A dopaminergic basis for working memory, learning and attentional shifting in Parkinsonism

Moustafa, Ahmed A.; Sherman, Scott J.; Frank, Michael J.

doi:10.1016/j.neuropsychologia.2008.07.011

Cited by 175 publications

(134 citation statements)

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“…It is noteworthy that DAT1 genotype is predictive of brain and behavioral responses to cognitive flexibility (GarciaGarcia et al, 2010) and, in particular, a recent study showed that DAT1 modulates striatal (caudate) activation as a function of working memory load in an updating task (Stollstorff et al, 2010). A role for striatal dopamine in cognitive flexibility and working memory updating is consistent with multiple behavioral pharmacological and imaging studies (Cools et al, 2007;Clatworthy et al, 2009;Frank and O'Reilly, 2006;Moustafa et al, 2008b). Thus, given the evidence that striatal activation predicts the extent to which cognitive training can be achieved with updating tasks (Dahlin et al, 2008a), future research should analyze the degree to which these training effects are modulated by variations with striatal dopaminergic genes such as DARPP-32, DAT1 and DRD2.…”

Section: Striatal Genetics Of Reinforcement and Decision Makingmentioning

confidence: 63%

“…Relatedly, baseline striatal DA synthesis predicts the extent to which DA drugs alter reinforcement learning processes (Cools et al, 2009). Furthermore, DA drugs can affect the degree to which working memory updating strategies are themselves learned across trials (Frank and O'Reilly, 2006;Moustafa et al, 2008b). Finally, a recent study showed that the extent to which stimulants cognitive function is predicted by drug-induced changes in D2 receptor availability in distinct striatal sub-regions, depending on the task (Clatworthy et al, 2009).…”

Section: Individual Differences In Response To Pharmacological Manipumentioning

confidence: 99%

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Neurogenetics and Pharmacology of Learning, Motivation, and Cognition

Frank

Fossella

2010

Neuropsychopharmacol

172

167

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Many of the individual differences in cognition, motivation, and learningFand the disruption of these processes in neurological conditionsFare influenced by genetic factors. We provide an integrative synthesis across human and animal studies, focusing on a recent spate of evidence implicating a role for genes controlling dopaminergic function in frontostriatal circuitry, including COMT, DARPP-32, DAT1, DRD2, and DRD4. These genetic effects are interpreted within theoretical frameworks developed in the context of the broader cognitive and computational neuroscience literature, constrained by data from pharmacological, neuroimaging, electrophysiological, and patient studies. In this framework, genes modulate the efficacy of particular neural computations, and effects of genetic variation are revealed by assays designed to be maximally sensitive to these computations. We discuss the merits and caveats of this approach and outline a number of novel candidate genes of interest for future study.

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Section: Striatal Genetics Of Reinforcement and Decision Makingmentioning

confidence: 63%

Section: Individual Differences In Response To Pharmacological Manipumentioning

confidence: 99%

Neurogenetics and Pharmacology of Learning, Motivation, and Cognition

Frank

Fossella

2010

Neuropsychopharmacol

172

167

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“…This was despite the fact that N1 amplitudes within the BG group were intact, even in the lesioned hemisphere. Although patients with unilateral BG neuropathology show deficits in attentional set shifting and general cognitive flexibility (19,30,50), the BG do not appear to play a critical role in the rapid allocation of visual attention. Rather, our BG patients show intact electrophysiology related to attentional allocation, whereas our PFC group has attentional impairments for contralesional stimuli.…”

Section: Discussionmentioning

confidence: 94%

“…In vivo, working memory maintenance is associated with sustained delay-period activity in the PFC (5,17) and BG (18), although the BG are thought to play a role in gating information into the PFC to allow it to update representations where necessary (19). Although neurons in both visual extrastriate and the PFC maintain VWM representations during delay periods, PFC neurons encode more information about the stimuli and are more resistant to distractors than visual extrastriate neurons (20).…”

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confidence: 99%

Prefrontal cortex and basal ganglia contributions to visual working memory

Voytek

Knight

2010

Proc. Natl. Acad. Sci. U.S.A.

171

116

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Visual working memory (VWM) is a remarkable skill dependent on the brain's ability to construct and hold an internal representation of the world for later comparison with an external stimulus. The prefrontal cortex (PFC) and basal ganglia (BG) interact within a cortical and subcortical network supporting VWM. We used scalp electroencephalography in groups of patients with unilateral PFC or BG lesions to provide evidence that these regions play complementary but dissociable roles in VWM. PFC patients show behavioral and electrophysiological deficits manifested by attenuation of extrastriate attention and VWM-related neural activity only for stimuli presented to the contralesional visual field. In contrast, patients with BG lesions show behavioral and electrophysiological VWM deficits independent of the hemifield of stimulus presentation but have intact extrastriate attention activity. The results support a model wherein the PFC is critical for top-down intrahemispheric modulation of attention and VWM with the BG involved in global support of VWM processes.attention | electroencephalography | lesion | stroke E ven a seemingly simple action such as determining which of two bananas is riper requires us to compare real world visual information, such as the color of the banana you are currently looking at in the store, with your memory of the yellowness of the other banana you just put down. This relies in part on visual working memory (VWM), a remarkable ability wherein we construct and hold an internal model of a real-world visual stimulus that we then later compare against another stimulus. In essence, we construct and hold a model of the visual world and compare that model against subsequent inputs from the external world. VWM relies upon an intact and functioning prefrontal cortex (PFC), and damage to this region, such as from stroke, causes VWM impairments (1-3). However, cognitive processes do not localize to specific brain regions per se and a behavior as complex as VWM recruits a distributed network of cortical and subcortical structures (4-8), including the basal ganglia (BG) (9, 10) and visual extrastriate regions (11)(12)(13).Most computational models of VWM rely upon intercommunication between the PFC and the striatum such that memories are maintained via recurrent activation in fronto-striatal loops (14-16). In vivo, working memory maintenance is associated with sustained delay-period activity in the PFC (5, 17) and BG (18), although the BG are thought to play a role in gating information into the PFC to allow it to update representations where necessary (19). Although neurons in both visual extrastriate and the PFC maintain VWM representations during delay periods, PFC neurons encode more information about the stimuli and are more resistant to distractors than visual extrastriate neurons (20). Animal research shows that the BG rapidly learn task-relevant rules and may send relevant, preprocessed information to the PFC for subsequent selection and further processing (21). Anatomically, the BG are situate...

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“…Impaired updating in PD may be caused by difficulties to select actions that were previously irrelevant (Moustafa et al, 2008), or by impaired inhibition of previously selected actions, allowing them to compete with novel motor representations (Rubchinsky et al, 2003). The latter account is consistent with the reduced switch-related activity observed in the globus pallidus: given the inhibitory effect of the globus pallidus onto the cortex, focused action selection involves the excitation of a large pallidal territory surrounding a functional center, while concurrent inhibition of the functional center allows specific recruitment of cortical representations (Mink, 1996).…”

Section: The Effect Of Striatal Dysfunction On Action Switchingmentioning

confidence: 99%

Increased Dependence of Action Selection on Recent Motor History in Parkinson's Disease

Helmich

Aarts²,

Lange³

et al. 2009

J. Neurosci.

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It is well known that the basal ganglia are involved in switching between movement sequences. Here we test the hypothesis that this contribution is an instance of a more general role of the basal ganglia in selecting actions that deviate from the context defined by the recent motor history, even when there is no sequential structure to learn or implement. We investigated the effect of striatal dopamine depletion [in Parkinson's disease (PD)] on the ability to switch between independent action plans. PD patients with markedly lateralized signs performed a hand laterality judgment task that involved action selection of their most and least affected hand. Trials where patients selected the same (repeat) or the alternative (switch) hand as in a previous trial were compared, and this was done separately for the most and least affected hand. Behaviorally, PD patients showed switch-costs that were specific to the most affected hand and that increased with disease severity. Functional magnetic resonance imaging (fMRI) showed that this behavioral effect was related to the state of the frontostriatal system: as disease severity increased, contributions of the basal ganglia to the selection process and their effective connectivity with the medial frontal cortex (MFC) decreased, whereas involvement of the MFC increased. We conclude that the basal ganglia are important for rapidly switching toward novel motor plans even when there is no sequential structure to learn or implement. The enhanced MFC activity may result either from reduced focusing abilities of the basal ganglia or from compensatory processes.

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A dopaminergic basis for working memory, learning and attentional shifting in Parkinsonism

Cited by 175 publications

References 123 publications

Neurogenetics and Pharmacology of Learning, Motivation, and Cognition

Neurogenetics and Pharmacology of Learning, Motivation, and Cognition

Prefrontal cortex and basal ganglia contributions to visual working memory

Increased Dependence of Action Selection on Recent Motor History in Parkinson's Disease

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