Effects of Sensory Flicker and Electrical Flicker Stimulation

Neurophysiological and Behavioral Effects of Sensory Flicker and Electrical Flicker Stimulation

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.

Study Overview

• Status: Completed
• Conditions: Brain Diseases
• Intervention / Treatment: Device: Blackrock CereStim; Device: Customized version of DAVID device

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.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Device: 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.
Active Comparator: Electrical Flicker Stimulation; Participants will be exposed to direct electrical brain stimulation with low-amplitude current, at given flicker frequencies. Participants will be exposed to frequencies ranging from 5-100Hz, for up to 10 seconds at a time. Initially, frequencies of 5.5Hz and 40Hz will be tested. During brain stimulation sessions, bipolar electrical stimulation will be applied to one or more areas of the brain at a time either with or without associated memory tasks. Stimulation in the absence of any memory task will be applied to assess the subject's neurophysiological response to stimulation and to identify the optimal stimulation parameters for use during memory tasks. Stimulation during behavioral tasks will be applied in an attempt to affect the subject's memory.	Device: Blackrock 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	During experiment session (up to 2 hours) during hospital admission (up to 2 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	During experiment session (up to 2 hours) during hospital admission (up to 2 weeks)

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: Georgia Institute of Technology
• Investigators: Principal Investigator: Joseph Manns, PhD, Emory University

Publications and helpful links

General Publications

• Blanpain LT, Chen E, Park J, Walelign MY, Gross RE, Cabaniss BT, Willie JT, Singer AC. Multisensory Flicker Modulates Widespread Brain Networks and Reduces Interictal Epileptiform Discharges in Humans. medRxiv [Preprint]. 2023 Mar 17:2023.03.14.23286691. doi: 10.1101/2023.03.14.23286691.

Helpful Links

• Multisensory Flicker Modulates Widespread Brain Networks and Reduces Interictal Epileptiform Discharges in Humans

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2020
• Primary Completion (Actual): November 22, 2022
• Study Completion (Actual): November 22, 2022

Study Registration Dates

• First Submitted: December 4, 2019
• First Submitted That Met QC Criteria: December 5, 2019
• First Posted (Actual): December 6, 2019

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Sensory Flicker Stimulation; Electrical Flicker Stimulation; Neurophysiological Effects; Behavioral Effects; Brain circuits modulation; Steady-state evoked potentials
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Brain Diseases
• Other Study ID Numbers: IRB00107577

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant and data that underlie the results reported after de-identification (text, tables, figures, and appendices) will be available. The study protocol, statistical analysis plan, analytic code will be made available immediately following publication with no end date.
• IPD Sharing Time Frame: Immediately following publication. No end date.
• IPD Sharing Access Criteria: De-identified, minimally processed data and processed data will be made available upon request. Data may be requested by contacting Dr. Annabelle Singer at annabelle.singer@bme.edu
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No