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

Sari Goldstein Ferber, Aron Weller, Hermona Soreq

Research output: Contribution to journalArticlepeer-review


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 electrophysiologi-cal waves, attesting for signal variability. By adopting Boltzmann’s theorem as a thermodynamic con-ceptualization of brain work, we found deviations from excitation-inhibition balance and wave decou-pling, 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 equilib-rium. 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 Boltzmanni-an thermodynamic and energy-production perspective, the option of reversibility to a healthier time-to-action, reducing entropy is implied. We employed logic gates to show deviations from healthy level-wise communication and the reversed conditions through compensations implying the role of non-neural cells and the extracellular matrix in return to excitation-inhibition balance and accuracy in the time-to-action signaling.

Original languageEnglish
Pages (from-to)1762-1777
Number of pages16
JournalCurrent Neuropharmacology
Issue number11
Early online date18 Mar 2024
StatePublished - 2024

Bibliographical note

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© 2024 Bentham Science Publishers.


  • Biological clocks
  • boltzmann’s theorem
  • brain timescales
  • goal-oriented behavior
  • logic gates
  • psychopathology


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