4.6 Article

Functional connectivity correlates of reduced goal-directed behaviors in behavioural variant frontotemporal dementia

Journal

BRAIN STRUCTURE & FUNCTION
Volume 227, Issue 9, Pages 2971-2989

Publisher

SPRINGER HEIDELBERG
DOI: 10.1007/s00429-022-02519-5

Keywords

Frontotemporal dementia; Apathy; Goal-directed behavior; Ecological design; fMRI; Resting-state functional connectivity

Funding

  1. program Investissements d'avenir [ANR-10-IAIHU-06]
  2. foundation Fondation pour la recherche medicale [FRM DEQ20150331725]
  3. Malakoff Mederic Humanis company
  4. Federation pour la Recherche sur le Cerveau (FRC)
  5. Fondation Vaincre Alzheimer
  6. Fondation Recherche Alzheimer
  7. ENEDIS company
  8. France Alzheimer Foundation
  9. Philippe Chatrier Foundation
  10. Rosita Gomez association

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This study investigated the relationship between resting state functional connectivity and apathy in behavioral variant frontotemporal dementia (bvFTD). Two dimensions of apathy - global reduction of goal-directed behaviors and specific deficit of self-initiation - were identified using behavioral metrics and questionnaires. The findings revealed that global apathy was associated with decreased prefrontal cortex activity and reduced connectivity of salience network hubs, while the decrease in self-initiation was related to increased connectivity of parietal default-mode network hubs. This dimensional approach provided insights into the functional connectivity correlates of apathy in bvFTD, specifically highlighting the role of connectivity in the volitional process.
We explored the resting state functional connectivity correlates of apathy assessed as a multidimensional construct, using behavioral metrics, in behavioral variant frontotemporal dementia (bvFTD). We recorded the behavior of 20 bvFTD patients and 16 healthy controls in a close-to-real-life situation including a free phase (FP-in which actions were self-initiated) and a guided phase (GP-in which initiation of actions was facilitated by external guidance). We investigated the activity time and walking episode features as quantifiers of apathy. We used the means ((FP + GP)/2) and the differences (FP-GP) calculated for these metrics as well as measures by questionnaires to extract apathy dimensions by factor analysis. We assessed two types of fMRI-based resting state connectivity measures (local activity and seed-based connectivity) and explored their relationship with extracted apathy dimensions. Apathy in bvFTD was associated with lower time spent in activity combined with walking episodes of higher frequency, lower acceleration and higher duration. Using these behavioral metrics and apathy measures by questionnaires, we disentangled two dimensions: the global reduction of goal-directed behaviors and the specific deficit of self-initiation. Global apathy was associated with lower resting state activity within prefrontal cortex and lower connectivity of salience network hubs while the decrease in self-initiation was related to increased connectivity of parietal default-mode network hubs. Through a novel dimensional approach, we dissociated the functional connectivity correlates of global apathy and self-initiation deficit. We discussed in particular the role of the modified connectivity of lateral parietal cortex in the volitional process.

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