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.