A review of acute aerobic exercise and transcranial direct current stimulation effects on cognitive functions and their potential synergies

Today, several pharmaceutic and non-pharmaceutic approaches exist to treat psychiatric and neurological diseases. Because of the lack of treatment procedures that are medication free and the lack of severe side effects, transcranial direct current stimulation (tDCS) and aerobic exercise (AE) have been tested to explore the potential for initiating and modulating neuroplasticity in the human brain. Both tDCS and AE could support cognition and behavior in the clinical and non-clinical context to improve the recovery process within neurological or psychiatric conditions or to increase performance. As these techniques still lack meaningful effects, although they provide multiple beneficial opportunities within disease and health applications, there is emerging interest to find improved tDCS and AE protocols. Since multimodal approaches could provoke synergetic effects, several recent studies have begun to combine tDCS and AE within different settings such as in cognitive training in health or for treatment purposes within clinical settings, all of which show superior effects compared to single technique applications. The beneficial outcomes of both techniques depend on several parameters and the understanding of neural mechanisms that are not yet fully understood. Recent studies have begun to directly combine tDCS and AE within one session, although their interactions on the behavioral, neurophysiological and neurochemical levels are entirely unclear. Therefore, this review a) provides an overview of acute behavioral, neurophysiological, and neurochemical effects that both techniques provoke within only one single application in isolation; b) gives an overview regarding the mechanistic pathways; and c) discusses potential interactions and synergies between tDCS and AE that might be provoked when directly combining both techniques. From this literature review focusing primarily on the cognitive domain in term of specific executive functions (inhibition, updating, and switching), it is concluded that a direct combination of tDCS and AE provides multiple beneficial opportunities for synergistic effects. A combination could be useful within non-clinical settings in health and for treating several psychiatric and neurologic conditions. However, there is a lack of research and there are several possibly interacting moderating parameters that must be considered and more importantly must be systematically investigated in the future

Does Anodal tDCS Over the Left Prefrontal Cortex Using the C3-RSO Montage Improve Cognitive Control?

Executive function is the ability to change one’s behavior in order to achieve a goal, which is supported by the prefrontal cortex (for review, Abdullah et al., 2021). Transcranial Direct Current Stimulation (tDCS) is a noninvasive brain stimulation technique that changes the likelihood of neuronal firing by sending current through at least two electrodes on the scalp. Prior work in our lab found no enhancement of executive function on healthy participants when at- tempting to stimulate the dorsolateral prefrontal cortex using anodal tDCS with the F3-RSO montage (Darling et al., 2020). However, current modeling suggests that the C3-RSO montage may be more likely to stimulate dorsolateral prefrontal cortex (Datta et al., 2012). Therefore we examine whether using the C3-RSO montage to target the prefrontal cortex could enhance executive function in healthy participants

Investigation of brain networks for personalized rTMS in healthy subjects and patients with major depressive disorder: A translational study

Depression is a complex psychiatric disorder with emotional dysregulation at its core. The first line of treatment includes cognitive behaviour therapy and pharmacological antidepressants. However, up to one third of patients with depression fail to respond to these treatment interventions. The past decades have seen an increasing use of repetitive Transcranial Magnetic Stimulation (rTMS) in clinical studies, as an alternative treatment for depression. Several large-scale, multicentre randomized controlled trials have led the Food and Drugs Administration (FDA), USA to approve two rTMS protocols for clinical application in the treatment of depression - 10 Hz rTMS and intermittent Theta Burst Stimulation (iTBS). However, only 30-50% of patients receiving rTMS respond to the treatment. The large variability in response to rTMS likely stems from multiple reasons, one being the targeting method currently employed for delivering rTMS at the left dorsolateral prefrontal cortex (DLPFC). Previous functional connectivity studies have shown that stimulation at left DLPFC targets with larger negative correlation to the subgenual anterior cingulate cortex (sgACC) may result in greater therapeutic response than those with lower negative correlation. However, current use of rTMS ignores functional connectivity in choosing the left DLPFC target, thus largely discarding functional architectural differences of the brain across subjects. Furthermore, despite widespread clinical use of rTMS, the basic network mechanisms behind these rTMS protocols remain elusive. This work presents a novel personalization method of left DLPFC target selection based on their negative functional connectivity to the sgACC. The default mode network (DMN) is a large-scale brain network commonly involved in self-referential thought processing and plays an essential role in the pathophysiology of depression. I use the novel personalization method and identical study designs to delineate DMN mechanisms from a single session of 10 Hz rTMS and iTBS in healthy subjects. Arguably, an understanding of basic mechanisms of clinically relevant rTMS protocols in healthy subjects will help improve the current therapeutic effect of rTMS, and possibly expand the therapeutic role of rTMS. My work shows, for the first time, strong but different modulations of DMN connectivity by single personalized sessions of 10 Hz rTMS and iTBS. Such modulations can be predicted using the personality trait harm avoidance (HA). Given that initial results show that the method is robust and reproducible, its adaptation to patient cohorts is likely to result in improved therapeutic benefits. Therefore, the novel method of personalization is translated to clinical setting by using accelerated iTBS (aiTBS) in patients with depression. Additionally, a comparison is made between effects resulting from personalized and nonpersonalized (10-20 EEG system F3 position) aiTBS in patients with depression. By evaluating the DMN, and heart rate variability, I show precise modulatory effects of personalized aiTBS, which is not seen in the standard aiTBS group. The work presented here introduces an important method to reduce variability and increase precision in rTMS modulation by personalizing the left DLPFC target selection. Even though DMN and cardiac effects already point towards the advantage of personalization, the still preliminary analysis fails to show significant differences in treatment response. Lack of greater therapeutic benefits viii from personalized aiTBS in this ongoing study probably stems from a still limited sample size. In case personalization proves clinically advantageous to standard iTBS by the final sample size, this work can sediment the first step towards systems medicine in the field of psychiatry.2022-02-0

The clinical spectrum and pathophysiology of neuropathic tremor

This thesis describes a series of studies involving patients with neuropathies and healthy controls. In the studies of disease, two groups were recruited: patients with inflammatory neuropathies and those with hereditary neuropathies. Each group was separated into those with and those without tremor and compared with healthy controls. Clinical assessments and neurophysiological tests were employed to correlate cerebellar function with tremor. The final study of healthy participants investigated the effect of transcranial direct current stimulation (TDCS) on the cerebellum during finger tapping. 1) Tremor was most common in IgM paraproteinaemic neuropathies, also occurring in 58% of those with chronic inflammatory demyelinating polyradiculoneuropathy and 56% of those with multifocal motor neuropathy with conduction block (MMNCB). Tremor was generally refractory to treatment and contributed to disability in some patients. Although tremor severity correlated with F wave latency, it was insufficient to distinguish those with, from those without tremor. 2) Impaired eyeblink classical conditioning and paired associative stimulation in patients with inflammatory neuropathy and tremor differentiated them from neuropathy patients without tremor and healthy controls, strongly suggesting impairment of cerebellar function is linked to the production of tremor in these patients. 3) The prevalence study in CMT1A patients revealed tremor in 21% and in 42% of those it caused impairment. Eyeblink conditioning, visuomotor adaptation and electro-oculography were no different between tremulous and non-tremulous patients and healthy controls. This argues against a prominent role for an abnormal cerebellum in tremor generation in the patients studied. Rather, they suggest an enhancement of the central neurogenic component of physiological tremor as a possible mechanism. 4) TDCS of the lateral cerebellum and its effect on paced finger tapping was examined. There was no effect on accuracy or variability of the intertap interval, providing no support for a direct role of the cerebellum in event based timing