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Case Reports
. 2024 Aug 8:4:1426743.
doi: 10.3389/fnetp.2024.1426743. eCollection 2024.

Case report: Bridging limbic network epilepsy with psychiatric, memory, and sleep comorbidities: case illustrations of reversible psychosis symptoms during continuous, high-frequency ANT-DBS

Lydia Wheeler  1   2 , Samuel E Worrell  3 , Irena Balzekas  1   2 , Jordan Bilderbeek  2 , Dora Hermes  2 , Paul Croarkin  4 , Steven Messina  5 , Jamie Van Gompel  3 , Kai J Miller  3 , Vaclav Kremen  1   2   6 , Gregory A Worrell  1   2
Affiliations
Case Reports

Case report: Bridging limbic network epilepsy with psychiatric, memory, and sleep comorbidities: case illustrations of reversible psychosis symptoms during continuous, high-frequency ANT-DBS

Lydia Wheeler et al. Front Netw Physiol. .

Abstract

The network nature of focal epilepsy is exemplified by mesial temporal lobe epilepsy (mTLE), characterized by focal seizures originating from the mesial temporal neocortex, amygdala, and hippocampus. The mTLE network hypothesis is evident in seizure semiology and interictal comorbidities, both reflecting limbic network dysfunction. The network generating seizures also supports essential physiological functions, including memory, emotion, mood, and sleep. Pathology in the mTLE network often manifests as interictal behavioral disturbances and seizures. The limbic circuit is a vital network, and here we review one of the most common focal epilepsies and its comorbidities. We describe two people with drug resistant mTLE implanted with an investigational device enabling continuous hippocampal local field potential sensing and anterior nucleus of thalamus deep brain stimulation (ANT-DBS) who experienced reversible psychosis during continuous high-frequency stimulation. The mechanism(s) of psychosis remain poorly understood and here we speculate that the anti-epileptic effect of high frequency ANT-DBS may provide insights into the physiology of primary disorders associated with psychosis.

Keywords: ANT-DBS; Epilepsy; limbic network; psychosis; seizure.

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Conflict of interest statement

Unrelated to this research GW and JVG. are inventors of intellectual property developed at Mayo Clinic and licensed to Cadence Neuroscience Inc. Mayo Clinic has received research support and consulting fees on behalf of GW from Cadence Neuroscience and Medtronic. GW is on the scientific advisory boards of LivaNova Inc., NeuroPace Inc., and Cadence Neuroscience Inc. PC has received research grant support from Neuronetics, NeoSync, and Pfizer; grant in kind (equipment support) from Assurex, MagVenture, and Neuronetics; and served as a consultant for Engrail Therapeutics, Myriad Neuroscience, Procter and Gamble, and Sunovion. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Limbic Circuit of Papez and MacLean: McLean modified Papez version of the limbic circuitry and emphasized the amygdala and septum in addition to hippocampus [20]. (A) Schematic of Limbic Circuit highlighting the closed-loop pathway from the entorhinal cortical (EC) input to hippocampus (HC). The outflow of HC via the Fornix (fx) fibers spans the corpus callosum (CC) and divides into pre- (terminate in Septal Nuclei (SN)) and post- (terminate in the mammillary bodies (MB)) CC commissural fibers. The post-commissural fibers project through the hypothalamus to the MB, and MB fibers project via mammillary thalamic tract (MTT) to the anterior nucleus of the thalamus (ANT). (Note: The MTT is widely used for direct targeting of the ANT for ANT-DBS). The ANT output via anterior thalamocortical fibers to the anterior Cingulate Gyrus and back to EC and HC via the Cingulum. (B) Diffusion tensor imaging (DTI) demonstrating white matter tracks discussed above. (C) Fast gray matter acquisition T1 inversion recovery (FGATIR) MRI sequence visualizing the MB, MTT and ANT. (D) Human brain dissection demonstrating the MB and MTT connecting MB and ANT. (B) modified from Ojeda Valencia, Gabriela, et al. “Signatures of Electrical Stimulation Driven Network Interactions in the Human Limbic System.” Journal of Neuroscience: 43, no. 39 (27 September 2023): 6697–6711. (C,D) modified from Grewal, S., et al. “Fast Gray Matter Acquisition T1 Inversion Recovery MRI to Delineate the Mammillothalamic Tract for Preoperative Direct Targeting of the Anterior Nucleus of the Thalamus for Deep Brain Stimulation in Epilepsy.” Neurosurgical Focus 45, no. 2 (2018).
FIGURE 2
FIGURE 2
Human limbic circuit electrophysiology. Continuous LFP streaming was used to track mesial temporal lobe and ANT electrophysiology in people with mTLE living in their natural home environment. (A) Synchronized bidirectional communications between patients, implantable neural sensing-stimulation devices, mobile devices, and cloud computing infrastructure enable monitoring electrophysiology. Top) Implanted neural sensing and stimulation device in subclavicular pocket (1). The implanted devices have bidirectional communication with the mobile device (2) and cloud environment (3). Bottom) Lateral x-ray post-implant showing the 4 leads implanted in bilateral ANT and AMG-HPC. (B) Top) Continuous LFP over multiple hours. Bottom) Circles highlight automated IES and seizure detections on mobile devices (tablet computers). (C) Co-registration of CT and MRI-DTI demonstrating the posterior approach to the AMG-HPC and ANT for brain sensing and stimulation electrodes.
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