Quantifying tACS-driven Improvement of Working Memory in Depression

TACS is an emergent method of non-invasive neuromodulation which can engage frequency-specific brain oscillations. It is increasingly recognized that neural oscillations play a system-organizing role in the brain. Evidence suggests that disorganized neural oscillations may also influence functionality of cognitive processes such as working memory. Thus, as TACS can affect neural oscillatory activity in the human brain in a non-invasive manner, it has promise to transform mental health care. The premise of this proposed work is that tACS concurrent with multi-session working memory (WM) focused skills will facilitate durable working memory and stabilized neural oscillations. Depression offers an excellent model to study the effects of tACS. The study seeka to administer 2mA of tACS using theta oscillations to improve working memory concerns associated with depression. The purpose of this study is to investigate the electrophysiological and behavioral effects of transcranial alternating current stimulation (tACS) in humans and to explore specific improvements in working memory and depressive symptoms. This study is placebo-controlled study. Participants will undergo pre- and post-assessments and either theta or sham tACS for 5 days. During each session, the volunteer will perform cognitive tasks while receiving tACS. Assessment sessions will include cognitive tasks, questionnaires, a clinical interview, and EEG.

Study Overview

• Status: Withdrawn
• Conditions: Depression
• Intervention / Treatment: Other: sham tACS stimulation; Other: theta tACS stimulation

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age between 18 and 60 years old.
• Stated willingness to participate and comply with all study procedures.
• Stated availability for the duration of the study.
• Meet criteria for Major Depressive Disorder.
• Agreement to adhere to lifestyle considerations throughout study duration.
• No conflict of interest with the Department of Biomedical Engineering at the University of Minnesota.
• Confident level of English language.

Exclusion Criteria:

• History or evidence of chronic neurological disorder (e.g., history of seizures, epilepsy, unexplained episodes of loss of consciousness, serious brain injury, severe or frequent headaches)
• Metal or electric implant in the head, neck or chest area.
• Implanted pacemakers or other electrically, magnetically, ir mechanically activated implant
• Vascular clips or other electrically sensitive support systems in the brain
• Serious health conditions (e.g., congestive heart failure pulmonary obstructive chronic disease, active neoplasia)
• History of head injuries.
• Pregnancy or breast-feeding.
• Significant damage of skin at sites of stimulation or other skin concerns, such as dermatitis, psoriasis, or eczema
• Alcohol or drug addiction.
• Any legal reason why the candidate cannot participate.
• Concurrent enrollment in another scientific or clinical study.
• Estimated IQ is below 70, defined by the WTAR.
• Active suicidality or other non-controlled neuropsychiatric illness. Active suicidality will be excluded based on a C-SSRS score of 3 or above in the last 6 months. Severe depression is defined as a PHQ-9 score above 20, which will also be excluded.
• A lifetime suicide attempt.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: control group; participants with depressive disorder	Other: sham tACS stimulation; A placebo control stimulation will use an identical montage to the stimulation montage. However, polarities of the electrodes will be such that only a minimal amount of current reaches the brain, which is achieved through controlled current shunting between neighboring electrodes. This so-called ActiSham protocol is a verified method to imitate the sensations of actual tACS, with minimal stimulation of the brain .
Experimental: Active group; participants with depressive disorder	Other: theta tACS stimulation; The low intensity transcranial electrical stimulation will be administered with a battery-powered, current-controlled, multi-channel stimulator from Neuroelectrics® Starstim 8. This device comes with a neoprene headcap to hold the electrodes in place. TACS will be delivered concurrently with the task. The multichannel, current-driven stimulator (Neuroelectrics StarStim 8) will be used to control independent stimulation electrodes on the scalp of the volunteer. The stimulation intensity will be up to 2 mA.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
working memory skills	Using a cognitive task that will consist of test responses (correct / incorrect) and reaction time (in ms). The task will include looking at faces expressing different emotions and matching them with previous images.	Day 5
Resting state EEG	examine theta power and connectivity with the EEG recordings	Day 6
Resting state EEG	examine theta power and connectivity with the EEG recordings	Day 35
task-based EEG	examine theta power and connectivity with the EEG recordings	Day 6
task-based EEG	examine theta power and connectivity with the EEG recordings	Day 35

Collaborators and Investigators

• Sponsor: University of Minnesota
• Investigators: Principal Investigator: Kelvin Lim, MD, University of Minnesota; Principal Investigator: Alexander Opitz, PhD, University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2023
• Primary Completion (Actual): August 16, 2024
• Study Completion (Actual): August 16, 2024

Study Registration Dates

• First Submitted: October 16, 2023
• First Submitted That Met QC Criteria: October 29, 2023
• First Posted (Actual): November 1, 2023

Study Record Updates

• Last Update Posted (Actual): September 23, 2024
• Last Update Submitted That Met QC Criteria: September 19, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder
• Other Study ID Numbers: PSYCH-2023-31635

Drug and device information, study documents

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