How Circadian Rhythms Influence Our Brains & Cognitive Behavior

Have you ever wondered why you are mentally sharper at certain times of day?  

Why some people hit the gym at 6:00am and others tell you they never go to sleep before midnight and prefer to sleep in until 10:00am or 11:00am?

Why is it that some people love mornings, while others hate getting up?

Circadian preference or “chronotype” is used by researchers to describe a person’s physical and behavioral preference for earlier or later sleep timing because of the union between internal circadian cycles and the need for sleep⁽¹⁾.

Early risers are called “larks” and are more active in the morning, while those that sleep later and remain active past midnight are called “owls.”

These mentally sharp times of the day can be characterized as “in the zone” and are considered our most productive hours of the day. These times are different for everyone and are related to our circadian rhythms which show significant variation within humans.

They are essentially basic, daily cyclical processes that affect a wide range of physiological and behavioral manifestations. Research in the last two decades was primarily dedicated to molecular and cellular links between circadian rhythms and physiological processes in humans⁽²⁾.

Recent research has broadened to fields such as genetics, brain physiology, and cognition.

The technological advances in human cognitive neuroscience have renewed the interest of circadian rhythm effects on human brain physiology and cognition.

The modern lifestyle is becoming less dependent on the 24 hour day-night cycle, therefore the enhanced understanding of how the human brain and cognitive functions are influenced by chronotype and optimal time of day has wide-ranging implications for human well-being, public health, working environments, school performance, and disease-related pathophysiology⁽³⁾.
 
A recent study was the first to systematically investigate the modulatory impact of chronotype and time of day on cortical excitability and stimulation-induced neuroplasticity in the model of the human motor cortex.

Researchers explored how chronotype is associated with performance on a motor learning task which is associated with motor cortical plasticity.

They finally investigated the association of chronotype with higher-order cognitive functions that are dependent on cortical excitability and usually controlled by non-motor areas such as the prefrontal cortex.

In all behavioral tasks, electroencephalography (EEG) was recorded to further explore electrophysiological correlates of cognition under different chronotypes and times of the day. All measurements were conducted on two groups of “early chronotypes” (i.e., morning type), and “late chronotypes” (i.e., evening-types) at two fixed times in the morning and evening to capture circadian peaks and troughs at participants’ circadian-preferred and non-preferred times⁽⁴⁾.

This studies main aim was to determine how human cognition and related brain physiology are modulated by chronotype.

This research indicates converging evidence of how chronotypes and time of day are associated with behavioral/cognitive performance of healthy individuals and demonstrate the physiological foundations of these effects by daytime-dependent cortical excitability, neuroplasticity, and brain information processing parameters.  

A specific causal effect of chronotype on these variables, however, cannot be concluded unless the confounding influence of sleep pressure is controlled for directly.

Fig A: A schematic illustration depicting the converging impact of chronotype on brain physiology, behavior, and cognition

The significantly higher cortical facilitation and lower cortical inhibition at the circadian-preferred time in both chronotypes argue for specific differences of cortical physiology mediated by chronotype and time of day. Specifically, results from this research indicate that at the circadian-preferred time, intracortical facilitation is enhanced predominantly by increased activity of glutamatergic synapses.

Conversely, cortical inhibition is significantly pronounced at the circadian non-preferred time presumably through enhanced GABAergic activation. Chronotype effects on brain physiology were not specifically addressed in previous research but this recent evidence demonstrates chronotype-specific modulation of cortical excitability⁽⁴⁾.  

This research proposes that a brain state of enhanced glutamatergic activity, and reduced GABAergic inhibition, as present at the circadian-preferred times of day for early and late chronotype, would facilitate plasticity induction presumably via the optimal intracellular calcium concentration which determines the plasticity zones (see figure below).

Fig B: Proposed mechanism of the neuroplasticity induction at circadian-preferred and non-preferred time based on the association between intracellular calcium concentration (x axis) and induction of tDCS-induced neuroplastic changes.

These findings are consistent with previous animal work that revealed a strong effect of the circadian clock on hippocampal plasticity and complement those of human studies that showed that plasticity response to a given paired-associative stimulation is regulated by circadian rhythms⁽⁵⁾.
 
Results of this work have specific implications for the field of human neurophysiology and cognitive neuroscience as well as broad implications for human behavior in healthy and clinical populations.

Results show that cortical excitability and neuroplasticity are strongly related to chronotype in humans.

Beyond genetic determinants, chronotype is dependent on social pressures and our modern lifestyle that is increasingly deviating from the 24-hour cycle. Given that chronotype has a clear effect on sleep timing, it is highly relevant for working and educational environments. Working at a circadian-antagonistic time can disrupt the circadian cycle and thereby the shift workers’ health⁽⁶⁾.

Learning materials and studying, which are dependent on learning, memory, and attention, can be hindered at circadian non-preferred times.

Beyond the interactions with general well-being and some neuropsychiatric conditions, circadian disruption is also linked to cardiometabolic disorders and the pathophysiology of neurodegenerative diseases (e.g., Parkinson’s and Alzheimer’s diseases) and should be considered in personalized medicine and timing of interventions for higher efficacy.

Despite the interindividual confounding effects due to sleep pressure that were not accounted for directly, these findings still show a strong association of chronotype with human brain physiology and cognition⁽⁴⁾.

The main takeaway is that both groups showed enhanced plasticity at specific times of the day congruent with their respective chronotype.
In support of the research above, recent work at Boston Children’s Hospital spelled out the relationship between circadian rhythms and the brain connections known as synapses. This is the first evidence to provide a cellular and molecular explanation for natural fluctuations over the day in alertness, cognition, and the ability to learn and remember⁽⁷⁾.

A “clock” protein called BMAL1 masterminds the timing of protein production in cells⁽⁸⁾.

Results of this research demonstrate that BMAL1 shows up at brain synapses at particular times of day, regulating the synapses’ ability to respond to changes in the environment and thereby enabling the brain to learn and encode memories.

Cognitive processes are highly energetically demanding and it is plausible that the brain takes advantage of our natural circadian rhythms to conserve energy for when it is needed⁽⁷⁾.

This study has focused almost exclusively on excitatory hippocampal neurons. However, BMAL1 is expressed in most brain cells which leaves open the question whether these findings are generalizable to other brain regions, other synaptic types, or modes of plasticity.  

Nonetheless, because disruption of synaptic plasticity and circadian rhythms are commonly implicated in schizophrenia, autism, and Alzheimer’s disease, targeting BMAL1 could represent a manageable therapeutic for mitigating circadian, synaptic, and cognitive dysfunction without disruption of the core circadian timekeeper⁽⁷⁾.

Summary

In summary, these results show an association of circadian preference with learning and cognition including memory formation and attentional functions as well as the brain physiology underlying these cognitive processes including cortical excitability, neuroplasticity, and electrophysiological correlates of cognitive processes.

Whether you are a “morning lark” or “night owl” it is clear from the research that it is important to optimize your particular “zone of productive hours” and schedule your mentally cognitive tasks during this period. 

On the other hand, working against your circadian rhythm will essentially result in lower cognitive performance and production.

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References:
    1.    Jones SE, Lane JM, Wood AR, et al: Genome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms. Nat Commun 10:343, 2019
    2.    Dibner C, Schibler U: Circadian timing of metabolism in animal models and humans. J Intern Med 277:513-27, 2015
    3.    Heyde I, Kiehn JT, Oster H: Mutual influence of sleep and circadian clocks on physiology and cognition. Free Radic Biol Med 119:8-16, 2018
    4.    Salehinejad MA, Wischnewski M, Ghanavati E, et al: Cognitive functions and underlying parameters of human brain physiology are associated with chronotype. Nat Commun 12:4672, 2021
    5.    Ridding MC, Ziemann U: Determinants of the induction of cortical plasticity by non-invasive brain stimulation in healthy subjects. J Physiol 588:2291-304, 2010
    6.    Abbott SM, Malkani RG, Zee PC: Circadian disruption and human health: A bidirectional relationship. Eur J Neurosci 51:567-583, 2020
    7.    Barone I, Gilette NM, Hawks-Mayer H, et al: Synaptic BMAL1 phosphorylation controls circadian hippocampal plasticity. Sci Adv 9:eadj1010, 2023
    8.    Lipton JO, Yuan ED, Boyle LM, et al: The Circadian Protein BMAL1 Regulates Translation in Response to S6K1-Mediated Phosphorylation. Cell 161:1138-1151, 2015