Trial Outcomes & Findings for Investigating the Causal Role of Prefrontal Control in Decision-making in Patients With Anhedonia (NCT NCT05084924)

Last Updated: 2024-06-25

Results Overview

In the Expenditure of Effort for Reward Task, participants are faced with a decision on every trial: to choose an easy task with a low effort exertion for a chance at winning a low amount of money or a hard task with a high effort exertion for a chance at winning a greater amount of money. The incentive for the high effort exertion is changed on each trial and the participant gets physically tired from repeated effort exertion. Goal-directed behavior was calculated as the percentage of trials in which the participant decides to perform the high effort exertion. The average of the 4 blocks prior to stimulation served as a baseline (1st hour). The effect of the intervention was the average of the next 8 blocks during stimulation (hours 2 through 3).

Recruitment status

COMPLETED

Study phase

Target enrollment

35 participants

Primary outcome timeframe

Baseline (Hour 1), Stimulation (Hours 2 through 3)

Results posted on

2024-06-25

Participant Flow

Participant milestones

Participant milestones
Measure	Delta-beta tACS The study is investigating the use of transcranial alternating current stimulation (tACS). The stimulation is delivered at 1 milliampere (mA) zero-to-peak amplitude at the target electrodes and 2 mA zero to-peak amplitude at the return electrode. For the experimental arm, the tACS will be delivered using the cross-frequency stimulation waveform delta-beta (3-20Hz). Cross-frequency transcranial alternating current stimulation via the NeuroConn Direct Current Stimulator Plus: Stimulation will be delivered via the NeuroConn Direct Current Stimulator Plus, an investigational electrical non-invasive brain stimulation device that is being used for foundational neuroscience and translational research.	Theta-gamma tACS This arm serves as an active control where tACS will be delivered using the cross-frequency stimulation waveform theta-gamma (5-50Hz). Cross-frequency transcranial alternating current stimulation via the NeuroConn Direct Current Stimulator Plus: Stimulation will be delivered via the NeuroConn Direct Current Stimulator Plus, an investigational electrical non-invasive brain stimulation device that is being used for foundational neuroscience and translational research.	Active-sham tACS For active sham stimulation, either delta-beta or theta-gamma stimulation is delivered for 10 seconds and then returns to baseline. This is intended to mimic the skin sensations (e.g., itching, burning, tingling) that are experienced at the onset of stimulation, assisting with blinding the participant's assignment. Cross-frequency transcranial alternating current stimulation via the NeuroConn Direct Current Stimulator Plus: Stimulation will be delivered via the NeuroConn Direct Current Stimulator Plus, an investigational electrical non-invasive brain stimulation device that is being used for foundational neuroscience and translational research.
Overall Study STARTED	11	12	12
Overall Study COMPLETED	11	12	12
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Investigating the Causal Role of Prefrontal Control in Decision-making in Patients With Anhedonia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Delta-beta tACS n=11 Participants The study is investigating the use of transcranial alternating current stimulation (tACS). The stimulation is delivered at 1 milliampere (mA) zero-to-peak amplitude at the target electrodes and 2 mA zero to-peak amplitude at the return electrode. For the experimental arm, the tACS will be delivered using the cross-frequency stimulation waveform delta-beta (3-20Hz). Cross-frequency transcranial alternating current stimulation via the NeuroConn Direct Current Stimulator Plus: Stimulation will be delivered via the NeuroConn Direct Current Stimulator Plus, an investigational electrical non-invasive brain stimulation device that is being used for foundational neuroscience and translational research.	Theta-gamma tACS n=12 Participants This arm serves as an active control where tACS will be delivered using the cross-frequency stimulation waveform theta-gamma (5-50Hz). Cross-frequency transcranial alternating current stimulation via the NeuroConn Direct Current Stimulator Plus: Stimulation will be delivered via the NeuroConn Direct Current Stimulator Plus, an investigational electrical non-invasive brain stimulation device that is being used for foundational neuroscience and translational research.	Active-sham tACS n=12 Participants For active sham stimulation, either delta-beta or theta-gamma stimulation is delivered for 10 seconds and then returns to baseline. This is intended to mimic the skin sensations (e.g., itching, burning, tingling) that are experienced at the onset of stimulation, assisting with blinding the participant's assignment. Cross-frequency transcranial alternating current stimulation via the NeuroConn Direct Current Stimulator Plus: Stimulation will be delivered via the NeuroConn Direct Current Stimulator Plus, an investigational electrical non-invasive brain stimulation device that is being used for foundational neuroscience and translational research.	Total n=35 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	11 Participants n=5 Participants	12 Participants n=7 Participants	12 Participants n=5 Participants	35 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	27.8 years STANDARD_DEVIATION 12.9 • n=5 Participants	27.0 years STANDARD_DEVIATION 10.3 • n=7 Participants	31.8 years STANDARD_DEVIATION 15.6 • n=5 Participants	28.9 years STANDARD_DEVIATION 12.9 • n=4 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	9 Participants n=7 Participants	8 Participants n=5 Participants	26 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	9 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants	12 Participants n=7 Participants	11 Participants n=5 Participants	33 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) White	9 Participants n=5 Participants	10 Participants n=7 Participants	10 Participants n=5 Participants	29 Participants n=4 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	11 Participants n=5 Participants	12 Participants n=7 Participants	12 Participants n=5 Participants	35 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline (Hour 1), Stimulation (Hours 2 through 3)

Outcome measures

Outcome measures
Measure	Delta-beta tACS n=11 Participants The study is investigating the use of transcranial alternating current stimulation (tACS). The stimulation is delivered at 1 milliampere (mA) zero-to-peak amplitude at the target electrodes and 2 mA zero to-peak amplitude at the return electrode. For the experimental arm, the tACS will be delivered using the cross-frequency stimulation waveform delta-beta (3-20Hz). Cross-frequency transcranial alternating current stimulation via the NeuroConn Direct Current Stimulator Plus: Stimulation will be delivered via the NeuroConn Direct Current Stimulator Plus, an investigational electrical non-invasive brain stimulation device that is being used for foundational neuroscience and translational research.	Theta-gamma tACS n=12 Participants This arm serves as an active control where tACS will be delivered using the cross-frequency stimulation waveform theta-gamma (5-50Hz). Cross-frequency transcranial alternating current stimulation via the NeuroConn Direct Current Stimulator Plus: Stimulation will be delivered via the NeuroConn Direct Current Stimulator Plus, an investigational electrical non-invasive brain stimulation device that is being used for foundational neuroscience and translational research.	Active-sham tACS n=12 Participants For active sham stimulation, either delta-beta or theta-gamma stimulation is delivered for 10 seconds and then returns to baseline. This is intended to mimic the skin sensations (e.g., itching, burning, tingling) that are experienced at the onset of stimulation, assisting with blinding the participant's assignment. Cross-frequency transcranial alternating current stimulation via the NeuroConn Direct Current Stimulator Plus: Stimulation will be delivered via the NeuroConn Direct Current Stimulator Plus, an investigational electrical non-invasive brain stimulation device that is being used for foundational neuroscience and translational research.
Change in the Percentage of Trials That the Participant Chooses to Perform the Hard Task	-0.30 percentage of trials Standard Deviation 0.15	-0.22 percentage of trials Standard Deviation 0.12	-0.09 percentage of trials Standard Deviation 0.29

SECONDARY outcome

Timeframe: Baseline (Hour 1), Stimulation (Hours 2 through 3)

Coupling strength was estimated using the Mean Vector Length calculation between the phase of low-frequency electrical activity in prefrontal electrodes and amplitude of high-frequency activity in posterior cortex. A hybrid signal was created using high-frequency amplitude and low-frequency phase. The magnitude of the average of this signal over time is the coupling strength. Coupling strength was normalized using a z-transformation relative to a null distribution generated by randomly time-shifting the high-frequency data relative to the low-frequency data (z-score). A value of zero represents no coupling. A higher value represents greater coupling strength, which is generally associated with better cognition. Values range from -3 to 3 and a score greater than 1.6 means the coupling is present. The average of the 4 blocks prior to stimulation served as a baseline (1st hour). The effect of the intervention was the average of the next 8 blocks during stimulation (hours 2 through 3).

Outcome measures

Outcome measures
Measure	Delta-beta tACS n=11 Participants The study is investigating the use of transcranial alternating current stimulation (tACS). The stimulation is delivered at 1 milliampere (mA) zero-to-peak amplitude at the target electrodes and 2 mA zero to-peak amplitude at the return electrode. For the experimental arm, the tACS will be delivered using the cross-frequency stimulation waveform delta-beta (3-20Hz). Cross-frequency transcranial alternating current stimulation via the NeuroConn Direct Current Stimulator Plus: Stimulation will be delivered via the NeuroConn Direct Current Stimulator Plus, an investigational electrical non-invasive brain stimulation device that is being used for foundational neuroscience and translational research.	Theta-gamma tACS n=12 Participants This arm serves as an active control where tACS will be delivered using the cross-frequency stimulation waveform theta-gamma (5-50Hz). Cross-frequency transcranial alternating current stimulation via the NeuroConn Direct Current Stimulator Plus: Stimulation will be delivered via the NeuroConn Direct Current Stimulator Plus, an investigational electrical non-invasive brain stimulation device that is being used for foundational neuroscience and translational research.	Active-sham tACS n=12 Participants For active sham stimulation, either delta-beta or theta-gamma stimulation is delivered for 10 seconds and then returns to baseline. This is intended to mimic the skin sensations (e.g., itching, burning, tingling) that are experienced at the onset of stimulation, assisting with blinding the participant's assignment. Cross-frequency transcranial alternating current stimulation via the NeuroConn Direct Current Stimulator Plus: Stimulation will be delivered via the NeuroConn Direct Current Stimulator Plus, an investigational electrical non-invasive brain stimulation device that is being used for foundational neuroscience and translational research.
Change in Coupling Strength Between Low-frequency Prefrontal Signals and High-frequency Posterior Signals	0.95 Z-score Standard Deviation 0.68	-0.97 Z-score Standard Deviation 1.04	0.13 Z-score Standard Deviation 1.78

Adverse Events

Delta-beta tACS

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Theta-gamma tACS

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Active-sham tACS

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Delta-beta tACS n=11 participants at risk The study is investigating the use of transcranial alternating current stimulation (tACS). The stimulation is delivered at 1 milliampere (mA) zero-to-peak amplitude at the target electrodes and 2 mA zero to-peak amplitude at the return electrode. For the experimental arm, the tACS will be delivered using the cross-frequency stimulation waveform delta-beta (3-20Hz). Cross-frequency transcranial alternating current stimulation via the NeuroConn Direct Current Stimulator Plus: Stimulation will be delivered via the NeuroConn Direct Current Stimulator Plus, an investigational electrical non-invasive brain stimulation device that is being used for foundational neuroscience and translational research.	Theta-gamma tACS n=12 participants at risk This arm serves as an active control where tACS will be delivered using the cross-frequency stimulation waveform theta-gamma (5-50Hz). Cross-frequency transcranial alternating current stimulation via the NeuroConn Direct Current Stimulator Plus: Stimulation will be delivered via the NeuroConn Direct Current Stimulator Plus, an investigational electrical non-invasive brain stimulation device that is being used for foundational neuroscience and translational research.	Active-sham tACS n=12 participants at risk For active sham stimulation, either delta-beta or theta-gamma stimulation is delivered for 10 seconds and then returns to baseline. This is intended to mimic the skin sensations (e.g., itching, burning, tingling) that are experienced at the onset of stimulation, assisting with blinding the participant's assignment. Cross-frequency transcranial alternating current stimulation via the NeuroConn Direct Current Stimulator Plus: Stimulation will be delivered via the NeuroConn Direct Current Stimulator Plus, an investigational electrical non-invasive brain stimulation device that is being used for foundational neuroscience and translational research.
Skin and subcutaneous tissue disorders Scalp Pain	0.00% 0/11 • 1 week Adverse events were systematically assessed after the 3 hour session for all three arms. Each session was approximately 1 week apart. Thus, adverse events were monitored for approximately 1 week.	8.3% 1/12 • Number of events 1 • 1 week Adverse events were systematically assessed after the 3 hour session for all three arms. Each session was approximately 1 week apart. Thus, adverse events were monitored for approximately 1 week.	0.00% 0/12 • 1 week Adverse events were systematically assessed after the 3 hour session for all three arms. Each session was approximately 1 week apart. Thus, adverse events were monitored for approximately 1 week.
General disorders Sleepiness	0.00% 0/11 • 1 week Adverse events were systematically assessed after the 3 hour session for all three arms. Each session was approximately 1 week apart. Thus, adverse events were monitored for approximately 1 week.	16.7% 2/12 • Number of events 2 • 1 week Adverse events were systematically assessed after the 3 hour session for all three arms. Each session was approximately 1 week apart. Thus, adverse events were monitored for approximately 1 week.	8.3% 1/12 • Number of events 1 • 1 week Adverse events were systematically assessed after the 3 hour session for all three arms. Each session was approximately 1 week apart. Thus, adverse events were monitored for approximately 1 week.
General disorders Trouble Concentrating	9.1% 1/11 • Number of events 1 • 1 week Adverse events were systematically assessed after the 3 hour session for all three arms. Each session was approximately 1 week apart. Thus, adverse events were monitored for approximately 1 week.	0.00% 0/12 • 1 week Adverse events were systematically assessed after the 3 hour session for all three arms. Each session was approximately 1 week apart. Thus, adverse events were monitored for approximately 1 week.	0.00% 0/12 • 1 week Adverse events were systematically assessed after the 3 hour session for all three arms. Each session was approximately 1 week apart. Thus, adverse events were monitored for approximately 1 week.
Eye disorders Flickering Lights	18.2% 2/11 • Number of events 2 • 1 week Adverse events were systematically assessed after the 3 hour session for all three arms. Each session was approximately 1 week apart. Thus, adverse events were monitored for approximately 1 week.	0.00% 0/12 • 1 week Adverse events were systematically assessed after the 3 hour session for all three arms. Each session was approximately 1 week apart. Thus, adverse events were monitored for approximately 1 week.	0.00% 0/12 • 1 week Adverse events were systematically assessed after the 3 hour session for all three arms. Each session was approximately 1 week apart. Thus, adverse events were monitored for approximately 1 week.
Nervous system disorders Headache	0.00% 0/11 • 1 week Adverse events were systematically assessed after the 3 hour session for all three arms. Each session was approximately 1 week apart. Thus, adverse events were monitored for approximately 1 week.	0.00% 0/12 • 1 week Adverse events were systematically assessed after the 3 hour session for all three arms. Each session was approximately 1 week apart. Thus, adverse events were monitored for approximately 1 week.	0.00% 0/12 • 1 week Adverse events were systematically assessed after the 3 hour session for all three arms. Each session was approximately 1 week apart. Thus, adverse events were monitored for approximately 1 week.
Musculoskeletal and connective tissue disorders Neck Pain	0.00% 0/11 • 1 week Adverse events were systematically assessed after the 3 hour session for all three arms. Each session was approximately 1 week apart. Thus, adverse events were monitored for approximately 1 week.	0.00% 0/12 • 1 week Adverse events were systematically assessed after the 3 hour session for all three arms. Each session was approximately 1 week apart. Thus, adverse events were monitored for approximately 1 week.	0.00% 0/12 • 1 week Adverse events were systematically assessed after the 3 hour session for all three arms. Each session was approximately 1 week apart. Thus, adverse events were monitored for approximately 1 week.
Skin and subcutaneous tissue disorders Tingling	0.00% 0/11 • 1 week Adverse events were systematically assessed after the 3 hour session for all three arms. Each session was approximately 1 week apart. Thus, adverse events were monitored for approximately 1 week.	0.00% 0/12 • 1 week Adverse events were systematically assessed after the 3 hour session for all three arms. Each session was approximately 1 week apart. Thus, adverse events were monitored for approximately 1 week.	0.00% 0/12 • 1 week Adverse events were systematically assessed after the 3 hour session for all three arms. Each session was approximately 1 week apart. Thus, adverse events were monitored for approximately 1 week.
Skin and subcutaneous tissue disorders Burning Sensation	0.00% 0/11 • 1 week Adverse events were systematically assessed after the 3 hour session for all three arms. Each session was approximately 1 week apart. Thus, adverse events were monitored for approximately 1 week.	0.00% 0/12 • 1 week Adverse events were systematically assessed after the 3 hour session for all three arms. Each session was approximately 1 week apart. Thus, adverse events were monitored for approximately 1 week.	0.00% 0/12 • 1 week Adverse events were systematically assessed after the 3 hour session for all three arms. Each session was approximately 1 week apart. Thus, adverse events were monitored for approximately 1 week.
Skin and subcutaneous tissue disorders Local redness	0.00% 0/11 • 1 week Adverse events were systematically assessed after the 3 hour session for all three arms. Each session was approximately 1 week apart. Thus, adverse events were monitored for approximately 1 week.	0.00% 0/12 • 1 week Adverse events were systematically assessed after the 3 hour session for all three arms. Each session was approximately 1 week apart. Thus, adverse events were monitored for approximately 1 week.	0.00% 0/12 • 1 week Adverse events were systematically assessed after the 3 hour session for all three arms. Each session was approximately 1 week apart. Thus, adverse events were monitored for approximately 1 week.
Psychiatric disorders Change in mood	0.00% 0/11 • 1 week Adverse events were systematically assessed after the 3 hour session for all three arms. Each session was approximately 1 week apart. Thus, adverse events were monitored for approximately 1 week.	0.00% 0/12 • 1 week Adverse events were systematically assessed after the 3 hour session for all three arms. Each session was approximately 1 week apart. Thus, adverse events were monitored for approximately 1 week.	0.00% 0/12 • 1 week Adverse events were systematically assessed after the 3 hour session for all three arms. Each session was approximately 1 week apart. Thus, adverse events were monitored for approximately 1 week.
Ear and labyrinth disorders Ringing in ear	0.00% 0/11 • 1 week Adverse events were systematically assessed after the 3 hour session for all three arms. Each session was approximately 1 week apart. Thus, adverse events were monitored for approximately 1 week.	0.00% 0/12 • 1 week Adverse events were systematically assessed after the 3 hour session for all three arms. Each session was approximately 1 week apart. Thus, adverse events were monitored for approximately 1 week.	0.00% 0/12 • 1 week Adverse events were systematically assessed after the 3 hour session for all three arms. Each session was approximately 1 week apart. Thus, adverse events were monitored for approximately 1 week.
Nervous system disorders Dizziness	0.00% 0/11 • 1 week Adverse events were systematically assessed after the 3 hour session for all three arms. Each session was approximately 1 week apart. Thus, adverse events were monitored for approximately 1 week.	0.00% 0/12 • 1 week Adverse events were systematically assessed after the 3 hour session for all three arms. Each session was approximately 1 week apart. Thus, adverse events were monitored for approximately 1 week.	0.00% 0/12 • 1 week Adverse events were systematically assessed after the 3 hour session for all three arms. Each session was approximately 1 week apart. Thus, adverse events were monitored for approximately 1 week.

Additional Information

Justin Riddle, PhD

University of North Carolina at Chapel Hill

Phone: 850-644-9869

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place