Interictal spikes with and without high-frequency oscillation have different single-neuron correlates.

Interictal epileptiform discharges (IEDs) are a widely used biomarker in patients with epilepsy but lack specificity. It has been proposed that there are truly epileptogenic and less pathological or even protective IEDs. Recent studies suggest that highly pathological IEDs are characterized by high-frequency oscillations (HFOs). Here, we aimed to dissect these 'HFO-IEDs' at the single-neuron level, hypothesizing that the underlying mechanisms are distinct from 'non-HFO-IEDs'. Analysing hybrid depth electrode recordings from patients with temporal lobe epilepsy, we found that single-unit firing rates were higher in HFO- than in non-HFO-IEDs. HFO-IEDs were characterized by a pronounced pre-peak increase in firing, which coincided with the preferential occurrence of HFOs, whereas in non-HFO-IEDs, there was only a mild pre-peak increase followed by a post-peak suppression. Comparing each unit's firing during HFO-IEDs to its baseline activity, we found many neurons with a significant increase during the HFO component or ascending part, but almost none with a decrease. No such imbalance was observed during non-HFO-IEDs. Finally, comparing each unit's firing directly between HFO- and non-HFO-IEDs, we found that most cells had higher rates during HFO-IEDs and, moreover, identified a distinct subset of neurons with a significant preference for this IED subtype. In summary, our study reveals that HFO- and non-HFO-IEDs have different single-unit correlates. In HFO-IEDs, many neurons are moderately activated, and some participate selectively, suggesting that both types of increased firing contribute to highly pathological IEDs.

MEG detection of high frequency oscillations and intracranial-EEG validation in pediatric epilepsy surgery.

OBJECTIVE: To assess the feasibility of automatically detecting high frequency oscillations (HFOs) in magnetoencephalography (MEG) recordings in a group of ten paediatric epilepsy surgery patients who had undergone intracranial electroencephalography (iEEG). METHODS: A beamforming source-analysis method was used to construct virtual sensors and an automatic algorithm was applied to detect HFOs (80-250 Hz). We evaluated the concordance of MEG findings with the sources of iEEG HFOs, the clinically defined seizure onset zone (SOZ), the location of resected brain structures, and with post-operative outcome. RESULTS: In 8/9 patients there was good concordance between the sources of MEG HFOs and iEEG HFOs and the SOZ. Significantly more HFOs were detected in iEEG relative to MEG t(71) = 2.85, p < .05. There was good concordance between sources of MEG HFOs and the resected area in patients with good and poor outcome, however HFOs were also detected outside of the resected area in patients with poor outcome. CONCLUSION: Our findings demonstrate the feasibility of automatically detecting HFOs non-invasively in MEG recordings in paediatric patients, and confirm compatibility of results with invasive recordings. SIGNIFICANCE: This approach provides support for the non-invasive detection of HFOs to aid surgical planning and potentially reduce the need for invasive monitoring, which is pertinent to paediatric patients.

Intracranial correlates of small sharp spikes.

OBJECTIVE: To identify cortical correlates of scalp small sharp spikes (SSS) using simultaneous scalp and intracranial EEG recordings. METHODS: Patients were retrospectively evaluated based on a database of intracranial long-term recordings at the Epilepsy Center Freiburg. Inclusion criteria were: simultaneous recordings with intracranial and scalp EEGs and the presence of at least five unequivocal SSS in the scalp EEG. Intracranial recordings were analyzed regarding the co-occurring intracranial potentials during scalp SSS. RESULTS: 33 patients, aged 9-60y, 17 females, fulfilled the above-mentioned criteria. Almost all patients had intracranial SSS correlates in the form of spike/polyspike-waves in the temporal lobe, predominantly in the hippocampus (24/28), less frequently involving the amygdala (5/29), temporal basal (3/18), lateral neocortical (4/32), entorhinal cortices (1/12), and the parietal lobe (2/13). Amplitudes of intrahippocampal spikes or polyspikes co-occurring with SSS were significantly higher than intracranial discharges without scalp correlates. In 45% of patients, intracranial spikes accompanying SSS were located within the seizure onset zone (SOZ). CONCLUSIONS: Our results strongly support an epileptic origin of SSS and provide evidence about their heterogenous generators. SIGNIFICANCE: This study suggests that SSS cannot with certainty be classified as "benign" but rather considered as one of the EEG manifestations of focal epilepsy.

An electronic neuromorphic system for real-time detection of high frequency oscillations (HFO) in intracranial EEG.

The analysis of biomedical signals for clinical studies and therapeutic applications can benefit from embedded devices that can process these signals locally and in real-time. An example is the analysis of intracranial EEG (iEEG) from epilepsy patients for the detection of High Frequency Oscillations (HFO), which are a biomarker for epileptogenic brain tissue. Mixed-signal neuromorphic circuits offer the possibility of building compact and low-power neural network processing systems that can analyze data on-line in real-time. Here we present a neuromorphic system that combines a neural recording headstage with a spiking neural network (SNN) processing core on the same die for processing iEEG, and show how it can reliably detect HFO, thereby achieving state-of-the-art accuracy, sensitivity, and specificity. This is a first feasibility study towards identifying relevant features in iEEG in real-time using mixed-signal neuromorphic computing technologies.

MRI-Compatible and Conformal Electrocorticography Grids for Translational Research.

Intraoperative electrocorticography (ECoG) captures neural information from the surface of the cerebral cortex during surgeries such as resections for intractable epilepsy and tumors. Current clinical ECoG grids come in evenly spaced, millimeter-sized electrodes embedded in silicone rubber. Their mechanical rigidity and fixed electrode spatial resolution are common shortcomings reported by the surgical teams. Here, advances in soft neurotechnology are leveraged to manufacture conformable subdural, thin-film ECoG grids, and evaluate their suitability for translational research. Soft grids with 0.2 to 10 mm electrode pitch and diameter are embedded in 150 µm silicone membranes. The soft grids are compatible with surgical handling and can be folded to safely interface hidden cerebral surface such as the Sylvian fold in human cadaveric models. It is found that the thin-film conductor grids do not generate diagnostic-impeding imaging artefacts (<1 mm) nor adverse local heating within a standard 3T clinical magnetic resonance imaging scanner. Next, the ability of the soft grids to record subdural neural activity in minipigs acutely and two weeks postimplantation is validated. Taken together, these results suggest a promising future alternative to current stiff electrodes and may enable the future adoption of soft ECoG grids in translational research and ultimately in clinical settings.

Global and Parallel Cortical Processing Based on Auditory Gamma Oscillatory Responses in Humans.

Gamma oscillations are physiological phenomena that reflect perception and cognition, and involve parvalbumin-positive γ-aminobutyric acid-ergic interneuron function. The auditory steady-state response (ASSR) is the most robust index for gamma oscillations, and it is impaired in patients with neuropsychiatric disorders such as schizophrenia and autism. Although ASSR reduction is known to vary in terms of frequency and time, the neural mechanisms are poorly understood. We obtained high-density electrocorticography recordings from a wide area of the cortex in 8 patients with refractory epilepsy. In an ASSR paradigm, click sounds were presented at frequencies of 20, 30, 40, 60, 80, 120, and 160 Hz. We performed time-frequency analyses and analyzed intertrial coherence, event-related spectral perturbation, and high-gamma oscillations. We demonstrate that the ASSR is globally distributed among the temporal, parietal, and frontal cortices. The ASSR was composed of time-dependent neural subcircuits differing in frequency tuning. Importantly, the frequency tuning characteristics of the late-latency ASSR varied between the temporal/frontal and parietal cortex, suggestive of differentiation along parallel auditory pathways. This large-scale survey of the cortical ASSR could serve as a foundation for future studies of the ASSR in patients with neuropsychiatric disorders.

Imaging of focal seizures with Electrical Impedance Tomography and depth electrodes in real time.

Intracranial EEG is the current gold standard technique for localizing seizures for surgery, but it can be insensitive to tangential dipole or distant sources. Electrical Impedance Tomography (EIT) offers a novel method to improve coverage and seizure onset localization. The feasibility of EIT has been previously assessed in a computer simulation, which revealed an improved accuracy of seizure detection with EIT compared to intracranial EEG. In this study, slow impedance changes, evoked by cell swelling occurring over seconds, were reconstructed in real time by frequency division multiplexing EIT using depth and subdural electrodes in a swine model of epilepsy. EIT allowed to generate repetitive images of ictal events at similar time course to fMRI but without its significant limitations. EIT was recorded with a system consisting of 32 parallel current sources and 64 voltage recorders. Seizures triggered with intracranial injection of benzylpenicillin (BPN) in five pigs caused a repetitive peak impedance increase of 3.4 ± 1.5 mV and 9.5 ± 3% (N =205 seizures); the impedance signal change was seen already after a single, first seizure. EIT enabled reconstruction of the seizure onset 9 ± 1.5 mm from the BPN cannula and 7.5 ± 1.1 mm from the closest SEEG contact (p<0.05, n =37 focal seizures in three pigs) and it could address problems with sampling error in intracranial EEG. The amplitude of the impedance change correlated with the spread of the seizure on the SEEG (p <<0.001, n =37). The results presented here suggest that combining a parallel EIT system with intracranial EEG monitoring has a potential to improve the diagnostic yield in epileptic patients and become a vital tool in improving our understanding of epilepsy.

Multimodal in vivo recording using transparent graphene microelectrodes illuminates spatiotemporal seizure dynamics at the microscale.

Neurological disorders such as epilepsy arise from disrupted brain networks. Our capacity to treat these disorders is limited by our inability to map these networks at sufficient temporal and spatial scales to target interventions. Current best techniques either sample broad areas at low temporal resolution (e.g. calcium imaging) or record from discrete regions at high temporal resolution (e.g. electrophysiology). This limitation hampers our ability to understand and intervene in aberrations of network dynamics. Here we present a technique to map the onset and spatiotemporal spread of acute epileptic seizures in vivo by simultaneously recording high bandwidth microelectrocorticography and calcium fluorescence using transparent graphene microelectrode arrays. We integrate dynamic data features from both modalities using non-negative matrix factorization to identify sequential spatiotemporal patterns of seizure onset and evolution, revealing how the temporal progression of ictal electrophysiology is linked to the spatial evolution of the recruited seizure core. This integrated analysis of multimodal data reveals otherwise hidden state transitions in the spatial and temporal progression of acute seizures. The techniques demonstrated here may enable future targeted therapeutic interventions and novel spatially embedded models of local circuit dynamics during seizure onset and evolution.

Neuro-inflammatory Sequelae of Minimal Trauma in the Non-traumatized Human Brain: A Microdialysis Study.

Cytokine measurement directly from the brain parenchyma by means of microdialysis has documented the activation of certain procedures in vivo, after brain trauma in humans. However, the intercalation of the micro-catheter insertion with the phenomena triggered by the head trauma renders the assessment of the findings problematic. The present study attempts to elucidate the pure effect of minimal trauma, represented by the insertion of the micro-catheter, on the non-traumatized human brain. Microdialysis catheters were implanted in 12 patients with drug-resistant epilepsy, and subjected to invasive electroencephalography with intracranial electrodes. Samples were collected during the first 5 days of monitoring. The dialysate was analyzed using bead flow cytometry, and the concentrations of interleukin (IL)-1, IL-6, IL-8, IL-10, IL-12, and tumor necrosis factor-α (TNF-α) were measured. The levels of IL-1 and IL-8 were found to be raised until 48 h post-implantation, and thereafter they reached a plateau of presumably baseline values. The temporal profile of the IL-6 variation was different, with the increase being much more prolonged, as its concentration had not returned to baseline levels at the fifth day post-insertion. TNF-α was found to be significantly raised only 2 h after implantation. IL-10 and IL-12 did not have any significant response to micro-trauma. These findings imply that the reaction of the neuro-inflammatory mechanisms of the brain exist even after minimal trauma, and is unexpectedly intense for IL-6. Questions may arise regarding the objectivity of findings attributed by some studies to inflammatory perturbation after head injury.

Responsive Neurostimulation as a Novel Palliative Option in Epilepsy Surgery.

Patients with drug-resistant focal onset epilepsy are not always suitable candidates for resective surgery, a definitive intervention to control their seizures. The alternative surgical treatment for these patients in Japan has been vagus nerve stimulation (VNS). Besides VNS, epileptologists in the United States can choose a novel palliative option called responsive neurostimulation (RNS), a closed-loop neuromodulation system approved by the US Food and Drug Administration in 2013. The RNS System continuously monitors neural electroencephalography (EEG) activity at the possible seizure onset zone (SOZ) where electrodes are placed and responds with electrical stimulation when a pre-defined epileptic activity is detected. The controlled clinical trials in the United States have demonstrated long-term utility and safety of the RNS System. Seizure reduction rates have continued to improve over time, reaching 75% over 9 years of treatment. The incidence of implant-site infection, the most frequent device-related adverse event, is similar to those of other neuromodulation devices. The RNS System has shown favorable efficacy for both mesial temporal lobe epilepsy (TLE) and neocortical epilepsy of the eloquent cortex. Another unique advantage of the RNS System is its ability to provide chronic monitoring of ambulatory electrocorticography (ECoG). Valuable information obtained from ECoG monitoring provides a better understanding of the state of epilepsy in each patient and improves clinical management. This article reviews the developmental history, structure, and clinical utility of the RNS System, and discusses its indications as a novel palliative option for drug-resistant epilepsy.

Multimodal Detection for Cryptogenic Epileptic Seizures Based on Combined Micro Sensors.

The cryptogenic epilepsy of the neocortex is a disease in which the seizure is accompanied by intense cerebral nerve electrical activities but the lesions are not observed. It is difficult to locate disease foci. Electrocorticography (ECoG) is one of the gold standards in seizure focus localization. This method detects electrical signals, and its limitations are inadequate resolution which is only 10 mm and lack of depth information. In order to solve these problems, our new method with implantable micro ultrasound transducer (MUT) and photoplethysmogram (PPG) device detects blood changes to achieve higher resolution and provide depth information. The basis of this method is the neurovascular coupling mechanism, which shows that intense neural activity leads to sufficient cerebral blood volume (CBV). The neurovascular coupling mechanism established the relationship between epileptic electrical signals and CBV. The existence of mechanism enables us to apply our new methods on the basis of ECoG. Phantom experiments and in vivo experiments were designed to verify the proposed method. The first phantom experiments designed a phantom with two channels at different depths, and the MUT was used to detect the depth where the blood concentration changed. The results showed that the MUT detected the blood concentration change at the depth of 12 mm, which is the position of the second channel. In the second phantom experiments where a PPG device and MUT were used to monitor the change of blood concentration in a thick tube, the results showed that the trend of superficial blood concentration change provided by the PPG device is the same as that provided by the MUT within the depth of 2.5 mm. Finally, in the verification of in vivo experiments, the blood concentration changes on the surface recorded by the PPG device and the changes at a certain depth recorded by the MUT all matched the seizure status shown by ECoG. These results confirmed the effectiveness of the combined micro sensors.

Cortical Encoding of Manual Articulatory and Linguistic Features in American Sign Language.

The fluent production of a signed language requires exquisite coordination of sensory, motor, and cognitive processes. Similar to speech production, language produced with the hands by fluent signers appears effortless but reflects the precise coordination of both large-scale and local cortical networks. The organization and representational structure of sensorimotor features underlying sign language phonology in these networks remains unknown. Here, we present a unique case study of high-density electrocorticography (ECoG) recordings from the cortical surface of profoundly deaf signer during awake craniotomy. While neural activity was recorded from sensorimotor cortex, the participant produced a large variety of movements in linguistic and transitional movement contexts. We found that at both single electrode and neural population levels, high-gamma activity reflected tuning for particular hand, arm, and face movements, which were organized along dimensions that are relevant for phonology in sign language. Decoding of manual articulatory features revealed a clear functional organization and population dynamics for these highly practiced movements. Furthermore, neural activity clearly differentiated linguistic and transitional movements, demonstrating encoding of language-relevant articulatory features. These results provide a novel and unique view of the fine-scale dynamics of complex and meaningful sensorimotor actions.

Polyherbal Formulation Enhancing Cerebral Slow Waves in Sleeping Rats.

Polyherbal medicines are composed of multiple herbs and have traditionally been used in East Asian countries for the remedy of physiological symptoms. Although the effects of polyherbal formulations have been investigated at the molecular and behavioral levels, less is known about whether and how medicinal herbs affect the central nervous system in terms of neurophysiology. We introduced a novel blended herbal formulation that consisted of 35% linden, 21% mulberry, 20% lavandin, 20% butterfly pea, and 4% tulsi. After intraperitoneal administration of this formulation or saline, we simultaneously recorded epidural electrocorticograms (ECoGs) from the olfactory bulb (OB), primary somatosensory cortex (S1), and primary motor cortex (M1), along with electromyograms (EMGs) and electrocardiograms (ECGs), of rats exploring an open field arena. Using the EMGs and OB ECoGs, we segmented the behavioral states of rats into active awake, quiet awake, and sleeping states. Compared to saline, herbal medicine significantly shortened the total sleep time. Moreover, we converted the ECoG signal into a frequency domain using a fast Fourier transform (FFT) and calculated the powers at various ECoG oscillation frequencies. In the sleeping state, a slow component (0.5-3 Hz) of S1 ECoGs was significantly enhanced following the administration of the formulation, which suggests a region- and frequency-specific modulation of extracellular field oscillations by the polyherbal medicine.

Traumatic brain injury neuroelectrochemical monitoring: behind-the-ear micro-instrument and cloud application.

BACKGROUND: Traumatic Brain Injury (TBI) is a leading cause of fatality and disability worldwide, partly due to the occurrence of secondary injury and late interventions. Correct diagnosis and timely monitoring ensure effective medical intervention aimed at improving clinical outcome. However, due to the limitations in size and cost of current ambulatory bioinstruments, they cannot be used to monitor patients who may still be at risk of secondary injury outside the ICU. METHODS: We propose a complete system consisting of a wearable wireless bioinstrument and a cloud-based application for real-time TBI monitoring. The bioinstrument can simultaneously record up to ten channels including both ECoG biopotential and neurochemicals (e.g. potassium, glucose and lactate), and supports various electrochemical methods including potentiometry, amperometry and cyclic voltammetry. All channels support variable gain programming to automatically tune the input dynamic range and address biosensors' falling sensitivity. The instrument is flexible and can be folded to occupy a small space behind the ear. A Bluetooth Low-Energy (BLE) receiver is used to wirelessly connect the instrument to a cloud application where the recorded data is stored, processed and visualised in real-time. Bench testing has been used to validate device performance. RESULTS: The instrument successfully monitored spreading depolarisations (SDs) - reproduced using a signal generator - with an SNR of 29.07 dB and NF of 0.26 dB. The potentiostat generates a wide voltage range from -1.65V to +1.65V with a resolution of 0.8mV and the sensitivity of the amperometric AFE was verified by recording 5 pA currents. Different potassium, glucose and lactate concentrations prepared in lab were accurately measured and their respective working curves were constructed. Finally,the instrument achieved a maximum sampling rate of 1.25 ksps/channel with a throughput of 105 kbps. All measurements were successfully received at the cloud. CONCLUSION: The proposed instrument uniquely positions itself by presenting an aggressive optimisation of size and cost while maintaining high measurement accuracy. The system can effectively extend neuroelectrochemical monitoring to all TBI patients including those who are mobile and those who are outside the ICU. Finally, data recorded in the cloud application could be used to help diagnosis and guide rehabilitation.

Stereoelectroencephalography Versus Subdural Strip Electrode Implantations: Feasibility, Complications, and Outcomes in 500 Intracranial Monitoring Cases for Drug-Resistant Epilepsy.

BACKGROUND: Both stereoelectroencephalography (SEEG) and subdural strip electrodes (SSE) are used for intracranial electroencephalographic recordings in the invasive investigation of patients with drug-resistant epilepsy. OBJECTIVE: To compare SEEG and SSE with respect to feasibility, complications, and outcome in this single-center study. METHODS: Patient characteristics, periprocedural parameters, complications, and outcome were acquired from a pro- and retrospectively managed databank to compare SEEG and SSE cases. RESULTS: A total of 500 intracranial electroencephalographic monitoring cases in 450 patients were analyzed (145 SEEG and 355 SSE). Both groups were of similar age, gender distribution, and duration of epilepsy. Implantation of each SEEG electrode took 13.9 ± 7.6 min (20 ± 12 min for each SSE; P < .01). Radiation exposure to the patient was 4.3 ± 7.7 s to a dose area product of 14.6 ± 27.9 rad*cm2 for SEEG and 9.4 ± 8.9 s with 21 ± 22.4 rad*cm2 for SSE (P < .01). There was no difference in the length of stay (12.2 ± 7.2 and 12 ± 6.3 d). The complication rate was low in both groups. No infections were seen in SEEG cases (2.3% after SSE). The rate of hemorrhage was 2.8% for SEEG and 1.4% for SSE. Surgical outcome was similar. CONCLUSION: SEEG allows targeting deeply situated foci with a non-inferior safety profile to SSE and seizure outcome comparable to SSE.

Fabrication of Ti3C2 MXene Microelectrode Arrays for In Vivo Neural Recording.

Implantable microelectrode technologies have been widely used to elucidate neural dynamics at the microscale to gain a deeper understanding of the neural underpinnings of brain disease and injury. As electrodes are miniaturized to the scale of individual cells, a corresponding rise in the interface impedance limits the quality of recorded signals. Additionally, conventional electrode materials are stiff, resulting in a significant mechanical mismatch between the electrode and the surrounding brain tissue, which elicits an inflammatory response that eventually leads to a degradation of the device performance. To address these challenges, we have developed a process to fabricate flexible microelectrodes based on Ti3C2 MXene, a recently discovered nanomaterial that possesses remarkably high volumetric capacitance, electrical conductivity, surface functionality, and processability in aqueous dispersions. Flexible arrays of Ti3C2 MXene microelectrodes have remarkably low impedance due to the high conductivity and high specific surface area of the Ti3C2 MXene films, and they have proven to be exquisitely sensitive for recording neuronal activity. In this protocol, we describe a novel method for micropatterning Ti3C2 MXene into microelectrode arrays on flexible polymeric substrates and outline their use for in vivo micro-electrocorticography recording. This method can easily be extended to create MXene electrode arrays of arbitrary size or geometry for a range of other applications in bioelectronics and it can also be adapted for use with other conductive inks besides Ti3C2 MXene. This protocol enables simple and scalable fabrication of microelectrodes from solution-based conductive inks, and specifically allows harnessing the unique properties of hydrophilic Ti3C2 MXene to overcome many of the barriers that have long hindered the widespread adoption of carbon-based nanomaterials for high-fidelity neural microelectrodes.

Utility and lower limits of frequency detection in surface electrode stimulation for somatosensory brain-computer interface in humans.

OBJECTIVE: Stimulation of the primary somatosensory cortex (S1) has been successful in evoking artificial somatosensation in both humans and animals, but much is unknown about the optimal stimulation parameters needed to generate robust percepts of somatosensation. In this study, the authors investigated frequency as an adjustable stimulation parameter for artificial somatosensation in a closed-loop brain-computer interface (BCI) system. METHODS: Three epilepsy patients with subdural mini-electrocorticography grids over the hand area of S1 were asked to compare the percepts elicited with different stimulation frequencies. Amplitude, pulse width, and duration were held constant across all trials. In each trial, subjects experienced 2 stimuli and reported which they thought was given at a higher stimulation frequency. Two paradigms were used: first, 50 versus 100 Hz to establish the utility of comparing frequencies, and then 2, 5, 10, 20, 50, or 100 Hz were pseudorandomly compared. RESULTS: As the magnitude of the stimulation frequency was increased, subjects described percepts that were "more intense" or "faster." Cumulatively, the participants achieved 98.0% accuracy when comparing stimulation at 50 and 100 Hz. In the second paradigm, the corresponding overall accuracy was 73.3%. If both tested frequencies were less than or equal to 10 Hz, accuracy was 41.7% and increased to 79.4% when one frequency was greater than 10 Hz (p = 0.01). When both stimulation frequencies were 20 Hz or less, accuracy was 40.7% compared with 91.7% when one frequency was greater than 20 Hz (p < 0.001). Accuracy was 85% in trials in which 50 Hz was the higher stimulation frequency. Therefore, the lower limit of detection occurred at 20 Hz, and accuracy decreased significantly when lower frequencies were tested. In trials testing 10 Hz versus 20 Hz, accuracy was 16.7% compared with 85.7% in trials testing 20 Hz versus 50 Hz (p < 0.05). Accuracy was greater than chance at frequency differences greater than or equal to 30 Hz. CONCLUSIONS: Frequencies greater than 20 Hz may be used as an adjustable parameter to elicit distinguishable percepts. These findings may be useful in informing the settings and the degrees of freedom achievable in future BCI systems.

Flexible and stretchable opto-electric neural interface for low-noise electrocorticogram recordings and neuromodulation in vivo.

Optogenetic-based neuromodulation tools is evolving for the basic neuroscience research in animals combining optical manipulation and electrophysiological recordings. However, current opto-electric integrated devices attaching on cerebral cortex for electrocorticogram (ECoG) still exist potential damage risks for both brain tissue and electrode, due to the mechanical mismatch and brain deformation. Here, we propose a stretchable opto-electric integrated neural interface by integrating serpentine-shaped electrodes and multisite micro-LEDs onto a hyperelastic substrate, as well as a serpentine-shaped metal shielding embedded in recording electrode for low-noise signal acquisition. The delicate structure design, ultrasoft encapsulation and independent fabrication followed by assembly are beneficial to the conformality, reliability and yield. In vitro accelerated deterioration and reciprocating tensile have demonstrated good performance and high stability. In vivo optogenetic activation of focal cortical areas of awaked mouse expressing Channelrhodopsin-2 is realized with simultaneous high-quality recording. We highlight the potential use of this multifunctional neural interface for neural applications.

A 0.0023 mm 2/ch. Delta-Encoded, Time-Division Multiplexed Mixed-Signal ECoG Recording Architecture With Stimulus Artifact Suppression.

This article demonstrates a scalable, time-division multiplexed biopotential recording front-end capable of real-time differential- and common-mode artifact suppression. A delta-encoded recording architecture exploits the power spectral density (PSD) characteristics of Electrocorticography (ECoG) recordings, combining an 8-bit ADC, and an 8-bit DAC to achieve 14 bits of dynamic range. The flexibility of the digital feedback architecture is leveraged to time-division multiplex 64 differential input channels onto a shared mixed-signal front-end, reducing channel area by 2x compared to the state-of-the-art. The feedback DAC used for delta-encoding also serves to cancel differential artifacts with an off-chip adaptive loop. Analysis of this architecture and measured silicon performance of a 65 nm CMOS test-chip implementation, both on the bench and in-vivo, are included with this paper.

An Energy-Efficient CMOS Dual-Mode Array Architecture for High-Density ECoG-Based Brain-Machine Interfaces.

This article presents an energy-efficient electrocorticography (ECoG) array architecture for fully-implantable brain machine interface systems. A novel dual-mode analog signal processing method is introduced that extracts neural features from high- γ band (80-160 Hz) at the early stages of signal acquisition. Initially, brain activity across the full-spectrum is momentarily observed to compute the feature weights in the digital back-end during full-band mode operation. Subsequently, these weights are fed back to the front-end and the system reverts to base-band mode to perform feature extraction. This approach utilizes a distinct optimized signal pathway based on power envelope extraction, resulting in 1.72× power reduction in the analog blocks and up to 50× potential power savings for digitization and processing (implemented off-chip in this article). A prototype incorporating a 32-channel ultra-low power signal acquisition front-end is fabricated in 180 nm CMOS process with 0.8 V supply. This chip consumes 1.05  µW (0.205  µW for feature extraction only) power and occupies 0.245 [Formula: see text] die area per channel. The chip measurement shows better than 76.5-dB common-mode rejection ratio (CMRR), 4.09 noise efficiency factor (NEF), and 10.04 power efficiency factor (PEF). In-vivo human tests have been carried out with electroencephalography and ECoG signals to validate the performance and dual-mode operation in comparison to commercial acquisition systems.