Biology subjects

Chaitanya, G.

Publications and source records attributed to Chaitanya, G..

5 recordsLinked to original sources

bioRxiv2020

Anterior Nucleus of Thalamus Gates Progression of Mesial Temporal Seizures by Modulating Thalamocortical Synchrony

The anterior nucleus of the thalamus (ANT) mediates cortical-subcortical interactions between the limbic system and is hypothesized to facilitate the early organization of temporal lobe seizures. We set out to investigate the dynamic changes in synchronization parameters between the seizure onset zone (SOZ) and ANT during seizure stages (pre-onset to post-termination) in seven patients (n=26 seizures) with drug-resistant nonlesional temporal lobe epilepsy. Using local field potentials recorded directly from the limbic system and the ANT during stereoelectroencephalography, we confirm that the onset of mesial temporal lobe seizure is associated with increased thalamocortical network excitability and phase-amplitude coupling. The increase in thalamocortical phase synchronization preceded seizure onset, thereby suggesting that the early organization of temporal lobe seizures involves the integration of the ANT within the epileptic network. Towards seizure termination, there is a significant decrease in thalamic excitability, thalamocortical synchronization, and decoupling, thereby suggesting a breakdown in thalamocortical connectivity. A higher disease burden is significantly correlated with increased synchronization between the ANT and epileptic networks. Collectively, the results elucidate mechanistic insights and provide the temporal architecture of thalamocortical interactions that can be targeted in the rational designing of closed-loop seizure abortive interventions. HighlightsO_LIAnterior nucleus of thalamus is coactivated at the onset of temporal lobe seizures C_LIO_LIIncrease thalamocortical synchronization and excitability is observed at seizure onset C_LIO_LISeizure termination is characterized by a breakdown in thalamocortical connectivity C_LIO_LIIncreased seizure burden affects thalamocortical synchronization C_LI

neuroscience↗

bioRxiv2020

Implantation technique, safety and complications of robot-assisted stereoelectroencephalography exploration of the limbic thalamus in human focal epilepsy

IntroductionDespite numerous imaging studies highlighting the importance of thalamus in surgical prognosis, human electrophysiological studies involving the limbic thalamic nuclei are limited. The objective of this study was to evaluate the safety and accuracy of robot-assisted stereotactic electrode placement in the limbic thalamic nuclei in patients with suspected temporal lobe epilepsy (TLE). MethodsAfter obtaining informed consent, 24 adults with drug-resistant suspected TLE undergoing Stereo-EEG evaluation were enrolled in this prospective study. The trajectory of one electrode planned for clinical sampling the operculo-insular cortex was modified to extend to the thalamus, thereby preventing the need for additional electrode placement for research. The anterior thalamus (ANT) (N=13) and the medial group of thalamic nuclei (MED) (N=11), including mediodorsal (MD) and centromedian (CeM) were targeted. The post-implantation CT was co-registered to the pre-operative MRI, and Morels thalamic atlas was used to confirm the accuracy of implantation. ResultsTen out of 13 (77%) in the ANT group and 10 out of 11 patients (90%) in the medial group had electrodes accurately placed in the thalamic nuclei. None of the patients had a thalamic hemorrhage. However, trace asymptomatic hemorrhages at the cortical level entry site were noted in 20.8% of patients and they did not require additional surgical intervention. SEEG data from all the patients were interpretable and analyzable. The trajectories for the ANT implant differed slightly from the medial group at the entry point i.e., precentral gyrus in the former and postcentral gyrus in the latter. ConclusionsUsing judiciously planned robot-assisted SEEG, we demonstrate the safety of electrophysiological sampling from various thalamic nuclei for research recordings, presenting a technique that avoids implanting additional depth electrodes, or comprising clinical care. With these results, we propose that if patients are fully informed of the risks involved, there are potential benefits of gaining mechanistic insights to seizure genesis, which may help to develop neuromodulation therapies.

neuroscience↗

bioRxiv2019

Tonic resting-state hubness supports high-frequency activity defined verbal-memory encoding network in epilepsy

High-frequency gamma activity of verbal-memory encoding using invasive-electroencephalogram coupled has laid the foundation for numerous studies testing the integrity of memory in diseased populations. Yet, the functional connectivity characteristics of networks subserving these HFA-memory linkages remains uncertain. By integrating this electrophysiological biomarker of memory encoding from IEEG with resting-state BOLD fluctuations, we estimated the segregation and hubness of HFA-memory regions in drug-resistant epilepsy patients and matched healthy controls. HFA-memory regions express distinctly different hubness compared to neighboring regions in health and in epilepsy, and this hubness was more relevant than segregation in predicting verbal memory encoding. The HFA-memory network comprised regions from both the cognitive control and primary processing networks, validating that effective verbal-memory encoding requires multiple functions, and is not dominated by a central cognitive core. Our results demonstrate a tonic intrinsic set of functional connectivity, which provides the necessary conditions for effective, phasic, task-dependent memory encoding.\n\nHighlightsO_LIHigh frequency memory activity in IEEG corresponds to specific BOLD changes in resting-state data.\nC_LIO_LIHFA-memory regions had lower hubness relative to control brain nodes in both epilepsy patients and healthy controls.\nC_LIO_LIHFA-memory network displayed hubness and participation (interaction) values distinct from other cognitive networks.\nC_LIO_LIHFA-memory network shared regional membership and interacted with other cognitive networks for successful memory encoding.\nC_LIO_LIHFA-memory network hubness predicted both concurrent task (phasic) and baseline (tonic) verbal-memory encoding success.\nC_LI

neuroscience↗

bioRxiv2019

Early Ictal Recruitment of Midline Thalamus in Mesial Temporal Lobe Epilepsy

The causal role of midline thalamus in the initiation and early organization of mesial temporal lobe seizures is studied. Three patients undergoing stereoelectroencephalography were enrolled for the placement of an additional depth electrode targeting the midline thalamus. The midline thalamus was recruited in all three patients at varying points of seizure initiation (0-13 seconds) and early propagation (9-60 seconds). Stimulation of either thalamus or hippocampus induced similar habitual seizures. Seizure-induced in the hippocampus rapidly recruited the thalamus. Evoked potentials demonstrated stronger connectivity from the hippocampus to the thalamus than in the opposite direction. The midline thalamus can be within the seizure initiation and symptomatogenic circuits.

neuroscience↗

bioRxiv2019

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

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, as well as unfavorable treatment outcomes. Achieving greater understanding of its underlying circuitry offers better opportunity to control these particularly serious seizures. Towards this goal, we provide a network science perspective of the interactive pathways among basal ganglia, thalamus and the 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 magnetic resonance imaging 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 over one 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 the 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.

neuroscience↗