How causal perspectives can inform neuroscience data analysis

Abstract

Over the past two decades, considerable strides have been made in advancing neuroscientific techniques, yet challenges remain in attributing causality to observed associations. This review addresses a fundamental issue in observational neuroscience studies and advocates for incorporating causal inference frameworks into standard practice. We systematically introduce necessary definitions and concepts, emphasizing how causal assumptions underlie statistical analyses even when not explicitly stated. Through a running example on sleep quality and white matter integrity, we illustrate how persistent challenges, including confounding and selection biases, can be conceptualized and addressed using causal frameworks. We demonstrate practical approaches for making assumption violations transparent through hands-on examples: supplementary case studies using multi-site harmonization and head motion exclusion procedures provide step-by-step diagnostic techniques for checking covariate overlap and identifying selection bias through exclusion pattern analysis. We explore how these causal perspectives can inform both experimental design and analytical choices, particularly for observational studies where traditional randomization is infeasible. Together, we believe this framework offers concrete tools for strengthening causal interpretations and inspiring more robust approaches to problems in neuroscience.