Cortical Deactivation Induced by Subcortical Network Dysfunction in Limbic Seizures

Englot, Dario J.; Modi, Badri; Mishra, Asht M.; DeSalvo, Matthew N.; Hyder, Fahmeed; Blumenfeld, Hal

doi:10.1523/jneurosci.3846-09.2009

Cited by 108 publications

(136 citation statements)

References 49 publications

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“…The recent development of an animal model has shed additional light on the mechanisms by which focal temporal lobe seizures cause loss of consciousness via long-range disruption by subcortical activating systems of neocortex [23][24][25]. In particular, fMRI decreases were found in the orbital frontal, anterior cingulate, and posterior cingulate cortex / retrosplenial cortex during seizures similar to changes observed in human patients.…”

Section: Default Mode Network Involvement In Complex Partial Seizuresmentioning

confidence: 74%

The Default Mode Network and Altered Consciousness in Epilepsy

Danielson

Guo

Blumenfeld

2011

Behavioural Neurology

139

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Abstract. The default mode network has been hypothesized based on the observation that specific regions of the brain are consistently activated during the resting state and deactivated during engagement with task. The primary nodes of this network, which typically include the precuneus/posterior cingulate, the medial frontal and lateral parietal cortices, are thought to be involved in introspective and social cognitive functions. Interestingly, this same network has been shown to be selectively impaired during epileptic seizures associated with loss of consciousness. Using a wide range of neuroimaging and electrophysiological modalities, decreased activity in the default mode network has been confirmed during complex partial, generalized tonic-clonic, and absence seizures. In this review we will discuss these three seizure types and will focus on possible mechanisms by which decreased default mode network activity occurs. Although the specific mechanisms of onset and propagation differ considerably across these seizure types, we propose that the resulting loss of consciousness in all three types of seizures is due to active inhibition of subcortical arousal systems that normally maintain default mode network activity in the awake state. Further, we suggest that these findings support a general "network inhibition hypothesis," by which active inhibition of arousal systems by seizures in certain cortical regions leads to cortical deactivation in other cortical areas. This may represent a push-pull mechanism similar to that seen operating between cortical networks under normal conditions.

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Section: Default Mode Network Involvement In Complex Partial Seizuresmentioning

confidence: 74%

The Default Mode Network and Altered Consciousness in Epilepsy

Danielson

Guo

Blumenfeld

2011

Behavioural Neurology

139

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“…10,11 Hippocampal seizures propagate to septal nuclei, 4,16 so how can we explain our finding of septal enlargement rather than atrophy in patients with TLE without MTS?…”

Section: 2mentioning

confidence: 96%

Septal nuclei enlargement in human temporal lobe epilepsy without mesial temporal sclerosis

Butler

Záborszky²,

Wang³

et al. 2013

Neurology

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Objective: To measure the volume of basal forebrain septal nuclei in patients with temporal lobe epilepsy (TLE) as compared to patients with extratemporal epilepsy and controls. In animal models of TLE, septal lesions facilitate epileptogenesis, while septal stimulation is antiepileptic.Method: Subjects were recruited from 2 sites and consisted of patients with pharmacoresistant focal epilepsy (20 with TLE and mesial temporal sclerosis [MTS], 24 with TLE without MTS, 23 with extratemporal epilepsy) and 114 controls. Septal volume was measured using high-resolution MRI in association with newly developed probabilistic septal nuclei maps. Septal volume was compared between subject groups while controlling for relevant factors.Results: Patients with TLE without MTS had significantly larger septal nuclei than patients with extratemporal epilepsy and controls. This was not true for patients with MTS. These results are interpreted with reference to prior studies demonstrating expansion of the septo-hippocampal cholinergic system in animal models of TLE and human TLE surgical specimens. Human septal nuclei, located in the basal forebrain, consist of the medial septum and diagonal band of Broca. Septal nuclei provide the main cholinergic input to the hippocampus via the fimbria/fornix 1 and are critical for hippocampal theta oscillations that mediate learning and memory. 2,3 In animal models of temporal lobe epilepsy (TLE), medial septal lesions facilitate epileptogenesis, and chemical or electrical septal stimulation can stop and prevent seizures. Conclusion:4-8 To our knowledge, no studies have examined septal nuclei structure in human TLE.We used MRI in association with probabilistic maps of human septal nuclei 9 to measure septal volume in patients with TLE either with or without mesial temporal sclerosis (MTS), patients with partial epilepsy not involving the hippocampus (extratemporal epilepsy [ETE]), and healthy controls. Based on prior human MRI studies showing atrophy of hippocampi and connected limbic regions in TLE including the fornix, 10,11 we initially hypothesized that septal volume would be reduced in TLE. Contrary to this hypothesis, we found septal enlargement in TLE without MTS.METHODS Subjects. All subjects provided informed consent to participate in this institutional review board-approved study. Patients with epilepsy were recruited from either the New York University (NYU) or University of California, San Diego (UCSD) Epilepsy Center. See table 1 for subject information. All patients had medically intractable seizures and were being considered for epilepsy surgery. Seizure focus lateralization/localization was made by experienced epileptologists based on clinical criteria including neuroimaging, video-EEG, and intracranial EEG (icEEG) when available. Patients with TLE were categorized as having MTS (TLE-MTS) or not based on standard criteria.12 PatientsFrom the Comprehensive Epilepsy Center (T.B., X

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“…This hints that in partial seizures with impaired responsiveness, it is the disruption of arousal (vs specific cognitive deficits) that usually accounts for the patient's inability to attend to the surrounding environment. Together with recent advances in the physiologic understanding of impaired consciousness in epilepsy, 10,14,16,23,29,32 these findings support the traditional clinical division between complex partial and simple partial seizures. 20,37 We believe that this is an important distinction with implications both for patient safety and for improved treatments aimed at preventing impairment in partial seizures.…”

Section: Figure 2 Behavior On Different Test Times Remains Consistentmentioning

confidence: 59%

“…Findings from human neuroimaging, 10 intracranial EEG, 23,28 and animal models 29,30 have led us to propose the network inhibition hypothesis, 8,31 in which partial seizures propagate to subcortical structures and inhibit arousal. Decreased arousal and altered thalamocortical functioning then produces sleep-like slow waves and reduced metabolism in multiple cortical regions, resulting in a unique state of depressed consciousness.…”

Section: Figure 2 Behavior On Different Test Times Remains Consistentmentioning

confidence: 99%

Impaired consciousness in partial seizures is bimodally distributed

Cunningham

Chen

Shorten³

et al. 2014

Neurology

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Objective: To investigate whether impaired consciousness in partial seizures can usually be attributed to specific deficits in the content of consciousness or to a more general decrease in the overall level of consciousness.Methods: Prospective testing during partial seizures was performed in patients with epilepsy using the Responsiveness in Epilepsy Scale (n 5 83 partial seizures, 30 patients). Results were compared with responsiveness scores in a cohort of patients with severe traumatic brain injury evaluated with the JFK Coma Recovery Scale-Revised (n 5 552 test administrations, 184 patients).Results: Standardized testing during partial seizures reveals a bimodal scoring distribution, such that most patients were either fully impaired or relatively spared in their ability to respond on multiple cognitive tests. Seizures with impaired performance on initial test items remained consistently impaired on subsequent items, while other seizures showed spared performance throughout. In the comparison group, we found that scores of patients with brain injury were more evenly distributed across the full range in severity of impairment.Conclusions: Partial seizures can often be cleanly separated into those with vs without overall impaired responsiveness. Results from similar testing in a comparison group of patients with brain injury suggest that the bimodal nature of Responsiveness in Epilepsy Scale scores is not a result of scale bias but may be a finding unique to partial seizures. These findings support a model in which seizures either propagate or do not propagate to key structures that regulate overall arousal and thalamocortical function. Future investigations are needed to relate these behavioral findings to the physiology underlying impaired consciousness in partial seizures. Impaired consciousness is a major cause of disability in people with epilepsy; however, the mechanisms for loss of consciousness remain incompletely understood. In other disorders of consciousness, patients often show deficits in both the overall level of consciousness and the specific cognitive functions comprising the content of consciousness.

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Cortical Deactivation Induced by Subcortical Network Dysfunction in Limbic Seizures

Cited by 108 publications

References 49 publications

The Default Mode Network and Altered Consciousness in Epilepsy

The Default Mode Network and Altered Consciousness in Epilepsy

Septal nuclei enlargement in human temporal lobe epilepsy without mesial temporal sclerosis

Impaired consciousness in partial seizures is bimodally distributed

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