Abstract
Depression, anxiety and apathy are distinct neuropsychiatric symptoms that highly overlap in Parkinson’s disease (PD). It remains unknown whether each symptom is uniquely associated with a functional network dysfunction. Here, we examined whether individual differences in each neuropsychiatric symptom predict functional connectivity patterns in PD patients while controlling for all other symptoms and motor function. Resting-state functional connectivity MRI were acquired from 27 PD patients and 29 healthy controls. Widespread reduced functional connectivity was identified in PD patients and explained by either the neuropsychiatric or motor symptoms. Depression in PD predicted increased functional connectivity between the orbitofrontal, hippocampal complex, cingulate, caudate and thalamus. Apathy in PD predicted decreased caudate-thalamus and orbitofrontal-parahippocampal connectivity. Anxiety in PD predicted three distinct types of functional connectivity not described before: (i) increased limbic-orbitofrontal cortex; (ii) decreased limbic-dorsolateral prefrontal cortex and orbitofrontal-dorsolateral prefrontal cortices and (iii) decreased sensorimotor-orbitofrontal cortices. The first two types of functional connectivity suggest less voluntary and more automatic emotion regulation. The last type is argued to be specific to PD and reflect an impaired ability of the orbitofrontal cortex to guide goal-directed motor actions in anxious PD patients.
Highlights
Neuropsychiatric symptoms constitute an integral part of Parkinson’s disease (PD) and include depression, anxiety and apathy[1]
To help fill in these gaps, we aimed to determine whether individual differences in each neuropsychiatric symptom among PD patients predict the strength of intrinsic functional connectivity, i.e. the synchronization of BOLD fluctuations between brain regions in the absence of external stimuli, while accounting for the individual differences in all other neuropsychiatric symptoms and motor function
We identified resting-state functional connectivity patterns that vary as a function of a specific neuropsychiatric symptom in PD patients while accounting for the effect of all other neuropsychiatric symptoms
Summary
Neuropsychiatric symptoms constitute an integral part of Parkinson’s disease (PD) and include depression, anxiety and apathy[1]. Cumulative evidence shows that these symptoms are not merely a reaction to psychological distress due to motor disability, but are more likely a direct consequence of the pathology of the disease[3] Their incidence in PD exceeds the rates in general population as well as in other chronic and/or neurodegenerative diseases[4,5] with up to 89% of PD patients having at least one symptom[6]. To help fill in these gaps, we aimed to determine whether individual differences in each neuropsychiatric symptom among PD patients predict the strength of intrinsic functional connectivity, i.e. the synchronization of BOLD fluctuations between brain regions in the absence of external stimuli, while accounting for the individual differences in all other neuropsychiatric symptoms and motor function For these purposes, resting-state functional MRI data were acquired from 27 PD patients with varying degrees of depression, anxiety and apathy and a multiple linear regression model was tested. A matched group of 29 healthy control subjects was recruited to evaluate whole-brain functional connectivity patterns associated with PD
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