Effects of sleep deprivation on sleep homeostasis and restoration during methadone-maintenance: a [31]P MRS brain imaging study

Abstract

Insomnia afflicts many individuals, but particularly those in chronic methadone treatment. Studies examining sleep deprivation (SD) have begun to identify sleep restoration processes involving brain bioenergetics. The technique ([31])P magnetic resonance spectroscopy (MRS) can measure brain changes in the high-energy phosphates: alpha-, beta-, and gamma-nucleoside triphosphate (NTP). In the present study, 21 methadone-maintained (MM) and 16 control participants underwent baseline (BL), SD (40 wakeful hours), recovery1 (RE1), and recovery2 (RE2) study nights. Polysomnographic sleep was recorded each night and ([31])P MRS brain scanning conducted each morning using a 4T MR scanner (dual-tuned proton/phosphorus head-coil). Interestingly, increases in total sleep time (TST) and sleep efficiency index (SEI) commonly associated with RE sleep were not apparent in MM participants. Analysis of methadone treatment duration revealed that the lack of RE sleep increases in TST and SEI was primarily exhibited by short-term MM participants (methadone <12 months), while RE sleep in long-term MM (methadone >12 months) participants was more comparable to control participants. Slow wave sleep increased during RE1, but there was no difference between MM and control participants. Spectral power analysis revealed that compared to control participants; MM participants had greater delta, theta, and alpha spectral power during BL and RE sleep. ([31])P MRS revealed that elevations in brain beta-NTP (a direct measure of ATP) following RE sleep were greater in MM compared to control participants. Results suggest that differences in sleep and brain chemistry during RE in MM participants may be reflective of a disruption in homeostatic sleep function.

Figure 1

A) Numbered 1–6 phosphorus ^[31]P MRS spectrum from example voxels on the corresponding mid-axial slice. B) Representative mid-axial slice indicating the location of ^[31]P MRS acquisition with voxel locations 1–6 corresponding to spectral output. C) Representative ^[31]P MRS spectrum indicating labeled phosphorus containing peaks, modeled fit and residual. All spectra are displayed with 15 Hz exponential filtering for display.

Figure 2

Polysomnogram sleep measures recorded for baseline, recovery1, and recovery2 sleep nights in control and methadone maintained participants. A) Slow Wave Sleep (SWS)-participants exhibited a reliable increase in SWS during recovery1 sleep compared to baseline sleep B) Sleep Onset Latency (SOL)- participants exhibited a marked decrease SOL during recovery1 sleep compared to baseline sleep C) Rapid Eye Movement (REM) Sleep- participants exhibited a reliable increase in REM during recovery1 sleep compared to baseline sleep. All values are represented as mean ± SEM with an alpha of p<0.05. * denotes significantly different than baseline sleep data.

Figure 3

A) Total sleep time (TST)- measures recorded for baseline, recovery1, and recovery2 sleep nights in control and methadone-maintained participants. B) Total sleep time (TST)-secondary analysis of methadone treatment duration for baseline, recovery1, and recovery2 for control, short-term methadone-maintained, and long-term methadone-maintained participants. All values are represented as mean ± SEM with an alpha of p<0.05. * denotes significantly different from control participant data.

Figure 4

A) Wake after sleep onset (WASO)- measures recorded for baseline, recovery1, and recovery2 sleep nights in control and methadone-maintained participants. B) Wake after sleep onset (WASO)- secondary analysis of methadone treatment duration for baseline, recovery1, and recovery2 for control, short-term methadone-maintained, and long-term methadone-maintained participants. All values are represented as mean ± SEM with an alpha of p<0.05. * denotes significantly different from control participant data.

Figure 5

A) Sleep efficiency Index (SEI)- measures recorded for baseline, recovery1, and recovery2 sleep nights in control and methadone-maintained participants. B) Sleep efficiency index (SEI)-secondary analysis of methadone treatment duration for baseline, recovery1, and recovery2 for control, short-term methadone-maintained, and long-term methadone-maintained participants. All values are represented as mean ± SEM with an alpha of p<0.05. * denotes significantly different from control participant data and denotes significantly different from control and long-term MM participant data.

Figure 6

Spectral power analysis (SPA) of polysomnogram sleep measures for baseline, recovery1, and recovery2 sleep nights in control and methadone maintained participants. A) Delta (0.5–4Hz) B) Theta (4–8Hz) C) Alpha (8–12Hz). All values are represented as mean ± SEM with an alpha of p<0.05. * denotes significantly different than control participant SPA data.

Figure 7

Global brain phosphorus ^[31]P MRS measurements recorded the mornings following baseline, sleep deprivation (Sleep Dep), recovery1, and recovery2 sleep nights. A) Brain beta-NTP across study nights in all participants. B) beta-NTP- in control and methadone-maintained subjects C) total-NTP- in control and methadone-maintained subjects. Values are represented as mean ± SEM with an alpha of p<0.05. *denotes significant difference between beta-NTP levels following recovery1 when compared to baseline. * denotes significantly different than controls subjects.