Aging, Depressive Disorder, Major Depressive Disorder, Healthy Volunteer
Conditions
Keywords
UHF fMRI, DLPFC, fMRI, HD-tDCS, Cognitive Control, Noninvasive Brain Stimulation, Depression, Aging
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.
Interventions
DEVICEActive high-definition transcranial direct current stimulation (HD-tDCS) - anodal F3/F4
Participants receive anodal HD-tDCS targeting the left or right DLPFC (F3/F4).
DEVICESham 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.
DEVICEActive 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).
DEVICESham 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.
Sponsors
University of Bern
ki:elements
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Masking description
Participants and experimentors are blinded to the intervention. The principal investigator managing randomization and code assignment is unblinded. Outcomes assessors remain blinded during data collection but will be unblinded after data collection is completed for final analysis.
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Switzerland
Contacts
CONTACTMaya D Yilmaz, M.Sc.
PRINCIPAL_INVESTIGATORJessica Peter, PhD
University of Bern
Outcome results
None listed