Biological validation of mathematically derived hypothesis in neuroscience

Because of the complexity of the central nervous system, it is often difficult to biologically demonstrate the mathematically derived hypothesis in neuroscience studies. Most of the computational studies are terminated at proposing hypothesis. Here, we show an example of biological demonstration of mathematically derived hypothesis, targeting the contribution of the interhemispheric pathway to recovery of hand dexterity after spinal cord injury in macaque monkeys. The studies started from the whole brain functional imaging with low temporal resolution, followed by multichannel electrocorticography recordings with higher temporal resolution, non-biased analysis of whose extensive datasets yielded the hypothesis about critical contribution of a particular neuronal pathway. The hypothesis was then validated by using the pathway-selective chemogenetic manipulation technique with designer receptor exclusively activated by designer drugs. We believe this kind of framework of study paradigms would be critical for us to shift the systems neuroscience from “correlation analysis” to “causal demonstration”.