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 (LLD) would help predicting poor prognosis of the disease such as dementia. Actimetry provides an objective and ecological measure of apathy from patients' daily motor activity. We aimed to determine if patterns of motor activity were associated with apathy and brain connectivity in networks underlying goal-directed behaviors. METHODS: Resting-state functional MRI and diffusion MRI were collected from 38 non-demented LLD subjects. Apathy was evaluated using the diagnostic criteria for apathy, the apathy evaluation scale (AES) and the apathy motivation index (AMI). Functional principal components (fPC) of motor activity were derived from actimetry recordings of 72 hours. Associations between fPC and apathy were estimated by linear regression. Subnetworks whose connectivity was significantly associated with fPC were identified via the 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 two fPC associated with apathy: mean diurnal activity, negatively associated with AES, and an early chronotype, negatively associated with AMI. Mean diurnal activity was associated with increased connectivity in the default-mode, the cingulo-opercular and the frontoparietal networks, while chronotype was associated with a more heterogenous connectivity pattern in the same networks. We did not find significant associations between microstructural metrics and fPCs. CONCLUSION: Our findings suggest that mean diurnal activity and chronotype could provide indirect ambulatory measures of apathy in LLD, associated with modified functional connectivity of brain networks underlying goal-directed behaviors.

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.

The priming effect of repetitive transcranial magnetic stimulation on clinical response to electroconvulsive therapy in treatment-resistant depression: a randomized, double-blind, sham-controlled study.

BACKGROUND: Electroconvulsive therapy (ECT) is one of the most effective treatments for treatment-resistant depression (TRD). However, due to response delay and cognitive impairment, ECT remains an imperfect treatment. Compared to ECT, repetitive transcranial magnetic stimulation (rTMS) is less effective at treating severe depression, but has the advantage of being quick, easy to use, and producing almost no side effects. In this study, our objective was to assess the priming effect of rTMS sessions before ECT on clinical response in patients with TRD. METHODS: In this multicenter, randomized, double-blind, sham-controlled trial, 56 patients with TRD were assigned to active or sham rTMS before ECT treatment. Five sessions of active/sham neuronavigated rTMS were administered over the left dorsolateral prefrontal cortex (20 Hz, 90% resting motor threshold, 20 2 s trains with 60-s intervals, 800 pulses/session) before ECT (which was active for all patients) started. Any relative improvements were then compared between both groups after five ECT sessions, in order to assess the early response to treatment. RESULTS: After ECT, the active rTMS group exhibited a significantly greater relative improvement than the sham group [43.4% (28.6%) v. 25.4% (17.2%)]. The responder rate in the active group was at least three times higher. Cognitive complaints, which were assessed using the Cognitive Failures Questionnaire, were higher in the sham rTMS group compared to the active rTMS group, but this difference was not corroborated by cognitive tests. CONCLUSIONS: rTMS could be used to enhance the efficacy of ECT in patients with TRD. ClinicalTrials.gov: NCT02830399.

A Prospective Open-Label Pilot Study of Transcranial Direct Current Stimulation in High-Functioning Autistic Patients with a Dysexecutive Syndrome.

BACKGROUND: Executive functions (EF) are often impaired in autism spectrum disorder (ASD). Such dysfunctions are associated with anxiety, depression, and a lack of autonomy. Transcranial direct current stimulation (tDCS) has been shown to enhance EF in healthy adults and clinical populations and to improve working memory - a component of the EF - in adults with high-functioning ASD (HF-ASD). We hypothesized that tDCS could improve the EF of HF-ASD patients. Such enhancement could improve their adaptive behaviors. METHOD: Eight patients with HF-ASD received 10 consecutive cathodal tDCS sessions (2 mA) over the left dorsolateral prefrontal cortex (F3) for 15 min each in an open trial. EF (with the Stroop test, Trail Making Test [TMT] A and B, Modified Wisconsin Card Sorting Test [mWCST], and Verbal Fluency Test) and behavioral dysexecutive syndrome (with the Behavioral Dysexecutive Syndrome Inventory and the Repetitive and Restricted Behaviour scale) were assessed before and 10 days after treatment. RESULTS: This study showed significant improvement in initiation (TMT-A time: p = 0.018) and cognitive flexibility (TMT-B time: p = 0.009; letter Verbal Fluency Test: p = 0.017; mWCST total errors: p = 0.028) after tDCS. Regarding behavior, the hypoactivity of the patients improved, as well as their repetitive and restrictive behaviors. In addition, this noninvasive neurostimulation technique was well tolerated. CONCLUSIONS: Flexibility and initiation are the most impaired EF in autism. These are promising results which justify a randomized and placebo-controlled study in a wider population. If these results were confirmed by a randomized controlled trial, tDCS could be an easy and well-tolerated adjunctive treatment aiming to improve the quality of life and the autonomy of ASD patients.