Neurocognitive monitoring in congenital central hypoventilation syndrome with the NIH Toolbox®

Remi Z. Welbel, Casey M. Rand, Amy Zhou, Allaa Fadl-Alla, Maida Lynn Chen, Debra E. Weese-Mayer, Frank A. Zelko*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Congenital central hypoventilation syndrome (CCHS) is a rare neurocristopathy, caused by mutations in the paired-like homeobox gene PHOX2B, which alters control of breathing and autonomic nervous system regulation, necessitating artificial ventilation as life-support. A broad range of neurocognitive performance has been reported in CCHS, including an array of cognitive deficits. We administered the NIH Toolbox® Cognition Battery (NTCB), a novel technology comprised of seven tasks presented via an interactive computer tablet application, to a CCHS cohort and studied its convergent and divergent validity relative to traditional clinical neurocognitive measures. The NTCB was administered to 51 CCHS participants, including a subcohort of 24 who also received traditional clinical neurocognitive testing (Wechsler Intelligence Scales). Age-corrected NTCB scores from the overall sample and subcohort were compared to population norms. Associations between NTCB indices and Wechsler Intelligence scores were studied to determine the convergent and divergent validity of the NTCB. NTCB test results indicated reduced Fluid Cognition, which measures new learning and speeded information processing (p < 0.001), but intact Crystallized Cognition, which measures past learning, in CCHS relative to population norms. Moderate to strong associations (r > 0.60) were found between age-corrected NTCB Fluid and Crystallized indices and comparable Wechsler indices, supporting the convergent and discriminant validity of the NTCB. Results reveal deficits of Fluid Cognition in individuals with CCHS and indicate that the NTCB is a valid and sensitive measure of cognitive outcomes in this population. Our findings suggest that the NTCB may play a useful role in tracking neurocognition in CCHS.

Original languageEnglish (US)
Pages (from-to)2040-2047
Number of pages8
JournalPediatric Pulmonology
Issue number9
StatePublished - Sep 2022


  • PHOX2B
  • artificial ventilation
  • attention
  • autonomic (dys)regulation
  • cognition
  • control of breathing
  • executive functioning
  • intelligence
  • neuropsychology
  • processing speed

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Pediatrics, Perinatology, and Child Health


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