Network based neuromodulation for mesial temporal lobe epilepsy
Drug resistant epilepsy afflicts nearly a million Americans. In a substantial proportion (~40%) of patients with refractory focal epilepsy, seizures originate in the medial temporal lobe where they adversely impact the neural substrates for episodic memory. While many patients with mesial temporal lobe epilepsy (MTLE) are candidates for focal resection, resective or ablative therapies carry unacceptable risk in patients with preserved memory. The structures targeted by surgical resections – the hippocampus and para-hippocampal gyrus – are crucial to episodic memory and their destruction is likely to result in further, potentially catastrophic, memory decline. Such patients with drug resistant dominant hippocampal epilepsy with preserved memory (“epilepsy in a precious hippocampus”: EPH) are frequently encountered at tertiary epilepsy programs. Despite the severely disabling consequences of this illness and its management, few effective therapeutic options are presently available. Current neuromodulation therapies for EPH or BiMTLE (i.e., anterior nucleus of thalamus [ANT] stimulation and NeuroPaceTM) are palliative interventions. Responder rates are around 50% and modestly durable responses in small fractions (~ 15% for >3-6 months. Further, few (8.5%) patients show significant improvements in memory following neuromodulation, suggesting that the epileptic process persists despite neuromodulation.
We seek to improve on these technologies by viewing MTLE as a hyper-excitable network distributed over multiple regions rather than a single locus. Using a novel neuromodulation approach, we aim to diminish the hyperexcitability of this network via sub-threshold, low frequency stimulation targeting distributed components of the limbic epilepsy network. Low frequency low threshold stimulation has been shown for decades to be effective in “quenching” hyperexcitability. Surprisingly, its impact on human epilepsy has never been systematically studied. Given the dearth of ecologically relevant animal models of MTLE and the relatively ineffective therapeutic options currently available, we propose an ambitious, innovative approach to neuromodulation of MTLE in EPH.
Nitin Tandon, MD
Professor and Chair ad interim Director, Epilepsy Surgery Program University of Texas Houston, McGovern School of Medicine
Behnaam Aazhang, PhD
J.S. Abercrombie Professor, Electrical and Computer Engineering Director, Rice Neuroengineering Initiative (NEI), Rice University
Gregory Worrell, MD, PhD
Bioelectronics Neurophysiology and Engineering Lab, Mayo Clinic
Sandipan Pati, MD
Associate Professor Director, Epilepsy Fellowship Program, University of Texas Houston, McGovern School of Medicine
Aila Teimouri
Gradaute Student, Aazhang Group, Rice University
Jasper Wang
Graduate Student, Aazhang Group, Rice University
A, Receiver operating characteristic curves for individual patients (N = 10). B, Histogram of number of resected electrodes in each parcellation over all patients. C, Anatomical representation of epileptogenic network at the group level in a bihemispherical circular layout of all parcellations. Parcellations are depicted by the same surface color as in Figure S2. Connections are color-coded based on the average normalized (z score) strength of connections (warm = high, cool = low). The total number of recorded electrodes and number of spikes within each region are represented in concentric heat maps inside the parcellation labels of the connectogram. Within each heatmap, values are depicted by graded saturation of either green or red, except zero values indicated by black. The outer heatmap closer to the labels depicts the number of electrodes implanted in each region. The second heatmap illustrates the normalized number of spikes recorded in each region. Abbreviations in B and C correspond to different parcellations or brain regions listed in the Appendix. ACos/LinS, anterior medial occipitotemporal sulcus and lingual sulcus; AFuG, anterior fusiform gyrus; Amg, amygdala; ATrCoS, anterior transverse collateral sulcus; Hip, hippocampus; InfCirInS, inferior circular sulcus of the insula; InfFGTrip, triangular part of the inferior frontal gyrus; InfTG, inferior temporal gyrus; InfTS, inferior temporal sulcus; L, left; MTG, middle temporal gyrus; OrG, orbital gyri; PaHipG, parahippocampal gyrus; PoPI, polar plane of superior temporal gyrus; PosFuG, posterior fusiform gyrus; R, right; SupTGLp, lateral superior temporal gyrus; Tpo, temporal pole