Effects of Sensory Flicker and Electrical Flicker Stimulation

Study Overview
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Brief Summary
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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
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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.

Official Title
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Neurophysiological and Behavioral Effects of Sensory Flicker and Electrical Flicker Stimulation

Conditions
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Brain Diseases

Intervention / Treatment
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* Device: Customized version of DAVID device
* Device: Blackrock CereStim


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sensory Flicker Stimulation<br>Patients will be exposed to Sensory Flicker Stimulation. In one experiment, patients will be exposed, for about 10 minutes at a time, to a sequence of sensory flicker trials each lasting a few seconds. Each trial may include the following modalities and frequencies of flicker: Modalities: auditory only, visual only, or audiovisual combined. Subjects may be exposed to individual pulses of light and/or sound (i.e. around or less than 1 pulse per second). Frequencies: random, or anywhere from 5Hz to 100Hz. Subjects may be exposed to sensory flicker at a given frequency or random frequency for up to 1h at a time In another experiment, patients will undergo a behavioral task in which they will be exposed to one of 2 flicker conditions on separate days. Comfortable parameters (e.g., light intensity and volume intensity) for the subject will be found. If such parameters cannot be found, exposure of the patient to visual and/or auditory stimuli will be stopped. | Device: Customized version of DAVID device<br>* A customized version of the DAVID device will be used to expose patients 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.<br>|
| Active Comparator: Electrical Flicker Stimulation<br>Patients will be exposed to direct electrical brain stimulation with low-amplitude current, at given flicker frequencies. Patients 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 behavioral task. Stimulation in the absence of any behavioral task will be applied in order to assess the subject's neurophysiological response to stimulation and to identify the optimal stimulation parameters for use during behavioral task. Stimulation during behavioral task will be applied in an attempt to affect the subject's behavior. | Device: Blackrock CereStim<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of sensory flicker exposure on local field potential (LFP): comparing mean power spectral density at the frequency of flicker being presented and nearby frequencies | Power spectral density of the LFP will be measured across stimulus frequencies and modalities of sensory flicker stimuli in auditory areas, hippocampus and medial prefrontal cortex. Comparisons will be drawn between the mean power spectral density measured in dB/Hz at the frequency of flicker being presented, and nearby frequencies (+/- 20Hz). | Up to 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of sensory flicker on interictal epileptiform discharges (IEDs) | The effect of the sensory flicker will be evaluated by the comparison of the rate of IEDs between a given sensory flicker stimulation condition (involving specific frequency and modality of stimulation) and baseline (no stimulation) condition. | Up to 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sensory Flicker Stimulation, Electrical Flicker Stimulation, Neurophysiological Effects, Behavioral Effects, Brain circuits modulation, Steady-state evoked potentials