Quantifying Apathy in Late-Life Depression: Unraveling Neurobehavioral Links Through Daily Activity Patterns and Brain Connectivity Analysis.

BACKGROUND: Better understanding apathy in late-life depression would help improve prediction of poor prognosis of diseases such as dementia. Actimetry provides an objective and ecological measure of apathy from patients' daily motor activity. We aimed to determine whether patterns of motor activity were associated with apathy and brain connectivity in networks that underlie goal-directed behaviors. METHODS: Resting-state functional magnetic resonance imaging and diffusion magnetic resonance imaging were collected from 38 nondemented participants with late-life depression. Apathy was evaluated using the diagnostic criteria for apathy, Apathy Evaluation Scale, and Apathy Motivation Index. Functional principal components (fPCs) of motor activity were derived from actimetry recordings taken for 72 hours. Associations between fPCs and apathy were estimated by linear regression. Subnetworks whose connectivity was significantly associated with fPCs were identified via threshold-free network-based statistics. The relationship between apathy and microstructure metrics was estimated along fibers by diffusion tensor imaging and a multicompartment model called neurite orientation dispersion and density imaging via tractometry. RESULTS: We found 2 fPCs associated with apathy: mean diurnal activity, negatively associated with Apathy Evaluation Scale scores, and an early chronotype, negatively associated with Apathy Motivation Index scores. Mean diurnal activity was associated with increased connectivity in the default mode, cingulo-opercular, and frontoparietal networks, while chronotype was associated with a more heterogeneous connectivity pattern in the same networks. We did not find significant associations between microstructural metrics and fPCs. CONCLUSIONS: Our findings suggest that mean diurnal activity and chronotype could provide indirect ambulatory measures of apathy in late-life depression, associated with modified functional connectivity of brain networks that underlie goal-directed behaviors.

Structural Brain Connectivity and Treatment Improvement in Mood Disorder.

Background: The treatment of depressive episodes is well established, with clearly demonstrated effectiveness of antidepressants and psychotherapies. However, more than one-third of depressed patients do not respond to treatment. Identifying the brain structural basis of treatment-resistant depression could prevent useless pharmacological prescriptions, adverse events, and lost therapeutic opportunities. Methods: Using diffusion magnetic resonance imaging, we performed structural connectivity analyses on a cohort of 154 patients with mood disorder (MD) and 77 sex- and age-matched healthy control (HC) participants. To assess illness improvement, the patients with MD went through two clinical interviews at baseline and at 6-month follow-up and were classified based on the Clinical Global Impression-Improvement score into improved or not-improved (NI). First, the threshold-free network-based statistics (NBS) was conducted to measure the differences in regional network architecture. Second, nonparametric permutations tests were performed on topological metrics based on graph theory to examine differences in connectome organization. Results: The threshold-free NBS revealed impaired connections involving regions of the basal ganglia in patients with MD compared with HC. Significant increase of local efficiency and clustering coefficient was found in the lingual gyrus, insula, and amygdala in the MD group. Compared with the NI, the improved displayed significantly reduced network integration and segregation, predominately in the default-mode regions, including the precuneus, middle temporal lobe, and rostral anterior cingulate. Conclusions: This study highlights the involvement of regions belonging to the basal ganglia, the fronto-limbic network, and the default mode network, leading to a better understanding of MD disease and its unfavorable outcome.

Connectivity patterns of the core resting-state networks associated with apathy in late-life depression.

BACKGROUND: Apathy is associated with reduced antidepressant response and dementia in late-life depression (LLD). However, the functional cerebral basis of apathy is understudied in LLD. We investigated the functional connectivity of 5 resting-state networks (RSN) hypothesized to underlie apathy in LLD. METHODS: Resting-state functional MRI data were collected from individuals with LLD who did not have dementia as well as healthy older adults between October 2019 and April 2022. Apathy was evaluated using the diagnostic criteria for apathy (DCA), the Apathy Evaluation Scale (AES) and the Apathy Motivation Index (AMI). Subnetworks whose connectivity was significantly associated with each apathy measure were identified via the threshold-free network-based statistics. Regions that were consistently associated with apathy across the measures were reported as robust findings. RESULTS: Our sample included 39 individuals with LLD who did not have dementia and 26 healthy older adults. Compared with healthy controls, individuals with LLD had an altered intra-RSN and inter-RNS connectivity in the default mode, the cingulo-opercular and the frontoparietal networks. All 3 apathy measurements showed associations with modified intra-RSN connectivity in these networks, except for the DCA in the cingulo-opercular network. The AMI scores showed stronger associations with the cingulo-opercular and frontoparietal networks, whereas the AES had stronger associations with the default mode network and the goal-oriented behaviour network. LIMITATIONS: The study was limited by the small number of participants without apathy according to the DCA, which may have reduced the statistical power of between-group comparisons. Additionally, the reliance on specific apathy measures may have influenced the observed overlap in brain regions. CONCLUSION: Our findings indicate that apathy in LLD is consistently associated with changes in both intra-RSN and inter-RSN connectivity of brain regions implicated in goal-oriented behaviours. These results corroborate previous findings of altered functional RSN connectivity in severe LLD.