Robotic Outcome Assessment in a Non-Human Primate Model of Middle Cerebral Artery Stroke

Stroke is a prevalent disorder with immense socioeconomic impact. A variety of chronic neurological deficits result from stroke. In particular, sensorimotor deficits are a significant barrier to achieving post-stroke independence. Unfortunately, the majority of pre-clinical studies that show improved outcomes in animal stroke models have failed in clinical trials. Pre-clinical studies using non-human primate (NHP) stroke models prior to initiating human trials are a potential step to improving translation from animal studies to clinical trials. Robotic assessment tools represent a quantitative, reliable, and reproducible means to assess reaching behaviour following stroke in both humans and NHPs. We investigated the use of robotic technology to assess sensorimotor impairments in NHPs following middle cerebral artery occlusion (MCAO). Two cynomolgus macaques underwent transient MCAO for 90 minutes. Approximately 1.5 years following the procedure these NHPs and two non-stroke control monkeys were trained in a reaching task with both arms in the KINARM exoskeleton. This robot permits elbow and shoulder movements in the horizontal plane. The task required NHPs to make reaching movements from a centrally positioned start target to 1 of 8 peripheral targets uniformly distributed around the first target. We analyzed four movement parameters: reaction time, movement time (MT), initial direction error (IDE), and number of speed maxima to characterize sensorimotor deficiencies. We hypothesized reduced performance in these attributes during a neurobehavioural task with the paretic limb of NHPs following MCAO compared to controls. Reaching movements in the non-affected limbs of control and experimental NHPs showed bell-shaped velocity profiles. In contrast, the reaching movements with the affected limbs were highly variable. We found distinctive patterns in MT, IDE, and number of speed peaks between control and experimental monkeys and between limbs of NHPs with MCAO. NHPs with MCAO demonstrated more speed peaks, longer MTs, and greater IDE in their paretic limb compared to controls. These initial results qualitatively match human stroke subjects’ performance, suggesting that robotic neurobehavioural assessment in NHPs with stroke is feasible and could have translational relevance in subsequent human studies. Further studies will be necessary to replicate and expand on these preliminary findings.

TOWARD A POLITICAL CONCEPTION OF MINORITY RIGHTS: RECONCILING SOVEREIGNTY, HUMAN RIGHTS AND MINORITY CLAIMS

The question that I will explore in this research dissertation is whether one can defend the rights of homeland minorities as a progressive extension of the existing norms of human rights. This question calls for several deeper inquiries about the nature, the function and the underlying justifications for both human rights and minority rights. In particular, this research project will examine the following issues: on what normative grounds the available norms of human rights and minority rights are justified; if there is any methodic way to use the normative logic of human rights to support substantial forms of minority claims, such as the right to self-determination; whether human rights can take the form of group rights; and finally, whether there is any non-sectarian basis for justifying the minority norms, which can be acceptable from both liberal and non-liberal perspectives. This research project has some implications for both theories of minority rights and human rights. On the one hand, the research employs the topic of minority rights to shed light on deficiencies of the existing political theories of human rights. On the other hand, it uses the political theory to shed light on how existing theories of minority rights could be improved and amended. The inquiry will ultimately clarify how to judge the merit of the claim that minority rights are or should be a part of human rights norms.