Apathy is defined as a quantitative reduction in voluntary and goal-directed behavior. To address this, the investigators propose an ethological approach to assess apathy objectively and quantitatively by observing patients in real-life situations.

The ECOCAPTURE paradigm involves a structured, multi-step scenario conducted in a functional exploration platform. This platform is equipped with an advanced data acquisition system integrating video recordings and sensors to precisely monitor and analyze participants' behavior.

Primary objective:

Develop a diagnostic tool for apathy using metrics derived from video recordings and sensor data. This tool aims to provide objective measures to identify and quantify apathy.

Secondary Objectives:

• Validation of ICM_APATHY_TASKS: This novel experimental task is designed to evaluate three primary mechanisms thought to underlie apathy: Motivation, Cognitive inertia (difficulty initiating tasks), The interaction between motivation and action execution.
• Identification of the pathophysiological mechanisms of apathy by investigate the cognitive, behavioral, neural, and neurohormonal underpinnings of apathy.

This will enable the classification of apathetic patients into subtypes (or several forms of apathy) based on the dominant mechanisms and provide insights into which processes best explain apathy in individual cases.

This innovative framework aims to deepen the understanding of apathy, improve diagnostic precision, and pave the way for tailored interventions.

A pilot study, ECOCAPTURE (ClinicalTrials.gov/NCT02496312, 2015), was conducted with participants diagnosed with the behavioral variant of frontotemporal dementia (bvFTD) matched for age, gender, and education level with healthy controls (n=7 per group). This study successfully validated the feasibility and conceptual framework of the ECOCAPTURE approach.

The aim of this trial is to further develop and expand the ECOCAPTURE tool by applying it to a larger population, including individuals with the behavioral variant of frontotemporal dementia (bvFTD) and healthy control participants.

The objectives of this study are to evaluate goal-directed behavior and identify apathy by analyzing data to establish a behavioral signature of apathy. Additionally, the study seeks to refine patient profiles by delineating the pathophysiological mechanisms underlying apathy, including cognitive processes, neural substrates, and neurohormonal pathways.

The experiments take place on an experimental platform dedicated to the functional exploration of human behavior (PRISME, ICM core facility, Salpêtrière Hospital, Paris, France), to assess behavior under ecological conditions. The ECOCAPTURE paradigm mimics a naturalistic situation (i.e., waiting comfortably in a waiting room). Participants undergo a structured 45-minute controlled scenario, during which their behavior is systematically monitored to evaluate apathy and disinhibition.

The PRISME platform is transformed into a furnished waiting room containing specific objects that provides opportunities to interact with the environment. The platform is equipped with a six-ceiling camera system (not hidden) covering the entire waiting room. The Media Recorder® software (NOLDUS Information Technology, Wageningen, the Netherlands) facilitates simultaneous video recordings from multiple cameras, ensuring synchronized capture across different viewpoints for comprehensive behavioral analysis. During the experiment, individuals' behavior is video-recorded, and their movement acceleration is measured using a wireless body sensor (Move II® triaxial accelerometer, Movisens GmbH, Karlsruhe, Germany) worn on the right hip. An eye-tracking system (SMI Eye Tracking Glasses 2 Wireless, ®SensoMotoric Instruments, Teltow, Germany / Tobii Pro Glasses 3, ®Tobii AB, Danderyd, Sweden) is added to the multimodal recording system, and the subjects wear eye-tracking glasses for a 7-minute period during the 45-minute experimental session. The subjects are informed at the time of initial consent that their behavior would be tracked and recorded by video cameras located in the room.

Video data analysis is performed with The Observer XT software (Version 14.0, NOLDUS, Wageningen, The Netherlands) to identify the frequency and duration of behaviors. Behavioral metrics are obtained by behavioral coding from 45-minute video footage for each individual. Behavioral coding data is collected through the continuous sampling method, to identify all occurrences of behaviors and their duration. Behavioral coding is conducted based on two ethograms - the ECOCAPTURE apathy ethogram, the ECOCAPTURE disinhibition ethogram - (Batrancourt et al. 2022, "The ECOCAPTURE ethograms: apathy ethogram and disinhibition ethogram", Mendeley Data, V2, doi: 10.17632/mv8hndcd95.2) The ECOCAPTURE apathy ethogram includes behaviors divided in two behavioral categories: Motor patterns, Activity states. The ECOCAPTURE disinhibition ethogram includes behaviors divided in three disinhibition categories: Compulsivity, Impulsivity, Social disinhibition.

Metrics built from collected data (video, sensors) are analyzed to reveal a behavioral signature of apathy.

The study consists of two separate visits, each occurring on a different day, and includes the following components: the ECOCAPTURE observation phase in ecological conditions, a comprehensive neuropsychological assessment, a series of experimental tasks (some of which are computer-based), an MRI scan (including T1, T2, rs-fMRI, and MS-DWI), and a blood sample collection.

Inclusion Criteria:

Eligibility Criteria for All Groups:

• Demonstrates the ability to provide informed consent for participation in the study.
• Capable of understanding study instructions and performing cognitive tasks as required.
• Enrolled in a valid health insurance plan.

Eligibility Criteria for Patients:

• Mini-Mental State Examination (MMSE): Score ≥ 17.
• Medical History: Absence of any other neurological or psychiatric conditions.
• Caregiver Requirement: Must have a caregiver present.

Patient Groups:

• Diagnosed with behavioral variant frontotemporal dementia (bvFTD) based on the Rascovsky criteria (Rascovsky et al., 2011).
• Diagnosed with Major Depressive Disorder (MDD) according to DSM-IV criteria.

Eligibility Criteria for Healthy Age-, Sex-, and Education-Matched Controls:

• Mini-Mental State Examination (MMSE): Score > 27.
• Medical History: No history of neurological or psychiatric disorders.

Exclusion Criteria:

• MRI Contraindications: Standard contraindications to magnetic resonance imaging (e.g., pacemaker, metallic implants, claustrophobia).
• Cognitive Barriers: Inability to comprehend study instructions.
• Legal Restrictions: Individuals referenced in Articles L.1121-5 to L.1121-8 and L.1122-12 of the French Public Health Code.

The scientific leaders of the ECOCAPTURE research project aim to participate in international OPEN DATA initiatives. In this context, the following fully anonymized data will be made available to the scientific community:

• Data collected from the accelerometer-type sensor.
• Data on the subject's ocular behavior (events such as saccades or fixations) from the eye-tracking sensor. The videos from the glasses will not be shared.
• Behavioral data from video coding based on the ECOCAPTURE ethogram. The videos will not be shared.
• Scores from the neuropsychological assessment
• MRI data
• Blood test data.

2026-2030

Researchers must contact the scientific leaders of the study, and an agreement must be established with the sponsor (INSERM).