Preictal and ictal neurovascular and metabolic coupling surrounding a seizure focus

Abstract

Epileptic events initiate a large focal increase in metabolism and cerebral blood flow (CBF) to the ictal focus. In contrast, decreasesin CBF have been demonstrated surrounding the focus, the etiology of which is unknown (i.e., arising either from active shunting of blood or passive steal). The relationship between these events and neuronal activity and metabolism are also unknown. We investigated neuro-vascular and neurometabolic coupling in the ictal surround using optical imaging of light scattering and cerebral blood volume, auto-fluorescence flavoprotein imaging (AFI), direct measurementsofthe cortical metabolic rateof oxygen and two-photon imaging ofblood vessel diameter in a rat model of ictal events elicited with focal injection of 4-aminopyridine. We discovered a novel phenomenon, in which ictal events are preceded by preictal vasoconstriction of blood vesselsin the surround, occurring 1-5sbefore seizure onset, which may serve to actively shunt oxygenated blood to the imminently hypermetabolic focus or may be due to small local decreases in metabolism in the surround. Early ictal hypometabolism, transient decreases in cell swelling and cerebral blood volume in the surround are consistent with early ictal surround inhibition as a precipitating event in seizure onset as well as shaping the evolving propagating ictal wavefront, although the exact mechanism of these cerebrovascular and metabolic changes is currently unknown. AFI was extremely sensitive to the ictal onset zone and may be a useful mapping technique with clinical applications. © 2011 the authors.