Trial Outcomes & Findings for Noninvasive Modulation of Motivational Brain Regions in Healthy Volunteers (NCT NCT04972786)
NCT ID: NCT04972786
Last Updated: 2024-07-16
Results Overview
Encoding of trial-by-trial immediate expected value (IEV) in dorsal anterior cingulate cortex (dACC) region-of-interest that was targeted with rTMS. Expressed in units of BOLD % signal change. This primary outcome reflects IEV encoding in this region immediately after active rTMS.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
21 participants
Primary outcome timeframe
30 minutes post-rTMS
Results posted on
2024-07-16
Participant Flow
Enrollment of participants from the local Albuquerque NM community began on 8/1/21 and ended on 6/21/23. Please note that a significant number of recruited participants attended our first baseline fMRI session but did not return for the followup rTMS intervention visits. This includes a participant that completed their baseline visit on 6/21/2023 but did not return for followup due to scheduling conflicts. In total, N=12 participants completed the intervention.
Participant milestones
| Measure |
Active rTMS First, Then Sham rTMS
Participants first complete a Baseline Visit to identify a neural target for rTMS. Then, on Visit 2 participants receive active rTMS for 10-20 minutes prior to collection of outcome measures via fMRI. Lastly, on Visit 3, participants receive sham rTMS for 10-20 minutes, and the same outcome measures are collected.
Repetitive Transcranial Magnetic Stimulation (rTMS): TMS pulses will be delivered through an air-cooled coil in either a figure-eight or double-cone shape, with the latter being particularly useful for targeting deeper structures such as dACC. The first phase of the TMS protocol will involve a standardized motor-thresholding procedure, wherein peripheral responses evoked by single TMS pulses are recorded via an electromyographic recording device. In this phase, the TMS coil's stimulation intensity is titrated to a level that is comfortable yet effective at reliably exciting neuronal populations orthogonal to the coil (50% motor-evoked potentials ≥50 microvolts; typical duration≈20-40 mins). Then repetitive TMS (rTMS) will be administered to a pre-determined cortical target based on the individual's pre-TMS fMRI scan using a Localite Neuronavigation system (duration≈10-20 mins). The rTMS protocol will involve the delivery of a train of TMS pulses over a cortical target prior to performance of behavioral tasks during a post-rTMS fMRI scan.
|
Sham rTMS First, Then Active rTMS.
Participants first complete a Baseline Visit to identify a neural target for rTMS. Then, on Visit 2 participants receive sham rTMS for 10-20 minutes prior to collection of outcome measures via fMRI. Lastly, on Visit 3, participants receive active rTMS for 10-20 minutes, and the same outcome measures are collected.
Repetitive Transcranial Magnetic Stimulation (rTMS): TMS pulses will be delivered through an air-cooled coil in either a figure-eight or double-cone shape, with the latter being particularly useful for targeting deeper structures such as dACC. The first phase of the TMS protocol will involve a standardized motor-thresholding procedure, wherein peripheral responses evoked by single TMS pulses are recorded via an electromyographic recording device. In this phase, the TMS coil's stimulation intensity is titrated to a level that is comfortable yet effective at reliably exciting neuronal populations orthogonal to the coil (50% motor-evoked potentials ≥50 microvolts; typical duration≈20-40 mins). Then repetitive TMS (rTMS) will be administered to a pre-determined cortical target based on the individual's pre-TMS fMRI scan using a Localite Neuronavigation system (duration≈10-20 mins). The rTMS protocol will involve the delivery of a train of TMS pulses over a cortical target prior to performance of behavioral tasks during a post-rTMS fMRI scan.
|
|---|---|---|
|
Baseline MRI Scan (1 Day)
STARTED
|
11
|
10
|
|
Baseline MRI Scan (1 Day)
COMPLETED
|
11
|
10
|
|
Baseline MRI Scan (1 Day)
NOT COMPLETED
|
0
|
0
|
|
First Intervention (1 Day)
STARTED
|
8
|
5
|
|
First Intervention (1 Day)
COMPLETED
|
7
|
5
|
|
First Intervention (1 Day)
NOT COMPLETED
|
1
|
0
|
|
Washout (7 or More Days)
STARTED
|
7
|
5
|
|
Washout (7 or More Days)
COMPLETED
|
7
|
5
|
|
Washout (7 or More Days)
NOT COMPLETED
|
0
|
0
|
|
Second Intervention (1 Day)
STARTED
|
7
|
5
|
|
Second Intervention (1 Day)
COMPLETED
|
7
|
5
|
|
Second Intervention (1 Day)
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Active rTMS First, Then Sham rTMS
Participants first complete a Baseline Visit to identify a neural target for rTMS. Then, on Visit 2 participants receive active rTMS for 10-20 minutes prior to collection of outcome measures via fMRI. Lastly, on Visit 3, participants receive sham rTMS for 10-20 minutes, and the same outcome measures are collected.
Repetitive Transcranial Magnetic Stimulation (rTMS): TMS pulses will be delivered through an air-cooled coil in either a figure-eight or double-cone shape, with the latter being particularly useful for targeting deeper structures such as dACC. The first phase of the TMS protocol will involve a standardized motor-thresholding procedure, wherein peripheral responses evoked by single TMS pulses are recorded via an electromyographic recording device. In this phase, the TMS coil's stimulation intensity is titrated to a level that is comfortable yet effective at reliably exciting neuronal populations orthogonal to the coil (50% motor-evoked potentials ≥50 microvolts; typical duration≈20-40 mins). Then repetitive TMS (rTMS) will be administered to a pre-determined cortical target based on the individual's pre-TMS fMRI scan using a Localite Neuronavigation system (duration≈10-20 mins). The rTMS protocol will involve the delivery of a train of TMS pulses over a cortical target prior to performance of behavioral tasks during a post-rTMS fMRI scan.
|
Sham rTMS First, Then Active rTMS.
Participants first complete a Baseline Visit to identify a neural target for rTMS. Then, on Visit 2 participants receive sham rTMS for 10-20 minutes prior to collection of outcome measures via fMRI. Lastly, on Visit 3, participants receive active rTMS for 10-20 minutes, and the same outcome measures are collected.
Repetitive Transcranial Magnetic Stimulation (rTMS): TMS pulses will be delivered through an air-cooled coil in either a figure-eight or double-cone shape, with the latter being particularly useful for targeting deeper structures such as dACC. The first phase of the TMS protocol will involve a standardized motor-thresholding procedure, wherein peripheral responses evoked by single TMS pulses are recorded via an electromyographic recording device. In this phase, the TMS coil's stimulation intensity is titrated to a level that is comfortable yet effective at reliably exciting neuronal populations orthogonal to the coil (50% motor-evoked potentials ≥50 microvolts; typical duration≈20-40 mins). Then repetitive TMS (rTMS) will be administered to a pre-determined cortical target based on the individual's pre-TMS fMRI scan using a Localite Neuronavigation system (duration≈10-20 mins). The rTMS protocol will involve the delivery of a train of TMS pulses over a cortical target prior to performance of behavioral tasks during a post-rTMS fMRI scan.
|
|---|---|---|
|
First Intervention (1 Day)
Adverse Event
|
1
|
0
|
Baseline Characteristics
Noninvasive Modulation of Motivational Brain Regions in Healthy Volunteers
Baseline characteristics by cohort
| Measure |
Active rTMS First, Then Sham rTMS
n=11 Participants
Participants first complete a Baseline Visit to identify a neural target for rTMS. Then, on Visit 2 participants receive active rTMS for 10-20 minutes prior to collection of outcome measures via fMRI. Lastly, on Visit 3, participants receive sham rTMS for 10-20 minutes, and the same outcome measures are collected.
Repetitive Transcranial Magnetic Stimulation (rTMS): TMS pulses will be delivered through an air-cooled coil in either a figure-eight or double-cone shape, with the latter being particularly useful for targeting deeper structures such as dACC. The first phase of the TMS protocol will involve a standardized motor-thresholding procedure, wherein peripheral responses evoked by single TMS pulses are recorded via an electromyographic recording device. In this phase, the TMS coil's stimulation intensity is titrated to a level that is comfortable yet effective at reliably exciting neuronal populations orthogonal to the coil (50% motor-evoked potentials ≥50 microvolts; typical duration≈20-40 mins). Then repetitive TMS (rTMS) will be administered to a pre-determined cortical target based on the individual's pre-TMS fMRI scan using a Localite Neuronavigation system (duration≈10-20 mins). The rTMS protocol will involve the delivery of a train of TMS pulses over a cortical target prior to performance of behavioral tasks during a post-rTMS fMRI scan.
|
Sham rTMS First, Then Active rTMS
n=10 Participants
Participants first complete a Baseline Visit to identify a neural target for rTMS. Then, on Visit 2 participants receive sham rTMS for 10-20 minutes prior to collection of outcome measures via fMRI. Lastly, on Visit 3, participants receive active rTMS for 10-20 minutes, and the same outcome measures are collected.
Repetitive Transcranial Magnetic Stimulation (rTMS): TMS pulses will be delivered through an air-cooled coil in either a figure-eight or double-cone shape, with the latter being particularly useful for targeting deeper structures such as dACC. The first phase of the TMS protocol will involve a standardized motor-thresholding procedure, wherein peripheral responses evoked by single TMS pulses are recorded via an electromyographic recording device. In this phase, the TMS coil's stimulation intensity is titrated to a level that is comfortable yet effective at reliably exciting neuronal populations orthogonal to the coil (50% motor-evoked potentials ≥50 microvolts; typical duration≈20-40 mins). Then repetitive TMS (rTMS) will be administered to a pre-determined cortical target based on the individual's pre-TMS fMRI scan using a Localite Neuronavigation system (duration≈10-20 mins). The rTMS protocol will involve the delivery of a train of TMS pulses over a cortical target prior to performance of behavioral tasks during a post-rTMS fMRI scan.
|
Total
n=21 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
|
11 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
28.14 years
STANDARD_DEVIATION 9.67 • n=5 Participants
|
28.14 years
STANDARD_DEVIATION 9.67 • n=7 Participants
|
28.14 years
STANDARD_DEVIATION 9.67 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
9 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
15 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
|
4 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
5 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
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
7 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
16 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
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
11 participants
n=5 Participants
|
10 participants
n=7 Participants
|
21 participants
n=5 Participants
|
|
Immediate Expected Value (IEV)
|
1.27 beta coefficient
STANDARD_DEVIATION 0.75 • n=5 Participants
|
1.34 beta coefficient
STANDARD_DEVIATION 1.10 • n=7 Participants
|
1.30 beta coefficient
STANDARD_DEVIATION 0.93 • n=5 Participants
|
|
Effort-Based Discounting
|
0.15 beta coefficient
STANDARD_DEVIATION 1.08 • n=5 Participants
|
0.13 beta coefficient
STANDARD_DEVIATION 1.43 • n=7 Participants
|
0.14 beta coefficient
STANDARD_DEVIATION 1.26 • n=5 Participants
|
|
dACC BOLD signal
|
-1.39 Percentage of BOLD signal change
STANDARD_DEVIATION 1.26 • n=5 Participants
|
-0.92 Percentage of BOLD signal change
STANDARD_DEVIATION 1.12 • n=7 Participants
|
-1.16 Percentage of BOLD signal change
STANDARD_DEVIATION 1.19 • n=5 Participants
|
PRIMARY outcome
Timeframe: 30 minutes post-rTMSPopulation: Several participants came for baseline visit but did not return for rTMS visits. Once participant from Arm 1 elected to discontinue rTMS and did not return for their sham visit.
Encoding of trial-by-trial immediate expected value (IEV) in dorsal anterior cingulate cortex (dACC) region-of-interest that was targeted with rTMS. Expressed in units of BOLD % signal change. This primary outcome reflects IEV encoding in this region immediately after active rTMS.
Outcome measures
| Measure |
Active rTMS First, Then Sham rTMS
n=8 Participants
Participants first complete a Baseline Visit to identify a neural target for rTMS. Then, on Visit 2 participants receive active rTMS for 10-20 minutes prior to collection of outcome measures via fMRI. Lastly, on Visit 3, participants receive sham rTMS for 10-20 minutes, and the same outcome measures are collected.
Repetitive Transcranial Magnetic Stimulation (rTMS): TMS pulses will be delivered through an air-cooled coil in either a figure-eight or double-cone shape, with the latter being particularly useful for targeting deeper structures such as dACC. The first phase of the TMS protocol will involve a standardized motor-thresholding procedure, wherein peripheral responses evoked by single TMS pulses are recorded via an electromyographic recording device. In this phase, the TMS coil's stimulation intensity is titrated to a level that is comfortable yet effective at reliably exciting neuronal populations orthogonal to the coil (50% motor-evoked potentials ≥50 microvolts; typical duration≈20-40 mins). Then repetitive TMS (rTMS) will be administered to a pre-determined cortical target based on the individual's pre-TMS fMRI scan using a Localite Neuronavigation system (duration≈10-20 mins). The rTMS protocol will involve the delivery of a train of TMS pulses over a cortical target prior to performance of behavioral tasks during a post-rTMS fMRI scan.
|
Sham rTMS First, Then Active rTMS
n=5 Participants
Participants first complete a Baseline Visit to identify a neural target for rTMS. Then, on Visit 2 participants receive sham rTMS for 10-20 minutes prior to collection of outcome measures via fMRI. Lastly, on Visit 3, participants receive active rTMS for 10-20 minutes, and the same outcome measures are collected.
Repetitive Transcranial Magnetic Stimulation (rTMS): TMS pulses will be delivered through an air-cooled coil in either a figure-eight or double-cone shape, with the latter being particularly useful for targeting deeper structures such as dACC. The first phase of the TMS protocol will involve a standardized motor-thresholding procedure, wherein peripheral responses evoked by single TMS pulses are recorded via an electromyographic recording device. In this phase, the TMS coil's stimulation intensity is titrated to a level that is comfortable yet effective at reliably exciting neuronal populations orthogonal to the coil (50% motor-evoked potentials ≥50 microvolts; typical duration≈20-40 mins). Then repetitive TMS (rTMS) will be administered to a pre-determined cortical target based on the individual's pre-TMS fMRI scan using a Localite Neuronavigation system (duration≈10-20 mins). The rTMS protocol will involve the delivery of a train of TMS pulses over a cortical target prior to performance of behavioral tasks during a post-rTMS fMRI scan.
|
|---|---|---|
|
dACC BOLD Signal (After Active rTMS Session)
|
-1.14 Percentage of BOLD signal change
Standard Deviation 0.92
|
-1.27 Percentage of BOLD signal change
Standard Deviation 0.91
|
PRIMARY outcome
Timeframe: 30 minutes post-rTMSPopulation: Several participants completed baseline visit but did not return for rTMS visits.
A normative computational model (POMDP) is run to fit behavioral performance on a 3-armed bandit reinforcement learning task. Weighting of immediate expected value (IEV) on this model can be generated for each subject, indicating the degree to which they relied on immediate value to drive their decisions. This between-subjects IEV parameter reflects a standardized coefficient from a multinomial logistic regression (softmax) model. Higher values indicate a greater tendency to rely on IEV when making choices.
Outcome measures
| Measure |
Active rTMS First, Then Sham rTMS
n=8 Participants
Participants first complete a Baseline Visit to identify a neural target for rTMS. Then, on Visit 2 participants receive active rTMS for 10-20 minutes prior to collection of outcome measures via fMRI. Lastly, on Visit 3, participants receive sham rTMS for 10-20 minutes, and the same outcome measures are collected.
Repetitive Transcranial Magnetic Stimulation (rTMS): TMS pulses will be delivered through an air-cooled coil in either a figure-eight or double-cone shape, with the latter being particularly useful for targeting deeper structures such as dACC. The first phase of the TMS protocol will involve a standardized motor-thresholding procedure, wherein peripheral responses evoked by single TMS pulses are recorded via an electromyographic recording device. In this phase, the TMS coil's stimulation intensity is titrated to a level that is comfortable yet effective at reliably exciting neuronal populations orthogonal to the coil (50% motor-evoked potentials ≥50 microvolts; typical duration≈20-40 mins). Then repetitive TMS (rTMS) will be administered to a pre-determined cortical target based on the individual's pre-TMS fMRI scan using a Localite Neuronavigation system (duration≈10-20 mins). The rTMS protocol will involve the delivery of a train of TMS pulses over a cortical target prior to performance of behavioral tasks during a post-rTMS fMRI scan.
|
Sham rTMS First, Then Active rTMS
n=5 Participants
Participants first complete a Baseline Visit to identify a neural target for rTMS. Then, on Visit 2 participants receive sham rTMS for 10-20 minutes prior to collection of outcome measures via fMRI. Lastly, on Visit 3, participants receive active rTMS for 10-20 minutes, and the same outcome measures are collected.
Repetitive Transcranial Magnetic Stimulation (rTMS): TMS pulses will be delivered through an air-cooled coil in either a figure-eight or double-cone shape, with the latter being particularly useful for targeting deeper structures such as dACC. The first phase of the TMS protocol will involve a standardized motor-thresholding procedure, wherein peripheral responses evoked by single TMS pulses are recorded via an electromyographic recording device. In this phase, the TMS coil's stimulation intensity is titrated to a level that is comfortable yet effective at reliably exciting neuronal populations orthogonal to the coil (50% motor-evoked potentials ≥50 microvolts; typical duration≈20-40 mins). Then repetitive TMS (rTMS) will be administered to a pre-determined cortical target based on the individual's pre-TMS fMRI scan using a Localite Neuronavigation system (duration≈10-20 mins). The rTMS protocol will involve the delivery of a train of TMS pulses over a cortical target prior to performance of behavioral tasks during a post-rTMS fMRI scan.
|
|---|---|---|
|
Immediate Expected Value (IEV; After Active rTMS Visit)
|
1.22 beta coefficient
Standard Deviation 0.76
|
1.62 beta coefficient
Standard Deviation 0.87
|
PRIMARY outcome
Timeframe: 30 minutes post-rTMSPopulation: Several participants did the baseline visit but did not return to complete the rTMS visits.
Participants make a series of effort - value tradeoff decisions on our Effort-Based Decision-Making task. Values reflect a standardized coefficient of the random subject-level intercept from a hierarchical logistic regression model fit with an interaction term, between effort and value, to index "effort-based discounting" of reward (i.e., the degree to which increases in effort level change the motivational salience of reward value on decisions). Higher values indicate a greater tendency to de-value rewards based on increasing effort level.
Outcome measures
| Measure |
Active rTMS First, Then Sham rTMS
n=8 Participants
Participants first complete a Baseline Visit to identify a neural target for rTMS. Then, on Visit 2 participants receive active rTMS for 10-20 minutes prior to collection of outcome measures via fMRI. Lastly, on Visit 3, participants receive sham rTMS for 10-20 minutes, and the same outcome measures are collected.
Repetitive Transcranial Magnetic Stimulation (rTMS): TMS pulses will be delivered through an air-cooled coil in either a figure-eight or double-cone shape, with the latter being particularly useful for targeting deeper structures such as dACC. The first phase of the TMS protocol will involve a standardized motor-thresholding procedure, wherein peripheral responses evoked by single TMS pulses are recorded via an electromyographic recording device. In this phase, the TMS coil's stimulation intensity is titrated to a level that is comfortable yet effective at reliably exciting neuronal populations orthogonal to the coil (50% motor-evoked potentials ≥50 microvolts; typical duration≈20-40 mins). Then repetitive TMS (rTMS) will be administered to a pre-determined cortical target based on the individual's pre-TMS fMRI scan using a Localite Neuronavigation system (duration≈10-20 mins). The rTMS protocol will involve the delivery of a train of TMS pulses over a cortical target prior to performance of behavioral tasks during a post-rTMS fMRI scan.
|
Sham rTMS First, Then Active rTMS
n=5 Participants
Participants first complete a Baseline Visit to identify a neural target for rTMS. Then, on Visit 2 participants receive sham rTMS for 10-20 minutes prior to collection of outcome measures via fMRI. Lastly, on Visit 3, participants receive active rTMS for 10-20 minutes, and the same outcome measures are collected.
Repetitive Transcranial Magnetic Stimulation (rTMS): TMS pulses will be delivered through an air-cooled coil in either a figure-eight or double-cone shape, with the latter being particularly useful for targeting deeper structures such as dACC. The first phase of the TMS protocol will involve a standardized motor-thresholding procedure, wherein peripheral responses evoked by single TMS pulses are recorded via an electromyographic recording device. In this phase, the TMS coil's stimulation intensity is titrated to a level that is comfortable yet effective at reliably exciting neuronal populations orthogonal to the coil (50% motor-evoked potentials ≥50 microvolts; typical duration≈20-40 mins). Then repetitive TMS (rTMS) will be administered to a pre-determined cortical target based on the individual's pre-TMS fMRI scan using a Localite Neuronavigation system (duration≈10-20 mins). The rTMS protocol will involve the delivery of a train of TMS pulses over a cortical target prior to performance of behavioral tasks during a post-rTMS fMRI scan.
|
|---|---|---|
|
Effort-Based Discounting (After Active rTMS)
|
0.35 beta coefficient
Standard Deviation 1.01
|
-0.62 beta coefficient
Standard Deviation 0.65
|
PRIMARY outcome
Timeframe: 30 minutes post-rTMSPopulation: Several participants came for baseline visit but did not return for rTMS visits. Once participant from Arm 1 elected to discontinue rTMS and did not return for their sham visit.
Encoding of trial-by-trial immediate expected value (IEV) in dorsal anterior cingulate cortex (dACC) region-of-interest that was targeted with rTMS. Expressed in units of BOLD % signal change. This primary outcome reflects IEV encoding in this region immediately after sham rTMS.
Outcome measures
| Measure |
Active rTMS First, Then Sham rTMS
n=8 Participants
Participants first complete a Baseline Visit to identify a neural target for rTMS. Then, on Visit 2 participants receive active rTMS for 10-20 minutes prior to collection of outcome measures via fMRI. Lastly, on Visit 3, participants receive sham rTMS for 10-20 minutes, and the same outcome measures are collected.
Repetitive Transcranial Magnetic Stimulation (rTMS): TMS pulses will be delivered through an air-cooled coil in either a figure-eight or double-cone shape, with the latter being particularly useful for targeting deeper structures such as dACC. The first phase of the TMS protocol will involve a standardized motor-thresholding procedure, wherein peripheral responses evoked by single TMS pulses are recorded via an electromyographic recording device. In this phase, the TMS coil's stimulation intensity is titrated to a level that is comfortable yet effective at reliably exciting neuronal populations orthogonal to the coil (50% motor-evoked potentials ≥50 microvolts; typical duration≈20-40 mins). Then repetitive TMS (rTMS) will be administered to a pre-determined cortical target based on the individual's pre-TMS fMRI scan using a Localite Neuronavigation system (duration≈10-20 mins). The rTMS protocol will involve the delivery of a train of TMS pulses over a cortical target prior to performance of behavioral tasks during a post-rTMS fMRI scan.
|
Sham rTMS First, Then Active rTMS
n=5 Participants
Participants first complete a Baseline Visit to identify a neural target for rTMS. Then, on Visit 2 participants receive sham rTMS for 10-20 minutes prior to collection of outcome measures via fMRI. Lastly, on Visit 3, participants receive active rTMS for 10-20 minutes, and the same outcome measures are collected.
Repetitive Transcranial Magnetic Stimulation (rTMS): TMS pulses will be delivered through an air-cooled coil in either a figure-eight or double-cone shape, with the latter being particularly useful for targeting deeper structures such as dACC. The first phase of the TMS protocol will involve a standardized motor-thresholding procedure, wherein peripheral responses evoked by single TMS pulses are recorded via an electromyographic recording device. In this phase, the TMS coil's stimulation intensity is titrated to a level that is comfortable yet effective at reliably exciting neuronal populations orthogonal to the coil (50% motor-evoked potentials ≥50 microvolts; typical duration≈20-40 mins). Then repetitive TMS (rTMS) will be administered to a pre-determined cortical target based on the individual's pre-TMS fMRI scan using a Localite Neuronavigation system (duration≈10-20 mins). The rTMS protocol will involve the delivery of a train of TMS pulses over a cortical target prior to performance of behavioral tasks during a post-rTMS fMRI scan.
|
|---|---|---|
|
dACC BOLD Signal (After Sham rTMS Session)
|
-1.18 Percentage of BOLD signal change
Standard Deviation 1.61
|
-0.96 Percentage of BOLD signal change
Standard Deviation 0.94
|
PRIMARY outcome
Timeframe: 30 minutes post-rTMSPopulation: Several participants completed baseline visit but did not return for rTMS visits.
A normative computational model (POMDP) is run to fit behavioral performance on a 3-armed bandit reinforcement learning task. Weighting of immediate expected value (IEV) on this model can be generated for each subject, indicating the degree to which they relied on immediate value to drive their decisions. This between-subjects IEV parameter reflects a standardized coefficient from a multinomial logistic regression (softmax) model. Higher values indicate a greater tendency to rely on IEV when making choices.
Outcome measures
| Measure |
Active rTMS First, Then Sham rTMS
n=8 Participants
Participants first complete a Baseline Visit to identify a neural target for rTMS. Then, on Visit 2 participants receive active rTMS for 10-20 minutes prior to collection of outcome measures via fMRI. Lastly, on Visit 3, participants receive sham rTMS for 10-20 minutes, and the same outcome measures are collected.
Repetitive Transcranial Magnetic Stimulation (rTMS): TMS pulses will be delivered through an air-cooled coil in either a figure-eight or double-cone shape, with the latter being particularly useful for targeting deeper structures such as dACC. The first phase of the TMS protocol will involve a standardized motor-thresholding procedure, wherein peripheral responses evoked by single TMS pulses are recorded via an electromyographic recording device. In this phase, the TMS coil's stimulation intensity is titrated to a level that is comfortable yet effective at reliably exciting neuronal populations orthogonal to the coil (50% motor-evoked potentials ≥50 microvolts; typical duration≈20-40 mins). Then repetitive TMS (rTMS) will be administered to a pre-determined cortical target based on the individual's pre-TMS fMRI scan using a Localite Neuronavigation system (duration≈10-20 mins). The rTMS protocol will involve the delivery of a train of TMS pulses over a cortical target prior to performance of behavioral tasks during a post-rTMS fMRI scan.
|
Sham rTMS First, Then Active rTMS
n=5 Participants
Participants first complete a Baseline Visit to identify a neural target for rTMS. Then, on Visit 2 participants receive sham rTMS for 10-20 minutes prior to collection of outcome measures via fMRI. Lastly, on Visit 3, participants receive active rTMS for 10-20 minutes, and the same outcome measures are collected.
Repetitive Transcranial Magnetic Stimulation (rTMS): TMS pulses will be delivered through an air-cooled coil in either a figure-eight or double-cone shape, with the latter being particularly useful for targeting deeper structures such as dACC. The first phase of the TMS protocol will involve a standardized motor-thresholding procedure, wherein peripheral responses evoked by single TMS pulses are recorded via an electromyographic recording device. In this phase, the TMS coil's stimulation intensity is titrated to a level that is comfortable yet effective at reliably exciting neuronal populations orthogonal to the coil (50% motor-evoked potentials ≥50 microvolts; typical duration≈20-40 mins). Then repetitive TMS (rTMS) will be administered to a pre-determined cortical target based on the individual's pre-TMS fMRI scan using a Localite Neuronavigation system (duration≈10-20 mins). The rTMS protocol will involve the delivery of a train of TMS pulses over a cortical target prior to performance of behavioral tasks during a post-rTMS fMRI scan.
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Immediate Expected Value (IEV; After Sham rTMS Visit)
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1.06 beta coefficient
Standard Deviation 0.56
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1.32 beta coefficient
Standard Deviation 1.10
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PRIMARY outcome
Timeframe: 30 minutes post-rTMSPopulation: Several participants did the baseline visit but did not return to complete the rTMS visits.
Participants make a series of effort - value tradeoff decisions on our Effort-Based Decision-Making task. Values reflect a standardized coefficient of the random subject-level intercept from a hierarchical logistic regression model fit with an interaction term, between effort and value, to index "effort-based discounting" of reward (i.e., the degree to which increases in effort level change the motivational salience of reward value on decisions). Higher values indicate a greater tendency to de-value rewards based on increasing effort level.
Outcome measures
| Measure |
Active rTMS First, Then Sham rTMS
n=8 Participants
Participants first complete a Baseline Visit to identify a neural target for rTMS. Then, on Visit 2 participants receive active rTMS for 10-20 minutes prior to collection of outcome measures via fMRI. Lastly, on Visit 3, participants receive sham rTMS for 10-20 minutes, and the same outcome measures are collected.
Repetitive Transcranial Magnetic Stimulation (rTMS): TMS pulses will be delivered through an air-cooled coil in either a figure-eight or double-cone shape, with the latter being particularly useful for targeting deeper structures such as dACC. The first phase of the TMS protocol will involve a standardized motor-thresholding procedure, wherein peripheral responses evoked by single TMS pulses are recorded via an electromyographic recording device. In this phase, the TMS coil's stimulation intensity is titrated to a level that is comfortable yet effective at reliably exciting neuronal populations orthogonal to the coil (50% motor-evoked potentials ≥50 microvolts; typical duration≈20-40 mins). Then repetitive TMS (rTMS) will be administered to a pre-determined cortical target based on the individual's pre-TMS fMRI scan using a Localite Neuronavigation system (duration≈10-20 mins). The rTMS protocol will involve the delivery of a train of TMS pulses over a cortical target prior to performance of behavioral tasks during a post-rTMS fMRI scan.
|
Sham rTMS First, Then Active rTMS
n=5 Participants
Participants first complete a Baseline Visit to identify a neural target for rTMS. Then, on Visit 2 participants receive sham rTMS for 10-20 minutes prior to collection of outcome measures via fMRI. Lastly, on Visit 3, participants receive active rTMS for 10-20 minutes, and the same outcome measures are collected.
Repetitive Transcranial Magnetic Stimulation (rTMS): TMS pulses will be delivered through an air-cooled coil in either a figure-eight or double-cone shape, with the latter being particularly useful for targeting deeper structures such as dACC. The first phase of the TMS protocol will involve a standardized motor-thresholding procedure, wherein peripheral responses evoked by single TMS pulses are recorded via an electromyographic recording device. In this phase, the TMS coil's stimulation intensity is titrated to a level that is comfortable yet effective at reliably exciting neuronal populations orthogonal to the coil (50% motor-evoked potentials ≥50 microvolts; typical duration≈20-40 mins). Then repetitive TMS (rTMS) will be administered to a pre-determined cortical target based on the individual's pre-TMS fMRI scan using a Localite Neuronavigation system (duration≈10-20 mins). The rTMS protocol will involve the delivery of a train of TMS pulses over a cortical target prior to performance of behavioral tasks during a post-rTMS fMRI scan.
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|---|---|---|
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Effort-Based Discounting (After Sham rTMS)
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0.08 beta coefficient
Standard Deviation 0.12
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0.13 beta coefficient
Standard Deviation 0.18
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Adverse Events
Active rTMS
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Sham rTMS
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Active rTMS
n=12 participants at risk
Repetitive Transcranial Magnetic Stimulation (rTMS): TMS were delivered through an air-cooled coil in either a double-cone shape placed over dACC. The first phase of the TMS protocol involved a standardized motor-thresholding procedure, wherein peripheral responses evoked by single TMS pulses were recorded via an electromyographic recording device. In this phase, the TMS coil's stimulation intensity is titrated to a level that is comfortable yet effective at reliably exciting neuronal populations orthogonal to the coil (50% motor-evoked potentials ≥50 microvolts; typical duration≈20-40 mins). Then repetitive TMS (rTMS) was administered to a pre-determined cortical target based on the individual's pre-TMS fMRI scan using a Localite Neuronavigation system (duration≤10 mins). The rTMS protocol will involve the delivery of a train of TMS pulses over a cortical target prior to performance of behavioral tasks during a post-rTMS fMRI scan.
|
Sham rTMS
n=12 participants at risk
Sham Repetitive Transcranial Magnetic Stimulation (sham rTMS): TMS were delivered through an air-cooled coil in either a double-cone shape placed over dACC. The first phase of the TMS protocol involved a standardized motor-thresholding procedure, wherein peripheral responses evoked by single TMS pulses were recorded via an electromyographic recording device. In this phase, the TMS coil's stimulation intensity is titrated to a level that is comfortable yet effective at reliably exciting neuronal populations orthogonal to the coil (50% motor-evoked potentials ≥50 microvolts; typical duration≈20-40 mins). Then repetitive TMS (rTMS) was administered to a pre-determined cortical target based on the individual's pre-TMS fMRI scan using a Localite Neuronavigation system (duration≤10 mins). The rTMS protocol will involve the delivery of a train of TMS pulses over a cortical target prior to performance of behavioral tasks during a post-rTMS fMRI scan.
For the sham procedure, subtle tactile stimulation was applied via electrodes underneath the rTMS coil. A sham coil was used that mimicked the sound of the active rTMS delivery without modulating brain activity. This was used to mirror the sensory and placebo effects of the rTMS intervention without neuromodulation.
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Product Issues
Discomfort during Active rTMS
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8.3%
1/12 • Number of events 1 • The duration of time over which each participant was assessed was a median of 41.5 days across the sample of participants that completed all three study visits.
Three types of adverse event data are to be reported: "All-Cause Mortality," "Serious," and "Other (Not Including Serious)" Adverse Events. 1. All-Cause Mortality. 2. Serious Adverse Events. 3. Other (Not Including Serious) Adverse Events.
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0.00%
0/12 • The duration of time over which each participant was assessed was a median of 41.5 days across the sample of participants that completed all three study visits.
Three types of adverse event data are to be reported: "All-Cause Mortality," "Serious," and "Other (Not Including Serious)" Adverse Events. 1. All-Cause Mortality. 2. Serious Adverse Events. 3. Other (Not Including Serious) Adverse Events.
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place