Disentangling the Role of Working Memory in Parkinson’s Disease

Abstract

Working memory (WM) represents a core cognitive function with a major striatal contribution, and thus WM deficits, commonly observed in Parkinson's disease (PD), could also relate to many other problems in PD patients. Our online study aimed to determine the subdomains of WM that are particularly affected in PD and to clarify the links between WM and everyday cognitive deficits, other executive functions, psychiatric and PD symptoms, as well as early cognitive impairment. Fifty-two mild-to-moderate PD patients and 54 healthy controls performed seven WM tasks tapping selective updating, continuous monitoring, or maintenance of currently active information. Self-ratings of everyday cognition, depression, and apathy symptoms, as well as screenings of global cognitive impairment, were also collected. The data were analyzed using structural equation modeling. Of the three WM domains, only selective updating was directly predictive of PD group membership. More widespread WM deficits were observed only in relation to global cognitive impairment in PD patients. Self-rated everyday cognition or psychiatric symptoms were not linked to WM performance but correlated with each other. Our findings suggest that WM has a rather limited role in the clinical manifestation of PD. Nevertheless, due to its elementary link to striatal function, the updating component of WM could be a candidate for a cognitive marker of PD also in patients who are otherwise cognitively well-preserved.

Computational Psychiatry Needs Time and Context

“…Accordingly, in the computational models, this mechanism alters gating not only of motor actions, but also cognitive ones, such as the entrance of cortical content into working memory. Empirical work confirms parallels in how motor actions and working memory content are gated, and that these are related to striatal DA mechanisms in PD (Salmi et al, 2020;Wiecki & Frank, 2010). Within a given corticostriatal circuit, DA depletion also induces hyperactivity of the subthalamic nucleus (STN).…”

Analogous computations in working memory input, output and motor gating: Electrophysiological and computational modeling evidence

“…Indeed, striatal dysfunctions such as in Parkinson’s disease causes not only progressive motor degeneration but also cognitive deficits that are both related to the dysfunction of the gating system [83]. More recent work also found that degraded ability to perform selective updating of WM is the key marker of the cognitive deficits in Parkinson’s [84].…”

The influence of working memory and processing speed on other aspects of cognitive functioning in de novo Parkinson's disease: Initial findings from network modelling and graph theory

“…Executive functioning, working memory and processing speed deficits are thought to arise from dopaminergically mediated abnormalities in frontostriatal circuits (Grogan et al, 2018; Moustafa et al, 2008; Warden et al, 2016) and visuospatial deficits from cholinergic and posterior cortical degeneration (Kehagia et al, 2012; Robbins & Cools, 2014). Working memory and processing speed deficits can be marked (McKinlay et al, 2010); although, the exact prevalence and magnitude of these likely depends on the specific construct (Revonsuo et al, 1993; Salmi et al, 2020) and the task employed (Sawamoto et al, 2002). Primary working memory and processing speed deficits may lead to secondary difficulties in other cognitive functions.…”