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journal article·2026-06-12Open access

Personalized Network‐Guided Neuromodulation Enhances Human Working Memory

Ahsan Khan, Hongming Li, Camille Blaine, Julie Grier, Ethan Hammett, Almaris Figueroa‐Gonzalez, Sarai Garcia, Romain Duprat, Justin Reber, Joseph Deluisi, Christos Davatzikos, Theodore D. Satterthwaite, Yong Fan, Desmond J. Oathes

Advanced Science
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Abstract

ABSTRACT The next frontier in cognitive neuromodulation is defined by personalized and adaptive protocols, necessitating approaches tailored to individual functional neuroanatomy and brain‐state fluctuations. Here, we introduce an adaptive neuromodulation framework that integrates individualized network targeting with real‐time decoding of brain states to precisely target working memory functional networks. Using concurrent transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI), we first mapped participant‐specific networks and identified personalized targets. A real‐time decoder then tracked stimulation‐evoked neural dynamics to empirically determine the optimal frequency (i.e., the best‐performing within a tested set of 5, 10, and 20 Hz) and a corresponding suboptimal frequency for each individual. In a multi‐session crossover study, only the optimal‐frequency stimulation significantly improved working memory, with the decoder's output predicting behavioral gains. A key finding is the substantial inter‐individual variability in the optimal frequency, providing evidence against the notion of a universal “best” frequency. Our results demonstrate that cognitive enhancement is governed by the precise interaction between stimulation target and frequency. This work provides a causal demonstration of personalized, network‐based neuromodulation and offers proof of concept for a generalizable, biomarker‐driven framework, representing a step toward advancing cognitive therapeutics. Trial Registration : This study is registered at ClinicalTrials.gov (identifier: NCT04402294).
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Research context

OpenAlex topics: Transcranial Magnetic Stimulation Studies · Neurological disorders and treatments · Functional Brain Connectivity Studies

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Center For Brain Imaging and Stimulation Department of Psychiatry Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USA

Center For Neuromodulation in Depression and Stress Department of Psychiatry Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USA

Department of Education and Psychology Academy of Wellness and Human Development Faculty of Arts and Social Sciences Hong Kong Baptist University Kowloon Tong Hong Kong SAR China

Center For Biomedical Image Computing and Analytics Department of Radiology Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USA

Center for AI and Data Science for Integrated Diagnostics University of Pennsylvania Philadelphia PA USA

Lifespan Informatics & Neuroimaging Center Department of Psychiatry Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USA

Lifespan Brain Institute Children's Hospital of Philadelphia University of Pennsylvania Philadelphia Pennsylvania USA

Penn Brain Science Translation Innovation and Modulation Center University of Pennsylvania Philadelphia Pennsylvania USA

Departments of Neuroscience Bioengineering Neurology and Neurosurgery Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USA

Funding

National Institutes of Health · National Institute of Mental Health

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