A pragmatic reevaluation of the efficacy of nonhuman primate optogenetics

Abstract

A recent paper published in Neuron by Tremblay et al. (2020) introduces an openly available resource detailing published and unpublished studies using optogenetics to manipulate nonhuman primate (NHP) brain. The open science efforts of team are important and rare in NHP neuroscience, but conclusions drawn about success rate of optogenetics in NHP brain are problematic for quantitative and theoretical reasons. Quantitively, analyses in paper are performed at a level relevant to rodent but not NHP brain (single injections) and individual injections are clustered within a few monkeys and a few studies. Theoretically, report makes strong claims about importance of technology for disease related functional outcomes, but behavior was not widely tested. The original article reports a 91% success rate for optogenetic experiments in NHPs based on presence of any outcome (histological, physiological, or behavioral outcomes) after an injection of viral vectors. Reanalysis of data clustered at level of brain region and animal with a modified definition of success that included a behavioral and biological effect reveals that rate of success was approximately 62.5%, and only 53.1% for strong outcomes, in experiments that attempted to measure a behavioral and a biological effect. Only 6% of experiments in total database successfully achieved histological, physiological, and behavioral endpoints. This calls into question current efficacy of optogenetic techniques in NHP brain and suggests that we are a long way from being able to leverage them in the service of patients with neurological or psychiatric conditions.