Correlation between volumetric oxygenation responses and electrophysiology identifies deep thalamocortical activity during epileptic seizures

Visualization of whole brain activity during epileptic seizures is essential for both fundamental research into the disease mechanisms and the development of efficient treatment strategies. It has been previously discussed that pathological synchronization originating from cortical areas may reinforce backpropagating signaling from the thalamic neurons, leading to massive seizures through enhancement of high frequency neural activity in the thalamocortical loop. However, the study of deep brain neural activity is challenging with the existing functional neuroimaging methods due to lack of adequate spatiotemporal resolution or otherwise insufficient penetration into subcortical areas. To investigate the role of thalamocortical activity during epileptic seizures, we developed a new functional neuroimaging framework based on spatiotemporal correlation of volumetric optoacoustic hemodynamic responses with the concurrent electroencephalogram recordings and anatomical brain landmarks. The method is shown to be capable of accurate three-dimensional mapping of the onset, spread, and termination of the epileptiform events in a 4-aminopyridine acute model of focal epilepsy. Our study is the first to demonstrate entirely noninvasive real-time visualization of synchronized epileptic foci in the whole mouse brain, including the neocortex and subcortical structures, thus opening new vistas in systematic studies toward the understanding of brain signaling and the origins of neurological disorders.