Epilepsy, Working Memory
Conditions
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.
Interventions
DEVICEDirect cortical stimulation (DCS) Alpha
Rhythmic alpha stimulation
DEVICEDirect cortical stimulation (DCS) Theta
Rhythmic theta stimulation applied
DEVICESham Direct cortical stimulation (DCS)
Arrhythmic stimulation paradigm applied
DEVICEDirect cortical stimulation (DCS) In-Phase Theta
Rhythmic in-phase theta stimulation applied
DEVICEDirect cortical stimulation (DCS) Anti-Phase Theta
Rhythmic anti-phase theta stimulation applied
Sponsors
University of North Carolina, Chapel Hill
National Institute of Mental Health (NIMH)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Working Memory Task Performance - Pashler's working memory capacity metric (k) | During the 1- to 1.5-hour test at Baseline and Stimulation Session conducted over a 1 to 2 day period | The participant will be presented with three colored squares in both visual fields during a practice session. Then the participant is presented with an informative retro-cue, an arrow to the left or right, that is 100% predictive of the upcoming probe, or an uninformative neural cue, an arrow pointing in both directions. Finally, in the probe epoch participants are presented with an array of squares on the left or the right side of the screen. Participants must determine if the array of colored squares is the same or different from those held in memory. Performance will be defined as: k=N\*(HR\*FA)/(1-FA) where N is the number of the items that are held in memory. HR is the hit rate defined as the percent correct for trials where the probe does not match the encoding array. FA is the false alarm rate defined as the percent incorrect for trials where the probe does match the encoding array. |
| Change in Working Memory Task Performance - Reaction Time | During the 1- to 1.5-hour test at Baseline and Stimulation Session conducted over a 1 to 2 day period | The participant will be presented with three colored squares in both visual fields during a practice session. Then the participant is presented with an informative retro-cue, an arrow to the left or right, that is 100% predictive of the upcoming probe, or an uninformative neural cue, an arrow pointing in both directions. Finally, in the probe epoch participants are presented with an array of squares on the left or the right side of the screen. Participants must determine if the array of colored squares is the same or different from those held in memory. Reaction times will be quantified in milliseconds. |
| Intracranial EEG Multi-taper fft | During the 1- to 1.5-hour test at Baseline and Stimulation Session conducted over a 1 to 2 day period | Time-frequency analysis of electrophysiology data will be performed using methods like multi-taper fft. This will be compared between sham (arrhythmic) and stimulation trials to identify if stimulation enhances neuronal entrainment. |
| Intracranial EEG weighted phase lag index (wPLI) | During the 1- to 1.5-hour test at Baseline and Stimulation Session conducted over a 1 to 2 day period | Functional connectivity will be measured using weighted phase lag index (WPLI). To calculate WPLI, first Morlet wavelet convolution is performed to extract instantaneous phase and amplitude for the frequency of interest for the two target sites. Next, the cross-spectral density is calculated (one signal multiplied by the complex conjugate of the other). From the cross-spectral density the imaginary component of the resulting signal is extracted. Then those imaginary values are averaged over the time frame of instance (here, the second half of the stimulation train). Finally, the magnitude of the resulting vector is taken to be the wPLI. This metric quantifies the consistency of phase lag between the two target regions and is weighted towards signals with a 90 or 270 degree offset to address a common confound in electrophysiology, volume conduction. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Intracranial EEG Wavelets | During the 1- to 1.5-hour test at Baseline and Stimulation Session conducted over a 1 to 2 day period | Spectral analysis and functional connectivity analysis of electrophysiology data will be performed using methods like wavelets. This will be compared between sham (arrhythmic) and stimulation trials to identify if stimulation enhances neuronal entrainment. |
| Intracranial EEG phase locking | During the 1- to 1.5-hour test at Baseline and Stimulation Session conducted over a 1 to 2 day period | Spectral analysis and functional connectivity analysis of electrophysiology data will be performed using methods like phase locking. This will be compared between sham (arrhythmic) and stimulation trials to identify if stimulation enhances neuronal entrainment. |
| Intracranial EEG Granger causality | During the 1- to 1.5-hour test at Baseline and Stimulation Session conducted over a 1 to 2 day period | Spectral analysis and functional connectivity analysis of electrophysiology data will be performed using methods like Granger causality. This will be compared between sham (arrhythmic) and stimulation trials to identify if stimulation enhances neuronal entrainment. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORFlavio Frohlich, PhD
UNC Chapel Hill
Outcome results
None listed