Boltzmann's Theorem Revisited: Inaccurate Time-to-Action Clocks in Affective Disorders.

Timely goal-oriented behavior is essential for survival and is shaped by experience. In this paper, a multileveled approach was employed, ranging from the polymorphic level through thermodynamic molecular, cellular, intracellular, extracellular, non-neuronal organelles and electrophysiological waves, attesting for signal variability. By adopting Boltzmann's theorem as a thermodynamic conceptualization of brain work, we found deviations from excitation-inhibition balance and wave decoupling, leading to wider signal variability in affective disorders compared to healthy individuals. Recent evidence shows that the overriding on-off design of clock genes paces the accuracy of the multilevel parallel sequencing clocks and that the accuracy of the time-to-action is more crucial for healthy behavioral reactions than their rapidity or delays. In affective disorders, the multilevel clocks run free and lack accuracy of responsivity to environmentally triggered time-to-action as the clock genes are not able to rescue mitochondria organelles from oxidative stress to produce environmentally-triggered energy that is required for the accurate time-to-action and maintenance of the thermodynamic equilibrium. This maintenance, in turn, is dependent on clock gene transcription of electron transporters, leading to higher signal variability and less signal accuracy in affective disorders. From a Boltzmannian thermodynamic and energy-production perspective, the option of reversibility to a healthier time-toaction, reducing entropy is implied. We employed logic gates to show deviations from healthy levelwise communication and the reversed conditions through compensations implying the role of nonneural cells and the extracellular matrix in return to excitation-inhibition balance and accuracy in the time-to-action signaling.