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.

Temporal preparation has been investigated extensively by manipulating the foreperiod, the interval between a warning stimulus and target stimulus requiring a speeded response. Although such research has revealed many effects of both the duration and distribution of foreperiods on reaction times, the underlying cognitive mechanism is still largely unknown. Here, we test a recent proposal that temporal preparation is driven by the retrieval of memory traces of past experiences from long-term memory rather than by knowledge about upcoming events. Two groups of participants received different foreperiod distributions in an acquisition phase, which was followed a week later by a transfer phase, in which both groups received the same distribution of foreperiods. We found that the effects of the different foreperiod distributions presented in the acquisition phase were still apparent a week later during the transfer phase, as the reaction time patterns of both groups reflected the old distributions. This occurred even though both groups were provided with full information about the change in the distribution of foreperiods at the start of the transfer phase. These findings provide compelling evidence that long-term memory plays an important role in temporal preparation.

Ignoring distracting information and updating current contents are essential components of working memory (WM). Yet, although both require controlling irrelevant information, it is unclear whether they have the same effects on recall and produce the same level of misbinding errors (incorrectly joining the features of different memoranda). Moreover, the likelihood of misbinding may be affected by the feature similarity between the items already encoded into memory and the information that has to be filtered out (ignored) or updated into memory. Here, we investigate these questions. Participants were sequentially presented with two pairs of arrows. The first pair of arrows always had to be encoded into memory, but the second pair either had to be ignored (ignore condition) or allowed to displace the previously encoded items (update condition). To investigate the effect of similarity on recall, we also varied, in a factorial manner, whether the items that had to be ignored or updated were presented in the same or different colours and/or same or different spatial locations to the original memoranda. By applying a computational model, we were able to quantify the levels of misbinding. Ignoring, but not updating, increased overall recall error as well as misbinding rates, even when accounting for the retention period. This indicates that not all manipulations of attention in WM are equal in terms of their effects on recall and misbinding. Misbinding rates in the ignore condition were affected by the colour and spatial congruence of relevant and irrelevant information to a greater extent than in the update condition. This finding suggests that attentional templates are used to evaluate relevant and irrelevant information in different ways during ignoring and updating. Together, the results suggest that differences between the two functions might occur due to higher levels of attentional compartmentalisation – or protection – during updating compared to ignoring.

Background:There is currently no consensus about the extent of gray matter (GM) atrophy that can be attributed to secondary changes following white matter (WM) lesions, or the temporal and spatial relationships between the two phenomena. Elucidating this interplay will broaden the understanding of the combined inflammatory and neurodegenerative pathophysiology of multiple sclerosis (MS), and separating atrophic changes due to primary and secondary neurodegenerative mechanisms will then be pivotal to properly evaluate treatment effects, especially if these treatments target the different processes individually.Objective:To untangle these complex pathological mechanisms, this systematic review provides an essential first step: an objective and comprehensive overview of the existing in vivo knowledge of the relationship between brain WM lesions and GM atrophy, in patients diagnosed with MS. The overall aim was to clarify the extent to which WM lesions associate with both global and regional GM atrophy, and how this may differ in the different disease subtypes.Methods:We searched MEDLINE (through PubMed) and Embase for reports containing direct associations between brain GM and WM lesion measures obtained by conventional MRI sequences in patients with clinically isolated syndrome (CIS) and MS. No restriction was applied for publication date. The quality and risk of bias in included studies was evaluated using the Quality Assessment Tool for observational cohort and cross-sectional studies (NIH, Bethesda, MA). Qualitative and descriptive analyses were performed.Results:A total of 90 articles were included. WM lesion volumes were mostly related to global, cortical and deep GM volumes, and those significant associations were almost without exception negative, indicating that higher WM lesion volumes were associated with lower GM volumes or lower cortical thicknesses. The most consistent relation between WM lesions and GM atrophy was seen in early (relapsing) disease, and less so in progressive MS.Conclusion:The findings suggest that GM neurodegeneration is mostly secondary to damage in the WM during early disease stages, while becoming more detached and dominated by other, possibly primary neurodegenerative disease mechanisms, in progressive MS.