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

Ali Gordjinejad^1*Andreas Matusch¹Sophie Kleedörfer²Harshal Jayeshkumar Patel²Alexander Drzezga^1,3,4David Elmenhorst^1,3Ferdinand Binkofski²Andreas Bauer¹

• ¹Molecular Organization of the Brain (INM-2), Institute of Neuroscience and Medicine, Julich Research Center, Helmholtz Association of German Research Centres (HZ), Jülich, North Rhine-Westphalia, Germany
• ²Department of Clinical Cognitive Sciences, RWTH Aachen University, Aachen, North Rhine-Westphalia, Germany
• ³Department of Nuclear Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Germany., Cologne, Germany
• ⁴German Center for Neurodegenerative Diseases, Helmholtz Association of German Research Centers (HZ), Bonn, North Rhine-Westphalia, Germany

The human brain exhibits asymmetric hemispheric activity at night, which plays a crucial role in cognitive impairment during 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 hours) and performance of cognitive tests. In our new analysis, we investigated differences and asymmetries in 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 by a higher response 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.