Trial Outcomes & Findings for Theta Connectivity in Working Memory (NCT NCT05204381)
NCT ID: NCT05204381
Last Updated: 2025-11-20
Results Overview
The number of remembered items, often referred to as working memory capacity, is calculated as the number of items to be remembered (2, 3, or 4) times the hit rate minus the false alarm rate, divided by one minus the false alarm rate. The range of values is 0 to 4 where larger values mean better performance.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
71 participants
Primary outcome timeframe
Measured concurrent with stimulation throughout a 3-hour session
Results posted on
2025-11-20
Participant Flow
Sessions prior to randomization: Session 1 (S1;baseline behavioral task), Session 2 (S2;baseline EEG), Session 3 (S3;MRI). 71 participants enrolled in S1 (n=1 did not complete, n=13 excluded for performance). n=7 lost to follow-up prior to S2. 50 started S2 (n=1 excluded for performance). n=3 lost to follow-up prior to S3. 46 participants started S3 (n=1 excluded, MRI contraindication). n=6 lost to follow-up prior to S4. 39 participants were randomized to intervention groups.
Participant milestones
| Measure |
Theta Stimulation
Rhythmic transcranial magnetic stimulation (TMS) is delivered to frontal and parietal cortex during performance of a cognitive control task while electroencephalography (EEG) is recorded. In the 4th and 5th sessions, TMS is delivered in near-zero phase lag theta-frequency, anti-synchrony theta-frequency, near-zero phase lag arrhythmic-in-synchrony, and arrhythmic-independent TMS. The near-zero phase lag arrhythmic-in-synchrony and arrhythmic-independent TMS is delivered in both the 4th and 5th session to serve as an active control.
Theta-frequency near-zero phase lag stimulation: Rhythmic transcranial magnetic stimulation (TMS) is delivered to both frontal and parietal cortex in theta-frequency (approximately 6 Hz) with a near-zero phase lag.
Theta-frequency anti-synchrony stimulation: Rhythmic transcranial magnetic stimulation (TMS) is delivered to both frontal and parietal cortex in theta-frequency (approximately 6 Hz) with a 180 degree phase offset, anti-synchrony.
Arrhythmic near-zero phase lag stimulation: Rhythmic transcranial magnetic stimulation (TMS) is delivered to both frontal and parietal cortex in an arrhythmic pattern with a near-zero phase lag matched in duration to the rhythmic stimulation for that session.
Arrhythmic independent stimulation: Rhythmic transcranial magnetic stimulation (TMS) is delivered to both frontal and parietal cortex in different independent arrhythmic patterns matched in duration to the rhythmic stimulation for that session.
|
Alpha Stimulation
Rhythmic transcranial magnetic stimulation (TMS) is delivered to frontal and parietal cortex during performance of a cognitive control task while electroencephalography (EEG) is recorded. In the 4th and 5th sessions, TMS is delivered in near-zero phase lag alpha-frequency, anti-synchrony alpha-frequency, near-zero phase lag arrhythmic-in-synchrony and arrhythmic-independent TMS. The near-zero phase lag arrhythmic-in-synchrony and arrhythmic-independent TMS is delivered in both the 4th and 5th session to serve as an active control.
Arrhythmic near-zero phase lag stimulation: Rhythmic transcranial magnetic stimulation (TMS) is delivered to both frontal and parietal cortex in an arrhythmic pattern with a near-zero phase lag matched in duration to the rhythmic stimulation for that session.
Arrhythmic independent stimulation: Rhythmic transcranial magnetic stimulation (TMS) is delivered to both frontal and parietal cortex in different independent arrhythmic patterns matched in duration to the rhythmic stimulation for that session.
Alpha-frequency near-zero phase lag stimulation: Rhythmic transcranial magnetic stimulation (TMS) is delivered to both frontal and parietal cortex in alpha-frequency (approximately 10 Hz) with a near-zero phase lag.
Alpha-frequency anti-synchrony stimulation: Rhythmic transcranial magnetic stimulation (TMS) is delivered to both frontal and parietal cortex in alpha-frequency (approximately 10 Hz) with a 180 degree phase offset, anti-synchrony.
|
|---|---|---|
|
Session 4
STARTED
|
16
|
23
|
|
Session 4
COMPLETED
|
15
|
21
|
|
Session 4
NOT COMPLETED
|
1
|
2
|
|
Washout (At Least 1 Day)
STARTED
|
15
|
21
|
|
Washout (At Least 1 Day)
COMPLETED
|
15
|
18
|
|
Washout (At Least 1 Day)
NOT COMPLETED
|
0
|
3
|
|
Session 5
STARTED
|
15
|
18
|
|
Session 5
COMPLETED
|
15
|
18
|
|
Session 5
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Theta Connectivity in Working Memory
Baseline characteristics by cohort
| Measure |
Theta Stimulation
n=16 Participants
Rhythmic transcranial magnetic stimulation (TMS) is delivered to frontal and parietal cortex during performance of a cognitive control task while electroencephalography (EEG) is recorded. In the 4th and 5th sessions, TMS is delivered in near-zero phase lag theta-frequency, anti-synchrony theta-frequency, near-zero phase lag arrhythmic-in-synchrony, and arrhythmic-independent TMS. The near-zero phase lag arrhythmic-in-synchrony and arrhythmic-independent TMS is delivered in both the 4th and 5th session to serve as an active control.
|
Alpha Stimulation
n=23 Participants
Rhythmic transcranial magnetic stimulation (TMS) is delivered to frontal and parietal cortex during performance of a cognitive control task while electroencephalography (EEG) is recorded. In the 4th and 5th sessions, TMS is delivered in near-zero phase lag alpha-frequency, anti-synchrony alpha-frequency, near-zero phase lag arrhythmic-in-synchrony and arrhythmic-independent TMS. The near-zero phase lag arrhythmic-in-synchrony and arrhythmic-independent TMS is delivered in both the 4th and 5th session to serve as an active control.
|
Total
n=39 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=8 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
16 Participants
|
23 Participants
n=4 Participants
|
39 Participants
n=8 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=8 Participants
|
|
Age, Continuous
|
21.4 years
STANDARD_DEVIATION 4.0
|
22.0 years
STANDARD_DEVIATION 3.7 • n=4 Participants
|
21.7 years
STANDARD_DEVIATION 3.8 • n=8 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
|
14 Participants
n=4 Participants
|
25 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
|
9 Participants
n=4 Participants
|
14 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
|
4 Participants
n=4 Participants
|
4 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
16 Participants
|
19 Participants
n=4 Participants
|
35 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Asian
|
4 Participants
|
8 Participants
n=4 Participants
|
12 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=8 Participants
|
|
Race (NIH/OMB)
White
|
11 Participants
|
15 Participants
n=4 Participants
|
26 Participants
n=8 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=8 Participants
|
|
Region of Enrollment
United States
|
16 Participants
|
23 Participants
n=4 Participants
|
39 Participants
n=8 Participants
|
PRIMARY outcome
Timeframe: Measured concurrent with stimulation throughout a 3-hour sessionPopulation: Arrhythmic near-zero phase lag stimulation and Arrhythmic independent stimulation were delivered in both intervention arms (Theta stimulation arm AND Alpha stimulation arm); therefore, the number analyzed for Arrhythmic near-zero phase lag stimulation and Arrhythmic independent stimulation includes all randomized participants from both arms.
The number of remembered items, often referred to as working memory capacity, is calculated as the number of items to be remembered (2, 3, or 4) times the hit rate minus the false alarm rate, divided by one minus the false alarm rate. The range of values is 0 to 4 where larger values mean better performance.
Outcome measures
| Measure |
Theta-frequency Near-zero Phase Lag Stimulation
n=15 Participants
Rhythmic transcranial magnetic stimulation (TMS) is delivered to both frontal and parietal cortex in theta-frequency (approximately 6 Hz) with a near-zero phase lag.
This intervention was only delivered in the Theta stimulation arm.
|
Theta-frequency Anti-synchrony Stimulation
n=15 Participants
Rhythmic transcranial magnetic stimulation (TMS) is delivered to both frontal and parietal cortex in theta-frequency (approximately 6 Hz) with a 180 degree phase offset, anti-synchrony.
This intervention was only delivered in the Theta stimulation arm.
|
Arrhythmic Near-zero Phase Lag Stimulation
n=33 Participants
Rhythmic transcranial magnetic stimulation (TMS) is delivered to both frontal and parietal cortex in an arrhythmic pattern with a near-zero phase lag matched in duration to the rhythmic stimulation for that session.
This active control stimulation was delivered in both arms of the study (Theta stimulation intervention arm AND Alpha stimulation intervention arm).
|
Arrhythmic Independent Stimulation
n=33 Participants
Rhythmic transcranial magnetic stimulation (TMS) is delivered to both frontal and parietal cortex in different independent arrhythmic patterns matched in duration to the rhythmic stimulation for that session.
This active control stimulation was delivered in both arms of the study (Theta stimulation intervention arm AND Alpha stimulation intervention arm).
|
Alpha-frequency Near-zero Phase Lag Stimulation
n=18 Participants
Rhythmic transcranial magnetic stimulation (TMS) is delivered to both frontal and parietal cortex in alpha-frequency (approximately 10 Hz) with a near-zero phase lag.
This intervention was only delivered in the Alpha stimulation arm.
|
Alpha-frequency Anti-synchrony Stimulation
n=18 Participants
Rhythmic transcranial magnetic stimulation (TMS) is delivered to both frontal and parietal cortex in alpha-frequency (approximately 10 Hz) with a 180 degree phase offset, anti-synchrony.
This intervention was only delivered in the Alpha stimulation arm.
|
|---|---|---|---|---|---|---|
|
Number of Remembered Items
|
1.72 remembered items
Standard Deviation 0.48
|
1.68 remembered items
Standard Deviation 0.42
|
1.68 remembered items
Standard Deviation 0.38
|
1.65 remembered items
Standard Deviation 0.37
|
1.71 remembered items
Standard Deviation 0.38
|
1.72 remembered items
Standard Deviation 0.40
|
PRIMARY outcome
Timeframe: Measured concurrent with stimulation throughout a 3-hour sessionPopulation: Arrhythmic near-zero phase lag stimulation and Arrhythmic independent stimulation were delivered in both intervention arms (Theta stimulation arm AND Alpha stimulation arm); therefore, the number analyzed for Arrhythmic near-zero phase lag stimulation and Arrhythmic independent stimulation includes all randomized participants from both arms.
Functional connectivity will be measured using weighted phase lag index (wPLI) which is the mean of the imaginary component of the difference in theta-frequency phase between frontal and parietal electrical activity during the second half of the stimulation train for every trial. The values range from 0 to 1 where a greater value represents greater functional connectivity.
Outcome measures
| Measure |
Theta-frequency Near-zero Phase Lag Stimulation
n=15 Participants
Rhythmic transcranial magnetic stimulation (TMS) is delivered to both frontal and parietal cortex in theta-frequency (approximately 6 Hz) with a near-zero phase lag.
This intervention was only delivered in the Theta stimulation arm.
|
Theta-frequency Anti-synchrony Stimulation
n=15 Participants
Rhythmic transcranial magnetic stimulation (TMS) is delivered to both frontal and parietal cortex in theta-frequency (approximately 6 Hz) with a 180 degree phase offset, anti-synchrony.
This intervention was only delivered in the Theta stimulation arm.
|
Arrhythmic Near-zero Phase Lag Stimulation
n=33 Participants
Rhythmic transcranial magnetic stimulation (TMS) is delivered to both frontal and parietal cortex in an arrhythmic pattern with a near-zero phase lag matched in duration to the rhythmic stimulation for that session.
This active control stimulation was delivered in both arms of the study (Theta stimulation intervention arm AND Alpha stimulation intervention arm).
|
Arrhythmic Independent Stimulation
n=33 Participants
Rhythmic transcranial magnetic stimulation (TMS) is delivered to both frontal and parietal cortex in different independent arrhythmic patterns matched in duration to the rhythmic stimulation for that session.
This active control stimulation was delivered in both arms of the study (Theta stimulation intervention arm AND Alpha stimulation intervention arm).
|
Alpha-frequency Near-zero Phase Lag Stimulation
n=18 Participants
Rhythmic transcranial magnetic stimulation (TMS) is delivered to both frontal and parietal cortex in alpha-frequency (approximately 10 Hz) with a near-zero phase lag.
This intervention was only delivered in the Alpha stimulation arm.
|
Alpha-frequency Anti-synchrony Stimulation
n=18 Participants
Rhythmic transcranial magnetic stimulation (TMS) is delivered to both frontal and parietal cortex in alpha-frequency (approximately 10 Hz) with a 180 degree phase offset, anti-synchrony.
This intervention was only delivered in the Alpha stimulation arm.
|
|---|---|---|---|---|---|---|
|
Strength of Functional Connectivity Between Frontal and Parietal Cortex in Theta-frequency
|
0.143 weighted phase lag index
Standard Deviation 0.118
|
0.167 weighted phase lag index
Standard Deviation 0.158
|
0.116 weighted phase lag index
Standard Deviation 0.074
|
0.086 weighted phase lag index
Standard Deviation 0.057
|
0.149 weighted phase lag index
Standard Deviation 0.104
|
0.156 weighted phase lag index
Standard Deviation 0.126
|
SECONDARY outcome
Timeframe: Measured concurrent with stimulation throughout a 3-hour sessionPopulation: Arrhythmic near-zero phase lag stimulation and Arrhythmic independent stimulation were delivered in both intervention arms (Theta stimulation arm AND Alpha stimulation arm); therefore, the number analyzed for Arrhythmic near-zero phase lag stimulation and Arrhythmic independent stimulation includes all randomized participants from both arms.
Phase lag is calculated as the resulting phase angle after averaging the phase difference between frontal and parietal cortex electrical signals during the second half of the stimulation train for every trial. The values range from 0 to 360 degrees. A value closer to 0 degrees or closer to 360 degrees represent a near-zero phase lag, where as a value closer to 180 degree represent a larger phase lag.
Outcome measures
| Measure |
Theta-frequency Near-zero Phase Lag Stimulation
n=15 Participants
Rhythmic transcranial magnetic stimulation (TMS) is delivered to both frontal and parietal cortex in theta-frequency (approximately 6 Hz) with a near-zero phase lag.
This intervention was only delivered in the Theta stimulation arm.
|
Theta-frequency Anti-synchrony Stimulation
n=15 Participants
Rhythmic transcranial magnetic stimulation (TMS) is delivered to both frontal and parietal cortex in theta-frequency (approximately 6 Hz) with a 180 degree phase offset, anti-synchrony.
This intervention was only delivered in the Theta stimulation arm.
|
Arrhythmic Near-zero Phase Lag Stimulation
n=33 Participants
Rhythmic transcranial magnetic stimulation (TMS) is delivered to both frontal and parietal cortex in an arrhythmic pattern with a near-zero phase lag matched in duration to the rhythmic stimulation for that session.
This active control stimulation was delivered in both arms of the study (Theta stimulation intervention arm AND Alpha stimulation intervention arm).
|
Arrhythmic Independent Stimulation
n=33 Participants
Rhythmic transcranial magnetic stimulation (TMS) is delivered to both frontal and parietal cortex in different independent arrhythmic patterns matched in duration to the rhythmic stimulation for that session.
This active control stimulation was delivered in both arms of the study (Theta stimulation intervention arm AND Alpha stimulation intervention arm).
|
Alpha-frequency Near-zero Phase Lag Stimulation
n=18 Participants
Rhythmic transcranial magnetic stimulation (TMS) is delivered to both frontal and parietal cortex in alpha-frequency (approximately 10 Hz) with a near-zero phase lag.
This intervention was only delivered in the Alpha stimulation arm.
|
Alpha-frequency Anti-synchrony Stimulation
n=18 Participants
Rhythmic transcranial magnetic stimulation (TMS) is delivered to both frontal and parietal cortex in alpha-frequency (approximately 10 Hz) with a 180 degree phase offset, anti-synchrony.
This intervention was only delivered in the Alpha stimulation arm.
|
|---|---|---|---|---|---|---|
|
Average Phase Lag of Functional Connectivity Between Frontal and Parietal Cortex in Theta-frequency
|
182.2 degrees
Standard Deviation 5.73
|
177.4 degrees
Standard Deviation 14.43
|
182.2 degrees
Standard Deviation 4.16
|
181.2 degrees
Standard Deviation 4.32
|
183.1 degrees
Standard Deviation 6.03
|
183.1 degrees
Standard Deviation 6.69
|
Adverse Events
Theta Stimulation
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Alpha Stimulation
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Theta Stimulation
n=16 participants at risk
Rhythmic transcranial magnetic stimulation (TMS) is delivered to frontal and parietal cortex during performance of a cognitive control task while electroencephalography (EEG) is recorded. In the 4th and 5th sessions, TMS is delivered in near-zero phase lag theta-frequency, anti-synchrony theta-frequency, near-zero phase lag arrhythmic-in-synchrony, and arrhythmic-independent TMS. The near-zero phase lag arrhythmic-in-synchrony and arrhythmic-independent TMS is delivered in both the 4th and 5th session to serve as an active control.
|
Alpha Stimulation
n=23 participants at risk
Rhythmic transcranial magnetic stimulation (TMS) is delivered to frontal and parietal cortex during performance of a cognitive control task while electroencephalography (EEG) is recorded. In the 4th and 5th sessions, TMS is delivered in near-zero phase lag alpha-frequency, anti-synchrony alpha-frequency, near-zero phase lag arrhythmic-in-synchrony and arrhythmic-independent TMS. The near-zero phase lag arrhythmic-in-synchrony and arrhythmic-independent TMS is delivered in both the 4th and 5th session to serve as an active control.
|
|---|---|---|
|
General disorders
Trouble concentrating
|
6.2%
1/16 • Number of events 1 • Adverse Events were not assessed prior to randomization and group assignment at the start of Session 4. Adverse Events were monitored at Session 4 (up to 3 hours) and Session 5 (up to 3 hours). A systematic assessment was conducted at the end of Session 4 and at the end of Session 5.
A stimulation adverse effects questionnaire was used based on common side effects experience with TMS. This questionnaire was administered at the end of each session in which the participant receives TMS (sessions 4 and 5). This questionnaire was used as a safety measure and to collect data on participant experience. Following the questionnaire, a structured interview was conducted as needed based upon responses on the stimulation adverse effects questionnaire.
|
4.3%
1/23 • Number of events 1 • Adverse Events were not assessed prior to randomization and group assignment at the start of Session 4. Adverse Events were monitored at Session 4 (up to 3 hours) and Session 5 (up to 3 hours). A systematic assessment was conducted at the end of Session 4 and at the end of Session 5.
A stimulation adverse effects questionnaire was used based on common side effects experience with TMS. This questionnaire was administered at the end of each session in which the participant receives TMS (sessions 4 and 5). This questionnaire was used as a safety measure and to collect data on participant experience. Following the questionnaire, a structured interview was conducted as needed based upon responses on the stimulation adverse effects questionnaire.
|
|
General disorders
Scalp pain
|
0.00%
0/16 • Adverse Events were not assessed prior to randomization and group assignment at the start of Session 4. Adverse Events were monitored at Session 4 (up to 3 hours) and Session 5 (up to 3 hours). A systematic assessment was conducted at the end of Session 4 and at the end of Session 5.
A stimulation adverse effects questionnaire was used based on common side effects experience with TMS. This questionnaire was administered at the end of each session in which the participant receives TMS (sessions 4 and 5). This questionnaire was used as a safety measure and to collect data on participant experience. Following the questionnaire, a structured interview was conducted as needed based upon responses on the stimulation adverse effects questionnaire.
|
4.3%
1/23 • Number of events 1 • Adverse Events were not assessed prior to randomization and group assignment at the start of Session 4. Adverse Events were monitored at Session 4 (up to 3 hours) and Session 5 (up to 3 hours). A systematic assessment was conducted at the end of Session 4 and at the end of Session 5.
A stimulation adverse effects questionnaire was used based on common side effects experience with TMS. This questionnaire was administered at the end of each session in which the participant receives TMS (sessions 4 and 5). This questionnaire was used as a safety measure and to collect data on participant experience. Following the questionnaire, a structured interview was conducted as needed based upon responses on the stimulation adverse effects questionnaire.
|
|
General disorders
Change in Mood
|
6.2%
1/16 • Number of events 1 • Adverse Events were not assessed prior to randomization and group assignment at the start of Session 4. Adverse Events were monitored at Session 4 (up to 3 hours) and Session 5 (up to 3 hours). A systematic assessment was conducted at the end of Session 4 and at the end of Session 5.
A stimulation adverse effects questionnaire was used based on common side effects experience with TMS. This questionnaire was administered at the end of each session in which the participant receives TMS (sessions 4 and 5). This questionnaire was used as a safety measure and to collect data on participant experience. Following the questionnaire, a structured interview was conducted as needed based upon responses on the stimulation adverse effects questionnaire.
|
4.3%
1/23 • Number of events 1 • Adverse Events were not assessed prior to randomization and group assignment at the start of Session 4. Adverse Events were monitored at Session 4 (up to 3 hours) and Session 5 (up to 3 hours). A systematic assessment was conducted at the end of Session 4 and at the end of Session 5.
A stimulation adverse effects questionnaire was used based on common side effects experience with TMS. This questionnaire was administered at the end of each session in which the participant receives TMS (sessions 4 and 5). This questionnaire was used as a safety measure and to collect data on participant experience. Following the questionnaire, a structured interview was conducted as needed based upon responses on the stimulation adverse effects questionnaire.
|
Additional Information
Zachary Stewart
University of North Carollina at Chapel Hill
Phone: 919-966-9929
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place