Impulsive Behavior
Conditions
Brief summary
As a first step toward investigating whether modulation of impulsivity and associated neural pathways may yield clinically meaningful changes in risk for adolescent suicidal behavior, the R21 is a proof-of concept study evaluating the potential for tDCS targeting brain regions associated with behavioral impulsivity (right inferior frontal gyrus \[rIFG\]) and cognitive impulsivity (left orbitofrontal cortex \[lOFC\]) to modulate these facets of impulsivity in a sample of adolescent suicide attempters. Participants will be randomly assigned to receive anodal tDCS over the rIFG, anodal tDCS over the lOFC, or a sham stimulation condition, in a three-group design. Task-based measures of behavioral and cognitive impulsivity will be administered before and after tDCS or sham stimulation. Additionally, electroencephalography (EEG) and event-related potential (ERP) data will be collected during the impulsivity tasks, and resting-state EEG data will be collected pre- and post-tDCS administration to confirm engagement of the targeted brain regions and to delineating the neural pathways underlying the effects of tDCS on impulsivity.
Detailed description
Suicide is one of the leading causes of death in adolescence. To improve the ability to predict and prevent suicidal behavior, there is a pressing need for research in this area to advance beyond identifying risk factors toward a greater focus on the mechanisms of risk for this behavior. In particular, elucidating the neural pathways underlying risk for suicidal behavior is important insofar as such work may yield specific and modifiable targets for clinical intervention. The adoption of new experimental paradigms providing experimental control over potentially modifiable risk factors has been recommended as a means of meaningfully advancing the field in this regard. Although yet to be applied to the study of suicidality, transcranial direct current stimulation (tDCS), in conjunction with measures of electroencephalography (EEG) and event-related potentials (ERPs), may hold promise as an experimental paradigm in the study of potentially modifiable risk factors, and underlying neural mechanisms, for suicidality. One such risk factor of particular relevance to suicide in adolescence is state-sensitive aspects of impulsivity. Impulsivity has been consistently linked with suicidality, with this association appearing to be stronger in adolescence than adulthood. As a first step toward investigating whether modulation of impulsivity and associated neural pathways may yield clinically meaningful changes in risk for adolescent suicidal behavior, the R21 is a proof-of concept study evaluating the potential for tDCS targeting brain regions associated with behavioral impulsivity (right inferior frontal gyrus \[rIFG\]) and cognitive impulsivity (left orbitofrontal cortex \[lOFC\]) to modulate these facets of impulsivity in a sample of adolescent suicide attempters. Participants will be randomly assigned to receive anodal tDCS over the rIFG, anodal tDCS over the lOFC, or a sham stimulation condition, in a three-group design. Task-based measures of behavioral and cognitive impulsivity will be administered before and after tDCS or sham stimulation. Additionally, EEG and ERP data will be collected during the impulsivity tasks, and resting-state EEG data will be collected pre- and post-tDCS administration to confirm engagement of the targeted brain regions and to delineating the neural pathways underlying the effects of tDCS on impulsivity.
Interventions
DEVICEanodal tDCS over the rIFG,
tDCS at a constant current of 1.5 milliampere (mA) will be applied for one 20-minute session over the right inferior frontal gyrus . Resting-state EEG for 10 minutes will be recorded immediately prior to and after tDCS. After post-tDCS resting state EEG is acquired, EEG is recorded to extract Evoked Response Potentials in a single-blind procedure. The participants and assessors will be blind to experimental condition.
DEVICEanodal tDCS over the lOFC,
tDCS at a constant current of 1.5 mA will be applied for one 20-minute session over the left orbitofrontal cortex . Resting-state EEG for 10 minutes will be recorded immediately prior to and after tDCS. After post-tDCS resting state EEG is acquired, EEG is recorded to extract Evoked Response Potentials in a single-blind procedure. The participants and assessors will be blind to experimental condition.
DEVICEsham tDCS stimulation condition
In the sham condition, the current will be ramped up to 1.5 mA for 30 seconds and then ramped back down to 0. As this commonly used sham procedure produces a brief tingling sensation, participants are kept unaware of their experimental condition. Resting-state EEG for 10 minutes will be recorded immediately prior to and after the sham tDCS. After post-sham stimulation resting state EEG is acquired, EEG is recorded to extract Evoked Response Potentials in a single-blind procedure. The participants and assessors will be blind to experimental condition.
Sponsors
Lifespan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
Neither participant or outcome aware of condition
Intervention model description
anodal tDCS over the rIFG, anodal tDCS over the lOFC, sham stimulation condition
Eligibility
Sex/Gender
ALL
Age
13 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* have attempted suicide prior to admission * speak and read English fluently * do not display evidence of significant cognitive impairment, based on a standard psychiatric exam as well as school records on admission * are not actively psychotic at time of intake.
Exclusion criteria
* a significant general medical condition * history of seizure, head injury, brain surgery or tumor * intracranial metallic implants or implanted electrical devices * substance abuse or dependence in the past six months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Stop Signal Task (SST) | Within an hour post-stimulation condition | The Stop-Signal Task (SST) is a task requiring inhibition of a prepotent motor response. The SST requires participants to respond to a target stimulus as quickly and accurately as possible by pressing a button, but also to withhold their response when they hear an auditory signal. Thus, this task involves a competition between activating and inhibiting processes. The primary outcome variable is change in the stop signal reaction time (SSRT) for the task administered seconds to minutes before and seconds to minutes after stimulation. The theoretical minimum is zero seconds and there is no theoretical maximum. Higher SSRT scores reflect greater impulsivity. |
| Delay Discounting Task | Within an hour post-stimulation condition | This task assessed discounting larger future rewards for smaller immediate ones. The point where a person is equally likely to prefer immediate vs delayed reward (the indifference point) is determined for several and combinations of reward sizes and lengths of time. Area under the curve (AUC) is calculated by summing the results of the following for each delay and indifference point pair: x2-x1\[(y1 + y2)/2\]. x1 and x2 are successive delays and y1 and y2 are indifference points for those delays. AUC range=0-1. Larger AUCs reflect less impulsivity. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Anodal tDCS Over the rIFG, anodal tDCS over the rIFG,
anodal tDCS over the rIFG,: tDCS at a constant current of 1.5 milliampere (mA) will be applied for one 20-minute session over the right inferior frontal gyrus . Resting-state EEG for 10 minutes will be recorded immediately prior to and after tDCS. After post-tDCS resting state EEG is acquired, EEG is recorded to extract Evoked Response Potentials in a single-blind procedure. The participants and assessors will be blind to experimental condition. | 18 |
| Anodal tDCS Over the lOFC anodal tDCS over the lOFC
anodal tDCS over the lOFC,: tDCS at a constant current of 1.5 mA will be applied for one 20-minute session over the left orbitofrontal cortex . Resting-state EEG for 10 minutes will be recorded immediately prior to and after tDCS. After post-tDCS resting state EEG is acquired, EEG is recorded to extract Evoked Response Potentials in a single-blind procedure. The participants and assessors will be blind to experimental condition. | 21 |
| Sham tDCS Stimulation sham tDCS stimulation
sham tDCS stimulation condition: In the sham condition, the current will be ramped up to 1.5 mA for 30 seconds and then ramped back down to 0. As this commonly used sham procedure produces a brief tingling sensation, participants are kept unaware of their experimental condition. Resting-state EEG for 10 minutes will be recorded immediately prior to and after the sham tDCS. After post-sham stimulation resting state EEG is acquired, EEG is recorded to extract Evoked Response Potentials in a single-blind procedure. The participants and assessors will be blind to experimental condition. | 19 |
| Total | 58 |
Baseline characteristics
| Characteristic | Anodal tDCS Over the rIFG, | Anodal tDCS Over the lOFC | Sham tDCS Stimulation | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants | 21 Participants | 19 Participants | 58 Participants |
| Conners-3 Self-Report Hyperactivity/impulsivity subscale | 14 units on a scale STANDARD_DEVIATION 7 | 17 units on a scale STANDARD_DEVIATION 7 | 12 units on a scale STANDARD_DEVIATION 7 | 14.39285714 units on a scale STANDARD_DEVIATION 7.191354839 |
| Conners-3 Self-Report Inattention subscale | 16 units on a scale STANDARD_DEVIATION 8 | 16 units on a scale STANDARD_DEVIATION 9 | 15 units on a scale STANDARD_DEVIATION 8 | 15.67857143 units on a scale STANDARD_DEVIATION 8.250855918 |
| Delay discounting task | .45 score on a scale STANDARD_DEVIATION 0.3 | .31 score on a scale STANDARD_DEVIATION 0.22 | .5 score on a scale STANDARD_DEVIATION 0.31 | 0.415454545 score on a scale STANDARD_DEVIATION 0.284301081 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 5 Participants | 2 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 16 Participants | 17 Participants | 46 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| PROMIS Depression | 49 units on a scale STANDARD_DEVIATION 10 | 47 units on a scale STANDARD_DEVIATION 12 | 47 units on a scale STANDARD_DEVIATION 12 | 47.64285714 units on a scale STANDARD_DEVIATION 11.22728587 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 2 Participants | 3 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 7 Participants | 6 Participants | 3 Participants | 16 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 7 Participants | 12 Participants | 12 Participants | 31 Participants |
| Region of Enrollment United States | 18 participants | 21 participants | 19 participants | 58 participants |
| Sex: Female, Male Female | 14 Participants | 17 Participants | 14 Participants | 45 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 5 Participants | 13 Participants |
| Stop Signal Task | 353 milliseconds STANDARD_DEVIATION 414 | 276 milliseconds STANDARD_DEVIATION 328 | 233 milliseconds STANDARD_DEVIATION 247 | 284.8076923 milliseconds STANDARD_DEVIATION 330.2148165 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 22 | 0 / 20 |
| other Total, other adverse events | 0 / 22 | 0 / 22 | 0 / 20 |
| serious Total, serious adverse events | 0 / 22 | 0 / 22 | 0 / 20 |
Outcome results
Primary
Delay Discounting Task
This task assessed discounting larger future rewards for smaller immediate ones. The point where a person is equally likely to prefer immediate vs delayed reward (the indifference point) is determined for several and combinations of reward sizes and lengths of time. Area under the curve (AUC) is calculated by summing the results of the following for each delay and indifference point pair: x2-x1\[(y1 + y2)/2\]. x1 and x2 are successive delays and y1 and y2 are indifference points for those delays. AUC range=0-1. Larger AUCs reflect less impulsivity.
Time frame: Within an hour post-stimulation condition
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Anodal tDCS Over the rIFG, | Delay Discounting Task | .53 score on a scale | Standard Deviation 0.31 |
| Anodal tDCS Over the lOFC | Delay Discounting Task | .4 score on a scale | Standard Deviation 0.25 |
| Sham tDCS Stimulation | Delay Discounting Task | .57 score on a scale | Standard Deviation 0.29 |
Primary
Stop Signal Task (SST)
The Stop-Signal Task (SST) is a task requiring inhibition of a prepotent motor response. The SST requires participants to respond to a target stimulus as quickly and accurately as possible by pressing a button, but also to withhold their response when they hear an auditory signal. Thus, this task involves a competition between activating and inhibiting processes. The primary outcome variable is change in the stop signal reaction time (SSRT) for the task administered seconds to minutes before and seconds to minutes after stimulation. The theoretical minimum is zero seconds and there is no theoretical maximum. Higher SSRT scores reflect greater impulsivity.
Time frame: Within an hour post-stimulation condition
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Anodal tDCS Over the rIFG, | Stop Signal Task (SST) | 255 milliseconds | Standard Deviation 463 |
| Anodal tDCS Over the lOFC | Stop Signal Task (SST) | 215 milliseconds | Standard Deviation 278 |
| Sham tDCS Stimulation | Stop Signal Task (SST) | 297 milliseconds | Standard Deviation 278 |