Functional Connectivity Alterations Between Intrinsic Networks and Arousal Structures and Their Neurocognitive Correlates in TLE
Abstract number :
3.243
Submission category :
5. Neuro Imaging / 5B. Functional Imaging
Year :
2021
Submission ID :
1825740
Source :
www.aesnet.org
Presentation date :
12/6/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:50 AM
Authors :
Dario Englot, MD, PhD - Vanderbilt University Medical Center; Hernan Gonzalez, PhD - Vanderbilt University Medical Center; Saramati Narasimhan, PhD – Postdoctoral Research Fellow, Neurological Surgery, Vanderbilt University Medical Center; Sarah Goodale, B.E. – Graduate Student, Biomedical Engineering, Vanderbilt University; Graham Johnson, B.S. – Graduate Student, Biomedical Engineering, Vanderbilt University; Kristin Wills, B.S. – Research Assistant, Neurological Surgery, Vanderbilt University Medical Center; Danika Paulo, M.D. – Resident Physician, Neurological Surgery, Vanderbilt University Medical Center; Monica Jacobs, PsyD – Assistant Professor, Psychiatry, Vanderbilt University Medical Center; Peter Konrad, MD, PhD – Neurological Surgery – West Virginia University; Victoria Morgan, PhD – Professor, Radiology & Radiological Sciences, Vanderbilt University Medical Center; Catie Chang, PhD – Assistant Professor, Electrical Engineering and Computer Science, Vanderbilt University
Rationale: Although temporal lobe epilepsy (TLE) is a focal epilepsy, TLE patients experience broad connectivity abnormalities and global neurocognitive deficits unrelated to temporal lobe functions. We have previously shown that subcortical arousal structures (including brainstem, thalamus, and basal forebrain nuclei) exhibit abnormal connectivity in TLE which are associated with measures of disease severity. Others, have shown that TLE patients have perturbed connectivity within and between intrinsic connectivity networks (ICNs; e.g. default mode network). No prior studies have examined how decreased connectivity within ICNS may relate to subcortical arousal networks (Fig 1). We sought to determine if TLE patients have abnormalities in functional connectivity (FC) between arousal structures and ICNs.
Methods: We acquired resting-state fMRI in 50 TLE patients (28 female; 39.9±12.2yrs) and 50 matched controls (28 female; 39.8±12.3yrs). We calculated non-directed FC (Fisher z-scored correlation) and directed FC (Granger causality laterality index: GCLI) within ICNs (default mode network: DMN, salience network: SN, and central executive network: CEN) and between arousal structures (brainstem ascending reticular activating system, intralaminar thalamus, and nucleus basalis of Meynert) and ICNs. We compared FC in patients vs. controls, and associated FC with disease metrics and neurocognitive testing. Finally, we used an fMRI-based measure of alertness to preliminarily relate changes in alertness to resting-state FC of arousal structures.
Results: We noted decreased (Fig 2) non-directed FC within DMN in patients (5.73±1.44) vs. controls (6.75±1.38, p=0.0008, t-test) and within SN in patients (9.27±2.19) vs. controls (10.40±2.33, p=0.0008, t-test). We found decreased FC between arousal network and SN in patients (1.12±1.03) vs. controls (2.04±1.27, p=0.0001, t-test). Larger decreases in non-directed FC between nucleus basalis of Meynert (NBM) and SN were associated with worse processing speed index (r=0.251, p=0.033, Pearson correlation). Lower non-directed FC between pedunculopontine nucleus and SN associated with worse verbal comprehension index (r=0.350, p=0.015, Pearson correlation) and full-scale IQ (r=0.296, p=0.043, Pearson correlation). We noted abnormal GCLI between arousal network and SN in patients (-0.095±0.21) vs. controls (-0.26±0.24, p=0.0012, t-test), meaning SN exerts influence on arousal structures in controls, but not patients. After surgery, we noted some recovery of non-directed FC between NBM and SN. With a preliminary fMRI-based alertness measure, we found that patients, but not controls, may exhibit reduced alertness during fMRI but that FC did not change with alertness.
Conclusions: These results suggest that in TLE patients, abnormal FC between subcortical arousal structures and ICNs may partially underlie neurocognitive deficits often attributed to abnormal FC within ICNs.
Funding: Please list any funding that was received in support of this abstract.: NIH F31NS106735, R00NS097618, R01NS112252, T32EB021937, T32GM007347, T32EB001628, R01NS110130, R01NS108445. R01NS075270, R01NS108445, R01NS110130.
Neuro Imaging