Yuqi Feng^1,2,3 (), An Ping², Songping Yao^1,2, Sunhang Shi^1,2, Meilan Liu^1,2, Henry Evrard⁴, Jianbao Wang⁵, Anna Roe^6,7; ¹Key Laboratory for Biomedical Engineering of Ministry of Education, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China, ²Department of Neurosurgery of the Second Affiliated Hospital, Interdisciplinary Institute of Neuroscience and Technology, School of Medicine, Zhejiang University, Hangzhou, China, ³Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA, ⁴International Center for Primate Brain Research, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China, ⁵Affiliated Mental Health Center & Hangzhou Seventh People's Hospital, School of Medicine, Zhejiang University, Hangzhou, China, ⁶Translational Neuroscience Laboratory Division, Center for Biomedical Imaging and Neuromodulation (C-BIN), Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA, ⁷New York University Grossman School of Medicine, New York, NY, USA

Introduction: In human and nonhuman primates, the pulvinar is a key hub for visual pathways, and supports higher-order functions such as attention and emotion. We previously showed, using a novel functional connectivity mapping method INS-fMRI (Infrared Neural Stimulation in ultra-high-field fMRI, 1 site: 1 brainwide network), that focal stimulation (1) in PL/PI (lateral/inferior pulvinar) led to mesoscale (mm-scale), topographic activations in visual cortical areas (in ventral and dorsal pathways) and (2) surprisingly, INS in PM (medial pulvinar) activated limbic areas (cingulate, insula, amygdala) in highly organized patchy fashion. Here, we extend this investigation to activated areas in prefrontal cortex. Methods: INS stimulation (1875nm, activating <500um-sized clusters of neurons, pulse trains 200 Hz, duration 0.5 sec; pulse width 0.25 msec, 200 μm optical fiber) was delivered to 28 loci in pulvinar (PI, PL and PM) of 2 anesthetized macaque monkeys in 7T fMRI (BOLD GRE-EPI, 1.5mm isotropic). Statistical tests and controls revealed reproducibility of activation sites. Results: (1) Each INS site in pulvinar PI, PL, and PM subnuclei activated brain-wide functional networks consisting of arrays of mesoscale activations. (a) Consistent with anatomical studies, the mesoscale functional connections of PL/PI and PM are distinct. Whereas INS in PI and PL revealed connections with visual areas (V1-V4, TPO, TEO, LIP, VIP), INS in PM revealed patterns of connections with limbic, medial and orbitofrontal (13,14) areas. Interestingly, stimulation sites in the foveal region of PI/PL revealed activations in high-order regions such as area 7a and dorsolateral prefrontal (8, 46) areas. All activations were consistently mesoscale in size and distributed in patchy, non-overlapping fashion. Conclusion: We extend and strengthen the view that pulvinar provides environmental context for both visual (PL/PI) and emotion-related (PM) function. Functional connections exhibit mesoscale, non-overlapping organization. Connectivity of foveal PI/PL with prefrontal areas suggest a potential specialization in foveal engagement.