magnetic resonance imaging (fMRI) study, 30 US military veterans exhibiting a range of PTSD severity completed an emotional working memory task. Each subject received both placebo and the catechol-O-methyl transferase inhibitor tolcapone, which increases cortical dopamine tone, in randomized, double-blind, counterbalanced fashion. Mnemonic discriminability (calculated with d', an index of the detectability of working memory signals) and response bias were evaluated in the context of task-related brain activations. Subjects with more severe PTSD showed both greater tolcapone-mediated improvements in d' and larger tolcapone-mediated reductions in liberally-biased responding for fearful stimuli. FMRI revealed that tolcapone augmented activity within bilateral frontoparietal control regions during the decision phase of the task. Specifically, tolcapone increased cortical responses to fearful relative to neutral stimuli in higher severity PTSD subjects, and reduced cortical responses to fearful stimuli for lower severity PTSD subjects. Moreover, tolcapone modulated prefrontal connectivity with areas overlapping the default mode network. These findings suggest that enhancing cortical dopamine tone may represent an approach to remediating cognitive and affective dysfunction in individuals with more severe PTSD symptoms.

D’Esposito.  2008.  Working memory., 2008. Handbook of Clinical Neurology / edited by P.J. Vinken and G.W. Bruyn. 88:237-247. Abstract2008_desposito_wm.pdf


Nee, DE, D'Esposito M.  2018.  Working memory: An evolving concept. The Stevens' Handbook of Experimental Psychology and Cognitive Neuroscience, 4th Edition. : John Wiley and Sons