An Automated Test of Rat Forelimb Supination Quantifies Motor Function Loss and Recovery After Corticospinal Injury

Abstract

Background. Rodents are the primary animal model of corticospinal injury and repair, yet current behavioral tests do not show the large deficits after injury observed in humans. Forearm supination is critical for hand function and is highly impaired by corticospinal injury in both humans and rats. Current tests of rodent forelimb function do not measure this movement. Objective. To determine if quantification of forelimb supination in rats reveals large-scale functional loss and partial recovery after corticospinal injury. Methods. We developed a knob supination device that quantifies supination using automated and objective methods. Rats in a reaching box have to grasp and turn a knob in supination in order to receive a food reward. Performance on this task and the single pellet reaching task were measured before and after 2 manipulations of the pyramidal tract: a cut lesion of 1 pyramid and inactivation of motor cortex using 2 different drug doses. Results. A cut lesion of the corticospinal tract produced a large deficit in supination. In contrast, there was no change in pellet retrieval success. Supination function recovered partially over 6 weeks after injury, and a large deficit remained. Motor cortex inactivation produced a dose-dependent loss of knob supination; the effect on pellet reaching was more subtle. Conclusions. The knob supination task reveals in rodents 3 signature hand function changes observed in humans with corticospinal injury: (1) large-scale loss with injury, (2) partial recovery in the weeks after injury, and (3) loss proportional to degree of dysfunction.

Dexterity: A MATLAB-based analysis software suite for processing and visualizing data from tasks that measure arm or forelimb function

“…After a subject reached baseline, four consecutive sessions were collected. Then, the subject received a pyramidotomy, which is a unilateral cut injury to the corticospinal tract, as we have done previously (Brus-Ramer, Carmel, Chakrabarty, & Martin, 2007; Brus-Ramer, Carmel, & Martin, 2009; Carmel et al, 2010; Carmel, Kimura, & Martin, 2014; Sindhurakar et al, 2016; Sindhurakar et al, 2017). Testing was performed at 3, 7, 14, 21, 28, and 35 days after injury.…”

“…Below, Dexterity is described in the context of Vulintus’ MotoTrak system, specifically, the knob supination task (Meyers et al, 2016; Sindhurakar et al, 2016). Rats are placed into a reaching box, and the target of the reach is a knob that must be grasped and turned in supination to a success criterion (Figure 2F, “Supination”).…”

“…A. Hays et al, 2013; Meyers et al, 2016; Sindhurakar et al, 2016; Wong, Ramanathan, Gulati, Won, & Ganguly, 2015). Meanwhile, others have focused on automating arm and hand tests in humans (Bosecker, Dipietro, Volpe, & Krebs, 2010; Wikholm & Bohannon, 1991).…”

“…Automated tasks offer several advantages over manual tasks: objectivity, increased throughput, and decreased analysis time. In some cases, they provide a more sensitive loss of dexterity than conventional tasks (Sindhurakar et al, 2016). In addition, they allow neuroscientists to utilize some of the advantages of large data that weren’t previously possible with non-automated tasks, such as analyzing kinetic and kinematic information in addition to success rate; quantifying learning or skill acquisition; and analyzing the quality of training (Gomez-Marin, Paton, Kampff, Costa, & Mainen, 2014).…”

“…Dexterity incorporates tools we have used for analysis of an automated forelimb reaching task and has been made general for analysis of other forelimb or arm specific tasks (Sindhurakar et al, 2016). To add additional tasks to Dexterity’s capabilities, the software needs to be modified at the file reading level, and our intention is to collaborate with other researchers to add more tests of dexterity to the software’s capabilities.…”