Causal Role of Top-Down Theta Oscillations in Prioritization

Official title

Modulating Oscillations and Working Memory in Patients With Subdural Electrodes

Overview

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.

Interventions

• Device Direct cortical stimulation (DCS) Alpha
  Rhythmic alpha stimulation
• Device Direct cortical stimulation (DCS) Theta
  Rhythmic theta stimulation applied
• Device Sham Direct cortical stimulation (DCS)
  Arrhythmic stimulation paradigm applied
• Device Direct cortical stimulation (DCS) In-Phase Theta
  Rhythmic in-phase theta stimulation applied
• Device Direct cortical stimulation (DCS) Anti-Phase Theta
  Rhythmic anti-phase theta stimulation applied

Primary outcome measures

• Change in Working Memory Task Performance - Pashler's working memory capacity metric (k) [Time frame: During the 1- to 1.5-hour test at Baseline and Stimulation Session conducted over a 1 to 2 day period]
• Change in Working Memory Task Performance - Reaction Time [Time frame: During the 1- to 1.5-hour test at Baseline and Stimulation Session conducted over a 1 to 2 day period]
• Intracranial EEG Multi-taper fft [Time frame: During the 1- to 1.5-hour test at Baseline and Stimulation Session conducted over a 1 to 2 day period]
• Intracranial EEG weighted phase lag index (wPLI) [Time frame: During the 1- to 1.5-hour test at Baseline and Stimulation Session conducted over a 1 to 2 day period]

Secondary outcome measures (3)

• Intracranial EEG Wavelets [Time frame: During the 1- to 1.5-hour test at Baseline and Stimulation Session conducted over a 1 to 2 day period]
• Intracranial EEG phase locking [Time frame: During the 1- to 1.5-hour test at Baseline and Stimulation Session conducted over a 1 to 2 day period]
• Intracranial EEG Granger causality [Time frame: During the 1- to 1.5-hour test at Baseline and Stimulation Session conducted over a 1 to 2 day period]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Basic science

Study locations

United States · 1 center

• University of North Carolina at Chapel Hill — Chapel Hill

Publications

• 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. PMID 31775030
• 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. PMID 30268847

Identifiers

NCT: NCT06252532 · 23-1652 · 5R01MH124387

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗