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| ID | Type | Description | Link |
|---|---|---|---|
| NNX16AO30G | Other Grant/Funding Number | National Aeronautics and Space Administration (NASA) |
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The objective of this randomized, double-blind, sham-controlled, crossover study is to evaluate the effects of transcranial electrical stimulation (tES) on complex cognitive task performance in healthy adult volunteers.
The primary questions this study aims to answer are:
Participants will:
Transcranial electrical stimulation (tES) is a non-invasive neuromodulation technique that delivers low-intensity electrical currents (e.g., <2 mA) through scalp electrodes to modulate brain activity. Numerous studies have shown that tES can enhance cognitive functions such as learning, memory, attention, and decision-making in healthy individuals, as well as provide therapeutic benefits in psychiatric and neurological populations. Despite these findings, substantial knowledge gaps remain regarding the effects of tES, particularly in the context of complex, operationally relevant tasks.
Existing research has primarily focused on the effects of tES on simple cognitive tasks, with limited investigation into task that require multiple cognitive domain to operate simultaneously. Performance on complex tasks, such as those involving motor coordination, visual-spatial process, decision-making, and rapid response, may respond differently to tES than simple, isolated tasks. Understanding these effects could have broad applications in optimizing cognitive performance across various high-demand settings.
This study is designed to address several key uncertainties:
To investigate these questions, healthy adults perform a computerized track-and-capture task requiring real-time motor control and decision-making using dual-hand controllers. Participants undergo both active and sham stimulation in a randomized, double-blind, crossover design. Stimulation will target either the left dorsolateral prefrontal cortex or the left anterior insula, guided by current flow modeling software. Performance is assessed during stimulation, immediately after, and at 24 and 48 hours post-stimulation to evaluate both immediate and short-term after-effects.
Outcome measures include task performance metrics (e.g., speed, accuracy, overall success) and neurophysiological data collected via non-invasive monitoring with functional near-infrared spectroscopy (fNIRS). The study is part of a broader research effort to characterize the functional impact of tES on complex behavior and to inform future applications in cognitive performance enhancement.
All stimulation procedures follow established safety guidelines for low-intensity tES, including continuous monitoring of electrode impedance and post-session adverse event questionnaires assessing discomfort, mood, and cognitive status. The Soterix Medical MXN-33 HD-tES system includes built-in safeguards to prevent excessive current delivery and to ensure safe electrode contact throughout the stimulation. Participants serve as their own controls in a within-subject crossover design, increasing statistical power for detecting within-subject differences between active and sham conditions.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| DLPFC Stimulation Group | Experimental | Participants receive transcranial electrical stimulation (tES) targeting the left dorsolateral prefrontal cortex (DLPFC) and perform a complex cognitive-motor task using the Robotic On-Board Trainer for Research (ROBoT-r) under both active and sham stimulation in a randomized, crossover design. |
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| Anterior Insula Stimulation Group | Experimental | Participants receive transcranial electrical stimulation (tES) targeting the left anterior insula and perform a complex cognitive-motor task using the Robotic On-Board Trainer for Research (ROBoT-r) under both active and sham stimulation in a randomized, crossover design. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Active Transcranial Electrical Stimulation | Device | Active tES delivered using the Soterix Medical MXN-33 HD-tES stimulator. Stimulation is applied via high definition electrodes targeting either the left DLPFC or L-aINS at intensities up to 1.9 mA. Stimulation is performed for up to 45 minutes during task execution. Participants perform the ROBoT-r task during stimulation. |
| Measure | Description | Time Frame |
|---|---|---|
| ROBoT-r Task Performance Score (During Stimulation) | Performance on the ROBoT-r computerized track-and-capture task assessed using a weighted performance score that integrates accuracy, speed, and task success metrics. Scores are scaled from 0 to 100, with higher scores indicating better performance. Participants used dual-hand controllers to grapple a simulated spacecraft in a time-limited, physics-based environment. Performance was assessed during task execution concurrent with stimulation. | 5 minutes after stimulation onset |
| ROBoT-r Task Performance Score (Post-Stimulation) | Performance on the ROBoT-r task 15 minutes after completion of tES. Performance is quantified using a weighted composite score. Scores range from 0 to 100, with higher scores indicating better overall task performance. | 15 minutes post stimulation |
| ROBoT-r Task Performance Score (Post-Stimulation Follow-up) | Performance on ROBoT-r task at 24 and 48 hours after completion of tES. Performance is quantified using a weighted composite score. Scores range from 0 to 100, with higher scores indicating better overall task performance. | 24 and 48 hours post-stimulation |
| Measure | Description | Time Frame |
|---|---|---|
| tES Adverse Effects Questionnaire | Self-reported adverse effects were recorded immediately following the 45-minute stimulation. Participants reported common stimulation-related sensations (e.g., tingling, scalp pain, itching, burning, headache). Effects were recorded for both active and sham stimulation conditions. | Immediately following each stimulation session (active and sham), up to approximately 45 minutes per session. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Gary Strangman, PhD | Massachusetts General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital Research Institute | Charlestown | Massachusetts | 02129 | United States |
All IPD from this project will be anonymized IPD and shared. Data will be coded with a key only available to the Principal Investigator.
Data will be made available by the end-date of the funded project (estimated 12/25/2025) and retained indefinitely.
Researchers will be allowed to request the data form the NASA NLSP through their website https://nlsp.nasa.gov/explore/page/home. NASA will be responsible for vetting requests and providing the data as requested.
A total of 44 participants provided informed consent and were enrolled. Four participants withdrew prior to assignment to a stimulation group due to scheduling conflicts and did not receive any study intervention. Therefore, 40 participants were assigned to study groups and are included in the participant flow.
Participants were recruited from the greater Boston area. Enrollment occurred between December 1, 2022 and October 10, 2024. All participants were screened for eligibility prior to enrollment
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| ID | Title | Description |
|---|---|---|
| FG000 | DLPFC: Active to Sham | Participants assigned to left dorsolateral prefrontal cortex (DLPFC) stimulation who received active transcranial electrical stimulation during the first intervention period followed by sham stimulation during the second intervention period in a randomized crossover design. |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| First Intervention Period (Active or Sha |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 4, 2024 |
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Participants are randomized to one of two stimulation location groups: (1) left dorsolateral prefrontal cortex (DLPFC) or (2) left anterior insula (L-aINS). Randomization is valances based on gender, age, and video gaming experience. Within each group, participants undergo a crossover design in which they receive both active and sham transcranial electrical stimulation (tES) in randomized order. This design allows for within-subject comparisons between stimulation conditions while assessing the impact of stimulation site on task performance.
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Participants and investigators were blinded to stimulation conditions (active vs. sham) and to which pre-programmed stimulation protocol (A or B) corresponded to active stimulation. The investigator was aware of the assigned stimulation location (DLPFC or L-aINS), but not whether stimulation protocol A or B was active or sham. The tES device was operated in double-blind model, with stimulation order randomized.
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| Sham Transcranial Electrical Stimulation | Device | Sham tES using the same Soterix Medical MXN-33 HD-tES stimulator and electrode placements. Stimulation ramps up and down over 20 seconds to mimic sensation but provides no continuous current. Participants perform the ROBoT-R task under sham conditions. |
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| fNIRS Data Availability | Functional near-infrared spectroscopy (fNIRS) data were collected during task performance. This outcome reports the number of participants with usable fNIRS data available within each stimulation location group. Hemodynamic activation analyses are not reported here and may be provided in a future update. | Throughout study sessions when fNIRS was collected (during stimulation and post-stimulation follow-ups). |
| DLPFC: Sham to Active |
Participants assigned to left dorsolateral prefrontal cortex (DLPFC) stimulation who received sham stimulation during the first intervention period followed by active transcranial electrical stimulation during the second intervention period in a randomized crossover design. |
| FG002 | Anterior Insula: Active to Sham | Participants assigned to left anterior insula stimulation who received active transcranial electrical stimulation during the first intervention period followed by sham stimulation during the second intervention period in a randomized crossover design |
| FG003 | Anterior Insula: Sham to Active | Participants assigned to left anterior insula stimulation who received sham stimulation during the first intervention period followed by active transcranial electrical stimulation during the second intervention period in a randomized crossover design. |
| COMPLETED |
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| NOT COMPLETED |
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| Washout / Interval |
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| Second Intervention Period (Crossover) |
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The baseline analysis population included all participants who completed the study protocol and were assigned to a stimulation target group. Baseline demographic characteristics were assessed prior to experimental procedures, and did not differ from the participant flow assignments
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| ID | Title | Description |
|---|---|---|
| BG000 | DLPFC Stimulation Group | Participants receive transcranial electrical stimulation (tES) targeting the left dorsolateral prefrontal cortex (DLPFC) and perform a complex cognitive-motor task using the Robotic On-Board Trainer for Research (ROBoT-r) under both active and sham stimulation in a randomized, crossover design. Active Transcranial Electrical Stimulation: Active tES delivered using the Soterix Medical MXN-33 HD-tES stimulator. Stimulation is applied via high definition electrodes targeting either the left DLPFC or L-aINS at intensities up to 1.9 mA. Stimulation is performed for up to 45 minutes during task execution. Participants perform the ROBoT-r task during stimulation. Sham Transcranial Electrical Stimulation: Sham tES using the same Soterix Medical MXN-33 HD-tES stimulator and electrode placements. Stimulation ramps up and down over 20 seconds to mimic sensation but provides no continuous current. Participants perform the ROBoT-R task under sham conditions. |
| BG001 | Anterior Insula Stimulation Group | Participants receive transcranial electrical stimulation (tES) targeting the left anterior insula and perform a complex cognitive-motor task using the Robotic On-Board Trainer for Research (ROBoT-r) under both active and sham stimulation in a randomized, crossover design. Active Transcranial Electrical Stimulation: Active tES delivered using the Soterix Medical MXN-33 HD-tES stimulator. Stimulation is applied via high definition electrodes targeting either the left DLPFC or L-aINS at intensities up to 1.9 mA. Stimulation is performed for up to 45 minutes during task execution. Participants perform the ROBoT-r task during stimulation. Sham Transcranial Electrical Stimulation: Sham tES using the same Soterix Medical MXN-33 HD-tES stimulator and electrode placements. Stimulation ramps up and down over 20 seconds to mimic sensation but provides no continuous current. Participants perform the ROBoT-R task under sham conditions. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | ROBoT-r Task Performance Score (During Stimulation) | Performance on the ROBoT-r computerized track-and-capture task assessed using a weighted performance score that integrates accuracy, speed, and task success metrics. Scores are scaled from 0 to 100, with higher scores indicating better performance. Participants used dual-hand controllers to grapple a simulated spacecraft in a time-limited, physics-based environment. Performance was assessed during task execution concurrent with stimulation. | Participants contributed data to both active and sham stimulation conditions within their assigned stimulation target as part of a within-subject crossover design. Outcome data are reported by stimulation target and intervention condition. Inferential effects of stimulation condition, location, session, and difficulty were evaluated using linear mixed-effects regression models accounting for repeated measures within participants. | Posted | Mean | Standard Deviation | score on a scale (0-100) | 5 minutes after stimulation onset |
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| Primary | ROBoT-r Task Performance Score (Post-Stimulation) | Performance on the ROBoT-r task 15 minutes after completion of tES. Performance is quantified using a weighted composite score. Scores range from 0 to 100, with higher scores indicating better overall task performance. | Participants contributed data to both active and sham stimulation conditions within their assigned stimulation target as part of a within-subject crossover design. Outcome data are reported by stimulation target and intervention condition. Inferential effects of stimulation condition, location, session, and difficulty were evaluated using linear mixed-effects regression models accounting for repeated measures within participants. | Posted | Mean | Standard Deviation | score on scale (0-100) | 15 minutes post stimulation |
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| Primary | ROBoT-r Task Performance Score (Post-Stimulation Follow-up) | Performance on ROBoT-r task at 24 and 48 hours after completion of tES. Performance is quantified using a weighted composite score. Scores range from 0 to 100, with higher scores indicating better overall task performance. | All participants who completed the study protocol and contributed ROBoT-r performance data at 24 and/0r 48 hours post-stimulation were included in the analysis. Results are based on mixed-effects regression models accounting for repeated measures within participants. | Posted | Mean | Standard Deviation | score on scale (0-100) | 24 and 48 hours post-stimulation |
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| Secondary | tES Adverse Effects Questionnaire | Self-reported adverse effects were recorded immediately following the 45-minute stimulation. Participants reported common stimulation-related sensations (e.g., tingling, scalp pain, itching, burning, headache). Effects were recorded for both active and sham stimulation conditions. | Participants completed the adverse effects questionnaire following both active and sham stimulation sessions as part of a within-subject crossover design. Adverse effects are reported separately by stimulation target and intervention condition. | Posted | Count of Participants | Participants | Immediately following each stimulation session (active and sham), up to approximately 45 minutes per session. |
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| Secondary | fNIRS Data Availability | Functional near-infrared spectroscopy (fNIRS) data were collected during task performance. This outcome reports the number of participants with usable fNIRS data available within each stimulation location group. Hemodynamic activation analyses are not reported here and may be provided in a future update. | All participants assigned to each stimulation location group with fNIRS data collection were included. This outcome reports data availability (the number of participants with usable fNIRS data) at each stimulation location, rather than hemodynamic activation values. | Posted | Number | Participants | Throughout study sessions when fNIRS was collected (during stimulation and post-stimulation follow-ups). |
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Adverse events were monitored throughout all study sessions throughout the 7 study visits across the 2.5-week study timeline. Events were identified through post-session questionnaires and through direct observation by study staff. Any participant-reported symptoms, observed discomfort, and any procedural or device-related issues were documented according to study protocol.
This study used a within-subject crossover design in which participants completed both active and sham stimulation sessions at their assigned stimulation target. Adverse events are reported separately by stimulation target and intervention condition, with participants contributing to both conditions within their assigned target.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | DLPFC Active | Participants received active high-definition tES targeting the DLPFC while performing the ROBoT-r cognitive-motor task. Stimulation was delivered using the Soterix Medical MXN-33 HD-tES system at intensities up to 1.9 mA for up to 45 minutes | 0 | 19 | 0 | 19 | 12 | 19 |
| EG001 | DLPFC Sham | Participants received sham high-definition tES targeting DLPFC while performing the ROBoT-r cognitive-motor task. Sham stimulation used identical electrode placement and ramp-up/down procedures (approximately 20 seconds) without delivering sustained current. | 0 | 20 | 0 | 20 | 11 | 20 |
| EG002 | Anterior Insula Active | Participants received active high-definition tES targeting the L-aINS whole performing the ROBoT-r cognitive motor task. Stimulation was delivered using the Soterix Medical MXN-33 HD-tES system at intensities up to 1.9 mA for up to 45 minutes. | 0 | 20 | 0 | 20 | 14 | 20 |
| EG003 | Anterior Insula Sham | Participants received sham high-definition tES targeting L-aINS while performing the ROBoT-r cognitive-motor task. Sham stimulation used identical electrode placement and ramp-up/down procedures (approximately 20 seconds) without delivering sustained current. | 0 | 20 | 0 | 20 | 13 | 20 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | Systematic Assessment |
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| Neck Pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Scalp Pain | General disorders | Systematic Assessment |
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| Tingling | Nervous system disorders | Systematic Assessment |
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| Itching | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Burning Sensation | General disorders | Systematic Assessment |
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| Skin Redness | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Sleepiness | Nervous system disorders | Systematic Assessment |
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| Trouble Concentrating | Nervous system disorders | Systematic Assessment |
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| Acute Mood Change | Psychiatric disorders | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | Systematic Assessment |
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Analyses of secondary fNIRS outcomes are ongoing and are not included.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Gary Strangman, PhD | Massachusetts General Hospital | 617-724-0662 | strang@mgh.harvard.edu |
| Dec 31, 2025 |
| Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Apr 4, 2024 | Dec 31, 2025 | ICF_001.pdf |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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Mixed-effects regression model (two-sided test)
| OG002 | Anterior Insula Active | Participants received active tES targeting the L-aINS using the Soterix Medical MXN-33 HD-tES stimulator. Stimulation was delivered at intensities up to 1.9 mA for up to 45 minutes during task execution. Outcome measures reflect performance assessed after completion of the stimulation session. |
| OG003 | Anterior Insula Sham | Participants received sham tES targeting the L-aINS using the Soterix Medical MXN-33 HD-tES stimulator and identical electrode placement. Stimulation ramped up and down over approximately 20 seconds without sustained current. Outcome measures reflect performance assessed after completion of the sham session. |
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| OG002 | Anterior Insula Active | Participants received active tES targeting the L-aINS using the Soterix Medical MXN-33 HD-tES stimulator. Stimulation was delivered at intensities up to 1.9 mA for up to 45 minutes during task execution. Outcome measures reflect performance assessed at follow-up timepoints (24 and 48 hours) after completion of the stimulation session. |
| OG003 | Anterior Insula Sham | Participants received sham tES targeting the L-aINS using the Soterix Medical MXN-33 HD-tES stimulator and identical electrode placement. Stimulation ramped up and down over approximately 20 seconds without sustained current. Outcome measures reflect performance assessed at follow-up timepoints (24 and 48 hours) after completion of the stimulation session. |
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Participants received active tES targeting the L-aINS using the Soterix Medical MXN-33 HD-tES stimulation. Stimulation was delivered via high-definition electrodes at intensities up to 1.9 mA for up to 45 minutes during task execution. |
| OG003 | Anterior Insula Sham | Participants received sham tES targeting the L-aINS using the Soterix Medical MXN-33 HD-tES stimulator and identical electrode placement. Stimulation ramped up and down over approximately 20 seconds to mimic sensation without delivering continuous current. |
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| OG002 | Anterior Insula Active | Participants receive tES targeting the left anterior insula and perform a complex cognitive-motor task using the Robotic On-Board Trainer for Research (ROBoT-r) under both active and sham stimulation in a randomized, crossover design. Active tES delivered using the Soterix Medical MXN-33 HD-tES stimulator. Stimulation is applied via high definition electrodes targeting either the left DLPFC or L-aINS at intensities up to 1.9 mA. Stimulation is performed for up to 45 minutes during task execution. Participants perform the ROBoT-r task during stimulation. |
| OG003 | Anterior Insula Sham | Sham tES using the same Soterix Medical MXN-33 HD-tES stimulator and electrode placements. Stimulation ramps up and down over 20 seconds to mimic sensation but provides no continuous current. Participants perform the ROBoT-R task under sham conditions. |
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