The consequences of the new European reclassification of non-invasive brain stimulation devices and the medical device regulations pose an existential threat to research and treatment: An invited opinion paper.

A significant amount of European basic and clinical neuroscience research includes the use of transcranial magnetic stimulation (TMS) and low intensity transcranial electrical stimulation (tES), mainly transcranial direct current stimulation (tDCS). Two recent changes in the EU regulations, the introduction of the Medical Device Regulation (MDR) (2017/745) and the Annex XVI have caused significant problems and confusions in the brain stimulation field. The negative consequences of the MDR for non-invasive brain stimulation (NIBS) have been largely overlooked and until today, have not been consequently addressed by National Competent Authorities, local ethical committees, politicians and by the scientific communities. In addition, a rushed bureaucratic decision led to seemingly wrong classification of NIBS products without an intended medical purpose into the same risk group III as invasive stimulators. Overregulation is detrimental for any research and for future developments, therefore researchers, clinicians, industry, patient representatives and an ethicist were invited to contribute to this document with the aim of starting a constructive dialogue and enacting positive changes in the regulatory environment.

Limited output transcranial electrical stimulation 2023 (LOTES-2023): Updates on engineering principles, regulatory statutes, and industry standards for wellness, over-the-counter, or prescription devices with low risk.

The objective and scope of this Limited Output Transcranial Electrical Stimulation 2023 (LOTES-2023) guidance is to update the previous LOTES-2017 guidance. These documents should therefore be considered together. The LOTES provides a clearly articulated and transparent framework for the design of devices providing limited output (specified low-intensity range) transcranial electrical stimulation for a variety of intended uses. These guidelines can inform trial design and regulatory decisions, but most directly inform manufacturer activities - and hence were presented in LOTES-2017 as "Voluntary industry standard for compliance controlled limited output tES devices". In LOTES-2023 we emphasize that these standards are largely aligned across international standards and national regulations (including those in USA, EU, and South Korea), and so might be better understood as "Industry standards for compliance controlled limited output tES devices". LOTES-2023 is therefore updated to reflect a consensus among emerging international standards, as well as best available scientific evidence. "Warnings" and "Precautions" are updated to align with current biomedical evidence and applications. LOTES standards applied to a constrained device dose range, but within this dose range and for different use-cases, manufacturers are responsible to conduct device-specific risk management.

Digitalized transcranial electrical stimulation: A consensus statement.

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.

Using Remotely Supervised At-Home TES for Enhancing Mental Resilience.

We are in the midst of a mental health crisis with major depressive disorder being the most prevalent among mental health disorders and up to 30% of patients not responding to first-line treatments. Noninvasive Brain Stimulation (NIBS) techniques have proven to be effective in treating depression. However, there is a fundamental problem of scale. Currently, any type of NIBS treatment requires patients to repeatedly visit a clinic to receive brain stimulation by trained personnel. This is an often-insurmountable barrier to both patients and healthcare providers in terms of time and cost. In this perspective, we assess to what extent Transcranial Electrical Stimulation (TES) might be administered with remote supervision in order to address this scaling problem and enable neuroenhancement of mental resilience at home. Social, ethical, and technical challenges relating to hardware- and software-based solutions are discussed alongside the risks of stimulation under- or over-use. Solutions to provide users with a safe and transparent ongoing assessment of aptitude, tolerability, compliance, and/or misuse are proposed, including standardized training, eligibility screening, as well as compliance and side effects monitoring. Looking into the future, such neuroenhancement could be linked to prevention systems which combine home-use TES with digital sensor and mental monitoring technology to index decline in mental wellbeing and avoid relapse. Despite the described social, ethical legal, and technical challenges, the combination of remotely supervised, at-home TES setups with dedicated artificial intelligence systems could be a powerful weapon to combat the mental health crisis by bringing personalized medicine into people's homes.

Applying the neuroscience of creativity to creativity training.

This article investigates how neuroscience in general, and neuroscience of creativity in particular, can be used in teaching "applied creativity" and the usefulness of this approach to creativity training. The article is based on empirical data and our experiences from the Applied NeuroCreativity (ANC) program, taught at business schools in Denmark and Canada. In line with previous studies of successful creativity training programs the ANC participants are first introduced to cognitive concepts of creativity, before applying these concepts to a relevant real world creative problem. The novelty in the ANC program is that the conceptualization of creativity is built on neuroscience, and a crucial aspect of the course is giving the students a thorough understanding of the neuroscience of creativity. Previous studies have reported that the conceptualization of creativity used in such training is of major importance for the success of the training, and we believe that the neuroscience of creativity offers a novel conceptualization for creativity training. Here we present pre/post-training tests showing that ANC students gained more fluency in divergent thinking (a traditional measure of trait creativity) than those in highly similar courses without the neuroscience component, suggesting that principles from neuroscience can contribute effectively to creativity training and produce measurable results on creativity tests. The evidence presented indicates that the inclusion of neuroscience principles in a creativity course can in 8 weeks increase divergent thinking skills with an individual relative average of 28.5%.