Our observations through intraoperative monitoring of spinal cord function during spine surgery guided us to test the potential role of cortico-spinal tract (CST) anomalies in the etiopathogenesis of idiopathic scoliosis (IS). CST function was assessed in awake IS and non-scoliotic (control) subjects by neurophysiological (single-pulse transcranial magnetic stimulation (TMS) of motor cortex) and functional (Complete Minnesota and Purdue Pegboard dexterity tests) approaches. The threshold intensity at which muscles are recruited by TMS can serve as an indirect measure of the density of innervation between CST axons and motoneurons of a given pool. TMS-evoked motor responses were recorded bilaterally (via surface electrodes) for several cervically (extensor carpi radialis, abductor pollicis brevis, and abductor digiti minimi) or subcervically (rectus abdominis, quadriceps femoris, and abductor hallucis) innervated muscles. In all subjects participating in our study, left-right (L-R) differencies in motor threshold (MT) were observed. In our 13 control subjects, large (>15%) asymmetries in MT were never seen, but occurred in 3 of our 11 (27%) IS subjects. The largest L-R asymmetries were revealed in subjects with Cobb angles higher than 40°. In addition, finger and hand dexterity was lower in IS subjects relative to controls. These findings suggest a different CST functional organization in IS, further underscoring the importance of neural factors in the etiopathogenesis of IS.