Genetic Influences on Cortical Regionalization in the Human Brain

A core brain network is engaged in remembering the past and envisioning the future. This network overlaps with the so-called default-mode network, the activity of which increases when demands for focused attention are low. Because of their shared brain substrates, an intriguing hypothesis is that default-mode activity, measured at rest, is related to performance in separate attentionfocused recall and imagination tasks. However, we do not know how functional connectivity of the default-mode network is related to individual differences in reconstruction of the past and imagination of the future. Here, we show that functional connectivity of the default-mode network in children and adolescents is related to the quality of past remembering and marginally to future imagination. These results corroborate previous findings of a common neuronal substrate for memory and imagination and provide evidence suggesting that mental time travel is modulated by the task-independent functional architecture of the default-mode network in the developing brain. A further analysis showed that local cortical arealization also contributed to explain recall of the past and imagination of the future, underscoring the benefits of studying both functional and structural properties to understand the brain basis for complex human cognition.cortical area | development | fMRI | independent component analysis I t is widely accepted that reconstruction and "re-experience" are important aspects of vivid episodic memory. Reconstruction of memories based on impoverished bits of information represents an economical way of storing information and may also facilitate anticipation of the future (1). A reconstructive memory system, enables mental time travel by use of previous experiences as a basis for construction of imagined future situations (2). Thus, there is a theoretical and empirical connection between the ability to reconstruct and re-experience our own personal past and the ability to imagine new experiences (3). However, little is known about individual differences in the brain characteristics underlying the ability to form rich representations of the past and future and, especially, how these characteristics support episodic recall and imagination during development. The purpose of the present study was to delineate both functional and structural brain correlates of vividness in recall and future imagination in children and adolescents.Brain lesion (4, 5) and functional magnetic resonance imaging (fMRI) studies (3, 6) have yielded evidence for a common core network of brain areas involved in recall of episodic memories and imagination of future scenarios. This network includes the medial temporal cortex, posterior cingulate/retrosplenial cortex/ precuneus, lateral parietal (inferior parietal lobule, temporo-parietal junction), medial prefrontal, and lateral temporal cortices (3), although the role played by the hippocampus in imagination is debated (7-9). These areas overlap to a substantial degree with the default-mode network (10) and may...

Section: Functional Connectivity and Vivid Experiences Of Past And Fucontrasting

confidence: 66%

mentioning

confidence: 99%

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Mental time travel and default-mode network functional connectivity in the developing brain

Østby

Walhovd

Tamnes

et al. 2012

“…This variation is significantly greater than variation in total cortical area, and therefore, both the absolute area and proportion of the cortical sheet allocated to processing vision varies between individuals. Moreover, a recent human twin study showed strong genetic correlations between the area of V1 and the remainder of occipital cortex but not other cortical lobes (9), suggesting that occipital visual areas share common genetic influences. However, it is still largely unknown what specific genetic and environmental factors contribute to normal variation in the absolute and proportional size of occipital cortex.…”

Section: −8mentioning

confidence: 99%

Association of common genetic variants in GPCPD1 with scaling of visual cortical surface area in humans

Bakken

Roddey

Djurovic

et al. 2012

Visual cortical surface area varies two-to threefold between human individuals, is highly heritable, and has been correlated with visual acuity and visual perception. However, it is still largely unknown what specific genetic and environmental factors contribute to normal variation in the area of visual cortex. To identify SNPs associated with the proportional surface area of visual cortex, we performed a genome-wide association study followed by replication in two independent cohorts. We identified one SNP (rs6116869) that replicated in both cohorts and had genome-wide significant association (P combined = 3.2 × 10 −8). Furthermore, a metaanalysis of imputed SNPs in this genomic region identified a more significantly associated SNP (rs238295; P = 6.5 × 10 −9) that was in strong linkage disequilibrium with rs6116869. These SNPs are located within 4 kb of the 5′ UTR of GPCPD1, glycerophosphocholine phosphodiesterase GDE1 homolog (Saccharomyces cerevisiae), which in humans, is more highly expressed in occipital cortex compared with the remainder of cortex than 99.9% of genes genome-wide. Based on these findings, we conclude that this common genetic variation contributes to the proportional area of human visual cortex. We suggest that identifying genes that contribute to normal cortical architecture provides a first step to understanding genetic mechanisms that underlie visual perception.allometry | brain morphometry | imaging genetics | V1

“…Although spatial proximity is likely to be a primary factor constraining gene expression across the cerebral cortex (54,55), the current analysis presents a different perspective: relative expression patterns of a small number of genes that are uniquely expressed in human upper cortical layers compared with mouse are correlated in distributed patterns across the cerebral cortex. Their spatial distributions across the cortex are closely linked to cortical subtypes and their associated connectivity profiles.…”

Section: And 7)mentioning

confidence: 99%

Transcriptional profiles of supragranular-enriched genes associate with corticocortical network architecture in the human brain

Krienen

Yeo

et al. 2016

208

203

The human brain is patterned with disproportionately large, distributed cerebral networks that connect multiple association zones in the frontal, temporal, and parietal lobes. The expansion of the cortical surface, along with the emergence of long-range connectivity networks, may be reflected in changes to the underlying molecular architecture. Using the Allen Institute's human brain transcriptional atlas, we demonstrate that genes particularly enriched in supragranular layers of the human cerebral cortex relative to mouse distinguish major cortical classes. The topography of transcriptional expression reflects large-scale brain network organization consistent with estimates from functional connectivity MRI and anatomical tracing in nonhuman primates. Microarray expression data for genes preferentially expressed in human upper layers (II/III), but enriched only in lower layers (V/VI) of mouse, were cross-correlated to identify molecular profiles across the cerebral cortex of postmortem human brains (n = 6). Unimodal sensory and motor zones have similar molecular profiles, despite being distributed across the cortical mantle. Sensory/motor profiles were anticorrelated with paralimbic and certain distributed association network profiles. Tests of alternative gene sets did not consistently distinguish sensory and motor regions from paralimbic and association regions: (i) genes enriched in supragranular layers in both humans and mice, (ii) genes cortically enriched in humans relative to nonhuman primates, (iii) genes related to connectivity in rodents, (iv) genes associated with human and mouse connectivity, and (v) 1,454 gene sets curated from known gene ontologies. Molecular innovations of upper cortical layers may be an important component in the evolution of long-range corticocortical projections.corticocortical connectivity | human transcriptome | association cortex | supragranular | brain evolution P atterns of gene expression in the cerebral cortex are generally conserved across species, reflecting strong constraints in the development and evolution of cortical architecture (1-6). Previous work examining transcriptional variation in nonhuman primates and rodents indicate that molecular similarities between cortical regions in the adult brain are best explained by spatial proximity (7, 8). Molecular variation often takes the form of graded expression along a principal axis, in many cases appearing as rostrocaudal gradients across the cortex (8). The strong tendency for transcriptional variation to follow spatial proximity in the adult cortex likely reflects both functional gradients, as well as their developmental origins in terms of physical and temporal adjacency during neurogenesis of cells destined for neighboring locations in the cortex (at least for cells derived from the ventricular proliferative pool) (7).Spatial proximity likely captures the major features governing how molecular profiles vary across the cortex in all species, including humans. However, the expansion of the cerebral cortex in primates...