Chronic subthreshold cortical stimulation: A promising therapy for motor cortex seizures.

Chronic subthreshold cortical stimulation (CSCS) is a form of neurostimulation consisting of continuous or cyclic, open-loop, subthreshold electrical stimulation of a well-defined epileptogenic zone (EZ). CSCS has seen limited clinical use but could be a safe and effective long-term treatment of focal drug resistant epilepsy, in particular when the EZ is located in the motor cortex. We present a case of a 49-year-old woman suffering from debilitating focal motor seizures. Treatment with CSCS resulted in significant clinical improvement, enabling her to walk unaided for the first time in years.

In vivo inhibition of epileptiform afterdischarges in rat hippocampus by light-activated chloride channel, stGtACR2.

AIMS: The blue light-sensitive chloride-conducting opsin, stGtACR2, provides potent optogenetic silencing of neurons. The present study investigated whether activation of stGtACR2 in granule cells of the dentate gyrus (DG) inhibits epileptic afterdischarges in a rat model. METHODS: Rats were bilaterally injected with 0.9 µl of AAV2/7-CaMKIIα-stGtACR2-fusionred in the DG. Three weeks later, afterdischarges were recorded from the DG by placing an optrode at the injection site and a stimulation electrode in the perforant path (PP). Afterdischarges were evoked every 10 min by unilateral electrical stimulation of the PP (20 Hz, 10 s). During every other afterdischarge, the DG was illuminated for 5 or 30 s, first ipsilaterally and then bilaterally to the PP stimulation. The line length metric of the afterdischarges was compared between illumination conditions. RESULTS: Ipsilateral stGtACR2 activation during afterdischarges decreased the local field potential line length only during illumination and specifically at the illuminated site but did not reduce afterdischarge duration. Bilateral illumination did not terminate the afterdischarges. CONCLUSION: Optogenetic inhibition of excitatory neurons using the blue-light sensitive chloride channel stGtACR2 reduced the amplitude of electrically induced afterdischarges in the DG at the site of illumination, but this local inhibitory effect was insufficient to reduce the duration of the afterdischarge.

Cognitive tasks propagate the neural entrainment in response to a visual 40 Hz stimulation in humans.

Introduction: Alzheimer's disease is one of the great challenges in the coming decades, and despite great efforts, a widely effective disease-modifying therapy in humans remains elusive. One particular promising non-pharmacological therapy that has received increased attention in recent years is based on the Gamma ENtrainment Using Sensory stimulation (GENUS), a high-frequency neural response elicited by a visual and/or auditory stimulus at 40 Hz. While this has shown to be effective in animal models, studies on human participants have reported varying success. The current work hypothesizes that the varying success in humans is due to differences in cognitive workload during the GENUS sessions. Methods: We recruited a cohort of 15 participants who underwent a scalp-EEG recording as well as one epilepsy patient who was implanted with 50 subdural surface electrodes over temporo-occipital and temporo-basal cortex and 14 depth contacts that targeted the hippocampus and insula. All participants completed several GENUS sessions, in each of which a different cognitive task was performed. Results: We found that the inclusion of a cognitive task during the GENUS session not only has a positive effect on the strength and extent of the gamma entrainment, but also promotes the propagation of gamma entrainment to additional neural areas including deep ones such as hippocampus which were not recruited when no cognitive task was required from the participants. The latter is of particular interest given that the hippocampal complex is considered to be one of the primary targets for AD therapies. Discussion: This work introduces a possible improvement strategy for GENUS therapy that might contribute to increasing the efficacy of the therapy or shortening the time needed for the positive outcome.

Parallel roles of neuroinflammation in feline and human epilepsies.

Autoimmune encephalitis refers to a group of disorders characterised by a non-infectious encephalitis, often with prominent seizures and surface neuronal autoantibodies. AE is an important cause of new-onset refractory status epilepticus in humans and is frequently responsive to immunotherapies including corticosteroids, plasma exchange, intravenous immunoglobulin G and rituximab. Recent research suggests that parallel autoantibodies can be detected in non-human mammalian species. The best documented example is leucine-rich glioma-inactivated 1 (LGI1)-antibodies in domestic cats with limbic encephalitis (LE). In this review, we discuss the role of neuroinflammation and autoantibodies in human and feline epilepsy and LE.

Continuous theta burst stimulation for drug-resistant epilepsy.

Introduction: Repetitive transcranial magnetic stimulation (rTMS) may have anti-epileptic effects, especially in patients with neocortical lesions. Initial clinical trials demonstrated that the duration of the seizure reducing effect is relatively short-lived. In the context of a chronic condition like epilepsy, theta burst stimulation (TBS) may represent a potential solution in optimizing treatment practicality and durability as it was demonstrated to be associated with longer-lasting after-effects. TBS has been studied extensively in diverse neuropsychiatric conditions, but a therapeutic TBS protocol has not previously been applied in epilepsy patients. Materials and methods: We performed a prospective open-label pilot study of 4-day accelerated continuous TBS (cTBS) treatment in patients with neocortical drug-resistant epilepsy (DRE). A treatment session consisted of 5 cTBS trains, each comprising 600 pulses presented in 50 Hz triplet bursts every 200 ms, delivered at 10-min intertrain-intervals, targeted over the epileptic focus (EF) using a neuronavigation-guided figure-of-8 coil. Safety and feasibility, and seizure frequency were assessed as primary and secondary endpoints, respectively, over a 4-week baseline period, a 1-week treatment period and a 7-week follow-up period, using adverse event logging, electro-encephalography, cognitive, and psychological questionnaires and a seizure diary kept by the patients and/or caregivers. Results: Seven subjects (4M:3F; median age 48, interquartile ranges 25) underwent the treatment protocol. Adverse events were reported in all subjects but were mild and transient. No clinical or electrographic seizures were evoked during or immediately following stimulation. No deterioration was found in cognition nor in psycho-emotional well-being following treatment. Treatment burden was acceptable, but seems to depend on clinical effect, duration of ongoing effect and stimulation site. Median weekly seizure frequency and ratio of seizure-free weeks did not change significantly in this small patient cohort. Conclusion: We report the results of the first ever trial of cTBS as a treatment for neocortical DRE. A 4-day accelerated cTBS protocol over the EF appears safe and feasible. Although the design and sample size of this open-label pilot study is unfit to reliably identify a therapeutic effect, results encourage further exploration of cTBS as an anti-epileptic treatment and potential optimization compared to conventional rTMS in a dedicated randomized controlled trial. (clinicaltrials.gov: NCT02635633).

The potential of invasive and non-invasive vagus nerve stimulation to improve verbal memory performance in epilepsy patients.

It has been demonstrated that acute vagus nerve stimulation (VNS) improves word recognition memory in epilepsy patients. Transcutaneous auricular vagus nerve stimulation (taVNS) has gained interest as a non-invasive alternative to improve cognition. In this prospective randomized cross-over study, we investigated the effect of both invasive VNS and taVNS on verbal memory performance in 15 patients with drug-resistant epilepsy. All patients conducted a word recognition memory paradigm in 3 conditions: VNS ON, VNS OFF and taVNS (3-period 3-treatment cross-over study design). For each condition, patients memorized 21 highlighted words from text paragraphs. Afterwards, the intervention was delivered for 30 s. Immediate recall and delayed recognition scores were obtained for each condition. This memory paradigm was repeated after 6 weeks of VNS therapy in 2 conditions: VNS ON and VNS OFF (2-period 2-treatment cross-over study design). Acute VNS and taVNS did not improve verbal memory performance. Immediate recall and delayed recognition scores were significantly improved after 6 weeks of VNS treatment irrespective of the acute intervention. We can conclude that the previously described positive effects of invasive VNS on verbal memory performance could not be replicated with invasive VNS and taVNS. An improved verbal memory performance was seen after 6 weeks of VNS treatment, suggesting that longer and more repetitive stimulation of the vagal pathway is required to modulate verbal memory performance.Clinical trial registration number: NCT05031208.

Laryngeal Muscle-Evoked Potential Recording as an Indicator of Vagal Nerve Fiber Activation.

BACKGROUND: Vagus nerve stimulation (VNS) is an adjunctive therapy for drug-resistant epilepsy. Noninvasive evoked potential recordings in laryngeal muscles (LMEPs) innervated by vagal branches may provide a marker to assess effective vagal nerve fiber activation. We investigated VNS-induced LMEPs in patients with epilepsy in acute and chronic settings. MATERIALS AND METHODS: A total of 17 of 25 patients underwent LMEP recordings at initiation of therapy (acute group); 15 of 25 patients after one year of VNS (chronic group); and 7 of 25 patients were tested at both time points (acute + chronic group). VNS-induced LMEPs were recorded following different pulse widths and output currents using six surface laryngeal EMG electrodes to calculate input/output curves and estimate LMEP latency, threshold current for minimal (Ithreshold), half-maximal (I50), and 95% of maximal (I95) response induction and amplitude of maximal response (Vmax). These were compared with the acute + chronic group and between responders and nonresponders in the acute and chronic group. RESULTS: VNS-induced LMEPs were present in all patients. Ithreshold and I95 values ranged from 0.25 to 1.00 mA and from 0.42 to 1.77 mA, respectively. Estimated mean LMEP latencies were 10 ± 0.1 milliseconds. No significant differences between responders and nonresponders were observed. In the acute + chronic group, Ithreshold values remained stable over time. However, at the individual level in this group, Vmax was lower in all patients after one year compared with baseline. CONCLUSIONS: Noninvasive VNS-induced LMEP recording is feasible both at initiation of VNS therapy and after one year. Low output currents (0.25-1.00 mA) may be sufficient to activate vagal Aα-motor fibers. Maximal LMEP amplitudes seemed to decrease after chronic VNS therapy in patients.

In vivoblue light illumination for optogenetic inhibition: effect on local temperature and excitability of the rat hippocampus.

Objective.The blue light-activated inhibitory opsin, stGtACR2, is gaining prominence as a neuromodulatory tool due its ability to shunt-inhibit neurons and is being frequently used inin vivoexperimentation. However, experiments involving stGtACR2 use longer durations of blue light pulses, which inadvertently heat up the local brain tissue and confound experimental results. Therefore, the heating effects of illumination parameters used forin vivooptogenetic inhibition must be evaluated.Approach.To assess blue light (473 nm)-induced heating of the brain, we used a computational model as well as direct temperature measurements using a fiber Bragg grating (FBG). The effects of different light power densities (LPDs) and pulse durations on evoked potentials (EP) recorded from dentate gyrus were assessed. For opsin-negative rats, LPDs between 127 and 636 mW mm-2and pulse durations between 20 and 5120 ms were tested while for stGtACR2 expressing rats, LPD of 127 mW mm-2and pulse durations between 20 and 640 ms were tested.Main results.Increasing LPDs and pulse durations logarithmically increased the peak temperature and significantly decreased the population spike (PS) amplitude and latencies of EPs. For a pulse duration of 5120 ms, the tissue temperature increased by 0.6 °C-3.4 °C. All tested LPDs decreased the PS amplitude in opsin-negative rats, but 127 mW mm-2had comparatively minimal effects and a significant effect of increasing light pulse duration was seen from 320 ms and beyond. This corresponded with an average temperature increase of 0.2 °C-1.1 °C at the recorded site. Compared to opsin-negative rats, illumination in stGtACR2-expressing rats resulted in much greater inhibition of EPs.Significance.Our study demonstrates that light-induced heating of the brain can be accurately measuredin vivousing FBG sensors. Such light-induced heating alone can affect neuronal excitability. Useful neuromodulation by the activation of stGtACR2 is still possible while minimizing thermal effects.

Attenuation of Hippocampal Evoked Potentials in vivo by Activation of GtACR2, an Optogenetic Chloride Channel.

AIM: GtACR2, a light-activated chloride channel, is an attractive tool for neural inhibition as it can shunt membrane depolarizations. In this study, we assessed the effect of activating GtACR2 on in vivo hippocampal CA1 activity evoked by Schaffer collateral (SC) stimulation. METHODS: Adult male Wistar rats were unilaterally injected with 0.5 µL of adeno associated viral vector for induction of GtACR2-mCherry (n = 10, GtACR2 group) or mCherry (n = 4, Sham group) expression in CA1 pyramidal neurons of the hippocampus. Three weeks later, evoked potentials (EPs) were recorded from the CA1 subfield placing an optrode (bipolar recording electrode attached to an optic fiber) at the injection site and a stimulation electrode targeting SCs. Effects of illumination parameters required to activate GtACR2 such as light power densities (LPDs), illumination delays, and light-pulse durations were tested on CA1 EP parameters [population spike (PS) amplitude and field excitatory postsynaptic potential (fEPSP) slope]. RESULTS: In the GtACR2 group, delivery of a 10 ms light-pulse induced a negative deflection in the local field potential which increased with increasing LPD. When combined with electrical stimulation of the SCs, light-induced activation of GtACR2 had potent inhibitory effects on CA1 EPs. An LPD of 160 mW/mm2 was sufficient to obtain maximal inhibition CA1 EPs. To quantify the duration of the inhibitory effect, a 10 ms light-pulse of 160 mW/mm2 was delivered at increasing delays before the CA1 EPs. Inhibition of EPs was found to last up to 9 ms after the cessation of the light-pulse. Increasing light-pulse durations beyond 10 ms did not result in larger inhibitory effects. CONCLUSION: Precisely timed activation of GtACR2 potently blocks evoked activity of CA1 neurons. The strength of inhibition depends on LPD, lasts up to 9 ms after a light-pulse of 10 ms, and is independent of the duration of the light-pulse given.

Long-term chemogenetic suppression of seizures in a multifocal rat model of temporal lobe epilepsy.

OBJECTIVE: One third of epilepsy patients do not become seizure-free using conventional medication. Therefore, there is a need for alternative treatments. Preclinical research using designer receptors exclusively activated by designer drugs (DREADDs) has demonstrated initial success in suppressing epileptic activity. Here, we evaluated whether long-term chemogenetic seizure suppression could be obtained in the intraperitoneal kainic acid rat model of temporal lobe epilepsy, when DREADDs were selectively expressed in excitatory hippocampal neurons. METHODS: Epileptic male Sprague Dawley rats received unilateral hippocampal injections of adeno-associated viral vector encoding the inhibitory DREADD hM4D(Gi), preceded by a cell-specific promotor targeting excitatory neurons. The effect of clozapine-mediated DREADD activation on dentate gyrus evoked potentials and spontaneous electrographic seizures was evaluated. Animals were systemically treated with single (.1 mg/kg/24 h) or repeated (.1 mg/kg/6 h) injections of clozapine. In addition, long-term continuous release of clozapine and olanzapine (2.8 mg/kg/7 days) using implantable minipumps was evaluated. All treatments were administered during the chronic epileptic phase and between 1.5 and 13.5 months after viral transduction. RESULTS: In the DREADD group, dentate gyrus evoked potentials were inhibited after clozapine treatment. Only in DREADD-expressing animals, clozapine reduced seizure frequency during the first 6 h postinjection. When administered repeatedly, seizures were suppressed during the entire day. Long-term treatment with clozapine and olanzapine both resulted in significant seizure-suppressing effects for multiple days. Histological analysis revealed DREADD expression in both hippocampi and some cortical regions. However, lesions were also detected at the site of vector injection. SIGNIFICANCE: This study shows that inhibition of the hippocampus using chemogenetics results in potent seizure-suppressing effects in the intraperitoneal kainic acid rat model, even 1 year after viral transduction. Despite a need for further optimization, chemogenetic neuromodulation represents a promising treatment prospect for temporal lobe epilepsy.

Pre-ictal heart rate variability alterations in focal onset seizures and response to vagus nerve stimulation.

PURPOSE: Vagus nerve stimulation (VNS) is an effective and well-known treatment for drug resistant epilepsy (DRE) patients since 1997, yet prediction of treatment response before implantation is subject of ongoing research. Neuroimaging and neurophysiological studies investigating the vagal afferent network in resting state documented that differences in between epilepsy patients were related to treatment response. This study investigated whether an event-related parameter, pre-ictal heart rate variability (HRV) is associated with response to VNS therapy. METHODS: DRE patients underwent video-electroencephalography (EEG) recording before VNS implantation. HRV parameters (time, non-linear and frequency domain) were assessed for every seizure during two 10 min timeframes: baseline (60 min before seizure onset) and pre-ictal (10 min before seizure onset). Pre-ictal HRV parameter alterations were correlated with VNS response after one year of VNS therapy and seizure characteristics (temporal/extratemporal, left/right or bilateral). RESULTS: 104 seizures from 22 patients were evaluated. Eleven patients were VNS responders with a seizure frequency reduction of ≥ 50 % after one year of VNS. In VNS responders no changes in HRV parameters were found while in VNS non-responders the time domain and non-linear HRV variables decreased significantly (p = 0.024, p = 0.005, p = 0.005) during the pre-ictal time frame. 10/11 VNS non-responders had a seizure lateralization to the left compared to 4/11 VNS responders. CONCLUSION: VNS non-responders were characterized by a significant decrease of pre-ictal HRV (time domain/non-linear variables) suggesting a sudden autonomic imbalance probably due to an impaired central autonomic function that makes it at the same time unlikely to respond to VNS.

Localization of deep brain activity with scalp and subdural EEG.

To what extent electrocorticography (ECoG) and electroencephalography (scalp EEG) differ in their capability to locate sources of deep brain activity is far from evident. Compared to EEG, the spatial resolution and signal-to-noise ratio of ECoG is superior but its spatial coverage is more restricted, as is arguably the volume of tissue activity effectively measured from. Moreover, scalp EEG studies are providing evidence of locating activity from deep sources such as the hippocampus using high-density setups during quiet wakefulness. To address this question, we recorded a multimodal dataset from 4 patients with refractory epilepsy during quiet wakefulness. This data comprises simultaneous scalp, subdural and depth EEG electrode recordings. The latter was located in the hippocampus or insula and provided us with our "ground truth" for source localization of deep activity. We applied independent component analysis (ICA) for the purpose of separating the independent sources in theta, alpha and beta frequency band activity. In all patients subdural- and scalp EEG components were observed which had a significant zero-lag correlation with one or more contacts of the depth electrodes. Subsequent dipole modeling of the correlating components revealed dipole locations that were significantly closer to the depth electrodes compared to the dipole location of non-correlating components. These findings support the idea that components found in both recording modalities originate from neural activity in close proximity to the depth electrodes. Sources localized with subdural electrodes were ~70% closer to the depth electrode than sources localized with EEG with an absolute improvement of around ~2cm. In our opinion, this is not a considerable improvement in source localization accuracy given that, for clinical purposes, ECoG electrodes were implanted in close proximity to the depth electrodes. Furthermore, the ECoG grid attenuates the scalp EEG, due to the electrically isolating silastic sheets in which the ECoG electrodes are embedded. Our results on dipole modeling show that the deep source localization accuracy of scalp EEG is comparable to that of ECoG. SIGNIFICANCE STATEMENT: Deep and subcortical regions play an important role in brain function. However, as joint recordings at multiple spatial scales to study brain function in humans are still scarce, it is still unresolved to what extent ECoG and EEG differ in their capability to locate sources of deep brain activity. To the best of our knowledge, this is the first study presenting a dataset of simultaneously recorded EEG, ECoG and depth electrodes in the hippocampus or insula, with a focus on non-epileptiform activity (quiet wakefulness). Furthermore, we are the first study to provide experimental findings on the comparison of source localization of deep cortical structures between invasive and non-invasive brain activity measured from the cortical surface.

High-gamma oscillations precede visual steady-state responses: A human electrocorticography study.

The robust steady-state cortical activation elicited by flickering visual stimulation has been exploited by a wide range of scientific studies. As the fundamental neural response inherits the spectral properties of the gazed flickering, the paradigm has been used to chart cortical characteristics and their relation to pathologies. However, despite its widespread adoption, the underlying neural mechanisms are not well understood. Here, we show that the fundamental response is preceded by high-gamma (55-125 Hz) oscillations which are also synchronised to the gazed frequency. Using a subdural recording of the primary and associative visual cortices of one human subject, we demonstrate that the latencies of the high-gamma and fundamental components are highly correlated on a single-trial basis albeit that the latter is consistently delayed by approximately 55 ms. These results corroborate previous reports that top-down feedback projections are involved in the generation of the fundamental response, but, in addition, we show that trial-to-trial variability in fundamental latency is paralleled by a highly similar variability in high-gamma latency. Pathology- or paradigm-induced alterations in steady-state responses could thus originate either from deviating visual gamma responses or from aberrations in the neural feedback mechanism. Experiments designed to tease apart the two processes are expected to provide deeper insights into the studied paradigm.

Long-term chemogenetic suppression of spontaneous seizures in a mouse model for temporal lobe epilepsy.

OBJECTIVE: More than one-third of patients with temporal lobe epilepsy (TLE) continue to have seizures despite treatment with antiepileptic drugs, and many experience severe drug-related side effects, illustrating the need for novel therapies. Selective expression of inhibitory Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) allows cell-type-specific reduction of neuronal excitability. In this study, we evaluated the effect of chemogenetic suppression of excitatory pyramidal and granule cell neurons of the sclerotic hippocampus in the intrahippocampal mouse model (IHKA) for temporal lobe epilepsy. METHODS: Intrahippocampal IHKA mice were injected with an adeno-associated viral vector carrying the genes for an inhibitory DREADD hM4Di in the sclerotic hippocampus or control vector. Next, animals were treated systemically with different single doses of clozapine-N-oxide (CNO) (1, 3, and 10 mg/kg) and clozapine (0.03 and 0.1 mg/kg) and the effect on spontaneous hippocampal seizures, hippocampal electroencephalography (EEG) power, fast ripples (FRs) and behavior in the open field test was evaluated. Finally, animals received prolonged treatment with clozapine for 3 days and the effect on seizures was monitored. RESULTS: Treatment with both CNO and clozapine resulted in a robust suppression of hippocampal seizures for at least 15 hours only in DREADD-expressing animals. Moreover, total EEG power and the number of FRs were significantly reduced. CNO and/or clozapine had no effects on interictal hippocampal EEG, seizures, or locomotion/anxiety in the open field test in non-DREADD epileptic IHKA mice. Repeated clozapine treatment every 8 hours for 3 days resulted in almost complete seizure suppression in DREADD animals. SIGNIFICANCE: This study shows the potency of chemogenetics to robustly and sustainably suppress spontaneous epileptic seizures and pave the way for an epilepsy therapy in which a systemically administered exogenous drug selectively modulates specific cell types in a seizure network, leading to a potent seizure suppression devoid of the typical drug-related side effects.

Semantic and perceptual priming activate partially overlapping brain networks as revealed by direct cortical recordings in humans.

Facilitation of object processing in the brain due to a related context (priming) can be influenced by both semantic connections and perceptual similarity. It is thus important to discern these two when evaluating the spatio-temporal dynamics of primed object processing. The repetition-priming paradigm frequently used to study perceptual priming is, however, unable to differentiate between the mentioned priming effects, possibly leading to confounded results. In the current study, we recorded brain signals from the scalp and cerebral convexity of nine patients with refractory epilepsy in response to related and unrelated image-pairs, all of which shared perceptual features while only related ones had a semantic connection. While previous studies employing a repetition-priming paradigm observed largely overlapping networks between semantic and perceptual priming effects, our results suggest that this overlap is only partial (both temporally and spatially). These findings stress the importance of controlling for perceptual features when studying semantic priming.

Preparing for hard times: Scalp and intracranial physiological signatures of proactive cognitive control.

Based on reward and difficulty information, people can strategically adjust proactive cognitive control. fMRI research shows that motivated proactive control is implemented through fronto-parietal control networks that are triggered by reward and difficulty cues. Here, we investigate electrophysiological signatures of proactive control. Previously, the contingent negative variation (CNV) in the ERPs and oscillatory power in the theta (4-8 Hz) and alpha band (8-14 Hz) have been suggested as signatures of control implementation. However, experimental designs did not always separate control implementation from motor preparation. Critically, we used a mental calculation task to investigate effects of proactive control implementation on the CNV and on theta and alpha power, in absence of motor preparation. In the period leading up to task onset, we found a more negative CNV, increased theta power, and decreased alpha power for hard versus easy calculations, showing increased proactive control implementation when a difficult task was expected. These three measures also correlated with behavioral performance, both across trials and across subjects. In addition to scalp EEG in healthy participants, we collected intracranial local field potential recordings in an epilepsy patient. We observed a slow-drift component that was more pronounced for hard trials in a hippocampal location, possibly reflecting task-specific preparation for hard mental calculations. The current study thus shows that difficulty information triggers proactive control in absence of motor preparation and elucidates its neurophysiological signatures.

Decoding Steady-State Visual Evoked Potentials From Electrocorticography.

We report on a unique electrocorticography (ECoG) experiment in which Steady-State Visual Evoked Potentials (SSVEPs) to frequency- and phase-tagged stimuli were recorded from a large subdural grid covering the entire right occipital cortex of a human subject. The paradigm is popular in EEG-based Brain Computer Interfacing where selectable targets are encoded by different frequency- and/or phase-tagged stimuli. We compare the performance of two state-of-the-art SSVEP decoders on both ECoG- and scalp-recorded EEG signals, and show that ECoG-based decoding is more accurate for very short stimulation lengths (i.e., less than 1 s). Furthermore, whereas the accuracy of scalp-EEG decoding benefits from a multi-electrode approach, to address interfering EEG responses and noise, ECoG decoding enjoys only a marginal improvement as even a single electrode, placed over the posterior part of the primary visual cortex, seems to suffice. This study shows, for the first time, that EEG-based SSVEP decoders can in principle be applied to ECoG, and can be expected to yield faster decoding speeds using less electrodes.

Representation of steady-state visual evoked potentials elicited by luminance flicker in human occipital cortex: An electrocorticography study.

Despite the widespread use of steady-state visual evoked potentials (SSVEPs) elicited by luminance flicker in clinical and research settings, their spatial and temporal representation in the occipital cortex largely remain elusive. We performed intracranial-EEG recordings in response to targets flickering at frequencies from 11 to 15 Hz using a subdural electrode grid covering the entire right occipital cortex of a human subject, and we were able to consistently locate the gazed stimulus frequency at the posterior side of the primary visual cortex (V1). Peripheral flickering, undetectable in scalp-EEG, elicited activations in the interhemispheric fissure at locations consistent with retinotopic maps. Both foveal and peripheral activations spatially coincided with activations in the high gamma band. We detected localized alpha synchronization at the lateral edge of V2 during stimulation and transient post-stimulation theta band activations at the posterior part of the occipital cortex. Scalp-EEG exhibited only a minor occipital post-stimulation theta activation, but a strong transient frontal activation.