Polarity- and valence-dependent effects of prefrontal transcranial direct current stimulation on heart rate variability and salivary cortisol

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Cardiovascular and cerebrovascular regulatory systems are vital control mechanisms responsible for guaranteeing homeostasis and are affected by respiration. This work proposes the investigation of cardiovascular and cerebrovascular control systems and the nonlinear influences of respiration on both regulations through joint symbolic analysis (JSA), conditioned or unconditioned on respiration. Interactions between cardiovascular and cerebrovascular regulatory systems were evaluated as well by performing correlation analysis between JSA indexes describing the two control systems. Heart period, systolic and mean arterial pressure, mean cerebral blood flow velocity and respiration were acquired on a beat-to-beat basis in 13 subjects experiencing recurrent syncope episodes (SYNC) and 13 healthy individuals (non-SYNC) in supine resting condition and during head-up tilt test at 60° (TILT). Results showed that JSA distinguished conditions and groups, whereas time domain parameters detected only the effect of TILT. Respiration affected cardiovascular and cerebrovascular regulatory systems in a nonlinear way and was able to modulate the interactions between the two control systems with different outcome in non-SYNC and SYNC groups, thus suggesting that the analysis of the impact of respiration on cardiovascular and cerebrovascular regulatory systems might improve our understanding of the mechanisms underpinning the development of postural-related syncope.

Dorsolateral prefrontal cortex (DLPFC) hypoactivity and subcortical hyperactivity have been associated to cognitive impairment for non-emotional ("cold") and emotional ("hot") working memory tasks in major depressive disorder (MDD). We investigated whether an increase of DLPFC activity using transcranial direct current stimulation (tDCS) would differently influence the performance in working memory tasks in depressed and healthy subjects. Forty young adult participants (20 with MDD and 20 healthy controls) were randomized to a single, sham-controlled, bifrontal (left anodal / right cathodal), 2mA, 30-min tDCS session in a parallel design. The n-back and the Internal Shift Task (IST) were used as proxies of cold and hot working memory performance, respectively. Active tDCS compared to sham promoted more accurate and faster responses to the n-back task for both patients and controls.Conversely, only patients presented an improvement in response times for the IST task. Our findings suggest that the mechanisms of tDCS in MDD involve modulation of both cold and hot working memory. We discuss these findings considering the modulatory top-down effects of tDCS on subcortical structures via prefrontal activation, and how spreading of activation might be different for healthy volunteers versus depressed patients. We also discuss the role of tDCS in cognitive amelioration for depressed patients. Finally, the distinct effects of tDCS in the "hot" cognition task for healthy and depressed participants are indicative that tDCS outcomes are also regulated by differences in baseline activity of the stimulated network. KeywordsTranscranial direct current stimulation; major depressive disorder; working memory; cognition. 4 List of abbreviationsMajor depressive disorder (MDD); dorsolateral prefrontal cortex (DLPFC); transcranial direct current stimulation (tDCS); Internal Shift Task (IST); Mini International Neuropsychiatric Interview (MINI); Hamilton Depression Rating Scale (HDRS); analyses of variance (ANOVAs); response times (RTs); standard deviation (SD). HighlightsMDD patients present non-emotional and emotional working memory impairment.The DLPFC is associated with MDD and cognitive deficits.We used tDCS to acutely increase DLPFC activity in MDD and controls.MDD patients presented improvement in emotional and non-emotional cognition.We discuss pathophysiological mechanisms and clinical implications of our findings. 5