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| ID | Type | Description | Link |
|---|---|---|---|
| P20GM103645 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of General Medical Sciences (NIGMS) | NIH |
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Low-frequency brain rhythms in the alpha (8-14Hz) and beta (15-29Hz) bands are strong predictors of perception and functional performance in a range of tasks, and are disrupted in several disease states. The purpose of this study is to investigate a direct causal relationship between low-frequency brain rhythms and sensory perception, and to optimize commonly used TMS paradigms to impact sensory processing and perception in a similar manner as endogenous rhythms. To do so, this study combines human magnetic resonance imaging (MRI), electroencephalography (EEG), non-invasive brain stimulation (transcranial magnetic stimulation; TMS), and biophysically principled computational neural modeling.
Prior studies have shown that high power low-frequency brain rhythms in the alpha (8-14) and beta (15-29 Hz) bands in primary somatosensory cortex (SI) are associated with a decreased probability of perceiving tactile stimuli at perceptual threshold, and can be modulated with attention. Furthermore, high power beta activity in SI emerges as brief "events" (<150ms) in un-averaged data, the rate and timing of which underlie the attentional and perceptual effects associated with high beta power.
In this study, human electroencephalography (EEG) and a non-painful tactile detection task are used to assess if TMS that is hypothesized to mimic endogenous beta-frequency events impact touch perception in a similar manner.
The TMS-EEG components of this study will use a within-subjects crossover design. In initial study sessions, all participants will have an MRI. In subsequent study sessions, participants will complete a tactile detection task while EEG data is recorded concurrent with online active, active control or sham control TMS. Analyses will focus on comparing detection probabilities of tactile stimuli presented at perceptual threshold and tactile evoked response potential waveforms between trials with and without concurrent TMS.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Active SI-Hand TMS vs. Active Control TMS | Experimental | Participants receive perceptual threshold-level tactile stimuli to the third digit of the right hand and report detection or non-detection. EEG is recorded and TMS is applied concurrently during the task. In one study session, active TMS is applied over the hand region of primary somatosensory cortex (SI-Hand). In another study session, active TMS is applied over a control brain region, in a more superior and lateral location within SI. |
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| Active SI-Hand TMS vs. Sham SI-Hand TMS | Experimental | Participants receive perceptual threshold-level tactile stimuli to the third digit of the right hand and report detection or non-detection. EEG is recorded and TMS is applied concurrently during the task. In one study session, active TMS is applied over the hand region of primary somatosensory cortex (SI-Hand). In another study session, sham TMS is applied over the same target location (SI-Hand) |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Online Active SI-Hand TMS | Device | Single pulses of TMS will be delivered using an active coil. One pulse will be delivered per trial (at least 5 seconds apart) "online" (during the tactile detection task), at 80% active motor threshold. TMS will target the hand area of primary somatosensory cortex (SI-Hand). |
| Measure | Description | Time Frame |
|---|---|---|
| Threshold-Level Tactile Detection Hit Rate | Participants receive one or zero tactile stimuli per trial and report detection or non-detection using a button press. Tactile stimuli are delivered at participants' individual perceptual threshold level (perceived roughly half the time). On a given trial, TMS may also be delivered 100 msec before the tap ('TMS100'), 25 msec after the tap ('TMS25'), or not at all ('TMS Null'), each for an equal number of trials. The 'hit rate' is defined as the number of trials with correctly detected tactile stimuli divided by the total number of trials on which a tactile stimulus was presented. | Tactile detection was assessed between TMS and no TMS trials continuously during the TMS interventions - during the Active SI TMS session, and during either the Active Control TMS or Sham Control TMS session. The sessions were at least 1 week apart. |
| Measure | Description | Time Frame |
|---|---|---|
| EEG Tactile Evoked Response Potential (ERP) | Participants receive one tactile stimulus per trial concurrent with EEG recording. The EEG-measured ERP immediately following each tactile stimulus is assessed and compared across conditions, with and without TMS at different latencies. 'TMS null' refers to trials in which no TMS was delivered, 'TMS100' refers to trials in which TMS was delivered 100 msec before the tactile stimulus, and 'TMS25' refers to trials in which TMS was delivered 25 msec after the tactile stimulus. 'Hit trials' are trials in which the tactile stimulus was delivered and corrected detected, and 'miss trials' are trials in which the tactile stimulus was delivered but incorrectly not detected. The outcome measure calculated here represents a time window between 78-161 msec after the tactile stimulus, where we expected to see a significant difference in signal amplitude between hit and miss trials based on prior publications. |
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Inclusion Criteria:
Exclusion Criteria:
Contraindicated medications:
alcohol Amitriptyline Amphetamines ampicillin Anticholinergics Antihistamines aripiprazole BCNU **bupropion** cephalosporins chlorambucil chloroquine Chlorpromazine citalopram Clozapine Cocaine cyclosporine cytosine arabinoside Doxepine duloxetine fluoxetine fluphenazine fluvoxamine Foscarnet gamma-hydroxybutyrate (GHB) Ganciclovir haloperidol imipenem Imipramine isoniazid ketamine levofloxacin Lithium Maprotiline MDMA (ecstasy) mefloquine methotrexate metronidazole mianserin mirtazapine Nortriptyline olanzapine paroxetine penicillin phencyclidine (PCP, angel's dust) pimozide quetiapine reboxetine risperidone Ritonavir **Sertraline** Sympathomimetic theophylline venlafaxine vincristine ziprasidone
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| Name | Affiliation | Role |
|---|---|---|
| Stephanie R Jones, PhD | Brown University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Brown University, Carney Institute for Brain Science Human Testing Space (HuTS) | Providence | Rhode Island | 02906 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20943916 | Background | Jones SR, Kerr CE, Wan Q, Pritchett DL, Hamalainen M, Moore CI. Cued spatial attention drives functionally relevant modulation of the mu rhythm in primary somatosensory cortex. J Neurosci. 2010 Oct 13;30(41):13760-5. doi: 10.1523/JNEUROSCI.2969-10.2010. | |
| 27469163 | Background | Sherman MA, Lee S, Law R, Haegens S, Thorn CA, Hamalainen MS, Moore CI, Jones SR. Neural mechanisms of transient neocortical beta rhythms: Converging evidence from humans, computational modeling, monkeys, and mice. Proc Natl Acad Sci U S A. 2016 Aug 16;113(33):E4885-94. doi: 10.1073/pnas.1604135113. Epub 2016 Jul 28. |
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39 participants met criteria for enrollment, were consented and completed an MRI. 26 were assigned to receive Active SI-Hand and Active Control TMS, 13 were assigned to receive Active SI-Hand and Sham SI-Hand TMS, in different sessions at least one week apart (repeated measures design). One participant was consented once, and received Active SI-Hand TMS and both control arms (Active Control & Sham) - but is counted once in the 'Active SI-Hand/Control' group for baseline characteristics.
Healthy adult participants (ages 18-65 years) were recruited from the greater Providence, RI area. Inclusion criteria included the ability to provide informed consent, english fluency, and right-handedness. Exclusion criteria included any prior or existing condition(s) that could increase the risk of side effects or complications from TMS or MRI, neurological or medical conditions that could confound experimental results, and any pharmaceutical agents that could increase seizure risk from TMS.
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| ID | Title | Description |
|---|---|---|
| FG000 | Active SI-Hand TMS vs. Active Control TMS | Participants receive perceptual threshold-level tactile stimuli to the third digit of the right hand and report detection or non-detection. EEG is recorded and TMS is applied concurrently during the task. In one study session, active TMS is applied over the hand region of primary somatosensory cortex (SI-Hand). In another study session, active TMS is applied over a control brain region, in a more superior and lateral location within SI. |
| FG001 | Active SI-Hand TMS vs. Sham SI-Hand TMS | Participants receive perceptual threshold-level tactile stimuli to the third digit of the right hand and report detection or non-detection. EEG is recorded and TMS is applied concurrently during the task. In one study session, active TMS is applied over the hand region of primary somatosensory cortex (SI-Hand). In another study session, sham TMS is applied over the same target location (SI-Hand). |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
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| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Active SI-Hand TMS vs. Active Control TMS | Participants receive perceptual threshold-level tactile stimuli to the third digit of the right hand and report detection or non-detection. EEG is recorded and TMS is applied concurrently during the task. In one study session, active TMS is applied over the hand region of primary somatosensory cortex (SI-Hand). In another study session, active TMS is applied over a control brain region, in a more superior and lateral location within SI. |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 | Threshold-Level Tactile Detection Hit Rate | Participants receive one or zero tactile stimuli per trial and report detection or non-detection using a button press. Tactile stimuli are delivered at participants' individual perceptual threshold level (perceived roughly half the time). On a given trial, TMS may also be delivered 100 msec before the tap ('TMS100'), 25 msec after the tap ('TMS25'), or not at all ('TMS Null'), each for an equal number of trials. The 'hit rate' is defined as the number of trials with correctly detected tactile stimuli divided by the total number of trials on which a tactile stimulus was presented. | The numbers of participants analyzed in this section are lower than the number in the 'baseline characteristics' section because only participants who completed two sessions (Active SI-Hand TMS and a control session) were included in the within-subjects analysis. One subject completed both control conditions, and it counted in both the 'Active Control Group' and the 'Sham Control Group'. | Posted | Mean | Standard Deviation | # hit trials/(total # hit + miss trials) | Tactile detection was assessed between TMS and no TMS trials continuously during the TMS interventions - during the Active SI TMS session, and during either the Active Control TMS or Sham Control TMS session. The sessions were at least 1 week apart. |
Adverse events were assessed at each study visit (MRI, first TMS-EEG, second TMS-EEG, third TMS-EEG if applicable), and covered the periods during and between visits, up to a total of 2 years (between the MRI to final TMS-EEG visits).
All adverse events were unrelated to the study, but occurred after the first TMS-EEG session and resulted in the participant dropping out of the study and not completing the second TMS-EEG session.
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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 | MRI Only | Participants receive an MRI to inform TMS targeting and analysis. | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Migraine | Nervous system disorders | Non-systematic Assessment | Participant reported vestibular migraine in the weeks following but unrelated to the first TMS-EEG session, and noted fear of inducing another migraine as a reason for dropping out of the study. |
A study limitation is that the active control TMS site was close in proximity within primary somatosensory cortex to our target site, and likely highly functionally connected. This may be why we found similar behavioral effects of TMS on tactile detection hit rate for TMS delivered to the active target and control locations, and is why we followed up by adding on a sham control group.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Danielle Sliva, Postdoctoral Research Associate | Brown University | (203) 673-2194 | danielle_sliva@brown.edu |
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_ICF | Yes | No | Yes | Study Protocol and Informed Consent Form | Feb 24, 2021 | Dec 16, 2025 | Prot_ICF_000.pdf |
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All participants will complete an initial MRI. MRIs are subsequently used for TMS neuronavigation (region of interest targeting). There is no intervention applied during the MRI session.
In one of two subsequent concurrent TMS-EEG sessions, all participants will receive active TMS to the hand area of primary somatosensory cortex (SI; active SI-Hand TMS) while carrying out a tactile detection task. During the other TMS-EEG session, participants will either receive active TMS over a control brain region in a more medial and superior region of SI (active control TMS), or sham TMS over the hand area of SI (sham SI-Hand control TMS).
The order of active SI TMS vs. control (active control or sham SI control) will be randomized across participants.
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Participants will be unaware of the TMS target, type of coil (active vs. sham) and order in which they receive TMS interventions.
|
| Online Sham SI-Hand TMS | Device | Single pulses of TMS will be delivered using a sham coil. One pulse will be delivered per trial (at least 5 seconds apart) "online" (during the tactile detection task), at 80% active motor threshold. TMS will target the hand area of primary somatosensory cortex (SI-Hand). This control condition is intended to mimic the peripheral (e.g. cranial/facial muscle and/or nerve activation, auditory evoked response), but not biological effects of TMS specifically related to somatosensory perception. |
|
| Online Active Control TMS | Device | Single pulses of TMS will be delivered using an active coil. One pulse will be delivered per trial (at least 5 seconds apart) "online" (during the tactile detection task), at 80% active motor threshold. TMS will target a control brain region, in a more superior and lateral location within SI. This control condition is intended to mimic the peripheral (e.g. cranial/facial muscle and/or nerve activation, auditory evoked response), but not biological effects of TMS specifically related to somatosensory perception. |
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| EEG measures were assessed between TMS and no TMS trials continuously during the TMS interventions - during the Active SI TMS session, and during either the Active Control TMS or Sham Control TMS session. The sessions were at least 1 week apart. |
| 29106374 | Background | Shin H, Law R, Tsutsui S, Moore CI, Jones SR. The rate of transient beta frequency events predicts behavior across tasks and species. Elife. 2017 Nov 6;6:e29086. doi: 10.7554/eLife.29086. |
| 17913909 | Background | Jones SR, Pritchett DL, Stufflebeam SM, Hamalainen M, Moore CI. Neural correlates of tactile detection: a combined magnetoencephalography and biophysically based computational modeling study. J Neurosci. 2007 Oct 3;27(40):10751-64. doi: 10.1523/JNEUROSCI.0482-07.2007. |
| 19812290 | Background | Jones SR, Pritchett DL, Sikora MA, Stufflebeam SM, Hamalainen M, Moore CI. Quantitative analysis and biophysically realistic neural modeling of the MEG mu rhythm: rhythmogenesis and modulation of sensory-evoked responses. J Neurophysiol. 2009 Dec;102(6):3554-72. doi: 10.1152/jn.00535.2009. Epub 2009 Oct 7. |
| Withdrawal by Subject |
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| Lab equipment broke during session |
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| BG001 | Active SI-Hand TMS vs. Sham SI-Hand TMS | Participants receive perceptual threshold-level tactile stimuli to the third digit of the right hand and report detection or non-detection. EEG is recorded and TMS is applied concurrently during the task. In one study session, active TMS is applied over the hand region of primary somatosensory cortex (SI-Hand). In another study session, sham TMS is applied over the same target location (SI-Hand). |
| BG002 | Total | Total of all reporting groups |
| Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Active SI-Hand Tactile Detection Threshold. | To calibrate the tactile detection task, each participant's baseline threshold for tactile detection (detected ~50% of the time) was assessed using a parameter estimation by sequential testing (PEST) procedure (Dai, 1995; Leek, 2001). Stimuli were delivered using a custom device comprised of a plastic screw mounted on top of a piezoelectric bender. The threshold value corresponds to the voltage generated when 10msec 100Hz current was passed through the piezoelectric material, causing it to bend at various intensities. | The population numbers represent enrolled participants who completed the behavioral testing procedure for two full sessions, Active SI-Hand TMS and one of the two control sessions. The other participants either dropped out before doing any TMS session, or after the first TMS session. | Mean | Standard Deviation | Volts (V) |
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| ID | Title | Description |
|---|---|---|
| OG000 | Active SI TMS Null (Active Control Group) | These participants received TMS using an active coil to the study main region of interest, hand representation of primary somatosensory cortex (SI). TMS not delivered on these trials. |
| OG001 | Active SI TMS25 (Active Control Group) | These participants received TMS using an active coil to the study main region of interest, hand representation of primary somatosensory cortex (SI). TMS was delivered 25 msec after the threshold-level finger tap. |
| OG002 | Active SI TMS100 (Active Control Group) | These participants received TMS using an active coil to the study main region of interest, hand representation of primary somatosensory cortex (SI). TMS was delivered 100 msec before the threshold-level finger tap. |
| OG003 | Active Control TMS Null | These participants received TMS using an active coil to a control region within outside of the study main region of interest. TMS not delivered on these trials. |
| OG004 | Active Control TMS25 | These participants received TMS using an active coil to a control region within outside of the study main region of interest. TMS was delivered 25 msec after the threshold-level finger tap. |
| OG005 | Active Control TMS100 | These participants received TMS using an active coil to a control region within outside of the study main region of interest. TMS was delivered 100 msec before the threshold-level finger tap. |
| OG006 | Sham Control TMS Null | These participants received TMS using a sham coil to the study main region of interest, hand representation of primary somatosensory cortex (SI). TMS not delivered on these trials. |
| OG007 | Sham Control TMS25 | These participants received TMS using a sham coil to the study main region of interest, hand representation of primary somatosensory cortex (SI). TMS was delivered 25 msec after the threshold-level finger tap. |
| OG008 | Sham Control TMS100 | These participants received TMS using a sham coil to the study main region of interest, hand representation of primary somatosensory cortex (SI). TMS was delivered 100 msec before the threshold-level finger tap. |
| OG009 | Active SI TMS Null (Sham Control Group) | These participants received TMS using an active coil to the study main region of interest, hand representation of primary somatosensory cortex (SI). TMS was delivered 25 msec after the threshold-level finger tap. |
| OG010 | Active SI TMS25 (Sham Control Group) | These participants received TMS using an active coil to the study main region of interest, hand representation of primary somatosensory cortex (SI). TMS was delivered 25 msec after the threshold-level finger tap. |
| OG011 | Active SI TMS100 (Sham Control Group) | These participants received TMS using an active coil to the study main region of interest, hand representation of primary somatosensory cortex (SI). TMS was delivered 100 msec before the threshold-level finger tap. |
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| Secondary | EEG Tactile Evoked Response Potential (ERP) | Participants receive one tactile stimulus per trial concurrent with EEG recording. The EEG-measured ERP immediately following each tactile stimulus is assessed and compared across conditions, with and without TMS at different latencies. 'TMS null' refers to trials in which no TMS was delivered, 'TMS100' refers to trials in which TMS was delivered 100 msec before the tactile stimulus, and 'TMS25' refers to trials in which TMS was delivered 25 msec after the tactile stimulus. 'Hit trials' are trials in which the tactile stimulus was delivered and corrected detected, and 'miss trials' are trials in which the tactile stimulus was delivered but incorrectly not detected. The outcome measure calculated here represents a time window between 78-161 msec after the tactile stimulus, where we expected to see a significant difference in signal amplitude between hit and miss trials based on prior publications. | The numbers and arms of participants analyzed in this section are different than that of the 'primary outcome' section because we only included participants with high-quality EEG data, and only assessed the Active SI-Hand TMS Group, as we were interested in following up on the behavioral effect of TMS timing on hit rate (primary outcome measure) in our target location. | Posted | Mean | Standard Deviation | EEG signal amplitude (microvolts) | EEG measures were assessed between TMS and no TMS trials continuously during the TMS interventions - during the Active SI TMS session, and during either the Active Control TMS or Sham Control TMS session. The sessions were at least 1 week apart. |
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| 39 |
| 0 |
| 39 |
| 0 |
| 39 |
| EG001 | Active SI-Hand TMS | Participants receive perceptual threshold-level tactile stimuli to the third digit of the right hand and report detection or non-detection. EEG is recorded and active TMS is applied concurrently over the hand region of primary somatosensory cortex (SI-Hand) during the task. | 0 | 39 | 0 | 39 | 0 | 39 |
| EG002 | Active Control TMS | Participants receive perceptual threshold-level tactile stimuli to the third digit of the right hand and report detection or non-detection. EEG is recorded and active TMS is applied concurrently over a control brain region, in a more superior and lateral location within SI, during the task. | 0 | 26 | 0 | 26 | 1 | 26 |
| EG003 | Sham SI-Hand TMS | Participants receive perceptual threshold-level tactile stimuli to the third digit of the right hand and report detection or non-detection. EEG is recorded and sham TMS is applied concurrently over the hand region of primary somatosensory cortex (SI-Hand) during the task. | 0 | 13 | 0 | 13 | 2 | 13 |
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| New psychiatric medication | Psychiatric disorders | Non-systematic Assessment | Participant reported that they started taking a new psychiatric medication in the weeks following but unrelated to the first TMS-EEG session, suggesting a new psychiatric diagnosis. |
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| New antibiotic medication | Skin and subcutaneous tissue disorders | Non-systematic Assessment | Participant reported that they started taking a new antibiotic medication for a skin condition in the weeks following but unrelated to the first TMS-EEG session. Body region affected was not in the same area as study electrode placement. |
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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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| Unknown or Not Reported |
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| Is the mean amplitude of the EEG signal averaged over a 78-161 msec post-stimulus time window different between hit and miss trials? | t-test, 2 sided | 0.0469 | Reported p-values are corrected for multiple comparisons across TMS conditions (TMS100, TMS25, TMS null) using the Benjamini-Hochberg (BH) step-up procedure (Benjamini and Hochberg, 1995) with a False Discovery Rate of 0.05. | Other | Our hypothesis was that the signal would differ between hit vs miss trials, we were not inherently testing whether any of these outcomes were "better" or "not worse than" any others. |
| Is the mean amplitude of the EEG signal averaged over a 78-161 msec post-stimulus time window different between hit and miss trials? | t-test, 2 sided | 0.9451 | Reported p-values are corrected for multiple comparisons across TMS conditions (TMS100, TMS25, TMS null) using the Benjamini-Hochberg (BH) step-up procedure (Benjamini and Hochberg, 1995) with a False Discovery Rate of 0.05. | Other | Our hypothesis was that the signal would differ between hit vs miss trials, we were not inherently testing whether any of these outcomes were "better" or "not worse than" any others. |