High-density cortical µECoG arrays concurrently track spreading depolarizations and long-term evolution of stroke in awake rats.

Spreading depolarizations (SDs) are widely recognized as a major contributor to the progression of tissue damage from ischemic stroke even if blood flow can be restored. They are characterized by negative intracortical waveforms of up to -20 mV, propagation velocities of 3 - 6 mm/min, and massive disturbance of membrane ion homeostasis. High-density, micro-electrocorticographic (µECoG) epidural electrodes and custom, DC-coupled, multiplexed amplifiers, were used to continuously characterize and monitor SD and µECoG cortical signal evolution in awake, moving rats over days. This highly innovative approach can define these events over a large brain surface area (~ 3.4 × 3.4 mm), extending across the boundaries of the stroke, and offers sufficient electrode density (60 contacts total per array for a density of 5.7 electrodes / mm2) to measure and determine the origin of SDs in relation to the infarct boundaries. In addition, spontaneous ECoG activity can simultaneously be detected to further define cortical infarct regions. This technology allows us to understand dynamic stroke evolution and provides immediate cortical functional activity over days. Further translational development of this approach may facilitate improved treatment options for acute stroke patients.

Temporally non-regular patterns of deep brain stimulation (DBS) enhance assessment of evoked potentials while maintaining motor symptom management in Parkinson's disease (PD).

BACKGROUND: Traditional deep brain stimulation (DBS) at fixed regular frequencies (>100 Hz) is effective in treating motor symptoms of Parkinson's disease (PD). Temporally non-regular patterns of DBS are a new parameter space that may help increase efficacy and efficiency. OBJECTIVE: To compare the effects of temporally non-regular patterns of DBS to traditional regularly-spaced pulses. METHODS: We simultaneously recorded local field potentials (LFP) and monitored motor symptoms (tremor and bradykinesia) in persons with PD during DBS in subthalamic nucleus (STN). We quantified both oscillatory activity and DBS local evoked potentials (DLEPs) from the LFP. RESULTS: Temporally non-regular patterns were as effective as traditional pulse patterns in modulating motor symptoms, oscillatory activity, and DLEPs. Moreover, one of our novel patterns enabled recording of longer duration DLEPs during clinically effective stimulation. CONCLUSIONS: Stimulation gaps of 50 ms can be used to increase efficiency and to enable regular assessment of long-duration DLEPs while maintaining effective symptom management. This may be a promising paradigm for closed-loop DBS with biomarker assessment during the gaps.

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

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.

Long-term recording reliability of liquid crystal polymer µECoG arrays.

OBJECTIVE: The clinical use of microsignals recorded over broad cortical regions is largely limited by the chronic reliability of the implanted interfaces. APPROACH: We evaluated the chronic reliability of novel 61-channel micro-electrocorticographic (µECoG) arrays in rats chronically implanted for over one year and using accelerated aging. Devices were encapsulated with polyimide (PI) or liquid crystal polymer (LCP), and fabricated using commercial manufacturing processes. In vitro failure modes and predicted lifetimes were determined from accelerated soak testing. Successful designs were implanted epidurally over the rodent auditory cortex. Trends in baseline signal level, evoked responses and decoding performance were reported for over one year of implantation. MAIN RESULTS: Devices fabricated with LCP consistently had longer in vitro lifetimes than PI encapsulation. Our accelerated aging results predicted device integrity beyond 3.4 years. Five implanted arrays showed stable performance over the entire implantation period (247-435 d). Our regression analysis showed that impedance predicted signal quality and information content only in the first 31 d of recordings and had little predictive value in the chronic phase (>31 d). In the chronic phase, site impedances slightly decreased yet decoding performance became statistically uncorrelated with impedance. We also employed an improved statistical model of spatial variation to measure sensitivity to locally varying fields, which is typically concealed in standard signal power calculations. SIGNIFICANCE: These findings show that µECoG arrays can reliably perform in chronic applications in vivo for over one year, which facilitates the development of a high-density, clinically viable interface.

A low-cost, multiplexed µECoG system for high-density recordings in freely moving rodents.

OBJECTIVE: Micro-electrocorticography (µECoG) offers a minimally invasive neural interface with high spatial resolution over large areas of cortex. However, electrode arrays with many contacts that are individually wired to external recording systems are cumbersome and make recordings in freely behaving rodents challenging. We report a novel high-density 60-electrode system for µECoG recording in freely moving rats. APPROACH: Multiplexed headstages overcome the problem of wiring complexity by combining signals from many electrodes to a smaller number of connections. We have developed a low-cost, multiplexed recording system with 60 contacts at 406 µm spacing. We characterized the quality of the electrode signals using multiple metrics that tracked spatial variation, evoked-response detectability, and decoding value. Performance of the system was validated both in anesthetized animals and freely moving awake animals. MAIN RESULTS: We recorded µECoG signals over the primary auditory cortex, measuring responses to acoustic stimuli across all channels. Single-trial responses had high signal-to-noise ratios (SNR) (up to 25 dB under anesthesia), and were used to rapidly measure network topography within ∼10 s by constructing all single-channel receptive fields in parallel. We characterized evoked potential amplitudes and spatial correlations across the array in the anesthetized and awake animals. Recording quality in awake animals was stable for at least 30 days. Finally, we used these responses to accurately decode auditory stimuli on single trials. SIGNIFICANCE: This study introduces (1) a µECoG recording system based on practical hardware design and (2) a rigorous analytical method for characterizing the signal characteristics of µECoG electrode arrays. This methodology can be applied to evaluate the fidelity and lifetime of any µECoG electrode array. Our µECoG-based recording system is accessible and will be useful for studies of perception and decision-making in rodents, particularly over the entire time course of behavioral training and learning.

In vitro assessment of long-term reliability of low-cost µECoG arrays.

Micro-electrocorticographic (µECοG) electrode arrays provide a minimally invasive, high-resolution neural interface with broad cortical coverage. Previously, we fabricated µECoG arrays at a lower cost than commercially available devices using low-cost industrial processes [1], [2]. Here, we report the in vitro electrical performance of five µECoG designs undergoing an accelerated aging protocol. The impedance and yield of the µECoG arrays were tracked over time. The equivalent lifetime at 37°C depended on the manufacturer and material stack-up, and ranged between 30 and greater than 760 days (ongoing). The main failure modes of these devices were delamination at the site of the electrode contact and broken traces due to metal dissolution. Based on these in vitro results, we offer several recommendations for µECoG designs suitable for chronic implantation.