TAMI-66. FUNCTIONAL ALTERATIONS IN CORTICAL PROCESSING OF SPEECH IN GLIOMA-INFILTRATED CORTEX

INTRODUCTION Recent developments in the biology of malignant gliomas have demonstrated that glioma cells interact with neurons through both paracrine signaling and electrochemical synapses. Glioma-neuron interactions consequently modulate the excitability of local neuronal circuits, and it is unclear the extent to which glioma-infiltrated cortex can meaningfully participate in neural computations. For example, gliomas may result in a local disorganization of activity that impedes the transient synchronization of neural oscillations. Alternatively, glioma-infiltrated cortex may retain the ability to engage in synchronized activity, in a manner similar to normal-appearing cortex, but exhibit other altered spatiotemporal patterns of activity with subsequent impact on cognitive processing. METHODS Here, we acquired invasive electrophysiologic recordings to sample both normal-appearing and glioma-infiltrated cortex during speech initiation in order to measure language task-related circuit dynamics of IDH-wild-type glioblastoma patients. We then applied an information theoretical framework to directly compare the encoding capacity and decodability of signals arising from these regions. RESULTS We find that glioma-infiltrated cortex engages in synchronous activity during task performance in a manner similar to normal-appearing cortex, but recruits a diffuse spatial network. On a temporal scale, we show that glioma-infiltrated cortex has lower capacity for information encoding when performing nuanced tasks such as speech production of monosyllabic versus polysyllabic words. As a result, temporal decoding strategies for distinguishing monosyllabic from polysyllabic words were feasible for signals arising from normal-appearing cortex, but not from glioma-infiltrated cortex. CONCLUSION These findings inform our understanding of cognitive processing in patients with malignant gliomas and have implications for patient survival, neuromodulation, and prosthetics in patients with malignant gliomas.

Identifying the Location of an Accessory Pathway in Pre-Excitation Syndromes Using an Artificial Intelligence-Based Algorithm

(1) Background: The exact anatomic localization of the accessory pathway (AP) in patients with Wolff–Parkinson–White (WPW) syndrome still relies on an invasive electrophysiologic study, which has its own inherent risks. Determining the AP localization using a 12-lead ECG circumvents this risk but is of limited diagnostic accuracy. We developed and validated an artificial intelligence-based algorithm (location of accessory pathway artificial intelligence (locAP AI)) using a neural network to identify the AP location in WPW syndrome patients based on the delta-wave polarity in the 12-lead ECG. (2) Methods: The study included 357 consecutive WPW syndrome patients who underwent successful catheter ablation at our institution. Delta-wave polarity was assessed by four independent electrophysiologists, unaware of the site of successful catheter ablation. LocAP AI was trained and internally validated in 357 patients to identify the correct AP location among 14 possible locations. The AP location was also determined using three established tree-based, ECG-based algorithms (Arruda, Milstein, and Fitzpatrick), which provide limited resolutions of 10, 5, and 8 AP locations, respectively. (3) Results: LocAP AI identified the correct AP location with an accuracy of 85.7% (95% CI 79.6–90.5, p < 0.0001). The algorithms by Arruda, Milstein, and Fitzpatrick yielded a predictive accuracy of 53.2%, 65.6%, and 44.7%, respectively. At comparable resolutions, the locAP AI achieved a predictive accuracy of 95.0%, 94.9%, and 95.6%, respectively (p < 0.001 for differences). (4) Conclusions: Our AI-based algorithm provided excellent accuracy in predicting the correct AP location. Remarkably, this accuracy is achieved at an even higher resolution of possible anatomical locations compared to established tree-based algorithms.

Abstract 20168: Enhanced Endothelial Nitric Oxide Production and Cardiac Dysfunction in an Inducible Endothelial-Specific miR-130a Mouse Model

Introduction: MicroRNA-130a (miR130a) has been shown to be important in cardiovascular gene regulation in both normal and diseased states. We recently reported on the regulation of connexin43 by miR130a. Methods: We created an inducible mouse model to express miR-130a in endothelial cells under the control of the VE-cadherein promoter (VE-cad-miR130a). Overexpression of miR-130a was initiated in adult mice at weaning, approximately 4 weeks post-birth. Results: Survival analysis revealed >50% mortality by 9 weeks of age with overexpression of miR-130a. By 9 weeks of age, LV function was reduced (26.4% ± 4 vs 33.6% ± 6 in controls, p<0.001, n=10). Prior to the onset of LV dysfunction; we found numerous abnormalities in cardiac function. First, we noted significant bradycardia on ambulatory telemetric recordings (389bpm ± 90 vs 534bpm ± 72 in controls, p<0.0001, n=3). Moreover, the cardiac response to β-AR stimulation was blunted in VE-Cad-miR130a mice relative to control when challenged with isoproterenol. Interestingly, sinus node recovery time was significantly prolonged, supportive of sinus node dysfunction. While predominately in sinus rhythm, we found episodes of spontaneous atrial tachyarrhythmias, which were confirmed on invasive electrophysiologic testing. To investigate further, we performed patch clamp measurements of action potential duration (APD) in atrial cariomyocytes. APD was significantly prolonged in VE-Cad-miR130a myocytes (APD90 325ms vs 60ms, p<0.00001, n=3). Next, we performed invasive blood measure measurements and found a significant decrease in mean arterial blood pressure (76.9mmHg ± 3 vs 94.3mmHg ± 5 in controls, p<0.01, n=4). Based on previous reports of increased nitric oxide in the setting of loss of endothelial connexin43, we found significant elevation of NO concentration in VE-Cad-miR130a. Inhibition of NO synthase via IP administration of L-NAME increased MAP in VE-Cad-miR130a to a maximum steady-state mimicking that of control mice. Conclusions: Overexpression of miR-130a in endothelial cells promotes impaired cardiovascular function and abnormal atrial conduction. These results suggest a newly identified role for endothelial miR-130a in the development of hypotension and cardiac dysrhythmias.