Authors :
Presenting Author: Venkata Sita Priyanka Illapani, MS – Children's National Medical Center
Lauren Reppert, BS – Children's National Medical Center; Madeline Marcelle, BS – Children's National Medical Center; Gabrielle Sarlo, PhD – Children's National Medical Center; William Theodore, MD – National Institute of Neurological Disorders & Stroke, NIH; William Gaillard, MD – Children's National Medical Center; Madison Berl, PhD – Children's National Medical Center; Mohamad Koubeissi, MD – George Washington University; Sara Inati, PhD – Children's National Medical Center; Leigh Sepeta, PhD – Children's National Medical Center
Rationale:
Fornix and cingulum bundle play a major role in memory encoding and retrieval. In adult unilateral TLE patients, differences in white matter organization have been observed with increased mean diffusivity and reduced fractional anisotropy bilaterally in fornix and cingulum bundle tracts (Concha L 2009). These tracts can be affected during surgery, therefore understanding these pathways is an important step to aid in better surgical outcomes. Our objective was to investigate fornix and cingulum bundle’s integrity in patients with temporal lobe epilepsy and determine association with memory ability. We hypothesize that greater white matter organization (higher fractional anisotropy [FA]) in the fornix and cingulum bundle would correlate with better memory performance.
Methods:
Twenty-seven adult participants who had epilepsy were included from a larger multi scanner NIH study (Mean age [SD] = 35[12]). Eight had temporal lobe epilepsy (Mean age [SD] = 39 [14]). Participants were scanned in Siemens (3T) scanner to obtain 45 direction multi b shell (3 B0, b-value - 200,500 and 1100) diffusion weighted images and a T1-weighted image. FSL software was used to correct for eddy current induced distortions and movement artifact. Probabilistic tractography was conducted using the Markov Chain Monte Carlo sampling method through BedpostX. This approach accounted for crossing fibers in the tractography modeling process. A combination of linear and non-linear registration techniques was employed to register diffusion images to standard space (MNI152 1mm template). We utilized xtract tool along with warp files from registration to generate automated streamlines for the fornix and cingulum bundle (dorsal, peri-genual, and temporal regions) in standard space. These streamlines were created using pre-defined seed, target, and exclusion masks provided by xtract. Mean fractional anisotropy (FA) values were extracted for each tract in both hemispheres. Weschler Memory Scale (WMS-III/IV: Visual Reproduction, Logical Memory, Verbal Paired Associates subtests) was obtained. Pearson correlations were performed using R-studio.
Results:
Mean FA of left fornix and cingulum bundle (temporal) showed association with Verbal Paired Associates immediate (r=0.56 p=0.05 and r=0.53, p=0.03). Left cingulum bundle (temporal) was also associated with Verbal Paired Associates delayed (r=0.59, p=0.02). Similarly, Mean FA in right cingulum bundle (dorsal) were correlated with Verbal Pair Associates Immediate and delayed (r=0.52, p=0.02 and r=0.81, p=0.03 respectively).
Conclusions:
Our hypothesis was confirmed that greater white matter organization in the cingulum bundle and fornix correlated with better memory ability. Paired associate learning ability showed strong associations with integrity of memory tracts. This is not surprising given that paired association learning, particularly for word pairs, engages memory systems maximally and is sensitive to damage to the MTL (Bookheimer SY 2000, Rausch R 1993).
Funding: Susan Spencer Clinical Research Fellowship; K23 NS093152 from NINDS to LNS; NINDS Division of Intramural Research; NIH/NICHD DC-IDDRC Award P50HD105328 (PI: V. Gallo); Hess Foundation