Lateral frontoparietal functional connectivity based on individual sulcal morphology.

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. Recent studies have emphasized putative tertiary sulci (pTS): small, shallow, late-developing, and evolutionarily new sulci that have been posited to serve as functional landmarks in association cortices. A fruitful approach to characterizing brain architecture has been to delineate regions based on transitions in fMRI-based functional connectivity profiles; however, exact regional boundaries can change depending on the data used to generate the parcellation. As sulci are fixed neuroanatomical structures, here, we propose to anchor functional connectivity to individual-level sulcal anatomy. We characterized fine-grained patterns of functional connectivity across 42 sulci in lateral prefrontal (LPFC) and lateral parietal cortices (LPC) in a pediatric sample (N = 43; 20 female; ages 7-18). Further, we test for relationships between pTS morphology and functional network architecture, focusing on depth as a defining characteristic of these shallow sulci, and one that has been linked to variability in cognition. We find that 1) individual sulci have distinct patterns of connectivity, but nonetheless cluster together into groups with similar patterns - in some cases with distant rather than neighboring sulci, 2) there is moderate agreement in cluster assignments at the group and individual levels, underscoring the need for individual-level analyses, and 3) across individuals, greater depth was associated with higher network centrality for several pTS. These results highlight the importance of considering individual sulcal morphology for understanding functional brain organization. Significance Statement: A salient, and functionally relevant, feature of the human brain is its pronounced cortical folding. However, the links between sulcal anatomy and brain function are still poorly understood - particularly for small, shallow, individually variable sulci in association cortices. Here, we explore functional connectivity among individually defined sulci in lateral prefrontal and parietal regions. We find that individual sulci have distinct patterns of connectivity but nonetheless cluster together into groups with similar connectivity - in some cases spanning lateral prefrontal and parietal sulci. We further show that the network centrality of specific sulci is positively associated with their depth, thereby helping to bridge the gap between individual differences in brain anatomy and functional networks leveraging the sulcal anatomy of the individual.

Sulcal variability in anterior lateral prefrontal cortex contributes to variability in reasoning performance among young adults.

Identifying structure-function correspondences is a major goal among biologists, cognitive neuroscientists, and brain mappers. Recent studies have identified relationships between performance on cognitive tasks and the presence or absence of small, shallow indentations, or sulci, of the human brain. Building on the previous finding that the presence of the ventral para-intermediate frontal sulcus (pimfs-v) in the left anterior lateral prefrontal cortex (aLPFC) was related to reasoning task performance in children and adolescents, we tested whether this relationship extended to a different sample, age group, and reasoning task. As predicted, the presence of this aLPFC sulcus was also associated with higher reasoning scores in young adults (ages 22-36). These findings have not only direct developmental, but also evolutionary relevance-as recent work shows that the pimfs-v is exceedingly rare in chimpanzees. Thus, the pimfs-v is a key developmental, cognitive, and evolutionarily relevant feature that should be considered in future studies examining how the complex relationships among multiscale anatomical and functional features of the brain give rise to abstract thought.

Defining putative tertiary sulci in lateral prefrontal cortex in chimpanzees using human predictions.

Similarities and differences in brain structure and function across species are of major interest in systems neuroscience, comparative biology, and brain mapping. Recently, increased emphasis has been placed on tertiary sulci, which are shallow indentations of the cerebral cortex that appear last in gestation, continue to develop after birth, and are largely either human or hominoid specific. While tertiary sulcal morphology in lateral prefrontal cortex (LPFC) has been linked to functional representations and cognition in humans, it is presently unknown if small and shallow LPFC sulci also exist in non-human hominoids. To fill this gap in knowledge, we leveraged two freely available multimodal datasets to address the following main question: Can small and shallow LPFC sulci be defined in chimpanzee cortical surfaces from human predictions of LPFC tertiary sulci? We found that 1-3 components of the posterior middle frontal sulcus (pmfs) in the posterior middle frontal gyrus are identifiable in nearly all chimpanzee hemispheres. In stark contrast to the consistency of the pmfs components, we could only identify components of the paraintermediate frontal sulcus (pimfs) in two chimpanzee hemispheres. Putative LPFC tertiary sulci were relatively smaller and shallower in chimpanzees compared to humans. In both species, two of the pmfs components were deeper in the right compared to the left hemisphere. As these results have direct implications for future studies interested in the functional and cognitive role of LPFC tertiary sulci, we share probabilistic predictions of the three pmfs components to guide the definitions of these sulci in future studies.

Sulcal variability in anterior lateral prefrontal cortex contributes to variability in reasoning performance among young adults.

Identifying structure-function correspondences is a major goal among biologists, cognitive neuroscientists, and brain mappers. Recent studies have identified relationships between performance on cognitive tasks and the presence or absence of small, shallow indentations, or sulci, of the human brain. Building on the previous finding that the presence of one such sulcus in the left anterior lateral prefrontal cortex (aLPFC) was related to reasoning task performance in children and adolescents, we tested whether this relationship extended to a different sample, age group, and reasoning task. As predicted, the presence of this aLPFC sulcus-the ventral para-intermediate frontal sulcus-was also associated with higher reasoning scores in young adults (ages 22-36). These findings have not only direct developmental, but also evolutionary relevance-as recent work shows that the pimfs-v is exceedingly rare in chimpanzees. Thus, the pimfs-v is a novel developmental, cognitive, and evolutionarily relevant feature that should be considered in future studies examining how the complex relationships among multiscale anatomical and functional features of the brain give rise to abstract thought.

Hominoid-specific sulcal variability is related to face perception ability.

The relationship among brain structure, brain function, and behavior is of major interest in neuroscience, evolutionary biology, and psychology. This relationship is especially intriguing when considering hominoid-specific brain structures because they cannot be studied in widely examined models in neuroscience such as mice, marmosets, and macaques. The fusiform gyrus (FG) is a hominoid-specific structure critical for face processing that is abnormal in individuals with developmental prosopagnosia (DPs)-individuals who have severe deficits recognizing the faces of familiar people in the absence of brain damage. While previous studies have found anatomical and functional differences in the FG between DPs and NTs, no study has examined the shallow tertiary sulcus (mid-fusiform sulcus, MFS) within the FG that is a microanatomical, macroanatomical, and functional landmark in humans, as well as was recently shown to be present in non-human hominoids. Here, we implemented pre-registered analyses of neuroanatomy and face perception in NTs and DPs. Results show that the MFS was shorter in DPs than NTs. Furthermore, individual differences in MFS length in the right, but not left, hemisphere predicted individual differences in face perception. These results support theories linking brain structure and function to perception, as well as indicate that individual differences in MFS length can predict individual differences in face processing. Finally, these findings add to growing evidence supporting a relationship between morphological variability of late developing, tertiary sulci and individual differences in cognition.

Sulcal depth in prefrontal cortex: a novel predictor of working memory performance.

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.

Uncovering a tripartite landmark in posterior cingulate cortex.

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?

Presence or absence of a prefrontal sulcus is linked to reasoning performance during child development.

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.

Cognitive insights from tertiary sulci in prefrontal cortex.

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.

Overlooked Tertiary Sulci Serve as a Meso-Scale Link between Microstructural and Functional Properties of Human Lateral Prefrontal Cortex.

Understanding the relationship between neuroanatomy and function in portions of cortex that perform functions largely specific to humans such as lateral prefrontal cortex (LPFC) is of major interest in systems and cognitive neuroscience. When considering neuroanatomical-functional relationships in LPFC, shallow indentations in cortex known as tertiary sulci have been largely unexplored. Here, by implementing a multimodal approach and manually defining 936 neuroanatomical structures in 72 hemispheres (in both 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 individual participants. 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 meta-analyses 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 with 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.SIGNIFICANCE STATEMENT Lateral prefrontal cortex (LPFC) is critical for functions that are thought to be specific to humans compared with other mammals. However, relationships between fine-scale neuroanatomical structures largely specific to hominoid cortex and functional properties of LPFC remain elusive. Here, we show that these structures, which have been largely unexplored throughout history, surprisingly serve as markers for anatomical and functional organization in human LPFC. These findings have theoretical, methodological, developmental, and evolutionary implications for improved understanding of neuroanatomical-functional relationships not only in LPFC, but also in association cortices more broadly. Finally, these findings ignite new questions regarding how morphological features of these neglected neuroanatomical structures contribute to functions of association cortices that are critical for human-specific aspects of cognition.

Sulcal morphology of ventral temporal cortex is shared between humans and other hominoids.

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.