Novel Cross-Species Neurophysiological Assays of Reward and Cognitive Domains

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:

1. advanced neurophysiological and computational modeling techniques to record and analyze EEG activity within and across species; and
2. 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.

Study Overview

• Status: Completed
• Conditions: Translational Electrophysiology
• Intervention / Treatment: Drug: Methylphenidate

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 222

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Belmont, Massachusetts, United States, 02478
      • McLean Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Healthy adults

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

4

Cohorts and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Mclean Hospital
• Investigators: Principal Investigator: Diego A Pizzagalli, PhD, McLean Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2020
• Primary Completion (Actual): August 31, 2021
• Study Completion (Actual): August 31, 2021

Study Registration Dates

• First Submitted: July 11, 2016
• First Submitted That Met QC Criteria: August 1, 2016
• First Posted (Estimated): August 4, 2016

Study Record Updates

• Last Update Posted (Actual): October 30, 2024
• Last Update Submitted That Met QC Criteria: October 28, 2024
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Electrophysiology; Translational
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Membrane Transport Modulators; Central Nervous System Stimulants; Dopamine Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Dopamine Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Wakefulness-Promoting Agents; Modafinil; Methylphenidate
• Other Study ID Numbers: 2015P001757/MGH

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All collected IPD will be shared via NIMH Data Archive (as part of data submission agreement)
• IPD Sharing Time Frame: All collected IPD are shared every 6 months (1/15 and 7/15 of each year). Uploading will begin in 2019.
• IPD Sharing Access Criteria: Investigators may request for access for approval by the NIMH.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• product manufactured in and exported from the U.S.: No