The challenges of understanding the immensely complex spatiotemporally variable neural circuitry in the normal and diseased brain

A recent detailed analysis of how well neuroscientists understand brain function concluded thatwe have highly overestimated this ability. Here, we support this view but argue for importantexceptions whose identification serves useful didactic purposes. For example, the highly-studiedSuperior Colliculus (SC), known best as involved in controlling gaze shifts, has a much morecomplex functional organization than originally assumed; being involved in encoding manydifferent behaviours including cognitive functions not even requiring eye movements. Anadditionally important, but less understood, brain mechanism regards how sequences of differentbehaviors are generated rapidly, each often requiring a unique brain-wide spatiotemporal patternof neural activity. How are different complex neural circuits selected and rapidly switched,sequentially, from one brain-wide spatiotemporal configuration to another? What experimentalapproaches are needed to understand major circuit complexity and how can this knowledge beapplied to research on neurological diseases? Here, we consider these questions using, asexamples, two brain regions: the highly studied midbrain’s SC and visual area V4, both of whomhave profuse connectivity to cortical and subcortical brain regions but with the SC’s dynamicmulti-functional connectivity being far better understood. We suggest that comparisons betweenthe best understood SC and less understood V4 can guide reflections on what experimental andevolutionary-based theoretical approaches are important to understand brain-wide dynamic neuralsignal processing.