Clinical trial NCT06252532: Causal Role of Top-Down Theta Oscillations in Prioritization
Official title: Modulating Oscillations and Working Memory in Patients With Subdural Electrodes
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: Working Memory
Epilepsy
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2024-02-09
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: Purpose: The purpose of this pilot study is to investigate the dynamics between theta and alpha oscillations in the control of working memory. These findings will be informative of what types of brain stimulation are most effective at modulating brain activity. Deep brain stimulation and transcranial magnetic stimulation are used for an increasing number of neurological and psychiatric disorders. Participants: Eligible participants are patients who have previously had electrodes implanted to monitor epilepsy (outside of research activity). 50 participants will be recruited, 25 participants for each phase of the study. Procedures (methods): The participants will perform a cognitive control task. During the task, rhythmic trains of direct cortical stimulation will be delivered to the frontal cortex alone or to the frontal and parietal cortex. Electrocorticography will be collected concurrent with stimulation.

Detailed description: The aim of this study is to investigate the causal role of functional interactions between frontal-theta dependent selection processes and posterior-alpha dependent suppression processes in the context of cognitive control by targeting theta and alpha oscillations in frontal and parietal cortex separately in phase one of the experiment. Theta and alpha oscillations are hypothesized to play complementary roles such that theta oscillations are excitatory (related to active processing) whereas alpha oscillations are inhibitory (related to suppression of processing).

Thus, the investigators hypothesize that rhythmic brain stimulation can be used to drive activity in opposite directions. In the second phase of the experiment the investigators target functional connectivity between these regions. In particular, theta oscillations are hypothesized to play a critical role in orchestrating the prioritization and suppression of information across the cerebral cortex. Thus, the investigators hypothesize that in-phase theta frequency connectivity will be causally related to working memory success, but alpha frequency connectivity will be inconsequential and anti-phase theta connectivity will be detrimental. Together these findings suggest an overall model by which the amplitude of theta oscillations in prefrontal and the amplitude of alpha oscillations in parietal play a causal role in prioritization and suppression respectively, but functional connectivity between frontal and parietal cortex within the theta frequency band alone is critical to these cognitive processes. This experiment is of critical importance to the design of future interventions that use brain stimulation for the treatment of psychiatric and neurological disorders. For example, the use of frequency specific brain stimulation is key to controlling the impact of brain stimulation on neural activity. Design considerations like this one might be fundamental to improving the efficacy of future interventions such as the use of deep brain stimulation for the treatment of Parkinson's disease and for the use of transcranial magnetic stimulation for the treatment of major depressive disorder.

Eligibility criteria: Inclusion Criteria:

* Able to provide informed consent
* History of medically intractable epilepsy
* Speak and understand English
* For the stimulation session, the participant must have electrodes in the relevant locations

Exclusion Criteria:

* Current diagnosis of other neurological illnesses including ischemic stroke, intracerebral hemorrhage, brain neoplasm
* Major systemic illness
* Severe cognitive impairment - diagnosed by clinician in neuropsychiatric evaluation
* Severe psychiatric illness
* Excessive use of alcohol or other substances
* Anything that, in the opinion of the investigator, would place the participant at increased risk or preclude the participant's full compliance with or completion of the study

Primary outcomes:
measure: Change in Working Memory Task Performance - Pashler's working memory capacity metric (k)
timeFrame: During the 1- to 1.5-hour test at Baseline and Stimulation Session conducted over a 1 to 2 day period
measure: Change in Working Memory Task Performance - Reaction Time
timeFrame: During the 1- to 1.5-hour test at Baseline and Stimulation Session conducted over a 1 to 2 day period
measure: Intracranial EEG Multi-taper fft
timeFrame: During the 1- to 1.5-hour test at Baseline and Stimulation Session conducted over a 1 to 2 day period
measure: Intracranial EEG weighted phase lag index (wPLI)
timeFrame: During the 1- to 1.5-hour test at Baseline and Stimulation Session conducted over a 1 to 2 day period
Secondary outcomes:
measure: Intracranial EEG Wavelets
timeFrame: During the 1- to 1.5-hour test at Baseline and Stimulation Session conducted over a 1 to 2 day period
measure: Intracranial EEG phase locking
timeFrame: During the 1- to 1.5-hour test at Baseline and Stimulation Session conducted over a 1 to 2 day period
measure: Intracranial EEG Granger causality
timeFrame: During the 1- to 1.5-hour test at Baseline and Stimulation Session conducted over a 1 to 2 day period
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
Study officials:
affiliation: UNC Chapel Hill
name: Flavio Frohlich, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Alagapan S, Riddle J, Huang WA, Hadar E, Shin HW, Frohlich F. Network-Targeted, Multi-site Direct Cortical Stimulation Enhances Working Memory by Modulating Phase Lag of Low-Frequency Oscillations. Cell Rep. 2019 Nov 26;29(9):2590-2598.e4. doi: 10.1016/j.celrep.2019.10.072.
citation: Alagapan S, Lustenberger C, Hadar E, Shin HW, Frӧhlich F. Low-frequency direct cortical stimulation of left superior frontal gyrus enhances working memory performance. Neuroimage. 2019 Jan 1;184:697-706. doi: 10.1016/j.neuroimage.2018.09.064. Epub 2018 Sep 27.