Normal Physiology
Conditions
Keywords
Memory performance, Neural Biomarkers, EEG, Noninvasive transcranial magnetic stimulation
Brief summary
Background: Transcranial magnetic stimulation (TMS) of the brain has been used to change the activity and connections in the brain to improve memory. Researchers are interested in how these brain changes cause memory improvements and how activity at the time of stimulation may change the effects of TMS. Objective: To learn how brain stimulation can be used to improve memory. Eligibility: Healthy adults ages 18-40 Design: Participants will be screened with a medical record review. Participants will have 3 study visits. At visit 1, participants will have a physical exam and will talk about their health. They will have magnetic resonance imaging (MRI). The MRI scanner is a metal cylinder surrounded by a strong magnetic field. During the MRI, participants will lie on a table that can slide in and out of the scanner. A coil will be placed over the head. Participants will be asked to keep their eyes focused on a small cross on a computer screen inside the scanner. The scanner makes loud noises. Participants will get earplugs. At visits 2 and 3, participants will have TMS and perform tasks. For TMS, a wire coil encased in plastic is held on the scalp. When the coil is triggered, a brief electrical current passes through the coil and creates a magnetic pulse that stimulates the brain. During TMS, an electroencephalogram (EEG) will record brain activity. For the EEG, a cloth cap with electrodes is fitted on the participant s head. Participants will complete a memory task and a spatial processing task. They will also complete surveys about their mental state. Participation will last 2-3 weeks.
Detailed description
Study Description: The Behavioral Neurology Unit studies the human brain systems underlying learning and adaptation with the goal of finding interventions to make these processes more efficient. In this study, we are interested in examining how the task state of the episodic memory network influences the effect of faciliatory TMS on memory and its EEG neural correlates. It is hypothesized that Network-targeted parietal-TMS will improve memory performance and enhance EEG biomarkers of successful memory performance, but that these changes will be modulated by the ongoing task activity during stimulation. Objectives: Primary Objectives: Investigate how TMS modulates EEG neural measures of successful memory and the association of this modulation with behavioral performance Examine how memory task state influences susceptibility to plasticity via TMS and determine the optimal neural state for improving memory Exploratory Objectives: Search for MRI predictors of the effects of TMS Endpoints: Primary Endpoints: Memory performance, Late Positive Posterior ERP, evoked theta/alpha power (secondary), EEG functional connectivity (secondary) Exploratory Endpoints: fMRI resting state functional connectivity, fractional anisotropy
Interventions
DEVICETMS
The intervention of interest will be TMS delivered to the region of the left posterior parietal cortex with the greatest connectivity with the left hippocampus derived from the baseline resting-state fMRI session. This region was chosen because of its dense connections with the hippocampus, allowing stimulation of this location to modulate function of the hippocampal-cortical network. The control intervention target will be vertex, a commonly used active control site which does not influence neural or behavioral activity.
Sponsors
National Institute of Neurological Disorders and Stroke (NINDS)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
In order to be eligible to participate in this study, an individual must meet all of the following criteria: 1. Stated willingness to comply with all study procedures and availability for the duration of the study 2. Ability of subject to understand and the willingness to sign a written informed consent document. 3. Age 18-40 (inclusive)
Exclusion criteria
An individual who meets any of the following criteria will be excluded from participation in this study: 1. Any current major neurological or psychiatric disorder such as (but not limited to) stroke, Parkinson disease, Alzheimer disease, schizophrenia or major depression 2. History of seizure 3. Medications acting on the central nervous system, such as those that lowers the seizure threshold such as neuroleptics, beta lactams, isoniazid, metronidazole; benzodiazepines, tricyclic or other antidepressants; or prescription stimulants. 4. Inability to provide informed consent 5. Ferromagnetic metal in the cranial cavity or eye, implanted neural stimulator, cochlear implant, or ocular foreign body 6. Implanted cardiac pacemaker or auto-defibrillator or pump 7. Non-removable body piercing 8. Claustrophobia 9. Inability to lie supine for 1 hour 10. Pregnancy, or plans to become pregnant during the study. 11. Members of the NINDS BNU 12. Subjects who have contraindications to MRI will follow the NMR Center guidelines for MR safety.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Memory Performance | 1 hour | Participants completed a memory task with simultaneous EEG acquisition and transcranial magnetic stimulation (TMS) delivered to either a memory-relevant parietal lobe target or a vertex control site. Participants were shown a series of objects in one of four quadrants on the screen, with TMS delivered either prior to or concurrent with the trial onset. They were instructed to remember the object and the location. This outcome measure examines the accuracy of memory for the item and the location (context), presented as the percentage of successful trials. Accuracy is shown for each stimulation condition (parietal or vertex location, before or during the trial) |
| Late Positive Posterior (ERP) Event Related Potential | During encoding (with TMS) and during retrieval (after TMS) | Participants completed a memory task with simultaneous EEG acquisition and transcranial magnetic stimulation (TMS) delivered to either a memory-relevant parietal lobe target or a vertex control site. Participants were shown a series of objects in one of four quadrants on the screen, with TMS delivered either prior to or concurrent with the trial onset. They were instructed to remember the object and the location. This outcome measure examines the neural response to trials which were later remembered relative to trials which were later forgotten. Values represent the difference in average EEG amplitude, in uV, between remembered and forgotten trials and compared across each stimulation condition (parietal or vertex location, before or during the trial) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Theta/Alpha Power | During encoding (with TMS) and during retrieval (after TMS) | Participants completed a memory task with simultaneous EEG acquisition and transcranial magnetic stimulation (TMS) delivered to either a memory-relevant parietal lobe target or a vertex control site. Participants were shown a series of objects in one of four quadrants on the screen, with TMS delivered either prior to or concurrent with the trial onset. They were instructed to remember the object and the location. This outcome measure examines the neural response to trials which were later remembered relative to trials which were later forgotten. Values represent the difference in average task-evoked power in the theta/alpha range (4-13Hz), in uV, between remembered and forgotten trials and compared across each stimulation condition (parietal or vertex location, before or during the trial) |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from the NIH healthy volunteer database and the NIH postbac list serve, as well as individuals who self-referred. Recruitment of study participants occurred from July 2021 to February 2023.
Pre-assignment details
43 participants were consented to the study and 32 participants successfully completed all study requirements.
Participants by arm
| Arm | Count |
|---|---|
| Healthy Participants Healthy participants undergoing all study procedures | 32 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | High stimulation threshold | 3 |
| Overall Study | Screen Failure | 1 |
| Overall Study | Withdrawal by Subject | 7 |
Baseline characteristics
| Characteristic | Healthy Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 32 Participants |
| Age, Continuous | 25.1 years STANDARD_DEVIATION 4.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 15 Participants |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 32 |
| other Total, other adverse events | 0 / 32 |
| serious Total, serious adverse events | 0 / 32 |
Outcome results
Primary
Late Positive Posterior (ERP) Event Related Potential
Participants completed a memory task with simultaneous EEG acquisition and transcranial magnetic stimulation (TMS) delivered to either a memory-relevant parietal lobe target or a vertex control site. Participants were shown a series of objects in one of four quadrants on the screen, with TMS delivered either prior to or concurrent with the trial onset. They were instructed to remember the object and the location. This outcome measure examines the neural response to trials which were later remembered relative to trials which were later forgotten. Values represent the difference in average EEG amplitude, in uV, between remembered and forgotten trials and compared across each stimulation condition (parietal or vertex location, before or during the trial)
Time frame: During encoding (with TMS) and during retrieval (after TMS)
Population: Due to EEG trigger issues, only 14 subjects were able to complete the retrieval arm and have data analyzed as ERPs.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Item | Late Positive Posterior (ERP) Event Related Potential | Parietal, before TMS | 1.49 uV | Standard Deviation 0.83 |
| Item | Late Positive Posterior (ERP) Event Related Potential | Parietal, during TMS | 1.43 uV | Standard Deviation 0.63 |
| Item | Late Positive Posterior (ERP) Event Related Potential | Vertex, before TMS | 0.96 uV | Standard Deviation 0.76 |
| Item | Late Positive Posterior (ERP) Event Related Potential | Vertex, during TMS | -1.07 uV | Standard Deviation 1.41 |
| Context | Late Positive Posterior (ERP) Event Related Potential | Vertex, during TMS | 0.79 uV | Standard Deviation 2.16 |
| Context | Late Positive Posterior (ERP) Event Related Potential | Parietal, before TMS | -0.11 uV | Standard Deviation 1.47 |
| Context | Late Positive Posterior (ERP) Event Related Potential | Vertex, before TMS | -0.91 uV | Standard Deviation 1.35 |
| Context | Late Positive Posterior (ERP) Event Related Potential | Parietal, during TMS | 1.29 uV | Standard Deviation 1.88 |
Primary
Memory Performance
Participants completed a memory task with simultaneous EEG acquisition and transcranial magnetic stimulation (TMS) delivered to either a memory-relevant parietal lobe target or a vertex control site. Participants were shown a series of objects in one of four quadrants on the screen, with TMS delivered either prior to or concurrent with the trial onset. They were instructed to remember the object and the location. This outcome measure examines the accuracy of memory for the item and the location (context), presented as the percentage of successful trials. Accuracy is shown for each stimulation condition (parietal or vertex location, before or during the trial)
Time frame: 1 hour
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Item | Memory Performance | Parietal, before TMS | 0.89 proportion accuracy | Standard Deviation 0.01 |
| Item | Memory Performance | Parietal, during TMS | 0.91 proportion accuracy | Standard Deviation 0.01 |
| Item | Memory Performance | Vertex, before TMS | 0.92 proportion accuracy | Standard Deviation 0.01 |
| Item | Memory Performance | Vertex, during TMS | 0.89 proportion accuracy | Standard Deviation 0.01 |
| Context | Memory Performance | Vertex, during TMS | 0.66 proportion accuracy | Standard Deviation 0.03 |
| Context | Memory Performance | Parietal, before TMS | 0.64 proportion accuracy | Standard Deviation 0.03 |
| Context | Memory Performance | Vertex, before TMS | 0.69 proportion accuracy | Standard Deviation 0.02 |
| Context | Memory Performance | Parietal, during TMS | 0.66 proportion accuracy | Standard Deviation 0.03 |
Secondary
Theta/Alpha Power
Participants completed a memory task with simultaneous EEG acquisition and transcranial magnetic stimulation (TMS) delivered to either a memory-relevant parietal lobe target or a vertex control site. Participants were shown a series of objects in one of four quadrants on the screen, with TMS delivered either prior to or concurrent with the trial onset. They were instructed to remember the object and the location. This outcome measure examines the neural response to trials which were later remembered relative to trials which were later forgotten. Values represent the difference in average task-evoked power in the theta/alpha range (4-13Hz), in uV, between remembered and forgotten trials and compared across each stimulation condition (parietal or vertex location, before or during the trial)
Time frame: During encoding (with TMS) and during retrieval (after TMS)
Population: Due to EEG trigger issues, only 14 subjects had retrieval data analyzed as task-evoked power
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Item | Theta/Alpha Power | Parietal, before trial TMS | 1.46 uV | Standard Deviation 2.29 |
| Item | Theta/Alpha Power | Parietal during trial TMS | 0.94 uV | Standard Deviation 3.2 |
| Item | Theta/Alpha Power | Vertex, before trial TMS | 2.25 uV | Standard Deviation 5.04 |
| Item | Theta/Alpha Power | Vertex, during trial TMS | 1.07 uV | Standard Deviation 3.5 |
| Context | Theta/Alpha Power | Vertex, during trial TMS | -0.06 uV | Standard Deviation 0.56 |
| Context | Theta/Alpha Power | Parietal, before trial TMS | -0.18 uV | Standard Deviation 0.56 |
| Context | Theta/Alpha Power | Vertex, before trial TMS | 0.18 uV | Standard Deviation 0.5 |
| Context | Theta/Alpha Power | Parietal during trial TMS | 0.06 uV | Standard Deviation 0.46 |