Brain Diseases
Conditions
Keywords
Sensory Flicker Stimulation, Electrical Flicker Stimulation, Neurophysiological Effects, Behavioral Effects, Brain circuits modulation, Steady-state evoked potentials
Brief summary
The study will evaluate whether sensory flicker can modulate neural activity of deep brain regions in humans, and whether it can have relevant effects on behavior. Moreover, it will compare those effects to the gold-standard method of modulating brain circuits, direct electrical stimulation of the brain (the same mechanism as deep brain stimulation), using a powerful within-subjects design.
Detailed description
Clinical trials have explored the modulation of brain circuits to treat several brain disorders, including Parkinson's Disease, Alzheimer's Disease (AD), depression, and Obsessive-Compulsive Disorder (OCD). However, current means to non-invasively modulate brain activity are limited. The study will evaluate whether sensory flicker can modulate neural activity of deep brain regions in humans, and whether it can have relevant effects on behavior. Moreover, it will compare those effects to the gold-standard method of modulating brain circuits, direct electrical stimulation of the brain (the same mechanism as deep brain stimulation), using a powerful within-subjects design.
Interventions
DEVICECustomized version of DAVID device
A customized version of the DAVID device will be used to expose participants to sensory flicker. The device consists of opaque glasses containing LEDs to present flickering light, as well as earbuds or headphones to present flickering sound.
DEVICEBlackrock CereStim
The Blackrock CereStim is a fully programmable neurostimulator. The current pulses generated by the Blackrock CereStim are intended to stimulate neurons in proximity to a set of electrodes.
Sponsors
Georgia Institute of Technology
Emory University
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult (\>18 years, regardless of gender, race or ethnicity). * To be implanted with intracranial depth or grid/strip electrodes for surgical evaluation. * Patient was not shown, during phase I seizure monitoring, to exhibit abnormal EEG activity in response to photic stimulation, and is not clinically suspected to be susceptible to photic-induced seizures. * Patient has no pre-existing diagnosis of autism. * Patient is not considered at risk for psychogenic nonepileptic seizures (PNES) triggered by sensory stimulation. * Fluent in English. * Able to understand an informed consent (comprehend potential risks and benefits). * Give written and verbal informed consent to all experiments patient would participate in.
Exclusion criteria
* Failure to meet any one inclusion criteria.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fold-change in Oscillatory Activity (Power Spectral Density) in Response to Exposure to Sensory Flicker: Comparing Mean Power Spectral Density at the Frequency of Flicker Being Presented Between Flicker and Baseline Periods | During experiment session (up to 2 hours) during hospital admission (up to 2 weeks) | The power spectral density of the LFP will be measured across stimulus frequencies and modalities of sensory flicker stimuli in visual areas, auditory areas, hippocampus, and prefrontal cortex. To evaluate the effects of sensory flicker on brain activity in various brain regions, researchers compared the average increase in oscillatory neural activity of given recorded brain regions during sensory stimulation, among the total number of recording locations that showed a significant response to sensory stimulation compared to baseline. In participants in whom a condition was repeated across multiple experimental sessions. If a location showed a significant response in multiple sessions, the data point that showed the highest level of response was kept. The average fold-change increase in oscillatory activity, 25th and 75th percentiles, within a region of interest is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect of Sensory Flicker on the Rate of Interictal Epileptiform Discharges (IEDs) Which Represent Pathological Activity Often Observed in Epilepsy | During experiment session (up to 2 hours) during hospital admission (up to 2 weeks) | The change of of the sensory flicker effect will be evaluated by the comparison of the whole-brain rate of IEDs between sensory flicker stimulation and baseline (no stimulation). |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from Emory University Hospital in Atlanta, Georgia, USA. Participant enrollment began January 10, 2020, and all follow up was complete by November 22, 2022.
Pre-assignment details
Participants only had the Sensory Flicker Stimulation. In the initial IRB protocol submission, the research team intended to potentially do electrical flicker experiments as further exploration of their project but ended up opting not to pursue this avenue.
Participants by arm
| Arm | Count |
|---|---|
| Sensory Flicker Stimulation Participants will be exposed for about 10 to 60 minutes at a time, to a sequence of sensory flicker trials each lasting a few seconds to 5 minutes, while their eyes are open or closed. Each trial may include the following modalities and frequencies of flicker:
* Modalities: auditory only, visual only, or audiovisual combined.
* Frequencies: random, or anywhere from 3Hz to 200Hz.
Additionally, subjects may be exposed to individual pulses of light and/or sound, i.e. around or less than 1 pulse /second, for up to 20 minutes at a time.
Customized version of DAVID device: A customized version of the DAVID device will be used to expose participants to sensory flicker. The device consists of opaque glasses containing LEDs to present flickering light, as well as earbuds or headphones to present flickering sound. | 23 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Participants did not complete enough proportion of experiment(s) to be included in analysis | 4 |
Baseline characteristics
| Characteristic | Sensory Flicker Stimulation |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants |
| Age, Continuous | 33.7 years STANDARD_DEVIATION 11.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 16 Participants |
| Region of Enrollment United States | 23 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 23 |
| other Total, other adverse events | 16 / 23 |
| serious Total, serious adverse events | 0 / 23 |
Outcome results
Primary
Fold-change in Oscillatory Activity (Power Spectral Density) in Response to Exposure to Sensory Flicker: Comparing Mean Power Spectral Density at the Frequency of Flicker Being Presented Between Flicker and Baseline Periods
The power spectral density of the LFP will be measured across stimulus frequencies and modalities of sensory flicker stimuli in visual areas, auditory areas, hippocampus, and prefrontal cortex. To evaluate the effects of sensory flicker on brain activity in various brain regions, researchers compared the average increase in oscillatory neural activity of given recorded brain regions during sensory stimulation, among the total number of recording locations that showed a significant response to sensory stimulation compared to baseline. In participants in whom a condition was repeated across multiple experimental sessions. If a location showed a significant response in multiple sessions, the data point that showed the highest level of response was kept. The average fold-change increase in oscillatory activity, 25th and 75th percentiles, within a region of interest is reported.
Time frame: During experiment session (up to 2 hours) during hospital admission (up to 2 weeks)
Population: Participants who completed study procedures and had valid data points for each frequency and region are included.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sensory Flicker Stimulation | Fold-change in Oscillatory Activity (Power Spectral Density) in Response to Exposure to Sensory Flicker: Comparing Mean Power Spectral Density at the Frequency of Flicker Being Presented Between Flicker and Baseline Periods | Visual Region to 5.5Hz-V | 4.6 Fold-change in power |
| Sensory Flicker Stimulation | Fold-change in Oscillatory Activity (Power Spectral Density) in Response to Exposure to Sensory Flicker: Comparing Mean Power Spectral Density at the Frequency of Flicker Being Presented Between Flicker and Baseline Periods | Visual Region to 40Hz-V | 4 Fold-change in power |
| Sensory Flicker Stimulation | Fold-change in Oscillatory Activity (Power Spectral Density) in Response to Exposure to Sensory Flicker: Comparing Mean Power Spectral Density at the Frequency of Flicker Being Presented Between Flicker and Baseline Periods | Visual Region to 80Hz-V | 1.1 Fold-change in power |
| Sensory Flicker Stimulation | Fold-change in Oscillatory Activity (Power Spectral Density) in Response to Exposure to Sensory Flicker: Comparing Mean Power Spectral Density at the Frequency of Flicker Being Presented Between Flicker and Baseline Periods | Visual Region to 5.5Hz-A | 0.5 Fold-change in power |
| Sensory Flicker Stimulation | Fold-change in Oscillatory Activity (Power Spectral Density) in Response to Exposure to Sensory Flicker: Comparing Mean Power Spectral Density at the Frequency of Flicker Being Presented Between Flicker and Baseline Periods | Visual Region to 40Hz-A | 0.4 Fold-change in power |
| Sensory Flicker Stimulation | Fold-change in Oscillatory Activity (Power Spectral Density) in Response to Exposure to Sensory Flicker: Comparing Mean Power Spectral Density at the Frequency of Flicker Being Presented Between Flicker and Baseline Periods | Visual Region to 80Hz-A | 0.6 Fold-change in power |
| Sensory Flicker Stimulation | Fold-change in Oscillatory Activity (Power Spectral Density) in Response to Exposure to Sensory Flicker: Comparing Mean Power Spectral Density at the Frequency of Flicker Being Presented Between Flicker and Baseline Periods | Auditory Region to 5.5Hz-V | 0.9 Fold-change in power |
| Sensory Flicker Stimulation | Fold-change in Oscillatory Activity (Power Spectral Density) in Response to Exposure to Sensory Flicker: Comparing Mean Power Spectral Density at the Frequency of Flicker Being Presented Between Flicker and Baseline Periods | Auditory Region to 40Hz-V | 0.7 Fold-change in power |
| Sensory Flicker Stimulation | Fold-change in Oscillatory Activity (Power Spectral Density) in Response to Exposure to Sensory Flicker: Comparing Mean Power Spectral Density at the Frequency of Flicker Being Presented Between Flicker and Baseline Periods | Auditory Region to 80Hz-V | 0.7 Fold-change in power |
| Sensory Flicker Stimulation | Fold-change in Oscillatory Activity (Power Spectral Density) in Response to Exposure to Sensory Flicker: Comparing Mean Power Spectral Density at the Frequency of Flicker Being Presented Between Flicker and Baseline Periods | Auditory Region to 5.5Hz-A | 0.7 Fold-change in power |
| Sensory Flicker Stimulation | Fold-change in Oscillatory Activity (Power Spectral Density) in Response to Exposure to Sensory Flicker: Comparing Mean Power Spectral Density at the Frequency of Flicker Being Presented Between Flicker and Baseline Periods | Auditory Region to 40Hz-A | 1.6 Fold-change in power |
| Sensory Flicker Stimulation | Fold-change in Oscillatory Activity (Power Spectral Density) in Response to Exposure to Sensory Flicker: Comparing Mean Power Spectral Density at the Frequency of Flicker Being Presented Between Flicker and Baseline Periods | Auditory Region to 80Hz-A | 1 Fold-change in power |
| Sensory Flicker Stimulation | Fold-change in Oscillatory Activity (Power Spectral Density) in Response to Exposure to Sensory Flicker: Comparing Mean Power Spectral Density at the Frequency of Flicker Being Presented Between Flicker and Baseline Periods | Medial temporal lobe (MTL) Region to 5.5Hz-V | 0.6 Fold-change in power |
| Sensory Flicker Stimulation | Fold-change in Oscillatory Activity (Power Spectral Density) in Response to Exposure to Sensory Flicker: Comparing Mean Power Spectral Density at the Frequency of Flicker Being Presented Between Flicker and Baseline Periods | MTL Region to 40Hz-V | 0.8 Fold-change in power |
| Sensory Flicker Stimulation | Fold-change in Oscillatory Activity (Power Spectral Density) in Response to Exposure to Sensory Flicker: Comparing Mean Power Spectral Density at the Frequency of Flicker Being Presented Between Flicker and Baseline Periods | MTL Region to 80Hz-V | 0.6 Fold-change in power |
| Sensory Flicker Stimulation | Fold-change in Oscillatory Activity (Power Spectral Density) in Response to Exposure to Sensory Flicker: Comparing Mean Power Spectral Density at the Frequency of Flicker Being Presented Between Flicker and Baseline Periods | MTL Region to 5.5Hz-A | 0.7 Fold-change in power |
| Sensory Flicker Stimulation | Fold-change in Oscillatory Activity (Power Spectral Density) in Response to Exposure to Sensory Flicker: Comparing Mean Power Spectral Density at the Frequency of Flicker Being Presented Between Flicker and Baseline Periods | MTL Region to 40Hz-A | 0.6 Fold-change in power |
| Sensory Flicker Stimulation | Fold-change in Oscillatory Activity (Power Spectral Density) in Response to Exposure to Sensory Flicker: Comparing Mean Power Spectral Density at the Frequency of Flicker Being Presented Between Flicker and Baseline Periods | MTL Region to 80Hz-A | 0.5 Fold-change in power |
| Sensory Flicker Stimulation | Fold-change in Oscillatory Activity (Power Spectral Density) in Response to Exposure to Sensory Flicker: Comparing Mean Power Spectral Density at the Frequency of Flicker Being Presented Between Flicker and Baseline Periods | PFC Region to 5.5Hz-V | 0.5 Fold-change in power |
| Sensory Flicker Stimulation | Fold-change in Oscillatory Activity (Power Spectral Density) in Response to Exposure to Sensory Flicker: Comparing Mean Power Spectral Density at the Frequency of Flicker Being Presented Between Flicker and Baseline Periods | PFC Region to 40Hz-V | 0.5 Fold-change in power |
| Sensory Flicker Stimulation | Fold-change in Oscillatory Activity (Power Spectral Density) in Response to Exposure to Sensory Flicker: Comparing Mean Power Spectral Density at the Frequency of Flicker Being Presented Between Flicker and Baseline Periods | PFC Region to 80Hz-V | 0.5 Fold-change in power |
| Sensory Flicker Stimulation | Fold-change in Oscillatory Activity (Power Spectral Density) in Response to Exposure to Sensory Flicker: Comparing Mean Power Spectral Density at the Frequency of Flicker Being Presented Between Flicker and Baseline Periods | PFC Region to 5.5Hz-A | 0.5 Fold-change in power |
| Sensory Flicker Stimulation | Fold-change in Oscillatory Activity (Power Spectral Density) in Response to Exposure to Sensory Flicker: Comparing Mean Power Spectral Density at the Frequency of Flicker Being Presented Between Flicker and Baseline Periods | PFC Region to 40Hz-A | 0.5 Fold-change in power |
| Sensory Flicker Stimulation | Fold-change in Oscillatory Activity (Power Spectral Density) in Response to Exposure to Sensory Flicker: Comparing Mean Power Spectral Density at the Frequency of Flicker Being Presented Between Flicker and Baseline Periods | PFC Region to 80Hz-A | 0.4 Fold-change in power |
Secondary
Effect of Sensory Flicker on the Rate of Interictal Epileptiform Discharges (IEDs) Which Represent Pathological Activity Often Observed in Epilepsy
The change of of the sensory flicker effect will be evaluated by the comparison of the whole-brain rate of IEDs between sensory flicker stimulation and baseline (no stimulation).
Time frame: During experiment session (up to 2 hours) during hospital admission (up to 2 weeks)
Population: Participants who completed study procedures and had valid data points for each frequency and region are included.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Sensory Flicker Stimulation | Effect of Sensory Flicker on the Rate of Interictal Epileptiform Discharges (IEDs) Which Represent Pathological Activity Often Observed in Epilepsy | -3.0 Percent change |