Focused Modulation of Brain Activity: A Narrative Review
Zhantleuova A. Karimova A. Andreou A.P. Kustubayeva A.M. Giniatullin R. Davletov B.
August 2025Multidisciplinary Digital Publishing Institute (MDPI)
Biomedicines
2025#13Issue 8
A wide range of strategies have been developed to modulate dysfunctional brain activities. This narrative review provides a comparative analysis of biophysical, genetic, and biological neuromodulation approaches with an emphasis on their known or unknown molecular targets and translational potential. The review incorporates data from both preclinical and clinical studies covering deep brain stimulation, transcranial electrical and magnetic stimulation, focused ultrasound, chemogenetics, optogenetics, magnetogenetics, and toxin-based neuromodulation. Each method was assessed based on specificity, safety, reversibility, and mechanistic clarity. Biophysical methods are widely used in clinical practice but often rely on empirical outcomes due to undefined molecular targets. Genetic tools offer cell-type precision in experimental systems but face translational barriers related to delivery and safety. Biological agents, such as botulinum neurotoxins, provide long-lasting yet reversible inhibition via well-characterized molecular pathways. However, they require stereotaxic injections and remain invasive. To overcome individual limitations and improve targeting, delivery, and efficacy, there is a growing interest in the synthesis of multiple approaches. This review highlights a critical gap in the mechanistic understanding of commonly used methods. Addressing this gap by identifying molecular targets may help to improve therapeutic precision. This concise review could be valuable for researchers looking to enter the evolving field of the neuromodulation of brain function.
chemogenetics , deep brain stimulation , focused ultrasound stimulation , magnetogenetics , neuromodulation , optogenetics , toxins , transcranial electrical stimulation , transcranial magnetic stimulation
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Department of Biophysics, Biomedicine and Neuroscience, Al-Farabi Kazakh National University, Almaty, A15E3C7, Kazakhstan
Headache Research, Wolfson Centre for Age-Related Diseases, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, SE1 1UL, United Kingdom
Neuresta, Inc., San Diego, 91991, CA, United States
A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, 80101, Finland
Department of Biomedical Science, University of Sheffield, Sheffield, S10 2JA, United Kingdom
Department of Biophysics
Headache Research
Neuresta
A.I. Virtanen Institute for Molecular Sciences
Department of Biomedical Science
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