Trial Outcomes & Findings for Modulating the Hippocampal and Striatal Memory Networks With rTMS (NCT NCT03994120)
NCT ID: NCT03994120
Last Updated: 2022-07-06
Results Overview
Participants underwent repetitive transcranial magnetic stimulation (rTMS) to the caudate network, which supports learning skills. rTMS uses electric currents to activate brain cells, which can temporarily change brain connections and memory. We measured how rTMS affects caudate network brain connectivity. These changes were observed with MRI. To measure brain connection strength, we calculated how closely neural activity correlates in the caudate network. We measured how rTMS affects connection strength before and 1 day after stimulation (immediate effects), and before and 14-21 days after stimulation (long-term effects) and then calculated the change as a Z-transformation score. A change in the Fisher Z-transformation correlation coefficient score of 0 suggests no difference in the connections between brain areas after rTMS; a score of \< 0 suggests a weakening of the connections between brain areas; and a score of \> 0 suggests a strengthening of the connections between brain areas.
COMPLETED
NA
13 participants
Baseline, 1 day and 14-21 days after rTMS
2022-07-06
Participant Flow
Healthy Volunteers were recruited and enrolled between September 2019 and March 2020 through the NIH Recruitment Office.
Participants were randomized to receive either rTMS of the Motor Cortex or rTMS to the Vertex region of the brain. No subjects were randomized to the third arm of the study, i.e., rTMS to the Posterior Parietal Cortex, therefore this arm of the study was not included in the study analysis.
Participant milestones
| Measure |
Motor Cortex Stimulation
Healthy participants undergoing stimulation of the motor cortex with rTMS
|
Vertex Stimulation
Healthy participants undergoing stimulation of the vertex with rTMS
|
|---|---|---|
|
Overall Study
STARTED
|
7
|
6
|
|
Overall Study
COMPLETED
|
4
|
5
|
|
Overall Study
NOT COMPLETED
|
3
|
1
|
Reasons for withdrawal
| Measure |
Motor Cortex Stimulation
Healthy participants undergoing stimulation of the motor cortex with rTMS
|
Vertex Stimulation
Healthy participants undergoing stimulation of the vertex with rTMS
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
3
|
1
|
Baseline Characteristics
Modulating the Hippocampal and Striatal Memory Networks With rTMS
Baseline characteristics by cohort
| Measure |
Motor Cortex Stimulation
n=4 Participants
Healthy participants undergoing stimulation of the motor cortex with rTMS
|
Vertex Stimulation
n=5 Participants
Healthy participants undergoing stimulation of the vertex with rTMS
|
Total
n=9 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
|
|
Age, Categorical
Between 18 and 65 years
|
4 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
2 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 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
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, 1 day and 14-21 days after rTMSParticipants underwent repetitive transcranial magnetic stimulation (rTMS) to the caudate network, which supports learning skills. rTMS uses electric currents to activate brain cells, which can temporarily change brain connections and memory. We measured how rTMS affects caudate network brain connectivity. These changes were observed with MRI. To measure brain connection strength, we calculated how closely neural activity correlates in the caudate network. We measured how rTMS affects connection strength before and 1 day after stimulation (immediate effects), and before and 14-21 days after stimulation (long-term effects) and then calculated the change as a Z-transformation score. A change in the Fisher Z-transformation correlation coefficient score of 0 suggests no difference in the connections between brain areas after rTMS; a score of \< 0 suggests a weakening of the connections between brain areas; and a score of \> 0 suggests a strengthening of the connections between brain areas.
Outcome measures
| Measure |
Motor Cortex Stimulation
n=4 Participants
Healthy participants undergoing stimulation of the motor cortex with rTMS
|
Vertex Stimulation
n=5 Participants
Healthy participants undergoing stimulation of the vertex with rTMS
|
|---|---|---|
|
Change From Baseline in Resting-state Functional Connectivity Between the Caudate and the Caudate Network
Change one day after rTMS
|
-0.073 Fisher Z-Transformation Score
Standard Deviation 0.073
|
-0.021 Fisher Z-Transformation Score
Standard Deviation 0.046
|
|
Change From Baseline in Resting-state Functional Connectivity Between the Caudate and the Caudate Network
Change 14-21 days after rTMS
|
-0.029 Fisher Z-Transformation Score
Standard Deviation 0.004
|
-0.007 Fisher Z-Transformation Score
Standard Deviation 0.048
|
PRIMARY outcome
Timeframe: Baseline, one day and 14-21 days after rTMSParticipants underwent repetitive transcranial magnetic stimulation (rTMS) to the targeted memory network, i.e., caudate network. rTMS uses electric currents to activate brain cells, which can temporarily change brain connections and memory. We measured how rTMS affects caudate network brain connectivity on MRI during a Weather Prediction Task. To measure brain connection strength, we calculated how closely neural activity correlates in the caudate network. We measured how rTMS affects connection strength and skill learning by measuring them before and 1 day after stimulation (immediate effects), and before and 14-21 days after stimulation (long-term effects) and then calculated the change as a Z-transformation score. A change in the Fisher Z-transformation score of 0 suggests no difference in the connections between brain areas; a score of \< 0 suggests a weakening of the connections between brain areas; and a score of \> 0 suggests a strengthening of connections between brain areas.
Outcome measures
| Measure |
Motor Cortex Stimulation
n=4 Participants
Healthy participants undergoing stimulation of the motor cortex with rTMS
|
Vertex Stimulation
n=5 Participants
Healthy participants undergoing stimulation of the vertex with rTMS
|
|---|---|---|
|
Change From Baseline in Task-based Functional Connectivity Between the Caudate and the Caudate Network
Changes one day after rTMS
|
0.028 Fisher Z-Transformation score
Standard Deviation 0.107
|
-0.083 Fisher Z-Transformation score
Standard Deviation 0.115
|
|
Change From Baseline in Task-based Functional Connectivity Between the Caudate and the Caudate Network
Changes 14-21 days after rTMS
|
0.121 Fisher Z-Transformation score
Standard Deviation 0.026
|
-0.026 Fisher Z-Transformation score
Standard Deviation 0.094
|
SECONDARY outcome
Timeframe: Changes are calculated before and one day after rTMS and before and 14-21 days after rTMSThe Feedback Weather Prediction Task (WPT-F) tests the participant's ability to learn an association by trial and error. One, two, or three-card combinations of four possible cards are presented on a computer and the subject is asked to predict the "weather;" i.e. whether it will be rainy or sunny. After each prediction, the subject receives corrective feedback. Each card is independently associated with one outcome with a fixed probability. Participants learn the probabilistic relationship between stimuli and outcomes through feedback (reward). The WPT-F was administered during the MRI session at three time periods, i.e., prior to rTMS, one day after rTMS, and 14-21 days after rTMS. The proportion of trials where the participant selected the best option, i.e., the option most tightly linked to reward, was calculated at each visit. Changes in scores between baseline and one day after and 14-21 days after rTMS were calculated.
Outcome measures
| Measure |
Motor Cortex Stimulation
n=4 Participants
Healthy participants undergoing stimulation of the motor cortex with rTMS
|
Vertex Stimulation
n=5 Participants
Healthy participants undergoing stimulation of the vertex with rTMS
|
|---|---|---|
|
Feedback Weather Prediction Task (WPT-F)
Changes one day after rTMS
|
0.003 Proportion change in score
Standard Deviation 0.167
|
-0.109 Proportion change in score
Standard Deviation 0.153
|
|
Feedback Weather Prediction Task (WPT-F)
Changes 14-21 days after rTMS
|
-0.040 Proportion change in score
Standard Deviation 0.151
|
-0.198 Proportion change in score
Standard Deviation 0.211
|
SECONDARY outcome
Timeframe: Changes are calculated before and one day after rTMS and before and 14-21 days after rTMSThe Observational Weather Prediction Task (WPT-O) is a paired associates test where the cue and feedback are displayed on the screen together. After all pairs are shown the cards are again shown and the participant is asked to remember which feedback outcome (sun or rain) is paired with that set of cards. Participants learn the pairing between sets of stimuli and one of two outcomes through memorization. The WPT-O was administered during the MRI session at three time periods, i.e., prior to rTMS, one day after rTMS, and 14-21 days after rTMS. The proportion of trials where the participant accurately remembered the pair, was calculated at each visit. Changes in scores between baseline and one day after and 14-21 days after rTMS will be calculated.
Outcome measures
| Measure |
Motor Cortex Stimulation
n=4 Participants
Healthy participants undergoing stimulation of the motor cortex with rTMS
|
Vertex Stimulation
n=5 Participants
Healthy participants undergoing stimulation of the vertex with rTMS
|
|---|---|---|
|
Observational Weather Prediction Task (WPT-O)
Changes one day after rTMS
|
-0.026 Proportion change in score
Standard Deviation 0.107
|
-0.150 Proportion change in score
Standard Deviation 0.165
|
|
Observational Weather Prediction Task (WPT-O)
Changes 14-21 days after rTMS
|
-0.005 Proportion change in score
Standard Deviation 0.087
|
-0.027 Proportion change in score
Standard Deviation 0.049
|
SECONDARY outcome
Timeframe: Baseline, one day and 14-21 days after rTMSParticipants underwent repetitive transcranial magnetic stimulation (rTMS) to the hippocampal network, which supports learning skills. rTMS uses electric currents to activate brain cells, which can temporarily change brain connections and memory. We measured how rTMS affects hippocampal network brain connectivity. These changes can be observed with MRI. To measure brain connection strength, we calculated how closely neural activity correlates in the hippocampal network. We measured how rTMS affects connection strength before and 1 day after stimulation (immediate effects), and before and 14-21 days after stimulation (long-term effects) and then calculated the change as a Z-transformation score. A change in the Fisher Z-transformation score of 0 suggests no difference in the connections between brain areas after rTMS; a score of \< 0 suggests a weakening of the connections between brain areas; and a score of \> 0 suggests a strengthening of the connections between brain areas.
Outcome measures
| Measure |
Motor Cortex Stimulation
n=4 Participants
Healthy participants undergoing stimulation of the motor cortex with rTMS
|
Vertex Stimulation
n=5 Participants
Healthy participants undergoing stimulation of the vertex with rTMS
|
|---|---|---|
|
Change From Baseline in Resting-state Functional Connectivity Between the Caudate and the Hippocampal Network
Changes one day after rTMS
|
-0.054 Fisher Z-Transformation score
Standard Deviation 0.073
|
-0.049 Fisher Z-Transformation score
Standard Deviation 0.080
|
|
Change From Baseline in Resting-state Functional Connectivity Between the Caudate and the Hippocampal Network
Changes 14-21 days after rTMS
|
-0.093 Fisher Z-Transformation score
Standard Deviation 0.013
|
-0.024 Fisher Z-Transformation score
Standard Deviation 0.033
|
SECONDARY outcome
Timeframe: Baseline, one day and 14-21 days after rTMSParticipants underwent repetitive transcranial magnetic stimulation (rTMS) to the targeted memory network, i.e., hippocampal network. rTMS uses electric currents to activate brain cells, and this can temporarily change brain connections and memory. We measured how rTMS affects hippocampal network brain connectivity on MRI during a Weather Prediction Task. To measure brain connection strength, we calculated how closely neural activity correlates in the hippocampal network. We measured how rTMS affects connection strength and skill learning before and 1 day after stimulation (immediate effects), and before and 14-21 days after stimulation (long-term effects) and then calculated the change as a Z-transformation score. A change in the Fisher Z-transformation score of 0 suggests no difference in the connections between brain areas; a score of \< 0 suggests a weakening of the connections between brain areas; and a score of \> 0 suggests a strengthening of the connections between brain areas.
Outcome measures
| Measure |
Motor Cortex Stimulation
n=4 Participants
Healthy participants undergoing stimulation of the motor cortex with rTMS
|
Vertex Stimulation
n=5 Participants
Healthy participants undergoing stimulation of the vertex with rTMS
|
|---|---|---|
|
Change From Baseline in Task-based Functional Connectivity Between the Caudate and the Hippocampal Network
Changes one day after rTMS
|
0.027 Fisher Z-Transformation score
Standard Deviation 0.165
|
-0.066 Fisher Z-Transformation score
Standard Deviation 0.181
|
|
Change From Baseline in Task-based Functional Connectivity Between the Caudate and the Hippocampal Network
Changes 14-21 days after rTMS
|
-0.168 Fisher Z-Transformation score
Standard Deviation 0.025
|
0.034 Fisher Z-Transformation score
Standard Deviation 0.176
|
Adverse Events
Motor Cortex Stimulation
Vertex Stimulation
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place