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The Relationship Add Title
       Click to between Absolute
Beta Power and rCMRglc in Primary
    Insomnia during REM sleep
             Click to Add Speaker Information

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

                  Washington & Jefferson College
                  1



Department of Psychiatry, University of Pittsburgh School of Medicine
2
Conflict of Interest Disclosures
                                                   Speaker:
X     1. I do not have any potential conflicts of interest to disclose, OR

      2. I wish to disclose the following potential conflicts of interest:

     Type of Potential Conflict                             Details of Potential Conflict
     Grant/Research Support
             Consultant
        Speakers’ Bureaus
         Financial support
                Other
      3. The material presented in this lecture has no relationship with any of these potential conflicts,
      OR

      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:
1.
2.
3.
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.
PET
                      Lab Room

EEG
EMG
EOG

      saline




      [radiotracer]
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.


                            Coordinates      K      Corrected p-
                                                      values

                             -10, 48, 10    3219       0.03
                             52, -66, 14    10431      0.001

                             -34, -44.-20   3034       0.04
Results: Region 1
• Significant Areas:

   – Left cingulate gyrus
                                    Cingulate Gyrus
                                                       Frontal
                                                       Gyri

   – Inferior and middle
                                                            9
     frontal gyri                                           8
                                                            7
                                                            6
                                                            5
                                                            4
                                                            3
                                                            2
                                                            1
                                                            0
                            Continuous Voxels: 3219
                            Coordinates: -10, 48, 10
                            Z=3.36, p=0.03
Results: Region 2
                                                                            Superior Parietal Lobule

• Significant Areas:




                               -14.1, -64.3, 31.8




                                                                                              -16.4, -51.8, 5.2
  – Right temporal gyri
                                                                                            Temporal Gyri
                                                           ParrahippocampalGyrus/
                                                           Hippocampus

  – Parahippocampal gyrus
    and hippocampus


                                       -16.4, -51.8, 5.2
                                                                                                                  9
                                                                                                                  8
                                                                                                                  7
                                                                                                                  6
                                                                                                                  5

  – Superior parietal lobule                                                                                      4
                                                                                                                  3
                                                                                                                  2
                                                                                                                  1
                                                                                                                  0
                                                    Continuous Voxels: 10431
                                                    Coordinates: 52, -66, 14
                                                    Z=4.15, p<.001
Results: Region 3
                              Fusiform gyrus
• Significant Areas:




                           -35.2, -57.2, -10.4




                                                                  34, -44.-20
   – Left fusiform gyrus


   – Temporal gyri
                                                  Temporal Gyri
                                                                                9
                                                                                8




                            -35.2, -57.2, -10.4
                                                                                7
                                                                                6
                                                                                5
                                                                                4
                                                                                3
                                                                                2
                                                                                1
                                                                                0




                           Continuous Voxels: 3034 Coordinates:
                           -34, -44.-20
                           Z=4.38, p=.04
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)

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The Relationship between Absolute Beta Power and rCMRglc in Primary Insomnia during REM Sleep

  • 1.
  • 2. The Relationship Add Title Click to between Absolute Beta Power and rCMRglc in Primary Insomnia during REM sleep Click to Add Speaker Information Jennifer Alman1, David Cashmere2, Jean Miewald2, Eric Nofzinger, M.D.2, Daniel Buysse, M.D.2, and Anne Germain, Ph.D.2 Washington & Jefferson College 1 Department of Psychiatry, University of Pittsburgh School of Medicine 2
  • 3. Conflict of Interest Disclosures Speaker: X 1. I do not have any potential conflicts of interest to disclose, OR 2. I wish to disclose the following potential conflicts of interest: Type of Potential Conflict Details of Potential Conflict Grant/Research Support Consultant Speakers’ Bureaus Financial support Other 3. The material presented in this lecture has no relationship with any of these potential conflicts, OR 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: 1. 2. 3.
  • 4. 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.
  • 5. 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
  • 6. 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.
  • 7. 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.
  • 8. PET Lab Room EEG EMG EOG saline [radiotracer]
  • 9. 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).
  • 10. 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
  • 11. Results • Significant negative correlations were found between beta activity and rCMRglc during REM sleep in 3 brain regions. Coordinates K Corrected p- values -10, 48, 10 3219 0.03 52, -66, 14 10431 0.001 -34, -44.-20 3034 0.04
  • 12. Results: Region 1 • Significant Areas: – Left cingulate gyrus Cingulate Gyrus Frontal Gyri – Inferior and middle 9 frontal gyri 8 7 6 5 4 3 2 1 0 Continuous Voxels: 3219 Coordinates: -10, 48, 10 Z=3.36, p=0.03
  • 13. Results: Region 2 Superior Parietal Lobule • Significant Areas: -14.1, -64.3, 31.8 -16.4, -51.8, 5.2 – Right temporal gyri Temporal Gyri ParrahippocampalGyrus/ Hippocampus – Parahippocampal gyrus and hippocampus -16.4, -51.8, 5.2 9 8 7 6 5 – Superior parietal lobule 4 3 2 1 0 Continuous Voxels: 10431 Coordinates: 52, -66, 14 Z=4.15, p<.001
  • 14. Results: Region 3 Fusiform gyrus • Significant Areas: -35.2, -57.2, -10.4 34, -44.-20 – Left fusiform gyrus – Temporal gyri Temporal Gyri 9 8 -35.2, -57.2, -10.4 7 6 5 4 3 2 1 0 Continuous Voxels: 3034 Coordinates: -34, -44.-20 Z=4.38, p=.04
  • 15. 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.
  • 16. 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
  • 17. 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.
  • 18. 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
  • 19. 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.
  • 20. 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)

Editor's Notes

  1. Primary Insomnia is characterized by increased arousal, difficultly falling and staying asleep, and poor sleep quality which can cause significant impairment on daytime functioning. Neurobiological changes in the brain during REM sleep may have effects on the poor sleep patients suffer from The correlation of neurobiological underpinnings of primary insomnia during REM sleep have not been thoroughly studied
  2. The goal of this study was to explor the relationship between whole-night absolute beta power and relative regional cerebral metabolic rate of glucose during REM sleep in adults with PI using EEG and PET scans
  3. 10 participants with Primary Insomnia were included in this study. The mean age was 37.8 with a standard deviation of 9.38 years. All the subjects were free of medication and comorbid disorders?
  4. The participants spent three nights in the lab. The first night was used as an acclimation night to the lab for the patients and also to screen for sleep apnea and periodic limb movements. On the second night an EEG was recorded and used as the baseline sleep. The third night the patients were injected with FDG and after 20 min form sleep onset they were woken up and taken to the PET center for scanning
  5. The results showed no significant positive correlation between bet activity and rCMRglc. However, significant negative correlations were found between whole-night beta activity and rCMRglc during REM sleep in three brain regions
  6. The first region of significant is the left inferior and middle frontal gyri. This region also extended into the cingulate gyrus.
  7. The second area included the inferior, middle, and superior temporal gyri, fusiform gyrus, parahippocampal gyrus and the hippocampus. The significant are extended bilaterally to the posterior cingulate, precuneus, and the superior parietal lobule.
  8. The third region showed that the left fusiform gyrus, and the superior, inferior and middle temporal gyri were significantly correlated with increased rCMRglc with a decrease in beta activity.
  9. Contrary to our initial expectation, we observed a negative correlation between beta activity and rCMRglc during REM sleep in PI. Although unexpected, the negative correlation is nevertheless consistent with prior observations derived from topographic studies that have contrasted beta activity during wakefulness and REM sleep in healthy subjects. Therefore, the this pattern that may not be specific to physiological arousal in PI , but more broadly, may reflect the “decoupling” of cognitive processes during REM sleep. Frontal, parieto-occipital, and temporal regions are part of a broad perceptual/sensory integration and information processing network involved in conscious, attention-driven cognitive processes during wakefulness, and associated with beta activity. Activity in these associative cortical regions during REM sleep with low beta activity, therefore, may be involved in dreaming and perhaps disturbed REM slep in PI. P érez-Garci et al., SLEEP, 2001 Therefore, the negative correlation observed in this sample may relate to dream mentation, rather than heightened central arousal characteristics of PI. Perlis and colleagues suggested different dimensions of hyperarousal are relevant for insomnia, and REM sleep mentation may be one of them.