BACKGROUND:We aimed at evaluating the amplitude changes of the motor evoked potentials (MEPs) induced by of low-frequency (LF) repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) in10 patients with primary insomnia (PI) and in 10 age-matched healthy controls. METHODS:Median peak-to-peak MEP amplitudes were assessed in all subjects at three times: at baseline (T0), after the first train of a single rTMS session (T1), and after the whole rTMS procedure (T2). This consists of 20 trains of 1 Hz stimulation with 50 stimuli per train and an intertrain interval of 30 s. RESULTS:Resting motor threshold (RMT) and MEPs amplitude did not differ between the two groups at T0. A reduction of MEP size was observed at both T1 and T2 in all subjects, but this was significantly less pronounced in patients than in control subjects. CONCLUSIONS:The lack of MEP inhibition reflects an altered response to LF rTMS in patients with PI. These rTMS findings are indicative of an altered cortical plasticity in inhibitory circuits within M1 in PI. Subjects with PI exhibited an impairment of the LTD-like mechanisms induced by inhibitory rTMS, thus providing further support to the involvement of GABA neurotransmission in the pathophysiology of PI.