Delayed high-frequency suppression after automated single-pulse electrical stimulation identifies the seizure onset zone in patients with refractory epilepsy

Objective

Single-pulse electrical stimulation (SPES) of intracranial electrodes evokes responses that may help identify the seizure onset zone (SOZ); however, lack of automation and response variability has limited clinical adoption of this technique. We evaluated whether automated delivery of low-current SPES could evoke delayed high-frequency suppression (DHFS) of ongoing electrocorticography (ECoG) signals that, when combined with objective analytic techniques, may provide a reliable marker of this zone.

Comparison of somatosensory evoked high-frequency oscillations after posterior tibial and median nerve stimulation.

OBJECTIVE: We compared the high-frequency oscillations (HFOs) evoked by posterior tibial nerve (PTN) and median nerve (MN) stimulation. METHODS: Somatosensory evoked potentials (SEPs) were recorded with a filter set at 10-2000 Hz to right PTN and to right MN stimulation in 10 healthy subjects. The HFOs were obtained by digitally filtering the wide-band SEPs with a band-pass of 300-900 Hz. RESULTS: HFOs were recorded in 8 of the 10 subjects for PTN, and in all subjects for MN stimulation. The HFOs after both PTN and MN stimulation started approximately at or after the onset of the primary cortical response (P37 and N20) and ended around the middle of the second slope. HFO amplitudes and area after PTN stimulation were significantly smaller than those after MN stimulation. HFO duration after PTN stimulation was markedly longer than that after MN stimulation. However, HFO interpeak latencies did not differ between the two nerves. CONCLUSIONS: The present findings suggest that the HFOs after PTN and MN stimulation reflect a neural mechanism common to the hand and foot somatosensory cortex.     

Frequency-independent characteristics of high-frequency oscillations in epileptic and non-epileptic regions

Objective

The purpose of the presented study is to determine whether there are frequency-independent high-frequency oscillation (HFO) parameters which may differ in epileptic and non-epileptic regions.

Cardiac responses of vagus nerve stimulation: intraoperative bradycardia and subsequent chronic stimulation

OBJECTIVES: Few adverse events on heart rate have been reported with vagus nerve stimulation (VNS) for refractory epilepsy. We describe three cases with intraoperative bradycardia during device testing. PATIENTS AND METHODS: At our hospital 111 patients have received a VNS system. Intraoperative device testing is performed under ECG-monitoring. We reviewed the patients and their VNS-therapy follow-up outcome who experienced a change in heart rate, during device testing (Lead Test). RESULTS: Three patients with medically refractory epilepsy showed a bradycardia during intraoperative Lead Test. Postoperative the VNS-therapy started under ECG-monitoring. No change in cardiac rhythm occurred. Subsequent chronic stimulation is uneventful. All three have reduced seizure frequency. Two already have had their second implant, without the occurrence of bradycardia. CONCLUSION: In case of intraoperative bradycardia VNS-therapy onset should be done under ECG-monitoring. Subsequent chronic stimulation is safe in respect to heart rate. Bradycardia during intraoperative device testing is no reason to abort the operation.     

Value of electrical stimulation and high frequency oscillations (80–500 Hz) in identifying epileptogenic areas during intracranial EEG recordings

Purpose: Electrical stimulation (ES) is used during intracranial electroencephalography (EEG) investigations to delineate epileptogenic areas and seizure‐onset zones (SOZs) by provoking afterdischarges (ADs) or patients’ typical seizure. High frequency oscillations (HFOs—ripples, 80–250 Hz; fast ripples, 250–500 Hz) are linked to seizure onset. This study investigates whether interictal HFOs are more frequent in areas with a low threshold to provoke ADs or seizures. Methods: Intracranial EEG studies were filtered at 500 Hz and sampled at 2,000 Hz. HFOs were visually identified. Twenty patients underwent ES, with gradually increasing currents. Results were interpreted as agreeing or disagreeing with the intracranial study (clinical‐EEG seizure onset defined the SOZ). Current thresholds provoking an AD or seizure were correlated with the rate of HFOs of each channel. Results: ES provoked a seizure in 12 and ADs in 19 patients. Sixteen patients showed an ES response inside the SOZ, and 10 had additional areas with ADs. The response was more specific for mesiotemporal than for neocortical channels. HFO rates were negatively correlated with thresholds for ES responses; especially in neocortical regions; areas with low threshold and high HFO rate were colocalized even outside the SOZ. Discussion: Areas showing epileptic HFOs colocalize with those reacting to ES. HFOs may represent a pathologic correlate of regions showing an ES response; both phenomena suggest a more widespread epileptogenicity.     

Interictal high-frequency oscillations (80-500 Hz) are an indicator of seizure onset areas independent of spikes in the human epileptic brain

Purpose: High‐frequency oscillations (HFOs) known as ripples (80–250 Hz) and fast ripples (250–500 Hz) can be recorded from macroelectrodes inserted in patients with intractable focal epilepsy. They are most likely linked to epileptogenesis and have been found in the seizure onset zone (SOZ) of human ictal and interictal recordings. HFOs occur frequently at the time of interictal spikes, but were also found independently. This study analyses the relationship between spikes and HFOs and the occurrence of HFOs in nonspiking channels. Methods: Intracerebral EEGs of 10 patients with intractable focal epilepsy were studied using macroelectrodes. Rates of HFOs within and outside spikes, the overlap between events, event durations, and the percentage of spikes carrying HFOs were calculated and compared according to anatomical localization, spiking activity, and relationship to the SOZ. Results: HFOs were found in all patients, significantly more within mesial temporal lobe structures than in neocortex. HFOs could be seen in spiking as well as nonspiking channels in all structures. Rates and durations of HFOs were significantly higher in the SOZ than outside. It was possible to establish a rate of HFOs to identify the SOZ with better sensitivity and specificity than with the rate of spikes. Discussion: HFOs occurred to a large extent independently of spikes. They are most frequent in mesial temporal structures. They are prominent in the SOZ and provide additional information on epileptogenicity independently of spikes. It was possible to identify the SOZ with a high specificity by looking at only 10 min of HFO activity.     

Local and distant cortical responses to single pulse intracranial stimulation in the human brain are differentially modulated by specific stimulation parameters

BackgroundElectrical neuromodulation via direct electrical stimulation (DES) is an increasingly common therapy for a wide variety of neuropsychiatric diseases. Unfortunately, therapeutic efficacy is inconsistent, likely due to our limited understanding of the relationship between the massive stimulation parameter space and brain tissue responses.ObjectiveTo better understand how different parameters induce varied neural responses, we systematically examined single pulse-induced cortico-cortico evoked potentials (CCEP) as a function of stimulation amplitude, duration, brain region, and whether grey or white matter was stimulated.MethodsWe measured voltage peak amplitudes and area under the curve (AUC) of intracranially recorded stimulation responses as a function of distance from the stimulation site, pulse width, current injected, location relative to grey and white matter, and brain region stimulated (N = 52, n = 719 stimulation sites).ResultsIncreasing stimulation pulse width increased responses near the stimulation location. Increasing stimulation amplitude (current) increased both evoked amplitudes and AUC nonlinearly. Locally (<15 mm), stimulation at the boundary between grey and white matter induced larger responses. In contrast, for distant sites (>15 mm), white matter stimulation consistently produced larger responses than stimulation in or near grey matter. The stimulation location-response curves followed different trends for cingulate, lateral frontal, and lateral temporal cortical stimulation.ConclusionThese results demonstrate that a stronger local response may require stimulation in the grey-white boundary while stimulation in the white matter could be needed for network activation. Thus, stimulation parameters tailored for a specific anatomical-functional outcome may be key to advancing neuromodulatory therapy.     

Pathological responses to single‐pulse electrical stimuli in epilepsy: The role of feedforward inhibition

Delineation of epileptogenic cortex in focal epilepsy patients may profit from single‐pulse electrical stimulation during intracranial EEG recordings. Single‐pulse electrical stimulation evokes early and delayed responses. Early responses represent connectivity. Delayed responses are a biomarker for epileptogenic cortex, but up till now, the precise mechanism generating delayed responses remains elusive. We used a data‐driven modelling approach to study early and delayed responses. We hypothesized that delayed responses represent indirect responses triggered by early response activity and investigated this for 11 patients. Using two coupled neural masses, we modelled early and delayed responses by combining simulations and bifurcation analysis. An important feature of the model is the inclusion of feedforward inhibitory connections. The waveform of early responses can be explained by feedforward inhibition. Delayed responses can be viewed as second‐order responses in the early response network which appear when input to a neural mass falls below a threshold forcing it temporarily to a spiking state. The combination of the threshold with noisy background input explains the typical stochastic appearance of delayed responses. The intrinsic excitability of a neural mass and the strength of its input influence the probability at which delayed responses to occur. Our work gives a theoretical basis for the use of delayed responses as a biomarker for the epileptogenic zone, confirming earlier clinical observations. The combination of early responses revealing effective connectivity, and delayed responses showing intrinsic excitability, makes single‐pulse electrical stimulation an interesting tool to obtain data for computational models of epilepsy surgery.     

经颅电刺激咀嚼肌诱发电位的检测方法与正常值

目的　对健康个体进行经颅电刺激咀嚼肌运动诱发电位的研究 ,建立评估皮质脑干束的检查方法。方法　对 5 6名健康志愿者进行经颅电刺激 ,在双侧咀嚼肌同时接受 ,分别记录同侧的根运动诱发电位 ( R- MEP)和对侧的皮层运动诱发电位 ( C- MEP)的潜伏期、波幅。结果　在同侧记录的是兴奋同侧的三叉神经根所产生的动作电位 ,因此称为“root”MEP( R- MEP) ;在对侧轻收缩状态下记录的是兴奋对侧的皮质延髓束所产生的动作电位 ,因此称为“cortical”MEP( C- MEP)。 R- MEP的潜期为 3.5 5± 0 .44 ms,波幅为 3.49± 2 .73m V;C- MEP的潜期为5 .83± 1.40 ms,波幅为 5 6 3.84± 5 2 5 .0 7μV。C- MEP的潜期与年龄无明显相关性 ( P>0 .1)。结论　 C- MEP是一种非创伤性评估皮质脑干束的检测方法。     

Functional-anatomical studies on sperm release evoked by electrical stimulation of the olfactory tract in goldfish

Sperm release was evoked by electrical stimulation of the olfactory tracts in male goldfish. Thresholds as low as 5 microA were obtained using suction electrodes while slightly higher currents were necessary using metal electrodes (lowest thresholds of 15-20 microA). Several control procedures were carried out to insure that current-spread to nearby structures was not responsible for the evoked responses. Testing olfactory tract stimulation following transection of one or more divisions of the olfactory tract revealed that connections to the olfactory bulb and pathways involving the lateral olfactory tract were not necessary for the stimulation effect, whereas the medial olfactory tract appears to be both sufficient and necessary for mediation of evoked sperm release. The results are discussed with respect to possible involvement of each of the 3 known functional components constituting the medial olfactory tract: (1) secondary olfactory afferents; (2) olfactory efferents; and (3) fibers of the terminal nerve. The possibility that female sex pheromones normally influence central sperm release mechanisms via pathways in the medical olfactory tract is also considered.     

颅内电极皮层电刺激皮层后放电的抑制规律研究

目的:通过对后放电(AD)进行脉冲刺激抑制的研究,为皮层电刺激(ECS)治疗癫(痫)摸索合理的刺激参数.方法:回顾性研究2011～2012年行癫(痫)颅内电极埋置术并接受ECS病人的脑电图(EEG)资料共10例,如患者反复出现AD,即在相同位置给予相同参数的短暂脉冲刺激(BPS),有时可终止AD,对皮层AD的抑制规律进行分析.结果:对64个点重复刺激后可重复出现AD触点45个(70％),对这45个AD点给予BPS,其中13个(29％)在刺激后2s内AD终止,对比不同的AD波形、频率、部位、时相、累及范围、是否远隔、刺激潜伏期与BPS干预效果相关.结论:当在AD波形的负相峰及下降期,AD波形表现为棘慢波及节律性波,BPS潜伏期越短时,BPS干预AD更加有效.     

A fast and general method to empirically estimate the complexity of brain responses to transcranial and intracranial stimulations

BackgroundThe Perturbational Complexity Index (PCI) was recently introduced to assess the capacity of thalamocortical circuits to engage in complex patterns of causal interactions. While showing high accuracy in detecting consciousness in brain-injured patients, PCI depends on elaborate experimental setups and offline processing, and has restricted applicability to other types of brain signals beyond transcranial magnetic stimulation and high-density EEG (TMS/hd-EEG) recordings.ObjectiveWe aim to address these limitations by introducing PCI^ST, a fast method for estimating perturbational complexity of any given brain response signal.MethodsPCI^ST is based on dimensionality reduction and state transitions (ST) quantification of evoked potentials. The index was validated on a large dataset of TMS/hd-EEG recordings obtained from 108 healthy subjects and 108 brain-injured patients, and tested on sparse intracranial recordings (SEEG) of 9 patients undergoing intracranial single-pulse electrical stimulation (SPES) during wakefulness and sleep.ResultsWhen calculated on TMS/hd-EEG potentials, PCI^ST performed with the same accuracy as the original PCI, while improving on the previous method by being computed in less than a second and requiring a simpler set-up. In SPES/SEEG signals, the index was able to quantify a systematic reduction of intracranial complexity during sleep, confirming the occurrence of state-dependent changes in the effective connectivity of thalamocortical circuits, as originally assessed through TMS/hd-EEG.ConclusionsPCI^ST represents a fundamental advancement towards the implementation of a reliable and fast clinical tool for the bedside assessment of consciousness as well as a general measure to explore the neuronal mechanisms of loss/recovery of brain complexity across scales and models.     

Compound sensory action potentials evoked by tactile and by electrical stimulation in normal median and sural nerves

The compound sensory action potential evoked by electrical stimulation provides a measure of the number and physiological properties of myelinated fibers in the nerve but does not allow evaluation of the most distal part of the sensory nerve. This study compares the compound sensory action potential, evoked by electrical and tactile stimuli, and recorded through needle electrodes placed close to the median and sural nerves of 22 normal males aged 16–51 years. The tactile probe, with a slight preindentation, delivered an indentation of the skin of 200 μm at a rate of 400 μ/ms at the tip of digit III and the dorsolateral side of the foot. The responses were recorded from the median nerve at wrist and elbow and from the sural nerve at the lateral malleolus and midcalf. The amplitudes of the responses averaged 0.5 μV and 0.7 μV in the sural and the median nerves (P < 0.02), respectively, which was only 5–10% of the amplitude evoked by electrical stimulation. The mean maximal conduction velocity determined by tactile stimulation was 54 m/s in the sural nerve compared with 65 m/s in the median nerve and similar to that calculated after electrical stimulation. In the median nerve the sensory conduction velocity was 8% faster than the motor conduction velocity. These findings indicated that only a fraction of the fibers in the nerve were activated by the probe and that the response was conducted along large myelinated sensory fibers. The latency of the tactile response was longer than that of the electrically evoked response due to the receptor delay and conduction along thin distal fiber portions. The delay at the mechanoreceptors was about 1 ms in the sural and 0.65 ms in the median nerve (P < 0.01). © 1994 John Wiley & Sons, Inc.     

Symptom responses, long-term outcomes and adverse events beyond 3 years of high-frequency gastric electrical stimulation for gastroparesis

The aims were to determine symptom responses and long-term outcomes in gastroparetic patients receiving gastric electrical stimulation (GES) therapy beyond 3 years by presenting per protocol analysis and intention-to-treat (ITT) analysis. Data collected at baseline, 1 year and beyond 3 years in 55 patients included total symptom scores (TSS), nutritional status, weight, hospitalizations, the use of prokinetic and/or antiemetic medications, HbA1c in diabetics and adverse events. Of the 55 patients, 10 died of non-pacemaker-related complications, six had the devices removed and two could not be reached. The remaining 37 patients had the device activated for a mean of 45 months. Both per protocol and ITT analysis demonstrated that TSS, hospitalization days and the use of medications were all significantly reduced at 1 year and were sustained beyond 3 years. Average TSS decreased by 62.5% for the 37 patients completing 3 years of GES. At implantation, 15/37 patients required nutritional support and only five continued beyond 3 years. Mean HbA1c level in diabetics was significantly reduced from 9.5 to 7.9% at 3 years. We conclude that a significant improvement in symptoms and all measures of clinical outcome can be maintained for greater than 3 years with GES in patients with refractory gastroparesis.     

Oroalimentary automatisms induced by electrical stimulation of the fronto-opercular cortex in a patient without automotor seizures

Despite being a common sign in focal epilepsies, the exact symptomatogenic zone for oroalimentary automatisms remains largely unknown. We describe a patient with refractory complex partial seizures secondary to a right temporoparietal malformation of cortical development who underwent prolonged video/EEG monitoring with subdural electrodes. During his typical seizures, the patient manifested decreased awareness but never automatisms. However, during electrical cortical stimulation of two electrodes located over the right inferior frontal gyrus, oroalimentary automatisms with preserved consciousness were elicited, with no afterdischarges detected in the adjacent electrodes. These two electrodes were distant from the seizure onset zone and were not involved in seizure propagation. This case provides evidence that fronto-opercular cortex may be involved in the generation of oroalimentary automatisms.     

Comparison of cortical responses to the activation of retina by visual stimulation and transcorneal electrical stimulation

Background

Electrical stimulation has been widely used in many ophthalmic diseases to modulate neuronal activities or restore partial visual function. Due to the different processing pathways and mechanisms, responses to visual and electrical stimulation in the primary visual cortex and higher visual areas might be different. This differences would shed some light on the properties of cortical responses evoked by electrical stimulation.

Intestinal electrical stimulation improves delayed gastric emptying and vomiting induced by duodenal distension in dogs.

The aim of this study was to investigate the effects of short-pulse intestinal electrical stimulation (IES) on duodenal distention-induced delayed gastric emptying and vomiting in dogs and its possible mechanisms. The study was performed in 12 dogs with jejunal electrodes and a duodenal cannula in three separate experiments to investigate the effects of IES on duodenal distension (DD)-induced delayed gastric emptying and discomfort signs, vagal efferent activity, and jejunal tone. We found that: (i) IES significantly accelerated gastric emptying of liquid delayed by distension (18.05 +/- 4.06%vs. 7.18 +/- 1.99%, P = 0.036 at 60 min). (ii) IES significantly reduced vomiting and discomfort/pain induced by distension. The average signs score was 15.33 +/- 1.37 during distension which decreased to 6.50 +/- 0.91 (P = 0.0002) with IES. (iii) IES did not change vagal afferent activity, which was assessed by the spectral analysis of the heart rate variability. (iv) IES decreased jejunal tone. In conclusion, IES with parameters commonly used in gastric electrical stimulation for nausea and vomiting associated with gastroparesis improves DD-induced delayed gastric emptying and prevents DD-induced vomiting and discomfort signs. Further studies are warranted to investigate the therapeutic potential of IES for gastrointestinal symptoms associated with disturbances in motility and sensory function in small intestine.     

Somatosensory evoked potentials and high frequency oscillations are differently modulated by theta burst stimulation over primary somatosensory cortex in humans

Objective

The effects of theta burst stimulation (TBS) have been extensively investigated in primary motor cortex, where it leads to long-lasting LTP/LTD-like effects on synaptic plasticity. This study aimed to extend these observations to sensory cortex.

Methods

Fourteen healthy subjects participated in the study. Conditioning 600-pulse intermittent TBS (iTBS) and continuous TBS (cTBS) were delivered to left somatosensory cortex (S1) with an intensity of 80% active motor threshold. Somatosensory evoked potentials (SEPs) were evoked by median nerve electrical stimulation at right wrist. High frequency oscillations (HFOs) were obtained by digital filtering of original SEPs and divided into early and late subcomponents, relative to N20_peak latency.

Results

Repeated-measures ANOVA showed that iTBS facilitated N20_onset–N20_peak at 15 min and N20_peak–P25 at 15 and 30 min after conditioning, whereas cTBS did not. iTBS left the early and late HFOs unchanged. Conversely, cTBS facilitated the early HFOs, whereas it inhibited the late HFOs at 15 min after conditioning.

Conclusions

S1-iTBS facilitated SEPs without changes in HFOs whereas cTBS modulated early and late HFOs without changes in SEPs.

Significance

S1-TBS produces lasting changes in the excitability of intracortical circuits generating SEPs and HFOs differentially through mechanisms of LTP/LTD-like synaptic plasticity.