190 Mechanism for Sudden Unexpected Death in Epilepsy

Dlouhy, Brian J.; Gehlbach, Brian K.; Kreple, Collin J.; Kawasaki, Hiroto; Oya, Hiroyuki; Buzza, Colin; Granner, Mark A.; Welsh, Michael J.; Howard, Matthew A.; Wemmie, John A.; Richerson, George B.

doi:10.1227/01.neu.0000452464.34409.03

Cited by 5 publications

(4 citation statements)

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“…ICA often accompanies seizure activity in the amygdala (16,26), with direct electrical stimulation inducing apnea (14,16). The findings in functional pathology add to experimental animal evidence that subnuclei within the amygdala can pace inspiratory efforts (27).…”

Section: Overviewmentioning

confidence: 81%

“…One study in particular (44) highlighted that asymmetrical sympathetic activation may contribute to particularly dangerous cardiac arrythmias. However, as opposed to the insula, in the amygdala, the cardiorespiratory consequences do not appear to show laterality (14).…”

Section: Amygdala Microstructure and Breathing Disturbancesmentioning

confidence: 83%

“…Stimulation of the human amygdala triggers apnea, sometimes without subject awareness of breathing cessation (14)(15)(16), leading to the hypothesis that amygdala influences may affect respiratory recovery following seizures. Those influences may be enhanced or disrupted if the amygdala is damaged by recurrent seizures and epileptogenesis.…”

Section: Introductionmentioning

confidence: 99%

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Altered Amygdala Volumes and Microstructure in Focal Epilepsy Patients with Tonic-Clonic Seizures, Ictal and Post-Ictal Central Apnea

Zeicu

Legouhy

Scott

et al. 2023

Preprint

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Objectives: Sudden unexpected death in epilepsy (SUDEP) is a leading cause of death for patients with epilepsy; however, the pathophysiology remains unclear. Focal-to-bilateral tonic-clonic seizures (FBTCS) are a major risk factor, and centrally-mediated respiratory depression may increase the risk further. Here, we determined volume and microstructure of the amygdala, a key structure that can trigger apnea in people with focal epilepsy, stratified by presence or absence of FBTCS, ictal central apnea (ICA) and post-ictal central apnea (PICA). Methods: 73 patients with only-focal seizures and 30 with FBTCS recorded during video EEG (VEEG) with respiratory monitoring were recruited prospectively during presurgical investigations. We acquired high-resolution T1-weighted anatomical and multi-shell diffusion images, and computed neurite orientation dispersion and density imaging (NODDI) metrics in all epilepsy patients and 69 healthy controls. Amygdala volumetric and microstructure alterations were compared between healthy subjects, and patients with only-focal seizures or FBTCS The FBTCS group was further subdivided by presence of ICA and PICA, verified by VEEG. Results: Bilateral amygdala volumes were significantly increased in the FBTCS cohort compared to healthy controls and the focal cohort. Patients with recorded PICA had the highest increase in bilateral amygdala volume of the FBTCS cohort. Amygdala neurite density index (NDI) values were significantly decreased in both the focal and FBTCS groups relative to healthy controls, with values in the FBTCS group being the lowest of the two. The presence of PICA was associated with significantly lower NDI values vs the non-apnea FBTCS group (p=0.004). Significance: Individuals with FBTCS and PICA show significantly increased amygdala volumes and disrupted architecture bilaterally, with greater changes on the left side. The structural alterations reflected by NODDI and volume differences may be associated with inappropriate cardiorespiratory patterns mediated by the amygdala, particularly after FBTCS. Determination of amygdala volumetric and architectural changes may assist identification of individuals at risk.

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Section: Overviewmentioning

confidence: 81%

Section: Amygdala Microstructure and Breathing Disturbancesmentioning

confidence: 83%

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Altered Amygdala Volumes and Microstructure in Focal Epilepsy Patients with Tonic-Clonic Seizures, Ictal and Post-Ictal Central Apnea

Zeicu

Legouhy

Scott

et al. 2023

Preprint

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“…duration of the cardiac cycle) and neural firing rates, reporting evidence for cardiac coding in human anterior cingulate cortex and medial temporal lobe (Frysinger & Harper, 1990; K. Kim et al, 2019). For respiration, while prior intracranial studies in humans have shown local neural activity linked to breathing (Dlouhy et al, 2015;Seyal & Bateman, 2009), to date no study has, to the best of our knowledge, investigated the link between respiration and single neuron activity in humans.…”

Section: Introductionmentioning

confidence: 99%

Single neurons in thalamus and subthalamic nucleus process cardiac and respiratory signals in humans

Falco

Solcà

Bernasconi

et al. 2022

Preprint

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Visceral signals are constantly processed by our central nervous system, enable homeostatic regulation, and influence perception, emotion, and cognition. While visceral processes at cortical level have been extensively studied using non-invasive imaging techniques, very few studies have investigated how this information is processed at the single neuron level, both in humans and animals. Subcortical regions, relaying signals from peripheral interoceptors to cortical structures, are particularly understudied and how visceral information is processed in thalamic and subthalamic structures remains largely unknown. Here, we took advantage of intraoperative microelectrode recordings in patients undergoing surgery for deep brain stimulation (DBS) to investigate the activity of single neurons related to cardiac and respiratory functions in three subcortical regions: Ventral Intermedius nucleus (Vim) and Ventral caudalis nucleus (Vc) of the thalamus, and subthalamic nucleus (STN). We report that the activity of a large portion of the recorded neurons (about 70%) was modulated by either the heartbeat, the cardiac inter-beat interval, or the respiration. These cardiac and respiratory response patterns varied largely across neurons both in terms of timing and their kind of modulation. We observed neurons with increases or decreases in firing rate in response to either the heartbeat or the inter-beat interval. Peaks of neural activity were found at different phases of the cardiac and respiratory cycles. Whereas most neurons only responded to one of the tested signals, a substantial proportion of these visceral neurons (30%) was responsive to more than one of the tested signals, underlining specialization and integration of cardiac and respiratory signals in STN and thalamic neurons. By extensively describing for the first time single unit activity related to cardiorespiratory function in thalamic and subthalamic neurons, our results highlight the major role of these subcortical regions in the processing of visceral signals.

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Hypothesis: The central medial amygdala may be implicated in sudden unexpected death in epilepsy by melanocortinergic–sympathetic signaling

Guan

Liu

et al. 2014

Epilepsy & Behavior

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190 Mechanism for Sudden Unexpected Death in Epilepsy

Cited by 5 publications

References 0 publications

Altered Amygdala Volumes and Microstructure in Focal Epilepsy Patients with Tonic-Clonic Seizures, Ictal and Post-Ictal Central Apnea

Altered Amygdala Volumes and Microstructure in Focal Epilepsy Patients with Tonic-Clonic Seizures, Ictal and Post-Ictal Central Apnea

Single neurons in thalamus and subthalamic nucleus process cardiac and respiratory signals in humans

Hypothesis: The central medial amygdala may be implicated in sudden unexpected death in epilepsy by melanocortinergic–sympathetic signaling

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