Understanding the relationship between neuroanatomy and function in portions of human cortex that are expanded compared to other mammals such as lateral prefrontal cortex (LPFC) is of major interest in systems and cognitive neuroscience. When considering neuroanatomicalfunctional relationships in LPFC, shallow indentations in cortex known as tertiary sulci have been largely ignored. Here, by implementing a multi-modal approach and manually defining 936 neuroanatomical structures in 72 hemispheres (males and females), we show that a subset of these overlooked tertiary sulci serve as a meso-scale link between microstructural (myelin content) and functional (network connectivity) properties of human LPFC in individuals. For example, the posterior middle frontal sulcus (pmfs) is a tertiary sulcus with three components that differ in their myelin content, resting state connectivity profiles, and engagement across metaanalyses of 83 cognitive tasks. Further, generating microstructural profiles of myelin content across cortical depths for each pmfs component and the surrounding middle frontal gyrus (MFG) shows that both gyral and sulcal components of the MFG have greater myelin content in deeper compared to superficial layers and that the myelin content in superficial layers of the gyral components is greater than sulcal components. These findings support a classic, yet largely unconsidered theory that tertiary sulci may serve as landmarks in association cortices, as well as a modern cognitive neuroscience theory proposing a functional hierarchy in LPFC. As there is a growing need for computational tools that automatically define tertiary sulci throughout cortex, we share pmfs probabilistic sulcal maps with the field..

The lateral prefrontal cortex (LPFC) is disproportionately expanded in humans compared to non-human primates, although the relationship between LPFC brain structures and uniquely human cognitive skills is largely unknown. Here, we test the relationship between variability in LPFC tertiary sulcal morphology and reasoning scores in a cohort of children and adolescents. Using a data-driven approach in independent discovery and replication samples, we show that the depth of specific LPFC tertiary sulci is associated with individual differences in reasoning scores beyond age. To expedite discoveries in future neuroanatomical-behavioral studies, we share tertiary sulcal definitions with the field. These findings support a classic but largely untested theory linking the protracted development of tertiary sulci to late-developing cognitive processes.

Hominoid-specific brain structures are of particular importance in understanding the evolution of human brain structure and function, as they are absent in mammals that are widely studied in the extended neuroscience field. Recent research indicates that the human fusiform gyrus (FG), which is a hominoid-specific structure critical for complex object recognition, contains a tertiary, longitudinal sulcus (mid-fusiform sulcus, MFS) that bisects the FG into lateral and medial parallel gyri. The MFS is a functional and architectonic landmark in the human brain. Here, we tested if the MFS is specific to the human FG or if the MFS is also identifiable in other hominoids. Using magnetic resonance imaging and cortical surface reconstructions in 30 chimpanzees and 30 humans, we show that the MFS is also present in chimpanzees. The MFS is relatively deeper and cortically thinner in chimpanzees compared to humans. Additional histological analyses reveal that the MFS is not only present in humans and chimpanzees, but also in bonobos, gorillas, orangutans, and gibbons. Taken together, these results reveal that the MFS is a sulcal landmark that is shared between humans and other hominoids. These results require a reconsideration of the sulcal patterning in ventral temporal cortex across hominoids, as well as revise the compensation theory of cortical folding.

Understanding brain structure-function relationships, and their development and evolution, is central to neuroscience research. Here, we show that morphological differences in posterior cingulate cortex (PCC), a hub of functional brain networks, predict individual differences in macroanatomical, microstructural, and functional features of PCC. Manually labeling 4511 sulci in 572 hemispheres, we found a shallow cortical indentation (termed the inframarginal sulcus; ifrms ) within PCC that is absent from neuroanatomical atlases yet colocalized with a focal, functional region of the lateral frontoparietal network implicated in cognitive control. This structural-functional coupling generalized to meta-analyses consisting of hundreds of studies and thousands of participants. Additional morphological analyses showed that unique properties of the ifrms differ across the life span and between hominoid species. These findings support a classic theory that shallow, tertiary sulci serve as landmarks in association cortices. They also beg the question: How many other cortical indentations have we missed?

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.