Structural deviations of the posterior fossa and the cerebellum and their cognitive links in a neurodevelopmental deletion syndrome.

High-impact genetic variants associated with neurodevelopmental disorders provide biologically-defined entry points for mechanistic investigation. The 3q29 deletion (3q29Del) is one such variant, conferring a 40-100-fold increased risk for schizophrenia, as well as high risk for autism and intellectual disability. However, the mechanisms leading to neurodevelopmental disability remain largely unknown. Here, we report the first in vivo quantitative neuroimaging study in individuals with 3q29Del (N = 24) and neurotypical controls (N = 1608) using structural MRI. Given prior radiology reports of posterior fossa abnormalities in 3q29Del, we focused our investigation on the cerebellum and its tissue-types and lobules. Additionally, we compared the prevalence of cystic/cyst-like malformations of the posterior fossa between 3q29Del and controls and examined the association between neuroanatomical findings and quantitative traits to probe gene-brain-behavior relationships. 3q29Del participants had smaller cerebellar cortex volumes than controls, before and after correction for intracranial volume (ICV). An anterior-posterior gradient emerged in finer grained lobule-based and voxel-wise analyses. 3q29Del participants also had larger cerebellar white matter volumes than controls following ICV-correction and displayed elevated rates of posterior fossa arachnoid cysts and mega cisterna magna findings independent of cerebellar volume. Cerebellar white matter and subregional gray matter volumes were associated with visual-perception and visual-motor integration skills as well as IQ, while cystic/cyst-like malformations yielded no behavioral link. In summary, we find that abnormal development of cerebellar structures may represent neuroimaging-based biomarkers of cognitive and sensorimotor function in 3q29Del, adding to the growing evidence identifying cerebellar pathology as an intersection point between syndromic and idiopathic forms of neurodevelopmental disabilities.

White matter network topology relates to cognitive flexibility and cumulative neurological risk in adult survivors of pediatric brain tumors.

Adult survivors of pediatric brain tumors exhibit deficits in executive functioning. Given that brain tumors and medical treatments for brain tumors result in disruptions to white matter, a network analysis was used to explore the topological properties of white matter networks. This study used diffusion tensor imaging and deterministic tractography in 38 adult survivors of pediatric brain tumors (mean age in years = 23.11 (SD = 4.96), 54% female, mean years post diagnosis = 14.09 (SD = 6.19)) and 38 healthy peers matched by age, gender, handedness, and socioeconomic status. Nodes were defined using the Automated Anatomical Labeling (AAL) parcellation scheme, and edges were defined as the mean fractional anisotropy of streamlines that connected each node pair. Global efficiency and average clustering coefficient were reduced in survivors compared to healthy peers with preferential impact to hub regions. Global efficiency mediated differences in cognitive flexibility between survivors and healthy peers, as well as the relationship between cumulative neurological risk and cognitive flexibility. These results suggest that adult survivors of pediatric brain tumors, on average one and a half decades post brain tumor diagnosis and treatment, exhibit altered white matter topology in the form of suboptimal integration and segregation of large scale networks, and that disrupted topology may underlie executive functioning impairments. Network based studies provided important topographic insights on network organization in long-term survivors of pediatric brain tumor.

In vivo evaluation of optic nerve aging in adult rhesus monkey by diffusion tensor imaging.

Aging of the optic nerve can result in reduced visual sensitivity or vision loss. Normal optic nerve aging has been investigated previously in tissue specimens but poorly explored in vivo. In the present study, the normal aging of optic nerve was evaluated by diffusion tensor imaging (DTI) in non-human primates. Adult female rhesus monkeys at the ages of 9 to 13 years old (young group, n=8) and 21 to 27 years old (old group, n=7) were studied using parallel-imaging-based DTI on a clinical 3T scanner. Compared to young adults, the old monkeys showed 26% lower fractional anisotropy (P<0.01), and 44% greater radial diffusivity, although the latter difference was of marginal statistical significance (P=0.058). These MRI findings are largely consistent with published results of light and electron microscopic studies of optic nerve aging in macaque monkeys, which indicate a loss of fibers and degenerative changes in myelin sheaths.