Altered structure and functional connectivity of the hippocampus are associated with social and mathematical difficulties in nonverbal learning disability

Abstract

The hippocampus is known to play a critical role in a variety of complex abilities, including visual-spatial reasoning, social functioning, and math. Nonverbal learning disability (NVLD) is a neurodevelopmental disorder characterized by deficits in visualspatial reasoning that are accompanied by impairment in social function or mathematics, as well as motor or executive function skills. Despite the overlap between behaviors supported by the hippocampus and impairments in NVLD, the structure and function of the hippocampus in NVLD has not been studied. To address this gap in the literature, we first compared hippocampal volume and resting-state functional connectivity in children with NVLD (n = 24) and typically developing (TD) children (n = 20). We then explored associations between hippocampal structure, connectivity, and performance on measures of spatial, social, and mathematical ability. Relative to TD children, those with NVLD showed significant reductions in left hippocampal volume and greater hippocampal-cerebellar connectivity. In children with NVLD, reduced hippocampal volume associated with worse mathematical problem solving. Although children with NVLD exhibited more social problems (social responsiveness scale [SRS]) and higher hippocampal-cerebellar connectivity relative to TD children, greater connectivity was associated with fewer social problems among children with NVLD but not TD children. Such an effect may suggest a compensatory mechanism. These structural and functional alterations of the hippocampus may disrupt its putative role in organizing conceptual frameworks through cognitive mapping, thus contributing to the cross-domain difficulties that characterize NVLD.

Prenatal Exposure to Air Pollution and Early-Life Stress Effects on Hippocampal Subregional Volumes and Associations With Visuospatial Reasoning

“…Larger hippocampal volume has been associated with greater navigational experience in taxi drivers ( 50 , 51 ), and both severe hippocampal damage ( 45 ) and CA1 atrophy in patients with multiple sclerosis ( 52 ) are correlated with impaired spatial recall. Structural differences have been similarly identified in children with nonverbal learning disorder, which is characterized by visuospatial deficits ( 53 ). These visuospatial deficits are independently associated with differences in stress and air pollution exposure in early life ( 54 – 56 ), with 1 study reporting that higher PAH DNA-adducts, a biological marker of exposure, were associated with lower visuospatial intelligence among children who experienced material hardship ( 41 ).…”

Glutamine ameliorates hyperoxia-induced hippocampal damage by attenuating inflammation and apoptosis via the MKP-1/MAPK signaling pathway in neonatal rats

“…Frontiers in Pharmacology frontiersin.org (Banker et al, 2021). We found that hyperoxia caused brain tissue edema and hippocampal damage in neonatal rats, with significant deficits in spatial memory and learning ability observed during adolescence.…”

“…Long-term hyperoxia treatment can lead to behavioral abnormalities and neurocognitive and learning deficits in preterm infants, which is thought to be related to damage to hippocampal neurons caused by oxidative stress, inflammation, apoptosis, and reduced expression of neurotrophic factors ( Sifringer et al, 2015 ). Spatial cognition and memory are inseparable from hippocampal function, and alterations in hippocampal structure and function are associated with reduced spatial, social, and mathematical abilities ( Banker et al, 2021 ). We found that hyperoxia caused brain tissue edema and hippocampal damage in neonatal rats, with significant deficits in spatial memory and learning ability observed during adolescence.…”

Dysfunctions associated with the intraparietal sulcus and a distributed network in individuals with math learning difficulties: An ALE meta‐analysis

“…Of these 22 studies, 16 reported univariate functional activations, 2 reported functional connectivity differences, and 4 reported structural differences. Amongst the 22 papers, two studies examined participants of MLD with comorbid conditions of nonverbal learning disability (NVLD; Banker et al, 2021) or Turner syndrome (TS; Molko et al, 2003). All 22 studies reported group differences between MLD and TD, but not every study reported single-group results for MLD or TD F I G U R E 1 Flowchart of literature search, identification of eligible articles and proposed ALE analyses (Table 1).…”