Testing Proposed Neuronal Models of Effective Connectivity Within the Cortico-basal Ganglia-thalamo-cortical Loop During Loss of Consciousness.

In recent years, a number of brain regions and connectivity patterns have been proposed to be crucial for loss and recovery of consciousness but have not been compared in detail. In a 3 T resting-state functional magnetic resonance imaging paradigm, we test the plausibility of these different neuronal models derived from theoretical and empirical knowledge. Specifically, we assess the fit of each model to the dynamic change in effective connectivity between specific cortical and subcortical regions at different consecutive levels of propofol-induced sedation by employing spectral dynamic causal modeling. Surprisingly, our findings indicate that proposed models of impaired consciousness do not fit the observed patterns of effective connectivity. Rather, the data show that loss of consciousness, at least in the context of propofol-induced sedation, is marked by a breakdown of corticopetal projections from the globus pallidus. Effective connectivity between the globus pallidus and the ventral posterior cingulate cortex, present during wakefulness, fades in the transition from lightly sedated to full loss of consciousness and returns gradually as consciousness recovers, thereby, demonstrating the dynamic shift in brain architecture of the posterior cingulate "hub" during changing states of consciousness. These findings highlight the functional role of a previously underappreciated direct pallido-cortical connectivity in supporting consciousness.