Cognitive Control
Conditions
Brief summary
This is a study to determine whether particular forms of brain-stimulation, applied to superior frontal cortex/preSMA can affect cognition and associated frontal theta oscillations. To perform this study, the investigators first measure brain activity and cognitive performance using BrainE, a cognitive task platform that assesses cognition on sustained attention, response inhibition, working memory, interference processing and emotion processing assessments. Next, the investigators apply brain-stimulation over a mid-frontal region associated with these tasks (mid-line frontal activity overlying superior frontal cortex/pre-SMA area). Finally, human subjects perform the BrainE task assessments again immediately after the brain-stimulation. The investigators compare the effects of brain stimulation on average frontal activity evoked across the cognitive tasks, and on the cognitive performance averaged across tasks. The investigators primarily compare the effects of two types of brain-stimulation against each other: intermittent Theta-Burst Stimulation (a protocol designed to excite brain activity) and continuous Theta-Burst-Stimulation (a stimulation protocol designed to inhibit brain activity).
Detailed description
1. Brain/Behavior Recordings: to measure brain activity as described above, the investigators first ask subjects to engage in a cognitive assessment set while measuring EEG activity. For this study, the assessment set consists of the following tasks: (1) sustained attention; (2) response inhibition; (2) visuo-spatial working-memory; (3) Flanker interference processing, and (4) emotional interference processing. This battery takes about 30 minutes to complete. 24 channel EEG recordings are performed simultaneous to the cognitive tasks. Subjects perform the BrainE cognitive assessment, then receive brain-stimulation, and will then immediately be tested on the BrainE assessment again. 2. Brain-Stimulation: Each subject will be asked to come in twice for this study, separated by 1 week. On week one they will receive one stimulation protocol, and on the subsequent week they will receive the other (order determined randomly for each subject). The intermittent Theta-Burst-Stimulation protocol (iTBS) consists of a similar burst pattern (3 stimulation pulses 20ms apart; each burst applied every 200ms). However, after 10 bursts (2 seconds of stimulation) there is a pause for 8 seconds. 200 bursts are still applied, however due to the inter-burst intervals, this paradigm takes 200 seconds. The continuous Theta-Burst-Stimulation protocol (cTBS) consists of a burst of three stimulation pulses, applied 20ms apart; with each burst occurring every 200ms. Thus, every second participants receive 5 bursts. This continues for 40 seconds, such that participants in total receive 200 bursts or 600 pulses.
Interventions
DEVICEiTBS then cTBS
repetitive transcranial magnetic stimulation applied with intermittent theta-burst stimulation protocol applied in week 1 and continuous theta-burst stimulation protocol applied in week 2.
DEVICEcTBS then iTBS
repetitive transcranial magnetic stimulation applied with continuous theta-burst stimulation protocol applied in week 1 and intermittent theta-burst stimulation protocol applied in week 2.
Sponsors
University of California, San Diego
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Investigators will assess for each subject whether they have any guess, a priori, as to hypothesized effects of the iTBS vs. cTBS protocols (improve, impair or no change on cognition). Participant/care provider will know which stimulation is being applied (iTBS, cTBS based on labels A & B), but will not know the hypothesized effects of these two protocols. iTBS and cTBS protocols will be masked as treatment A and treatment B, prior to handing the data over to PI/outcomes assessor. Analyses will thus be performed to assess whether treatment A or treatment B has an effect on cognition; and whether there are differences between these treatment protocols.
Intervention model description
The investigators will test the effects of two different interventions (iTBS, cTBS) on cognitive control. Each participant will receive both interventions, labeled A & B, separated a week apart.
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
Adequate decisional capacity to make a choice about participating in this research study.
Exclusion criteria
* No major active neurologic/psychiatric disease * No contraindications for rTMS * No behavioral/medical factors that increase risk of seizure
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Post vs. Pre Change in Mid-frontal Theta Oscillations for iTBS vs. cTBS Stimulation | (Post-Pre) iTBS and (Post-Pre) cTBS signals were measured one week apart. | Change in superior frontal stimulus-evoked theta oscillations were measure on a set of cognitive tasks, specifically selective attention, response inhibition, working memory, interference processing and emotion processing tasks. The evoked EEG response (mid-frontal theta FCz as a source for superior frontal theta) was averaged across all cognitive tasks to yield a global cognitive task-averaged signal that was measured immediately before (Pre) and immediately after (Post) iTBS, and similarly immediately before (Pre) and immediately after (Post) cTBS. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Post vs. Pre Change in Cognitive Performance | (Post-Pre) iTBS and (Post-Pre) cTBS cognitive performance levels were measured one week apart. | Change in cognitive performance was measured on a set of cognitive tasks, specifically selective attention, response inhibition, working memory, interference processing and emotion processing tasks. The cognitive performance was averaged across all cognitive tasks to yield global cognitive task-averaged performance that was measured immediately before (Pre) and immediately after (Post) iTBS, and similarly immediately before (Pre) and immediately after (Post) cTBS. |
Countries
United States
Participant flow
Recruitment details
Participants were screened for this study prior to enrollment. Any individuals with a history of seizure disorder; vascular or other lesion of the brain; administration of drugs that lower the seizure threshold; implanted or non-removable metallic objects above the neck; implanted devices with electrical circuits were excluded from enrollment.
Pre-assignment details
No enrolled participants were excluded.
Participants by arm
| Arm | Count |
|---|---|
| cTBS Then iTBS Participants received cTBS at week 1 (1 day), washout (1 week) then iTBS at week 2 (1 day). | 13 |
| iTBS Then cTBS Participants received iTBS at week 1 (1 day), washout (1 week) then cTBS at week 2 (1 day). | 12 |
| Total | 25 |
Baseline characteristics
| Characteristic | cTBS Then iTBS | iTBS Then cTBS | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 12 Participants | 25 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 4 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants | 7 Participants | 14 Participants |
| Race (NIH/OMB) White | 2 Participants | 0 Participants | 2 Participants |
| Region of Enrollment United States | 13 participants | 12 participants | 25 participants |
| Sex: Female, Male Female | 9 Participants | 5 Participants | 14 Participants |
| Sex: Female, Male Male | 4 Participants | 7 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 25 |
| other Total, other adverse events | 0 / 25 | 0 / 25 |
| serious Total, serious adverse events | 0 / 25 | 0 / 25 |
Outcome results
Primary
Post vs. Pre Change in Mid-frontal Theta Oscillations for iTBS vs. cTBS Stimulation
Change in superior frontal stimulus-evoked theta oscillations were measure on a set of cognitive tasks, specifically selective attention, response inhibition, working memory, interference processing and emotion processing tasks. The evoked EEG response (mid-frontal theta FCz as a source for superior frontal theta) was averaged across all cognitive tasks to yield a global cognitive task-averaged signal that was measured immediately before (Pre) and immediately after (Post) iTBS, and similarly immediately before (Pre) and immediately after (Post) cTBS.
Time frame: (Post-Pre) iTBS and (Post-Pre) cTBS signals were measured one week apart.
Population: Although 25 participants enrolled, only 24 completed the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| cTBS | Post vs. Pre Change in Mid-frontal Theta Oscillations for iTBS vs. cTBS Stimulation | -0.043 microVolts (uV) at FCz EEG electrode | Standard Deviation 0.17 |
| iTBS | Post vs. Pre Change in Mid-frontal Theta Oscillations for iTBS vs. cTBS Stimulation | 0.017 microVolts (uV) at FCz EEG electrode | Standard Deviation 0.12 |
Secondary
Post vs. Pre Change in Cognitive Performance
Change in cognitive performance was measured on a set of cognitive tasks, specifically selective attention, response inhibition, working memory, interference processing and emotion processing tasks. The cognitive performance was averaged across all cognitive tasks to yield global cognitive task-averaged performance that was measured immediately before (Pre) and immediately after (Post) iTBS, and similarly immediately before (Pre) and immediately after (Post) cTBS.
Time frame: (Post-Pre) iTBS and (Post-Pre) cTBS cognitive performance levels were measured one week apart.
Population: Although 25 participants enrolled, only 24 completed the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| cTBS | Post vs. Pre Change in Cognitive Performance | 0.025 log(1/sec) | Standard Deviation 0.027 |
| iTBS | Post vs. Pre Change in Cognitive Performance | 0.013 log(1/sec) | Standard Deviation 0.02 |