The development of interventions to prevent congenital Zika syndrome (CZS) has been limited by the lack of an established nonhuman primate model. Here we show that infection of female rhesus monkeys early in pregnancy with Zika virus (ZIKV) recapitulates many features of CZS in humans. We infected 9 pregnant monkeys with ZIKV, 6 early in pregnancy (weeks 6-7 of gestation) and 3 later in pregnancy (weeks 12-14 of gestation), and compared findings with uninfected controls. 100% (6 of 6) of monkeys infected early in pregnancy exhibited prolonged maternal viremia and fetal neuropathology, including fetal loss, smaller brain size, and histopathologic brain lesions, including microcalcifications, hemorrhage, necrosis, vasculitis, gliosis, and apoptosis of neuroprogenitor cells. High-resolution MRI demonstrated concordant lesions indicative of deep gray matter injury. We also observed spinal, ocular, and neuromuscular pathology. Our data show that vascular compromise and neuroprogenitor cell dysfunction are hallmarks of CZS pathogenesis, suggesting novel strategies to prevent and to treat this disease.

Diffusion tensor imaging (DTI) of the white matter is a biomarker for neurological disease burden in tuberous sclerosis complex (TSC). To clarify the basis of abnormal diffusion in TSC, we correlated ex vivo high-resolution diffusion imaging with histopathology in four tissue types: cortex, tuber, perituber, and white matter.

Psychiatry is undergoing a paradigm shift from the acceptance of distinct diagnoses to a representation of psychiatric illness that crosses diagnostic boundaries. How this transition is supported by a shared neurobiology remains largely unknown. In this study, we first identify single nucleotide polymorphisms (SNPs) associated with psychiatric disorders based on 136 genome-wide association studies. We then conduct a joint analysis of these SNPs and brain structural connectomes in 678 healthy children in the PING study. We discovered a strong, robust, and transdiagnostic mode of genome-connectome covariation which is positively and specifically correlated with genetic risk for psychiatric illness at the level of individual SNPs. Similarly, this mode is also significantly positively correlated with polygenic risk scores for schizophrenia, alcohol use disorder, major depressive disorder, a combined bipolar disorder-schizophrenia phenotype, and a broader cross-disorder phenotype, and significantly negatively correlated with a polygenic risk score for educational attainment. The resulting "vulnerability network" is shown to mediate the influence of genetic risks onto behaviors related to psychiatric vulnerability (e.g., marijuana, alcohol, and caffeine misuse, perceived stress, and impulsive behavior). Its anatomy overlaps with the default-mode network, with a network of cognitive control, and with the occipital cortex. These findings suggest that the brain vulnerability network represents an endophenotype funneling genetic risks for various psychiatric illnesses through a common neurobiological root. It may form part of the neural underpinning of the well-recognized but poorly explained overlap and comorbidity between psychiatric disorders.

Autism spectrum disorder (ASD) is prevalent in tuberous sclerosis complex (TSC), occurring in approximately 50% of patients, and is hypothesized to be caused by disruption of neural circuits early in life. Tubers, or benign hamartomas distributed stochastically throughout the brain, are the most conspicuous of TSC neuropathology, but have not been consistently associated with ASD. Widespread neuropathology of the white matter, including deficits in myelination, neuronal migration, and axon formation, exist and may underlie ASD in TSC. We sought to identify the neural circuits associated with ASD in TSC by identifying white matter microstructural deficits in a prospectively recruited, longitudinally studied cohort of TSC infants.

Multi-site MRI studies are often necessary for recruiting sufficiently sized samples when studying rare conditions. However, they require pooling data from multiple scanners into a single data set, and therefore it is critical to evaluate the variability of quantitative MRI measures within and across scanners used in multi-site studies. The aim of this study was to evaluate the reproducibility of structural and diffusion weighted (DW) MRI measurements acquired on seven scanners at five medical centers as part of the Tuberous Sclerosis Complex Autism Center of Excellence Research Network (TACERN) multisite study.