Relationship of neurite architecture to brain activity during task-based fMRI

Functional MRI (fMRI) has been widely used to examine changes in neuronal activity during cognitive tasks. Commonly used measures of gray matter macrostructure (e.g., cortical thickness, surface area, volume) do not consistently appear to serve as structural correlates of brain function. In contrast, gray matter microstructure, measured using neurite orientation dispersion and density imaging (NODDI), enables the estimation of indices of neurite density (neurite density index; NDI) and organization (orientation dispersion index; ODI) in gray mat-ter. Our study explored the relationship among neurite architecture, BOLD (blood-oxygen-level-dependent) fMRI, and cognition, using a large sample ( n = 750) of young adults of the human connectome project (HCP) and two tasks that index more cortical (working memory) and more subcortical (emotion processing) targeting of brain functions. Using NODDI, fMRI, structural MRI and task performance data, hierarchical regression analyses re-vealed that higher working memory-and emotion processing-evoked BOLD activity was related to lower ODI in the right DLPFC, and lower ODI and NDI values in the right and left amygdala, respectively. Common measures of brain macrostructure (i.e., DLPFC thickness/surface area and amygdala volume) did not explain any addi-tional variance (beyond neurite architecture) in BOLD activity. A moderating effect of neurite architecture on the relationship between emotion processing task-evoked BOLD response and performance was observed. Our find-ings provide evidence that neuro-/social-affective cognition-related BOLD activity is partially driven by the local neurite organization and density with direct impact on emotion processing. In vivo gray matter microstructure represents a new target of investigation providing strong potential for clinical translation.