Feasibility, Safety, and Performance of Full-Head Subscalp EEG Using Minimally Invasive Electrode Implantation.

BACKGROUND AND OBJECTIVES: Current practice in clinical neurophysiology is limited to short recordings with conventional EEG (days) that fail to capture a range of brain (dys)functions at longer timescales (months). The future ability to optimally manage chronic brain disorders, such as epilepsy, hinges upon finding methods to monitor electrical brain activity in daily life. We developed a device for full-head subscalp EEG (Epios) and tested here the feasibility to safely insert the electrode leads beneath the scalp by a minimally invasive technique (primary outcome). As secondary outcome, we verified the noninferiority of subscalp EEG in measuring physiologic brain oscillations and pathologic discharges compared with scalp EEG, the established standard of care. METHODS: Eight participants with pharmacoresistant epilepsy undergoing intracranial EEG received in the same surgery subscalp electrodes tunneled between the scalp and the skull with custom-made tools. Postoperative safety was monitored on an inpatient ward for up to 9 days. Sleep-wake, ictal, and interictal EEG signals from subscalp, scalp, and intracranial electrodes were compared quantitatively using windowed multitaper transforms and spectral coherence. Noninferiority was tested for pairs of neighboring subscalp and scalp electrodes with a Bland-Altman analysis for measurement bias and calculation of the interclass correlation coefficient (ICC). RESULTS: As primary outcome, up to 28 subscalp electrodes could be safely placed over the entire head through 1-cm scalp incisions in a ∼1-hour procedure. Five of 10 observed perioperative adverse events were linked to the investigational procedure, but none were serious, and all resolved. As a secondary outcome, subscalp electrodes advantageously recorded EEG percutaneously without requiring any maintenance and were noninferior to scalp electrodes for measuring (1) variably strong, stage-specific brain oscillations (alpha in wake, delta, sigma, and beta in sleep) and (2) interictal spikes peak-potentials and ictal signals coherent with seizure propagation in different brain regions (ICC >0.8 and absence of bias). DISCUSSION: Recording full-head subscalp EEG for localization and monitoring purposes is feasible up to 9 days in humans using minimally invasive techniques and noninferior to the current standard of care. A longer prospective ambulatory study of the full system will be necessary to establish the safety and utility of this innovative approach. TRIAL REGISTRATION INFORMATION: clinicaltrials.gov/study/NCT04796597.

Designing next-generation subscalp devices for seizure monitoring: A systematic review and meta-analysis of established extracranial hardware.

Implantable brain recording and stimulation devices apply to a broad spectrum of conditions, such as epilepsy, movement disorders and depression. For long-term monitoring and neuromodulation in epilepsy patients, future extracranial subscalp implants may offer a promising, less-invasive alternative to intracranial neurotechnologies. To inform the design and assess the safety profile of such next-generation devices, we estimated extracranial complication rates of deep brain stimulation (DBS), cranial peripheral nerve stimulation (PNS), responsive neurostimulation (RNS) and existing subscalp EEG devices (sqEEG), as proxy for future implants. Pubmed was searched systematically for DBS, PNS, RNS and sqEEG studies from 2000 to February 2024 (48 publications, 7329 patients). We identified seven categories of extracranial adverse events: infection, non-infectious cutaneous complications, lead migration, lead fracture, hardware malfunction, pain and hemato-seroma. We used cohort sizes, demographics and industry funding as metrics to assess risks of bias. An inverse variance heterogeneity model was used for pooled and subgroup meta-analysis. The pooled incidence of extracranial complications reached 14.0%, with infections (4.6%, CI 95% [3.2 - 6.2]), surgical site pain (3.2%, [0.6 - 6.4]) and lead migration (2.6%, [1.0 - 4.4]) as leading causes. Subgroup analysis showed a particularly high incidence of persisting pain following PNS (12.0%, [6.8 - 17.9]) and sqEEG (23.9%, [12.7 - 37.2]) implantation. High rates of lead migration (12.4%, [6.4 - 19.3]) were also identified in the PNS subgroup. Complication analysis of DBS, PNS, RNS and sqEEG studies provides a significant opportunity to optimize the safety profile of future implantable subscalp devices for chronic EEG monitoring. Developing such promising technologies must address the risks of infection, surgical site pain, lead migration and skin erosion. A thin and robust design, coupled to a lead-anchoring system, shall enhance the durability and utility of next-generation subscalp implants for long-term EEG monitoring and neuromodulation.

A randomized, blinded study of photobiomodulation in a mouse model of Alzheimer's disease showed no preventive effect.

Photobiomodulation (PBM), the process of exposing tissue to red or near-infrared light, has become a topic of great interest as a therapy for diverse pathologies, including neurodegenerative disorders. Here, we aimed to evaluate the potential beneficial effect of PBM on Alzheimer's disease (AD) using behavioral and histological readouts from a well-established transgenic murine AD model (5xFAD mice) in a randomized and fully blinded long-term in-vivo study following GLP (Good Laboratory Practices) guidelines. The heads of the mice were illuminated with no (sham), low or high power 810 nm light, three times a week for 5 months from the first to the sixth month of life corresponding to the prodromal phase of the pathology. The results showed that there were no significant differences between the groups in behavioral tests, including the Morris water maze, novel object recognition, and Y-maze. Similarly, histological analyses showed no differences in amyloid load, neuronal loss or microglial response. In conclusion, under the conditions of our experiment, we were unable to demonstrate any therapeutic effect of PBM for AD. This study calls for further evidence and caution when considering PBM as an effective treatment for AD.

EEG error-related potentials encode magnitude of errors and individual perceptual thresholds.

Error-related potentials (ErrPs) are a prominent electroencephalogram (EEG) correlate of performance monitoring, and so crucial for learning and adapting our behavior. It is poorly understood whether ErrPs encode further information beyond error awareness. We report an experiment with sixteen participants over three sessions in which occasional visual rotations of varying magnitude occurred during a cursor reaching task. We designed a brain-computer interface (BCI) to detect ErrPs that provided real-time feedback. The individual ErrP-BCI decoders exhibited good transfer across sessions and scalability over the magnitude of errors. A non-linear relationship between the ErrP-BCI output and the magnitude of errors predicts individual perceptual thresholds to detect errors. We also reveal theta-gamma oscillatory coupling that co-varied with the magnitude of the required adjustment. Our findings open new avenues to probe and extend current theories of performance monitoring by incorporating continuous human interaction tasks and analysis of the ErrP complex rather than individual peaks.

Differential contributions of subthalamic beta rhythms and 1/f broadband activity to motor symptoms in Parkinson's disease.

Excessive beta oscillatory activity in the subthalamic nucleus (STN) is linked to Parkinson's Disease (PD) motor symptoms. However, previous works have been inconsistent regarding the functional role of beta activity in untreated Parkinsonian states, questioning such role. We hypothesized that this inconsistency is due to the influence of electrophysiological broadband activity -a neurophysiological indicator of synaptic excitation/inhibition ratio- that could confound measurements of beta activity in STN recordings. Here we propose a data-driven, automatic and individualized mathematical model that disentangles beta activity and 1/f broadband activity in the STN power spectrum, and investigate the link between these individual components and motor symptoms in thirteen Parkinsonian patients. We show, using both modeled and actual data, how beta oscillatory activity significantly correlates with motor symptoms (bradykinesia and rigidity) only when broadband activity is not considered in the biomarker estimations, providing solid evidence that oscillatory beta activity does correlate with motor symptoms in untreated PD states as well as the significant impact of broadband activity. These findings emphasize the importance of data-driven models and the identification of better biomarkers for characterizing symptom severity and closed-loop applications.

Action Monitoring Cortical Activity Coupled to Submovements.

Numerous studies have examined neural correlates of the human brain's action-monitoring system during experimentally segmented tasks. However, it remains unknown how such a system operates during continuous motor output when no experimental time marker is available (such as button presses or stimulus onset). We set out to investigate the electrophysiological correlates of action monitoring when hand position has to be repeatedly monitored and corrected. For this, we recorded high-density electroencephalography (EEG) during a visuomotor tracking task during which participants had to follow a target with the mouse cursor along a visible trajectory. By decomposing hand kinematics into naturally occurring periodic submovements, we found an event-related potential (ERP) time-locked to these submovements and localized in a sensorimotor cortical network comprising the supplementary motor area (SMA) and the precentral gyrus. Critically, the amplitude of the ERP correlated with the deviation of the cursor, 110 ms before the submovement. Control analyses showed that this correlation was truly due to the cursor deviation and not to differences in submovement kinematics or to the visual content of the task. The ERP closely resembled those found in response to mismatch events in typical cognitive neuroscience experiments. Our results demonstrate the existence of a cortical process in the SMA, evaluating hand position in synchrony with submovements. These findings suggest a functional role of submovements in a sensorimotor loop of periodic monitoring and correction and generalize previous results from the field of action monitoring to cases where action has to be repeatedly monitored.

Alertness opens the effective flow of sensory information through rat thalamic posterior nucleus.

Behavioural reactions to sensory stimuli vary with the level of arousal, but little is known about the underlying reorganization of neuronal networks. In this study, we use chronic recordings from the somatosensory regions of the thalamus and cortex of behaving rats together with a novel analysis of functional connectivity to show that during low arousal tactile signals are transmitted via the ventral posteromedial thalamic nucleus (VPM), a first-order thalamic relay, to the primary somatosensory (barrel) cortex and then from the cortex to the posterior medial thalamic nucleus (PoM), which plays a role of a higher-order thalamic relay. By contrast, during high arousal this network scheme is modified and both VPM and PoM transmit peripheral input to the barrel cortex acting as first-order relays. We also show that in urethane anaesthesia PoM is largely excluded from the thalamo-cortical loop. We thus demonstrate a way in which the thalamo-cortical system, despite its fixed anatomy, is capable of dynamically reconfiguring the transmission route of a sensory signal in concert with the behavioural state of an animal.

Modulation of the inter-hemispheric asymmetry of motor-related brain activity using brain-computer interfaces.

Non-invasive brain stimulation has shown promising results in neurorehabilitation for motor-impaired stroke patients, by rebalancing the relative involvement of each hemisphere in movement generation. Similarly, brain-computer interfaces have been used to successfully facilitate movement-related brain activity spared by the infarct. We propose to merge both approaches by using BCI to train stroke patients to rebalance their motor-related brain activity during motor tasks, through the use of online feedback. In this pilot study, we report results showing that some healthy subjects were able to learn to spontaneously up- and/or down-regulate their ipsilateral brain activity during a single session.

Errare machinale est: the use of error-related potentials in brain-machine interfaces.

The ability to recognize errors is crucial for efficient behavior. Numerous studies have identified electrophysiological correlates of error recognition in the human brain (error-related potentials, ErrPs). Consequently, it has been proposed to use these signals to improve human-computer interaction (HCI) or brain-machine interfacing (BMI). Here, we present a review of over a decade of developments toward this goal. This body of work provides consistent evidence that ErrPs can be successfully detected on a single-trial basis, and that they can be effectively used in both HCI and BMI applications. We first describe the ErrP phenomenon and follow up with an analysis of different strategies to increase the robustness of a system by incorporating single-trial ErrP recognition, either by correcting the machine's actions or by providing means for its error-based adaptation. These approaches can be applied both when the user employs traditional HCI input devices or in combination with another BMI channel. Finally, we discuss the current challenges that have to be overcome in order to fully integrate ErrPs into practical applications. This includes, in particular, the characterization of such signals during real(istic) applications, as well as the possibility of extracting richer information from them, going beyond the time-locked decoding that dominates current approaches.

Impact of meditation on emotional processing--a visual ERP study.

Impact of meditation on emotional processing, and its clinical applications, has recently drawn significant interest. In this visual event-related potential (ERP) study we investigated whether long-term meditation practitioners exhibit different ERP responses to the emotional load of stimuli (IAPS pictures) than control subjects with no experience in meditation. Differences were observed in the late positive potential (LPP). LPP amplitude is typically greater in ERPs evoked by emotionally arousing scenes, specifically negative images, compared to neutral scenes. This effect was also replicated in our study, but not in case of meditators' frontal scalp regions, who differed significantly in this respect from control subjects. Our findings provide support for different emotional processing in meditation practitioners: at high levels of processing meditators are less affected by stimuli with adverse emotional load, while processing of positive stimuli remains unaltered. To further confirm this observation, a long-term longitudinal random assignment study would be desirable.

The 5-12 Hz oscillations in the barrel cortex of awake rats--sustained attention during behavioral idling?

OBJECTIVE: 5-12 Hz oscillations, observed in cortical LFP of awake rats during quiet immobility, were proposed to be either (i) epileptic events or (ii) physiological alpha-like oscillations, manifesting an idling state of the cortex. We aimed to test this controversy. METHODS: We recorded LFP from the barrel cortex of awake Wistar rats, while applying weak tactile (whisker) and stronger arousing (electrical) stimuli. RESULTS: We observed a mean effect of desynchronization of the 5-12 Hz rhythm by the weak tactile stimulation. Arousal reduced the incidence of the 5-12 Hz oscillations and increased the desynchronizing power of tactile stimuli. CONCLUSIONS: Oscillations that can be disrupted by weak, purely tactile stimulation, and whose incidence is reduced by increased arousal, should be interpreted as a physiological phenomenon typical for behavioral idling while the cerebral cortex maintains sensory sensitivity. SIGNIFICANCE: Our results contradict the view that the 5-12 Hz oscillatory activity, often observed in fronto-parietal cortical regions of Wistar rats, represents epileptic discharges. Rather, this activity provides a model for studying the physiology of alpha/mu oscillations.

Cross-trial correlation analysis of evoked potentials reveals arousal-related attenuation of thalamo-cortical coupling.

We describe a computational method for assessing functional connectivity in sensory neuronal networks. The method, which we term cross-trial correlation, can be applied to signals representing local field potentials (LFPs) evoked by sensory stimulations and utilizes their trial-to-trial variability. A set of single trial samples of a given post-stimulus latency from consecutive evoked potentials (EPs) recorded at a given site is correlated with such sets for all other latencies and recording sites. The results of this computation reveal how neuronal activities at various sites and latencies correspond to activation of other sites at other latencies. The method was used to investigate the functional connectivity of thalamo-cortical network of somatosensory system in behaving rats at two levels of alertness: habituated and aroused. We analyzed potentials evoked by vibrissal deflections recorded simultaneously from the ventrobasal thalamus and barrel cortex. The cross-trial correlation analysis applied to the early post-stimulus period (<25 ms) showed that the magnitude of the population spike recorded in the thalamus at 5 ms post-stimulus correlated with the cortical activation at 6-13 ms post-stimulus. This correlation value was reduced at 6-9 ms, i.e. at early postsynaptic cortical response, with increased level of the animals' arousal. Similarly, the aroused state diminished positive thalamo-cortical correlation for subsequent early EP waves, whereas the efficacy of an indirect cortico-fugal inhibition (over 15 ms) did not change significantly. Thus we were able to characterize the state related changes of functional connections within the thalamo-cortical network of behaving animals.