A Paradigm Shift in Human Neuroscience Research: Progress, Prospects, and a Proof of Concept for Population Neuroscience

Abstract

Recent advances and reflections on reproducible human neuroscience, especially brain-wide association studies (BWAS) leveraging large datasets, have led to divergent and sometimes opposing views on research practices and priorities. The debates span multiple dimensions. Shifts along these axes have fractured consensus and further fragmented an already heterogeneous field of cognitive neuroscience. Here, we sketch a holistic and integrative response grounded in population neuroscience, organized around a closed-loop "design-analysis-interpretation" research cycle that aims to build consensus while bridging these divides. Our central claim is that population neuroscience offers a unique population-level vantage point for identifying general principles, characterizing inter-individual variabilities, and benchmarking intra-individual changes, thereby providing a supportive framework for small-scale, mechanism-focused studies at the individual level and allowing them to co-evolve with population-level studies. Population neuroscience is not simply about providing larger N for BWAS; its deeper goal is to accumulate a family of cross-scale priors and shared infrastructures that can support design, analysis, and interpretation of human neuroscience for decades to come. In this sense, we outline a "third-generation" view of population neuroscience that reorients the field from amassing isolated associations toward building integrative reference frameworks for future mechanistic and translational work.