The development of non-invasive techniques of cortical stimulation, such as transcranial magnetic stimulation (TMS), has opened new potential avenues for the treatment of neuropsychiatric diseases. We hypothesized that an increase in the activity in the motor cortex by cortical stimulation would increase its inhibitory influence on spinal excitability through the corticospinal tract and, thus, reduce the hyperactivity of the gamma and alpha neurons, improving spasticity. Seventeen participants (eight males, nine females; mean age 9y 1mo [SD 3y 2mo]) with cerebral palsy and spastic quadriplegia were randomized to receive sham, active 1Hz, or active 5Hz repetitive TMS of the primary motor cortex. Stimulation was applied for 5 consecutive days (90% of motor threshold). The results showed that there was a significant reduction of spasticity after 5Hz, but not sham or 1Hz, stimulation as indexed by the degree of passive movement; however this was not evident when using the Ashworth scale, although a trend for improvement was seen for elbow movement. The safety evaluation showed that stimulation with either 1Hz or 5Hz did not result in any adverse events as compared with sham stimulation. Results of this trial provide initial evidence to support further trials exploring the use of cortical stimulation in the treatment of spasticity. Spasticity is a common symptom in neurological disorders. One of the causes of spasticity is motor cortex damage that leads to a decrease in the cortical input to the corticospinal tract, resulting in a disinhibition of spinal, segmental excitabili-ty and an increase in the muscle tone. 1 This increase in muscle tone is marked by a velocity-dependent enhancement of the stretch reflex. 2-4 The role of the motor cortex in the development of spastici-ty has been extensively demonstrated in primate studies. Specifically, ablation of Brodmann's area 4 in macaque monkeys results in persistent spasticity in addition to partial motor impairment, 5 and bilateral removal of Brodmann's areas 4, 6, and 8, as well as the posterior parietal cortex (area 7) in infant monkeys leads to development of spastic paraplegia. 6 In humans, patients undergoing surgery for intractable epilepsy revealed the development of spasticity in cases of extensive motor or premotor ablations. 7 Cerebral palsy (CP) is a common cause of spasticity. CP results from a permanent static lesion of the cerebral motor cortex that occurs before, at, or within 2 years of birth. 8 The loss of descending inhibitory input through corticospinal tracts results in an increase in the excitability of gamma and alpha neurons, resulting in spasticity. 9 Spasticity is an important contributor to the quality of life of patients with CP as it leads to musculoskeletal complications such as contractures, pain, and subluxation. 10 Furthermore, the elimination of spasticity brings motor function improvement for these patients. 10 Although many therapies to reduce and control spasticity are available, they are associated with several disadvantages, such ...