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(Abst. 2.046), 2018

Interictal ECoG Features Correlate With Depression in Individuals With Epilepsy
Authors: Beata Jarosiewicz, NeuroPace, Inc.; Tara L. Skarpaas, NeuroPace, Inc.; David W. Loring, Emory University School of Medicine; Kimford J. Meador, Stanford University; Andres M. Kanner, University of Miami; and Martha J. Morrell, Stanford University / NeuroPace, Inc.
Content: Rationale: Depression is a common and debilitating comorbidity of epilepsy. In a randomized controlled trial of the RNS® System (NeuroPace, Inc., Mountain View, CA), brain-responsive neurostimulation was shown to treat focal onset seizures safely and effectively in individuals with medically resistant focal epilepsy. These patients also showed a modest improvement in the presence and severity of symptoms of depression, as assessed by the Beck Depression Inventory-II (BDI), after 1-2 years of treatment with the RNS System (Meador et al., Epilepsy & Behavior 2015). Here, we retrospectively examined the relationship between their BDI scores and interictal electrocorticographic (ECoG) activity recorded by the neurostimulator. Methods: Mood assessments were administered during a pre-implant baseline period (0 weeks), and at 20, 55, 80, and 104 weeks post-implant. The average spike rate, total spectral power, and power in delta (0-4), theta (4-8), alpha (8-12), beta (12-25), low gamma (25-50) and high gamma (50-125 Hz) bands were computed from 1-4 minute long interictal ECoG segments recorded roughly twice per day over the 3 month period preceding each time point (except for baseline). Changes in BDI mood scores over time and changes in ECoG features over time were assessed using weighted linear regression after baseline subtraction. Relationships between mood scores and ECoG  features were assessed within-patient using Pearson correlation (r) of the 2 measures across time, producing 1 r value per lead for which both measures were available at 2 or more timepoints. Mood scores were weighted by the % of questions completed at each timepoint, and ECoG features were weighted by the total length of the recorded ECoGs from which they were computed. Distributions of r values were compared to 0 using 2-tailed weighted t-tests. Results: Confirming and extending the results of Meador et al., 2015, we found that BDI scores significantly decreased (i.e. mood improved) over time post-implant (linear regression with time, N = 191 patients, p < 0.00001). Additionally, the following ECoG features significantly decreased over time: spike rates (p < 0.0001), theta power (p < 0.0001), and delta power (p < 0.0005). Changes over time in BDI scores were significantly correlated with changes over time in spike rates and theta power (Table 1). Performing the correlation analysis by lead location (Table 2) revealed that BDI scores were significantly correlated with spike rate only in neocortex (NC), and were inversely correlated with low and high gamma power in the mesial temporal lobe (MTL). Conclusions: These analyses support the hypothesis that treating focal onset epilepsy with brain-responsive neurostimulation might also help to improve mood. They also reveal that more severe depression in individuals with focal onset epilepsy is associated with higher theta power, higher interictal spike rates specifically in NC, and lower gamma power specifically in MTL. Future studies could examine prospectively whether neural stimulation in response to these ECoG features in people with epilepsy could have a causal role in improving mood. Funding: None
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