Abstract
Brain perturbation studies allow detailed causal inferences of behavioral and neural processes. Because the combination of brain perturbation methods and neural measurement techniques is inherently challenging, research in humans has predominantly focused on non-invasive, indirect brain perturbations, or neurological lesion studies. Non-human primates have been indispensable as a neurobiological system that is highly similar to humans while simultaneously being more experimentally tractable, allowing visualization of the functional and structural impact of systematic brain perturbation. This review considers the state of the art in non-human primate brain perturbation with a focus on approaches that can be combined with neuroimaging. We consider both non-reversible (lesions) and reversible or temporary perturbations such as electrical, pharmacological, optical, optogenetic, chemogenetic, pathway-selective, and ultrasound based interference methods. Method-specific considerations from the research and development community are offered to facilitate research in this field and support further innovations. We conclude by identifying novel avenues for further research and innovation and by highlighting the clinical translational potential of the methods.
Highlights
The brain is a complex dynamical network and an advanced understanding of its functional mechanisms requires both observational and perturbation studies
The utility of combined non-human primate lesion and functional Magnetic Resonance Imaging studies (fMRI) studies for understanding compensatory mechanisms could be increased by further studying lesion effects on changes in task-related fMRI activation in behaving primates
Deep brain stimulation (DBS) in Non-human primates (NHPs) led to major advances in the treatment of Parkinson’s disease (Mitchell et al, 2018; Roelfsema and Treue, 2014)
Summary
The brain is a complex dynamical network and an advanced understanding of its functional mechanisms requires both observational and perturbation studies. With other animal models lacking either the cognitive capacity, or the structural and functional similarities to humans, and human research limited in the potential for detailed and systematic invasive neuronal recording and perturbation, the NHP model is truly in a unique position to investigate primate brain mechanisms and their relation to behavior (Roelfsema and Treue, 2014). The potential translation of knowledge and methods from NHPs to humans is highlighted wherever currently relevant or foreseeable in the near future We survey both established and novel non-reversible (lesions) and reversible perturbation approaches using electrical, pharmacological, optical, optogenetic, chemogenetic, pathway selective, or ultrasound brain perturbation approaches. The PRIME Resource Exchange platform (Messinger et al, 2021), another PRIME-DE initiative, will support the resource and information exchange on brain perturbation approaches and neuroimaging in a dynamical community-driven way
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