Herberto Dhanis
Progression of Parkinson’s disease (PD) leads to debilitating non-motor symptoms, including cognitive impairment, hallucinations, and behavioural changes. While the cause of these symptoms is poorly understood, they are linked to alterations in functional properties of brain organisation. Specifically, time-invariant functional connectivity (FC), which reflects brain network architecture, and time-variant FC, which reflects network dynamics and communication over the architecture. Here, we directly interrogated if these properties capture non-motor symptom variance, by modelling network architecture and communication, and using such models to predict symptoms.
51 non-demented individuals with PD performed neurological examinations, resting-state fMRI, and many neuropsychological tests to characterize four domains: cognition, hallucinations, other neuropsychiatric, and behavioural (depression, loneliness, apathy, impulsivity). We recovered network architecture using ICA back-projection and generated probabilistic network dynamics representations using Hidden Markov Models. Both were used to predict patients’ symptoms via bootstrapped cross-validated Kernel Ridge Regression.
Network communication excelled at predicting scores of executive functioning (median explained variance: 30.22%, P < 0.001), active interference (24.18%, P<0.001), working memory (25.61%, P < 0.001) and visuospatial constructional ability (18.39%, P = 0.005), as well as frequency of visual hallucinations (18.25%, P = 0.005), amongst others of behavioural changes. The UPDRS-I, which broadly captures various non-motor symptoms was also significantly predicted (29.71%, P<0.001). Conversely, network architecture could not explain most symptoms aside from one cognitive and one behavioural score.
Our findings reveal network communication as an important dysfunction of brain organisation underpinning PD non-motor symptoms, and with predictive capabilities relevant for the clinical study of PD progression.