The role of circadian preferred time of day and sleep pressure in tDCS-induced neuroplasticity and associated cognition

Symposium title: Variability in transcranial electrical stimulation. results: The role of circadian factors, aging, anatomical difference, and stimulation parameters Symposium description: The use of transcranial electrical stimulation (tES) has exponentially grown in the last decade. While promises are held, null and unexpected results at neurophysiological and behavioral levels raised questions about the application of these techniques. On the other hand, there are still many uninvestigated intrinsic and external (methodological) factors that contribute to the variability of tES effects, some of which have just recently been studied. Physiological/arousal states under circadian rhythm and sleep pressure, and individual cortical geometry and the resultant electrical field are among the intrinsic factors. Aging and stimulation parameters are among the external or methodological factors. The impact of these factors is recently studied and this symposium aims to provide the latest results on the contribution of these factors to the variability of tES, specifically tDCS results. The first talk addresses the question of how circadian-preferred time of the day and sleep deprivation, which affect arousal/physiological states, modulate inducibility of LTP/LTD-like plasticity via tDCS, associated behavioral performance (e.g. motor learning) and cortical excitability pattern. Using a computational and imaging approach, The second talk addresses how interindividual variability in the aging brain, which undergoes structural decline, affects dosing parameters and induced electrical field via tES. Considering variability, especially in cognitive effects of tES, the next talk addresses interindividual variability in electrical stimulation of the dorsolateral prefrontal cortex (DLPFC) and discusses how the commonly applied tES protocols for DLPFC can or can not modulate the target region. The last talk discusses systematic investigation of stimulation polarity (anodal vs cathodal) and target region (frontal vs parital), as two important stimulation parameters, in cognitive effects of tES in depression. In sum, this symposium addresses some timely questions about tES variability and aims to emphasize optimizing and individualizing tES protocols by controlling these factors and/or taking them into account. Abstract Circadian rhythms have natural relative variations among humans known as chronotype or being a morning or evening person with specific physiological and behavioural manifestation. Sleep a ubiquitous physiological phenomenon, has extensive impacts on brain physiology and especially on parameters relevant to cognition such as brain excitability and plasticity too. We systematically investigated the impact of circadian preference and sleep deprivation on tDCS induced LTP/LTD like plasticity, intracortical facilitation/inhibition and associated cognitive functions (motor learning). In the experiment one, we (a) monitored motor cortical excitability, (b) tDCS-induced neuroplasticity, and (c) motor learning at circadian-preferred and non-preferred times of day in 32 evening-types (n=16) or morning types (n=16). In the second experiment we examined how overnight sleep deprivation vs overnight sufficient sleep affects (a) cortical excitability, measured by transcranial magnetic stimulation, (b) inducibility of LTP/LTD-like plasticity via tDCS, and (c) motor learning. We found a significantly larger induced LTP/LTD-like plasticity after anodal and cathodal tDCS and reduced intracortical inhibition when participants were at their circadian-preferred time of day and this was associated with improved motor learning at behavioral and electrophysiological level. One night sleep-deprivation, on the other hand, led to hyperexcitability of the brain and abolished tDCS-induced LTP-like plasticity after anodal tDCS while converted the inhibitory LTD-like plasticity after cathodal tDCS to excitatory LTP-like plasticity. This was associated with impaired motor learning as well. These data show that time of day and sleep pressure have huge impact of tDCS/TMS results and associated cognition functions and therefore should be controlled for or taken into account in tES research. The findings have implications for variability and optimal application of noninvasive brain stimulation. Research Category and Technology and Methods Basic Research: 9. Transcranial Direct Current Stimulation (tDCS) Keywords: Circadian rhythms, SLEEP, tDCS, variability