Research

A Neuroimaging Study of Children with NVLD

Under the direction of Dr. Amy Margolis, principal investigator at Columbia University (2013-2024) and The Ohio State University (2024-present), we conducted a neuroimaging study of children who have been diagnosed with NVLD. Neuroimaging research provides information about the structure, function, and connectivity of circuits in the brain. Disruptions in these circuits can lead to developmental disabilities and neuropsychiatric illness. Our research program aims to understand in-brain circuits that lead to or accompany NVLD.

One of our studies was aimed at determining whether the social problems experienced by children with NVLD differ from those observed in children with Autism Spectrum Disorder (ASD). We found that children with NVLD and ASD experience similar degrees of social problems as reported by their parents, but that these problems derive from distinct aberrations in the neural circuitry underlying social functioning. In other words, although both groups of children have social problems they are underpinned by different brain based problems. This work is published HERE.

Identifying unique features in their brains that are linked with features of NVLD would help validate NVLD as a clinically distinct diagnosis, suggesting that it is neurobiologically at one extreme along a continuum of verbal/perceptual reasoning differences found in the general population. This work is published HERE.

In another study, we reported that the neural circuit that supports visual-spatial processing is altered in youth with NVLD, relative to youth with reading disorder or typically developing youth. This study identifies a problem in an underlying circuit that is crucial for visual-spatial functioning and that is not functioning the same in youth with NVLD as typically developing youth or those with reading problems. Further, dysfunction in the circuit correlated with visual-spatial problems. Thus we identified a core underlying brain feature of NVLD. This work is published HERE.

In a third study, we reported that children with NVLD had smaller hippocampal volumes than typically developing youth. The hippocampus is important for visual-spatial reasoning, social functioning, and math, all reported problems in NVLD. Relative to typically developing children, those with NVLD showed significant reductions in left hippocampal volume and greater hippocampal-cerebellar connectivity. In children with NVLD, reduced hippocampal volume was associated with worse mathematical problem solving. This study can be found HERE.

In a fourth study, we examined cerebellar structure in youth with NVLD, as it is thought to contribute to social cognition. Children with NVLD showed altered white matter microstructure that was associated with social impairment as reported by parents. Our study provides evidence that the cerebellum contributes to both social cognition and the pathophysiology of NVLD.

Epidemiology

Epidemiologic research studies illnesses in general populations rather than in treatment clinics. Under the direction of Dr. Amy Margolis at Columbia University Medical Center, we helped support the first ever prevalence estimate of NVLD in the general population. Bringing together a team of psychiatrists and researchers from the Child Mind Institute, Nathan Kline Institute, and University of Toronto, Dr. Margolis estimated the prevalence of NVLD to be approximately 3 percent in North America. (Published HERE.) In further work, we are studying how components of the NVLD diagnosis co-occur in the general population, rather than only in patients identified in treatment clinics to help us understand how NVLD develops.

Mouse Model Study

Children with NVLD experience deficits in a type of memory called working memory. Dr. Alex Dranovsky’s laboratory at Columbia University used a mouse model to unravel a brain circuit mechanism, which causes lifelong working memory deficits in animals exposed to early life stress. The investigators hope to study how targeting this mechanism with known medications and with newly developed ones, can reverse working memory deficits in their mouse model. By combining behavioral, pharmacologic, and state of the art circuit and molecular studies, the scientists are making unprecedented advances in understanding the mechanisms of cognitive dysfunction associated with NVLD. Drs. Dranovsky and Amy Margolis hope to team up for testing if the newly discovered treatments can be used to improve functional impairments related to NVLD.

Microanalysis of Face-to-Face Nonverbal Communication

This study examined the development of infant communication through facial expression and eye gaze at four months using second-to-second lag weights (a statistical method in our laboratory) to determine if individual differences in these abilities predicted attachment or joint attention (as measured by social engagement) at one year. These outcome measures allowed us to differentiate between infants who may develop future autistic spectrum disorders rather than NVLD.

Specifically, we hypothesized that a group of infants exist who have aberrations in lag weights in gaze and face tracking, and that these differences will differentiate babies at one year who have insecure attachment but not problems in social engagement. We hypothesized that these infants may later develop NVLD. The potential autism spectrum infants are more likely to have deficits in social engagement whereas the potential NVLD infants will demonstrate anxiety and insecure attachment.