Novel Cross-Species Neurophysiological Assays of Reward and Cognitive Domains

Study Overview
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Brief Summary
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The overarching goal of this multi-disciplinary research program is to develop and optimize new cross-species translational assessments of reward and cognition that will not only be assessed in parallel in humans and rats, but also produce neurophysiological and behavioral metrics that can be objectively compared across species. The research will build on prior studies by further developing and optimizing (in Phase 1), then validating via pharmacological challenge (in Phase 2), the following assays in both humans and rats: advanced neurophysiological and computational modeling techniques to record and analyze EEG activity within and across species; and behavioral assessments of reward learning, cognitive control, and cognitive flexibility will be analyzed within and across species. The second phase of the study will test the translational validity of these assays, by assessing the impact of a targeted drug on task performance and EEG activity in both species.

Detailed Description
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The overarching goal of this multi-disciplinary research program is to develop and optimize new translational assessments of reward and cognition that will produce neurophysiological and behavioral metrics that enable objective comparison of drug effects. Phase 1 (2016-2018) will seek to develop and optimize computer-based tasks to measure of reward learning and cognition, to be administered during an EEG examination. Each participant will be asked to come for a single visit to complete a brief psychological assessment (interview and surveys), then perform two of the computer-based tasks while EEG data are collected. The three tasks are the Flanker Task, the Reversal Learning Task, and the Probabilistic Reward Task (PRT). In Phase 2 (2018-2021), a new set of participants will be enrolled for four visits. At the first visit they will have a brief psychological assessment (interview and surveys). They will then be assigned to one of the tasks developed during Phase I, and they will also be assigned to one of the study drugs: modafinil (a cognitive enhancer) or methylphenidate (a dopamine enhancer). At the second, third, and fourth visit, the subject will be given their drug in one of the three doses: a low dose, a higher dose, and a placebo. They will then perform the assigned task during an EEG exam.

Official Title
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Novel Cross-Species Neurophysiological Assays of Reward and Cognitive Domains

Conditions
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Translational Electrophysiology

Intervention / Treatment
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* Drug: Methylphenidate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adults Right-handed Exclusion Criteria: acute or chronic medical, neurological, or psychiatric illness any past/current diagnosis of mental health disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), including alcohol or substance abuse; use of any psychotropic medications in the past 6 months Current depressed mood (Beck Depression Inventory (BDI-II) score < 6) Current use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), warfarin, and other anticoagulants History of cocaine, stimulant, and other dopaminergic drug use (e.g., amphetamine, methylphenidate) Positive toxicology screen at any session

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Phase 1 Participants [No Study Drug]<br>Phase 1 participants are not being assigned to any study drug. | |
| Phase 2 Participants [Placebo]<br>Phase 2 participants that are randomly assigned to the placebo. | |
| Phase 2 Participants [Methylphenidate]<br>Phase 2 participants that are randomly assigned to take methylphenidate. | Drug: Methylphenidate<br>* cross-over, single-dose intervention<br>* Other names: Modafinil;|
| Phase 2 Participants [Modafinil]<br>Phase 2 participants that are randomly assigned to take modafinil. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feedback-related positivity (FRP) amplitudes over frontocentral scalp regions in response to rewarded trials versus no-reward trials. | Relative FRP response is the primary outcome measure for the probabilistic reward task (PRT) used in Phase 1. | 1 Day | 
| Event-related negativity (ERN) amplitudes over frontocentral scalp regions in response to correct trials versus incorrect trials. | Relative ERN response is the primary outcome measure for the flanker task. | 1 Day | 
| Feedback-related negativity (FRN) amplitudes over frontocentral scalp regions in response to negative feedback versus positive feedback. | Relative FRN response is the primary outcome measure for the reversal learning task. | 1 Day | 
| Behavioral Performance on the Flanker Task | The Flanker Task is a cognitive task that measures response inhibition to assess the ability to suppress responses that are inappropriate in a particular context. | 1 Day | 
| Behavioral Performance on the Reversal Learning Task | The task involves learning 'rule' which determine which of two abstract stimuli are selected. The rule changes in the middle of the block, and the goal is to see how quickly the participant can adapt to the rule change. Feedback is probabilistic. | 1 Day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Translational, Electrophysiology