Overall progress and impact: The laboratory has published 22 papers since this project started (2017) with substantial interest from the scientific community (PI: h-index = 33; 82 overall publications, >4,700 citations) and the media (Balezeau et al. Nat. Nsci. 2020 ranked 99th percentile in Altmetric score of 150,000 tracked articles of similar age with 42 news outlet articles and substantial social media interest 35K upvotes on reddit).
• Test for and establish correspondences between monkey and human intracranial recordings
We have established correspondences between intracranial recordings in humans and monkeys, and informed the human results with information not possible to obtain in humans (Kikuchi et al., PLoS Biology, 2017). We have also discovered a homolog of the human language pathway, pushing back it’s evolutionary origin by 20 million years (Balezeau et al., Nature Neuroscience, 2020). We have also established correspondences in effective functional connectivity using a new approach to visualize the impact of deep brain electrical stimulation (Rocchi, Oya et al., BioRxiv, 2020). These findings advance primates as an ideal model system for human cognition and identify pathways between auditory cortex and sites that are expected to be amodal or sensory input invariant (as is the language pathway and those that involve anterior temporal lobe sites).
• Translate technological approaches to humans by way of the work in monkeys
Our prior work in nonhuman primates used combined electrical stimulation and functional neuroimaging (esfMRI) to assess the impact of site-specific brain stimulation (Petkov et al., Nature Communications 2015). Given the importance of deep brain stimulation for treatment of debilitating neurological disorders, human neurosurgery teams have taken an interest in translating this approach to humans to allow neuroimaging to visualize the impact of deep brain stimulation. This led to a joint publication establishing the safety of the approach for human neurosurgery patients (Oya et al., J. Nsci. Meth. 2017). We also conducted the first study of effective connectivity in humans and monkeys using esfMRI and discovered remarkably similar effective connectivity to frontal and medial temporal lobe sites (Rocchi, Oya, BioRxiv, 2020). We are currently working on a global resource for human and monkey esfMRI to provide the broader scientific community with these rare date to support further discoveries. This is following on from a primate MRI resource that we contributed to and are now co-leading on (Milham et al., Neuron, 2018; Milham, Petkov et al., Neuron 2020).
• Identify neural mechanisms of sensory convergence for identifying individuals
Using a combination of both monkey neuronal and local field potential recordings, and human local field potential recordings we have obtained evidence of a more distributed set of amodal representation in the brain, challenging the notion of sensory convergent hubs. Yet, for identity specific processes there does seem to be a greater involvement of more anterior temporal lobe areas, providing support for the hub-and-spokes model of sensory convergence and concept formation (Muers et al., Society for Neuroscience 2019; paper in preparation for submission).
• Conduct site-specific brain perturbation to assess causal influences
We have conducted both electrical stimulation and neuroimaging (esfMRI) in both monkeys and humans and established evidence in humans for a privileged auditory to inferior frontal pathway as has been known in monkeys and equally indirect effective connectivity with medial temporal lobe sites (Rocchi, Oya et al., BioRxiv, 2020). In the nonhuman primates we have also begun optogenetic studies allowing us to control neural responses with light. This has led to us contributing to a resource (Trembley et al., submitted). Another project has assessed the impact of surgical resection of epileptic sites in the anterior temporal lobe on behaviour and neurophysiology of sites that are affected because of the loss of interconnectivity with the brain areas crucial for this grant proposal (Kocsis et al., Society for Neuroscience 2019; in preparation for submission). This observation has substantial implications for neurosurgical approaches and are now being pursued with primate models to understand the neurophysiological interactions between these brain areas in ways not possible in humans.
• Identify cognitive influences on sensory processing and test for and establish correspondences between monkeys as animal models and humans
We have established correspondences between monkeys and human for cognition using an audio-visual selective attention task in both species and functional neuroimaging (Rinne et al., Cerebral Cortex, 2017). We have also advanced paradigms to better assess cognitive influences in monkeys with a closer correspondence of effects in humans (Wikman et al., Sci. Rep.).
