From Protocols to Personalization: Highlights from the Methods in Brain Stimulation Collection

Tad Brunye^1*Frigyes Samuel Racz²

• ¹Cognitive Science, Center for Applied Brain and Cognitive Sciences, School of Engineering, Tufts University, Medford, United States
• ²University of Texas, Austin, United States

Non-invasive brain stimulation (NIBS) research is expanding at a rapid pace, driven by the promise of reliably altering cognition, emotion, and motor behavior across research, clinical, and other applied domains. The recent proliferation of electrical, magnetic, photonic, and ultrasonic brain stimulation approaches demonstrates an evolution towards an increasingly versatile toolbox for researchers and clinicians. However, this rapid technological progress has often outpaced the establishment of best practices, standardized protocols, and mechanistic understandings. The Methods in Brain Stimulation research topic was launched to help fill this knowledge gap.There were eight contributions to this research topic, most of which showed a strong emphasis on expanding and refining stimulation methodologies to meet clinical and applied demands. Hanlon and colleagues present a comprehensive review of a two-stage bilateral deep transcranial magnetic stimulation (TMS) protocol for Parkinson's disease, combining motor and prefrontal cortical stimulation to address both motor and non-motor symptoms (Hanlon et al., 2024). Their findings highlight not only moderate therapeutic efficacy but also the need for further investigation into dosing and durability. In a parallel effort to map and systematize the field, Liu and colleagues offer a scientometric review of transcranial alternating current stimulation (tACS), tracking its rapid expansion over the past decade (Liu, Luo, et al., 2024). Their analysis charts global trends and underscores a rising interest in oscillatory entrainment and applications to neurodegenerative diseases such as Alzheimer's Disease. Together, these contributions underscore a growing maturity in both the therapeutic ambition and methodological precision of the brain stimulation field.Several contributions grapple directly with the challenge of optimization, including how to best configure stimulation parameters for reliable, domain-specific outcomes. Santander and colleagues conduct a sweeping meta-regression across five cognitive domains, identifying within-subjects designs as more reliable and pointing to nuanced effects of stimulation polarity (Santander et al., 2024). Duffy and colleagues complement this work by examining tDCS outcomes in active-duty Soldiers, illustrating not only enhancement of executive function and attention, but also potential tradeoffs such as increased risk-taking and reduced working memory, raising real-world implications for safety and mission readiness (Duffy et al., 2024). Toth and colleagues further contextualize these findings in their conceptual overview, emphasizing five critical methodological pursuits, from closed-loop systems to bias reduction and improved dose-response modeling (Toth et al., 2024). These works collectively advocate for more tailored, context-aware approaches to stimulation design and evaluation in order to reliably establish causal inferences between brain function, NIBS and behavioral outcomes.Importantly, precision and personalization emerge as central themes across multiple contributions to this research topic. Liu and colleagues compare functional-and structural-connectivity guided repetitive TMS targeting and find greater reproducibility with structural methods, providing key support for connectome-informed protocols (Liu, Sundman, et al., 2024). Van der Groen and colleagues reinforce the need for context-specific validation in their systematic review of electrical stimulation in military settings, highlighting variable effects and methodological inconsistencies across real-world tasks (van der Groen et al., 2025). Finally, Alipour and colleagues look beyond conventional methods, reviewing magnetothermal neuromodulation as a next-generation approach with high spatial precision and minimal invasiveness (Alipour et al., 2025). Their contribution widens the scope of this special issue by exploring the biophysical underpinnings and clinical promise of magnetic field-based techniques. Across these studies, we see a clear push toward greater specificity, safety, and scalability in brain stimulation methods. There is also an emergent call for, as well as laying the foundation for, a new era of individualized, mechanism-driven neuromodulation.Articles published in this research topic used diverse methodological approaches including scientometric mapping, meta-analysis, connectome-informed targeting, and dual-domain protocols. Notably, five out of eight publications are review or systematic review articles, providing a wide coverage and synthesis of contemporary NIBS literature. At least three themes emerged from these efforts.First, several contributions highlight an emergent shift from "one-size-fits-all" stimulation to personalized approaches. These include Liu and colleagues' connectome-based targeting work (Liu, Sundman, et al., 2024), Toth and colleagues' call for individualized protocols (Toth et al., 2024), and Santander and colleagues' meta-analytic evidence for domain-and design-specific effects (Santander et al., 2024). Second, there is a complementarity between conceptual and empirical work. The theoretical reflections of Toth and colleagues (Toth et al., 2024) complement the data-driven explorations in other articles (Duffy et al., 2024;Hanlon et al., 2024;Santander et al., 2024), providing context for understanding the complexity of dose-response relationships and interindividual variability. Third, there are common calls for increased standardization and replication.Multiple articles point to a lack of harmonized protocols, consistent outcome measures, and adequately powered samples that limit field-wide synthesis and result in slow progress (Liu, Luo, et al., 2024;Santander et al., 2024;van der Groen et al., 2025).Looking ahead, several priority directions emerge for advancing methods in brain stimulation research. These include:-Parameter optimization frameworks leveraging multivariate and adaptive modeling to finetune stimulation settings. -Standardized outcome metrics to enable cross-study comparisons of efficacy and safety across diverse domains and populations. -Closed-loop and adaptive systems that dynamically adjust stimulation based on neural or behavioral feedback. -Greater integration of neuroimaging, electrophysiology, and computational modeling to capture stimulation effects across spatial and temporal scales. -Population-and context-specific validation, especially for applied groups such as military personnel, clinical populations, and older adults. -Ethical and regulatory considerations and continued dialogue among researchers, clinicians, ethicists, and policy makers to guide responsible NIBS development and deployment. -Emphasis on establishing causal inferences between intervention and outcome by better understanding the neurobiological effects of various NIBS modalities.This research topic highlighted the importance of methodological innovation, transparency, and rigor in brain stimulation research. Together, the eight contributions offer empirical evidence, conceptual clarity, and forward-looking frameworks that will inform the next generation of NIBS efforts. As brain stimulation becomes increasingly integrated into research, clinical practice, and other professional and recreational applications, method-focused work such as this becomes vital to ensuring maximal benefits and minimal harm.