Detection of spreading depolarization events and spatiotemporal analysis for advancing stroke therapy.

ABSTRACT

While the presence of spreading depolarization (SD) and associated spreading depression have been well studied and known to be associated with post-ischemic brain damage, the spatiotemporal spread of these events from the site of injury is not well understood. With the recent development of high-density micro-electrocorticographic (ECoG) electrode arrays, monitoring the spread of the depolarizing events and associated depression is possible. The goal of this work is to define the electrocorticographic features of SD and associated depression across the multichannel array and search for patterns in these features that emerge across both space and time. We present the spatial distribution of features found from chronic ECoG recordings acquired from awake behaving rats induced with a rodent model of stroke. SD events were detected with an unsupervised algorithm that searched for a stereotyped pattern in the first derivative of the ECoG. The algorithm yielded a 58% correct detection rate on average across four rats, and a 36% false positive rate. We defined key electrophysiological features and mapped them onto the physical brain regions using MATLAB, such as the peak-to-peak amplitude of each SD event, the width (or duration) of the SD event, direct current (DC) level, and average rate of decline in the signal baseline. We performed k-means clustering to the activity in this feature space which yielded three contiguous regions in physical space. The elbow optimization method was applied to a distortion metric and indicated that 3 clusters was optimal. These findings motivate us to conduct future studies that would verify whether these 3 clusters in electrode-space correspond to immunohistochemically defined regions of tissue health, namely, infarct, penumbra, and healthy tissue. Clinical Relevance- The extent and severity of damage that stroke ultimately causes is suspected to be related to the progression of spreading depolarization and associated depression. An understanding of how the features of these electrophysiological events progress across the brain and over time is an important step toward eventual development of closed-loop therapies which limit and minimize the long-term effects of stroke.