Sleep Architecture & Intrinsic Oscillatory and Network Connectivity in Cognition and Executive Dysfunction in TLE
Study Details
Study Description
Brief Summary
Temporal Lobe Epilepsy (TLE) patients and healthy controls will undergo a night of sleep at the UC Davis Epilepsy Monitoring Unit (EMU) to characterize sleep architecture. A subset of TLE patients will be randomly assigned to an Acoustic Stimulation (AS) or SHAM stimulation night and return at least 7 days later for the other condition. Cognitive tests will be conducted 90 minutes prior to sleep (learning and immediate recall) and again 1 hour after awakening for 120 minutes (delayed recall and attention), while monitoring neural networks using functional Magnetic Resonance Imaging (fMRI).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Detailed Description
Temporal Lobe Epilepsy (TLE) is characterized by disordered neural network activity and temporal lobe onset seizures. Individuals with TLE experience debilitating diseases and medical conditions including sleep disruption and cognitive deficits, which compromise daily activity and quality of life. While these conditions can be long-term consequences of repeated seizures and anti-seizure medications, research demonstrates that these conditions can occur before the first recognized seizure and worsen over time, even with successful seizure treatment. This suggests that early neural network abnormalities may underlie seizure development while simultaneously impairing sleep and cognitive development, even prior to the added effects of long term disease and treatments. Individuals with TLE experience sleep disruption, which impairs memory consolidation and sustained attention, both of which are compromised in TLE. A prominent, yet untested hypothesis is that TLE-related neural network activity including interictal epileptiform discharges (IEDs) interrupt non-rapid eye movement (NREM) sleep architecture, interfering with memory consolidation and attention. However, specific mechanisms by which abnormal neural network activity contributes to disordered sleep and cognition in TLE remain elusive.
Pilot data demonstrate that new-onset TLE patients exhibit cognitive deficits that are linked with reduced activation of key frontal-temporal neural networks, as measured by task-based functional magnetic resonance imaging (fMRI), which positively correlates with poor sleep. These new and exciting findings suggest that characterizing the sleep architecture patterns that contribute to less effective cognitive processing in TLE is critical to identifying modifiable sleep biomarkers, and ultimately improving cognitive function in TLE patients.
This study will begin to address the existing gap in knowledge by investigating sleep architecture patterns in TLE that directly contribute to cognitive deficits using both an observational and a mechanism-probing interventional approach. In NREM sleep, slow wave oscillations on electroencephalogram (EEG) are phase-locked and coupled with sleep spindle oscillations (SW-SSO), which facilitates memory consolidation and potentially improves attention. In TLE, disordered networks leading to IEDs and seizures may contribute to altered SW-SSO coupling during sleep, resulting in memory and attention deficits. A single night of acoustic stimulation (AS) has been demonstrated to improve cognitive performance and enhance SW-SSO coupling in healthy adults, but has not been studied in TLE. The central hypothesis for this study is that disordered networks in newly diagnosed TLE patients result in altered sleep patterns, disrupting memory consolidation and attention. This study will test this hypothesis by: (1) characterizing TLE sleep patterns using computational EEG - sleep spindle density, slow wave power, IEDs, and SW-SSO coupling, (2) linking these TLE-related sleep architecture alterations to cognitive processing; (3) determining if AS enhances SW-SSO coupling in TLE; and (4) determining if AS improves memory and attention in young adults with TLE.
First, we will characterize sleep architecture patterns in TLE and determine the relationship to cognitive processing. New-onset TLE patients and healthy controls will undergo one night of scalp EEG-monitored sleep to characterize sleep spindle density, slow wave power, IEDs, and SW-SSO coupling (i.e., phase-locking).
Hypothesis: Compared to controls, TLE patients will exhibit IEDs as well as reduced sleep spindle density and slow wave power with reduced SW-SSO coupling. The next morning, I will use fMRI to monitor network activation as participants perform an attention task and declarative memory recall, learned the night prior.
Hypothesis: Compared to controls, reduced SW-SSO coupling during sleep in TLE patients will be associated with reduced activation on task-based fMRI, as well as poorer memory and attention.
Next, the study will determine the effect of AS on sleep architecture patterns and cognitive processing in TLE. New-onset TLE patients will be randomly assigned to AS or SHAM stimulation as the initial condition in a cross-over design and will undergo a night of scalp EEG monitored sleep under each condition, separated by at least one week.
Hypothesis: AS will exhibit greater levels of SW-SSO coupling compared to SHAM. The next morning, I will use fMRI to monitor network activation as participants perform an attention task and declarative memory recall learned the night prior.
Hypothesis: Compared to SHAM, AS will show increased activation on task-based fMRI, and improved memory and attention.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Acoustic Stimulation (AS) Participants in this arm will be exposed to acoustic stimulation while they sleep during a night of monitoring in the UC Davis Epilepsy Monitoring Unit (EMU). |
Other: Acoustic Stimulation (AS)
Acoustic Stimulation will be administered while participants have their sleep monitored during one night in the UC Davis Epilepsy Monitoring Unit (EMU).
|
| Sham Comparator: SHAM Stimulation Participants in this arm will not be exposed to any stimulation while they have their sleep monitored for one night in the UC Davis Epilepsy Monitoring Unit (EMU). |
Other: SHAM Stimulation
No stimulation will be administered while participants have their sleep monitored during one night in the UC Davis Epilepsy Monitoring Unit (EMU).
|
Outcome Measures
Primary Outcome Measures
- Stanford Sleepiness Scale [participant completes over one week post EMU stay]
Alertness Test; charts how alert a participant feels for up to 18 hours of the day for 7 days; scale is from 1-7 with higher scores meaning more sleepiness; abnormal is 4 and above
- Pittsburgh Sleep Quality Index (PSQI) [screening]
used to measure quality and patterns of sleep in adults
- Epworth Sleepiness Scale [screening]
subjective measure of a patient's sleepiness; scores are from 0-24 with higher scores meaning more sleepiness; abnormal is 10 and above
- Karolinska Sleepiness Scale / Sleep Diary [screening]
Self-administered indication of sleepiness; scores are from 1-9 with higher scores meaning more sleepiness; abnormal is 7 and above
- Vigor Affect Visual Analog Scale [screening]
self-administered assessment of mood; scores are from 0-10; depending on the question, higher score can mean more sleepiness or less sleepiness
Eligibility Criteria
Criteria
Inclusion Criteria for TLE participants:
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new onset TLE (defined as less than or equal to 3 years from original TLE diagnosis based on clinical characteristics, EEG, vEEG, and high-resolution epilepsy protocol 3T MRI)
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epilepsy/neurology patients at UC Davis
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ADHD accepted
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Capacity to fully cooperate and follow directions, and provide consent
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No significant structural brain abnormalities (stroke or tumor)
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No circadian rhythm disorders
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No history of alcohol or substance abuse
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No claustrophobia
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Mesial temporal sclerosis and subtle diffuse cortical dysplasia accepted
Inclusion Criteria for Healthy Controls:
- age, education, and sex-matched without TLE and no family history of TLE
Exclusion Criteria:
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non-MRI compatible devices
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MRI safe metallic implants that distort MRI signal including braces
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Medications that affect cognition: topiramate, zonisamide, chronic barbiturates or benzos
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hearing loss/hearing aid
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Moderate to severe sleep apnea (apnea-hypopnea index>15 events/hour)
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Major neurologic disorders diagnosed or suspected
Exclusion Criteria for healthy controls:
- History of loss of consciousness for >5 minutes
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- University of California, Davis
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 1737425