Thalamocortical functional connectivity in Lennox–Gastaut syndrome is abnormally enhanced in executive‐control and default‐mode networks

Warren, Aaron E. L.; Abbott, David F.; Jackson, Graeme D.; Archer, John S.

doi:10.1111/epi.13932

Cited by 37 publications

(27 citation statements)

References 41 publications

(157 reference statements)

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“…Furthermore, understanding the CM’s functional connectivity may assist with presurgical planning. For example, observation of a connectivity pattern consistent with the one we report here may increase confidence in the accuracy of the planned electrode placement within the CM, whereas observation of a dissimilar pattern—as occurs when connectivity is calculated from a different thalamic nucleus in patients with LGS31—may suggest potential misplacement.…”

Section: Discussionsupporting

confidence: 68%

“…A study using 3T proton density-weighted MRI also reported delineation of the CM in controls29; however, the need for coarse slice thickness (~3 mm) to achieve sufficient signal-to-noise ratio may limit the method’s neurosurgical suitability. Functional approaches for localising CM, such as task-based fMRI paradigms that activate CM specifically30 or thalamic segmentations based on resting-state fMRI connectivity,31 may assist with refining the visualisation achievable by structural MRI; however, further clinical validation is needed.…”

Section: Discussionmentioning

confidence: 99%

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Targeting the centromedian thalamic nucleus for deep brain stimulation

Warren

Dalic

Thevathasan

et al. 2020

J Neurol Neurosurg Psychiatry

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ObjectivesDeep brain stimulation (DBS) of the centromedian thalamic nucleus (CM) is an emerging treatment for multiple brain diseases, including the drug-resistant epilepsy Lennox-Gastaut syndrome (LGS). We aimed to improve neurosurgical targeting of the CM by: (1) developing a structural MRI approach for CM visualisation, (2) identifying the CM’s neurophysiological characteristics using microelectrode recordings (MERs) and (3) mapping connectivity from CM-DBS sites using functional MRI (fMRI).Methods19 patients with LGS (mean age=28 years) underwent presurgical 3T MRI using magnetisation-prepared 2 rapid acquisition gradient-echoes (MP2RAGE) and fMRI sequences; 16 patients proceeded to bilateral CM-DBS implantation and intraoperative thalamic MERs. CM visualisation was achieved by highlighting intrathalamic borders on MP2RAGE using Sobel edge detection. Mixed-effects analysis compared two MER features (spike firing rate and background noise) between ventrolateral, CM and parafasicular nuclei. Resting-state fMRI connectivity was assessed using implanted CM-DBS electrode positions as regions of interest.ResultsThe CM appeared as a hyperintense region bordering the comparatively hypointense pulvinar, mediodorsal and parafasicular nuclei. At the group level, reduced spike firing and background noise distinguished CM from the ventrolateral nucleus; however, these trends were not found in 20%–25% of individual MER trajectories. Areas of fMRI connectivity included basal ganglia, brainstem, cerebellum, sensorimotor/premotor and limbic cortex.ConclusionsIn the largest clinical trial of DBS undertaken in patients with LGS to date, we show that accurate targeting of the CM is achievable using 3T MP2RAGE MRI. Intraoperative MERs may provide additional localising features in some cases; however, their utility is limited by interpatient variability. Therapeutic effects of CM-DBS may be mediated via connectivity with brain networks that support diverse arousal, cognitive and sensorimotor processes.

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Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Targeting the centromedian thalamic nucleus for deep brain stimulation

Warren

Dalic

Thevathasan

et al. 2020

J Neurol Neurosurg Psychiatry

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“…Several research‐only studies of specific epilepsies have also been undertaken at our center with targeted recruitment—these do not form any part of this cohort and are described elsewhere (childhood absence epilepsy; Lennox‐Gastaut syndrome; benign epilepsy with centrotemporal spikes).…”

Section: Methodsmentioning

confidence: 99%

“…Full details of the EEG‐fMRI protocol have been described previously (GE Signa Siemens Trio; Siemens Skyra). In brief, fMRI data were obtained using a gradient‐recalled echo planar imaging with blood oxygenation–level dependent (BOLD) weighting and whole‐brain slice coverage.…”

Section: Methodsmentioning

confidence: 99%

“…Multiple previous reviews have provided details of EEG‐fMRI technical basics, artifact correction, data acquisition, concurrent analysis techniques, limitations, as well as presented key findings from various research centers . In addition, we have published numerous technical advancements, applications, and comments regarding EEG‐fMRI in epilepsy (for example), some of which include subsets of patients that are included in this review.…”

Section: Introductionmentioning

confidence: 99%

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Clinical benefit of presurgical EEG‐fMRI in difficult‐to‐localize focal epilepsy: A single‐institution retrospective review

et al. 2019

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Objective: The aim of this report is to present our clinical experience of electroencephalography-functional magnetic resonance imaging (EEG-fMRI) in localizing the epileptogenic focus, and to evaluate the clinical impact and challenges associated with the use of EEG-fMRI in pharmacoresistant focal epilepsy. Methods: We identified EEG-fMRI studies (n = 118) in people with focal epilepsy performed at our center from 2003 to 2018. Participants were referred from our Comprehensive Epilepsy Program in an exploratory research effort to address often difficult clinical questions, due to complex and difficult-to-localize epilepsy. We assessed the success of each study, the clinical utility of the result, and when surgery was performed, the postoperative outcome. Results: Overall, 50% of EEG-fMRI studies were successful, meaning that data were of good quality and interictal epileptiform discharges were recorded. With an altered recruitment strategy since 2012 with increased inclusion of patients who were inpatients for video-EEG monitoring, we found that this patients in this selected group were more likely to have epileptic discharges detected during EEG-fMRI (96% of inpatients vs 29% of outpatients, P<.0001). To date, 48% (57 of 118) of patients have undergone epilepsy surgery. In 10 cases (17% of the 59 successful studies) the EEG-fMRI result had a "critical impact" on the surgical decision. These patients were difficult to localize because of subtle abnormalities, apparently normal MRI, or extensive structural abnormalities. All 10 had a good seizure outcome at 1 year after surgery (mean follow-up 6.5 years). Significance: EEG-fMRI results can assist identification of the epileptogenic focus in otherwise difficult-to-localize cases of pharmacoresistant focal epilepsy. Surgery determined largely by localization from the EEG-fMRI result can lead to good seizure outcomes. A limitation of this study is its retrospective design with nonconsecutive recruitment. Prospective clinical trials with well-defined inclusion criteria are needed to determine the overall benefit of EEG-fMRI for preoperative localization and postoperative outcome in focal epilepsy. K E Y W O R D SEEG, epilepsy surgery, fMRI, focal epilepsy 50 | KOWALCZYK et AL. SUPPORTING INFORMATIONAdditional supporting information may be found online in the Supporting Information section.

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The Optimal Target and Connectivity for Deep Brain Stimulation in Lennox–Gastaut Syndrome

Warren

Dalic

Bulluss

et al. 2022

Annals of Neurology

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Objective Deep brain stimulation (DBS) can reduce seizures in Lennox–Gastaut syndrome (LGS). However, little is known about the optimal target and whether efficacy depends on connectivity of the stimulation site. Using outcome data from the ESTEL trial, we aimed to determine the optimal target and connectivity for DBS in LGS. Methods A total of 20 patients underwent bilateral DBS of the thalamic centromedian nucleus (CM). Outcome was percentage seizure reduction from baseline after 3 months of DBS, defined using three measures (monthly seizure diaries, 24‐hour scalp electroencephalography [EEG], and a novel diary‐EEG composite). Probabilistic stimulation mapping identified thalamic locations associated with higher/lower efficacy. Two substitute diffusion MRI datasets (a normative dataset from healthy subjects and a “disease‐matched” dataset from a separate group of LGS patients) were used to calculate structural connectivity between DBS sites and a map of areas known to express epileptic activity in LGS, derived from our previous EEG‐fMRI research. Results Results were similar across the three outcome measures. Stimulation was most efficacious in the anterior and inferolateral “parvocellular” CM border, extending into the ventral lateral nucleus (posterior subdivision). There was a positive association between diary‐EEG composite seizure reduction and connectivity to areas of a priori EEG‐fMRI activation, including premotor and prefrontal cortex, putamen, and pontine brainstem. In contrast, outcomes were not associated with baseline clinical variables. Interpretation Efficacious CM‐DBS for LGS is linked to stimulation of the parvocellular CM and the adjacent ventral lateral nucleus, and is associated with connectivity to, and thus likely modulation of, the “secondary epileptic network” underlying the shared electroclinical manifestations of LGS. ANN NEUROL 2022;92:61–74

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Thalamocortical functional connectivity in Lennox–Gastaut syndrome is abnormally enhanced in executive‐control and default‐mode networks

Cited by 37 publications

References 41 publications

Targeting the centromedian thalamic nucleus for deep brain stimulation

Targeting the centromedian thalamic nucleus for deep brain stimulation

Clinical benefit of presurgical EEG‐fMRI in difficult‐to‐localize focal epilepsy: A single‐institution retrospective review

The Optimal Target and Connectivity for Deep Brain Stimulation in Lennox–Gastaut Syndrome

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