ABNORMAL PROPRIOCEPTIVE-MOTOR INTEGRATION CONTRIBUTES TO HYPOMETRIC POSTURAL RESPONSES OF SUBJECTS WITH PARKINSON’S DISEASE J. V. JACOBS a * AND F. B. HORAK a,b,c,d a Neurological Sciences Institute, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, OR 97006-3499, USA b Department of Neurology, Oregon Health & Science University, Port- land, OR, USA c Department of Physiology and Pharmacology, Oregon Health & Sci- ence University, Portland, OR, USA d Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR, USA Abstract—Subjects with Parkinson’s disease exhibit abnor- mally short compensatory steps in response to external pos- tural perturbations. We examined whether: (1) Parkinson’s disease subjects exhibit short compensatory steps due to abnormal central proprioceptive-motor integration, (2) this proprioceptive-motor deficit can be overcome by visual–mo- tor neural circuits using visual targets, (3) the proprioceptive- motor deficit relates to the severity of Parkinson’s disease, and (4) the dysfunction of central dopaminergic circuits con- tributes to the Parkinson’s disease subjects’ proprioceptive- motor deficit. Ten Parkinson’s disease subjects and 10 matched control subjects performed compensatory steps in response to backward surface translations in five conditions: with eyes closed, with eyes open, to a remembered visual target, to a target without seeing their legs, and to a target while seeing their legs. Parkinson’s disease subjects were separated into a moderate group and a severe group based on scores from the Unified Parkinson’s Disease Rating Scale and were tested off and on their dopamine medication. Par- kinson’s disease subjects exhibited shorter compensatory steps than did the control subjects, but all subjects increased their step length when stepping to targets. Compared with the other subject groups, the severe Parkinson’s disease subjects made larger accuracy errors when stepping to tar- gets, and the severe Parkinson’s disease subjects’ step ac- curacy worsened the most when they were unable to see their legs. Thus, Parkinson’s disease subjects exhibited short compensatory steps due to abnormal proprioceptive-motor integration and used visual input to take longer compensa- tory steps when a target was provided. In severe Parkinson’s disease subjects, however, visual input does not fully com- pensate because, even with a target and unobstructed vision, they still exhibited poor step accuracy. Medication did not consistently improve the length and accuracy of the Parkin- son’s disease subjects’ compensatory steps, suggesting that degeneration of dopamine circuits within the basal ganglia is not responsible for the proprioceptive-motor deficit that de- grades compensatory steps in Parkinson’s disease subjects. © 2006 IBRO. Published by Elsevier Ltd. All rights reserved. Key words: proprioception, posture, balance, vision, kines- thesia. Patients with Parkinson’s disease (PD) often suffer from postural instability, leading to falls and a decreased quality of life (Bloem et al., 2001; Wood et al., 2002; Keranen et al., 2003). PD subjects often fall because they respond to a sudden loss of balance with abnormally short (hypo- metric) steps that are inadequate for them to recover equi- librium (Fahn and Elton, 1987; Jacobs and Horak, 2004; Rocchi et al., 2004; Maki and McIlroy, 2005). Steps taken to maintain upright stance after a sudden loss of balance (compensatory steps) represent an important strategy for preventing a fall (Maki and McIlroy, 2005). Although it is known that PD subjects exhibit abnormally short compensa- tory steps, the neurological deficits that underlie their short- ened compensatory steps have not been characterized. Despite the lack of research on compensatory stepping in PD subjects, research on voluntary movement suggests that PD subjects may exhibit hypometria (abnormally short movements) because they overestimate the length of their movement due to abnormally integrated proprioceptive in- put (Demirci et al., 1997; Contreras-Vidal and Gold, 2004). This abnormal integration of proprioceptive input repre- sents a central dysfunction within the primary and second- ary sensorimotor regions of the cerebral cortex (Boecker et al., 1999; Seiss et al., 2003), not a peripheral dysfunc- tion of the proprioceptive receptors (Delwaide and Gonce, 1993). Therefore, PD subjects exhibit a central impairment of proprioceptive-motor integration, that is, abnormal cen- tral processing of proprioceptive input to form an internal representation of the body’s motion for accurately guiding movement. Studies on PD that assess abnormal proprio- ceptive-motor integration commonly utilize indirect behav- ioral measures of proprioceptive-motor function by com- paring the subjects’ movement in a condition which allows them to see their movement versus in a condition which does not allow them to see their movement in order to force them to rely on proprioceptive-motor integration for guiding their movement (Moore, 1987; Klockgether et al., 1995; Demirci et al., 1997; Jobst et al., 1997; Adamovich et al., 2001; Byblow et al., 2003; Maschke et al., 2003; Contreras-Vidal and Gold, 2004; Almeida et al., 2005; Keijsers et al., 2005). For example, when PD subjects try to duplicate an active or passive movement of their upper limb without being able to see that limb, they do not move *Corresponding author. Tel: +1-503-418-2603; fax: +1-503-418-2501. E-mail address: jacobsj@ohsu.edu (J. V. Jacobs). Abbreviations: ANOVA, analysis of variance; AP, anterior–posterior; dlPMC, dorsolateral premotor cortex; ML, medial–lateral; PD, Parkin- son’s disease; SMA, supplementary motor area; UPDRS, Unified Par- kinson’s Disease Rating Scale. Neuroscience 141 (2006) 999 –1009 0306-4522/06$30.00+0.00 © 2006 IBRO. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.neuroscience.2006.04.014 999