Throughout history, researchers who examine the structure and function of the brain debate one another about how cortical areas are defined, as well as how these areas should be named. Different pieces of empirical evidence are used to define brain areas and it is important to preserve the accurate history of this evidence and the timeline of studies that lead to areal definitions that are either still used today or have been modified. As such, this paper traces the early history of a brain area located at the junction between the occipital and temporal lobes of the macaque known as TEO. This historical analysis leads to four main findings. First, even though Bonin and Bailey are credited with the definition of area TEO in 1947, they did not have the cytoarchitectonic evidence to support the distinction of TEO from adjacent areas. Second, the first evidence definitively separating area TEO from TE was actually based on connectivity as identified with strychnine neuronography by Petr et al. in 1949. Third, causal evidence from ablation studies conducted by Iwai and Mishkin (Experimental Neurology 25(4):585-594, 1969) supported this distinction by showing that TEO and TE were functionally distinct from one another. Fourth, researchers in the 1970s began referring to TEO as posterior inferotemporal (PIT) and TE as anterior inferotemporal (AIT), which is an important historical clarification as the PIT/AIT nomenclature is presently attributed to studies conducted more than a decade later. Altogether, this paper aims to preserve the historical origin of area TEO, as well as the empirical evidence that was used to originally differentiate this cortical expanse from surrounding areas.

Transcriptomic contributions to the anatomical, functional, and network layout of the human cerebral cortex (HCC) have become a major interest in cognitive and systems neuroscience. Here, we tested if transcriptomic differences support a modern, algorithmic cytoarchitectonic parcellation of HCC. Using a data-driven approach, we identified a sparse subset of genes that differentially contributed to the cytoarchitectonic parcellation of HCC. A combined metric of cortical thickness and myelination (CT/M ratio), as well as cell density, correlated with gene expression. Enrichment analyses showed that genes specific to the cytoarchitectonic parcellation of the HCC were related to molecular functions such as transmembrane transport and ion channel activity. Together, the relationship between transcriptomics and cytoarchitecture bridges the gap among (i) gradients at the macro-scale (including thickness and myelination), (ii) areas at the meso-scale, and (iii) cell density at the microscale, as well as supports the recently proposed cortical spectrum theory and structural model.

We have an amazing ability to categorize objects in the world around us. Nevertheless, how cortical regions in human ventral temporal cortex (VTC), which is critical for categorization, support this behavioral ability, is largely unknown. Here, we examined the relationship between neural responses and behavioral performance during the categorization of morphed silhouettes of faces and hands, which are animate categories processed in cortically adjacent regions in VTC. Our results reveal that the combination of neural responses from VTC face- and body-selective regions more accurately explains behavioral categorization than neural responses from either region alone. Furthermore, we built a model that predicts a person's behavioral performance using estimated parameters of brain-behavior relationships from a different group of people. Moreover, we show that this brain-behavior model generalizes to adjacent face- and body-selective regions in lateral occipitotemporal cortex. Thus, while face- and body-selective regions are located within functionally distinct domain-specific networks, cortically adjacent regions from both networks likely integrate neural responses to resolve competing and perceptually ambiguous information from both categories.

pFs is a functionally-defined region in the human brain that is involved in recognizing objects. A recent trend refers to pFs as the posterior fusiform sulcus, which is a neuroanatomical structure that does not exist. Here, we correct this mistake. To achieve this goal, we first recount the original definitions of pFs and then review the identification of sulci within and surrounding the fusiform gyrus (FG) including the mid-fusiform sulcus (MFS), which is a tertiary sulcus within the FG. We highlight that tertiary sulci, such as the MFS, are often absent from brain atlases, which complicates the accurate localization of functional regions, as well as the understanding of structural-functional relationships in ventral temporal cortex (VTC). When considering the location of object-selective pFs from previously published data relative to the sulci surrounding the FG, as well as the MFS, we illustrate that (1) pFs spans several macroanatomical structures, which is consistent with the original definitions of pFs (Grill-Spector et al., 1999, 2000), and (2) the topological relationship between pFs and MFS has both stable and variable features. To prevent future confusion regarding the anatomical location of functional regions within VTC, as well as to complement tools that automatically identify sulci surrounding the FG, we provide a method to automatically identify the MFS in individual brains using FreeSurfer. Finally, we highlight the benefits of using cortical surface reconstructions in large datasets to identify and quantify tertiary sulci compared to classic dissection methods because the latter often fail to differentiate tertiary sulci from shallow surface indentations produced by veins and arteries. Altogether, we propose that the inclusion of definitions and labels for tertiary sulci in neuroanatomical atlases and neuroimaging software packages will enhance understanding of functional-structural relationships throughout the human brain.

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.

Primate cerebral cortex is highly convoluted with much of the cortical surface buried in sulcal folds. The origins of cortical folding and its functional relevance have been a major focus of systems and cognitive neuroscience, especially when considering stereotyped patterns of cortical folding that are shared across individuals within a primate species and across multiple species. However, foundational questions regarding organizing principles shared across species remain unanswered. Taking a cross-species comparative approach with a careful consideration of historical observations, we investigate cortical folding relative to primary visual cortex (area V1). We identify two macroanatomical structures-the retrocalcarine and external calcarine sulci-in 24 humans and 6 macaque monkeys. We show that within species, these sulci are identifiable in all individuals, fall on a similar part of the V1 retinotopic map, and thus, serve as anatomical landmarks predictive of functional organization. Yet, across species, the underlying eccentricity representations corresponding to these macroanatomical structures differ strikingly across humans and macaques. Thus, the correspondence between retinotopic representation and cortical folding for an evolutionarily old structure like V1 is species-specific and suggests potential differences in developmental and experiential constraints across primates.

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.

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.

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.