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The Relationship between Absolute Beta Power and rCMRglc in Primary

Insomnia during REM sleep

Jennifer Alman1, David Cashmere2, Jean Miewald2, Eric Nofzinger, M.D.2, Daniel Buysse, M.D.2, and Anne Germain,

Ph.D.2

1Washington & Jefferson College

2Department of Psychiatry, University of Pittsburgh School of Medicine

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4. This talk presents material that is related to one or more of these potential conflicts, and the following objective references are provided as support for this lecture:

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Background• Increased beta power has been shown in

primary insomnia (PI) during NREM sleep.e.g., Merica and Gaillard, 1998

• PI is a disorder characterized by hyperarousal.

• REM sleep is a state of hyperarousal, especially in limbic regions.

• The neurobiological correlates of beta power in PI during REM sleep have not been investigated.

Study Aim

• Explore relationship between absolute beta power and rCMRglc during REM in PI.

• Hypothesis: Positive correlation between beta power and rCMRglc in:

– Occipital gyrus– Anterior cingulate cortex– Gyrus rectus and posterior medial

orbitofrontal cortex

Participants

• 10 PI subjects

• Mean age: 37.86 ± 9.38 years

• 7 women, 3 men• All subjects were free of medication,

comorbid psychiatric, other sleep and medical disorders.

Procedures• 3 nights spent in the lab.

– Night 1: Sleep apnea screening

– Night 2: Baseline

– Night 3: PET sleep study

• Whole-night REM sleep beta (16-32Hz) power estimates obtained from Night 2 from artifact-free 4-second epochs, averaged across all REM sleep periods.

EEGEMGEOG

saline

Lab Room

[radiotracer]

PET

PET Data Analysis

• Correlation analyses were conducted to determine the relationships between beta activity and rCMRglc during REM sleep.

• Reported results are corrected for multiple comparisons (p < .05).

Results

• No significant positive correlation between beta activity and rCMRglc.

• Trends observed for: – Gyrus rectus *– Middle temporal gyrus– Middle frontal gyrus– Dorsal/anterior cingulate gyrus *– Parieto-occipital sulcus

Results

• Significant negative correlations were found between beta activity and rCMRglc during REM sleep in 3 brain regions.

3034

10431

3219

K Corrected p-values

Coordinates

0.04-34, -44.-20

0.00152, -66, 14

0.03-10, 48, 10

Results: Region 1

• Significant Areas:

– Left cingulate gyrus

– Inferior and middle frontal gyri 9

876543210

Cingulate GyrusFrontal Gyri

Continuous Voxels: 3219

Coordinates: -10, 48, 10

Z=3.36, p=0.03

Results: Region 2

• Significant Areas:

– Right temporal gyri

– Parahippocampal gyrus and hippocampus

– Superior parietal lobule

9876543210

-14.

1,

-64.

3,

31.8

-16.

4, -

51.8

, 5.

2

-16.

4,

-51.

8,

5.2

Temporal GyriParrahippocampalGyrus/Hippocampus

Superior Parietal Lobule

Continuous Voxels: 10431

Coordinates: 52, -66, 14

Z=4.15, p<.001

Results: Region 3

• Significant Areas:– Left fusiform gyrus

– Temporal gyri

9876543210

-35.

2,

-57.

2,

-10.

4-3

5.2,

-57

.2, -

10.4

34,

-44.

-20

Continuous Voxels: 3034 Coordinates: -34, -44.-20

Z=4.38, p=.04

Fusiform gyrus

Temporal Gyri

Conclusions

• No areas reached statistical significance for positive correlations between beta activity and rCMRglc at corrected level of significance.

• PI decreased whole-night beta activity was associated with increased rCMRglc during REM sleep.

Limitations

• Whole-night absolute beta power used was from Night 2.– Repeat with beta activity during uptake period

• Beta power was the only measure used to indicate arousal. – Assess correlations with other measures of

arousal:• Peripheral arousal with heart rate variability • Cognitive/dream content• Indices of somatic arousal

» Perlis et al., 2001

Discussion

• No areas reached statistical significance for positive correlations between beta activity and rCMRglc at corrected level of significance.

• Differences across studies may result from a difference between NREM vs. REM sleep.

• The small sample sizes warrant caution when interpreting these preliminary results.

Discussion• We observed a negative correlation between beta activity

and rCMRglc during REM sleep.

• This pattern may not be specific to central arousal in PI during REM sleep:

– Frontal, parieto-occipital, and temporal regions are part of a perceptual/sensory integration and information processing network also involved dreaming.

– Maquet et al., 1996

– Beta activity orchestrates activity across these brain regions during wakefulness, and is decreased during REM sleep.

– Pérez-Garci et al., 2001

• The observed pattern may reflect disturbed REM sleep mentation in PI.

– Perlis et al., 2001

Future Directions

1. Replication in larger samples.

2. Focus on beta activity during FDG uptake period.

3. Exploration and comparison of the relationships between beta activity and rCMRglc during REM and NREM sleep.

4. Contrast these relationships across healthy sleepers, subjects with PI or insomnia comorbid with other disorders such as PTSD and depression.

5. Obtain dream reports from subjects undergoing sleep neuroimaging studies.

Acknowledgements

• Gina Pietrone• Research participants • N-CTRC staff

US Department of Defense (PT073961-W81XWH-07-PTSD-IIRA)

National Institutes of Health (MH053035; MH024652; MH66227; RR024153)