Investigating the Neural Substrates of Working Memory in Williams Syndrome and Typically Developing Children

Poster Session D - Monday, April 15, 2024, 8:00 – 10:00 am EDT, Sheraton Hall ABC

Destiny S. Wright¹ (destiny.wright@nih.gov), Tiffany Nash¹, Michael D. Gregory¹, J. Shane Kippenhan¹, Anne K. Ilsley¹, Megan A. Spurney¹, Anna G. Kelemen¹, Madeline H. Garvey¹, Philip D. Kohn¹, Daniel P. Eisenberg¹, Carolyn B. Mervis², Karen F. Berman¹; ¹Section on Integrative Neuroimaging, Clinical and Translational Neuroscience Branch, National Institute of Mental Health, Intramural Research Program, National Institutes of Health, Bethesda, MD, ²Neurodevelopmental Sciences Laboratory, Department of Psychological and Brain Sciences, University of Louisville, Louisville, KY

Williams syndrome (WS) is a rare neurodevelopmental disorder caused by hemideletion of ~26 genes at chromosomal locus 7q11.23. While previous behavioral research has reported working memory (WM) problems in people with WS, the neural underpinnings of this finding remain largely unexplored. Using fMRI, we investigated the neural responses to a WM task in children with WS and typically developing children (TDs). 3T-fMRI data were longitudinally collected from 15 individuals with WS (mean age=16±3.9 years, 11 females, 48 visits) and 20 TDs (mean age=15±3.9 years, 16 females, 40 visits). Groups were matched for accuracy on the WM task (WS=75.1%, TD=74.6%), which consisted of viewing pairs of images presented separately and sequentially and then indicating whether the second image matched the first image in terms of either content or height on the screen. Using a voxel-wise, mixed-effects model, we tested for group differences in activation during working memory while controlling for age and sex. Results were thresholded at p<0.05, FDR corrected. We found that individuals with WS had altered recruitment of regions in the working memory network compared to TDs. The results included reduced activation bilaterally in inferior parietal lobules and increased activation in bilateral dorsolateral prefrontal cortex (DLPFC). Our findings of hypoactivation in parietal regions are consistent with prior research showing structural and functional alterations in WS. Additionally, we found that individuals with WS recruited DLPFC more than their TD peers. Together, our findings demonstrate alterations in neural processing in regions associated with working memory in WS.

Topic Area: EXECUTIVE PROCESSES: Working memory