It’s About Time: The Circadian Network as Time-Keeper for Cognitive Functioning, Locomotor Activity and Mental Health

Abstract

A variety of organisms including mammals have evolved a 24h, self-sustained timekeeping machinery known as the circadian clock (biological clock), which enables to anticipate, respond, and adapt to environmental influences such as the daily light and dark cycles. Proper functioning of the clock plays a pivotal role in the temporal regulation of a wide range of cellular, physiological, and behavioural processes. The disruption of circadian rhythms was found to be associated with the onset and progression of several pathologies including sleep and mental disorders, cancer, and neurodegeneration. Thus, the role of the circadian clock in health and disease, and its clinical applications, have gained increasing attention, but the exact mechanisms underlying temporal regulation require further work and the integration of evidence from different research fields. In this review, we address the current knowledge regarding the functioning of molecular circuits as generators of circadian rhythms and the essential role of circadian synchrony in a healthy organism. In particular, we discuss the role of circadian regulation in the context of behaviour and cognitive functioning, delineating how the loss of this tight interplay is linked to pathological development with a focus on mental disorders and neurodegeneration. We further describe emerging new aspects on the link between the circadian clock and physical exercise-induced cognitive functioning, and its current usage as circadian activator with a positive impact in delaying the progression of certain pathologies including neurodegeneration and brain-related disorders. Finally, we discuss recent epidemiological evidence pointing to an important role of the circadian clock in mental health.

Skeletal muscle gene expression dysregulation in long-term spaceflights and aging is clock-dependent

“…To remain aligned with the external environment, the clock must be daily re-adjusted, which can be achieved via external time cues known as Zeitgebers 14 . Light is the dominant environmental cue for the SCN and light therapy is reported to improve the sleep quality among patients with neurodegenerative disorders 15,16 , to decrease fatigue symptoms among cancer patients 17,18 , and to improve circadian misalignment in Space 19,20 . Besides light, the circadian system is also sensitive to other Zeitgebers related to meal timing (e.g., fasting and caloric restriction 21 ) or to physical exercise [22][23][24] .…”

Gene Signatures Associated with Temporal Rhythm as Diagnostic Markers of Major Depressive Disorder and Their Role in Immune Infiltration

“…Dysregulation of TR is associated with numerous neurodegenerative and mental disorders [ 9 , 16 ]. MDD is a severe, chronic, and highly prevalent disease with a high incidence that affects 120 million people worldwide.…”

“…It is a ubiquitous mechanism used by organisms to coordinate endogenous biochemical processes with the ambient environment [ 6 ]. Temporal rhythms (TR) govern almost every aspect of biology [ 7 , 8 , 9 ], and disruptions in TR are associated with human morbidities including cancer, sleep [ 10 ], mental disorders [ 11 ], and neurodegeneration [ 7 , 12 ]. Accumulating evidence has revealed a correlation between transcription factor (TF) and the pathogenesis of MDD.…”

The role of the cerebellum in internet gaming disorder—A systematic review

“…However, this perspective shifted with increasing numbers of reports of co‐existing motor and nonmotor cognitive impairments in patients with cerebellar lesions (e.g., 2,3 ). In recent years, many studies have corroborated the cerebellum's role in a variety of cognitive and affective functions such as working memory, 4–6 language and verbal fluency, 7,8 error and feedback processing, 9–11 performance monitoring in general, 12 emotion regulation, 13 visual attention, 14 executive control 15 and in circadian rhythmicity 16 . Interestingly, findings also suggest that the cerebellum is involved in drug craving 17 and addiction 18 .…”

“…In recent years, many studies have corroborated the cerebellum's role in a variety of cognitive and affective functions such as working memory, [4][5][6] language and verbal fluency, 7,8 error and feedback processing, [9][10][11] performance monitoring in general, 12 emotion regulation, 13 visual attention, 14 executive control 15 and in circadian rhythmicity. 16 Interestingly, findings also suggest that the cerebellum is involved in drug craving 17 and addiction. 18 Neuroimaging studies have discovered cerebellar activations when participants are craving following the presentation of drug-related cues.…”