Brain Changes in Blepharospasm

Objectives This proposal will evaluate the role of an increase in excitability of the orbicularis oculi (OO) muscle representation in the medial frontal areas (supplementary motor areas, SMA) and anterior rostral cingulate: M3) in excessive blinking in patients with benign essential blepharospasm (BEB). We hypothesize that: 1. at rest, the decrease of the MEP after 15 minutes of 1Hz rTMS, targeting the SMA-M3, is more prominent in patients with BEP than in healthy control subjects, 2. at rest, the decrease of the MEP after 15 minutes of 1Hz rTMS targeting M1, is almost the same in patients with BEP and in healthy control subjects, 3. at rest, sICI of OO muscle will be decreased and ICF increased after stimulation of the SMA-M3 facial cortical area, in patients with BEP compared to healthy control subjects, 4. at rest sICI and ICF of the OO muscle will be the same after stimulation of the M1 facial area in patients with BEP and healthy control subjects, 5. in healthy control subjects facilitation of the MEPs evoked from M1 is more prominent during voluntary blinking, 6. in healthy control subjects facilitation of the MEP evoked from SMA-M3 is more prominent during involuntary blinking, 7. in patients with BEB there is facilitation of MEPs evoked from M1 and SMA-M3 during voluntary and involuntary blinking. 8. it is possible to evoke consistent and reproducible motor evoked responses (MEP) in the orbicularis oculi (OO) muscles by stimulating the two main cortical representations of upper facial region: in the medial frontal wall (SMA and cingulate cortex - its rostral part, M3) and in the primary motor cortex (M1) with transcranial magnetic stimulation (TMS). Study population 36 patients with BEB but without severe forceful closure of eyelids, 36 normal volunteers. Study design Subjects will have 3 visits: Visit 1: screening and blepharospasm score Visit 2: stimulation of the OO muscle representation in SMA-M3 using low frequency rTMS (1Hz) with the Hesed coil (designed to stimulate deep brain). Visit 3: stimulation of the OO muscle representation in M1 using low frequency rTMS (1Hz) using a standard eight-shaped coil. Visits 2 and 3: single pulse TMS will be used to evoke MEPs from OO muscles. Paired pulse TMS will be used to assess sICI from OO muscles. The order of visits 2 and 3 will be randomly assigned. Outcome measures The main outcome measures will be the sizes of OO muscle MEPs and the amount of sICI assessed before and after 15 minutes of low frequency rTMS. The secondary outcome measures will be the sizes of OO muscle MEPs assessed before and during voluntary and involuntary blinks.