Hemispheric asymmetry in high-energy phosphate consumption during sleep-deprivation is balanced by creatine

Abstract

The human brain exhibits asymmetric hemispheric activity at night; this plays a crucial role in cognitive impairment from sleep deprivation. Although there have been many investigations on this topic, there are no studies on hemispheric differences in the consumption of high-energy phosphates (HEP). We present here a new data analysis of our previously published study in which subjects were measured for changes in high-energy phosphate (HEP), tCr/tNAA, and Glu/TNAA during subacute sleep deprivation (21 h) and cognitive tests. In our new analysis, we investigated differences and asymmetries in the metabolic consumption of both hemispheres. Comprehensive per-individual voxel-wise interhemispheric comparisons at all time points and conditions showed a greater decrease from baseline of ATP in the right than in the left hemisphere. Partial volume correction yielded an apparent higher decline of PCr/Pi in gray versus white matter. We also investigated whether creatine supplementation, which has been shown to prevent cognitive impairment during sleep deprivation, affected this hemispheric asymmetry. In a second session, the subjects took a high single dose of creatine monohydrate suspension (0.35 g/kg) after baseline measurements. Creatine balanced the sleep deprivation-induced asymmetry to a higher degree in the left hemisphere, which was due to an increase in PCr/Pi and decrease in ATP. Our results confirm-via the observed decrease in ATP level-a night-active right hemisphere. Creatine administration balanced this asymmetry.

Keywords: 31P-magnetic resonance spectroscopy; cognitive performance; creatine; hemispheric asymmetry; high energy phosphate; sleep deprivation.

Figure 1

(A) Study design: in one session, the subjects were administered creatine at 8:30 p.m. and in another they were administered a placebo. The order of the sessions was random. The interval between the two sessions was at least 5 days. In each session, cognitive and metabolic parameters were acquired in four runs. The baseline started at 6 p.m., the other at 0 a.m., 2 a.m., and 4 a.m. Each session included two ³¹P-MRS and three ¹H-MRS measurements, followed by fatigue scores, psychomotor vigilance tests (PVT), and other cognitive tasks (Cog.Test) and lasted 1 h and 35 min. (B) Positioning of two 8 × 8 ³¹P-MRS CSI grids. The isotropic voxel size was (25 mm)³ in the coronal, transversal, and sagittal view. The signals exploited were of ³¹P-MRS PCr, ATP-β, and Pi. (C) Positioning of two single voxel ¹H-MR-spectroscopy (PRESS) voxels each (25 mm)³. The signals of total creatine (tCr) and glutamate (Glu) were evaluated.

Figure 2

(A) PCr/Pi and ATP-ß/³¹P levels in averaged middle and upper grid voxels of the left and right hemisphere after placebo or creatine treatment at measurement time points 6 p.m., 0 p.m., 2 a.m., and 4 a.m. * = p ≤ 0.05 indicates significant differences. (B) Changes referenced to baseline (6 p.m.) in ATP-ß/³¹P in averaged voxels after placebo or creatine treatment at measurement time points 0 p.m., 2 a.m., and 4 a.m. * = p ≤ 0.05 indicates significant differences, ** = p ≤ 0.005 indicates significant differences withstanding the Bonferroni correction.

Figure 3

(A) Changes versus baseline (6 p.m.) in middle and upper grid voxels in PCr/Pi (large arrows) and ATP-ß/³¹P (small arrows) versus contralateral hemisphere after placebo or creatine administration pooled at 0 a.m., 2 a.m., and 4 a.m. Significance levels are color-coded. The illustration is in radiological orientation (the right side of the brain is on the left side of the viewer). Changes withstanding the Bonferroni correction are colored in red, those withstanding the Benjamini Hochberg correction are in dark red. (B) Positive correlations in baseline-related increases of PCr/PI in voxel versus contralateral regions and improvements in cognitive performance when pooled at three time points (0 p.m., 2 a.m., and 4 a.m.), withstanding the Bonferroni corrections.

Figure 4

Baseline-related (6 p.m.) changes in white matter (WM) and gray matter (GM) in PCr/Pi after placebo or creatine administration in (A) averaged middle and upper grids and in (B) gray versus white matter in voxels pooled at three time points (0 a.m., 2 a.m., and 4 a.m.). PCr/Pi (gray arrow) decreases significantly more than white matter, withstanding the Bonferroni correction.