Incidental motor sequence learning: Investigations into its cognitive basis and the effects of neurological impairment and treatment

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.To survive in a complex changing environment humans frequently need to adapt their behaviour incidentally from normal interactions in the environment without any specific intention to learn. Whilst there is a considerable body of research into incidental learning of sequential information there is still fundamental debate regarding its cognitive basis, the associated neural mechanisms and the way in which it is affected by neurological disease. These issues were explored, in normal participants and neurological patients, using manipulations of the Serial Reaction Task [SRT] in which participants gradually learn a stimulus sequence (usually screen locations) after responding to each item by pressing corresponding response buttons. The first two experiments (chapter 3) demonstrate that the specific metric used to quantify learning and the occurrence of highly salient repeat locations may inflate estimates of learning in tasks with increased motor demands. The next three experiments (chapter 4) examine whether a secondary (not directly behaviourally relevant) information source during the SRT facilitates chunking in memory and overall learning. In a spatial SRT task (specified by horizontal location), additional spatial information (vertical location) enhanced learning but a secondary perceptual property (colour) produced a cost. However, in a perceptual SRT a secondary perceptual property (colour) had no effect. The next study demonstrates that impairments of incidental learning in Parkinson’s disease are partially reduced by administration of l-Dopa. Implications for models of striatal function and studies suggesting implicit learning is impaired by l-Dopa are discussed. Finally, the impact of Deep Brain Stimulation of the GPi is investigated in a population known to have only limited cognitive deficits relating to their illness (dystonia). Despite previous reports of impaired intentional learning in participants with a high genetic risk of Dystonia, there was no evidence for any impairment before or after stimulation. Implications across studies and future research directions are also discussed

Effects of Dopamine Medication on Sequence Learning with Stochastic Feedback in Parkinson's Disease

A growing body of evidence suggests that the midbrain dopamine system plays a key role in reinforcement learning and disruption of the midbrain dopamine system in Parkinson's disease (PD) may lead to deficits on tasks that require learning from feedback. We examined how changes in dopamine levels (“ON” and “OFF” their dopamine medication) affect sequence learning from stochastic positive and negative feedback using Bayesian reinforcement learning models. We found deficits in sequence learning in patients with PD when they were “ON” and “OFF” medication relative to healthy controls, but smaller differences between patients “OFF” and “ON”. The deficits were mainly due to decreased learning from positive feedback, although across all participant groups learning was more strongly associated with positive than negative feedback in our task. The learning in our task is likely mediated by the relatively depleted dorsal striatum and not the relatively intact ventral striatum. Therefore, the changes we see in our task may be due to a strong loss of phasic dopamine signals in the dorsal striatum in PD

Action reprogramming in Parkinson's disease:response to prediction error is modulated by levels of dopamine

Humans are able to use knowledge of previous events to estimate the probability of future actions. Consequently, an unexpected event will elicit a prediction error as the prepared action has to be replaced by an unprepared option in a process known as “action reprogramming” (AR). Here we show that people with Parkinson's disease (PD) have a dopamine-sensitive deficit in AR that is proportional to the size of the prediction error. Participants performed a probabilistic reaction time (RT) task in the context of either a predictable or unpredictable environment. For an overall predictable sequence, PD patients, on and off dopamine medication, and healthy controls showed similar improvements in RT. However, in the context of a generally predictable sequence, PD patients off medication were impaired in reacting to unexpected events that elicit large prediction errors and require AR. Critically, this deficit in AR was modulated by the prediction error associated with the upcoming event. The prolongation of RT was not observed during an overall unpredictable sequence, in which relatively unexpected events evoke little prediction error and the requirement for AR should be minimal, given the context. The data are compatible with recent theoretical accounts suggesting that levels of dopamine encode the reliability, i.e., precision, of sensory information. In this scheme, PD patients off medication have low dopamine levels and may therefore be less confident about incoming sensory information and more reliant on top-down predictions. Consequently, when these internal predictions are incorrect, PD patients take longer to respond appropriately to unexpected sensory information.</jats:p

Implementing Remote Memory Clinics to Enhance Clinical Care During and After COVID-19

Social isolation is likely to be recommended for older adults due to COVID-19, with ongoing reduced clinical contact suggested for this population. This has increased the need for remote memory clinics, we therefore review the literature, current practices and guidelines on organizing such remote memory clinics, focusing on assessment of cognition, function and other relevant measurements, proposing a novel pathway based on three levels of complexity: simple telephone or video-based interviews and testing using available tests (Level 1), digitized and validated methods based on standard pen-and-paper tests and scales (Level 2), and finally fully digitized cognitive batteries and remote measurement technologies (RMTs, Level 3). Pros and cons of these strategies are discussed. Remotely collected data negates the need for frail patients or carers to commute to clinic and offers valuable insights into progression over time, as well as treatment responses to therapeutic interventions, providing a more realistic and contextualized environment for data-collection. Notwithstanding several challenges related to internet access, computer skills, limited evidence base and regulatory and data protection issues, digital biomarkers collected remotely have significant potential for diagnosis and symptom management in older adults and we propose a framework and pathway for how technologies can be implemented to support remote memory clinics. These platforms are also well-placed for administration of digital cognitive training and other interventions. The individual, societal and public/private costs of COVID-19 are high and will continue to rise for some time but the challenges the pandemic has placed on memory services also provides an opportunity to embrace novel approaches. Remote memory clinics' financial, logistical, clinical and practical benefits have been highlighted by COVID-19, supporting their use to not only be maintained when social distancing legislation is lifted but to be devoted extra resources and attention to fully potentiate this valuable arm of clinical assessment and care.This article is available to RD&E staff via NHS OpenAthens. Click on the Publisher URL, and log in with NHS OpenAthens if prompted.This paper represents independent research partly funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College Londonpublished version, accepted version, submitted versio