Memory
Conditions
Keywords
memory, healthy, TMS, MRI
Brief summary
The study is investigating working memory brain states by using transcranial magnetic stimulation (TMS) in combination with functional magnetic resonance imaging (fMRI). The study uses a novel, individualized targeting approach for TMS based on each subject's individual multi-modal fMRI data. The individualized target will be stimulated in a TMS/ fMRI imaging session to investigate working memory states and optimal stimulation frequencies.
Detailed description
Prior to any study visits, all subjects will be pre-screened through a REDCap online self-report screening REDCap. The study involves 11 study visits. The first study visit will consist of a consenting and extended screening visit. All participants will have the opportunity to ask questions before signing the electronic consent form. We will complete a semi-structured clinical interview and will demonstrate TMS to ensure the participant is comfortable with all study procedures. This visit will be completed both remote and in-person. The second study visit will involve a 1-hour MRI scan. During the scan, the participant will complete multiple computerized tasks. The MRI scan will include both structural and functional scans, and those scans will be used to localize the stimulation target for the subsequent sessions. The third study visit will be a 2-hour TMS/fMRI session, and the participant will engage in behavioral tasks while interleaved rTMS rounds are delivered at different excitatory frequencies (frequency range: 2Hz-20Hz). This scan will be used to determine the optimal stimulation frequency for the individual participant. The fourth, fifth, and sixth study visits will involve neuromodulation with either the optimized frequency or the frequency least successful in moving a participants brain state, as determined from the third study visit. Each subject will receive \ 3000 pulses in each session, including the pulses from the motor threshold determination. We will determine the stimulation amplitude by using the Stokes equation, which accounts for differences in cortical distance from the site relative to motor cortex (where the motor threshold is found). The seventh study visit will involve a 1-hour TMS/fMRI session while the participant is engaging in a behavioral task. This visit is designed to examine brain and behavioral changes after the first round of neuromodulation. The seventh and the eighth visit will be scheduled at least one week apart. The eighth, ninth, and tenth study visits will mirror the fourth, fifth, and sixth study visits and will involve neuromodulation with either the optimized or least-optimized individual frequency. The order of optimized and least-optimized frequencies will be counterbalanced across participants between Visit 4-6 and Visit 8-10 (i.e., half of the participants will receive stimulations of the two frequencies in one order, and the other half will receive stimulations of the two frequencies in the reverse order). The eleventh visit will mirror the seventh visit and will examine brain and behavioral changes after the second round of neuromodulation.
Interventions
DIAGNOSTIC_TESTFunctional Magnetic Resonance Imaging (fMRI)
Participants undergo resting-state and task-based fMRI to identify individualized transcranial magnetic stimulation (TMS) targets and determine optimal and sub-optimal stimulation frequencies. Additional fMRI scans are performed after each neuromodulation phase to assess changes following three days of stimulation at the optimal and sub-optimal frequencies.
DEVICERepetitive Transcranial Magnetic Stimulation (rTMS)
Participants first receive multiple rTMS frequencies during an fMRI scan to assess brain responses and determine individualized optimal and sub-optimal stimulation frequencies. They then complete two neuromodulation intervention periods, receiving rTMS at the identified optimal and sub-optimal frequencies. Each frequency is administered over three consecutive days, with the order of conditions randomized and counterbalanced.
Sponsors
National Institute of Mental Health (NIMH)
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Intervention model description
Task and resting fMRI will be used to determine an individualized brain target for each participant. In a subsequent session, participants will complete a task fMRI with repetitive TMS neuromodulation; during this session, various stimulation protocols will be interleaved with working memory task blocks to result in online brain readouts of the degree in which modulation affected the brain state in regards to working memory performance. Based on this testing, an optimal and sub-optimal TMS stimulation frequency will be determined for each individual participant. Each frequency will be administered separately across three stimulation days using a crossover design, with the order of frequencies being randomized and counterbalanced. Therefore, each subject will receive six days of TMS stimulation: three using the optimal frequency, and three using the sub-optimal frequency. The initial TMS/ task fMRI testing session will be completed at the midpoint and end of the study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
1)18-60 years old 2) Right handed 3) No psychiatric history as diagnosed by the SCID-V 4) Normal cognition 5) Capacity to give informed consent and follow study procedures 6) Sufficient command of English language to understand and respond to written as well as verbal instructions
Exclusion criteria
1. History of neurological disorder or traumatic brain injury (other than mild) 2. Unable to have an MRI scan, or current or prior medical condition that could interfere with the collection or interpretation of MRI data 3. Unable to receive TMS 4. Implanted devices, such as an aneurysm clip or cardiac pacemaker 5. History of stroke, epilepsy, or brain scarring 6. Recent use of psychoactive medications, as determined by investigators 7. Pregnant, nursing, or trying to become pregnant (self-attestation alone) 8. Color blindness 9. Otherwise determined by investigator to be unfit for study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reaction Time Changes During N-Back Task in Responses to Different TMS Frequencies | Single visit (~2 hours) | During the TMS/fMRI scan, participants perform a working memory task (N-back). To evaluate how different repetitive TMS frequencies (5, 10, and 20 Hz) impact reaction time during N-back task, each rTMS train is followed by a block of the N-back task. A decoder identifies one frequency as optimal frequency and another as suboptimal frequency. Reaction Time during optimal, suboptimal, and no stimulation condition is assessed by taking average of reaction time on accurate trials with faster reaction times indicating better performance. |
| Accuracy Changes During N-Back Task in Responses to Different TMS Frequencies | Single visit (~2 hours) | During the TMS/fMRI scan, participants perform a working memory task (N-back). To evaluate how different repetitive TMS frequencies (5, 10, and 20 Hz) impact accuracy during N-back task, each rTMS train is followed by a block of the N-back task. A decoder identifies one frequency as optimal frequency and another as suboptimal frequency. Accuracy during optimal, suboptimal, and no stimulation condition is assessed by taking average of all the trials with better accuracy indicating better performance. |
| Reaction Time Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Up to 1 month | Each subject completes two 3-day neuromodulation sessions, one using their 'optimal' rTMS frequency, and the other using their 'suboptimal' rTMS frequency, as determined by their TMS/fMRI visit. After each neuromodulation session, subjects complete a working memory task (Delayed Match to Sample). The delay period reflects how long participants can retain the information in working memory. Common delay periods used in research, including our study, are 0 seconds, 4 seconds, and 12 seconds.The outcome measure shows the reaction time for each of these variables. |
| Accuracy Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Up to 1 month | Each subject completes two 3-day neuromodulation sessions, one using their 'optimal' rTMS frequency, and the other using their 'suboptimal' rTMS frequency, as determined by their TMS/fMRI visit. After each neuromodulation session, subjects complete a working memory task (Delayed Match to Sample). The delay period reflects how long participants can retain the information in working memory. Common delay periods used in research, including our study, are 0 seconds, 4 seconds, and 12 seconds.The outcome measure shows the accuracy for each of these variables. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Reaction Time Changes in the Reaction Time Index Task Following Optimal vs. Suboptimal rTMS Stimulation | Up to 1 month | Each subject completes two 3-day neuromodulation sessions, one using their 'optimal' rTMS frequency, and the other using their 'suboptimal' rTMS frequency, as determined by their TMS/fMRI visit. After each neuromodulation session, subjects complete a reaction time index task that acted as a control task. The outcome measure shows the reaction time. |
| Movement Time Changes in the Reaction Time Index Task Following Optimal vs. Suboptimal rTMS Stimulation | Up to 1 month | Each subject completes two 3-day neuromodulation sessions, one using their 'optimal' rTMS frequency, and the other using their 'suboptimal' rTMS frequency, as determined by their TMS/fMRI visit. After each neuromodulation session, subjects complete a reaction time index task that acted as a control task. The outcome measure shows the movement time. |
Countries
United States
Participant flow
Pre-assignment details
Of the 27 participants enrolled in the study, 2 withdrew before group assignment during the baseline MRI visit; one due to MRI-related discomfort and one due to scheduling conflicts.
Participants by arm
| Arm | Count |
|---|---|
| Optimized TMS Frequency, Then Sub-Optimal TMS Frequency In the first neuromodulation session, participants will receive rTMS using their optimal TMS frequency. After washout period of 1 week (minimum), the participants will start their second neuromodulation session using their sub-optimal TMS frequency instead.
Repetitive Transcranial Magnetic Stimulation (rTMS): The investigators will create individualized TMS targets using deep learning methods on task and resting fMRI data to target working memory augmentation. The individualized target will be stimulated in a subsequent fMRI scan involving working memory task performance interleaved with repetitive TMS (rTMS) delivered at a variety of stimulation frequencies. Based on activation readouts in response to rTMS, an optimal and sub-optimal brain state frequency to impact working memory performance will be selected for each participant. Participants will receive rTMS at each frequency separately for three days (six days total), with the order of frequency randomly assigned and counterbalanced. Following each three day protocol, another fMRI working memory readout will be conducted to support the targeting and frequency selection algorithms. | 12 |
| Sub-Optimal TMS Frequency, Then Optimized TMS Frequency In the first neuromodulation session, participants will receive rTMS using their sub-optimal TMS frequency. After washout period of 1 week (minimum), the participants will start their second neuromodulation session using their optimal TMS frequency instead.
Repetitive Transcranial Magnetic Stimulation (rTMS): The investigators will create individualized TMS targets using deep learning methods on task and resting fMRI data to target working memory augmentation. The individualized target will be stimulated in a subsequent fMRI scan involving working memory task performance interleaved with repetitive TMS (rTMS) delivered at a variety of stimulation frequencies. Based on activation readouts in response to rTMS, an optimal and sub-optimal brain state frequency to impact working memory performance will be selected for each participant. Participants will receive rTMS at each frequency separately for three days (six days total), with the order of frequency randomly assigned and counterbalanced. Following each three day protocol, another fMRI working memory readout will be conducted to support the targeting and frequency selection algorithms. | 11 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Washout (at Least 7 Days) | Insufficient study funds to continue with their participation. | 0 | 1 |
| Washout (at Least 7 Days) | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Optimized TMS Frequency, Then Sub-Optimal TMS Frequency | Total | Sub-Optimal TMS Frequency, Then Optimized TMS Frequency |
|---|---|---|---|
| Age, Continuous | 28.51 years STANDARD_DEVIATION 5.98 | 25.43 years STANDARD_DEVIATION 5.71 | 22.67 years STANDARD_DEVIATION 3.91 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 9 Participants | 16 Participants | 7 Participants |
| Region of Enrollment United States | 12 Participants | 23 Participants | 11 Participants |
| Sex: Female, Male Female | 6 Participants | 12 Participants | 6 Participants |
| Sex: Female, Male Male | 6 Participants | 11 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 24 |
| other Total, other adverse events | 4 / 24 | 2 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 |
Outcome results
Primary
Accuracy Changes During N-Back Task in Responses to Different TMS Frequencies
During the TMS/fMRI scan, participants perform a working memory task (N-back). To evaluate how different repetitive TMS frequencies (5, 10, and 20 Hz) impact accuracy during N-back task, each rTMS train is followed by a block of the N-back task. A decoder identifies one frequency as optimal frequency and another as suboptimal frequency. Accuracy during optimal, suboptimal, and no stimulation condition is assessed by taking average of all the trials with better accuracy indicating better performance.
Time frame: Single visit (~2 hours)
Population: All 19 participants underwent three different stimulation periods including Optimal, Suboptimal, and No Stimulation. Four subjects who completed the study were not included in the analysis due to technical issues leading to unreliable or missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| N-Back Performance During Optimal Stimulation | Accuracy Changes During N-Back Task in Responses to Different TMS Frequencies | 91.27 Percentage | Standard Error 16.3 |
| N-back Performance During Suboptimal Stimulation | Accuracy Changes During N-Back Task in Responses to Different TMS Frequencies | 90.71 Percentage | Standard Error 12.87 |
| N-back Performance During No Stimulation | Accuracy Changes During N-Back Task in Responses to Different TMS Frequencies | 90.54 Percentage | Standard Error 13.14 |
Comparison: ANOVA (Optimal vs Suboptimal vs No Stimulation)p-value: 0.975ANOVA
Primary
Accuracy Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation
Each subject completes two 3-day neuromodulation sessions, one using their 'optimal' rTMS frequency, and the other using their 'suboptimal' rTMS frequency, as determined by their TMS/fMRI visit. After each neuromodulation session, subjects complete a working memory task (Delayed Match to Sample). The delay period reflects how long participants can retain the information in working memory. Common delay periods used in research, including our study, are 0 seconds, 4 seconds, and 12 seconds.The outcome measure shows the accuracy for each of these variables.
Time frame: Up to 1 month
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| N-Back Performance During Optimal Stimulation | Accuracy Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Accuracy (4 sec delay) | 79.5037 Percentage | Standard Error 2.6388 |
| N-Back Performance During Optimal Stimulation | Accuracy Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Accuracy (0 sec delay) | 84.2667 Percentage | Standard Error 3.2161 |
| N-Back Performance During Optimal Stimulation | Accuracy Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Accuracy (12 sec delay) | 79.4809 Percentage | Standard Error 2.7578 |
| N-back Performance During Suboptimal Stimulation | Accuracy Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Accuracy (4 sec delay) | 78.1085 Percentage | Standard Error 2.7024 |
| N-back Performance During Suboptimal Stimulation | Accuracy Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Accuracy (0 sec delay) | 88.1011 Percentage | Standard Error 2.0073 |
| N-back Performance During Suboptimal Stimulation | Accuracy Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Accuracy (12 sec delay) | 77.6172 Percentage | Standard Error 3.0897 |
| N-back Performance During No Stimulation | Accuracy Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Accuracy (4 sec delay) | 84.4127 Percentage | Standard Error 2.8358 |
| N-back Performance During No Stimulation | Accuracy Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Accuracy (0 sec delay) | 83.9079 Percentage | Standard Error 3.6464 |
| N-back Performance During No Stimulation | Accuracy Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Accuracy (12 sec delay) | 88.0465 Percentage | Standard Error 2.5656 |
| Suboptimal Neuromodulation Day-1 | Accuracy Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Accuracy (4 sec delay) | 78.2541 Percentage | Standard Error 3.068 |
| Suboptimal Neuromodulation Day-1 | Accuracy Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Accuracy (0 sec delay) | 86.0638 Percentage | Standard Error 2.7408 |
| Suboptimal Neuromodulation Day-1 | Accuracy Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Accuracy (12 sec delay) | 76.4133 Percentage | Standard Error 3.4818 |
| Suboptimal Neuromodulation Day-2 | Accuracy Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Accuracy (4 sec delay) | 81.3003 Percentage | Standard Error 3.5756 |
| Suboptimal Neuromodulation Day-2 | Accuracy Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Accuracy (0 sec delay) | 87.8524 Percentage | Standard Error 2.3671 |
| Suboptimal Neuromodulation Day-2 | Accuracy Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Accuracy (12 sec delay) | 76.1351 Percentage | Standard Error 3.1626 |
| Suboptimal Neuromodulation Day-3 | Accuracy Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Accuracy (0 sec delay) | 84.3748 Percentage | Standard Error 2.8921 |
| Suboptimal Neuromodulation Day-3 | Accuracy Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Accuracy (12 sec delay) | 79.9014 Percentage | Standard Error 3.4101 |
| Suboptimal Neuromodulation Day-3 | Accuracy Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Accuracy (4 sec delay) | 77.5741 Percentage | Standard Error 2.8761 |
Comparison: ANOVA, with neuromodulation stimulation type (optimal vs. suboptimal), stimulation days (1 to 3), and delay (0, 4, or 12 seconds) as within-subject variables.p-value: 0.644ANOVA
Primary
Reaction Time Changes During N-Back Task in Responses to Different TMS Frequencies
During the TMS/fMRI scan, participants perform a working memory task (N-back). To evaluate how different repetitive TMS frequencies (5, 10, and 20 Hz) impact reaction time during N-back task, each rTMS train is followed by a block of the N-back task. A decoder identifies one frequency as optimal frequency and another as suboptimal frequency. Reaction Time during optimal, suboptimal, and no stimulation condition is assessed by taking average of reaction time on accurate trials with faster reaction times indicating better performance.
Time frame: Single visit (~2 hours)
Population: All 19 participants underwent three different stimulation periods including Optimal, Suboptimal, and No Stimulation. Four subjects who completed the study were not included in the analysis due to technical issues leading to unreliable or missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| N-Back Performance During Optimal Stimulation | Reaction Time Changes During N-Back Task in Responses to Different TMS Frequencies | 0.5853 Seconds | Standard Deviation 0.098 |
| N-back Performance During Suboptimal Stimulation | Reaction Time Changes During N-Back Task in Responses to Different TMS Frequencies | 0.5978 Seconds | Standard Deviation 0.1496 |
| N-back Performance During No Stimulation | Reaction Time Changes During N-Back Task in Responses to Different TMS Frequencies | 0.6012 Seconds | Standard Deviation 0.0961 |
Comparison: ANOVA (Optimal vs Suboptimal vs No Stimulation)p-value: 0.5ANOVA
Primary
Reaction Time Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation
Each subject completes two 3-day neuromodulation sessions, one using their 'optimal' rTMS frequency, and the other using their 'suboptimal' rTMS frequency, as determined by their TMS/fMRI visit. After each neuromodulation session, subjects complete a working memory task (Delayed Match to Sample). The delay period reflects how long participants can retain the information in working memory. Common delay periods used in research, including our study, are 0 seconds, 4 seconds, and 12 seconds.The outcome measure shows the reaction time for each of these variables.
Time frame: Up to 1 month
Population: Participants underwent three consecutive optimal and three consecutive suboptimal neuromodulation sessions in a randomized sequence. The optimal and suboptimal sessions were separated by at least one week to allow the effects of the stimulation to dissipate. the DMTS task consisted of three conditions including 0 sec, 4 sec, and 12 sec delay conditions. Four subjects who completed the study were not included in the analysis due to technical issues leading to unreliable or missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| N-Back Performance During Optimal Stimulation | Reaction Time Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Reaction Time (4 sec delay) | 2.6640 Reaction Time (sec) | Standard Error 0.1936 |
| N-Back Performance During Optimal Stimulation | Reaction Time Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Reaction Time (0 sec delay) | 2.0173 Reaction Time (sec) | Standard Error 0.1423 |
| N-Back Performance During Optimal Stimulation | Reaction Time Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Reaction Time (12 sec delay) | 2.7351 Reaction Time (sec) | Standard Error 0.1588 |
| N-back Performance During Suboptimal Stimulation | Reaction Time Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Reaction Time (4 sec delay) | 2.4269 Reaction Time (sec) | Standard Error 0.1537 |
| N-back Performance During Suboptimal Stimulation | Reaction Time Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Reaction Time (0 sec delay) | 1.7568 Reaction Time (sec) | Standard Error 0.089 |
| N-back Performance During Suboptimal Stimulation | Reaction Time Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Reaction Time (12 sec delay) | 2.5593 Reaction Time (sec) | Standard Error 0.1995 |
| N-back Performance During No Stimulation | Reaction Time Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Reaction Time (4 sec delay) | 2.1726 Reaction Time (sec) | Standard Error 0.1292 |
| N-back Performance During No Stimulation | Reaction Time Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Reaction Time (0 sec delay) | 1.9316 Reaction Time (sec) | Standard Error 0.1862 |
| N-back Performance During No Stimulation | Reaction Time Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Reaction Time (12 sec delay) | 2.4400 Reaction Time (sec) | Standard Error 0.1602 |
| Suboptimal Neuromodulation Day-1 | Reaction Time Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Reaction Time (4 sec delay) | 2.3907 Reaction Time (sec) | Standard Error 0.1615 |
| Suboptimal Neuromodulation Day-1 | Reaction Time Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Reaction Time (0 sec delay) | 2.0608 Reaction Time (sec) | Standard Error 0.1542 |
| Suboptimal Neuromodulation Day-1 | Reaction Time Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Reaction Time (12 sec delay) | 2.4901 Reaction Time (sec) | Standard Error 0.1377 |
| Suboptimal Neuromodulation Day-2 | Reaction Time Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Reaction Time (4 sec delay) | 2.3268 Reaction Time (sec) | Standard Error 0.1694 |
| Suboptimal Neuromodulation Day-2 | Reaction Time Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Reaction Time (0 sec delay) | 1.9118 Reaction Time (sec) | Standard Error 0.1068 |
| Suboptimal Neuromodulation Day-2 | Reaction Time Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Reaction Time (12 sec delay) | 2.5741 Reaction Time (sec) | Standard Error 0.2054 |
| Suboptimal Neuromodulation Day-3 | Reaction Time Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Reaction Time (0 sec delay) | 1.9139 Reaction Time (sec) | Standard Error 0.1163 |
| Suboptimal Neuromodulation Day-3 | Reaction Time Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Reaction Time (12 sec delay) | 2.6478 Reaction Time (sec) | Standard Error 0.2501 |
| Suboptimal Neuromodulation Day-3 | Reaction Time Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation | Reaction Time (4 sec delay) | 2.4788 Reaction Time (sec) | Standard Error 0.2135 |
Comparison: ANOVA, with neuromodulation stimulation type (optimal vs. suboptimal), stimulation days (1 to 3), and delay (0, 4, or 12 seconds) as within-subject variables.p-value: 0.097ANOVA
Secondary
Movement Time Changes in the Reaction Time Index Task Following Optimal vs. Suboptimal rTMS Stimulation
Each subject completes two 3-day neuromodulation sessions, one using their 'optimal' rTMS frequency, and the other using their 'suboptimal' rTMS frequency, as determined by their TMS/fMRI visit. After each neuromodulation session, subjects complete a reaction time index task that acted as a control task. The outcome measure shows the movement time.
Time frame: Up to 1 month
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| N-Back Performance During Optimal Stimulation | Movement Time Changes in the Reaction Time Index Task Following Optimal vs. Suboptimal rTMS Stimulation | 0.411 seconds | Standard Deviation 0.049 |
| N-back Performance During Suboptimal Stimulation | Movement Time Changes in the Reaction Time Index Task Following Optimal vs. Suboptimal rTMS Stimulation | 0.417 seconds | Standard Deviation 0.087 |
| N-back Performance During No Stimulation | Movement Time Changes in the Reaction Time Index Task Following Optimal vs. Suboptimal rTMS Stimulation | 0.381 seconds | Standard Deviation 0.072 |
| Suboptimal Neuromodulation Day-1 | Movement Time Changes in the Reaction Time Index Task Following Optimal vs. Suboptimal rTMS Stimulation | 0.411 seconds | Standard Deviation 0.098 |
| Suboptimal Neuromodulation Day-2 | Movement Time Changes in the Reaction Time Index Task Following Optimal vs. Suboptimal rTMS Stimulation | 0.406 seconds | Standard Deviation 0.074 |
| Suboptimal Neuromodulation Day-3 | Movement Time Changes in the Reaction Time Index Task Following Optimal vs. Suboptimal rTMS Stimulation | 0.395 seconds | Standard Deviation 0.076 |
Comparison: Optimal Neuromodulation Day-1, Optimal Neuromodulation Day-2, Optimal Neuromodulation Day-3, Suboptimal Neuromodulation Day-1, Suboptimal Neuromodulation Day-2, Suboptimal Neuromodulation Day-3p-value: 0.563ANOVA
Secondary
Reaction Time Changes in the Reaction Time Index Task Following Optimal vs. Suboptimal rTMS Stimulation
Each subject completes two 3-day neuromodulation sessions, one using their 'optimal' rTMS frequency, and the other using their 'suboptimal' rTMS frequency, as determined by their TMS/fMRI visit. After each neuromodulation session, subjects complete a reaction time index task that acted as a control task. The outcome measure shows the reaction time.
Time frame: Up to 1 month
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| N-Back Performance During Optimal Stimulation | Reaction Time Changes in the Reaction Time Index Task Following Optimal vs. Suboptimal rTMS Stimulation | 0.716 Seconds | Standard Deviation 0.072 |
| N-back Performance During Suboptimal Stimulation | Reaction Time Changes in the Reaction Time Index Task Following Optimal vs. Suboptimal rTMS Stimulation | 0.722 Seconds | Standard Deviation 0.108 |
| N-back Performance During No Stimulation | Reaction Time Changes in the Reaction Time Index Task Following Optimal vs. Suboptimal rTMS Stimulation | 0.687 Seconds | Standard Deviation 0.085 |
| Suboptimal Neuromodulation Day-1 | Reaction Time Changes in the Reaction Time Index Task Following Optimal vs. Suboptimal rTMS Stimulation | 0.736 Seconds | Standard Deviation 0.117 |
| Suboptimal Neuromodulation Day-2 | Reaction Time Changes in the Reaction Time Index Task Following Optimal vs. Suboptimal rTMS Stimulation | 0.713 Seconds | Standard Deviation 0.102 |
| Suboptimal Neuromodulation Day-3 | Reaction Time Changes in the Reaction Time Index Task Following Optimal vs. Suboptimal rTMS Stimulation | 0.693 Seconds | Standard Deviation 0.093 |
Comparison: ANOVA, with neuromodulation stimulation type (optimal vs. suboptimal), and stimulation days (1 to 3) as within-subject variables.p-value: 0.439ANOVA