What goes wrong with balance in Parkinson s Disease? Fay B Horak, PhD, PT Professor of Neurology Oregon Health and Science. CoM

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1 What goes wrong with balance in Parkinson s Disease? Fay B Horak, PhD, PT Professor of Neurology Oregon Health and Science CoM CoM Course Objectives Understand different types of balance systems affected by PD Discover studies demonstrating balance impairments with progression of PD Consider how cognitive deficits affect functional mobility in PD Learn about why intense Cognitive-Agility exercises may help mobility in PD 1

2 Clinic or Lab OPALS by APDM APDM.com Long-Term Monitoring Synchronized, wireless sensors OHSU and Dr. Horak have a significant financial interest in APDM, a company that may have a commercial interest in the results of this research and technology. This potential conflict of interest has been reviewed and managed by OHSU and the Integrity Program Oversight Council. Balance problems can differ among people with PD BRADYKINESIA AND RIGIDITY Mobility Threshold for balance or gait problem POSTURAL INSTABILITY Progression of PD 2

3 Types of Balance Control Postural Alignment Postural Responses Anticipatory Posture Dynamic Balance Rigidity PD Impairments Bradykinesia Kinesthesia Freezing Executive Postural Responses are weak (bradykinetic) 3

4 Forward sway in response to backward surface motion tr Postural Alignment- Stooping worsens balance Upright Control Stooped Control Parkinson's disease 4

5 STOOPED INITIAL POSTURE REDUCES POSTURAL STABILITY IN RESPONSE TO PERTURBATIONS, ESPECIALLY BACKWARDS (LIKE PD SUBJECTS). Stability Margin (peak CoP - peak CoM) FL F 5 cm FR 10 5 CoP CoM Control Subject L R Time (s) 10 PD Subject BL B BR 5 CoP CoM Upright Controls Parkinson s Disease (PD) Stooped Controls DBS Surgery worsens postural responses St. George, et al The effects of STN and GPi DBS on postural responses in patients with Parkinson's disease. J Neurosurgery 2012 Jun;116(6):

6 DBS impairs Postural Responses St. George et al, J Neurosurg 2010 Pre ON Pre ON Dopa Post ON / ON Levodopa does NOT improve postural responses in Parkinson s Disease OFF Dopa Pull Test ON Dopa Pull Test 6

7 Freezing when a step is needed for stepping response Jacobs, J.V., et al, Knee trembling during freezing of gait represents multiple anticipatory postural adjustments. Exp Neurology 215(2): Poor Kinesthesia (body sense) impairs balance Reduced perception of surface angle PD need to see foot to step to target 60% correct instead of 85% Jacobs, et al, Abnormal proprioceptive-motor integration contributes to hypometric postural responses of subjects with Parkinson s disease Neuroscience. Aug 21;141(2): ,

8 People with PD can learn to improve postural responses with practice standing on a translating surface PD_Off (11) PD_On (11) Con (11) PD_Off (11) PD_On (11) Con (11) COM movement (m) Number of Steps hrs 24 hrs VOLUNTARY STEPPING Control PD Narrow PD Wide 8

9 Difficulty changing postural set for initial conditions WIDE NARROW cm cm Control Parkinson s Disease Patients with Parkinson s Disease do not scale up the size of APAs for wide stance Rocchi, Laura, et al Step initiation in Parkinson s disease: influence of initial stance conditions, NeurosciLett. Oct 2;406(1-2):128-32, Turning is harder than straight walking, esp. for PD cm PD Control cm 9

10 We make over 1,000 turns a day Quantity of activity is similar in PD and controls, but quality of turning is different 10

11 Figure-8-task in PD with low and high neck rigidity Franzen, et al, Reduced performance in balance, walking and turning tasks is associated with increased neck tone in Parkinson's disease Exp Neurol 219(2):430-8, 2009 LOW NECK TONE Earliest signs of PD gait: lack of arm swing and lack rotation trunk/neck HIGH NECK TONE Gait Variability across day and across week larger in people with PD than people 20 yrs older 11

12 Cognition and Balance Cognitively impaired older people fall twice more than cognitively intact PD patients with worse cognitive deficits have more falls (Segev-Jacubovski et al. 2011) Gait and balance are not automatic processes in older people, esp with PD (Stuss et al. 2000) Same parts of brain for thinking and balance Fronto-basal ganglia circuits, vital to control gait are also involved in executive functions Stuss et al Increased demands (stress, anxiety or challenging task), can lead to freezing of gait Vandenbossche et al

13 Cognitive problems related to mobility in Parkinson s disease Dual Tasking Dual-Task Interference Walking slows when talk Thinking slows when walk More difficult with Parkinson s Disease: Need more attention to walk and balance Reduced working memory Difficult to switch between tasks Make not prioritize balance Owen et al., 1997; Lewis et al

14 Balance and walking require more Attention in PD GGait Velocity Controls PD No Cognitive Task With Cognitive Task 14

15 Postural stability when walking is more affected by a dual-task in people with PD Rochester L et al, The nature of dual-task interference during gait in PD, Neuroscience, 265, 83-94) Dual Tasking can improve with training! 30 days Gait speed during serial subtraction of 3 s improved with practice in people with PD. Pichierriet al 2011; Yogevet al

16 Conflict Resolution Difficulty inhibiting inappropriate responses while activating the correct response Flankers Task: name the direction of the middle arrow Stroop Test- conflict resolution 16

17 Impairment of cognitive inhibition could contribute to FoG In gait, lifting of the stepping leg must be delayed until the APA is complete, but no longer. Failure to release inhibition of the stepping program and to inhibit the APA may lead to akinesia or repeated weight shifts without stepping, trembling of the legs associated with FoG. Posture/Locomotor Network Overlaps with Cognitive Network Hypothesis: FoG is due to abnormal connections between Medial-Frontal Cortex and Midbrain Locomotor Centers Prefrontal presma STN/ PPN is atrophied but more active fmri during imagined walking in Freezers Snijders et al., 2011 PPN PPN Fougere et al, NeuroImage 50:1589,

18 Executive Inhibition Flankers Congruent Accuracy Stroop Conflict Accuracy (% correct) ** Response time (s) ** * 0.93 HC FOG- FOG+ Congruent <<< < <<< Discongruent <<< > <<< 0 HC FOG- FOG+ Stroop: Name the Colors! Blue Green Purple Green Freezers have difficulty releasing inhibition so can Go 250 Rho = Stroop Score (s) Score on Freezing of Gait Questionnaire (FoG-Q) 18

19 Missing Connectivity of the Right Locomotor Network and bilateral Cerebellum in Freezers R L FoG subjects show reduce fiber tracts from PPN to RIGHT thalamus, putamen, GPI, cingulate, pre and postcentral gyrus, SMA and presma, Prefrontal and BILATERAL Cerebellum Fling et al. Brain 2013 Asymmetry of White Matter Tracks from PPN PPN Tract Laterality Index ** HC FOG- FOG+ * Fling et al. Brain

20 Asymmetry of white matter from PPN to medial frontal relates to Executive Inhibition in FoG+ HC FoG- FoG+ Stroop Conflict r = 0.61 p = 0.02 Flankers Accuracy Stroop Conflict (s) Accuracy (% correct) HC FoG- FoG r = p = PPN Tract Laterality Index PPN Tract Laterality Index Fling et al. Brain 2013 WHY RIGHT SIDE FOR FOG? Response Inhibition Circuit: Right STN-PreSMA Healthy Decreased Right Default Mode Network in PD (related to cognitive) Coxon, et al, J Neurosci 2012 Tessitore, Neurology,

21 What goes wrong with balance in PD? Bradykinesia Rigidity Kinesthesia Alignment Responses Anticipatory Gait Freezing Executive Does intense cognitive-agility exercise for PD improve Balance/Gait Executive Function Brain Functional Connectivity Hypothesis: Make balance and gait more automatic, (ie; less cortical control of locomotion circuit) so more attention for cognitive function. 21

22 Balance Disorders Lab OHSU and VA 2014 Grant Support: National Institutes on Aging, Nat Ctr Medical Rehab Research, National Institute of Neurological Disorders and Stroke, National MS Society, MRF, Kinetics Foundation, VA Merit 22