Remembering the null hypothesis when searching for brain sex differences

Human brain sex differences have fascinated scholars for centuries and become a key focus of neuroscientists since the dawn of MRI. We recently published a major review in Neuroscience and Biobehavioral Reviews showing that most male-female brain differences in humans are small and few have been reliably replicated. Although widely cited, this work was the target of a critical Commentary by DeCasien et al. (Biol Sex Differ 13:43, 2022). In this response, I update our findings and confirm the small effect sizes and pronounced scatter across recent large neuroimaging studies of human sex/gender difference. Based on the sum of data, neuroscientists would be well-advised to take the null hypothesis seriously: that men and women's brains are fundamentally similar, or "monomorphic". This perspective has important implications for how we study the genesis of behavioral and neuropsychiatric gender disparities.