AbstractIntroductionData‐driven approaches to transcranial magnetic stimulation (TMS) might yield more consistent and symptom‐specific results based on individualized functional connectivity analyses compared to previous traditional approaches due to more precise targeting. We provide a proof of concept for an agile target selection paradigm based on using connectomic methods that can be used to detect patient‐specific abnormal functional connectivity, guide treatment aimed at the most abnormal regions, and optimize the rapid development of new hypotheses for future study.MethodsWe used the resting‐state functional MRI data of 28 patients with medically refractory generalized anxiety disorder to perform agile target selection based on abnormal functional connectivity patterns between the Default Mode Network (DMN) and Central Executive Network (CEN). The most abnormal areas of connectivity within these regions were selected for subsequent targeted TMS treatment by a machine learning based on an anomalous functional connectivity detection matrix. Areas with mostly hyperconnectivity were stimulated with continuous theta burst stimulation and the converse with intermittent theta burst stimulation. An image‐guided accelerated theta burst stimulation paradigm was used for treatment.ResultsAreas 8Av and PGs demonstrated consistent abnormalities, particularly in the left hemisphere. Significant improvements were demonstrated in anxiety symptoms, and few, minor complications were reported (fatigue (n= 2) and headache (n= 1)).ConclusionsOur study suggests that a left‐lateralized DMN is likely the primary functional network disturbed in anxiety‐related disorders, which can be improved by identifying and targeting abnormal regions with a rapid, data‐driven, agile aTBS treatment on an individualized basis.