Sex-related differences in intrinsic brain dynamism and their neurocognitive correlates

The application of dynamic or time-varying connectivity techniques to neuroimaging data represents a new and complementary method to traditional static (time-averaged) methods, capturing additional patterns of variation in human brain function. Dynamic connectivity and related measures of brain dynamism have been detailed in neurotypical brain function, during human development and across neuropsychiatric disorders, and linked to cognitive control and executive function abilities. Despite this large and growing body of work, little is known about whether sex-related differences are present in dynamic connectivity and brain dynamism, a question pertinent to our understanding of brain function in both health and disease, given the sex bias observed in the prevalence of neuropsychiatric disorders, and well-demonstrated sex-related differences in the performance of certain neurocognitive tasks. We present the first analyses of sex-related effects in dynamic connectivity and brain dynamism referenced to neurocognitive function, in a large sample of sex-, age- and motion-matched subjects in 24- and 51-network whole brain functional parcellations. We demonstrate that sexual dimorphism is present in human dynamic connectivity and in multiple high-order measures of brain dynamism, as well as validating prior work that sex-related differences exist in static intrinsic connectivity. We also provide the first evidence suggesting a link between differential neurocognitive performance by males and females and brain functional dynamics. Reduced dynamism in females, who spend more time in certain brain states and switch states less frequently, may provide a 'stickier' functional substrate associated with slower response inhibition, whereas males exhibit greater dynamic fluidity, change between certain states more often and range over a larger state space, achieving superior performance in mental rotation, which demands an iterative visualization and problem-solving approach. We conclude that sex is an important variable to consider in functional MRI experiments and the analysis of dynamic connectivity and brain dynamism.