Sex-related differences in brain dynamism at rest as neural correlates of positive and negative valence system constructs

Clinical anxiety and depression are the most prevalent mental illnesses, likely representing maladaptive expressions of negative valence systems concerned with conditioned responses to fear, threat, loss, and frustrative nonreward. These conditions exhibit similar, striking sex/gender-related differences in onset, incidence, and severity for which the neural correlates are not yet established. In alarge sample of neurotypical young adults, we demonstrate that intrinsic brain dynamism metrics derived from sex-sensitive models of whole-brain network function are significantly associated with valence system traits. Surprisingly, we found that greater brain dynamism is strongly positively correlated to anxiety and depression traits in males, but almost wholly decoupled from traits for important cognitive control and reappraisal strategies associated with positive valence. Conversely, intrinsic brain dynamism is strongly positively coupled to drive, novelty-seeking and self-control in females with only rare or non-significant directional negative correlation with anxiety and depression traits. Our results suggest that the dynamic neural correlates of traits for valence, anxiety and depression are significantly different in males/men and females/women. These findings may relate to the known sex/gender-related differences in cognitive reappraisal of emotional experiences and clinical presentations of anxiety and depression, with potential relevance to gold standard therapies based on enhancing cognitive control strategies.