Dataset Information

Apathy and brain alterations in Parkinson's disease: a multimodal imaging study.

ABSTRACT:

Objective

Apathy is a common nonmotor symptom in Parkinson's disease (PD) affecting 40% of patients. The aim of the study was to investigate brain changes and correlates of frontal, striatal, and limbic pathways related to subclinical symptoms of apathy in PD patients.

Methods

Thirty-two PD patients divided into low-subclinical symptoms of apathy (LSA) (n = 18) and high-subclinical symptoms of apathy (HSA) (n = 14) and 25 healthy controls (HC) underwent a T1-weighted, diffusion-weighted, and resting-state functional MRI. Apathy was evaluated with the Lille Apathy Rating Scale. Voxel-based morphometry, tract-based spatial statistics, and resting-state functional connectivity (FC) analyses were performed with a region-of-interest approach.

Results

HSA-PD showed increased white matter axial and mean diffusivity compared with HC and increased white matter axial diffusivity compared with LSA-PD. HSA-PD showed decreased fronto-striatal and fronto-limbic FC compared with HC and decreased fronto-striatal FC compared with LSA-PD. LSA-PD showed decreased fronto-limbic but increased fronto-striatal FC (hyperconnectivity) compared with HC. No significant differences in grey matter were found. Fronto-striatal FC and white matter axial and mean diffusivity were associated with symptoms of apathy in HSA-PD. The fronto-striatal hyperconnectivity was associated with lower symptoms of apathy in LSA-PD.

Interpretation

Findings suggest distinct brain alterations in PD groups with subclinical symptoms of apathy. The increased pattern of activation in LSA-PD, accompanied with lower apathetic symptomatology, might be the initial manifestation of compensatory mechanisms for dysfunctional limbic pathway. The same pattern of hyperconnectivity has been found in other pathologies and the implication of these abnormalities as a cross-disease model for initial apathy symptomatology is further discussed.

SUBMITTER: Lucas-Jimenez O

PROVIDER: S-EPMC6043767 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Publications

Apathy and brain alterations in Parkinson's disease: a multimodal imaging study.

Lucas-Jiménez Olaia O Ojeda Natalia N Peña Javier J Cabrera-Zubizarreta Alberto A Díez-Cirarda María M Gómez-Esteban Juan Carlos JC Gómez-Beldarrain María Ángeles MÁ Ibarretxe-Bilbao Naroa N

Annals of clinical and translational neurology 20180525 7

<h4>Objective</h4>Apathy is a common nonmotor symptom in Parkinson's disease (PD) affecting 40% of patients. The aim of the study was to investigate brain changes and correlates of frontal, striatal, and limbic pathways related to subclinical symptoms of apathy in PD patients.<h4>Methods</h4>Thirty-two PD patients divided into low-subclinical symptoms of apathy (LSA) (<i>n</i> = 18) and high-subclinical symptoms of apathy (HSA) (<i>n</i> = 14) and 25 healthy controls (HC) underwent a T1-weighted ...[more]

PMID: 30009198

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Project description:Parkinson's disease (PD) patients show theory of mind (ToM) deficit since the early stages of the disease, and this deficit has been associated with working memory, executive functions and quality of life impairment. To date, neuroanatomical correlates of ToM have not been assessed with magnetic resonance imaging in PD. The main objective of this study was to assess cerebral correlates of ToM deficit in PD. The second objective was to explore the relationships between ToM, working memory and executive functions, and to analyse the neural correlates of ToM, controlling for both working memory and executive functions.Thirty-seven PD patients (Hoehn and Yahr median = 2.0) and 15 healthy controls underwent a neuropsychological assessment and magnetic resonance images in a 3T-scanner were acquired. T1-weighted images were analysed with voxel-based morphometry, and white matter integrity and diffusivity measures were obtained from diffusion weighted images and analysed using tract-based spatial statistics.PD patients showed impairments in ToM, working memory and executive functions; grey matter loss and white matter reduction compared to healthy controls. Grey matter volume decrease in the precentral and postcentral gyrus, middle and inferior frontal gyrus correlated with ToM deficit in PD. White matter in the superior longitudinal fasciculus (adjacent to the parietal lobe) and white matter adjacent to the frontal lobe correlated with ToM impairment in PD. After controlling for executive functions, the relationship between ToM deficit and white matter remained significant for white matter areas adjacent to the precuneus and the parietal lobe.Findings reinforce the existence of ToM impairment from the early Hoehn and Yahr stages in PD, and the findings suggest associations with white matter and grey matter volume decrease. This study contributes to better understand ToM deficit and its neural correlates in PD, which is a basic skill for development of healthy social relationships.

Project description:Apathy is a common and disabling complication of Parkinson's disease characterized by reduced goal-directed behaviour. Several studies have reported dysfunction within prefrontal cortical regions and projections from brainstem nuclei whose neuromodulators include dopamine, serotonin and noradrenaline. Work in animal and human neuroscience have confirmed contributions of these neuromodulators on aspects of motivated decision-making. Specifically, these neuromodulators have overlapping contributions to encoding the value of decisions, and influence whether to explore alternative courses of action or persist in an existing strategy to achieve a rewarding goal. Building upon this work, we hypothesized that apathy in Parkinson's disease should be associated with an impairment in value-based learning. Using a four-armed restless bandit reinforcement learning task, we studied decision-making in 75 volunteers; 53 patients with Parkinson's disease, with and without clinical apathy, and 22 age-matched healthy control subjects. Patients with apathy exhibited impaired ability to choose the highest value bandit. Task performance predicted an individual patient's apathy severity measured using the Lille Apathy Rating Scale (R = -0.46, P < 0.001). Computational modelling of the patient's choices confirmed the apathy group made decisions that were indifferent to the learnt value of the options, consistent with previous reports of reward insensitivity. Further analysis demonstrated a shift away from exploiting the highest value option and a reduction in perseveration, which also correlated with apathy scores (R = -0.5, P < 0.001). We went on to acquire functional MRI in 59 volunteers; a group of 19 patients with and 20 without apathy and 20 age-matched controls performing the Restless Bandit Task. Analysis of the functional MRI signal at the point of reward feedback confirmed diminished signal within ventromedial prefrontal cortex in Parkinson's disease, which was more marked in apathy, but not predictive of their individual apathy severity. Using a model-based categorization of choice type, decisions to explore lower value bandits in the apathy group activated prefrontal cortex to a similar degree to the age-matched controls. In contrast, Parkinson's patients without apathy demonstrated significantly increased activation across a distributed thalamo-cortical network. Enhanced activity in the thalamus predicted individual apathy severity across both patient groups and exhibited functional connectivity with dorsal anterior cingulate cortex and anterior insula. Given that task performance in patients without apathy was no different to the age-matched control subjects, we interpret the recruitment of this network as a possible compensatory mechanism, which compensates against symptomatic manifestation of apathy in Parkinson's disease.

Dataset Information

Apathy and brain alterations in Parkinson's disease: a multimodal imaging study.

Objective

Methods

Results

Interpretation

Publications

Apathy and brain alterations in Parkinson's disease: a multimodal imaging study.

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