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Apathy is one of the most disabling behavioural disorders in Parkinson's disease (PD). It corresponds to a set of behavioural, emotional and cognitive features, such as reduced interest and participation in the main activities of daily living, a lack of initiative, a trend towards early withdrawal from initiated activities, indifference and flattening of affect. Its prevalence in PD ranges from 17% to 70%.1 This broad variability is related to heterogeneous population characteristics (the general population, patients in specialist departments, institutionalised patients, etc), different assessment procedures (clinical assessments, scores on non-specific or specific scales, etc) and the overlap between the clinical manifestations of apathy and those of other disorders (such as depression, anhedonia, cognitive decline and even some personality traits). The mechanisms that underlie apathy in PD have not been clearly identified. Several studies have suggested that apathy results from mesolimbic dopaminergic denervation and thus dysfunction of the limbic system.2 However, apathy is sometimes even present in patients receiving optimal dopaminergic therapy.3 Another recurrent question is whether or not apathy in PD patients reflects bias in processing emotional information. In the paper by Robert et al,4 the severity of apathy and the degree of impairment in recognition of facial emotions (RFE) were assessed in 36 non-demented, non-depressed PD patients. All participants underwent 18F-fluorodeoxyglucose positron emission tomography (PET). Metabolic patterns were found to be correlated with apathy and measures of RFE. After controlling for the main confounding variables (age, medication and cognitive status), Robert et al4 found that the severity of apathy was negatively correlated with the level of performance in the RFE task. The severity of apathy was also correlated with elevated metabolic activity in the left posterior cingulate cortex, although impairment in the RFE task was correlated with low metabolic activity in the posterior cingulate cortex and the superior frontal gyrus, bilaterally. Moreover, a conjunction analysis revealed that the association between apathy and RFE was underpinned by a network that included the right premotor cortex, the right orbitofrontal cortex, the left middle frontal gyrus and the right posterior cingulate cortex.
One of the study’s strengths relates to having taken account of several confounding factors when assessing clinical–metabolic correlations. However, the study also had a number of limitations. First, it was based on a correlation analysis and so the results will have to be confirmed by comparing well-matched groups of PD patients with and without apathy. Second, the authors used a conjunction analysis to identify the regions involved in both apathy and RFE. A conjunction is defined as an ‘AND’ between truth statements. In neuroimaging, conjunction analysis is based on the identification of brain areas that are activated by two or more tasks, that is, a conjunction of tasks.5 However, Robert et al4 only used the most basic statistical method suggested by Friston et al,5 which does not have the correct null hypothesis for a logical ‘AND’ test and has led to confusion in the neuroimaging community.6 More appropriate conjunction analyses (such as those available in the latest versions of SPM software6 ,7) will thus be needed before one can conclude that apathy and RFE impairment networks are related in PD.
To resolve this issue, future research should adopt a multimodal imaging approach. For example, a specific task performed by PD patients with and without apathy during PET or functional MRI acquisition would take better account of apathy and emotion impairment. Next, the performance and clinical scores could be correlated with functional and structural features (such as resting-state functional connectivity, structural connectivity assessed with diffusion tensor imaging and atrophy assessed with structural MRI).
Competing interests None.
Provenance and peer review Commissioned; internally peer reviewed.
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