Although these techniques have been most successfully implemented in rodent models, they have the potential to be similarly impactful in studies of nonhuman primate brains. Common marmosets (Callithrix jacchus) have recently emerged as a candidate primate model for gene editing, providing a potentially powerful model for studies of neural circuitry and disease in primates. The application of viral transduction methods in marmosets for identifying and manipulating neuronal circuitry is a crucial step in developing this species for neuroscience research. In the present study we developed a novel, chronic method to successfully induce rapid photostimulation in individual cortical neurons transduced by adeno-associated virus to express channelrhodopsin (ChR2) in awake marmosets. We found that large proportions of neurons could be effectively photoactivated following viral transduction and that this procedure could be repeated for several months. These data suggest that techniques for viral transduction and optical manipulation of neuronal populations are suitable for marmosets and can be combined with existing behavioral preparations in the species to elucidate the functional neural circuitry underlying perceptual and cognitive processes.

Calcium imaging is a powerful tool for recording from large populations of neurons in vivo. Imaging in rhesus macaque motor cortex can enable the discovery of fundamental principles of motor cortical function and can inform the design of next generation brain-computer interfaces (BCIs). Surface two-photon imaging, however, cannot presently access somatic calcium signals of neurons from all layers of macaque motor cortex due to photon scattering. Here, we demonstrate an implant and imaging system capable of chronic, motion-stabilized two-photon imaging of neuronal calcium signals from macaques engaged in a motor task. By imaging apical dendrites, we achieved optical access to large populations of deep and superficial cortical neurons across dorsal premotor (PMd) and gyral primary motor (M1) cortices. Dendritic signals from individual neurons displayed tuning for different directions of arm movement. Combining several technical advances, we developed an optical BCI (oBCI) driven by these dendritic signalswhich successfully decoded movement direction online. By fusing two-photon functional imaging with CLARITY volumetric imaging, we verified that many imaged dendrites which contributed to oBCI decoding originated from layer 5 output neurons, including a putative Betz cell. This approach establishes new opportunities for studying motor control and designing BCIs via two photon imaging.

Calcium imaging has rapidly developed into a powerful tool for recording from large populations of 1 neurons in vivo. Imaging in rhesus macaque motor cortex can enable the discovery of new principles of 2 motor cortical function and can inform the design of next generation brain-computer interfaces (BCIs). 3Surface two-photon (2P) imaging, however, cannot presently access somatic calcium signals of neurons 4 from all layers of macaque motor cortex due to photon scattering. Here, we demonstrate an implant and 5 imaging system capable of chronic, motion-stabilized two-photon (2P) imaging of calcium signals from 6 in macaques engaged in a motor task. By imaging apical dendrites, some of which originated from deep 7 layer 5 neurons, as as well as superficial cell bodies, we achieved optical access to large populations of 8 deep and superficial cortical neurons across dorsal premotor (PMd) and gyral primary motor (M1) 9 cortices. Dendritic signals from individual neurons displayed tuning for different directions of arm 10 movement, which was stable across many weeks. Combining several technical advances, we developed 11 an optical BCI (oBCI) driven by these dendritic signals and successfully decoded movement direction 12 online. By fusing 2P functional imaging with CLARITY volumetric imaging, we verify that an imaged 13 dendrite, which contributed to oBCI decoding, originated from a putative Betz cell in motor cortical layer 14 5. This approach establishes new opportunities for studying motor control and designing BCIs. 15 Trautmann, O'Shea, Sun et al. activity by contextualizing activity within a dense, spatially localized, and genetically annotated map of 40 the neural tissue. Optical methods can also readily access large neural populations 23,24 , and can access 41 additional neurons or brain areas simply by translating the objective lens or adjusting the scan pattern. An 42 oBCI would thereby be particularly well suited for enabling researchers to explore the design space of 43 how best to measure from neural populations (which area(s) to record from, how many neurons are 44 needed, electrode density and distribution, etc). The knowledge gained can help set the design 45 specifications for future electrode-array based BCIs. Using optical techniques, it is possible to dissociate 46 the limitations of present-day electrode arrays, which are surgically implanted in a fixed location, from 47 to select an appropriate viral serotype tailored to the immune response of each monkey. (B) Viral 118 constructs were injected into cortex to deliver the calcium reporter gene. (C) A chamber designed for 119 chronic 2P imaging in premotor cortex and motor cortex was implanted. (D) Widefield (1P) imaging was 120 used to assess GCaMP expression and establish vascular fiducial markers for navigating to specific sites 121 on the cortex. (E) A macaque was trained to perform a reaching task to radially arranged targets. (F) 2P 122 imaging was used to obtain functional signals at single-cell resolution from motor cortex. (G) During 12...

A case report is presented detailing the successful use of awake intraoperative memory testing while using white matter stimulation in order to isolate the fornix tracks involved in memory function. The identification of the white matter tracks of the fornix that were involved in memory function was used to tailor the neurosurgical resection of a third ventricle tumor that was impinging on the fornix in order to successfully preserve memory functioning in the patient.

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