Disrupted basal ganglia–thalamocortical loops in focal to bilateral tonic-clonic seizures

Abstract

Focal to bilateral tonic-clonic seizures are associated with lower quality of life, higher risk of seizure-related injuries, increased chance of sudden unexpected death, and unfavourable treatment outcomes. Achieving greater understanding of their underlying circuitry offers better opportunity to control these seizures. Towards this goal, we provide a network science perspective of the interactive pathways among basal ganglia, thalamus and cortex, to explore the imprinting of secondary seizure generalization on the mesoscale brain network in temporal lobe epilepsy. Specifically, we parameterized the functional organization of both the thalamocortical network and the basal ganglia–thalamus network with resting state functional MRI in three groups of patients with different focal to bilateral tonic-clonic seizure histories. Using the participation coefficient to describe the pattern of thalamocortical connections among different cortical networks, we showed that, compared to patients with no previous history, those with positive histories of focal to bilateral tonic-clonic seizures, including both remote (none for >1 year) and current (within the past year) histories, presented more uniform distribution patterns of thalamocortical connections in the ipsilateral medial-dorsal thalamic nuclei. As a sign of greater thalamus-mediated cortico-cortical communication, this result comports with greater susceptibility to secondary seizure generalization from the epileptogenic temporal lobe to broader brain networks in these patients. Using interregional integration to characterize the functional interaction between basal ganglia and thalamus, we demonstrated that patients with current history presented increased interaction between putamen and globus pallidus internus, and decreased interaction between the latter and the thalamus, compared to the other two patient groups. Importantly, through a series of ‘disconnection’ simulations, we showed that these changes in interactive profiles of the basal ganglia–thalamus network in the current history group mainly depended upon the direct but not the indirect basal ganglia pathway. It is intuitively plausible that such disruption in the striatum-modulated tonic inhibition of the thalamus from the globus pallidus internus could lead to an under-suppressed thalamus, which in turn may account for their greater vulnerability to secondary seizure generalization. Collectively, these findings suggest that the broken balance between basal ganglia inhibition and thalamus synchronization can inform the presence and effective control of focal to bilateral tonic-clonic seizures. The mechanistic underpinnings we uncover may shed light on the development of new treatment strategies for patients with temporal lobe epilepsy.

Thalamus and focal to bilateral seizures

“… 49 Our findings also complement recent resting-state fMRI evidence for abnormal interactions between thalamic divisions and basal ganglia in TLE with recent FBTCS. 50 While differing methodologically, both analyses compellingly indicate a prominent role of the thalamus in shaping susceptibility to uncontrolled secondary generalization in TLE.…”

“…49 Our findings also complement recent resting-state fMRI evidence for abnormal interactions between thalamic divisions and basal ganglia in TLE with recent FBTCS. 50 advice. We also thank the anonymous reviewers for their suggestions to improve this manuscript.…”

When the Brakes Fail: Basal Ganglia and Seizure Generalization

“…In the highlighted work by He and colleagues, 2 the authors posit that impaired inhibitory interactions between basal ganglia and thalamus may contribute to abnormal corticothalamic synchronization that leads to secondary seizure generalization in temporal lobe epilepsy (TLE). To test this hypothesis, they performed a resting-state functional magnetic resonance imaging (fMRI) study of 96 patients with drugresistant TLE, including individuals with a recent, distant, or absent history of focal to bilateral tonic-clonic seizures.…”

Deep-learning based fully automatic segmentation of the globus pallidus interna and externa using ultra-high 7 Tesla MRI

“…GP-net is compared to the manual segmentation performed by domain experts and against four publicly available state-of-the-art atlases, to quantify its performance and validate its reliablity for patient-specific GPe/GPi segmentation: (1) DBS intrinsic template atlas (DISTAL, referred to as Ewert 2017) (Ewert et al, 2018); (2) California Institute of Technology (CIT) probabilistic high-resolution in vivo atlas of the human amygdala, also known as the CIT168 reinforcement learning atlas (referred to as Pauli 2020) (Pauli et al, 2018); (3) population-averaged atlas that was made with 3 T MRI of 25 PD patients (referred to as Xiao 2017) (Xiao et al, 2017); and (4) atlas of the basal ganglia and thalamus (referred to as He 2020) (He et al, 2020). All atlases were taken from the lead-DBS software package (Horn et al, 2019;Horn & Kühn, 2015), in which they are registered to the MNI ICMB2009b template [5].…”