Pulvinar and thalamo-cortical interactions

One central line of research, in a long-standing collaboration with Melanie Wilke, focuses on thalamic pulvinar-cortical circuitry supporting visuomotor decisions and actions, in normal and impaired states. Beyond a fundamental neuroscientific value, it has a strong translational perspective since it affords a macaque monkey model of neurological disorders, e.g. spatial neglect or optic ataxia. We use a combination of functional imaging, MRI-targeted electrophysiological recordings and causal perturbation techniques such as reversible pharmacological inactivation and electrical microstimulation 1. The overarching premise is that the distributed communication between cortical areas can only be understood in concert with the contribution of subcortical structures, e.g. second-order thalamic nuclei such as the pulvinar. The pulvinar expanded dramatically during course of primate evolution, reaching its relative maximum in humans, and it is reciprocally connected to a vast array of cortical circuits. The functional significance of pulvinar and pulvinar-cortical connectivity remains not well understood. It has been suggested to control the flow of information between cortical areas supporting visuospatial attention, but the work in our lab began to reveal its complementary role in decision-making and visuomotor integration, beyond purely visuospatial domain 2–7. Our combined perturbation-fMRI studies show that the unilateral dorsal pulvinar inactivation or microstimulation lead to widespread task- and hemifield-specific BOLD activity changes in fronto-parietal and parieto-temporal cortices, in both hemispheres 1,8. Such changes in spatial representations, reflecting both the inactivation-induced behavioral deficits as well as the putative compensatory mechanisms are partially similar to consequences of parietal cortex inactivation we studied earlier 9–11. This line of work is further pursued on the neuronal level with simultaneous pulvinar inactivation and bihemispheric neuronal recordings using multielectrode linear arrays (V/S-probes) in the parietal cortex (areas LIP and MIP), during instructed and free-choice saccade and reach movements. We observed largely push-pull changes in spatial and hand-specific tuning in both the inactivated and the opposite hemisphere on the level of neuronal firing and local field potential (LFP) power. Likewise, we found inactivation-induced changes of local (within each hemisphere) and inter-areal (across hemispheres) functional connectivity, at the level of LFP-LFP and spike-LFP coupling, in specific frequency bands. These bihemispheric cortical effects that might underlie contralesional hemifield impairments and hand action/choice deficits after pulvinar inactivation (in preparation). We also performed simultaneous recordings in the pulvinar and parietal cortex to characterize their functional connectivity. The next step is to relate specific inactivation effects on single neurons to their putative cell type (e.g. using spike waveforms) and spike-LFP connectivity profile, in layer-specific fashion when the cortical anatomy allows it.
References
1. Klink, P.C., Aubry, J.-F., Ferrera, V.P., Fox, A.S., Froudist-Walsh, S., Jarraya, B., Konofagou, E.E., Krauzlis, R.J., Messinger, A., Mitchell, A.S., et al. (2021). Combining brain perturbation and neuroimaging in non-human primates. NeuroImage 235, 118017. doi.org/10.1016/j.neuroimage.2021.118017.
2. Wilke, M., Kagan, I., and Andersen, R.A. (2013). Effects of pulvinar inactivation on spatial decision-making between equal and asymmetric reward options. Journal of Cognitive Neuroscience 25, 1270–1283. doi.org/10.1162/jocn_a_00399.
3. Wilke, M., Schneider, L., Dominguez-Vargas, A.-U., Schmidt-Samoa, C., Miloserdov, K., Nazzal, A., Dechent, P., Cabral-Calderin, Y., Scherberger, H., Kagan, I., et al. (2018). Reach and grasp deficits following damage to the dorsal pulvinar. Cortex 99, 135–149. doi.org/10.1016/j.cortex.2017.10.011.
4. Dominguez-Vargas, A.-U., Schneider, L., Wilke, M., and Kagan, I. (2017). Electrical Microstimulation of the Pulvinar Biases Saccade Choices and Reaction Times in a Time-Dependent Manner. J. Neurosci. 37, 2234–2257. doi.org/10.1523/JNEUROSCI.1984-16.2016.
5. Schneider, L., Dominguez-Vargas, A.-U., Gibson, L., Kagan, I., and Wilke, M. (2019). Eye position signals in the dorsal pulvinar during fixation and goal-directed saccades. Journal of Neurophysiology 123, 367–391. doi.org/10.1152/jn.00432.2019.
6. Schneider, L., Dominguez-Vargas, A.-U., Gibson, L., Wilke, M., and Kagan, I. (2023). Visual, delay, and oculomotor timing and tuning in macaque dorsal pulvinar during instructed and free choice memory saccades. Cerebral Cortex 33, 10877–10900. doi.org/10.1093/cercor/bhad333.
7. Kaduk, K., Wilke, M., and Kagan, I. (2024). Dorsal pulvinar inactivation leads to spatial selection bias without perceptual deficit. Sci Rep 14, 12852. doi.org/10.1038/s41598-024-62056-5.
8. Kagan, I., Gibson, L., Spanou, E., and Wilke, M. (2021). Effective connectivity and spatial selectivity-dependent fMRI changes elicited by microstimulation of pulvinar and LIP. NeuroImage 240, 118283. doi.org/10.1016/j.neuroimage.2021.118283.
9. Wilke, M., Kagan, I., and Andersen, R.A. (2012). Functional imaging reveals rapid reorganization of cortical activity after parietal inactivation in monkeys. Proceedings of the National Academy of Sciences 109, 8274–8279. doi.org/10.1073/pnas.1204789109.
10. Christopoulos, V.N., Kagan, I., and Andersen, R.A. (2018). Lateral intraparietal area (LIP) is largely effector-specific in freechoice decisions. Scientific Reports 8. doi.org/10.1038/s41598-018-26366-9.
11. Christopoulos, V.N., Bonaiuto, J., Kagan, I., and Andersen, R.A. (2015). Inactivation of parietal reach region affects reaching but not saccade choices in internally guided decisions. Journal of Neuroscience 35, 11719–11728. doi.org/10.1523/JNEUROSCI.1068-15.2015