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Abstract In the past decade, there has been major interest in understanding the role of transcriptomics in the functional and anatomical layout of the human brain. To date, almost all of the work linking transcriptomics to human brain function and structure has been restricted to the cerebral cortex. The culmination of this work has identified transcriptomics as an important shared principle that can tie together function, structure, and gene expression. However, largely missing from this work is the subcortex—namely the cerebellum. Here, we investigate whether transcriptomics offer a link between function and structure in the human cerebellum, using gene expression data from post-mortem cerebella and multi-modal brain atlases. We find that transcriptomic gradients from a sparse subset of genes align with a macroanatomical, rather than a functional - parcellation of the cerebellum, and the transition of the main gradient occurs at the horizontal fissure for the group, as well as individual cerebella. Conversely, when filtering for cortex-specific genes, there is an alignment with continuous functional gradients of the cerebellum, but not discrete parcellated areas. 

Abstract The lateral prefrontal cortex (LPFC) is an evolutionarily expanded region in humans that is critical for numerous complex functions, many of which are largely hominoid specific. Although recent work shows that the presence or absence of specific sulci in anterior LPFC is associated with cognitive performance across age groups, it is unknown whether the presence of these structures relates to individual differences in the functional organization of LPFC. To fill this gap in knowledge, we leveraged multimodal neuroimaging data from two samples encompassing 82 young adult humans (aged 22–36 years) and show that the dorsal and ventral components of the paraintermediate frontal sulcus, or pimfs, present distinct morphological (surface area), architectural (thickness and myelination), and functional (resting-state connectivity networks) properties. We further contextualize the pimfs components within classic and modern cortical parcellations. Taken together, the dorsal and ventral pimfs components mark transitions in LPFC anatomy and function, across metrics and parcellations. These results emphasize that the pimfs is a critical structure to consider when examining individual differences in the anatomical and functional organization of LPFC and suggest that future individual-level parcellations could benefit from incorporating sulcal anatomy when delineating LPFC cortical regions. 

Abstract The relationship between structural variability in late-developing association cortices like the lateral prefrontal cortex (LPFC) and the development of higher-order cognitive skills is not well understood. Recent findings show that the morphology of LPFC sulci predicts reasoning performance; this work led to the observation of substantial individual variability in the morphology of one of these sulci, the para-intermediate frontal sulcus (pimfs). Here, we sought to characterize this variability and assess its behavioral significance. To this end, we identified the pimfs in a developmental cohort of 72 participants, ages 6–18. Subsequent analyses revealed that the presence or absence of the ventral component of the pimfs was associated with reasoning, even when controlling for age. This finding shows that the cortex lining the banks of sulci can support the development of complex cognitive abilities and highlights the importance of considering individual differences in local morphology when exploring the neurodevelopmental basis of cognition. 

Abstract The neuroanatomical changes that underpin cognitive development are of major interest in neuroscience. Of the many aspects of neuroanatomy to consider, tertiary sulci are particularly attractive as they emerge last in gestation, show a protracted development after birth, and are either human- or hominoid-specific. Thus, they are ideal targets for exploring morphological-cognitive relationships with cognitive skills that also show protracted development such as working memory (WM). Yet, the relationship between sulcal morphology and WM is unknown—either in development or more generally. To fill this gap, we adopted a data-driven approach with cross-validation to examine the relationship between sulcal depth in lateral prefrontal cortex (LPFC) and verbal WM in 60 children and adolescents between ages 6 and 18. These analyses identified 9 left, and no right, LPFC sulci (of which 7 were tertiary) whose depth predicted verbal WM performance above and beyond the effect of age. Most of these sulci are located within and around contours of previously proposed functional parcellations of LPFC. This sulcal depth model outperformed models with age or cortical thickness. Together, these findings build empirical support for a classic theory that tertiary sulci serve as landmarks in association cortices that contribute to late-maturing human cognitive abilities. 

A salient neuroanatomical feature of the human brain is its pronounced cortical folding, and there is mounting evidence that sulcal morphology is relevant to functional brain architecture and cognition. However, the relationships between sulcal anatomy, brain activity, and behavior are still poorly understood. We previously found that the depth of three small, shallow sulci in the lateral prefrontal cortex (LPFC) was linked to reasoning performance during development (Voorhies et al., 2021). These findings beg the question: What is the linking mechanism between sulcal morphology and cognition? Here, we investigated functional connectivity among sulci in LPFC and the lateral parietal cortex in participants drawn from the same sample as our previous study. We leveraged manual parcellations (21 sulci/hemisphere, 1,806 total) and functional magnetic resonance imaging data from a reasoning task from 43 participants aged 7–18 years (20 females). We conducted clustering and classification analyses of individual-level functional connectivity among sulci. Broadly, we found that (1) connectivity patterns of individual sulci could be differentiated and more accurately than cortical patches equated for size and shape; (2) sulcal connectivity did not consistently correspond with that of probabilistic labels or large-scale networks; (3) sulci clustered based on connectivity patterns, not dictated by spatial proximity; and (4) across individuals, greater depth was associated with higher network centrality for several sulci under investigation. These results illustrate how sulcal morphology can be functionally relevant and provide proof of concept that using sulci to define an individual coordinate space for functional connectomes is a promising future direction. 

Abstract A growing body of literature indicates strong associations between indentations of the cerebral cortex (i.e., sulci) and individual differences in cognitive performance. Interruptions, or gaps, of sulci (historically known as pli de passage) are particularly intriguing as previous work suggests that these interruptions have a causal effect on cognitive development. Here, we tested how the presence and morphology of sulcal interruptions in the left posterior occipitotemporal sulcus (pOTS) longitudinally impact the development of a culturally-acquired skill: reading. Forty-three children were successfully followed from age 5 in kindergarten, at the onset of literacy instruction, to ages 7 and 8 with assessments of cognitive, pre-literacy, and literacy skills, as well as MRI anatomical scans at ages 5 and 8. Crucially, we demonstrate that the presence of a left pOTS gap at 5 years is a specific and robust longitudinal predictor of better future reading skills in children, with large observed benefits on reading behavior ranging from letter knowledge to reading comprehension. The effect of left pOTS interruptions on reading acquisition accumulated through time, and was larger than the impact of benchmark cognitive and familial predictors of reading ability and disability. Finally, we show that increased local U-fiber white matter connectivity associated with such sulcal interruptions possibly underlie these behavioral benefits, by providing a computational advantage. To our knowledge, this is the first quantitative evidence supporting a potential integrative gray-white matter mechanism underlying the cognitive benefits of macro-anatomical differences in sulcal morphology related to longitudinal improvements in a culturally-acquired skill.