Evolution provides an important window into how cortical organization shapes function and vice versa. The complex mosaic of changes in brain morphology and functional organization that have shaped the mammalian cortex during evolution, complicates attempts to chart cortical differences across species. It limits our ability to fully appreciate how evolution has shaped our brain, especially in systems associated with unique human cognitive capabilities that lack anatomical homologues in other species. Here, we develop a function-based method for cross-species alignment that enables the quantification of homologous regions between humans and rhesus macaques, even when their location is decoupled from anatomical landmarks. Critically, we find cross-species similarity in functional organization reflects a gradient of evolutionary change that decreases from unimodal systems and culminates with the most pronounced changes in posterior regions of the default mode network (angular gyrus, posterior cingulate and middle temporal cortices). Our findings suggest that the establishment of the default mode network, as the apex of a cognitive hierarchy, has changed in a complex manner during human evolution – even within subnetworks.

Glioblastoma is characterized by widespread genetic and transcriptional heterogeneity, yet little is known about the role of the epigenome in glioblastoma disease progression. Here, we present genome-scale maps of DNA methylation in matched primary and recurring glioblastoma tumors, using data from a highly annotated clinical cohort that was selected through a national patient registry. We demonstrate the feasibility of DNA methylation mapping in a large set of routinely collected FFPE samples, and we validate bisulfite sequencing as a multipurpose assay that allowed us to infer a range of different genetic, epigenetic, and transcriptional characteristics of the profiled tumor samples. On the basis of these data, we identified subtle differences between primary and recurring tumors, links between DNA methylation and the tumor microenvironment, and an association of epigenetic tumor heterogeneity with patient survival. In summary, this study establishes an open resource for dissecting DNA methylation heterogeneity in a genetically diverse and heterogeneous cancer, and it demonstrates the feasibility of integrating epigenomics, radiology, and digital pathology for a national cohort, thereby leveraging existing samples and data collected as part of routine clinical practice.

ObjectivesThis study aimed to assess the correlation of temporal muscle thickness (TMT), measured on routine cranial magnetic resonance (MR) images, with lumbar skeletal muscles obtained on computed tomography (CT) images in brain metastasis patients to establish a new parameter estimating skeletal muscle mass on brain MR images.MethodsWe retrospectively analyzed the cross-sectional area (CSA) of skeletal muscles at the level of the third lumbar vertebra on computed tomography scans and correlated these values with TMT on MR images of the brain in two independent cohorts of 93 lung cancer and 61 melanoma patients (overall: 154 patients) with brain metastases.ResultsPearson correlation revealed a strong association between mean TMT and CSA in lung cancer and melanoma patients with brain metastases (0.733; p<0.001). The two study cohorts did not differ significantly in patient characteristics, including age (p = 0.661), weight (p = 0.787), and height (p = 0.123). However, TMT and CSA measures differed significantly between male and female patients in both lung cancer and melanoma patients with brain metastases (p<0.001).ConclusionOur data indicate that TMT, measured on routine cranial MR images, is a useful surrogate parameter for the estimation of skeletal muscle mass in patients with brain metastases. Thus, TMT may be useful for prognostic assessment, treatment considerations, and stratification or a selection factor for clinical trials in patients with brain metastases. Further studies are needed to assess the association between TMT and clinical frailty parameters, and the usefulness of TMT in patients with primary brain tumors.

Temporal muscle thickness (TMT) was investigated as a novel surrogate marker on MRI examinations of the brain, to detect patients who may be at risk for sarcopenia. TMT was analyzed in a retrospective, normal collective cohort (n = 624), to establish standard reference values. These reference values were correlated with grip strength measurements and body mass index (BMI) in 422 healthy volunteers and validated in a prospective cohort (n = 130) of patients with various neurological disorders. Pearson correlation revealed a strong association between TMT and grip strength (retrospective cohort, ρ = 0.746; p < 0.001; prospective cohort, ρ = 0.649; p < 0.001). A low or no association was found between TMT and age (retrospective cohort, R2 correlation coefficient 0.20; p < 0.001; prospective cohort, ρ = −0.199; p = 0.023), or BMI (retrospective cohort, ρ = 0.116; p = 0.042; prospective cohort, ρ = 0.227; p = 0.009), respectively. Male patients with temporal wasting and unintended weight loss, respectively, showed significantly lower TMT values (p = 0.04 and p = 0.015, unpaired t-test). TMT showed a high correlation with muscle strength in healthy individuals and in patients with various neurological disorders. Therefore, TMT should be integrated into the diagnostic workup of neurological patients, to prevent, delay, or treat sarcopenia.

Evolution provides an important window into how cortical organization shapes function and vice versa. The complex mosaic of changes to brain morphology and functional organization that have shaped the mammalian cortex during evolution, complicates attempts to chart cortical differences across species. It limits our ability to fully appreciate how evolution has shaped our brain, especially in systems associated with unique human cognitive capabilities that lack anatomical homologues in other species. Here, we demonstrate a functional-based method for cross-species cortical alignment that leverages recent advances in understanding cortical organization and that enables the quantification of homologous regions across species, even when their location is decoupled from anatomical landmarks. Critically, our method establishes that cross-species similarity in cortical organization decreases with geodesic distance from unimodal systems, and culminates in the most pronounced changes in posterior regions of the default network (angular gyrus, posterior cingulate and middle temporal cortices). Our findings suggest that the establishment of the default network, as the apex of a cognitive hierarchy, as is seen in humans, is a relatively recent evolutionary adaptation. They also highlight functional changes in regions such as the posterior cingulate cortex and angular gyrus as key influences on uniquely human features of cognition.