Exploration Deficits Under Ecological Conditions as a Marker of Apathy in Frontotemporal Dementia

Abstract

Apathy is one of the six clinical criteria for the behavioral variant of frontotemporal dementia (bvFTD), and it is almost universal in this disease. Although its consequences in everyday life are debilitating, its underlying mechanisms are poorly known, its assessment is biased by subjectivity and its care management is very limited. In this context, we have developed "ECOCAPTURE," a method aimed at providing quantifiable and objective signature(s) of apathy in order to assess it and identify its precise underlying mechanisms. ECOCAPTURE consists of the observation and recording of the patient's behavior when the participant is being submitted to a multiple-phase scenario reproducing a brief real-life situation. It is performed in a functional exploration platform transformed into a fully furnished waiting room equipped with a video and sensor-based data acquisition system. This multimodal method allowed video-based behavior analyses according to predefined behavioral categories (exploration behavior, sustained activities or inactivity) and actigraphy analyses from a 3D accelerometer. The data obtained were also correlated with behavioral/cognitive tests and scales assessing global cognitive efficiency, apathy, cognitive disinhibition, frontal syndrome, depression and anxiety. Here, bvFTD patients (n = 14) were compared to healthy participants (n = 14) during the very first minutes of the scenario, when the participants discovered the room and were encouraged to explore it. We showed that, in the context of facing a new environment, healthy participants first explored it and then engaged in sustained activities. By contrast, bvFTD patients were mostly inactive and eventually explored this new place, but in a more irregular and less efficient mode than normal subjects. This exploration deficit was correlated with apathy, disinhibition and cognitive and behavioral dysexecutive syndromes. These findings led us to discuss the presumed underlying mechanisms responsible for the exploration deficit (an inability to self-initiate actions, to integrate reward valuation and to inhibit involuntary behavior). Altogether, these results pave the way for simple and objective assessment of behavioral changes that represents a critical step for the evaluation of disease progression and efficacy of treatment in bvFTD.

Keywords: apathy; behavior; dementia; disinhibition; frontotemporal lobar degeneration; motivation; neurodegenerative diseases; prefrontal cortex.

Figure 1

Schematic representation of the ECOCAPTURE scenario in the “waiting room.” (A) Screenshot from one of the video cameras installed in the room, showing some of the furniture and objects in the room. (B) A global and schematic representation of the full scenario timeline. Before entering the room, participants completed a questionnaire indicating their preferences for music, food, drinks and magazine reading. Then, they entered the room and were submitted to the multiple-step ECOCAPTURE scenario, starting with the self-guided (freely moving) phase, which was followed by several other phases (not discussed in the present study). After the ECOCAPTURE session, they performed classic neuropsychological tests. (C) The self-guided (freely moving) phase. It lasted 7 min (called the “FULL PERIOD”) and was divided into three “SUBPERIODS” (SP1, SP2, and SP3) of 2, 2, and 3 min. During this phase, participants were encouraged to explore the room and interact with the different items.

Figure 2

Apathy in bvFTD. Significant difference in Starkstein Apathy Scale scores (STARK) (p = 0.00003) and on the non-activity metric (F_NACT) (p = 0.002) in the whole freely moving (self-guided) phase (i.e., the FULL PERIOD) between bvFTD and healthy participants (healthy c.). Significant positive correlation (r = 0.58, p = 0.0013, p-adjust = 0.05) between Starkstein Apathy Scale scores (STARK) and the ECOCAPTURE metric non-activity (F_NACT) in the freely moving (self-guided) phase for the whole population.

Figure 3

Correlations between video-based metrics, sensor-based metrics and neuropsychological data in the whole population (bvFTD + healthy participants) during the freely moving (self-guided) phase (FULL PERIOD). Red dotted line: significant negative correlation; solid blue line: significant positive correlation (r, p < 0.05). Blue circles represent the video-based metrics: EXP, exploration; ACT, activity; NACT, non-activity; WLK, walking. The green circle represents the sensor-based metric; FAST_ACC, fast acceleration. Orange circles represent the neuropsychological data: FAB, Frontal Assessment Battery; HAYL_E, Hayling Test; STARK, Starkstein Apathy Scale. Note the following: (1) Exploration and walking were positively correlated with each other, and both were correlated with fast acceleration. (2) Activity was negatively correlated with cognitive disinhibition (Hayling E); (3) Non-activity was positively correlated with apathy and cognitive disinhibition (STARK & Hayling E) and negatively correlated with FAB; (4) FAB was inversely correlated with STARK and Hayling E (which were positively correlated with each other).

Figure 4

Temporal dynamics of exploration in bvFTD and healthy participants. When the full period (7′) was divided into three subperiods (SP1, SP2, and SP3), we observed differences in the successive behaviors adopted by healthy participants (healthy c.) and bvFTD patients. During SP1 (the first 2 min), non-activity was significantly higher in bvFTD patients than in controls (Wilcoxon, p = 0.013), while exploration was significantly higher in healthy participants (Welch two-sample t-test, p = 0,036). During SP2 (the next 2 min), although no significant difference was observed between the two groups for the four metrics, bvFTD patients tended to be less active (non-activity: p = 0.078), and healthy subjects tended to be more involved in activities (activity: p = 0.098). During SP3 (the last 3 min), activity was significantly more important in healthy participants (Wilcoxon, p = 0.0015), while exploration was significantly higher in bvFTD (Wilcoxon, p = 0.012). *significant difference was observed between the two groups for the specific metrics.

Figure 5

Scatterplots and correlations. Scatterplots showing correlations between apathy (Starkstein) and activity and non-activity in different periods and between disinhibition (Hayling E) and exploration. Red dot: bvFTD; blue dot: healthy control. (A) Correlations between apathy and non-activity in the FULL PERIOD. (B) Correlations between disinhibition (Hayling E) and exploration in the FULL PERIOD. (C) Correlations between apathy (Starkstein scale) and activity in the FULL PERIOD. (D) Correlations between apathy (Starkstein scale) and activity in SUBPERIOD 3.