Exploring the Role of the Prefrontal Cortex in Decision-Making

Not Applicable

Recruiting

• Conditions: Depressive Disorder, Major Depressive Disorder; Healthy Volunteer; Aging

• Registration Number: NCT07080489
• Lead Sponsor: University of Bern

Brief Summary

The goal of this study is to examine whether high-definition transcranial direct current stimulation (HD-tDCS) can influence decision-making for emotionally valenced content in younger and older adults, with or without major depression.

The main questions are:

In healthy adults, does brain stimulation modulate how people respond to emotionally valenced content during a decision-making task? What happens in the brain during modulation? Do these effects differ between younger and older adults?

In adults with depression, does brain stimulation help shift attention towards positive content during the task? What happens in the brain? Are these effects moderated by age (younger vs. older adults)?

The investigators will compare participants who receive real stimulation to those who receive sham (placebo) stimulation.

Participants will:

Receive high-definition transcranial direct current stimulation (HD-tDCS) of the dorsolateral prefrontal cortex (DLPFC)

Perform a decision-making task involving emotionally valenced words

Complete the task while undergoing a brain scan using ultra-high field 7 Tesla magnetic resonance imaging (MRI) to measure brain activity

Detailed Description

This study investigates whether non-invasive brain stimulation influences decision-making in four groups: younger adults (20-40 years) and older adults (60-75 years), healthy or with mild to moderate major depression. Participants with personality disorders or psychosis will be excluded.

The study builds on evidence that the dorsolateral prefrontal cortex (DLPFC) plays a key role in evaluating emotionally-valenced material and decision-making. The investigators will examine whether modulation of this region through high-definition transcranial direct current stimulation (HD-tDCS) affects responses to emotionally valenced information. Stimulation will be administered differently across groups based on theoretical models of hemispheric function in mood regulation.

To explore the effect of stimulation at neurotransmitter level, the investigators will use ultra-high field 7 Tesla magnetic resonance spectroscopy (MRS) to measure Gamma-aminobutyric acid (GABA) / Glutamate concentrations in regions of interest at baseline and after stimulation. This allows to examine whether changes in inhibitory/excitatory neurotransmitters are linked to altered emotional processing and decision making.

By combining brain stimulation, ultra-high field neuroimaging, and spectroscopy, this study examines how changes in brain network activity and neurotransmitter levels relate to decision-making in health and disease. The inclusion of both younger and older adults allows the investigators to explore age-related differences in these processes.

This project aims to provide mechanistic insights into decision-making in health and disease and to support the development of targeted neuromodulation therapies that could modulate emotional processing.

Study Timeline

• Study Start: 2025-03-04
• Status Verified: 2025-07
• Study First Submitted: 2025-07-10
• Study First Submitted QC: 2025-07-14
• Last Update Submitted: 2025-07-14
• Study First Posted: 2025-07-23
• Last Update Posted: 2025-07-23
• Primary Completion: 2027-07
• Study Completion: 2027-10-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 444

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Blood-oxygen-level-dependent (BOLD) signal changes during task-based functional magnetic resonance imaging (fMRI)	During study visit; measured continuously during the 20-minute stimulation period	Blood-oxygen-level-dependent (BOLD) signal changes will be measured using ultra-high field functional magnetic resonance imaging (fMRI) during a cognitive decision-making task designed to engage prefrontal cortex regions associated with cognitive control and decision making. Structural T1-weighted and T2-weighted images will also be acquired for anatomical localization and normalization. Primary regions of interest (ROIs) include the dorsolateral prefrontal cortex (DLPFC), subgenual anterior cingulate cortex (sgACC), amygdala, and hippocampus.
GABA concentration (baseline)	During study visit; during a 9-minute magnetic resonance spectroscopy (MRS) session performed up to 10 minutes prior to the 20-minute stimulation period	Magnetic resonance spectroscopy (MRS) will be used to measure Gamma-aminobutyric acid (GABA) concentrations in regions of interest at baseline. The goal is to examine stimulation-related neutransmitter changes.
GABA concentration (after stimulation)	During study visit; within 1 minute after the 20-minute stimulation period, during a 9-minute MRS scan	Magnetic resonance spectroscopy (MRS) will be used to measure Gamma-aminobutyric acid (GABA) concentrations in regions of interest after HD-tDCS. The goal is to examine stimulation-related neutransmitter changes.
Glutamate concentration (baseline)	During study visit; during a 9-minute magnetic resonance spectroscopy (MRS) session performed up to 10 minutes prior to the 20-minute stimulation period	Magnetic resonance spectroscopy (MRS) will be used to measure Glutamate concentrations in regions of interest at baseline. The goal is to examine stimulation-related neutransmitter changes.
Glutamate concentration (after stimulation)	During study visit; within 1 minute after the 20-minute stimulation period, during a 9-minute MRS scan	Magnetic resonance spectroscopy (MRS) will be used to measure Glutamate concentrations in regions of interest after HD-tDCS. The goal is to examine stimulation-related neutransmitter changes.

Secondary Outcome Measures

Name	Time	Method
Positive Affect measured by PANAS (baseline)	During study visit; at baseline, up to two hours before the 20-minute stimulation period	Positive Affect will be assessed using the Positive Affect subscale of the Positive and Negative Affect Schedule (PANAS). This subscale includes 10 items reflecting positive emotions. Each item is rated on a 5-point Likert scale. The sum score ranges from 10 to 50, with higher scores indicating greater levels of positive affect.
Negative Affect measured by PANAS (baseline)	During study visit; at baseline, up to two hours before the 20-minute stimulation period	Negative Affect will be assessed using the Negative Affect subscale of the Positive and Negative Affect Schedule (PANAS). This subscale includes 10 items reflecting negative emotions. Each item is rated on a 5-point Likert scale. The sum score ranges from 10 to 50, with higher scores indicating greater levels of negative affect.
Positive Affect measured by PANAS (after stimulation)	During study visit; after stimulation, up to 1 hour	Positive Affect will be assessed using the Positive Affect subscale of the Positive and Negative Affect Schedule (PANAS). This subscale includes 10 items reflecting positive emotions. Each item is rated on a 5-point Likert scale. The sum score ranges from 10 to 50, with higher scores indicating greater levels of positive affect.
Negative Affect measured by PANAS (after stimulation)	During study visit; after stimulation, up to 1 hour	Negative Affect will be assessed using the Negative Affect subscale of the Positive and Negative Affect Schedule (PANAS). This subscale includes 10 items reflecting negative emotions. Each item is rated on a 5-point Likert scale. The sum score ranges from 10 to 50, with higher scores indicating greater levels of negative affect.
Storytelling (baseline)	During study visit; at baseline, up to two hours before the 20-minute stimulation period	Participants will be asked to verbally recall one positive and one negative autobiographical memory. Verbal responses will be audio recorded and analyzed using automated speech analysis. The analysis will be performed by ki:elements, an external provider specialized in speech analysis.
Storytelling (after stimulation)	During study visit; after stimulation, up to 1 hour	Participants will be asked to verbally recall one positive and one negative autobiographical memory. Verbal responses will be audio recorded and analyzed using automated speech analysis. The analysis will be performed by ki:elements, an external provider specialized in speech analysis.

Trial Locations

Locations (1)

University of Bern, Department of Old Age Psychiatry and Psychotherapy; 🇨🇭 Bern, Switzerland