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Potential Scalp Stimulation Targets for Mental Disorders

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Potential Scalp Stimulation Targets for Mental Disorders Cao et al. J Transl Med (2021) 19:343 https://doi.org/10.1186/s12967-021-02993-1 Journal of Translational Medicine RESEARCH Open Access Potential scalp stimulation targets for mental disorders: evidence from neuroimaging studies Jin Cao, Thalia Celeste Chai‑Zhang, Yiting Huang, Maya Nicole Eshel and Jian Kong* Abstract Mental disorders widely contribute to the modern global disease burden, creating a signifcant need for improvement of treatments. Scalp stimulation methods (such as scalp acupuncture and transcranial electrical stimulation) have shown promising results in relieving psychiatric symptoms. However, neuroimaging fndings haven’t been well‑ integrated into scalp stimulation treatments. Identifying surface brain regions associated with mental disorders would expand target selection and the potential for these interventions as treatments for mental disorders. In this study, we performed large‑scale meta‑analyses separately on eight common mental disorders: attention defcit hyperactivity disorder, anxiety disorder, autism spectrum disorder, bipolar disorder, compulsive disorder, major depression, post‑ traumatic stress disorder and schizophrenia; utilizing modern neuroimaging literature to summarize disorder‑asso‑ ciated surface brain regions, and proposed neuroimaging‑based target protocols. We found that the medial frontal gyrus, the supplementary motor area, and the dorsal lateral prefrontal cortex are commonly involved in the patho‑ physiology of mental disorders. The target protocols we proposed may provide new brain targets for scalp stimulation in the treatment of mental disorders, and facilitate its clinical application. Keywords: Neuroimaging, Meta‑analysis, Scalp stimulation, Scalp acupuncture, Transcranial electrical stimulation, Mental disorder Introduction For instance, scalp acupuncture, a modern school of Mental disorders are a major component of the modern acupuncture developed on the basis of anatomical and global disease burden. However, the quality of the thera- neurophysiological knowledge [1], may be considered as peutic outcomes of pharmacologic treatments for mental an early scalp stimulation treatment. Scalp acupuncture disorders is ambiguous due to their side efects, with- aims to modulate certain brain areas, thereby providing drawal symptoms, and risk of abuse. Tus, increasing therapeutic benefts for a wide scope of diseases through attention has been given towards non-pharmacological the stimulation of specifc scalp areas corresponding to interventions over recent years. certain cortical areas. Scalp acupuncture may be applied Recently, scalp stimulation methods, i.e., applying tran- by manual stimulation or electrical stimulation (similar scranial stimulation on the scalp to modulate the func- to transcranial alternating current stimulation [tACS]). tion of corresponding brain areas to relive symptoms, Accumulating evidence has demonstrated the potential have drawn increased attention of investigators. Scalp of scalp acupuncture in relieving symptoms of mental stimulation methods may include many diferent current disorders [2, 3]. treatments. Nevertheless, current prescriptions of scalp acu- puncture for varying disorders are mainly based on an understanding of brain functions from the 1970s, *Correspondence: [email protected] when the practice was frst introduced. In recent dec- Department of Psychiatry, Massachusetts General Hospital, Harvard ades, there has been remarkable progress made in Medical School, Charlestown, MA 02129, USA © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco mmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Cao et al. J Transl Med (2021) 19:343 Page 2 of 28 understanding the neural circuitry of mental disorders Tus, with the aid of Neurosynth, this study aims to through cutting-edge brain imaging techniques [4–6]. develop neuroimaging-based target protocols for eight Unfortunately, these advances have yet to be incor- common mental disorders (attention defcit hyperactiv- porated into scalp acupuncture treatments for mental ity disorder (ADHD), anxiety disorder, autism spectrum disorders. disorder (ASD), bipolar disorder, compulsive disorder, Modern brain stimulation methods such as transcra- major depression, post-traumatic stress disorder (PTSD) nial electrical stimulation (tES) may also be considered and schizophrenia) for tES, scalp acupuncture, repeti- scalp stimulation methods. For example, transcranial tive transcranial magnetic stimulation (rTMS) [9, 14, 16], direct current stimulation (tDCS), a form of tES, is based focused ultrasound (FUS) [17] and other brain stimula- on the application of a weak, direct electric current deliv- tion methods when applicable. Specifcally, we frst used ered over the scalp to induce polarity dependent changes Neurosynth to generate large-scale meta-analyses for the in cortical excitability (anodal and cathodal stimulation above eight mental disorders. Ten, we further refned/ induce increasing and decreasing cortical excitability, simplifed the fndings from the neuroimaging analyses, respectively), and has shown promising results in amelio- and proposed neuroimaging-based scalp stimulation rating the symptoms of mental disorders [7–9]. Another target protocol for each disorder to facilitate its clinical method, transcranial alternating current stimulation application. We hypothesize that diferent mental disor- (tACS), a diferent form of tES, can modulate the rhythms ders will be associated with distinguishable scalp stimula- of endogenous oscillations by applying weak alternating tion targets, although there may be common/overlapping current through the scalp, and has also demonstrated targets across diferent disorders. potential in alleviating anxiety, depression, compulsive disorders, etc. [10–12]. Methods Literature suggests that multiple brain regions/net- To identify disorder-associated brain regions, we used works are involved in the pathophysiology of mental dis- Neurosynth (http:// neuro synth. org/: acces sed21 Septe orders. Yet as of current date, many tES studies have only mber2 020) as a metadata reference for neuroimaging used the prefrontal cortex as the target area for stimula- literature. In this study, we applied a Bayesian reverse tion [13, 14]. Identifying other brain regions associated inference term-based meta-analytic approach from Neu- with mental disorders (particularly among surface brain rosynth that extracted data from all published neuroim- areas which are suitable for tES) would expand target aging studies included in the Neurosynth database. Tis selection and may represent a crucial step to increasing method is diferent from the classic forward inference the potential for neuromodulation techniques as treat- that selected voxels for inclusion in a given map based on ment for mental disorders. their positive association with each mental disorder, and In recent decades, the development of brain neuroim- instead also included all negative fndings thus allowing aging techniques has spurred rapid growth of literature for greater specifcity [15]. Under the search string “disor- on human brain imaging studies of mental disorders der name” (i.e., search strings “ADHD”, “anxiety disorder”, and has signifcantly advanced our understanding of the “autism spectrum”, “bipolar disorder”, “compulsive disor- complex brain pathophysiology associated with these dis- der”, “major depression”, “PTSD”, and “schizophrenia”), orders. However, the rich literature also introduces new neuroimaging studies were identifed, and a uniformity challenges, i.e., we are now burdened with an excess of test map was generated to identify disorder-associated data to work through. It has therefore become necessary brain regions. Complete lists of the studies included for to develop new techniques for the large-scale aggregation each disorder extracted from Neurosynth can be found in and synthesis of human neuroimaging data [15]. Additional fle 1: Tables S1–S8. Neurosynth is a new brain mapping framework that Since scalp stimulations such as scalp acupuncture can incorporate text-mining, meta-analysis and machine- and tES will predominantly infuence the surface brain learning techniques to generate probabilistic mappings areas, similar to our previous studies [18–21], a brain between mental disorders and neural states that can be surface cortical mask was created using the SPM Wake used for a broad range of neuroimaging applications Forest University (WFU) PickAtlas toolbox (http:// fmri. and generate large-scale meta-analyses for hundreds of wfubmc.
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