The Effects of Context and Attention on Spiking Activity in Human Early Visual Cortex.

Here we report the first quantitative analysis of spiking activity in human early visual cortex. We recorded multi-unit activity from two electrodes in area V2/V3 of a human patient implanted with depth electrodes as part of her treatment for epilepsy. We observed well-localized multi-unit receptive fields with tunings for contrast, orientation, spatial frequency, and size, similar to those reported in the macaque. We also observed pronounced gamma oscillations in the local-field potential that could be used to estimate the underlying spiking response properties. Spiking responses were modulated by visual context and attention. We observed orientation-tuned surround suppression: responses were suppressed by image regions with a uniform orientation and enhanced by orientation contrast. Additionally, responses were enhanced on regions that perceptually segregated from the background, indicating that neurons in the human visual cortex are sensitive to figure-ground structure. Spiking responses were also modulated by object-based attention. When the patient mentally traced a curve through the neurons' receptive fields, the accompanying shift of attention enhanced neuronal activity. These results demonstrate that the tuning properties of cells in the human early visual cortex are similar to those in the macaque and that responses can be modulated by both contextual factors and behavioral relevance. Our results, therefore, imply that the macaque visual system is an excellent model for the human visual cortex.

In Vivo Accuracy of a Frameless Stereotactic Drilling Technique for Diagnostic Biopsies and Stereoelectroencephalography Depth Electrodes.

BACKGROUND: Accurate frameless neuronavigation is highly important in cranial neurosurgery. The accuracy demonstrated in phantom models might not be representative for results in patients. Few studies describe the in vivo quantitative accuracy of neuronavigation in patients. The use of a frameless stereotactic drilling technique for stereoelectroencephalography depth electrode implantation in epilepsy patients, as well as diagnostic biopsies, provides a unique opportunity to assess the accuracy with postoperative imaging of preoperatively planned trajectories. METHODS: In 7 patients with refractory epilepsy, 89 depth electrodes were implanted using a frameless stereotactic drilling technique. Each electrode was planned on a preoperative magnetic resonance and computed tomographic scan, and verified on postoperative computed tomographic scan. After fusion of preoperative and postoperative imaging, the accuracy for each electrode was calculated as the Euclidean distance between the planned and observed position of the electrode tip. RESULTS: The median Euclidean distance between planned and observed electrode implantations was 3.5 mm (95% confidence interval, 2.9-3.9 mm) with a range of 1.2-13.7 mm. CONCLUSIONS: In this study, we showed that the in vivo accuracy of our frameless stereotactic drilling technique, suitable for stereoelectroencephalography depth electrode placement and diagnostic brain biopsies, was 3.5 mm.

Learning of anticipatory responses in single neurons of the human medial temporal lobe.

Neuronal processes underlying the formation of new associations in the human brain are not yet well understood. Here human participants, implanted with depth electrodes in the brain, learned arbitrary associations between images presented in an ordered, predictable sequence. During learning we recorded from medial temporal lobe (MTL) neurons that responded to at least one of the pictures in the sequence (the preferred stimulus). We report that as a result of learning, single MTL neurons show asymmetric shifts in activity and start firing earlier in the sequence in anticipation of their preferred stimulus. These effects appear relatively early in learning, after only 11 exposures to the stimulus sequence. The anticipatory neuronal responses emerge while the subjects became faster in reporting the next item in the sequence. These results demonstrate flexible representations that could support learning of new associations between stimuli in a sequence, in single neurons in the human MTL.

Automated Seizure Onset Zone Approximation Based on Nonharmonic High-Frequency Oscillations in Human Interictal Intracranial EEGs.

A novel automated algorithm is proposed to approximate the seizure onset zone (SOZ), while providing reproducible output. The SOZ, a surrogate marker for the epileptogenic zone (EZ), was approximated from intracranial electroencephalograms (iEEG) of nine people with temporal lobe epilepsy (TLE), using three methods: (1) Total ripple length (TRL): Manually segmented high-frequency oscillations, (2) Rippleness (R): Area under the curve (AUC) of the autocorrelation functions envelope, and (3) Autoregressive model residual variation (ARR, novel algorithm): Time-variation of residuals from autoregressive models of iEEG windows. TRL, R, and ARR results were compared in terms of separability, using Kolmogorov-Smirnov tests, and performance, using receiver operating characteristic (ROC) curves, to the gold standard for SOZ delineation: visual observation of ictal video-iEEGs. TRL, R, and ARR can distinguish signals from iEEG channels located within the SOZ from those outside it (p < 0.01). The ROC AUC was 0.82 for ARR, while it was 0.79 for TRL, and 0.64 for R. ARR outperforms TRL and R, and may be applied to identify channels in the SOZ automatically in interictal iEEGs of people with TLE. ARR, interpreted as evidence for nonharmonicity of high-frequency EEG components, could provide a new way to delineate the EZ, thus contributing to presurgical workup.

A European survey on current practices in epilepsy monitoring units and implications for patients' safety.

OBJECTIVE: This study aimed to survey current practices in European epilepsy monitoring units (EMUs) with emphasis on safety issues. METHODS: A 37-item questionnaire investigating characteristics and organization of EMUs, including measures for prevention and management of seizure-related serious adverse events (SAEs), was distributed to all identified European EMUs plus one located in Israel (N=150). RESULTS: Forty-eight (32%) EMUs, located in 18 countries, completed the questionnaire. Epilepsy monitoring unit beds are 1-2 in 43%, 3-4 in 34%, and 5-6 in 19% of EMUs; staff physicians are 1-2 in 32%, 3-4 in 34%, and 5-6 in 19% of EMUs. Personnel operating in EMUs include epileptologists (in 69% of EMUs), clinical neurophysiologists trained in epilepsy (in 46% of EMUs), child neurologists (in 35% of EMUs), neurology and clinical neurophysiology residents (in 46% and in 8% of EMUs, respectively), and neurologists not trained in epilepsy (in 27% of EMUs). In 20% of EMUs, patients' observation is only intermittent or during the daytime and primarily carried out by neurophysiology technicians and/or nurses (in 71% of EMUs) or by patients' relatives (in 40% of EMUs). Automatic detection systems for seizures are used in 15%, for body movements in 8%, for oxygen desaturation in 33%, and for ECG abnormalities in 17% of EMUs. Protocols for management of acute seizures are lacking in 27%, of status epilepticus in 21%, and of postictal psychoses in 87% of EMUs. Injury prevention consists of bed protections in 96% of EMUs, whereas antisuffocation pillows are employed in 21%, and environmental protections in monitoring rooms and in bathrooms are implemented in 38% and in 25% of EMUs, respectively. The most common SAEs were status epilepticus reported by 79%, injuries by 73%, and postictal psychoses by 67% of EMUs. CONCLUSIONS: All EMUs have faced different types of SAEs. Wide variation in practice patterns and lack of protocols and of precautions to ensure patients' safety might promote the occurrence and severity of SAEs. Our findings highlight the need for standardized and shared protocols for an effective and safe management of patients in EMUs.

High frequency spectral components after secobarbital: the contribution of muscular origin--a study with MEG/EEG.

OBJECTIVES: Previously we found that benzodiazepines not only provoke beta-activity in the EEG, but also higher frequency activity. Knowing the origin of this high frequency activity is crucial if localisation of epileptogenic brain tissue is the query. We attempt to differentiate cerebral from muscular origin of such activity. METHODS: We postulate that EEG and MEG have similar sensitivity to brain activity, but different sensitivity to muscle activity, and compare co-recorded EEG and MEG signals in a group of five patients who had received short-lasting barbiturates to induce sleep. We performed principal components analysis over time and subtract the results for MEG from the EEG to see where the frequency spectra differ. RESULTS: The EEG showed activity in the gamma bands up to 270Hz for all patients; the MEG significantly less. We find no differences in the lower frequency bands. Topographically the differences localized over the frontotemporal regions. CONCLUSIONS: In the EEG benzodiazepines and/or barbiturates are not only associated with frequencies in the beta band, but also with wide range gamma activity. The latter seems to be of muscular origin. SIGNIFICANCE: Our study suggests that gamma activity in such measurements may not be cerebral in origin. MEG is less susceptible to contamination from muscle activity than the EEG.

Quantification of spontaneous and evoked HFO's in SEEG recording and prospective for pre-surgical diagnostics. Case study.

High frequency oscillations (HFO) in stereo electroencephalographic (SEEG) signals have been recently the focus of attention as biomarkers that can have potential predictive power for the spatial location and possibly the timing of the onset of epileptic seizures. In this work we present a case study where we compare two quantitative paradigms for automated detection of biomarkers, one based on spontaneous SEEG recordings of HFOs and the other using activity induced by direct electrical stimulation (relative Phase Clustering Index algorithm). We compare the performance of these automated methods with manually detected HFO ripples by a trained EEG analyst and explore their potential diagnostic relevance. Intracranial recordings from patients undergoing pre-surgical evaluation are processed with a combination of morphological filtering and the analysis of the auto-correlation function. The results were compared to those obtained by visual inspection and to results from an active paradigm involving stimulation with 20 Hz trains of biphasic pulses. The quantity of HFOs, estimated automatically, or "rippleness", was found to correspond to the findings of a trained EEG analyst. The relative phase clustering index (rPCI) obtained using periodic stimulation appeared to be associated with the closeness to the seizure onset zone (SOZ) detected from ictal epochs. The HFO estimates were also indicative for the SOZ but with less specificity.

An electro-encephalogram beta gap after induction with diazepam: a localization method in epileptogenic lesions.

OBJECTIVE: We clinically tested a quantitative EEG method to localize abnormal variations in benzodiazepine-induced fast rhythms to localize focal epileptogenic lesions, assuming altered quality/quantity of GABA receptors in the lesions. METHODS: During a 64-channel-EEG (sampled at 1 kHz) recording benzodiazepines were administered to five patients with localization related epilepsy associated with an MRI visible focal lesion. We determined the post-injection dominant spectral modulation using Gabor wavelets and analysed the symmetry of spatial distribution. This was compared to the localization of the lesion on the MRI scan. RESULTS: The principal component was found in the beta/gamma band. In all patients one region of decreased change was associated with the lesional hemisphere, and overlapped with the site of the lesion in four. Three patients underwent surgery: interictal corticographic findings concurred with the area of decreased benzodiazepine response. CONCLUSIONS: This simple method localized abnormal function associated with epileptogenic lesions. Further methodological validation is now justified. Final clinical validation must be done in MRI-negative cases as well. SIGNIFICANCE: This research may lead to techniques for non-invasive easy localization of epileptogenic tissue that is not visible on a structural MRI scan.