Navigating new opportunities for prognosis of neurodegenerative - PowerPoint PPT Presentation

Navigating new opportunities for prognosis of neurodegenerative disorders Tarkeshwar Singh Sensorimotor Neuroscience Laboratory Department of Kinesiology University of Georgia, Athens, GA 12/10/19 1

Overview of Today’s Presentation Background Theoretical framework of my research Previous Studies Stroke studies informing the theoretical model Current Studies Ongoing basic science and neurodegenerative studies Future Research Direction Basic science and neurodegenerative studies 2 University of Minnesota School of Kinesiology

Neurodegenerative Diseases Begin to Impact Mobility Before Diagnosis Ø 6.5 million people in the US are living with Alzheimer’s (AD) or Parkinson’s disease (PD) Ø Both diseases have distinct pathogenetic origins, but they are both complex multisystem disorders that start years to decades before clinical diagnosis of the disease Ø Even in the preclinical phase, they both impact the ability to drive and maintain postural balance (Darweesh et al. 2017; Roe et al. 2019) 3 University of Minnesota School of Kinesiology

Rapid Visuomotor Decision-making Tasks may Hold the Key to Detecting Early Signs of Neurodegeneration Ø NIH has identified early detection as a priority Ø We need both behavioral and structural biomarkers Ø Real-world tasks are impacted by subtle deficits in sensorimotor function Ø Real-world tasks involve Ø Multiple neural networks Ø Real-time multisensory integration and decision making Ø Executive functions 4 University of Minnesota School of Kinesiology

Postural Balance is Correlated with Visuo-cognitive Problems in PD but Causal Mechanisms are not Known Stuart, S., Lord, S., Hill, E., & Rochester, L. (2016). Neuroscience & Biobehavioral Reviews, 62 , 76-88. Srivastava, A., Ahmad, O. F., Pacia, C. P., Hallett, M., & Lungu, C. (2018). Journal of Movement Disorders, 11(3), 93-106. 5 University of Minnesota School of Kinesiology

Current Information Processing Models Pose Challenges to Early Detection The Serial Information Processing framework Kandel, E., et al. (2012). Principles of Neural Science (5th ed.): McGraw-Hill Professional. 6 University of Minnesota School of Kinesiology

Experiments Designed Using Serial Information Frameworks Conceal Functional Impairments Less-affected arm of many stroke survivors exhibits minimal impairment Semrau, J. A et al. (2017). Neurorehabilitation and Neural Repair, 31(6), 571-582. 7 University of Minnesota School of Kinesiology

Less-affected Arm Movement Exhibits Impairments on a Complex Time-constrained Neuropsych Test Healthy control (dominant arm) Stroke Survivor (less-affected arm) Total Time for TMT B =33.4 s Total Time for TMT B =118 s Serial information processing is not an optimal framework to study sensorimotor control on a single continuum in healthy and clinical populations 8 University of Minnesota School of Kinesiology

Affordance -Based Investigation of Visuomotor Control in Neurodegenerative Disorders Affordance: opportunities for action defined by the object or environment (Gibson, 1979) Ø Dorsal-dorsal stream – visuospatial function Ø Dorsal-ventral stream - motion-processing Ø Ventral stream – form- processing (shape, color) Ø Known anatomical pathways, but roles in Adapted from: Cisek, P., & Kalaska, J. F. (2010). Annual Review of Neuroscience, 33(1), 269-298. motor control not defined Yamasaki, T, et al. (2012). Journal of Alzheimer's Disease, 53(2), 661-676. Budisavljevic, S., et al. (2018). Cortex, 103, 224-239 9 University of Minnesota School of Kinesiology

Background Theoretical framework of my research Previous Studies Stroke studies informing the theoretical model Current Studies Ongoing basic science and neurodegenerative studies Future Research Direction Basic science and neurodegenerative studies 10 University of Minnesota School of Kinesiology

Functional Performance is Impaired in Stroke Survivors Even if Visually-guided Reaching is Intact Movements Are Stroke survivors performed TMT-A and TMT-B using augmented poorly despite making normal reality, eye-tracking and robotics center-out reaching movements with the less impaired hand Singh, T et al. (2017). Journal of Neurophysiology, 117(1), 79-92. 11 University of Minnesota School of Kinesiology

High Number of Saccades Made by Stroke Survivors may be Linked to Functional Impairment Visuo-perceptual and oculomotor functions were largely intact in our stroke survivors, but visuo-cognitive function was impaired Visuo-cognitive Visuo-perceptual Oculomotor Singh, T et al. (2017). J Neurophysiol, 117(1), 79-92. 12 University of Minnesota School of Kinesiology

Computational Model Reveals Concealed Visuospatial and Executive Impairments Topographic search Working memory Model fit 1) Stroke survivors exhibited deficits in working memory and topographic search. 2) Excessive saccades slowed down limb movements Singh, T et al. (2017). J Neurophysiol, 117(1), 79-92. Singh, T., et al. (2018). Neurorehab & Neural Repair, 32(8), 724-734. 13 University of Minnesota School of Kinesiology

Affordance- based Approach to Investigate Neurodegenerative Disorders Other tests of visuo-cognitive and sensorimotor impairments Motion-processing + form-processing Motion-processing task + working memory task Hit everything Hit circle and tall-triangle and avoid everything else Harrison, A et al. (under review) Perry, CM et al. (under review) 14 University of Minnesota School of Kinesiology

Background Theoretical framework of my research Previous Studies Stroke studies informing the theoretical model Current Studies Ongoing basic science and neurodegenerative studies Future Research Direction Basic science and neurodegenerative studies 15 University of Minnesota School of Kinesiology

1) Functional Impairments during Parkinson’s Disease (PD) Healthy control (dominant arm) PD patient (dominant arm) Total Time for TMT B =33.4 s Total Time for TMT B =169 s Ø Tested 12 PD patients (3 females), 70.5±5.9 years and age- matched controls Ø Hoehn-Yahr (2.04±0.43), UPDRS II (8±4.47), UPDRS III (31±10.55) Singh, T. et al. (in prep) 16 University of Minnesota School of Kinesiology

PD Patients Performed Poorly but don’t Exhibit Visuo-cognitive or Oculomotor Deficits Visuo-perceptual deficits may contribute to overall worse task performance in PD Visuo-cognitive Visuo-perceptual Oculomotor 17 University of Minnesota School of Kinesiology

2) Online Dorsal-ventral Interactions During Rapid Reach and INtercept (RaIN) Tasks Research Question: How does simultaneous motion and form-processing affect limb motor control? Reach Intercept Young (n=26, 10 m), 23.7±5.5 yrs Older (n=15, 4 m), 69.2±4.04 yrs Gómez-Granados, A, Barany, D., & Singh, T (in prep). Barany, D. A., Gómez-Granados, A., Schrayer, M., Cutts, S. A., & Singh, T. (under review). bioRxiv, 821074. 18 University of Minnesota School of Kinesiology

Decisions on Object Shapes Elicit Quicker Reactions in Older Adults for Moving Targets Gómez-Granados, A, Barany, D., & Singh, T (in prep). 19 University of Minnesota School of Kinesiology

Older Adults have Slower Saccadic Reactions, but Faster Limb Movement Initiation After Target Foveation Hypothesis: Looming objects may create stronger transient visual responses in older adults No Decision Decision Young Movement Initiation - 300 300 Older Gaze on Target (ms) 200 200 100 100 0 0 − 100 − 100 Boehnke, S. E., & Munoz, D. P. (2008). Reach Intercept Reach Intercept Current Opinion in Neurobiology, 18 (6), 544-551 20 University of Minnesota School of Kinesiology

Background Theoretical framework of my research Previous Studies Stroke studies informing the theoretical model Current Studies Ongoing basic science and neurodegenerative studies Future Research Direction Basic science and neurodegenerative studies 21 University of Minnesota School of Kinesiology

1) Rapid Reach and INtercept (RaIN II) Basic Science Studies Clinical Science Studies Ø Shape and color detection Ø Compared to the ventral (ventral stream) stream, dorsal stream Ø Object motion manipulation processing shows early signs (dorsal stream) of aging Ø Source modeling of visually Ø Color vision is impaired in PD evoked potentials during patients motion-processing Ø Motion-processing is impaired in PD patients 22 University of Minnesota School of Kinesiology

2) Force Impulse Control - Interception Paradigm Research question: How does visual motion-processing contribute to the learning of anticipatory and feedback postural responses? Gomez-Granados et al. (in prep) 23 University of Minnesota School of Kinesiology

2) Force Impulse Control – Anticipatory and Feedback Responses for Limb Posture Stabilization Anticipatory and feedback responses Ø How are long-latency reflexes (M2 in figure on the right) modulated with visual- motion processing? Ø What’s the nature of the relationship between anticipatory postural responses and reflex gains? Ø How does aging alter anticipatory postural responses and reflex gains? Gomez-Granados et al. (in prep) 24 University of Minnesota School of Kinesiology