Introduction: Cortical brain-machine interface (BMI) devices and subcortical single unit recordings have provided a great deal of insight into brain networks. However, to achieve greater understanding of complex networks, multi-unit recordings are needed from interconnected, deep areas of the brain. Since many studies will be performed in non-human primates (NHP), a reliable method of image-based targeting is needed to deliver devices with sub-millimeter precision. Here, we devised a precise and easily adaptable method of delivery to small, deep areas of the primate brain.

Methods: We performed magnetic resonance imaging (MRI) on 10 rhesus macaques (n = 7 male, 3 female; 4.7–11.5 kg) to determine optimal experimental design and transformation algorithm for MRI-based targeting. We also built a custom graphical user interface (GUI) to assist in planning, visualization, and analysis of optimal centroid–target locations. The protocol was then implemented n vivo for hippocampal catheter delivery in a rhesus macaque.

Results: Fiducial markers (1.5 x 4 mm titanium screws) were implanted via stab incisions in lightly sedated animals and were easily localized on MRI. Image-space coordinates were obtained and the animal was positioned into a stereotactic headframe to derive surgical coordinates. The GUI co-registered and transformed coordinate points, and also enabled analysis of fiducial registration error (FRE) in real-time. In addition, it provided estimates of the expected target registration error (TRE) based on fiducial configuration. An in vivo experiment verified catheter delivery to hippocampus using the described approach.

Conclusions: A reliable, precise method of image-based targeting in NHP brain is achievable using easily obtained materials, without the need for expensive equipment. Additionally, this novel method is not time-locked, enabling more practical use of operating rooms and pre-operative planning. This method will allow more extensive studies of multiple, deep, subcortical areas of interest for BMI device design.

Patient Care: This research will enable more extensive study of complex brain networks in a non-human primate model in order to inform future human clinical trials of neuropsychiatric neuromodulation and brain-machine interface device design.

Learning Objectives: By the end of this session, learners should be able to 1) describe the importance of deep brain targeting in the NHP model, 2) describe the barriers to accurate targeting, and 3) discuss this easily adaptable method of performing accurate targeting.

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