Neural Bases of Motivation (MOTIVACTION)

Civil Hospices of Lyon

Status: Enrolling

Conditions: Motivation; Healthy Volunteers; Action

Treatments: Behavioral: Neuropsychological scales; Procedure: Bifocal transcranial alternating current stimulation (tACS); Procedure: Transcranial direct current stimulation (tDCS); Procedure: Transcutaneous vagal nerve stimulation (tVNS); Procedure: Combining transcranial temporal interference stimulation (tTIS) and oscillatory TMS; Procedure: Pupillometry; Procedure: MEG; Procedure: EEG; Procedure: Cortico-cortical paired-associative stimulation (ccPAS); Procedure: MRI

Study type: Interventional

Funder types: Other

Identifiers

NCT07251816

2025-A00984-45 (Other Identifier)

69HCL25_0205

Details and patient eligibility

About

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.

Enrollment: 204 estimated patients

Sex: All

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Healthy volunteers aged between 18 and 40 years
• Participants without confounding factors such as neural alterations related to neurological pathology, whether neurodegenerative (e.g., Alzheimer, Parkinson, Huntington, multiple sclerosis, amyotrophic lateral sclerosis), motor (e.g., dystonia, essential tremors, cerebellar syndrome), traumatic (e.g., traumatic brain injury, medulla lesion) or psychiatric pathologies, whether mood disorders (e.g., depression, bipolarity), anxious troubles (e.g., obsessional compulsive disorder, post-traumatic stress disorder), psychotic (e.g., schizophrenia, delusion), substance-related (e.g., alcool, drug or medicine addiction), food-related (e.g., anorexia, bulimia), neurodevelopmental (e.g., autism, attention-deficit with hyperactivity disorder) or personality (e.g., borderline personality disorder, antisocial personality disorder, obsessive-compulsive disorder).
• Participants affiliated with a compulsory social security scheme.

Exclusion criteria

• Persons deprived of liberty by judicial or administrative decisions.
• Pregnant women, women in labor or breastfeeding women
• Persons admitted to a health or social institution for purposes other than research.
• Adults under legal protection measures (e.g., guardianship or curatorship).
• Participation in other interventional research with an ongoing non-inclusion period.
• Neurological or psychiatric disorders.
• Use of tricyclic antidepressants (amitriptyline, clomipramine, imipramine, nortriptyline), neuroleptics (chlorpromazine, haloperidol, risperidone, olanzapine, quetiapine), or recreational drugs within the past 48 hours.
• Regular use of recreational drugs.
• Sleep deprivation (< 5 hours regularly over the last 3 months)
• Left-handedness or ambidexterity.
• Physical injuries impacting motor tasks.
• Presence of metal implants in the head (excluding oral fillings).
• Presence of implanted medical devices (e.g., pacemaker).
• Presence of metallic injuries in the eyes.
• Claustrophobia.
• Piercings incompatible with MRI procedures.
• Contraindication to MRI
• Persons who refused to be informed of eventual medical anomalies discovered by the MRI
• Personal or family history (first-degree relatives) of epilepsy or seizures. Severe and/or frequent headaches (only for participants receiving transcranial magnetic stimulation, e.g preparatory experience 1 and experience 1)
• Baldness impeding electrode placement (only for participants receiving transcranial electrical stimulation and EEG measurements, e.g experiments 2, 3 and 4)
• Facial or ear pain and/or recent ear trauma (only for participants receiving transcutaneous vagal nerve stimulation, e.g experiment 5)

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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204 participants in 7 patient groups

Experiment 1

Experimental group

Description:

First, participant will undergo a structural magnetic resonance imaging (MRI). Then, participant will come to the scanner for 3 sessions. In each of the three sessions, participant will first perform the effort-based decision-making task in the functional (f)MRI scanner to establish baseline measures of decision behavior and connectivity. Following this, cortico-cortical paired associative stimulation will be applied using one of three conditions: 1. the supplementary motor area will be stimulated first, followed by the motor cortex. 2. the motor cortex will be stimulated first, followed by the supplementary motor area. 3. control stimulation, where the supplementary motor area will be stimulated first, followed by the motor cortex with a minimal 1 ms delay, which will not modulate effective connectivity. After stimulation, participant will again perform the effort-based decision-making task in the fMRI scanner.

Treatment:

Procedure: MRI

Procedure: Cortico-cortical paired-associative stimulation (ccPAS)

Procedure: Pupillometry

Behavioral: Neuropsychological scales

Experiment 2

Experimental group

Description:

First, participant will undergo a structural MRI scan. Then, participant will come for three sessions. In each session, participants will begin by performing the effort-based decision-making task while their baseline behavioral and neural activity is recorded using electroencephalography (EEG). Following this initial task, bifocal transcranial alternating current stimulation (tACS) will be applied under one of three conditions: 1. real, in-phase stimulation to synchronize oscillations between the supplementary motor area and motor cortex; 2. real, in-phase stimulation to synchronize oscillations between the orbitofrontal cortex and motor cortex; 3. control stimulation, where oscillations between the supplementary motor area and the motor cortex are applied in antiphase. Participant will perform the decision-making task during the stimulation. After the stimulation, participant will repeat the decision-making task with EEG recording.

Treatment:

Procedure: MRI

Procedure: EEG

Procedure: Pupillometry

Procedure: Bifocal transcranial alternating current stimulation (tACS)

Behavioral: Neuropsychological scales

Experiment 3

Experimental group

Description:

First, participant will undergo a structural MRI scan. Then, participants will come to the lab to record electroencephalography (EEG) for three sessions. In each session, participant will begin by performing the effort-based decision-making task with EEG recording. Following this initial task, combined oscillatory magnetic stimulation and temporal interference stimulation will be applied under one of three conditions: 1. real oscillatory magnetic stimulation combined with real temporal interference stimulation; 2. control oscillatory magnetic stimulation (using a control coil, making the same noise as a real stimulation) combined with real temporal interference stimulation; 3. both control oscillatory magnetic stimulation and a control temporal interference stimulation as a control condition. Participant will perform the decision-making task during stimulation. After the stimulation, participant will repeat the decision-making task with EEG recording.

Treatment:

Procedure: MRI

Procedure: EEG

Procedure: Pupillometry

Procedure: Combining transcranial temporal interference stimulation (tTIS) and oscillatory TMS

Behavioral: Neuropsychological scales

Experiment 4

Experimental group

Description:

Participant will come to the MRI facilities for three sessions. In each session, participants will begin by performing the effort-based decision-making task while their baseline behavioral and neural activity is recorded using fMRI. Following this initial task, transcranial direct current stimulation will be applied under one of three conditions: 1. real anodal stimulation, 2. real cathodal stimulation, 3. control stimulation. Participant will perform the decision-making task during stimulation. Further, stimulation will be realized in the scanner using an MRI-compatible set-up, to directly measured the changes in neural activity induced by the stimulation. After the stimulation, participants will repeat the decision-making task with fMRI recording.

Treatment:

Procedure: MRI

Procedure: Pupillometry

Procedure: Transcranial direct current stimulation (tDCS)

Behavioral: Neuropsychological scales

Experiment 5

Experimental group

Description:

Participant will come to the MRI facilities for one experimental session. In this single session, participant will first perform the task while transcutaneous vagal nerve stimulation will be applied under one of two conditions in separate blocks of trials: 1. real stimulation, aimed at modulating the activity of the locus coeruleus and influencing the noradrenergic system; 2. control stimulation, which serves as a control to account for non-specific effects of the procedure. During the stimulation, participant will continue performing the decision-making task.

Treatment:

Procedure: MRI

Procedure: Pupillometry

Procedure: Transcutaneous vagal nerve stimulation (tVNS)

Behavioral: Neuropsychological scales

Preparatory experiment 1

Experimental group

Description:

First, each participant will undergo a structural magnetic resonance imaging session at the CERMEP. The acquired data will be used for neuro-navigation, ensuring precise targeting of brain regions during the paired-pulse stimulation procedure. Then, participants will perform the effort-based decision-making task while paired-pulse stimulation is applied during the decision-making period. The stimulation will target circuits connecting the supplementary motor area and the motor cortex. Test pulses will be delivered to the motor cortex, either alone or preceded by a conditioning pulse to the supplementary motor area. These conditioned and unconditioned stimulations will occur at random intervals during the decision-making phase of the task. Motor-evoked potentials will be recorded with surface electromyography throughout the decision-making period.

Treatment:

Procedure: MRI

Procedure: Cortico-cortical paired-associative stimulation (ccPAS)

Procedure: Pupillometry

Behavioral: Neuropsychological scales

Preparatory experiment 2

Experimental group

Description:

First, participants will perform the effort-based decision-making task while MEG is used to record neural oscillatory activity (one session). This recording will take place at the MEG facility of the CERMEP, ensuring high temporal and spatial precision in capturing brain dynamics during task performance. Then, each of the participants will undergo a structural MRI scan that will be used to improve source localization during MEG data processing.

Treatment:

Procedure: MRI

Procedure: Pupillometry

Procedure: MEG

Behavioral: Neuropsychological scales