Abnormal Left-Hemispheric Sulcal Patterns in Adults With Simple Congenital Heart Defects Repaired in Childhood

Abstract

Background Children operated on for a simple congenital heart defect (CHD) are at risk of neurodevelopmental abnormalities. Abnormal cortical development and folding have been observed in fetuses with CHD. We examined whether sulcal folding patterns in adults operated on for simple CHD in childhood differ from those of healthy controls, and whether such differences are associated with neuropsychological outcomes. Methods and Results Patients (mean age, 24.5 years) who underwent childhood surgery for isolated atrial septal defect (ASD; n=33) or ventricular septal defect (VSD; n=30) and healthy controls (n=37) were enrolled. Sulcal pattern similarity to healthy controls was determined using magnetic resonance imaging and looking at features of sulcal folds, their intersulcal relationships, and sulcal graph topology. The sulcal pattern similarity values were tested for associations with comprehensive neuropsychological scores. Patients with both ASD and VSD had decreased sulcal pattern similarity in the left hemisphere compared with controls. The differences were found in the left temporal lobe in the ASD group and in the whole left hemisphere in the VSD group (P=0.033 and P=0.039, respectively). The extent of abnormal left hemispheric sulcal pattern similarity was associated with worse neuropsychological scores (intelligence, executive function, and visuospatial abilities) in the VSD group, and special educational support in the ASD group. Conclusions Adults who underwent surgery for simple CHD in childhood display altered left hemisphere sulcal folding patterns, commensurate with neuropsychological scores for patients with VSD and special educational support for ASD. This may indicate that simple CHD affects early brain development. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03871881.

Keywords: adult; brain; congenital heart defect; magnetic resonance imaging; sulcal pattern.

Figure 1. Example of the sulcal graph pattern matching and similarity measure (value from 0 to 1) in the temporal lobe between 2 subjects.

The black nodes in the graph structure represent sulcal pits and the corresponding sulcal basins (blue boundaries) that are automatically extracted on the white matter surface. When sulcal basins meet, sulcal pits in those basins are connected with an edge. The 2 sulcal graph patterns are optimally matched, and their similarity is measured by using the geometric features of the nodes (3‐dimensional position and depth and area of sulcal basin), their relationship, and sulcal graph topology. A pair having high similarity shows more similar geometric features of nodes and their interrelationship and sulcal arrangement than the pair having low similarity.

Figure 2. Unadjusted association between neurodevelopmental outcomes and sulcal pattern similarity for the participants with a ventricular septal defect (VSD).

Pearson correlation coefficients (r) and corresponding P values are shown. A, The left hemisphere sulcal pattern similarity and full‐scale intelligence quotient (IQ). B, Left hemisphere sulcal pattern similarity and Perceptual Reasoning Index (PRI). C, Left hemisphere sulcal pattern similarity and Processing Speed Index (PSI). D, Left hemisphere sulcal pattern similarity and executive function. E, Left hemisphere sulcal pattern similarity and visuospatial learning and memory. The full‐scale IQ, PRI, and PSI were measured using the Wechsler Adult Intelligence Scale–Fourth Edition and use scaled scores corresponding to the population mean of 100 (SD, ±15). Executive function represents the Design Fluency Test, a subtest of the Delis‐Kaplan Executive Function System using scaled scores with an expected mean of 10 (SD, ±3). The visuospatial learning and memory represents the Time to Copy Trail of the Rey‐Osterrieth Complex Figure Test using time measured in seconds. In the full‐scale IQ, PRI, PSI, and Design Fluency Test, a higher score indicates a better performance; and in the Time to Copy Trail, a higher score indicates a poorer performance.