Authors :
Presenting Author: Adam Goodman, PhD – University of Alabama at Birmingham
Wendy Lin, NA – University of Alabama at Birmingham; Jakaiya Bryant, NA – University of Alabama at Birmingham; Rodolphe Nenert, PhD – University of Alabama at Birmingham; Roy Martin, PhD – University of Alabama at Birmingham; Jerzy Szaflarski, MD, PhD – University of Alabama at Birmingham; Anna Moyana, BA – University of Alabama at Birmingham; Jennifer Pilkington, BA – University of Alabama at Birmingham; Goutham Selladurai, BA – University of Alabama at Birmingham; Brandon Mitchell, BA – University of Alabama at Birmingham; Jane Allendorfer, PhD – University of Alabama at Birmingham
Rationale: Poor global cognitive functioning is common in idiopathic generalized epilepsies (IGEs) (Chowhurdy et al., 2014). However, the associated underlying neural mechanisms remain unspecified. Aberrant resting state functional connectivity (rsFC) within the default mode network (DMN) has been well documented in IGEs, yet limited prior work has related these alterations to neurobehavioral measures of cognitive performance. We hypothesized that differences in executive function performance assessed during a Flanker task would correspond to changes in DMN connectivity during resting state functional magnetic resonance imaging (rs-fMRI) in patients with IGEs.
Methods: A total of 21 participants with documented and clinician-confirmed IGE completed two rs-fMRI runs on a Siemens 3T Prisma MRI scanner at the University of Alabama at Birmingham. Outside of the scanner, all participants also completed the Flanker task on an iPad as part of the NIH Toolbox Cognition Battery. Rs-fMRI data were processed using AFNI software and were concatenated into a single run before being submitted to standard preprocessing and denoising. An ROI seed-based analysis was used to identify regions with significant rsFC with the posterior cingulate cortex and bilateral parietal regions of the seizure initiation and propagation network (Allendorfer et al., 2019). Clusters of DMN connectivity (one sample t-test, H
O=0) showing relationships to individual differences in executive functioning were identified for each of the three ROI seeds. Specifically, Flanker task performance (incongruent >congruent reaction times, RTs) was included as a factor in each of the three models (3dttest++). Mean rsFC signal from surviving clusters were extracted for descriptive purposes.
Results: An initial paired samples t-test confirmed as a manipulation check that incongruent RTs (
M=731.0 ms) were significantly greater than congruent RTs (
M=625.2 ms) at the group level (t[20]=3.80, p< 0.001). A cluster volume extent threshold was calculated to correct for multiple comparisons using 3dclustsim (with -acf option) for a brain mask (2892 mm
3) based on a prior published DMN map (Laird et al., 2011). Tests revealed significant rsFC from the right parietal seed to the left angular gyrus (3272 mm
3; MNI peak: x=-42, y=70, z=37; Fig. 1A). Signal extraction (3dROIstats) for the angular gyrus cluster revealed positive correlation between differential RTs and DMN connectivity (r=0.843; Fig. 1B).
Conclusions: Prior work has shown that cortical hyperexcitability is associated with poorer attention in people with IGEs (Bolden et al., 2018). Further, aberrant DMN connectivity during rest (Holmes et al., 2012) and language or working memory tasks (Caciagli et al., 2023) has been reported in people with epilepsy. The current study provides a novel assessment for the potential role of DMN hyperconnectivity in poor executive functioning in IGEs. Future intervention studies that target this network can further test the hypothesis that DMN connectivity plays a key role in executive functioning impairments in IGEs.
Funding: This work was supported by the National Institutes of Health (R01HD102723 to JBA).