On the interplay between state-dependent reconfigurations of Global Signal Correlation and BOLD fluctuations: an fMRI study

Background: The dynamics of global, state-dependent reconfigurations in brain connectivity are yet unclear. We aimed at assessing reconfigurations of the global signal correlation coefficient (GSCORR), a measure of the connectivity between each voxel timeseries and the global signal, from resting-state to a stop-signal task. The secondary aim was to assess the relationship between GSCORR and blood-oxygen-level-dependent (BOLD) activations or deactivation across three different trial-conditions (GO, STOP-correct, and STOP-incorrect). Methods: As primary analysis we computed whole-brain, voxel-wise GSCORR during resting-state (GSCORR-rest) and stop-signal task (GSCORR-task) in 107 healthy subjects aged 21-50, deriving GSCORR-shift as GSCORR-task minus GSCORR-rest. GSCORR-tr and trGSCORR-shift were also computed on the task residual time series to quantify the impact of the task-related activity during the trials. To test the secondary aim, brain regions were firstly divided in one cluster showing significant task-related activation and one showing significant deactivation across the three trial conditions. Then, correlations between GSCORR-rest/task/shift and activation/deactivation in the two clusters were computed. As sensitivity analysis, GSCORR-shift was computed on the same sample after performing a global signal regression and GSCORR-rest/task/shift were correlated with the task performance. Results: Sensory and temporo-parietal regions exhibited a negative GSCORR-shift. Conversely, associative regions (ie. left lingual gyrus, bilateral dorsal posterior cingulate gyrus, cerebellum areas, thalamus, posterolateral parietal cortex) displayed a positive GSCORR-shift (FDR-corrected p<0.05). GSCORR-shift showed similar patterns to trGSCORR-shift (magnitude increased) and after global signal regression (magnitude decreased). Concerning BOLD changes, Brodmann area 6 and inferior parietal lobule showed activation, while posterior parietal lobule, cuneus, precuneus, middle frontal gyrus showed deactivation (FDR-corrected p<0.05). No correlations were found between GSCORR-rest/task/shift and beta-coefficients in the activation cluster, although negative correlations were observed between GSCORR-task and GO/STOP-correct deactivation (Pearson rho=-0.299/-0.273; Bonferroni-p<0.05). Weak associations between GSCORR and task performance were observed (uncorrected p<0.05). Conclusion: GSCORR state-dependent reconfiguration indicates a reallocation of functional resources to associative areas during stop-signal task. GSCORR, activation and deactivation may represent distinct proxies of brain states with specific neurofunctional relevance.