Fractionating the Neurocognitive Mechanisms Underlying Working Memory: Independent Effects of Dopamine and Parkinson’s Disease

Abstract

Deficits in working memory (WM) in Parkinson’s disease (PD) are often considered to be secondary to dopaminergic depletion. However, the neurocognitive mechanisms by which dopamine causes these deficits remain highly contested, and PD is now also known to be associated with nondopaminergic pathology. Here, we examined how PD and dopaminergic medication modulate three components of WM: maintenance over time, updating contents with new information and making memories distracter-resistant. Compared with controls, patients were disproportionately impaired when retaining information for longer durations. By applying a probabilistic model, we were able to reveal that the source of this error was selectively due to precision of memory representations degrading over time. By contrast, replenishing dopamine levels in PD improved executive control over both the ability to ignore and update, but did not affect maintenance of information across time. This was due to a decrease in guess responses, consistent with the view that dopamine serves to prevent WM representations being corrupted by irrelevant information, but has no impact on information decay. Cumulatively, these results reveal a dissociation in the neural mechanisms underlying poor WM: whereas dopamine reduces interference, nondopaminergic systems in PD appear to modulate processes that prevent information decaying more quickly over time.

Dopamine guides competition for cognitive control: Common effects of haloperidol on working memory and response conflict

“…If the above models of dopaminergic modulation of cognitive control are correct, then haloperidol should exert differential effects on these three different components of WM. A recent study in patients with Parkinson's disease (PD), using the same paradigm as in the present study, found that withdrawing mediation in PD patients impaired ignoring and updating performance but did not modulate the effect of retention period (Fallon et al, 2017). This suggests that dopamine affects both ignoring and updating.…”

“…Common to all experimental conditions was that the fidelity -or quality -of visual WM recall was assessed using a delayed adjustment task (Wilken & Ma, 2004). The version used here was exactly the same as in a previous study on patients with Parkinson's disease (Fallon, Mattiesing, Muhammed, Manohar, & Husain, 2017). In all conditions, participants were presented for 2 seconds with two differently coloured arrows (randomly orientated), presented at different spatial locations equidistant from screen centre.…”

“…The same modelling approach we previously applied for the effect of drug in PD patients (Fallon et al, 2017) was applied to the data (the experiments were identical). Thus, the models were fit separately for each participant and each drug session.…”

Abnormal distraction and load‐specific connectivity during working memory in cognitively normal Parkinson's disease

“…Despite numerous behavioral studies in PD (Siegert et al, 2008), neuroimaging studies have not characterized the coupling and uncoupling of brain interactions during different visuospatial WM processes, especially in situations where attention must be flexibly engaged to relevant information while handling distractions. Indeed, the ability to store information in WM and resist distractions can be impaired in PD (Fallon, Mattiesing, Muhammed, Manohar, & Husain, 2017;Lee, Cowan, Vogel, Rolan, & Valle-Inc, 2010).…”

“…Few studies have rigorously screened PD patients for mild cognitive impairment (MCI) (Poston et al, 2016), such that neurodegenerative changes before cognitive symptoms manifest are poorly understood. Scant attention has also been given to neurocognitive mechanisms that mediate different facets of WM, such as memory encoding, retrieval and distraction resistance, which may be more or less vulnerable in PD (Fallon, Mattiesing, et al, 2017;Lee et al, 2010;Pillon, Deweer, Agid, & Dubois, 1993). Notably, much of what we know about abnormal brain functioning during WM comes from comparisons between PD and control groups in regional activation (Mattay et al, 2002;Poston et al, 2016), which are insensitive to abnormal communications of WM hubs with other brain regions.…”