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Multifactorial motor behavior assessment for real-time evaluation of emerging therapeutics to treat neurologic impairments.

ABSTRACT: Integrating multiple assessment parameters of motor behavior is critical for understanding neural activity dynamics during motor control in both intact and dysfunctional nervous systems. Here, we described a novel approach (termed Multifactorial Behavioral Assessment (MfBA)) to integrate, in real-time, electrophysiological and biomechanical properties of rodent spinal sensorimotor network activity with behavioral aspects of motor task performance. Specifically, the MfBA simultaneously records limb kinematics, multi-directional forces and electrophysiological metrics, such as high-fidelity chronic intramuscular electromyography synchronized in time to spinal stimulation in order to characterize spinal cord functional motor evoked potentials (fMEPs). Additionally, we designed the MfBA to incorporate a body weight support system to allow bipedal and quadrupedal stepping on a treadmill and in an open field environment to assess function in rodent models of neurologic disorders that impact motor activity. This novel approach was validated using, a neurologically intact cohort, a cohort with unilateral Parkinsonian motor deficits due to midbrain lesioning, and a cohort with complete hind limb paralysis due to T8 spinal cord transection. In the SCI cohort, lumbosacral epidural electrical stimulation (EES) was applied, with and without administration of the serotonergic agonist Quipazine, to enable hind limb motor functions following paralysis. The results presented herein demonstrate the MfBA is capable of integrating multiple metrics of motor activity in order to characterize relationships between EES inputs that modulate mono- and polysynaptic outputs from spinal circuitry which in turn, can be used to elucidate underlying electrophysiologic mechanisms of motor behavior. These results also demonstrate that proposed MfBA is an effective tool to integrate biomechanical and electrophysiology metrics, synchronized to therapeutic inputs such as EES or pharmacology, during body weight supported treadmill or open field motor activities, to target a high range of variations in motor behavior as a result of neurological deficit at the different levels of CNS.

SUBMITTER: Islam R

PROVIDER: S-EPMC6848091 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Both D1R and D2R knock out (KO) mice of the major dopamine receptors show significant motor impairments. However, there are some discrepant reports, which may be due to the differences in genetic background and experimental procedures. In addition, only few studies directly compared the motor performance of D1R and D2R KO mice. In this paper, we examined the behavioral difference among N10 congenic D1R and D2R KO, and wild type (WT) mice. First, we examined spontaneous motor activity in the home cage environment for consecutive 5 days. Second, we examined motor performance using the rota-rod task, a standard motor task in rodents. Third, we examined motor ability with the Step-Wheel task in which mice were trained to run in a motor-driven turning wheel adjusting their steps on foothold pegs to drink water. The results showed clear differences among the mice of three genotypes in three different types of behavior. In monitoring spontaneous motor activities, D1R and D2R KO mice showed higher and lower 24 h activities, respectively, than WT mice. In the rota-rod tasks, at a low speed, D1R KO mice showed poor performance but later improved, whereas D2R KO mice showed a good performance at early days without further improvement. When first subjected to a high speed task, the D2R KO mice showed poorer rota-rod performance at a low speed than the D1R KO mice. In the Step-Wheel task, across daily sessions, D2R KO mice increased the duration that mice run sufficiently close to the spout to drink water, and decreased time to touch the floor due to missing the peg steps and number of times the wheel was stopped, which performance was much better than that of D1R KO mice. These incongruent results between the two tasks for D1R and D2R KO mice may be due to the differences in the motivation for the rota-rod and Step-Wheel tasks, aversion- and reward-driven, respectively. The Step-Wheel system may become a useful tool for assessing the motor ability of WT and mutant mice.

Project description:After a major upper limb amputation, the use of myoelectric prosthesis as assistive devices is possible. However, these prostheses remain quite difficult to control for grasping and manipulation of daily life objects. The aim of the present observational case study is to document the kinematics of grasping in a group of 10 below-elbow amputated patients fitted with a myoelectric prosthesis in order to describe and better understand their compensatory strategies. They performed a grasping to lift task toward 3 objects (a mug, a cylinder and a cone) placed at two distances within the reaching area in front of the patients. The kinematics of the trunk and upper-limb on the non-amputated and prosthetic sides were recorded with 3 electromagnetic Polhemus sensors placed on the hand, the forearm (or the corresponding site on the prosthesis) and the ipsilateral acromion. The 3D position of the elbow joint and the shoulder and elbow angles were calculated thanks to a preliminary calibration of the sensor position. We examined first the effect of side, distance and objects with non-parametric statistics. Prosthetic grasping was characterized by severe temporo-spatial impairments consistent with previous clinical or kinematic observations. The grasping phase was prolonged and the reaching and grasping components uncoupled. The 3D hand displacement was symmetrical in average, but with some differences according to the objects. Compensatory strategies involved the trunk and the proximal part of the upper-limb, as shown by a greater 3D displacement of the elbow for close target and a greater forward displacement of the acromion, particularly for far targets. The hand orientation at the time of grasping showed marked side differences with a more frontal azimuth, and a more "thumb-up" roll. The variation of hand orientation with the object on the prosthetic side, suggested that the lack of finger and wrist mobility imposed some adaptation of hand pose relative to the object. The detailed kinematic analysis allows more insight into the mechanisms of the compensatory strategies that could be due to both increased distal or proximal kinematic constraints. A better knowledge of those compensatory strategies is important for the prevention of musculoskeletal disorders and the development of innovative prosthetics.

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Multifactorial motor behavior assessment for real-time evaluation of emerging therapeutics to treat neurologic impairments.

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