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Objective: Although relatively costly and non-scalable, non-invasive neuromodulation interventions are treatment alternatives for neuropsychiatric disorders. The recent developments of highly-deployable transcranial electric stimulation (tES) systems, combined with mobile-Health technologies, could be incorporated in digital trials to overcome methodological barriers and increase equity of access. The study aims are to discuss the implementation of tES digital trials by performing a systematic scoping review and strategic process mapping, evaluate methodological aspects of tES digital trial designs, and provide Delphi-based recommendations for implementing digital trials using tES., Methods: We convened 61 highly-productive specialists and contacted 8 tES companies to assess 71 issues related to tES digitalization readiness, and processes, barriers, advantages, and opportunities for implementing tES digital trials. Delphi-based recommendations (>60% agreement) were provided., Results: The main strengths/opportunities of tES were: (i) non-pharmacological nature (92% of agreement), safety of these techniques (80%), affordability (88%), and potential scalability (78%). As for weaknesses/threats, we listed insufficient supervision (76%) and unclear regulatory status (69%). Many issues related to methodological biases did not reach consensus. Device appraisal showed moderate digitalization readiness, with high safety and potential for trial implementation, but low connectivity., Conclusions: Panelists recognized the potential of tES for scalability, generalizability, and leverage of digital trials processes; with no consensus about aspects regarding methodological biases., Significance: We further propose and discuss a conceptual framework for exploiting shared aspects between mobile-Health tES technologies with digital trials methodology to drive future efforts for digitizing tES trials., (Copyright © 2022 International Federation of Clinical Neurophysiology. All rights reserved.)

Motor threshold (MT) measured by transcranial magnetic stimulation (TMS) has diagnostic utility in central nervous system disorders. Its diagnostic sensitivity may be enhanced by identification of non-pathological factors which may influence this measure. The aim of this study was to provide a description of MT variability across physiological and non-pathological behaviour characteristics in a large cohort, including hemispheric asymmetries. In a cross-sectional study, age, handedness, physical activity level, body mass index, gender/menstrual cycle phase, glycemic index and degree of stress were collected from 115 healthy participants. The resting MT of the first dorsal interosseous muscle to TMS was recorded in both hemispheres and served as an indicator of the cortical excitability level. Repeated measures ANOVAs revealed higher MT values in the non-dominant hemisphere, elderly people, stressed individuals and women with amenorrhea. Other biological and behavioral individual characteristics did not influence cortical excitability. Although the degree of interhemispheric difference varied (range: 0.2 to 4.3), depending on biological and behavioral characteristics, this variation was not significant (0.1 ≤ p ≤ 0.8). In conclusion, MT varied considerably between subjects. The difference between the hemisphere excitability that was less influenced by external factors, may be an alternative method of TMS measure to identify pathological changes of cortical excitability., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: The aims of this paper are (i) to compare the excitability of visual cortex in migraine patients with healthy volunteers; and (ii) if an abnormal excitability has been found, to modulate cortical excitability in migraine patients with transcranial direct current stimulation (tDCS) and observe their clinical and neurophysiological effects., Methods: The study was divided into two steps. A cross-sectional study (step 1) was conducted to compare the cortical excitability of 23 migraineurs (11 with and 12 without aura) on 11 healthy individuals. On step 2, a randomized, double blinded, controlled pilot trial was carried on with 19 migraineurs, randomly divided into: experimental and control group. During 12 sessions, experimental and group received active tDCS to visual cortex and control group received sham tDCS. The headache diary was applied for a total of 90days (before, during and after tDCS sessions). Phosphene threshold (PT) induced by transcranial magnetic stimulation was recorded to measure the excitability of the visual cortex before and after each session., Results: Step 1 showed higher level of cortical excitability between migraineurs when compared to healthy volunteers; therefore, cathodal tDCS was applied over visual cortex in step 2. After tDCS application, a significant decrease was observed in a number of migraine attacks, painkiller intake and duration of each attack just in experimental group. The analysis of PT indicated no difference in cortical excitability after tDCS., Conclusions: Findings of the study suggested that inhibitory tDCS on visual cortex might be an alternative and non-pharmacological treatment for migraine prophylaxis. However the clinical improvements of patients after tDCS treatment are not correlated with changes in cortical excitability., (Copyright © 2014. Published by Elsevier B.V.)

Background: Non-invasive brain stimulation enables the induction of neuroplasticity in humans, however, with so far restricted duration of the respective cortical excitability modifications. Conventional anodal transcranial direct current stimulation (tDCS) protocols including one stimulation session induce NMDA receptor-dependent excitability enhancements lasting for about 1 h., Objective: We aimed to extend the duration of tDCS effects by periodic stimulation, consisting of two stimulation sessions, since periodic stimulation protocols are able to induce neuroplastic excitability alterations stable for days or weeks, termed late phase long term potentiation (l-LTP), in animal slice preparations. Since both, l-LTP and long term memory formation, require gene expression and protein synthesis, and glutamatergic receptor activity modifications, l-LTP might be a candidate mechanism for the formation of long term memory., Methods: The impact of two consecutive tDCS sessions on cortical excitability was probed in the motor cortex of healthy humans, and compared to that of a single tDCS session. The second stimulation was applied without an interval (temporally contiguous tDCS), during the after-effects of the first stimulation (during after-effects; 3, or 20 min interval), or after the after-effects of the first stimulation had vanished (post after-effects; 3 or 24 h interval)., Results: The during after-effects condition resulted in an initially reduced, but then relevantly prolonged excitability enhancement, which was blocked by an NMDA receptor antagonist. The other conditions resulted in an abolishment, or a calcium channel-dependent reversal of neuroplasticity., Conclusion: Repeated tDCS within a specific time window is able to induce l-LTP-like plasticity in the human motor cortex., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: The brain-derived neurotrophic factor (BDNF) gene is involved in mechanisms of synaptic plasticity in the adult brain. It has been demonstrated that BDNF also plays a significant role in shaping externally induced human brain plasticity. Plasticity induced in the human motor cortex by intermittent theta-burst stimulation (iTBS) was impaired in individuals expressing the Val66Met polymorphism., Methods: To explore whether this polymorphism is also important for other neuroplasticity-inducing tools in humans with modes of action differing from that of iTBS, namely, transcranial direct current (tDCS) and random noise stimulation (tRNS), we retrospectively analyzed the data of 64 subjects studied in our laboratory with regard to BDNF genotype., Results: Fifteen subjects with the Val66Met allele, 46 subjects with the Val66Val allele, and 3 Met66Met carriers were identified. The response of the Val66Met allele carriers to stimulation differed in two protocols compared with the response of Val66Val individuals. For iTBS (15 subjects, 5 heterozygotes), plasticity could be only induced in the Val66Val allele carriers. However, for facilitatory tDCS (24 subjects, 10 heterozygotes), as well as for inhibitory tDCS, (19 subjects, 8 heterozygotes), carriers of the Val66Met allele displayed enhanced plasticity, whereas for transcranial random noise stimulation (29 subjects, 8 heterozygotes), the difference between groups was not so pronounced., Conclusions: BDNF polymorphism has a definite impact on plasticity in humans, which might differ according to the mechanism of plasticity induction. This impact of BDNF on plasticity should be taken into account for future studies, as well as having wider ranging implications for the treatment of neuropsychiatric disorders with transcranial stimulation tools, as it may predetermine their efficacy for the treatment of disease and rehabilitation., (Copyright © 2010 Elsevier Inc. All rights reserved.)