Bipolar Transcranial Alternating Current Stimulation (tACS)

Enhancing Neural Synchrony and Affective Cognitive Control in Bipolar Disorder Using Personalized Transcranial Alternating Current Stimulation (tACS)

The purpose of this clinical trial is to measure the safety and effectiveness of a non-invasive brain stimulation device called Transcranial Alternating Current Stimulation (tACS) in participants with bipolar disorder (BD).

Participants will be asked to come in for 3 sessions. If participants qualify at the screening visit (session 1) then enrolled participants will complete sessions 2 and 3 as well as have a 30-day follow-up phone call.

Study Overview

• Status: Completed
• Conditions: Bipolar Disorder
• Intervention / Treatment: Device: Sham stimulation treatment; Device: tACS brain stimulation treatment

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Confirmed diagnosis of BD based on Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria being met from previous enrollment in the Prechter Bipolar Longitudinal Study
• This study will select BD patients that scored above published norms (upper 50th percentile) on the NEO-PI impulsivity facet to ensure that the recruited patients exhibit the network dysfunction targeted by the tACS paradigm and therefore have the potential to benefit from this neuromodulation technique.
• Patients must be on a stable dose of medication for two weeks prior to Sessions 2 and 3.

Exclusion Criteria:

• Significant neurological abnormalities, such as seizure disorder, mass lesions, etc.
• Known Mendelian disorder
• Active problematic substance use in the past 30 days (as determined by the Substance Use Disorder module of SCID)
• Evidence of suicidal intentions or behaviors in the past month, as judged by affirmative responses to question number 4 or number 5 on the Columbia Suicide Severity Rating Scale (CSSRS) or report of suicidal behaviors in the last 6 months
• Pregnant or trying to become pregnant, or currently lactating.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Sham stimulation treatment; Sham stimulation during a computerized task and electroencephalogram (EEG) recording.	Device: Sham stimulation treatment; Participants will wear an EEG cap on the head attached with EEG-recording and tACS electrodes. Sham tACS will be delivered by passing a transient (approximately 12 seconds ) small electrical current via the tACS electrodes during a computerized behavioral task. The effect of sham stimulation on EEG will be measured via EEG-recording electrodes during short rests (between stimulation blocks). The sham stimulation session will last for approximately 60 minutes. After treatment, participants will be asked about the experience and if there are any side effects.
Experimental: tACS brain stimulation treatment; tACS brain stimulation during a computerized task and EEG recording. Participants will receive tACS using individualized peak Phase-amplitude coupling (PAC) frequency pairs determined in Session 1.	Device: tACS brain stimulation treatment; Participants will wear an EEG cap on the head attached with EEG-recording and tACS electrodes. tACS will be delivered by passing a small electrical current via the tACS electrodes to the scalp to stimulate brain activity during a computerized behavioral task. The effect of active stimulation on EEG will be measured via EEG-recording electrodes during short rests (between stimulation blocks). The stimulation session will last for approximately 60 minutes. After treatment, participants will be asked about the experience and if there are any side effects.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of Side Effects Reported at End of Stimulation Session as Reported by the Participant on the Stimulation Side Effects Questionnaire.	The score was calculated by summing the severity score of items that were rated by the participant as related to stimulation on the Stimulation Side Effects Questionnaire. There was a total of 14 symptoms listed on the questionnaire. Participants rated each item rated on a scale of 0-4, with 0 meaning no relation and 4 meaning definitely related. The total possible range of the questionnaire was 0-56.	Up to 3 weeks
Participants Who Withdrew During or After the Stimulation Session	Results reflect the number of participants who withdrew from the trial during or after a stimulation session with either the tACS or the sham stimulation treatment.	Up to 3 weeks
Accuracy Signal Detection Theory Metric Sensitivity (d') Derived From the Behavioral Responses to Go and NoGo Trials on the Cognitive Control Task.	The Go/NoGo task was a cognitive task, where participants were shown "go" stimuli (i.e., go trials) and "no-go" stimuli and responded by pressing a button when seeing "go" stimuli and not responding when seeing the "no-go" stimuli. Accuracy was measured by calculating D' (D prime), which provided a measure of perceptual sensitivity to the differing stimuli. Larger values of D' indicated greater discernability (i.e., accuracy) between the Go and NoGo trials. D-prime, also called the sensitivity index represents how well someone can detect a signal amidst background noise. At its core, D-prime is the standardized difference between the means of the Signal Present and Signal Absent distributions, which can be calculated by taking the difference between the Z-score of the False Alarm Rate and the Z-scores of the Hit Rate. A D-prime of 0 means no sensitivity. Negative D-prime values are rare and may indicate errors or reversed interpretations of hits and false alarms.	Up to 3 weeks
Accuracy Signal Detection Theory Metric Response Bias Derived From the Behavioral Responses to Go and NoGo Trials on the Cognitive Control Task.	The Go/NoGo task was a cognitive task, where participants were shown "go" stimuli (i.e., go trials) and "no-go" stimuli and responded by pressing a button when seeing "go" stimuli and not responding when seeing the "no-go" stimuli. Response bias was measured using beta, such that more negative beta values indicated a stronger tendency to respond to all stimuli, regardless of "go" or "no-go" status. Response bias is indexed by taking the average between the Z-score of the False Alarm Rate and the Z-scores of the Hit Rate. A higher response bias indicates that the participant is more likely to respond "signal absent" (favors avoiding false alarms but increases misses). A response bias of 0 means the individual equally weighs the costs of misses and false alarms. A more negative response bias indicated that the participant is more likely to respond "signal present" (favors hits but increases false alarms).	Up to 3 weeks
Reaction Time (in Milliseconds) of Go Trials on the Cognitive Control Task	Participants' reaction time to responding to the "Go" signal during the Go/NoGo task was measured.	Up to 3 weeks
Theta-gamma Phase Amplitude Coupling (PAC) (Kullback-Leibler Modulation Index) During the Rest EEG Blocks Interleaved Between Stimulation Blocks.	Theta-gamma phase-amplitude coupling (PAC) is a neural phenomenon observed in the brain, where the phase of slower theta oscillations modulates the amplitude of faster gamma oscillations. This type of coupling is thought to play a critical role in various cognitive control. For the trial, higher PAC values indicated higher levels of coupling or connection between the two frequencies (i.e., increased cognitive control).	Up to 3 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Emotional Flanker Task - Accuracy	After completing the Emotion Go-NoGo task, participants will complete another cognitive control task (i.e., Emotional Flanker Task) with gray-scaled unpleasant, pleasant, and neural images from the International Affective Picture System. Participants are tasked with indicating which valance is presented in certain images while ignoring other images. Accuracy is defined as the percentage of trials that the participant correctly reports the valance of the target image. The total number of correct trials will be divided by the total number of trials to obtain an accuracy score. Average accuracy scores per condition and total will be calculated.	Approximately 30-60 minutes after the Go-NoGo task at all three time points (baseline, session 1, session 2)
Emotional Flanker Task - EEG	EEG will also be collected during the Emotional Flanker Task. Phase-amplitude coupling will be calculated and defined as the coupling between the amplitude of high frequency oscillations (e.g., gamma) and low frequency phase (e.g., theta). Average coupling scores per condition and total will be calculated.	Approximately 30-60 minutes after the Go-NoGo task at all three time points (baseline, session 1, session 2).
Emotional Flanker Task - Reaction Time	Reaction time will also be collected during the Emotional Flanker Task. Reaction time is defined as the length of time it takes the participant to respond after the onset of the stimuli. Average reaction times per condition and total will be calculated.	Approximately 30-60 minutes after the Go-NoGo task at all three time points (baseline, session 1, session 2).

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: Milken Institute; Baszucki Brain Research Fund
• Investigators: Principal Investigator: Stephan F Taylor, MD, University of Michigan

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2023
• Primary Completion (Actual): December 6, 2023
• Study Completion (Actual): January 6, 2024

Study Registration Dates

• First Submitted: July 26, 2022
• First Submitted That Met QC Criteria: July 27, 2022
• First Posted (Actual): July 29, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 19, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: electroencephalogram (EEG); transcranial alternating current stimulation (tACS)
• Additional Relevant MeSH Terms: Bipolar and Related Disorders; Mental Disorders; Mood Disorders; Bipolar Disorder
• Other Study ID Numbers: HUM00208557

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No