Genetic mapping and evolutionary analysis of human-expanded cognitive networks

Cognitive brain networks such as the default-mode network (DMN), frontoparietal network, and salience network, are key functional networks of the human brain. Here we show that the rapid evolutionary cortical expansion of cognitive networks in the human brain, and most pronounced the DMN, runs parallel with high expression of human-accelerated genes (HAR genes). Using comparative transcriptomics analysis, we present that HAR genes are differentially more expressed in higher-order cognitive networks in humans compared to chimpanzees and macaques and that genes with high expression in the DMN are involved in synapse and dendrite formation. Moreover, HAR and DMN genes show significant associations with individual variations in DMN functional activity, intelligence, sociability, and mental conditions such as schizophrenia and autism. Our results suggest that the expansion of higher-order functional networks subserving increasing cognitive properties has been an important locus of genetic changes in recent human brain evolution

Evolution of Brain Networks

The brain is an intricate organ responsible for dealing with our thoughts, feelings, and behaviors. The human brain tripled in size during recent evolution, while the rest of our body stayed more or less the same size. This remarkable change has inspired brain researchers to investigate why such brain expansion took place, and how it affects the way our brain works. In this thesis, we investigated the organization of the brain’s wiring by looking at the connections between each part of the brain and how they form a complex network — the connectome. We compared the human connectome to that of other primate species, including chimpanzees, gorillas, rhesus monkeys, and capuchin monkeys. We found that all these connectomes have important aspects in common: They are wired in an efficient way and contain ‘shortcuts’ between important brain regions for quick communication of information. At the same time, they show subtle differences in their wiring organization that are closely linked with their brain size. For example, larger brains have relatively less long-range connections, likely because long connections take up more and more space in larger brains. Larger brains also show more specialization of connectivity, especially between the left and right sides of the brain. The findings of this thesis help our understanding of human brain evolution by showing the relationships between brain size and connectome organization in a wide range of monkeys and apes. Our work suggests that primate brains are wired according to a shared connectome blueprint, with key aspects of connectome organization found in all the studied species. Brain size and adaptations to specific environments form the variations on this conserved blueprint. In the case of humans, our big brains may have paved the way for extensive specialization of brain connectivity, leading to specialized brain functions such as language and highly developed cognition

The human connectome from an evolutionary perspective

The connectome describes the comprehensive set of neuronal connections of a species' central nervous system. Identifying the network characteristics of the human macroscale connectome and comparing these features with connectomes of other species provides insight into the evolution of human brain connectivity and its role in brain function. Several network properties of the human connectome are conserved across species, with emerging evidence also indicating potential human-specific adaptations of connectome topology. This review describes the human macroscale structural and functional connectome, focusing on common themes of brain wiring in the animal kingdom and network adaptations that may underlie human brain function. Evidence is drawn from comparative studies across a wide range of animal species, and from research comparing human brain wiring with that of non-human primates. Approaching the human connectome from a comparative perspective paves the way for network-level insights into the evolution of human brain structure and function

Connection strength of the macaque connectome augments topological and functional network attributes

Mammalian brains constitute complex organized networks of neural projections. On top of their binary topological organization, the strength (or weight) of these neural projections can be highly variable across connections and is thus likely of additional importance to the overall topological and functional organization of the network. Here we investigated the specific distribution pattern of connection strength in the macaque connectome. We performed weighted and binary network analysis on the cortico-cortical connectivity of the macaque provided by the unique tract-tracing dataset of Markov and colleagues (2014) and observed in both analyses a small-world, modular and rich club organization. Moreover, connectivity strength showed a distribution augmenting the architecture identified in the binary network version by enhancing both local network clustering and the central infrastructure for global topological communication and integration. Functional consequences of this topological distribution were further examined using the Kuramoto model for simulating interactions between brain regions and showed that the connectivity strength distribution across connections enhances synchronization within modules and between rich club hubs. Together, our results suggest that neural pathway strength promotes topological properties in the macaque connectome for local processing and global network integration

Convergence of Brain Transcriptomic and Neuroimaging Patterns in Schizophrenia, Bipolar Disorder, Autism Spectrum Disorder, and Major Depressive Disorder

Background: Psychiatric conditions show overlap in their symptoms, genetics, and involvement in brain areas and circuits. Structural alterations in the brain have been found to run in parallel with expression profiles of risk genes at the level of the brain transcriptome, which may point toward a potential transdiagnostic vulnerability of the brain to disease processes. Methods: We characterized the transcriptomic vulnerability of the cortex across 4 major psychiatric disorders based on collated data from patients with psychiatric disorders (n = 390) and matched control participants (n = 293). We compared normative expression profiles of risk genes linked to schizophrenia, bipolar disorder, autism spectrum disorder, and major depressive disorder to examine cross-disorder overlap in spatial expression profiles across the cortex and their concordance with a magnetic resonance imaging–derived cross-disorder profile of structural brain alterations. Results: We showed high expression of psychiatric risk genes converging on multimodal cortical regions of the limbic, ventral attention, and default mode networks versus primary somatosensory networks. Risk genes were found to be enriched among genes associated with the magnetic resonance imaging cross-disorder profile, suggestive of a common link between brain anatomy and the transcriptome in psychiatric conditions. Characterization of this cross-disorder structural alteration map further shows enrichment for gene markers of astrocytes, microglia, and supragranular cortical layers. Conclusions: Our findings suggest that normative expression profiles of disorder risk genes confer a shared and spatially patterned vulnerability of the cortex across multiple psychiatric conditions. Transdiagnostic overlap in transcriptomic risk suggests a common pathway to brain dysfunction across psychiatric disorders

The human connectome from an evolutionary perspective

The connectome describes the comprehensive set of neuronal connections of a species' central nervous system. Identifying the network characteristics of the human macroscale connectome and comparing these features with connectomes of other species provides insight into the evolution of human brain connectivity and its role in brain function. Several network properties of the human connectome are conserved across species, with emerging evidence also indicating potential human-specific adaptations of connectome topology. This review describes the human macroscale structural and functional connectome, focusing on common themes of brain wiring in the animal kingdom and network adaptations that may underlie human brain function. Evidence is drawn from comparative studies across a wide range of animal species, and from research comparing human brain wiring with that of non-human primates. Approaching the human connectome from a comparative perspective paves the way for network-level insights into the evolution of human brain structure and function

Erratum: Evolutionary expansion of connectivity between multimodal association areas in the human brain compared with chimpanzees(PNAS (2019) 116:14(7101-7106) DOI: 10.1073/pnas.1818512116)

which was first published March 18, 2019; 10.1073/pnas.1818512116 (Proc Natl Acad Sci USA 116:7101–7106). The authors wish to note the following: “No new MRI data were acquired for this study. All chimpanzee MRIs were obtained from a data archive of scans obtained prior to the 2015 implementation of US Fish and Wildlife Service and National Institutes of Health regulations governing research with chimpanzees. All the scans reported in this publication were completed by the end of 2012. All chimpanzee MRI scans are part of the National Chimpanzee Brain Resource (http://www.chimpanzeebrain.org).