Neurophysiologic Correlates of Hypersomnia

Study Overview
=================
Brief Summary
-----------------
The goal of this project is to examine the neurophysiology of hypersomnia during sleep and wakefulness, to identify biomarkers for excessive sleepiness in neuropsychiatric disorders, and pilot acoustical slow wave induction during sleep in patients with hypersomnolence, to determine if this decreases daytime sleepiness in these patients. The primary study hypotheses are that individuals with hypersomnolence will have reduced slow wave activity (SWA) during sleep and increased waking theta/alpha activity during wake in specific brain regions. A secondary hypothesis is that acoustical slow wave induction in hypersomnolent patients will increase SWA during sleep, reduce theta/alpha activity during wake, and improve subjective sleepiness.

Official Title
-----------------
Neurophysiologic Correlates of Hypersomnia: a High Density EEG Investigation

Conditions
-----------------
Major Depressive Disorder, Primary Hypersomnia, Bipolar Disorder, Narcolepsy, Primary Insomnia

Intervention / Treatment
-----------------
* Other: Acoustical slow wave induction


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Meet Diagnostic and Statistical Manual edition IV criteria for neuropsychiatric disorders enumerated in study population description Exclusion Criteria: Exclusionary criteria for all subjects will include: evidence of a clinically significant sleep disorder that would cause hypersomnolence (e.g. moderate to severe obstructive sleep apnea, restless legs syndrome, shift-work sleep disorder), history of significant head trauma or loss of consciousness > 30 minutes; current smoking of more than 15 cigarettes per day; >3 caffeinated beverages per day; significant neurologic or medical illness; active drug/alcohol abuse/dependence (within 6 months of enrollment), women who are pregnant, <6 months post-partum, nursing or planning to become pregnant during the study; left-handedness (due to effects on sleep topography); and imminent risk for self-harm or suicide.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| MDD with Hypersomnia<br>Participants with Major Depressive Disorder and co-morbid hypersomnia | Other: Acoustical slow wave induction<br>* Brief tones (50 millisecond duration) at a frequency of 0.8 and 2 Hz, a rate that approximates the natural cellular oscillations of cortical neurons during sleep, will be played in blocks of 15-20 during non-rapid eye movement (NREM) sleep. Blocks of active acoustic slow wave induction will be followed by blocks of equal duration without induction, in order to make comparisons between stimulation periods (ON) and no stimulation periods (OFF). Tone intensity will be manually adjusted so as to be above an individual participant's auditory threshold during waking, but still quiet enough as not to awaken the subject from sleep. Sham slow wave induction will consist of auditory tones played prior to sleep, and during sleep of insufficient timing and intensity to alter slow wave activity.<br>|
| MDD without hypersomnia<br>Participants with Major Depressive Disorder but without co-morbid hypersomnia | |
| BPAD with hypersomnia<br>Participants with Bipolar Affective Disorder and co-morbid hypersomnia | Other: Acoustical slow wave induction<br>* Brief tones (50 millisecond duration) at a frequency of 0.8 and 2 Hz, a rate that approximates the natural cellular oscillations of cortical neurons during sleep, will be played in blocks of 15-20 during non-rapid eye movement (NREM) sleep. Blocks of active acoustic slow wave induction will be followed by blocks of equal duration without induction, in order to make comparisons between stimulation periods (ON) and no stimulation periods (OFF). Tone intensity will be manually adjusted so as to be above an individual participant's auditory threshold during waking, but still quiet enough as not to awaken the subject from sleep. Sham slow wave induction will consist of auditory tones played prior to sleep, and during sleep of insufficient timing and intensity to alter slow wave activity.<br>|
| BPAD without hypersomnia<br>Participants with Bipolar Affective Disorder without co-morbid hypersomnia | |
| Primary Hypersomnia<br>Patients with primary hypersomnia (idiopathic hypersomnia) | Other: Acoustical slow wave induction<br>* Brief tones (50 millisecond duration) at a frequency of 0.8 and 2 Hz, a rate that approximates the natural cellular oscillations of cortical neurons during sleep, will be played in blocks of 15-20 during non-rapid eye movement (NREM) sleep. Blocks of active acoustic slow wave induction will be followed by blocks of equal duration without induction, in order to make comparisons between stimulation periods (ON) and no stimulation periods (OFF). Tone intensity will be manually adjusted so as to be above an individual participant's auditory threshold during waking, but still quiet enough as not to awaken the subject from sleep. Sham slow wave induction will consist of auditory tones played prior to sleep, and during sleep of insufficient timing and intensity to alter slow wave activity.<br>|
| Primary Insomnia<br>Patients with primary insomnia | |
| Narcolepsy<br>Subjects with narcolepsy | Other: Acoustical slow wave induction<br>* Brief tones (50 millisecond duration) at a frequency of 0.8 and 2 Hz, a rate that approximates the natural cellular oscillations of cortical neurons during sleep, will be played in blocks of 15-20 during non-rapid eye movement (NREM) sleep. Blocks of active acoustic slow wave induction will be followed by blocks of equal duration without induction, in order to make comparisons between stimulation periods (ON) and no stimulation periods (OFF). Tone intensity will be manually adjusted so as to be above an individual participant's auditory threshold during waking, but still quiet enough as not to awaken the subject from sleep. Sham slow wave induction will consist of auditory tones played prior to sleep, and during sleep of insufficient timing and intensity to alter slow wave activity.<br>|
| Healthy Controls<br>healthy participants | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nocturnal Slow Wave Activity | EEG recordings during sleep will be analyzed to assess slow wave activity in the 1-4.5Hz range. | Individual nights of sleep recorded within an average of 4 weeks of enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Waking theta/alpha activity | Waking EEG activity across the 1-12Hz range will be analyzed. | Individual days of waking EEG will be recorded within an average of 4 weeks of enrollment |