Rodent fear-learning models posit that amygdala–infralimbic connections facilitate extinction while amygdala–prelimbic prefrontal connections mediate fear expression. Analogous amygdala–prefrontal circuitry between rodents and primates is not established. Using paired small volumes of neural tracers injected into the perigenual anterior cingulate cortex (pgACC; areas 24b and 32; a potential homologue to rodent prelimbic cortex) and subgenual anterior cingulate cortex (sgACC, areas 25 and 14c; a potential homologue to rodent infralimbic cortex) in a single hemisphere, we mapped amygdala projections to the pgACC and sgACC within single subjects. All injections resulted in dense retrograde labeling specifically within the intermediate division of the basal nucleus (Bi) and the magnocellular division of the accessory basal nucleus (ABmc). Areal analysis revealed a bias for connectivity with the sgACC, with the ABmc showing a greater bias than the Bi. Double fluorescence analysis revealed that sgACC and pgACC projections were intermingled within the Bi and ABmc, where a proportion were double labeled. We conclude that amygdala inputs to the ACC largely originate from the Bi and ABmc, preferentially connect to the sgACC, and that a subset collaterally project to both sgACC and pgACC. These findings advance our understanding of fear extinction and fear expression circuitry across species.

Creativity is the ability to produce work that is novel, high in quality, and appropriate to an audience. One domain of creativity comes from musical improvisation, in which individuals spontaneously create novel auditory-motor sequences that are aesthetically rewarding. Here we test the hypothesis that individual differences in creative behavior are subserved by mesial and lateral differences in white matter connectivity. We compare jazz improvising musicians against classical (non-improvising) musicians and non-musician control subjects in musical performance and diffusion tensor imaging. Subjects improvised on short musical motifs and underwent DTI.Statistical measures of fluency and entropy for musical performances predicted expert ratings of creativity for each performance. Tract-Based Spatial Statistics (TBSS) showed higher Fractional Anisotropy (FA) in the cingulate cortex and corpus callosum in jazz musicians. FA in the cingulate also correlated with entropy. Probabilistic tractography from these mesial regions to lateral seed regions of the arcuate fasciculus, a pathway known to be involved in sound perception and production, showed mesial-to-lateral connectivity that correlated with improvisation training. Results suggest that white matter connectivity between lateral and mesial structures may integrate domain-general and domain-specific components of creativity.

Creativity has been defined as requiring both novelty and effectiveness, but little is known about how this standard definition applies in music. Here, we present results from a pilot study in which we combine behavioral testing in musical improvisation and structural neuroimaging to relate brain structure to performance in a creative musical improvisation task. Thirty-eight subjects completed a novel improvisation continuation task and underwent T1 MRI. Recorded performances were rated by expert jazz instructors for creativity. Voxel-based morphometric analyses on T1 data showed that creativity ratings were negatively associated with gray matter volume in the right inferior temporal gyrus and bilateral hippocampus. The duration of improvisation training, which was significantly correlated with creativity ratings, was negatively associated with gray matter volume in the rolandic operculum. Together, results show that musical improvisation ability and training are associated with gray matter volume in regions that are previously linked to learning and memory formation, perceptual categorization, and sensory integration. The present study takes a first step towards understanding the neuroanatomical basis of musical creativity by relating creative musical improvisation to individual differences in gray matter structure.

Many epithelial compartments undergo constitutive renewal in homeostasis but activate unique regenerative responses following injury. The clear corneal epithelium is crucial for vision and is renewed from limbal stem cells (LSCs). Using single-cell RNA sequencing, we profiled the mouse corneal epithelium in homeostasis, aging, diabetes, and dry eye disease (DED), where tear deficiency predisposes the cornea to recurrent injury. In homeostasis, we capture the transcriptional states that accomplish continuous tissue turnover. We leverage our dataset to identify candidate genes and gene networks that characterize key stages across homeostatic renewal, including markers for LSCs. In aging and diabetes, there were only mild changes with <15 dysregulated genes. The constitutive cell types that accomplish homeostatic renewal were conserved in DED but were associated with activation of cell states that comprise “adaptive regeneration.” We provide global markers that distinguish cell types in homeostatic renewal vs. adaptive regeneration and markers that specifically define DED-elicited proliferating and differentiating cell types. We validate that expression of SPARC, a marker of adaptive regeneration, is also induced in corneal epithelial wound healing and accelerates wound closure in a corneal epithelial cell scratch assay. Finally, we propose a classification system for LSC markers based on their expression fidelity in homeostasis and disease. This transcriptional dissection uncovers the dramatically altered transcriptional landscape of the corneal epithelium in DED, providing a framework and atlas for future study of these ocular surface stem cells in health and disease.