Abstracts

Rationale: Direct electrical cortical stimulation of the amygdala (AM) has been found to induce apnoea of which patients are unaware, highlighting the importance of the structure in the central autonomic system. Other important cortical regions in respiratory and blood pressure (BP) regulation include the medial orbitofrontal cortex (OF), medial prefrontal cortex and anterior cingulate gyrus (AC). Meta analyses of functional connectivity have suggested co-activations of medial orbitofrontal cortex, cingulum and amygdala. Effective connectivity of the amygdala based on direct electrical cortical stimulation has rarely been reported. Using corticocortical potentials (CCEPs), we seek to clarify the presence and directionality of such connections. Methods: We reviewed single pulse stimulation of 10 patients who had undergone intracranial EEG investigations using SEEG, who had implantation of the amygdala (AM), orbitofrontal cortex (OF) and anterior cingulate (AC) regions (bilateral in one patient), amongst others to establish surgical candidacy. We performed single pulse electrical cortical stimulations using a Micromed Integrated Cortical Stimulator (biphasic pulses of 500 µs/phase duration delivered at a rate of 0.2 Hz, with currents ranging from 2.5 to 4 mA). CCEPs to and from those structures were visually analysed. Radiological verification of electrode location was performed on post-implantation MRI. Potentials were accepted if reproducible and of appreciable amplitude against baseline and preceding EEG with peak latency of the first major peak occurring earlier than 200ms following stimulus artefact. Potentials were assessed from the AM to OF and AC, and from OF and AC to AM for any bidirectional projections. Stimulation number ranged from 9 to 20, with a mean of 18. Results: The amygdala frequently showed projections to medial (8 of 9 patients, 89%) and lateral (4 of 6 patients, 67%) OF, with less frequent connectivity demonstrated to the AC (5 of 9, 56%). Projections from medial OF were seen in 5 of 9 (56%), with bidirectional projections identified in 4 of those 5. Lateral OF projected to the AM in 2 of 5 patients (40%) with no evidence of bidirectional projections. The AC showed no direct projections to the AM. Conclusions: The study revealed a high percentage of connectivity between AM and medial OF with bidirectional connectivity seen in half; such high effective connectivity may support common bidirectional influences between those structures, highly relevant for regulation of autonomic functions. Unidirectional connectivity from AM was demonstrated to the AC. Such networks are critical in maintaining both respiratory and BP regulation and damage and dysfunction in these areas as often present in epilepsy may predispose to centrally-mediated failure to recover from severe generalised tonic-clonic seizures, thus increasing the risk for Sudden Unexpected Death in Epilepsy. Funding: Dept. of Health's NIHR Biomedical Research Centres funding scheme. National Institute of Neurological Disorders and Stroke U01-NS090407 (The Center for SUDEP Research); Guarantors of Brain; The Wellcome Trust.