Neural Bases of Motivation

Summary

Effort-based decisions are essential in daily life but strongly impaired in apathy across various brain disorders. Now, significant research to unveil the neural causes of apathy is needed. A crucial corollary to this is the need to identify the brain network and neural mechanisms underlying effort-based decisions.

A fronto-striatal network and the noradrenergic system are involved in effort-based decision-making and apathy. Further, motor cortical structures may play a role in effort-based decision-making. However, the role of circuits connecting the fronto-striatal network and the noradrenergic system to the motor structures has been disregarded so far.

Non-invasive brain stimulation methods provide a unique and safe means to test the causal role of connectivity changes between fronto-subcortical and motor structures in effort-based decision-making.

It's now necessary to have an integrative, connectionnist framework to uncover the causal role of connectivity changes between fronto-subcortical and motor structures in effort-based decision-making.

The overarching goal of the present research protocol is to establish an integrative framework testing the causal role of connectivity within recurrent, bidirectional circuits between fronto-subcortical circuits and motor structures in effort-based decision-making. To achieve this overarching goal, investigators will quantifiy the causal role of effective connectivity and oscillatory synchrony in these circuits on effort-related behavior using a non-invasive brain stimulation strategy. Further, a secondary aim is to identify potential non-invasive brain stimulation methods that could increase engagement in effortful behavior, paving the way for translational clinical applications in the context of apathy.

The investigators hypothesize that effort-based decision-making in healthy subjects is governed by bidirectional interactions between fronto-subcortical circuits and motor structures such as the primary motor cortex, mediated by oscillatory synchrony in specific frequency bands (e.g., theta and gamma bands). Accordingly, they hypothesize that transient, non-invasive modulation of connectivity and oscillatory synchrony between these structures in healthy human subjects will directly modulate their decision to engage in effort. Specifically, five experiments will use complementary approaches to test the hypothesis.

Conditions

• Healthy Volunteers
• Motivation
• Action

Interventions

PROCEDURE

Cortico-cortical paired-associative stimulation (ccPAS)

Transcranial magnetic stimulation (TMS)

PROCEDURE

Bifocal transcranial alternating current stimulation (tACS)

Transcranial electrical stimulation (tES)

PROCEDURE

Combining transcranial temporal interference stimulation (tTIS) and oscillatory TMS

Transcranial electrical stimulation and transcranial magnetic stimulation

PROCEDURE

Transcranial direct current stimulation (tDCS)

Transcranial electrical stimulation

PROCEDURE

Transcutaneous vagal nerve stimulation (tVNS)

Transcutaneous vagal nerve stimulation (tVNS)

PROCEDURE

MRI

Magnetic Resonance Imaging

PROCEDURE

MEG

Magnetoencephalography

PROCEDURE

Pupillometry

Measurement and analysis of changes in pupil diameter over time, providing a non-invasive and straightforward method to investigate physiological and psychological processes. Using an eye tracker or pupillometer equipped with infrared cameras, pupil size is measured with high precision and temporal resolution. Pupil responses serve as a proxy for effort invigoration and are linked to multiple neuromodulatory systems, including the noradrenergic system. Recordings will be conducted throughout both experiments, with participants instructed to minimize movements and blinking to ensure data quality.

BEHAVIORAL

Neuropsychological scales

Different neuropsychological scales will be administered to assess various psychological and behavioral dimensions relevant to the study, such as: the Apathy Evaluation Scale (AES): To evaluate levels of apathy ; the Depression Anxiety Stress Scale (DASS): To assess depression, anxiety, and stress ; and the Snaith-Hamilton Pleasure Scale (SHAPS): To evaluate the inability to experience pleasure.

PROCEDURE

EEG

Electroencephalography

Sponsors & Collaborators

• Hospices Civils de Lyon

  lead OTHER

Study Design

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

40 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2026-01-14

Primary Completion

2033-01-31

Completion

2033-01-31

Countries

• France

Study Locations