Clinical trial NCT06489561: Neural Computations of Goal-directed Decision-making
Official title: Probing the Neural Computations Underlying Goal-directed Decision-making in Humans With Single-neuron Recordings
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: Epilepsy Intractable
Keywords: Epilepsy
Decision-making
Depth Electrode
Lead sponsor: Cedars-Sinai Medical Center
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
name: California Institute of Technology
First posted: 2024-07-08
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Decision Making (Firing Rates)
timeFrame: 5 years
measure: Decision Making (Power)
timeFrame: 5 years
measure: Decision Making (Timing)
timeFrame: 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
Study officials:
affiliation: Cedars-Sinai Medical Center
name: Ueli Rutishauser, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cedars-Sinai Medical Center
name: Adam Mamelak, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: California Institute of Technology
name: John O'Doherty, PhD
role: PRINCIPAL_INVESTIGATOR
References: