Cerebral adenosine receptor availability after sleep deprivation is associated with specific dynamic connectivity states determined by resting state fMRI

Ziel/Aim Adenosine is a neuromodulator directly linked to the energy metabolism by ATP breakdown and a mediator of sleep homeostasis. The net effect of adenosine is inhibitory, reducing neuronal activity. Sleep deprivation leads to increased adenosine concentrations and A₁ adenosine receptor (A₁AR) availability. Functional connectivity is switching constantly between distinct states (dynamic connectivity). Sleep deprivation amplifies this temporal fluctuation. The objective of the current study was to investigate whether A₁AR availability in humans measured by PET is related to specific dynamic connectivity patterns induced by sleep deprivation, as determined by fMRI.

Methodik/Methods 12 volunteers (m, 26.9 ± 5.2 y) participated in a F-18 CPFPX bolus/infusions-PET with metabolite correction and a resting state fMRI, after 52 hours sleep deprivation and after 14 hours of recoverysleep. PET: distribution volumes (V_T) were calculate by tissue to plasma ratio during steady state. fMRI: 34 functional components were identified using an independent component analysis. A sliding window was used to calculate covariance metrics. Time spent in the specified connectivity states were determined. A₁AR availabilities were correlated with these dynamic functional connectivity state parameters.

Ergebnisse/Results Three transient brain network states were identified in the fMRI data of which one state was present only after sleep deprivation. The time spent in this state (#2) was significantly increased after recovery sleep whereas the connectivity pattern of another state was significantly reduced (#3). Correlational analysis between changes in A₁AR availability and time spent in these states revealed significant correlations for several brain regions including thalamus, hippocampus and striatum (r values in the range of −0.6-0.7).

Schlussfolgerungen/Conclusions Our findings suggest an individual functional relationship between A₁AR availability and the occurrence of specific dynamic functional connectivity brain states after sleep deprivation.