Impaired sensory evidence accumulation and network function in Lewy body dementia.

Abstract:

Deficits in attention underpin many of the cognitive and neuropsychiatric features of Lewy body dementia. These attention-related symptoms remain difficult to treat and there are many gaps in our understanding of their neurobiology. An improved understanding of attention-related impairments can be achieved via mathematical modelling approaches, which identify cognitive parameters to provide an intermediate level between observed behavioural data and its underlying neural correlate. Here, we apply this approach to identify the role of impaired sensory evidence accumulation in the attention deficits that characterize Lewy body dementia. In 31 people with Lewy body dementia (including 13 Parkinson's disease dementia and 18 dementia with Lewy bodies cases), 16 people with Alzheimer's disease, and 23 healthy controls, we administered an attention task whilst they underwent functional 3 T MRI. Using hierarchical Bayesian estimation of a drift-diffusion model, we decomposed task performance into drift rate and decision boundary parameters. We tested the hypothesis that the drift rate-a measure of the quality of sensory evidence accumulation-is specifically impaired in Lewy body dementia, compared to Alzheimer's disease. We further explored whether trial-by-trial variations in the drift rate related to activity within the default and dorsal attention networks, to determine whether altered activity in these networks was associated with slowed drift rates in Lewy body dementia. Our results revealed slower drift rates in the Lewy body dementia compared to the Alzheimer's disease group, whereas the patient groups were equivalent for their decision boundaries. The patient groups were reduced relative to controls for both parameters. This highlights sensory evidence accumulation deficits as a key feature that distinguishes attention impairments in Lewy body dementia, consistent with impaired ability to efficiently process information from the environment to guide behaviour. We also found that the drift rate was strongly related to activity in the dorsal attention network across all three groups, whereas the Lewy body dementia group showed a divergent relationship relative to the Alzheimer's disease and control groups for the default network, consistent with altered default network modulation being associated with impaired evidence accumulation. Together, our findings reveal impaired sensory evidence accumulation as a specific marker of attention problems in Lewy body dementia, which may relate to large-scale network abnormalities. By identifying impairments in a specific sub-process of attention, these findings will inform future exploratory and intervention studies that aim to understand and treat attention-related symptoms that are a key feature of Lewy body dementia.