Cortical atrophy before and after surgery map to distinct brain networks in temporal lobe epilepsy

406 

Abstract Submission 

Sara Larivière¹, Ke Xie², Frederic Schaper¹, Jessica Royer³, William Drew⁴, Sheena Baratono⁵, Yifei Weng⁶, Zhengge Wang⁶, Zhiqiang Zhang⁷, Boris Bernhardt⁸, Michael Fox¹

¹Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, ²McGill University, Montreal, Quebec, ³Montreal Neurological Institute and Hospital, Montreal, QC, ⁴Brigham and Women's Hospital, Brookline, MA, ⁵Brigham and Women's Hospital, Boston, MA, ⁶Nanjing University, Nanjing, Nanjing, ⁷Jinling Hospital, the First School of Clinical Medicine, Southern Medical University, Nanjing, Jiangsu, ⁸Montreal Neurological Institute and Hospital, Montreal, Quebec

Sara Larivière  
Brigham and Women’s Hospital, Harvard Medical School
Boston, MA

Ke Xie  
McGill University
Montreal, Quebec

Frederic Schaper  
Brigham and Women’s Hospital, Harvard Medical School
Boston, MA

Jessica Royer  
Montreal Neurological Institute and Hospital
Montreal, QC

William Drew  
Brigham and Women's Hospital
Brookline, MA

Sheena Baratono  
Brigham and Women's Hospital
Boston, MA

Yifei Weng  
Nanjing University
Nanjing, Nanjing

Zhengge Wang  
Nanjing University
Nanjing, Nanjing

Zhiqiang Zhang  
Jinling Hospital, the First School of Clinical Medicine, Southern Medical University
Nanjing, Jiangsu

Boris Bernhardt  
Montreal Neurological Institute and Hospital
Montreal, Quebec

Michael Fox  
Brigham and Women’s Hospital, Harvard Medical School
Boston, MA

Surgery is the most effective treatment to control seizures in pharmaco-resistant temporal lobe epilepsy (TLE) [1-3]. Although this approach focuses on the hippocampus and nearby temporal lobe structures, most patients also show widespread cortical atrophy beyond this disease epicenter. How these alterations elsewhere in the brain are affected by a surgical lesion, however, remains a debate. Here, we assessed whether functional connectivity from surgical lesion locations map to brain networks that are associated with cortical atrophy before and after surgery.

We studied adults with pharmaco-resistant TLE (n=37) who underwent anterior temporal lobectomy as a treatment of their seizures. All patients underwent longitudinal MRI before and after surgery. We segmented patient-specific surgical lesions using the postoperative T1-weighted MRIs (Figure 1A). Using an atlas of normative connectivity (n=1000), we identified the brain networks that were functionally connected to each patient's surgical lesion (Figure 1B) [4, 5]. We then tested whether these brain networks could differentiate cortical regions that are atrophied before surgery, after surgery, or at both time points.

Surgical lesions in all patients were negatively correlated to fronto-parietal regions (henceforth, "anticorrelated lesion network") and positively correlated to the temporo-limbic, medial prefrontal, precuneus, and inferior parietal cortices (henceforth, "positive lesion network"; Figure 1B). Individualized pre- and postoperative cortical atrophy maps were then obtained by comparing cortical thickness in each patient with TLE versus a group of age- and sex-matched healthy controls (n=31). Preoperative cortical atrophy across individual patients peaked in bilateral fronto-central regions (maximum overlap of 51.3%), whereas postoperative atrophy peaked in ipsilateral temporo-insular regions (maximum overlap of 100%; Figure 2A). Testing for morphological associations with the anticorrelated and positive lesion networks revealed significantly more preoperative cortical atrophy in the anticorrelated, relative to the positive, network (t=–4.16, p=1.90×10^–4). In contrast, more postoperative cortical atrophy was observed in the positive, relative to anticorrelated, network (t=10.10, p=4.79×10^–12; Figure 2B). Cortical atrophy that was observed in the same regions before and after surgery showed no network preference (t=1.95, p=0.059).

Brain networks functionally connected to surgical lesions in TLE differentiate pre- from postoperative cortical atrophy patterns. Our findings suggest that atrophy before and after surgery may serve different functions (e.g., compensation vs. disconnection).

Neurodevelopmental/ Early Life (eg. ADHD, autism) ¹

fMRI Connectivity and Network Modeling ²

Computational Neuroscience

Epilepsy

FUNCTIONAL MRI

Other - surgery, lesions