Brain-derived neurotrophic factor haploinsufficiency impairs high-frequency cortical oscillations in mice.

Schizophrenia is a complex psychiatric disorder with a heterogeneous aetiology involving genetic and environmental factors. Deficiencies in both brain-derived neurotrophic factor (BDNF) and NMDA receptor function have been implicated in the disorder and may play causal and synergistic roles. Perturbations in the regulation of electrophysiological signals, including high-frequency (γ: 30-80 Hz and ß: 20-30 Hz) neuronal oscillations, are also associated with the disorder. This study investigated the influence of BDNF deficiency and NMDA receptor hypofunction on electrophysiological responses to brief acoustic stimuli. Adult BDNF heterozygote (BDNF+/- ) and wild-type littermate C57Bl/6J mice were surgically implanted with EEG recording electrodes. All mice underwent EEG recording sessions to measure ongoing and auditory-evoked electrophysiological responses following treatment with MK-801 (0.3 mg/kg ip) or vehicle. Western blotting on post-mortem cortical tissue assessed parvalbumin and GAD67 expression - markers of interneurons which are involved in the generation of gamma oscillations. Compared with wild-type controls, BDNF+/- mice exhibited markedly dampened electrophysiological responses to auditory stimuli, including reductions in the amplitude of multiple components of the event-related potential and auditory-evoked oscillations, as well as reduced ongoing cortical gamma oscillations. MK-801 elevated ongoing gamma power but suppressed evoked gamma power, and this was observed equally across genotypes. BDNF+/- mice also displayed reductions in parvalbumin, but not GAD67 expression. We conclude that reduced BDNF expression leads to impairments in the generation of high-frequency neural oscillations, but this is not synergistic with NMDA receptor hypofunction. Reduced parvalbumin expression associated with BDNF haploinsufficiency may provide a molecular explanation for these electrophysiological deficits.

Effects of aberrant gamma frequency oscillations on prepulse inhibition.

Emerging literature implicates abnormalities in gamma frequency oscillations in the pathophysiology of schizophrenia, with hypofunction of N-methyl-D-aspartate (NMDA) receptors implicated as a key factor. Prepulse inhibition (PPI) is a behavioural measure of sensorimotor gating, which is disrupted in schizophrenia. We studied relationships between ongoing and sensory-evoked gamma oscillations and PPI using pharmacological interventions designed to increase gamma oscillations (ketamine, MK-801); reduce gamma oscillations (LY379268); or disrupt PPI (amphetamine). We predicted that elevating ongoing gamma power would lead to increased 'neural noise' in cortical circuits, dampened sensory-evoked gamma responses and disrupted behaviour. Wistar rats were implanted with EEG recording electrodes. They received ketamine (5 mg/kg), MK-801 (0.16 mg/kg), amphetamine (0.5 mg/kg), LY379268 (3 mg/kg) or vehicle and underwent PPI sessions with concurrent EEG recording. Ketamine and MK-801 increased the power of ongoing gamma oscillations and caused time-matched disruptions of PPI, while amphetamine marginally affected ongoing gamma power. In contrast, LY379268 reduced ongoing gamma power, but had no effect on PPI. The sensory gamma response evoked by the prepulse was reduced following treatment with all psychotomimetics, associating with disruptions in PPI. This was most noticeable following treatment with NMDA receptor antagonists. We found that ketamine and MK-801 increase ongoing gamma power and reduce evoked gamma power, both of which are related to disruptions in sensorimotor gating. This appears to be due to antagonism of NMDA receptors, since amphetamine and LY379268 differentially impacted these outcomes and possess different neuropharmacological substrates. Aberrant gamma frequency oscillations caused by NMDA receptor hypofunction may mediate the sensory processing deficits observed in schizophrenia.

The effect of amygdala kindling on neuronal firing patterns in the lateral thalamus in the GAERS model of absence epilepsy.

OBJECTIVE: The co-occurrence of absence and mesial temporal lobe epilepsy is rare in both humans and animal models. Consistent with this, rat models of absence epilepsy, including genetic absence epilepsy rats from Strasbourg (GAERS), are resistant to experimental temporal lobe epileptogenesis, in particular by amygdala kindling. Structures within the cortical-thalamocortical system are critically involved in the generation and maintenance of the electrographic spike-and-wave discharges (SWDs) that characterize absence seizures. Using in vivo electrophysiologic recordings, this study investigated the role of thalamocortical circuitry in the generalization of amygdala-kindling induced seizures in the GAERS and the nonepileptic control (NEC) strain of Wistar rats. METHODS: GAERS and NEC rats were implanted with a stimulating electrode in amygdala and stimulated at afterdischarge threshold twice daily to a maximum number of 30 stimulations. Thereafter extracellular single neuron recordings were performed in vivo under neuroleptanesthesia in the thalamocortical network. RESULTS: In NEC rats, amygdala kindling induced convulsive class V seizures and altered characteristics of neuronal activity in the thalamic reticular nucleus (TRN), in particular decreased firing rates and increased burst firing patterns. Less marked changes were seen in other regions examined: the ventroposteromedial nucleus of thalamus (VPM), the CA3 region of the hippocampus, and the deep layers (V/VI) of the cortex. GAERS did not progress beyond class II seizures, with a matched number of kindling stimulations, and the thalamic neuronal firing alterations observed in NEC rats were not seen. SIGNIFICANCE: These data suggest that the TRN plays an important role in kindling resistance in GAERS and is central to the control of secondary generalization of limbic seizures.

A 'Total Unique Variation Analysis' for Brain-Machine Interfaces.

When designing a fully implantable brain-machine interface (BMI), the primary aim is to detect as much neural information as possible with as few channels as possible. In this paper, we present a total unique variance analysis (TUVA) for evaluating the signal unique to each channel that cannot be predicted by linear combination of signals on other channels. TUVA is a statistical method for determining the total unique variance in multidimensional data, ordering channels from most to least informative, to aid in the design of maximally-efficacious BMIs. We demonstrate how this method can be applied to the design of BMIs by comparing TUVA values computed for simulated lead-field maps for high-channel-count electrocorticography (ECoG) with values computed for recordings in the interictal period in the context of surgery planning for epileptic resection.Clinical Relevance- This paper introduces a new statistical method for comparison of neural interface designs, focused on quantifying recording efficiency by minimizing channel crosstalk, which may help improve the risk-benefit profile of invasive neural recording.

Differential Effects of Chronic Methamphetamine Treatment on High-Frequency Oscillations and Responses to Acute Methamphetamine and NMDA Receptor Blockade in Conscious Mice.

Dysregulation of high-frequency neuronal oscillations has been implicated in the pathophysiology of schizophrenia. Chronic methamphetamine (METH) use can induce psychosis similar to paranoid schizophrenia. The current study in mice aimed to determine the effect of chronic METH treatment on ongoing and evoked neuronal oscillations. C57BL/6 mice were treated with METH or vehicle control for three weeks and implanted with extradural recording electrodes. Two weeks after the last METH injection, mice underwent three EEG recording sessions to measure ongoing and auditory-evoked gamma and beta oscillatory power in response to an acute challenge with METH (2 mg/kg), the NMDA receptor antagonist MK-801 (0.3 mg/kg), or saline control. A separate group of mice pretreated with METH showed significantly greater locomotor hyperactivity to an acute METH challenge, confirming long-term sensitisation. Chronic METH did not affect ongoing or evoked gamma or beta power. Acute MK-801 challenge reduced ongoing beta power whereas acute METH challenge significantly increased ongoing gamma power. Both MK-801 and METH challenge suppressed evoked gamma power. Chronic METH treatment did not modulate these acute drug effects. There were minor effects of chronic METH and acute METH and MK-801 on selected components of event-related potential (ERP) waves. In conclusion, chronic METH treatment did not exert neuroplastic effects on the regulation of cortical gamma oscillations in a manner consistent with schizophrenia, despite causing behavioural sensitisation.

Motor neuroprosthesis implanted with neurointerventional surgery improves capacity for activities of daily living tasks in severe paralysis: first in-human experience.

BACKGROUND: Implantable brain-computer interfaces (BCIs), functioning as motor neuroprostheses, have the potential to restore voluntary motor impulses to control digital devices and improve functional independence in patients with severe paralysis due to brain, spinal cord, peripheral nerve or muscle dysfunction. However, reports to date have had limited clinical translation. METHODS: Two participants with amyotrophic lateral sclerosis (ALS) underwent implant in a single-arm, open-label, prospective, early feasibility study. Using a minimally invasive neurointervention procedure, a novel endovascular Stentrode BCI was implanted in the superior sagittal sinus adjacent to primary motor cortex. The participants undertook machine-learning-assisted training to use wirelessly transmitted electrocorticography signal associated with attempted movements to control multiple mouse-click actions, including zoom and left-click. Used in combination with an eye-tracker for cursor navigation, participants achieved Windows 10 operating system control to conduct instrumental activities of daily living (IADL) tasks. RESULTS: Unsupervised home use commenced from day 86 onwards for participant 1, and day 71 for participant 2. Participant 1 achieved a typing task average click selection accuracy of 92.63% (100.00%, 87.50%-100.00%) (trial mean (median, Q1-Q3)) at a rate of 13.81 (13.44, 10.96-16.09) correct characters per minute (CCPM) with predictive text disabled. Participant 2 achieved an average click selection accuracy of 93.18% (100.00%, 88.19%-100.00%) at 20.10 (17.73, 12.27-26.50) CCPM. Completion of IADL tasks including text messaging, online shopping and managing finances independently was demonstrated in both participants. CONCLUSION: We describe the first-in-human experience of a minimally invasive, fully implanted, wireless, ambulatory motor neuroprosthesis using an endovascular stent-electrode array to transmit electrocorticography signals from the motor cortex for multiple command control of digital devices in two participants with flaccid upper limb paralysis.

Distinct Neural Correlates Underlie Inhibitory Mechanisms of Motor Inhibition and Motor Imagery Restraint.

There is evidence to suggest that motor execution and motor imagery both involve planning and execution of the same motor plan, however, in the latter the output is inhibited. Currently, little is known about the underlying neural mechanisms of motor output inhibition during motor imagery. Uncovering the distinctive characteristics of motor imagery may help us better understand how we abstract complex thoughts and acquire new motor skills. The current study aimed to dissociate the cognitive processes involved in two distinct inhibitory mechanisms of motor inhibition and motor imagery restraint. Eleven healthy participants engaged in an imagined GO/NO-GO task during a 7 Tesla fMRI experiment. Participants planned a specific type of motor imagery, then, imagined the movements during the GO condition and restrained from making a response during the NO-GO condition. The results revealed that specific sub-regions of the supplementary motor cortex (SMC) and the primary motor cortex (M1) were recruited during the imagination of specific movements and information flowed from the SMC to the M1. Such condition-specific recruitment was not observed when motor imagery was restrained. Instead, general recruitment of the posterior parietal cortex (PPC) was observed, while the BOLD activity in the SMC and the M1 decreased below the baseline at the same time. Information flowed from the PPC to the SMC, and recurrently between the M1 and the SMC, and the M1 and the PPC. These results suggest that motor imagery involves task-specific motor output inhibition partly imposed by the SMC to the M1, while the PPC globally inhibits motor plans before they are passed on for execution during the restraint of responses.

In Vivo Impedance Characterization of Cortical Recording Electrodes Shows Dependence on Electrode Location and Size.

OBJECTIVE: Neural prostheses are improving the quality of life for those suffering from neurological impairments. Electrocorticography electrodes located in subdural, epidural, and intravascular positions show promise as long-term neural prostheses. However, chronic implantation affects the electrochemical environments of these arrays. METHODS: In the present work, the effect of electrode location on the electrochemical properties of the interface was compared. The impedances of the electrode arrays were measured using electrochemical impedance spectroscopy in vitro in saline and in vivo four-week postimplantation. RESULTS: There was not a significant effect of electrode location (subdural, intravascular, or epidural) on the impedance magnitude, and the effect of the electrode size on the impedance magnitude was frequency dependent. There was a frequency-dependent statistically significant effect of electrode location and electrode size on the phase angles of the three arrays. The subdural and epidural arrays showed phase shifts closer to -90° indicating the capacitive nature of the interface in these locations. The impact of placing electrodes within a blood vessel and adjacent to the blood vessel wall was most obvious when looking at the phase responses at frequencies below 10 kHz. CONCLUSION: Our results show that intravascular electrodes, like those in subdural and epidural positions, show electrical properties that are suitable for recording. These results provide support for the use of intravascular arrays in clinically relevant neural prostheses and diagnostic devices. SIGNIFICANCE: Comparison of electrochemical impedance of the epidural, intravascular, and subdural electrode array showed that all three locations are possible placement options, since impedances are in comparable ranges.

Effect of Implant Duration, Anatomical Location and Electrode Orientation on Bandwidth Recorded with a Chronically Implanted Endovascular Stent-Electrode Array.

Access to the brain to implant recording electrodes has conventionally required a craniotomy. To mitigate risks of open brain surgery, we previously developed a stent-electrode array that can be delivered to the cortex via cerebral vessels. Following implantation of a stent-electrode array (Stentrode) in a large animal model, we investigated the longevity of highquality signals, by measuring bandwidth in animals implanted for up to six months; no signal degradation was observed. We also investigated whether bandwidth was influenced by implant location with respect to the superior sagittal sinus and branching cortical veins; it was not. Finally, we assessed whether electrode orientation had an impact on recording quality. There was no significant difference in bandwidths from electrodes facing different orientations. Interestingly, electrodes facing the skull (180°) were still able to record neural information with high fidelity. Consequently, a minimally invasive surgical approach combined with a stent-electrode array is a safe and efficacious technique to acquire neural signals over a chronic duration.

Author Correction: Signal quality of simultaneously recorded endovascular, subdural and epidural signals are comparable.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Signal quality of simultaneously recorded endovascular, subdural and epidural signals are comparable.

Recent work has demonstrated the feasibility of minimally-invasive implantation of electrodes into a cortical blood vessel. However, the effect of the dura and blood vessel on recording signal quality is not understood and may be a critical factor impacting implementation of a closed-loop endovascular neuromodulation system. The present work compares the performance and recording signal quality of a minimally-invasive endovascular neural interface with conventional subdural and epidural interfaces. We compared bandwidth, signal-to-noise ratio, and spatial resolution of recorded cortical signals using subdural, epidural and endovascular arrays four weeks after implantation in sheep. We show that the quality of the signals (bandwidth and signal-to-noise ratio) of the endovascular neural interface is not significantly different from conventional neural sensors. However, the spatial resolution depends on the array location and the frequency of recording. We also show that there is a direct correlation between the signal-noise-ratio and classification accuracy, and that decoding accuracy is comparable between electrode arrays. These results support the consideration for use of an endovascular neural interface in a clinical trial of a novel closed-loop neuromodulation technology.

Focal stimulation of the sheep motor cortex with a chronically implanted minimally invasive electrode array mounted on an endovascular stent.

Direct electrical stimulation of the brain can alleviate symptoms associated with Parkinson's disease, depression, epilepsy and other neurological disorders. However, access to the brain requires invasive procedures, such as the removal of a portion of the skull or the drilling of a burr hole. Also, electrode implantation into tissue can cause inflammatory tissue responses and brain trauma, and lead to device failure. Here, we report the development and application of a chronically implanted platinum electrode array mounted on a nitinol endovascular stent for the localized stimulation of cortical tissue from within a blood vessel. Following percutaneous angiographic implantation of the device in sheep, we observed stimulation-induced responses of the facial muscles and limbs of the animals, similar to those evoked by electrodes implanted via invasive surgery. Proximity of the electrode to the motor cortex, yet not its orientation, was integral to achieving reliable responses from discrete neuronal populations. The minimally invasive endovascular surgical approach offered by the stent-mounted electrode array might enable safe and efficacious stimulation of focal regions in the brain.

An ovine model of cerebral catheter venography for implantation of an endovascular neural interface.

OBJECTIVE Neural interface technology may enable the development of novel therapies to treat neurological conditions, including motor prostheses for spinal cord injury. Intracranial neural interfaces currently require a craniotomy to achieve implantation and may result in chronic tissue inflammation. Novel approaches are required that achieve less invasive implantation methods while maintaining high spatial resolution. An endovascular stent electrode array avoids direct brain trauma and is able to record electrocorticography in local cortical tissue from within the venous vasculature. The motor area in sheep runs in a parasagittal plane immediately adjacent to the superior sagittal sinus (SSS). The authors aimed to develop a sheep model of cerebral venography that would enable validation of an endovascular neural interface. METHODS Cerebral catheter venography was performed in 39 consecutive sheep. Contrast-enhanced MRI of the brain was performed on 13 animals. Multiple telescoping coaxial catheter systems were assessed to determine the largest wide-bore delivery catheter that could be delivered into the anterior SSS. Measurements of SSS diameter and distance from the motor area were taken. The location of the motor area was determined in relation to lateral and superior projections of digital subtraction venography images and confirmed on MRI. RESULTS The venous pathway from the common jugular vein (7.4 mm) to the anterior SSS (1.2 mm) was technically challenging to selectively catheterize. The SSS coursed immediately adjacent to the motor cortex (< 1 mm) for a length of 40 mm, or the anterior half of the SSS. Attempted access with 5-Fr and 6-Fr delivery catheters was associated with longer procedure times and higher complication rates. A 4-Fr catheter (internal lumen diameter 1.1 mm) was successful in accessing the SSS in 100% of cases with no associated complications. Complications included procedure-related venous dissection in two major areas: the torcular herophili, and the anterior formation of the SSS. The bifurcation of the cruciate sulcal veins with the SSS was a reliable predictor of the commencement of the motor area. CONCLUSIONS The ovine model for cerebral catheter venography has generalizability to the human cerebral venous system in relation to motor cortex location. This novel model may facilitate the development of the novel field of endovascular neural interfaces that may include preclinical investigations for cortical recording applications such as paralysis and epilepsy, as well as other potential applications in neuromodulation.

Micro-CT and Histological Evaluation of an Neural Interface Implanted Within a Blood Vessel.

OBJECTIVE: Recently, we reported the development of a stent-mounted electrode array (Stentrode) capable of chronically recording neural signals from within a blood vessel with high fidelity. Preliminary data suggested incorporation of the Stentrode into the blood vessel wall was associated with improved recording sensitivity. We now investigate neointimal incorporation of the Stentrode, implanted in a cohort of sheep for up to 190 days. METHODS: Micro-CT, obtained from the Imaging and Medical Beamline at the Australian Synchrotron, and histomorphometic techniques developed specifically for evaluation of cerebral vasculature implanted with a stent-electrode array were compared as measures to assess device incorporation and vessel patency. RESULTS: Both micro-CT analysis and histomorphometry, revealed a strong correlation between implant duration and the number of incorporated stent struts. <10% (26/268) of stent struts were covered in neointima in sheep implanted for <2 weeks, increasing to >78% (191/243) between 2 and 4 weeks. Average strut-to-lumen thickness from animals implanted >12 weeks was comparable across both modalities, 339 ±15 µm measured using micro-CT and 331 ±19 µm ( n = 292) measured histologically. There was a strong correlation between lumen areas measured using the two modalities ( ), with no observation of vessel occlusion observed from any of the 12 animals implanted for up to 190 days. CONCLUSION: Micro-CT and the histomorphometric techniques we developed are comparable and can both be used to identify incorporation of a Stentrode implanted in cerebral vessels. SIGNIFICANCE: This study demonstrates preliminary safety of a stent-electrode array implanted in cerebral vasculature, which may facilitate technological advances in minimally invasive brain-computer interfaces.

The ovine motor cortex: A review of functional mapping and cytoarchitecture.

In recent years, sheep (Ovis aries) have emerged as a useful animal model for neurological research due to their relatively large brain and blood vessel size, their cortical architecture, and their docile temperament. However, the functional anatomy of sheep brain is not as well studied as that of non-human primates, rodents, and felines. For example, while the location of the sheep motor cortex has been known for many years, there have been few studies of the somatotopy of the motor cortex and there were a range of discrepancies across them. The motivation for this review is to provide a definitive resource for studies of the sheep motor cortex. This work critically reviews the literature examining the organization of the motor cortex in sheep, utilizing studies that have applied direct electrical stimulation and histological methods A clearer understanding of the sheep brain will facilitate and progress the use of this species as a scientific animal model for neurological research.

Suitability of nitinol electrodes in neural prostheses such as endovascular neural interfaces.

A major challenge facing neural prostheses is the development of electrodes that are well tolerated by the brain and body. A novel way to circumvent the need to perform an invasive craniotomy and penetration of the blood-brain barrier to implant electrodes, is to guide electrodes up into the cerebral veins and place electrodes on the vessel walls adjacent to neuronal populations. To aid in the development of these stent based devices, microelectrodes manufactured from Nitinol would allow electrodes to be implanted via a catheter and then once deployed, alter their shape to conform to the vessel walls. However, there is a paucity of data on whether Nitinol is a suitable material to record neural signals. Here we show that Nitinol is tolerated by the body and that it can effectively measure neural signals. Specifically, we electrochemically evaluate Nitinol electrodes in blood and record visually evoked potentials from sheep.

Chronic impedance spectroscopy of an endovascular stent-electrode array.

OBJECTIVE: Recently, we reported a minimally invasive stent-electrode array capable of recording neural signals from within a blood vessel. We now investigate the use of electrochemical impedance spectroscopy (EIS) measurements to infer changes occurring to the electrode-tissue interface from devices implanted in a cohort of sheep for up to 190 days. APPROACH: In a cohort of 15 sheep, endovascular stent-electrode arrays were implanted in the superior sagittal sinus overlying the motor cortex for up to 190 days. EIS was performed routinely to quantify viable electrodes for up to 91 days. An equivalent circuit model (ECM) was developed from the in vivo measurements to characterize the electrode-tissue interface changes occurring to the electrodes chronically implanted within a blood vessel. Post-mortem histological assessment of stent and electrode incorporation into the wall of the cortical vessels was compared to the electrical impedance measurements. MAIN RESULTS: EIS could be used to infer electrode viability and was consistent with x-ray analysis performed in vivo, and post-mortem evaluation. Viable electrodes exhibited consistent 1 kHz impedances across the 91 day measurement period, with the peak resistance frequency for the acquired data also stable over time. There was a significant change in 100 Hz phase angles, increasing from -67.8° ± 8.8° at day 0 to -43.8° ± 0.8° at day 91, which was observed to stabilize after eight days. ECM's modeled to the data suggested this change was due to an increase in the capacitance of the electrode-tissue interface. This was supported by histological assessment with >85% of the implanted stent struts covered with neointima and incorporated into the blood vessel within two weeks. CONCLUSION: This work demonstrated that EIS could be used to determine the viability of electrode implanted chronically within a blood vessel. Impedance measurements alone were not observed to be a useful predictor of alterations occurring at the electrode tissue interface. However, measurement of 100 Hz phase angles was in good agreement with the capacitive changes predicted by the ECM and consistent with suggestions that this represents protein absorption on the electrode surface. 100 Hz phase angles stabilized after 8 days, consistent with histologically assessed samples. SIGNIFICANCE: These findings demonstrate the potential application of this technology for use as a chronic neural recording system and indicate the importance of conducting EIS as a measure to identify viable electrodes and changes occurring at the electrode-tissue interface.

Development and Implementation of a Corriedale Ovine Brain Atlas for Use in Atlas-Based Segmentation.

Segmentation is the process of partitioning an image into subdivisions and can be applied to medical images to isolate anatomical or pathological areas for further analysis. This process can be done manually or automated by the use of image processing computer packages. Atlas-based segmentation automates this process by the use of a pre-labelled template and a registration algorithm. We developed an ovine brain atlas that can be used as a model for neurological conditions such as Parkinson's disease and focal epilepsy. 17 female Corriedale ovine brains were imaged in-vivo in a 1.5T (low-resolution) MRI scanner. 13 of the low-resolution images were combined using a template construction algorithm to form a low-resolution template. The template was labelled to form an atlas and tested by comparing manual with atlas-based segmentations against the remaining four low-resolution images. The comparisons were in the form of similarity metrics used in previous segmentation research. Dice Similarity Coefficients were utilised to determine the degree of overlap between eight independent, manual and atlas-based segmentations, with values ranging from 0 (no overlap) to 1 (complete overlap). For 7 of these 8 segmented areas, we achieved a Dice Similarity Coefficient of 0.5-0.8. The amygdala was difficult to segment due to its variable location and similar intensity to surrounding tissues resulting in Dice Coefficients of 0.0-0.2. We developed a low resolution ovine brain atlas with eight clinically relevant areas labelled. This brain atlas performed comparably to prior human atlases described in the literature and to intra-observer error providing an atlas that can be used to guide further research using ovine brains as a model and is hosted online for public access.

Feasibility of a chronic, minimally invasive endovascular neural interface.

Development of a neural interface that can be implanted without risky, open brain surgery will increase the safety and viability of chronic neural recording arrays. We have developed a minimally invasive surgical procedure and an endovascular electrode-array that can be delivered to overlie the cortex through blood vessels. Here, we describe feasibility of the endovascular interface through electrode viability, recording potential and safety. Electrochemical impedance spectroscopy demonstrated that electrode impedance was stable over 91 days and low frequency phase could be used to infer electrode incorporation into the vessel wall. Baseline neural recording were used to identify the maximum bandwidth of the neural interface, which remained stable around 193 Hz for six months. Cross-sectional areas of the implanted vessels were non-destructively measured using the Australian Synchrotron. There was no case of occlusion observed in any of the implanted animals. This work demonstrates the feasibility of an endovascular neural interface to safely and efficaciously record neural information over a chronic time course.

Minimally invasive endovascular stent-electrode array for high-fidelity, chronic recordings of cortical neural activity.

High-fidelity intracranial electrode arrays for recording and stimulating brain activity have facilitated major advances in the treatment of neurological conditions over the past decade. Traditional arrays require direct implantation into the brain via open craniotomy, which can lead to inflammatory tissue responses, necessitating development of minimally invasive approaches that avoid brain trauma. Here we demonstrate the feasibility of chronically recording brain activity from within a vein using a passive stent-electrode recording array (stentrode). We achieved implantation into a superficial cortical vein overlying the motor cortex via catheter angiography and demonstrate neural recordings in freely moving sheep for up to 190 d. Spectral content and bandwidth of vascular electrocorticography were comparable to those of recordings from epidural surface arrays. Venous internal lumen patency was maintained for the duration of implantation. Stentrodes may have wide ranging applications as a neural interface for treatment of a range of neurological conditions.