Genetic variations within human gained enhancer elements affect human brain sulcal morphology

The expansion of the cerebral cortex is one of the most distinctive changes in the evolution of the human brain. Cortical expansion and related increases in cortical folding may have contributed to emergence of our capacities for high-order cognitive abilities. Molecular analysis of humans, archaic hominins, and non-human primates has allowed identification of chromosomal regions showing evolutionary changes at different points of our phylogenetic history. In this study, we assessed the contributions of genomic annotations spanning 30 million years to human sulcal morphology measured via MRI in more than 18,000 participants from the UK Biobank. We found that variation within brain-expressed human gained enhancers, regulatory genetic elements that emerged since our last common ancestor with Old World monkeys, explained more trait heritability than expected for the left and right calloso-marginal posterior fissures and the right central sulcus. Intriguingly, these are sulci that have been previously linked to the evolution of locomotion in primates and later on bipedalism in our hominin ancestors.

No Evidence for an Association Between Variability in Sulcal Pattern and Academic Achievement

Investigating how the brain may constrain academic achievement is not only relevant to understanding brain structure but also to providing insight into the origins of individual differences in these academic abilities. In this pre-registered study, we investigated whether the variability of sulcal patterns, a qualitative feature of the brain determined in-utero and not affected by brain maturation and learning, accounted for individual differences in reading and mathematics. Participants were 97 typically developing 10-year-olds. We examined (a) the association between the sulcal pattern of the intraparietal sulcus (IPS) and mathematical ability; (b) the association between the sulcal pattern of the occipitotemporal sulcus (OTS) and reading ability; and (c) the overlap and specificity of sulcal morphology of IPS and OTS and their associations with mathematics and reading. Despite its large sample, the present study was unable to replicate a previously observed relationship between the IPS sulcal pattern and mathematical ability and a previously observed association between the Left posterior OTS sulcal pattern and reading. We found no evidence for a possible overlap or specificity in the effect of sulcal morphology on mathematics and reading. Possible explanations for this absence of an association between sulcal morphology and academic achievement and suggestions for future research are discussed.

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.

Mother-child similarity in brain morphology: A comparison of structural characteristics of the brain’s reading network

Background: Substantial evidence acknowledges the complex gene-environment interplay impacting brain development and learning. Intergenerational neuroimaging allows the assessment of familial transfer effects on brain structure, function and behavior by investigating neural similarity in caregiver-child dyads. Methods: Neural similarity in the human reading network was assessed through well-used measures of brain structure (i.e., surface area (SA), gyrification (lG), sulcal morphology, gray matter volume (GMV) and cortical thickness (CT)) in 69 mother-child dyads (children’s age~11y). Regions of interest for the reading network included left-hemispheric inferior frontal gyrus, inferior parietal lobe and fusiform gyrus. Mother-child similarity was quantified by correlation coefficients and familial specificity was tested by comparison to random adult-child dyads. Sulcal morphology analyses focused on occipitotemporal sulcus interruptions and similarity was assessed by chi-square goodness of fit. Results: Significant structural brain similarity was observed for mother-child dyads in the reading network for lG, SA and GMV (r=0.349/0.534/0.542, respectively), but not CT. Sulcal morphology associations were non-significant. Structural brain similarity in lG, SA and GMV were specific to parent- child pairs. Furthermore, structural brain similarity for SA and GMV was higher compared to CT. Conclusion: Intergenerational neuroimaging techniques promise to enhance our knowledge of familial transfer effects on brain development and disorders.

No Evidence for an Association Between Variability in Sulcal Pattern and Academic Achievement

Investigating how the brain may constrain academic achievement is not only relevant to understanding brain structure but also to providing insight into the origins of individual differences in these academic abilities. In this pre-registered study, we investigated whether the variability of sulcal patterns, a qualitative feature of the brain determined in-utero and not affected by brain maturation and learning, accounted for individual differences in reading and mathematics. Participants were 97 typically developing 10-year-olds. We examined (a) the association between the sulcal pattern of the intraparietal sulcus (IPS) and mathematical ability; (b) the association between the sulcal pattern of the occipitotemporal sulcus (OTS) and reading ability; and (c) the overlap and specificity of sulcal morphology of IPS and OTS and their associations with mathematics and reading. Despite its large sample, the present study was unable to replicate a previously observed relationship between the IPS sulcal pattern and mathematical ability and a previously observed association between the Left posterior OTS sulcal pattern and reading. We found no evidence for a possible overlap or specificity in the effect of sulcal morphology on mathematics and reading. Possible explanations for this absence of an association between sulcal morphology and academic achievement and suggestions for future research are discussed.

Longitudinal allometry of sulcal morphology in health and schizophrenia

Scaling between subcomponents of cortical folding and total brain volume (TBV) in healthy individuals (HI) is allometric, i.e. non-linear. It is unclear whether this is also true in individuals with schizophrenia (SZ) or first-episode psychosis (FEP). The current study first confirmed normative allometric scaling norms in HI using discovery and replication samples. Cross-sectional and longitudinal diagnostic differences in folding subcomponents were then assessed using an allometric analytic framework. Structural imaging from a longitudinal (sample 1: HI and SZ, nHI Baseline = 298, nSZ Baseline = 169, nHI Follow-up = 293, nSZ Follow-up = 168, a total of 1087 images, all individuals ≥ 2 images, age 16-69 years) and a cross-sectional sample (sample 2: nHI = 61 and nFEP = 89, age 10-30 years) is leveraged to calculate global folding and its nested subcomponents: sulcation index (SI, total sulcal/cortical hull area) and determinants of sulcal area; sulcal length and sulcal depth. Scaling of the SI, sulcal area, and sulcal length with TBV in SZ and FEP was allometric and did not differ from HI. Longitudinal age trajectories demonstrated steeper loss of SI and sulcal area through adulthood in SZ. Longitudinal allometric analysis revealed that both annual change in SI and sulcal area was significantly stronger related to change in TBV in SZ compared to HI. Our results detail the first evidence of the disproportionate contribution of changes in SI and sulcal area to TBV changes in SZ. Longitudinal allometric analysis of sulcal morphology provides deeper insight into lifespan trajectories of cortical folding in SZ.

Morphological and functional variability in central and subcentral motor cortex of the human brain

There is a long-established link between anatomy and function in the somatomotor system in the mammalian cerebral cortex. The morphology of the central sulcus is predictive of the location of functional activation peaks relating to movement of different effectors in individuals. By contrast, morphological variation in the subcentral region and its relationship to function is, as yet, unknown. Investigating the subcentral region is particularly important in the context of speech, since control of the larynx during human speech production is related to activity in this region. Here, we examined the relationship between morphology in the central and subcentral region and the location of functional activity during movement of the hand, lips, tongue, and larynx at the individual participant level. We provide a systematic description of the sulcal patterns of the subcentral and adjacent opercular cortex, including the inter-individual variability in sulcal morphology. We show that, in the majority of participants, the anterior subcentral sulcus is not continuous, but consists of two distinct segments. A robust relationship between morphology of the central and subcentral sulcal segments and movement of different effectors is demonstrated. Inter-individual variability of underlying anatomy might thus explain previous inconsistent findings, in particular regarding the ventral larynx area in subcentral cortex. A surface registration based on sulcal labels indicated that such anatomical information can improve the alignment of functional data for group studies.

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.

Sex differences in lifespan trajectories and variability of human sulcal and gyral morphology

Sex differences in development and aging of human sulcal morphology have been understudied. We charted sex differences in trajectories and inter-individual variability of global sulcal depth, width, and length, pial surface area, exposed (hull) gyral surface area, unexposed sulcal surface area, cortical thickness, and cortex volume across the lifespan in a longitudinal sample (700 scans, 194 participants two scans, 104 three scans, age range: 16-70 years) of neurotypical males and females. After adjusting for brain volume, females had thicker cortex and steeper thickness decline until age 40 years; trajectories converged thereafter. Across sexes, sulcal shortening was faster before age 40, while sulcal shallowing and widening were faster thereafter. While hull area remained stable, sulcal surface area declined and was more strongly associated with sulcal shortening than with sulcal shallowing and widening. Males showed greater variability for cortex volume and thickness and lower variability for sulcal width. Across sexes, variability decreased with age for all measures except for cortical volume and thickness. Our findings highlight the association between loss of sulcal area, notably through sulcal shortening, with cortex volume loss. Studying sex differences in lifespan trajectories may improve knowledge of individual differences in brain development and the pathophysiology of neuropsychiatric conditions.