Investigating cortical microstructure in early infancy: associations with later temperamental negative affectivity and psychopathology symptoms

The National Institute of Mental Health awarded Vanderbilt University $106,228 on November 1, 2026, under the Mental Health Research Grants program (CFDA 93.242) to investigate associations between cortical microstructure in early infancy and later temperamental negative affectivity and psychopathology symptoms.

The research examines neural correlates of negative affectivity (characterized by frequent and intense negative emotional responses such as fear, sadness, and frustration) in infants during the first months of life, prior to symptom onset. The work uses cortical microstructure indices—neurite density index and orientation dispersion index—to assess cortical myeloarchitecture and cytoarchitecture at higher specificity than prior macrostructural approaches. The study takes a network perspective to assess how dysfunction in arousal/salience and regulation systems, present at birth in some infants, drives structural substrates in cortical microstructure and relates to prospective negative affectivity and psychopathology symptoms. Findings are intended to inform early intervention strategies for infants at increased risk for anxiety and depression.

Work is performed in Nashville, Tennessee. The period of performance runs from November 1, 2026, through April 5, 2028. This is a project grant (assistance type), distinct from a procurement contract.

Abstract

Negative affectivity (NA) is an individual difference trait with high levels characterized by frequent and intense negative emotional responses such as fear, sadness, and frustration. NA can be reliably assessed within the first months of life; infants high in NA are at an increased risk for developing anxiety and depression later in life. Identifying the neural correlates of NA in early infancy-prior to the onset of psychopathology symptoms- can provide valuable insights into the mechanisms underlying emotional functioning in early development and inform early interventions. Previous research has established links between macrostructural gray matter (GM) variations and behavioral phenotypes associated with NA. However, these approaches lack the specificity needed to understand the underlying neurodevelopmental processes. Cortical microstructure, indexed by the neurite density index (NDI) and the orientation dispersion index (ODI), reflects cortical myeloarchitecture and cytoarchitecture, offering a more detailed view of neurodevelopment. Additionally, in human adults, behavioral phenotypes linked to NA, such as anxiety and depression, are characterized by hyperactivity in the arousal/salience systems and/or hypoactivity in the regulation systems. Importantly, emerging evidence suggests that some of the dysfunctions in arousal/salience and regulation systems are present at birth, before the onset of symptoms, and are linked to NA in early infancy. Given that brain structurual integrity is fundamental to supporting functioning, IT is plausible that dysfunction in arousal/salience and regulation systems is driven by structural substrates in cortical microstructure. Thus, we will examine associations between cortical microstructure and prospective NA and psychopathology symptoms from a network perspective, specifically focusing on the arousal/salience systems (ventral attention network [van] and cingulo-opercular network [CON] and top-down regulation systems (default mode network [DMN] and frontoparietal network [FPN]). Our central hypothesis is that higher microstructural indices in van/CON and lower indices in DMN/FPN shortly after birth would be associated with higher levels of NA later in infancy and psychopathology symptoms in toddlerhood. This project will fill a critical GAP in the developmental neuroscience literature by mapping the associations between cortical microstructure in early infancy and later NA and psychopathology symptoms. Through this project, the candidate will develop valuable expertise in early manifestations of psychopathology, neuroimaging data processing and computational skills, clinical neuroscience, and advanced writing and presentation skills. Obtaining such training will position the candidate as a competitive postdoctoral researcher and eventually an independent investigator at a research university, significantly contributing to mapping affective neurodevelopmental risk for psychopathology.