Neurophysiologic Correlates of Hypersomnia

Neurophysiologic Correlates of Hypersomnia: a High Density EEG Investigation

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.

Study Overview

• Status: Completed
• Conditions: Bipolar Disorder; Major Depressive Disorder; Primary Insomnia; Narcolepsy; Primary Hypersomnia
• Intervention / Treatment: Other: Acoustical slow wave induction

• Study Type: Observational
• Enrollment (Actual): 76

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53719
      • University of Wisconsin-Madison, Department of Psychiatry

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subjects will be recruited from the greater Madison, WI area. Hypersomnolent subject groups (n=30 in each group) may include unipolar MDD with hypersomnolence, primary hypersomnia (idiopathic hypersomnia), bipolar disorder with hypersomnolence, and narcolepsy. Non-hypersomnolent comparison groups (n=30 in each group) will include: MDD without hypersomnolence, bipolar disorder without hypersomnolence, primary insomnia, and healthy controls.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

8

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
MDD with Hypersomnia; Participants with Major Depressive Disorder and co-morbid hypersomnia	Other: Acoustical slow wave induction; 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.
MDD without hypersomnia; Participants with Major Depressive Disorder but without co-morbid hypersomnia
BPAD with hypersomnia; Participants with Bipolar Affective Disorder and co-morbid hypersomnia	Other: Acoustical slow wave induction; 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.
BPAD without hypersomnia; Participants with Bipolar Affective Disorder without co-morbid hypersomnia
Primary Hypersomnia; Patients with primary hypersomnia (idiopathic hypersomnia)	Other: Acoustical slow wave induction; 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.
Primary Insomnia; Patients with primary insomnia
Narcolepsy; Subjects with narcolepsy	Other: Acoustical slow wave induction; 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.
Healthy Controls; 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

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Investigators: Principal Investigator: David T Plante, University of Wisconsin, Madison

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2012
• Primary Completion (Actual): June 1, 2018
• Study Completion (Actual): June 1, 2018

Study Registration Dates

• First Submitted: October 24, 2012
• First Submitted That Met QC Criteria: October 29, 2012
• First Posted (Estimate): November 1, 2012

Study Record Updates

• Last Update Posted (Actual): December 24, 2018
• Last Update Submitted That Met QC Criteria: December 21, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Mood Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Bipolar and Related Disorders; Depressive Disorder; Disease; Sleep Initiation and Maintenance Disorders; Bipolar Disorder; Depressive Disorder, Major; Disorders of Excessive Somnolence; Narcolepsy
• Other Study ID Numbers: 2012-0201