Multimodal Differences in Effort-based Decision-Making in Depression (BBQS)

Multimodal Differences in Effort-based Decision-Making in Depression - - Brain Behavior Quantification and Synchronization

Major depressive disorder (MDD) is a serious condition that causes long-term symptoms such as feeling sad, losing interest in activities, and having thoughts of self-harm. Difficulty in making an effort is a key factor in functional impairment. Current methods to evaluate this difficulty use clinical assessments and computer-based tasks, but there is a gap between the measurements and real-life behavior. To address this, the study team proposes creating an instrumented behavioral test, HORMES, to objectively assess reduced motivation during everyday activities and measure physiological responses. The study will examine differences in brain activity, autonomic system function, and metabolic energy expenditure in patients with major depression during a decision-making task that involves physical effort.

Study Overview

• Status: Not yet recruiting
• Conditions: Depression; Anhedonia
• Intervention / Treatment: Other: Effort-based Decision-Making Task

Detailed Description

Major depressive disorder (MDD) is a debilitating neuropsychiatric condition characterized by multiple chronic symptoms, including sad mood, anhedonia, psychomotor symptoms, and suicidal thoughts. MDD induces significant personal and societal suffering, becoming the largest contributor to the overall disease burden in developed countries. There is clearly an urgent need to advance our understanding of MDD and its constituent symptoms. Of these, the inability to expend effort have proven harder to treat than mood-related symptoms and are key predictors of functional impairment and disease burden. The biological mechanisms that contribute to this impairment are not fully understood. Addressing this gap in knowledge will be helpful in developing therapy, including novel brain stimulation therapies that offer the ability to target brain circuits precisely.

Current evaluation approaches to characterizing reduced motivation rely on clinical assessments of patient symptoms through interviews and observation. While these typically assess functions relevant to patient quality of life, these assessments may be confounded by biases. On the other hand, translational research focuses on characterizing symptoms using computer-based tasks that provide quantitative objective markers (e.g., reaction time in pressing a key on a keyboard) but may not reflect real-life situations. In addition, studies investigating brain mechanisms often use functional magnetic resonance imaging (fMRI), which requires patients to be stationary. Thus, there is a fundamental disconnect between measurements of behavior and the behavior itself under study.

To overcome these limitations, the study team envisions developing an instrumented behavioral assay, HORMES, that allows the objective assessment of reduced motivation during naturalistic behavior with concurrent measurements of the central and autonomic nervous systems as well as metabolic energy expenditure. This assay will utilize a CAREN system at Human Augmentation Core, a core facility available at Georgia Tech that is currently used for biomechanics research.

The proposed study will investigate differences in brain activity, autonomic system function, and metabolic energy expenditure in patients with major depression and matched controls during an effort-based decision-making task. The study team will collect multiple physiological measures - brain activity, cardiac activity, breathing activity, and energy expenditure in patients with major depression when they walk on a treadmill. Biomechanical information will be obtained using motion capture. The amount of effort they will need to expend will be varied by adjusting the treadmill's incline. These measures will be compared against those from a control group with age, gender, and BMI-matched healthy individuals.

The outcome of this study will inform what differences exist between healthy individuals and individuals with depression. The participants will be recruited from the Atlanta metro area and will all be allocated to the intervention. which is a behavioral task. The task requires participants to maximize rewards by choosing to pursue actions of different levels of physical effort (walking).

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Christopher J Rozell, Ph.D.; Phone Number: 404-385-7671; Email: crozell@gatech.edu
• Study Contact Backup: Name: Sankaraleengam Alagapan, Ph.D.; Email: sankar.alagapan@gatech.edu

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Georgia Tech Manufacturing Institute
      • Contact: Christopher J Rozell, Ph.D.; Phone Number: 404-385-7671; Email: crozell@gatech.edu
      • Contact: Sankaraleengam Alagapan, Ph.D.; Email: sankar.alagapan@gatech.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Matched control group

  • 18-65 years old
  • Able-bodied
  • Fluent in English
  • Able to give written and verbal informed consent to the proposed experiment
  • Able to comprehend the study procedure, potential risks, and benefits

• Group with depression

  • Diagnosed with major depression
  • Quick Inventory of Depression Symptomology (QIDS) score > 5
  • 18-65 years old
  • Able-bodied
  • Fluent in English
  • Able to give written and verbal informed consent to the proposed experiment
  • Able to comprehend the study procedure, potential risks, and benefits

Exclusion Criteria:

• Matched control group

  • Current diagnosed psychiatric disorder (e.g., anxiety, depression, bipolar disorder)
  • Current pregnancy
  • BMI > 35
  • Currently on antipsychotics

• Group with depression

  • Diagnosed with psychotic symptoms
  • Diagnosed with other neurological or psychiatric disorders
  • Current pregnancy
  • BMI > 35
  • Currently on antipsychotics

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Effort-based decision-making; Participants perform a virtual-reality-based task in which they expend effort to receive virtual rewards.	Other: Effort-based Decision-Making Task; Virtual Reality-based multi-stage task in which individuals must explore distinct "rooms" in a virtual environment that vary in the amount of effort (walking) and reward (points) they receive.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time spent in high-effort "rooms"	Participants will be measured on how much time they spend in "rooms" that require high effort in the form of walking on an inclined treadmill as a proportion of the total duration of the task. This measures the willingness of participants to engage in effortful behavior.	1 day

Collaborators and Investigators

• Sponsor: Georgia Institute of Technology
• Collaborators: Icahn School of Medicine at Mount Sinai; Emory University
• Investigators: Principal Investigator: Christopher J Rozell, Ph.D., Georgia Institute of Technology

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): August 31, 2029
• Study Completion (Estimated): September 30, 2030

Study Registration Dates

• First Submitted: October 17, 2024
• First Submitted That Met QC Criteria: October 17, 2024
• First Posted (Actual): October 18, 2024

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Physical Effort; Effort-based decision-making
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Behavioral Symptoms; Neurobehavioral Manifestations; Pathological Conditions, Signs and Symptoms; Behavior; Signs and Symptoms; Depression; Anhedonia
• Other Study ID Numbers: H24306

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified data will be shared in the NIMH Data Archive (NDA) at the end of the project. De-identified data sets will be anonymized prior to posting on the public repository. Shared data will include behavioral task outcomes, physiological data, and participant demographics.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No