Seizure related perfusion changes demonstrated with optical imaging of intrinsic signals

Most functional neuroimaging techniques, such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), gauge neuronal activity by measuring changes in regional cerebral blood flow (rCBF). Proper interpretation of functional neuroimaging therefore requires characterization of the relationship between perfusion and activity. Specifically we must understand the limitations of the blood flow response. For example, when neural firing rates are pathologically high, does the perfusion response maintain tight coupling to neural activity? To investigate this question, we examined perfusion related responses to seizure using optical imaging of intrinsic signals (OIS). OIS is a functional neuroimaging technique which measures changes in cortical reflectance. These reflectance changes are related to neuronal and vascular activity. Previous studies have shown that these intrinsic signals are closely related to increases in cerebral blood volume. With physiological levels of somatosensory stimulation a decrease in reflectance is seen over the corresponding cortical area. In this study we actually saw the opposite response: increased reflectance during seizure. Methods: We measured optical intrinsic signals (850nm) over rodent parietal cortex and recorded neural activity with a surface electrode. Seizures were induced by topical administration of penicillin either ipsilateral or contralateral to the hemisphere that was being imaged. Results: We observed positive reflectance changes after penicillin administration. The magnitude of the optical changes correlated with the intensity of spiking activity, and the severity of clinical seizure. In some cases, the optical signal preceded electrophysiological spiking activity by several seconds. Positive reflectance changes spread in a propagating wave across the cortex at a rate of approximately 3mm/min. After the seizures subsided (based on electrophysiological and behavioral observation) there was a sustained decrease in reflectance below baseline. Conclusions: OIS can be used to detect rapid perfusion related changes during and after seizure. However, the perfusion response is unusual in that hypoperfusion was seen during seizure. and hyperperfusion was seen in the post-ictal state.