Authors :
Presenting Author: Joline Fan, MD – University of California, San Francisco
Benjamin Sipes, B.S. – UCSF; Kiwamu Kudo, PhD – UCSF; Kamalini Ranasinghe, MBBS, PhD – UCSF; Anne Findlay, B.S. – UCSF; Heidi Kirsch, MD – UCSF; Andrew Krystal, MD – UCSF; Ashish Raj, PhD – UCSF; Srikantan Nagarajan, PhD – UCSF
Rationale:
How the complex repertoire of functional activity is expressed on a static structural connectome remains an intriguing area of research. Prior studies have revealed reduced structure-function coupling in focal epilepsy during resting-state, but how the coupling is reduced across spatial scales has not yet been determined. We investigate whether epilepsy impacts the spatial repertoire of resting-state activity. We measure spatial repertoire by the spatial entropy and the relative loadings of the functional signal on structural integrative and segregative whole brain harmonics or eigenmodes. Alterations in this spatial repertoire may support network-wide dysfunction in epilepsy and provide a mechanism for network-based comorbidities, such as cognitive, mood, and sleep disorders.
Methods:
We evaluated 48 patients with focal epilepsy and 14 healthy controls undergoing magnetoencephalography (MEG) and simultaneous scalp EEG during resting-state and light non-rapid eye movement (NREM) sleep. Sixty seconds of artifact free recordings were selected for each subject and state. Elementary harmonics or eigenmodes of the structural connectome (SC) were derived from the normalized Laplacian of a group-averaged consensus SC in the Brainnetome atlas. Source-reconstructed MEG was then projected onto the SC eigenmodes to produce eigenmode loadings, which were ordered from low to high eigenvalues corresponding to integrative and segregative harmonics, respectively. For each canonical frequency band, we then computed the 1) spatial entropy, defined by the distribution of eigenmode loadings at each timepoint, and 2) loadings across integrative and segregative eigenmodes, defined by the mean loading across the top and bottom 10% of eigenmodes, respectively. Results:
We identified that features in the connectome harmonic loadings were distinct between healthy and epilepsy cohorts in both wakefulness and light NREM. When considering state and frequency as factors, we observed a decrease in spatial entropy in epilepsy versus healthy cohorts (F=24.6, p< 0.001). Additionally, as compared to healthy individuals, epilepsy patients exhibited increased mean loading of integrative eigenmodes (F=10.6, p=0.0012) and decreased mean loading of segregative eigenmodes (F=126.5, p< 0.001). These differences were consistent across delta through beta frequency bands.