Characterizing the Neural Bases of Motivational Disorders After Stroke

Study Overview
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Brief Summary
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The aim of the study is to quantify elementary mechanisms of motivation, with innovative tools adapted to clinical settings, in healthy subjects, and in stroke patients, and to investigate their predictive value related to morbimortality, disability, and dependence. The secondary aim of the study is to investigate the neural substrates of motivational mechanisms, and to study the impact of lesions in the grey and the white matter, the influence of lesion site, and the consequences of disconnection in functional networks.

Detailed Description
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Disorders of motivation, such as apathy, are among the most prevalent symptoms in neuropsychiatric disorders and during chronic diseases. They have a major impact on patients' physical activity and lifestyle, and on their involvement in their own care. They affect a wide range of morbidity outcomes, alter functional recovery in rehabilitation, impair long-term disability, and prevent patients from returning to an active and independent life. Yet, the neural bases of motivational deficits remain largely unknown. Current diagnostic tools are sparse and cannot distinguish between distinct mechanisms responsible for apathetic syndromes. Besides, current treatments remain extremely limited. However, recent advances in the field of neuroeconomics - the science of decision-making - have provided concept and tools to study the neurobiological bases of elementary cognitive processes underlying motivated behaviors. These theories suggest that the brain implements optimization processes that determine our behaviors by minimizing the cost of our actions while maximizing their expected benefits. The adaptation of tools developed for basic research now enables the assessment of these cognitive mechanisms. Elementary deficits of motivation will be assessed with a phenotyping battery of motivation tests in 20 healthy subjects (up to 10 healthy subjects can be replaced), 20 patients (up to 10 patients can be replaced) with a stroke in the medial prefrontal cortex, and 20 patients (up to 10 patients can be replaced) with a stroke in the insula. This battery will allow us to characterize, at the patient's level, elementary processes such as the encoding and the learning rate of goal values or effort costs, the modulation of value with delay or episodic context, the modulation of cost with fatigue, and the resolution of cost-benefit trade-offs. We will record morbimortality outcomes, such as functional recovery, disability, quality of life and burden for caregivers. Symptom-Lesion mapping studies and voxel-based morphometry studies will be performed using whole brain MRI measures of structural and functional integrity.

Official Title
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Characterizing the Neural Bases of Motivational Disorders After Stroke

Conditions
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Stroke

Intervention / Treatment
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* Diagnostic Test: Motivation tests


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (healthy volunteers): Right-handed Age > 18 years old Able to squeeze a hand-grip Signature of consent form Affiliation to an Health Insurance Scheme or beneficiary of such a scheme Inclusion Criteria (patients): Age > 18 years old Able to squeeze a hand-grip Signature of consent form Affiliation to an Health Insurance Scheme or beneficiary of such a scheme Stroke of the medial frontal lobe and not affecting the lateral frontal lobe OR stroke of the lateral frontal lobe and not affecting the medial frontal lobe Exclusion Criteria (healthy volunteers): Under justice protection History of neurological or psychiatric diseases Evolving disease that could impede volunteer participation during the whole study Ongoing psychotropic drug or stopped for less than 3 weeks Treatment that could interfer with subject performance Chronical use of illicit psychoactive drugs or the day of the exam Pregnant, parturient or breastfeeding woman Exclusion period of another research Contra-indication to MRI scan Comprehension difficulties or difficulties to perform the study cognitive tests Exclusion Criteria (patients): Under justice protection Evolving disease that could impede volunteer participation during the whole study Chronical use of illicit psychoactive drugs or the day of the exam Pregnant, parturient or breastfeeding woman Exclusion period of another research Contra-indication to MRI scan Comprehension difficulties or difficulties to perform the study cognitive tests Brain sequela with important cognitive deficiencies preventing cognitive test interpretation according to the investigator

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: medial frontal stroke<br>20 patients (up to 10 patients can be replaced) with a stroke in the medial frontal lobe will be included in this arm, and will undergo motivation phenotyping. | Diagnostic Test: Motivation tests<br>* Motivation tests will characterize elementary deficits of motivation<br>|
| Other: lateral frontal stroke<br>20 patients (up to 10 patients can be replaced) with a stroke in the lateral frontal lobe will be included in this arm, and will undergo motivation phenotyping. | Diagnostic Test: Motivation tests<br>* Motivation tests will characterize elementary deficits of motivation<br>|
| Other: Healthy participants<br>20 healthy participants (up to 10 healthy participants can be replaced) will be included in this arm, and will undergo motivation phenotyping. | Diagnostic Test: Motivation tests<br>* Motivation tests will characterize elementary deficits of motivation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reward sensitivity | The reward sensitivity measures the impact of reward values on behavior | 1 day | 
| Effort sensitivity | The effort sensitivity measures the impact of effort costs on behavior | 1 day |