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The frontal cortex is involved in motor, cognitive, and affective brain functions. In humans, however, neuroanatomy-function mappings are predominantly derived from correlative neuroimaging studies. Hence, exactly which frontal domains causally mediate which function remains largely elusive. Herein, we leverage a strategy that allows for causal inference using invasive neuromodulation. Studying 394 subthalamic deep brain stimulation electrodes in patients suffering from one of four brain disorders, we segregated the frontal cortex into cortical projection sites of modulated circuits by their involvement in specific functions. Modulating projections from sensory and motor cortices in dystonia, from primary motor cortex in Tourette’s syndrome, from supplementary motor cortex in Parkinson’s disease, and from ventromedial prefrontal, anterior cingulate, dorsolateral prefrontal and orbitofrontal cortices in obsessive-compulsive disorder linked to respective symptom improvements. Our findings showcase the combination of deep brain stimulation and brain connectomics as a tool for causal inference on structure-function mappings within the human brain.