Ictal recruitment of anterior nucleus of thalamus in human focal epilepsy

Tóth, Emília; Chaitanya, Ganne; Pizarro, Diana; Kumar, Sachin; Ilyas, Adeel; Romeo, Andrew; Riley, Kristen; Vlachos, Ioannis; David, Olivier; Balasubramanian, Karthi; Pati, Sandipan

doi:10.1101/788422

Cited by 3 publications

(2 citation statements)

References 70 publications

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“…A further study by Toth et al . 98 used an epileptogenicity index based on SEEG data and found that seizures that had an onset in the mesial temporal lobe (compared with other SOZs) had a higher and faster rate of ANT recruitment and that ANT recruitment preceded clinical onset. They also found that seizures that recruited the ANT lasted longer.…”

Section: Propagation Points Within the Epileptogenic Networkmentioning

confidence: 99%

Towards network-guided neuromodulation for epilepsy

Piper

Richardson

Worrell

et al. 2022

Brain

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Epilepsy is well-recognized as a disorder of brain networks. There is a growing body of research to identify critical nodes within dynamic epileptic networks with the aim to target therapies that halt the onset and propagation of seizures. In parallel, intracranial neuromodulation, including deep brain stimulation and responsive neurostimulation, are well-established and expanding as therapies to reduce seizures in adults with focal epilepsy; and there is emerging evidence for their efficacy in children and generalized seizure disorders. The convergence of these advancing fields is driving an era of ‘network-guided neuromodulation’ for epilepsy. In this review we distil the current literature on network mechanisms underlying neurostimulation for epilepsy. We discuss the modulation of key propagation points in the epileptogenic network, focusing primarily on thalamic nuclei targeted in current clinical practice. These include (a) the anterior nucleus of thalamus, now a clinically approved and targeted site for open loop stimulation, and increasingly targeted for responsive neurostimulation; and (b) the centromedian nucleus of the thalamus, a target for both deep brain stimulation and responsive neurostimulation in generalized-onset epilepsies. We discuss briefly the networks associated with other emerging neuromodulation targets, such as the pulvinar of the thalamus, piriform cortex, septal area, subthalamic nucleus, cerebellum and others. We report synergistic findings garnered from multiple modalities of investigation that revealed structural and functional networks associated with these propagation points – including scalp and invasive electroencephalography, diffusion and functional magnetic resonance imaging. We also report on intracranial recordings from implanted devices which provide us data on the dynamic networks we are aiming to modulate. Finally, we review the continuing evolution of network-guided neurostimulation for epilepsy to accelerate progress towards two major goals: (1) to use pre-surgical network analyses to determine patient candidacy for neurostimulation for epilepsy by providing network biomarkers that predict efficacy; and (2) to deliver precise, personalized and effective antiepileptic stimulation to prevent and arrest seizures, limit seizure propagation through mapping and modulation of each patients’ individual epileptogenic networks.

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Section: Propagation Points Within the Epileptogenic Networkmentioning

confidence: 99%

Towards network-guided neuromodulation for epilepsy

Piper

Richardson

Worrell

et al. 2022

Brain

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“…Here, we present a freely-available open-source toolbox that was designed to carry out neuroimaging-based DBS research on a group level. Although our own development focused on patients undergoing DBS with chronicallyimplanted electrodes, Lead group was recently used to localize stereotactic intracranial EEG (iEEG) electrodes as well (Toth et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Deep Brain Stimulation: Imaging on a group level

Treu

Strange

Oxenford

et al. 2020

Preprint

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Highlights We present a novel toolbox to carry out DBS imaging analyses on a grouplevel  Group electrodes are visualized in 2D and 3D and related to clinical regressors  A favorable target and connectivity profiles for the treatment of PD are validated Abstract Deep Brain Stimulation (DBS) is an established treatment option for movement disorders and is investigated to treat a growing number of other brain disorders. It has been shown that DBS effects are highly dependent on exact electrode placement, which is especially important when probing novel indications or stereotactic targets. Thus, considering precise electrode placement is crucial when investigating efficacy of DBS targets. To measure clinical improvement as a function of electrode placement, neuroscientific methodology and specialized software tools are needed. Such tools should have the goal to make electrode placement comparable across patients and DBS centers, and include statistical analysis options to validate and define optimal targets. Moreover, to allow for comparability across different research sites, these need to be performed within an algorithmically and anatomically standardized and openly available group space. With the publication of Lead-DBS software in 2014, an open-source tool was introduced that allowed for precise electrode reconstructions based on pre-and postoperative neuroimaging data. Here, we introduce Lead Group, implemented within the Lead-DBS environment and specifically designed to meet aforementioned demands. In the present article, we showcase the various processing streams of Lead Group in a retrospective cohort of 51 patients suffering from Parkinson's disease, who were implanted with DBS electrodes to the subthalamic nucleus (STN). Specifically, we demonstrate various ways to visualize placement of all electrodes in the group and map clinical improvement values to subcortical space. We do so by using active coordinates and volumes of tissue activated, showing converging evidence of an optimal DBS target in the dorsolateral STN. Second, we relate DBS outcome to the impact of each electrode on local structures by measuring overlap of stimulation volumes with the STN. Finally, we explore the software functions for connectomic mapping, which may be used to relate DBS outcomes to connectivity estimates with remote brain areas. We isolate a specific fiber bundlewhich structurally resembles the hyperdirect pathwaythat is associated with good clinical outcome in the cohort.The manuscript is accompanied by a walkthrough tutorial through which users are able to reproduce all main results presented in the present manuscript. All data and code needed to reproduce results are openly available.

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Functional network dynamics between the anterior thalamus and the cortex in deep brain stimulation for epilepsy

Aiello,

Ledergerber,

Dubcek

et al. 2023

Brain

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Owing to its unique connectivity profile with cortical brain regions, and its suggested role in the subcortical propagation of seizures, the anterior nucleus of the thalamus (ANT) has been proposed as a key deep brain stimulation (DBS) target in drug-resistant epilepsy. However, the spatio-temporal interaction dynamics of this brain structure, and the functional mechanisms underlying ANT DBS in epilepsy remain unknown. Here, we study how the ANT interacts with the neocortex in vivo in humans and provide a detailed neurofunctional characterization of mechanisms underlying the effectiveness of ANT DBS, aiming at defining intraoperative neural biomarkers of responsiveness to therapy, assessed at 6 months post-implantation as the reduction in seizure frequency. A cohort of 15 patients with drug-resistant epilepsy (n = 6 males, age = 41.6 ± 13.79 years) underwent bilateral ANT DBS implantation. Using intraoperative cortical and ANT simultaneous electrophysiological recordings, we found that the ANT is characterized by high amplitude θ (4–8 Hz) oscillations, mostly in its superior part. The strongest functional connectivity between the ANT and the scalp EEG was also found in the θ band in ipsilateral centro-frontal regions. Upon intraoperative stimulation in the ANT, we found a decrease in higher EEG frequencies (20–70 Hz) and a generalized increase in scalp-to-scalp connectivity. Crucially, we observed that responders to ANT DBS treatment were characterized by higher EEG θ oscillations, higher θ power in the ANT, and stronger ANT-to-scalp θ connectivity, highlighting the crucial role of θ oscillations in the dynamical network characterization of these structures. Our study provides a comprehensive characterization of the interaction dynamic between the ANT and the cortex, delivering crucial information to optimize and predict clinical DBS response in patients with drug-resistant epilepsy.

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Ictal recruitment of anterior nucleus of thalamus in human focal epilepsy

Cited by 3 publications

References 70 publications

Towards network-guided neuromodulation for epilepsy

Towards network-guided neuromodulation for epilepsy

Deep Brain Stimulation: Imaging on a group level

Functional network dynamics between the anterior thalamus and the cortex in deep brain stimulation for epilepsy

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