Cortical deactivation induced by subcortical network dysfunction in limbic seizures.

Englot DJ, Modi B, Mishra AM, DeSalvo M, Hyder F, Blumenfeld H
J Neurosci. 2009 29 (41): 13006-18

PMID: 19828814 · PMCID: PMC2778759 · DOI:10.1523/JNEUROSCI.3846-09.2009

Normal human consciousness may be impaired by two possible routes: direct reduced function in widespread cortical regions or indirect disruption of subcortical activating systems. The route through which temporal lobe limbic seizures impair consciousness is not known. We recently developed an animal model that, like human limbic seizures, exhibits neocortical deactivation including cortical slow waves and reduced cortical cerebral blood flow (CBF). We now find through functional magnetic resonance imaging (fMRI) that electrically stimulated hippocampal seizures in rats cause increased activity in subcortical structures including the septal area and mediodorsal thalamus, along with reduced activity in frontal, cingulate, and retrosplenial cortex. Direct recordings from the hippocampus, septum, and medial thalamus demonstrated fast poly-spike activity associated with increased neuronal firing and CBF, whereas frontal cortex showed slow oscillations with decreased neuronal firing and CBF. Stimulation of septal area, but not hippocampus or medial thalamus, in the absence of a seizure resulted in cortical deactivation with slow oscillations and behavioral arrest, resembling changes seen during limbic seizures. Transecting the fornix, the major route from hippocampus to subcortical structures, abolished the negative cortical and behavioral effects of seizures. Cortical slow oscillations and behavioral arrest could be reconstituted in fornix-lesioned animals by inducing synchronous activity in the hippocampus and septal area, implying involvement of a downstream region converged on by both structures. These findings suggest that limbic seizures may cause neocortical deactivation indirectly, through impaired subcortical function. If confirmed, subcortical networks may represent a target for therapies aimed at preserving consciousness in human temporal lobe seizures.

MeSH Terms (26)

Action Potentials Animals Biophysics Brain Mapping Cerebral Cortex Denervation Disease Models, Animal Electric Stimulation Electroencephalography Evoked Potentials Female Fornix, Brain Hippocampus Image Processing, Computer-Assisted Laser-Doppler Flowmetry Magnetic Resonance Imaging Male Neural Pathways Neurons Oxygen Rats Rats, Sprague-Dawley Seizures Septum of Brain Thalamus Wakefulness

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