Exploring the Role of the Prefrontal Cortex in Decision-Making

Overview

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.

Interventions

• Device Active high-definition transcranial direct current stimulation (HD-tDCS) - anodal F3/F4
  Participants receive anodal HD-tDCS targeting the left or right DLPFC (F3/F4).
• Device Sham high-definition transcranial direct current stimulation (HD-tDCS) - anodal F3/F4
  Participants receive sham HD-tDCS targeting the left or right DLPFC (F3/F4). The device mimics the sensation of stimulation without delivering active current.
• Device Active high-definition transcranial direct current stimulation (HD-tDCS) - anodal F3/ kathodal F4
  Participants receive anodal HD-tDCS targeting the left DLPFC (F3) and cathodal stimulation targeting the right DLPFC (F4).
• Device Sham high-definition transcranial direct current stimulation (HD-tDCS) - anodal F3/ kathodal F4
  Participants receive sham HD-tDCS targeting the left DLPFC (F3) and right DLPFC (F4). The device mimics the sensation of stimulation without delivering active current.

Primary outcome measures

• Blood-oxygen-level-dependent (BOLD) signal changes during task-based functional magnetic resonance imaging (fMRI) [Time frame: During study visit; measured continuously during the 20-minute stimulation period]
• GABA concentration (baseline) [Time frame: During study visit; during a 9-minute magnetic resonance spectroscopy (MRS) session performed up to 10 minutes prior to the 20-minute stimulation period]
• GABA concentration (after stimulation) [Time frame: During study visit; within 1 minute after the 20-minute stimulation period, during a 9-minute MRS scan]
• Glutamate concentration (baseline) [Time frame: During study visit; during a 9-minute magnetic resonance spectroscopy (MRS) session performed up to 10 minutes prior to the 20-minute stimulation period]
• Glutamate concentration (after stimulation) [Time frame: During study visit; within 1 minute after the 20-minute stimulation period, during a 9-minute MRS scan]

Secondary outcome measures (6)

• Positive Affect measured by PANAS (baseline) [Time frame: During study visit; at baseline, up to two hours before the 20-minute stimulation period]
• Negative Affect measured by PANAS (baseline) [Time frame: During study visit; at baseline, up to two hours before the 20-minute stimulation period]
• Positive Affect measured by PANAS (after stimulation) [Time frame: During study visit; after stimulation, up to 1 hour]
• Negative Affect measured by PANAS (after stimulation) [Time frame: During study visit; after stimulation, up to 1 hour]
• Storytelling (baseline) [Time frame: During study visit; at baseline, up to two hours before the 20-minute stimulation period]
• Storytelling (after stimulation) [Time frame: During study visit; after stimulation, up to 1 hour]

Eligibility criteria

Inclusion Criteria (Healthy):

• Written Informed Consent
• Age between 20-40 or 60-75 years
• Fluent in German
• Normal or corrected-to-normal vision
• No color blindness
• Right-handed
• Non-smoker

Exclusion Criteria (Healthy):

• History of neurological disorders
• History of psychiatric disorders
• Use of psychotropic medication
• Presence of magnetizable implants
• Alcohol or drug dependence

Inclusion Criteria (Patient):

• Written Informed Consent
• Diagnosed with mild to moderate depression
• Age between 20-40 or 60-75 years
• Fluent in German
• Normal or corrected-to-normal vision
• No color blindness

Exclusion Criteria (Patient):

• Intake of benzodiazepines or antipsychotic medication
• psychiatric disorders other than depression (e.g., psychosis, mania, personality disorders) or depression with organic cause
• Presence of magnetizable implants
• Alcohol or drug dependence

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Basic science

Study locations

Switzerland · 1 center

• University of Bern, Department of Old Age Psychiatry and Psychotherapy — Bern

Identifiers

NCT: NCT07080489 · 2024-01010

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗