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Method Article

A Fine Motor Task to Study Joint Kinematics in a Preclinical Model of Neurodegenerative Disease

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DOI:

10.3791/68128

June 13th, 2025

In This Article

Summary

The current study describes a fine motor behavior test for examining motor deficits in rodent models, including the TgF344-AD rat, using machine learning.

Abstract

Motor dysfunction is a critical, yet often underappreciated, component of neurodegenerative diseases such as Alzheimer's disease (AD) and related dementias. New research has shown that tasks involving fine motor behavior, visuospatial ability, and executive function in humans may have potential in early disease detection. However, little is known about the exact mechanisms by which these tasks predict cognitive and functional decline associated with AD. In the current method, a fine motor task, Kinematic Motor Ability Task (KINEMAT), was created to examine changes in motor ability across disease progression in preclinical models of AD relative to other neurodegenerative diseases and normal aging using free, open-source machine learning software. Here, proof-of-concept was established with the design, testing, and implementation of the fine motor task in a pilot study of Fisher 344 CDF rats with and without Harmaline-induced motor impairments. Additional validation, with an Alzheimer's disease rat model (TgF344-AD), further demonstrated model feasibility and task sensitivity. Rats were trained to reach through a small slot at the front of the chamber to retrieve a sugar pellet from one of three bowls with varying difficulty. Pellet retrieval was scored using one of three classifications: success (successfully grabbing and eating the sugar pellet), drop (grabs but drops the treat upon grasp), or failure (reach in which no pellet is procured, or pellets are knocked out of the bowl when attempting to grasp). Significant differences in motor ability were observed between control and Harmaline-treated rats, demonstrated by reduced total reaches and increased paw pose variability. TgF344-AD rats also showed reduced total reaches, as well as reduced successes across all bowls. In validating this as a fine motor task in rodents, it has future potential to study normal aging and preclinical models of neurodegenerative diseases, including AD, as pathology and symptoms emerge over time.

Introduction

Motor function has been shown to be impaired in people with dementia due to Alzheimer's disease (AD) or other subtypes (e.g., dementia with Lewy bodies). Grip strength and gait speed can distinguish between cognitively impaired and unimpaired older adults1,2, but cannot necessarily differentiate between different subtypes of dementias (i.e., low specificity)1,2. Thus, there continues to be a need for new diagnostic tools for early dementia, possibly paired with machine learning, for evaluating complex patterns and relationships between behavior and....

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Protocol

All methods described here have been approved by the Institutional Animal Care and Use Committee (IACUC) of Arizona State University.

1. Design and construction of the chamber

  1. Prepare the clear, acrylic panels. The schematics of the box are located at https://github.com/verpeutlab/ADFineMotorTask. Cut clear acrylic panels to the following dimensions (all panels are 1 cm thick):
    1. Cut out two side panels: 26 cm × 22 cm.
    2. Cut out a top panel: 27 cm × 12 cm.
    3. Cut out the first bottom panel: 26 cm x 10 cm
    4. Cut out the second bottom panel: 26 cm x 11 cm
    5. Cut of a fron....

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Results

After rats reached a 90% body weight food restriction, they were habituated to the chamber for 2 days, then underwent shaping procedures for 1-2 weeks. The number of successful, dropped, and failed reaches were scored by a trained observer blind to each condition. Over the course of 9 days (Baseline), rats were tested for fine motor ability on 3 different bowl configurations (Plain, Less, and Plinko). Then, the same rats (n = 5 per group, 1 removed after training bowl shaping due to illness) were injected with Harmaline .......

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Discussion

Reaching tasks for rodents are commonly restricted to single pellets and do not include obstructions or self-perturbing features, which are common struggles for patients with neurodegenerative pathology. The method presented here, using both a reimagined pellet-reaching task and machine learning, can detect both coordination and strategy through analysis of pose features and transitions, in addition to individual digit movements. The fine motor task created here detected coordination and strategy via analysis of pose and.......

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Disclosures

The authors declare no competing financial interests.

Acknowledgements

This work was supported by the Institute for Mental Health Research, Institute for Social Science Research, Arizona Department of Health Sciences [ADHS14-052688], US Department of Health and Human Services, National Institutes of Health [P30AG019610], Arizona Alzheimer's Disease Research Center REC Fellows Program, Arizona Alzheimer's Consortium, and Nancy Eisenberg Junior Faculty Scholar Award. Figures were created using Biorender.com. We would like to thank Nelson Yamada, Akash Kuppravalli, and Jeanne Kamau for their design assistance.

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Materials

List of materials used in this article
NameCompanyCatalog NumberComments
3D printing materialAmazon (Overture)B07PGY2JP1PLA Filament 1.75 mm PLA 3D Printer Filament, Dimensional Accuracy +/- 0.03 mm
CameraEdmond OpticsBFS-U3-13Y3M-C1.3 MP, Mono, 170 FPS, ON Semi PYTHON 1300 x2
Camera cablesEdmond OpticsACC-01-2300USB 3.1, 3 m, Type-A to Micro-B (Locking) Cable
Camera lensThor labsMVL5WA4.5 mm EFL, F/1.4, 1/2" Format Machine Vision Lens
Camera to tripod connectionEdmond Optics88-210Connection for camera to tripod
Cleaning wipesAmazon (Sani-Cloth)B00KMZ7KMOAF3 Surface Disinfectant Cleaner Wipe Canister Mild Scent 160 Ct P13872
ComputerDellPrecisionIntel Core i7-13700 @ 2.1 GHz, NVIDIA T1000 8 GB, RAM 16 GB
IR lightAmazon (Serlium)B0BJFDBT44Camera IR Light 48 LED IR Illuminators Lights Waterproof Infrared Night Visionss Light for Security CCTV Camera       
Panel glueAmazon (Sdintar)B0B1DLRPNZGlass glue
PlexiglassAmazon (TOOLINHAND  US)B0BRJ1L8TR12 × 12" Clear Cast Acrylic/Plexiglass Sheets - Transparent 1/8” Thick (3 mm) 
Python Python Software FoundationPython 3.7
SpinviewTeledyne TechnologiesVersion 3.1.0.79 
Sugar pellets (45 mg)BioservF002345 mg, Unflavored 50,000/Box; Ingredients: Sucrose, Dextrose, Magnesium Stearate, Calcium Silicate, Mineral Oil
TripodAmazon (YOUYI)B086PYJF9DAmazon Flexible Desk Webcam Tripod
TweezersFine Science Tools11064-07Iris Forceps
WaxAmazon (Orthomechanics)B00FKDC0UUGenuine Orthowax 

References

  1. Hooyman, A., Malek-Ahmadi, M., Fauth, E. B., Schaefer, S. Y. Challenging the relationship of grip strength with cognitive status in older adults. Int J Geriatr Psychiatry. 36 (3), 433-442 (2021).
  2. Hooyman, A., et al.

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Tags

Neurodegenerative Disease ModelMotor DysfunctionMachine Learning AnalysisBody Part TrackingFisher 344 RatsHarmaline TreatmentPellet RetrievalBehavioral Classification