Changes in White Matter and Neurite Morphology in Response to Neurobehavioral Therapy for Nonepileptic (Functional) Seizures
Abstract number :
2.454
Submission category :
5. Neuro Imaging / 5A. Structural Imaging
Year :
2022
Submission ID :
2232938
Source :
www.aesnet.org
Presentation date :
12/4/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:28 AM
Authors :
Christina Mueller, PhD – University of Alabama at Birmimgham Heersink School of Medicine; Adam Goodman, PhD – University of Alabama at Birmingham Heersink School of Medicine; Jane Allendorfer, PhD – University of Alabama at Birmingham Heersink School of Medicine; Rodolphe Nenert, PhD – University of Alabama at Birmingham Heersink School of Medicine; Tyler Gaston, MD – University of Alabama at Birmingham Heersink School of Medicine; Leslie Grayson, MD – University of Alabama at Birmingham Heersink School of Medicine; Stephen Correia, PhD – Butler Hospital / Brown University; Noah Philip, MD – VA Providence Healthcare System; William LaFrance, MD, MPH – Rhode Island Hospital / Brown University; Jerzy Szaflarski, MD, PhD – University of Alabama at Birmingham Heersink School of Medicine
This is a Late-Breaking abstract.
Rationale: We aimed to quantify changes in white matter morphology using neurite orientation dispersion and density imaging (NODDI) in response to neuro-behavioral therapy (NBT) aimed at reducing nonepileptic (functional) seizures (FS). Previous diffusion imaging studies in FS have identified abnormal white matter microstructure in the uncinate fasciculus, fornix/stria terminalis, cingulum, and corticospinal tract, suggesting the involvement of emotion regulation, sensorimotor, cognitive control, and multimodal integration brain systems in FS pathophysiology. We expected FS patients to exhibit alterations in white matter in these regions following NBT, and that these would correlate with changes in behavioral and quality of life measures.
Methods: Forty-two patients with traumatic brain injury (TBI) and FS (TBI+FS) underwent 12 sessions of NBT and provided pre-/post-intervention neuroimaging and behavioral data; 47 control individuals with TBI without FS (TBI-only) completed the same measures but did not receive NBT. The NODDI toolbox was used to quantify neurite density (NDI), orientation dispersion (ODI), and extracellular free water (FW), respective indicators of the density of axons and dendrites, the consistency of neurite orientations, and demyelination or edema. Mixed analyses of variance assessed the group-by-time interaction in the NODDI metrics in a-priori defined regions of interest (ROIs). Interactions were followed up with repeated-measures t-tests in each group. Pearson coefficients were computed between significant white matter changes and changes in clinical outcomes.
Results: Significant group-by-time interactions were identified for ODI in the left uncinate fasciculus (F(1,87)=6.108, p=0.015), right cingulum (F(1,87)=5.489, p=0.021), and left cingulum (F(1,87)=7.122, p=0.009). Post-hoc analyses revealed ODI increases in the left cingulum bundle in TBI+FS (t(41)=-2.070, p=0.045) that correlated with changes in depression (r=0.314, p=0.045) and seizure worry (r=-0.310, p=0.049). There was a significant group-by-time interaction for FW in the right cingulum (F(1,87)=9.715, p=0.002). Post-hoc analyses showed that FW increased in TBI-only (t(46)=-2.856, p=0.006) but not in TBI+FS (t(41)=1.522, p=0.136). The FW increases in TBI-only correlated with changes in psychological symptoms on a checklist (SCL-90; r=0.383, p=0.013) and with changes in post-traumatic symptoms on the PTSD checklist (PCL-S; r=0.349, p=0.025).
Conclusions: For the first time, we identified post-treatment white matter changes in patients with FS and their relation to clinical endpoints. Although we did not identify any brain substrates of the reduction in FS frequency, we found associations between indices of white matter integrity and common clinical co-morbidities of FS (depression, seizure worry), which are also targeted by the NBT intervention. NODDI could be incorporated into future mechanistic assessments of FS interventions.
Funding: CDMRP Epilepsy Research Program (W81XWH-17-1-0619) and VA RR&D Center for Neurorestoration and Neurotechnology (I50 RX002864)
Neuro Imaging