A pragmatic reevaluation of the efficacy of nonhuman primate optogenetics

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 (2020) introduces an openly available resource detailing published and unpublished studies using optogenetics to manipulate the nonhuman primate (NHP) brain. The open science efforts of the team are important and rare in NHP neuroscience, but the conclusions drawn about the success rate of optogenetics in the NHP brain are problematic for quantitative and theoretical reasons. Quantitively, the analyses in the paper are performed at a level relevant to the rodent but not NHP brain (single injections) and individual injections are clustered within a few monkeys and a few studies. Theoretically, the report makes strong claims about the importance of the 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 the presence of any outcome (histological, physiological, or behavioral outcomes) after an injection of viral vectors. Reanalysis of the data clustered at the level of brain region and animal with a modified definition of success that included a behavioral and biological effect reveals that the 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 the experiments in the total database successfully achieved histological, physiological, and behavioral endpoints. This calls into question the current efficacy of optogenetic techniques in the 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".