Functional Connectivity Correlates of Reduced Goal-directed Behaviors in Behavioural Variant Frontotemporal Dementia

Abstract

INTRODUCTION: We explored the resting state functional connectivity correlates of apathy assessed as a multidimensional construct, using behavioral metrics, in behavioral variant frontotemporal dementia (bvFTD).METHODS: We recorded the behavior of 20 bvFTD patients and 16 healthy controls (HC) 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 connectivity measures (local low-frequency signal power and distant seed-based functional connectivity) and explored their relationship with extracted apathy dimensions. RESULTS: 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 selfinitiation. 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. DISCUSSION: Through a new dimensional approach of apathy, we dissociated the functional connectivity correlates of global apathy and self-initiation deficit. This contributes to better understand the role of functional networks in the production of goal-directed behaviors.

Disentangling Clinical Profiles of Apathy in Behavioral Variant Frontotemporal Dementia

“…Results of a previous study [32] provided arguments supporting the validity of F1 and F2 as dimensions measuring global apathy and specific self-initiation deficit respectively (see Supplementary Material 2C for the summary of these results). In sum, F1 was found to: 1) distinguish bvFTD from controls;…”

“…directed behaviors) [32] (see Godefroy et al [32] and Supplementary Material 2A for further details on the extraction and validity tests of these metrics).…”

“…First, we performed analyses investigating the validity of these measures used to characterize apathy profiles. Analyses supporting the validity of measures by F1 and F2, as measures of global apathy and self-initiation deficit respectively, were performed in a previous study [32] (further details on the analyses performed are in Supplementary Material 2C). In this study, to investigate the validity of questionnaire-related time ratio (Questio time ratio) as a complementary measure of the ability to maintain focus on a goal-directed activity, we performed:…”