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

University of Minnesota School of Kinesiology 2

Overview of Today’s Presentation

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

University of Minnesota

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

• f 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)

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Neurodegenerative Diseases Begin to Impact Mobility Before Diagnosis

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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

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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.

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Current Information Processing Models Pose Challenges to Early Detection

Kandel, E., et al. (2012). Principles of Neural Science (5th ed.): McGraw-Hill Professional.

The Serial Information Processing framework

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Experiments Designed Using Serial Information Frameworks Conceal Functional Impairments

Semrau, J. A et al. (2017). Neurorehabilitation and Neural Repair, 31(6), 571-582.

Less-affected arm of many stroke survivors exhibits minimal impairment

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Less-affected Arm Movement Exhibits Impairments

• n a Complex Time-constrained Neuropsych Test

Healthy control (dominant arm) Total Time for TMT B =33.4 s Stroke Survivor (less-affected arm) 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

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Affordance-Based Investigation of Visuomotor Control in Neurodegenerative Disorders

Adapted from: Cisek, P., & Kalaska, J. F. (2010). Annual Review of Neuroscience, 33(1), 269-298. Yamasaki, T, et al. (2012). Journal of Alzheimer's Disease, 53(2), 661-676. Budisavljevic, S., et al. (2018). Cortex, 103, 224-239

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 motor control not defined Affordance: opportunities for action defined by the

• bject or environment

(Gibson, 1979)

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

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Functional Performance is Impaired in Stroke Survivors Even if Visually-guided Reaching is Intact Movements Are

TMT-A and TMT-B using augmented reality, eye-tracking and robotics

Singh, T et al. (2017). Journal of Neurophysiology, 117(1), 79-92.

Stroke survivors performed poorly despite making normal center-out reaching movements with the less impaired hand

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High Number of Saccades Made by Stroke Survivors may be Linked to Functional Impairment

Singh, T et al. (2017). J Neurophysiol, 117(1), 79-92.

Visuo-cognitive Visuo-perceptual Oculomotor

Visuo-perceptual and oculomotor functions were largely intact in our stroke survivors, but visuo-cognitive function was impaired

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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.

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Affordance-based Approach to Investigate Neurodegenerative Disorders

Motion-processing task Motion-processing + form-processing + working memory task

Harrison, A et al. (under review) Perry, CM et al. (under review)

Other tests of visuo-cognitive and sensorimotor impairments

Hit circle and tall-triangle and avoid everything else Hit everything

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

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1) Functional Impairments during Parkinson’s Disease (PD)

Healthy control (dominant arm) Total Time for TMT B =33.4 s PD patient (dominant arm) Total Time for TMT B =169 s

ØTested 12 PD patients (3 females), 70.5±5.9 years and age- matched controls ØHoehn-Yahr (2.04±0.43), UPDRS II (8±4.47), UPDRS III (31±10.55)

Singh, T. et al. (in prep)

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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

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2) Online Dorsal-ventral Interactions During Rapid Reach and INtercept (RaIN) Tasks

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.

Young (n=26, 10 m), 23.7±5.5 yrs Older (n=15, 4 m), 69.2±4.04 yrs

Reach Intercept

Research Question: How does simultaneous motion and form-processing affect limb motor control?

University of Minnesota 19 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).

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Older Adults have Slower Saccadic Reactions, but Faster Limb Movement Initiation After Target Foveation

Boehnke, S. E., & Munoz, D. P. (2008). Current Opinion in Neurobiology, 18(6), 544-551

Hypothesis: Looming

• bjects may create

stronger transient visual responses in older adults

Young Older

Reach Intercept

−100 100 200 300

No Decision

Reach Intercept

Decision

300 200 100 −100

Movement Initiation - Gaze on Target (ms)

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

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1) Rapid Reach and INtercept (RaIN II)

Basic Science Studies Ø Shape and color detection (ventral stream) Ø Object motion manipulation (dorsal stream) Ø Source modeling of visually evoked potentials during motion-processing Clinical Science Studies Ø Compared to the ventral stream, dorsal stream processing shows early signs

• f aging

Ø Color vision is impaired in PD patients Ø Motion-processing is impaired in PD patients

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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)

University of Minnesota

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?

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2) Force Impulse Control – Anticipatory and Feedback Responses for Limb Posture Stabilization

Anticipatory and feedback responses

Gomez-Granados et al. (in prep)

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Summary: Overall Framework for my Basic Science and Applied Research

Early prognosis of Neurodegenerative disorders Affordance based Theoretical Framework Basic Science Affordance based Clinical Tests

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Thank you!

Email: tsingh@uga.edu SinghTarkesh1 Colleagues and Collaborators

Sensorimotor Neuroscience Lab Ø Deborah Barany Ø Ana Gomez Ø Negar Bassiri Ø Margaret Schrayer Ø Sarah Cutts Ø Quinn Hlava Ø Regan Lohlein Ø Deep Patel Ø Sean Gordon Ø Christopher Mejias Ø Keith Schroder Ø Aly Shakoor Parkinson’s Disease Ø Cédrick Bonnet, Univ of Lille, France Ø Troy Herter, Univ of South Carolina Multisensory Integration Ø Jennifer Semrau, Univ of Delaware Ø Isaac Kurtzer, New York Institute of Technology Funding Sources Ø UGA Research Foundation Ø USC ASPIRE GRANTS