Call for Manuscripts on Neurobiology of Deep Brain Stimulation 1 Compensatory stepping in Parkinson ’ s Disease is still a problem after Deep 2 Brain Stimulation randomized to STN or GPi

23 The effects of Deep Brain Stimulation (DBS) on balance in people with Parkinson’s Disease 24 (PD) are not well established. This study examined whether DBS randomized to the 25 subthalamic nucleus (STN, n=11) or globus pallidus interna (GPi, n=10) improved 26 compensatory stepping to recover balance following a perturbation. The standing surface 27 translated backwards, forcing subjects to take compensatory steps forward. Kinematic and 28 kinetic responses were recorded. PD-DBS subjects were tested off and on their levodopa 29 medication before bilateral DBS surgery, and retested six months later off and on DBS, 30 combined with off and on levodopa medication. Responses were compared with PD-control 31 subjects (n=8) tested over the same time scale and 17 healthy control subjects. 32 Neither DBS nor levodopa improved the stepping response. Compensatory stepping in the 33 best-treated state after surgery (DBS+DOPA) was similar to the best-treated state before 34 surgery (DOPA) for the PD-GPi group and the PD control group. For the PD-STN group, 35 there were more lateral weight shifts, a delayed foot-off and a greater number of steps 36 required to recover balance in DBS+DOPA after surgery, compared to DOPA before surgery. 37 Within the STN group, 5 subjects who did not fall during the experiment before surgery fell 38 at least once after surgery, whereas the number of falls in the GPi and PD-control groups 39 were unchanged. 40 DBS did not improve the compensatory step response needed to recover from balance 41 perturbations in the GPi group and caused delays in the preparation phase of the step in the 42 STN group. 43 44