Neural Computations of Goal-directed Decision-making

NCT ID: NCT06489561

Last Updated: 2025-07-18

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: NA
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-08-01
• Study Completion Date: 2028-07-01

Brief Summary

The purpose of this research is to better understand how the human brain accomplishes the cognitive task of making goal-directed decisions. These investigations are critical to better understand human cognition and to design treatments for disorders of decision making and performance monitoring.

Detailed Description

Flexible goal-directed decision-making is a core aspect of higher-order adaptive biological intelligence. A number of psychiatric disorders involve impairments in goal-directed decision-making, yet the current lack of even a basic understanding of how goal-directed action selection is implemented at the neuronal level in humans hinders the ability to pinpoint these neuropsychiatric dysfunctions. In particular, it is completely unknown how goals, and the stimuli and actions that need to be selected from in order to pursue them, are represented at the level of single neurons, nor how goals get selected from available possible goals.

The study experiments utilize the rare opportunity to record in-vivo from human single neurons simultaneously in multiple brain areas in patients undergoing treatment for drug resistant epilepsy. The study will utilize a combination of (i) in-vivo recordings in awake behaving humans assessing decision making accuracy and ability through choice ratings, (ii) computational analysis and modeling.

These techniques will be applied to characterize the functional contribution of human ventromedial prefrontal (vmPFC), dorsal anterior cingulate (dACC) and pre-supplementary motor area (pre-SMA) in these processes. Investigators will first test the longstanding proposal never tested at the neuronal level in humans that the value of stimuli is especially represented by neurons in vmPFC, while the value of actions are more represented by neurons in dorsal cortical areas such as the pre-SMA. Investigators will then address how goals themselves are represented. In the real world, animals including humans need to select a goal before any action is performed. Thus, there is a hierarchical process of goal selection followed by action selection. Investigators hypothesize that the vmPFC plays a specific role in goal-valuation and selection, while neurons in dorsomedial areas including pre-SMA and dACC will play more of a role in valuing and selecting the actions that implement the chosen goal.

The expected outcome of this work is a comprehensive understanding of the functions of the human PFC in goal-directed decision-making at cellular resolution while shedding light on the neural mechanisms of goal-representation and selection which hitherto has been virtually unstudied.

Conditions

Epilepsy Intractable

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Behavioral Testing

Behavioral and Neuronal Recordings

Group Type: EXPERIMENTAL

Cedrus RB-844 response pad; Adtech Behnke-Fried micro-electrodes; Neurolynx electrophysiology system

Intervention Type: BEHAVIORAL

Devices listed are components of a single intervention that includes: Record patient responses (Cedrus RB-844), record neuronal activity (Neurolynx) from electrodes (Adtech Behnke-Fried)

Interventions

Cedrus RB-844 response pad; Adtech Behnke-Fried micro-electrodes; Neurolynx electrophysiology system

Devices listed are components of a single intervention that includes: Record patient responses (Cedrus RB-844), record neuronal activity (Neurolynx) from electrodes (Adtech Behnke-Fried)

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• Intractable epilepsy, undergoing invasive monitoring
• Age ≥13
• Full Scale Intelligence Quotient > 70
• Ability to comprehend and perform simple behavioral tasks by pressing buttons on laptop computer in response to questions

Exclusion Criteria

• Determination by clinicians and investigators that a patient is unable to complete the behavioral tasks required for the protocol due to either cognitive limits, psychological limits, or pain

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

California Institute of Technology

OTHER

Sponsor Role: collaborator

Cedars-Sinai Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Adam Mamelak, MD

Staff Physician III

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ueli Rutishauser, PhD

Role: PRINCIPAL_INVESTIGATOR

Cedars-Sinai Medical Center

Adam Mamelak, MD

Role: PRINCIPAL_INVESTIGATOR

Cedars-Sinai Medical Center

John O'Doherty, PhD

Role: PRINCIPAL_INVESTIGATOR

California Institute of Technology

Locations

Cedars-Sinai Medical Center

Los Angeles, California, United States

Countries

United States

Other Identifiers

R01MH133729

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MOD00001351

Identifier Type: -

Identifier Source: org_study_id