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The Khambhati Lab for Network Optimization and Therapeutics (KNOT Lab) studies the intricate threads that weave together to form the fabric of the human brain—unraveling how learning, plasticity, and network reorganization give rise to both resilience and dysfunction. We trace network architecture by combining neural recordings from implanted devices and neuroimaging with computational modeling and systems neuroscience. Our research investigates how targeted interventions—such as electrical stimulation and other perturbative approaches—can rethread these circuits to guide the brain toward healthier states. By crafting adaptive neurotechnologies that interface with the brain’s own patterns of activity, the KNOT Lab transforms mechanistic insight into precision tools for treating disorders of brain network connectivity and restoring function.