Simultaneously recorded intracranial and scalp high frequency oscillations help identify patients with poor postsurgical seizure outcome

ObjectiveHigh frequency oscillations (HFO) between 80–500 Hz are markers of epileptic areas in intracranial and maybe also scalp EEG. We investigate simultaneous recordings of scalp and intracranial EEG and hypothesize that scalp HFOs provide important additional clinical information in the presurgical setting.MethodsSpikes and HFOs were visually identified in all intracranial scalp EEG channels. Analysis of correlation of event location between intracranial and scalp EEG as well as relationship between events and the SOZ and zone of surgical removal was performed.Results24 patients could be included, 23 showed spikes and 19 HFOs on scalp recordings. In 15/19 patients highest scalp HFO rate was located over the implantation side, with 13 patients having the highest scalp and intracranial HFO rate over the same region. 17 patients underwent surgery, 7 became seizure free. Patients with poor post-operative outcome showed significantly more regions with HFO than those with seizure free outcome.ConclusionsScalp HFOs are mostly located over the SOZ. Widespread scalp HFOs are indicative of a larger epileptic network and associated with poor postsurgical outcome.SignificanceAnalysis of scalp HFO add clinically important information about the extent of epileptic areas during presurgical simultaneous scalp and intracranial EEG recordings.     

A ventromedial prefrontal dysrhythmia in obsessive-compulsive disorder is attenuated by nucleus accumbens deep brain stimulation

BackgroundObsessive-compulsive disorder (OCD) has consistently been linked to abnormal frontostriatal activity. The electrophysiological disruption in this circuit, however, remains to be characterized.Objective/hypothesisThe primary goal of this study was to investigate the neuronal synchronization in OCD patients. We predicted aberrant oscillatory activity in frontal regions compared to healthy control subjects, which would be alleviated by deep brain stimulation (DBS) of the nucleus accumbens (NAc).MethodsWe compared scalp EEG recordings from nine patients with OCD treated with NAc-DBS with recordings from healthy controls, matched for age and gender. Within the patient group, EEG activity was compared with DBS turned off vs. stimulation at typical clinical settings (3.5 V, frequency of stimulation 130 Hz, pulse width 60 μs). In addition, intracranial EEG was recorded directly from depth macroelectrodes in the NAc in four OCD patients.ResultsCross-frequency coupling between the phase of alpha/low beta oscillations and amplitude of high gamma was significantly increased over midline frontal and parietal electrodes in patients when stimulation was turned off, compared to controls. Critically, in patients, beta (16–25 Hz) -gamma (110–166 Hz) phase amplitude coupling source localized to the ventromedial prefrontal cortex, and was reduced when NAc-DBS was active. In contrast, intracranial EEG recordings showed no beta-gamma phase amplitude coupling. The contribution of non-sinusoidal beta waveforms to this coupling are reported.ConclusionWe reveal an increased beta-gamma phase amplitude coupling in fronto-central scalp sensors in patients suffering from OCD, compared to healthy controls, which may derive from ventromedial prefrontal regions implicated in OCD and is normalized by DBS of the nucleus accumbens. This aberrant cross-frequency coupling could represent a biomarker of OCD, as well as a target for novel therapeutic approaches.     

Scalp EEG interictal high frequency oscillations as an objective biomarker of infantile spasms

ObjectiveTo investigate the diagnostic utility of high frequency oscillations (HFOs) via scalp electroencephalogram (EEG) in infantile spasms.MethodsWe retrospectively analyzed interictal slow-wave sleep EEGs sampled at 2,000 Hz recorded from 30 consecutive patients who were suspected of having infantile spasms. We measured the rate of HFOs (80–500 Hz) and the strength of the cross-frequency coupling between HFOs and slow-wave activity (SWA) at 3–4 Hz and 0.5–1 Hz as quantified with modulation indices (MIs).ResultsTwenty-three patients (77%) exhibited active spasms during the overnight EEG recording. Although the HFOs were detected in all children, increased HFO rate and MIs correlated with the presence of active spasms (p < 0.001 by HFO rate; p < 0.01 by MIs at 3–4 Hz; p = 0.02 by MIs at 0.5–1 Hz). The presence of active spasms was predicted by the logistic regression models incorporating HFO-related metrics (AUC: 0.80–0.98) better than that incorporating hypsarrhythmia (AUC: 0.61). The predictive performance of the best model remained favorable (87.5% accuracy) after a cross-validation procedure.ConclusionsIncreased rate of HFOs and coupling between HFOs and SWA are associated with active epileptic spasms.SignificanceScalp-recorded HFOs may serve as an objective EEG biomarker for active epileptic spasms.     

Electrophysiological differences between upper and lower limb movements in the human subthalamic nucleus

ObjectiveFunctional processes in the brain are segregated in both the spatial and spectral domain. Motivated by findings reported at the cortical level in healthy participants we test the hypothesis in the basal ganglia of Parkinson’s disease patients that lower frequency beta band activity relates to motor circuits associated with the upper limb and higher beta frequencies with lower limb movements.MethodsWe recorded local field potentials (LFPs) from the subthalamic nucleus using segmented “directional” DBS leads, during which patients performed repetitive upper and lower limb movements. Movement-related spectral changes in the beta and gamma frequency-ranges and their spatial distributions were compared between limbs.ResultsWe found that the beta desynchronization during leg movements is characterised by a strikingly greater involvement of higher beta frequencies (24–31 Hz), regardless of whether this was contralateral or ipsilateral to the limb moved. The spatial distribution of limb-specific movement-related changes was evident at higher gamma frequencies.ConclusionLimb processing in the basal ganglia is differentially organised in the spectral and spatial domain and can be captured by directional DBS leads.SignificanceThese findings may help to refine the use of the subthalamic LFPs as a control signal for adaptive DBS and neuroprosthetic devices.     

High density microelectrode recording predicts span of therapeutic tissue activation volumes in subthalamic deep brain stimulation for Parkinson disease

BackgroundSubthalamic deep brain stimulation alleviates motor symptoms of Parkinson disease by activating precise volumes of neural tissue. While electrophysiological and anatomical correlates of clinically effective electrode sites have been described, therapeutic stimulation likely acts through multiple distinct neural populations, necessitating characterization of the full span of tissue activation. Microelectrode recordings have yet to be mapped to therapeutic tissue activation volumes and surveyed for predictive markers.ObjectiveCombine high-density, broadband microelectrode recordings with detailed computational models of tissue activation to describe and to predict regions of therapeutic tissue activation.MethodsElectrophysiological features were extracted from microelectrode recordings along 23 subthalamic deep brain stimulation implants in 16 Parkinson disease patients. These features were mapped in space against tissue activation volumes of therapeutic stimulation, modeled using clinically-determined stimulation programming parameters and fully individualized, atlas-independent anisotropic tissue properties derived from 3T diffusion tensor magnetic resonance images. Logistic LASSO was applied to a training set of 17 implants out of the 23 implants to identify predictors of therapeutic stimulation sites in the microelectrode recording. A support vector machine using these predictors was used to predict therapeutic activation. Performance was validated with a test set of six implants.ResultsAnalysis revealed wide variations in the distribution of therapeutic tissue activation across the microelectrode recording-defined subthalamic nucleus. Logistic LASSO applied to the training set identified six oscillatory predictors of therapeutic tissue activation: theta, alpha, beta, high gamma, high frequency oscillations (HFO, 200–400 Hz), and high frequency band (HFB, 500–2000 Hz), in addition to interaction terms: theta x HFB, alpha x beta, beta x HFB, and high gamma x HFO. A support vector classifier using these features predicted therapeutic sites of activation with 64% sensitivity and 82% specificity in the test set, outperforming a beta-only classifier. A probabilistic predictor achieved 0.87 area under the receiver-operator curve with test data.ConclusionsTogether, these results demonstrate the importance of personalized targeting and validate a set of microelectrode recording signatures to predict therapeutic activation volumes. These features may be used to improve the efficiency of deep brain stimulation programming and highlight specific neural oscillations of physiological importance.     

Recording cortico-cortical evoked potentials of the human arcuate fasciculus under general anaesthesia

ObjectiveWe examined the feasibility of using cortico-cortical evoked potentials (CCEPs) to monitor the major cortical white matter tract involved in language, the arcuate fasciculus (AF), during surgery under general anaesthesia.MethodsWe prospectively recruited nine patients undergoing surgery for lesions in the left peri-sylvian cortex, for whom awake surgery was not indicated. High angular resolution diffusion imaging (HARDI) tractography was used to localise frontal and temporal AF terminations, which guided intraoperative cortical strip placement.ResultsCCEPs were successfully evoked in 5/9 patients, showing a positive potential (P1) at 12 ms and a negative component (N1) at 21 ms when stimulating from the frontal lobe and recording in the temporal lobe. CCEP responses peaked in the posterior middle temporal gyrus. No CCEPs were evoked when stimulating temporal sites and recording from frontal contacts.ConclusionFor the first time, we show that CCEPs can be evoked from the peri-sylvian cortices also in adult patients who are not candidates for awake procedures. Our results are akin to those described in the awake setting and suggest the recorded activity is conveyed by the arcuate fasciculus.SignificanceThis intraoperative approach may have promising implications in reducing deficits in patients that require surgery in language areas under general anesthesia.     

A prewarning sign for hearing loss by brainstem auditory evoked potentials during microvascular decompression surgery for hemifacial spasm

ObjectiveWe aimed to define the prewarning sign of brainstem auditory evoked potentials (BAEPs) associated with cerebellar retraction (CR) during microvascular decompression surgery for hemifacial spasm.MethodsA total of 241 patients with a latency prolongation of 1 ms or an amplitude decrement of 50% of wave V were analyzed. According to BAEPs before significant changes during CR, patients were classified into Groups A (latency prolongation of wave I [≥0.5 ms] without prolongation of the I–III interpeak interval [<0.5 ms]) and B (no latency prolongation of wave I [<0.5 ms] with prolongation of the I–III interpeak interval [≥0.5 ms]). BAEPs and postoperative hearing loss (HL) were compared between the two groups.ResultsGroup B comprised 160 (66.4%) patients. With maximal changes in wave V, latency prolongation (≥1 ms) with amplitude decrement (≥50%) was more common in Group B (p < 0.018). At the end of the operation, wave V loss was observed in 11 patients, including 10 patients from Group B. Five patients developed postoperative HL; all were from Group B.ConclusionsLatency prolongation of wave III during CR was associated with serious BAEPs changes and postoperative HL.SignificanceLatency prolongation of wave III is a significant prewarning sign.     

Enlarged high frequency oscillations of the median nerve somatosensory evoked potential and survival in amyotrophic lateral sclerosis

ObjectiveA large N20 and P25 of the median nerve somatosensory evoked potential (SEP) predicts short survival in amyotrophic lateral sclerosis (ALS). We investigated whether high frequency oscillations (HFOs) over N20 are enlarged and associated with survival in ALS.MethodsA total of 145 patients with ALS and 57 healthy subjects were studied. We recorded the median nerve SEP and measured the onset-to-peak amplitude of N20 (N20o-p), and peak-to-peak amplitude between N20 and P25 (N20p-P25p). We obtained early and late HFO potentials by filtering SEP between 500 and 1 kHz, and measured the peak-to-peak amplitude. We followed up patients until endpoints (death or tracheostomy) and analyzed the relationship between SEP or HFO amplitudes and survival using a Cox analysis.ResultsPatients showed larger N20o-p, N20p-P25p, and early and late HFO amplitudes than the control values. N20p-P25p was associated with survival periods (p = 0.0004), while early and late HFO amplitudes showed no significant association with survival (p = 0.4307, and p = 0.6858, respectively).ConclusionsThe HFO amplitude in ALS is increased, but does not predict survival.SignificanceThe enlarged HFOs in ALS might be a compensatory phenomenon to the hyperexcitability of the sensory cortex pyramidal neurons.     

High frequency oscillations relate to cognitive improvement after epilepsy surgery in children

ObjectiveTo investigate how high frequency oscillations (HFOs; ripples 80–250 Hz, fast ripples (FRs) 250–500 Hz) and spikes in intra-operative electrocorticography (ioECoG) relate to cognitive outcome after epilepsy surgery in children.MethodsWe retrospectively included 20 children who were seizure free after epilepsy surgery using ioECoG and determined their intelligence quotients (IQ) pre- and two years postoperatively. We analyzed whether the number of HFOs and spikes in pre- and postresection ioECoGs, and their change in the non-resected areas relate to cognitive improvement (with ≥ 5 IQ points increase considered to be clinically relevant (=IQ+ group) and < 5 IQ points as irrelevant (=IQ− group)).ResultsThe IQ+ group showed significantly more FRs in the resected tissue (p = 0.01) and less FRs in the postresection ioECoG (p = 0.045) compared to the IQ− group. Postresection decrease of ripples on spikes was correlated with postoperative cognitive improvement (correlation coefficient = −0.62 with p = 0.01).ConclusionsPostoperative cognitive improvement was related to reduction of pathological HFOs signified by removing FR generating areas with subsequently less residual FRs, and decrease of ripples on spikes in the resection edge of the non-resected area.SignificanceHFOs recorded in ioECoG could play a role as biomarkers in the prediction and understanding of cognitive outcome after epilepsy surgery.     

Neuromodulation effects of deep brain stimulation on beta rhythm: A longitudinal local field potential study

BackgroundDeep brain stimulation (DBS) holds great promise in treating various brain diseases but its chronic therapeutic mechanisms are unclear.ObjectiveTo explore the immediate and chronic effects of DBS on brain oscillations, and understand how different sub-bands of oscillations may be related to symptom improvement in Parkinson's patients.MethodsWe carried out a longitudinal study to examine the effects of DBS on local field potentials recorded by sensing-enabled neurostimulators in the subthalamic nuclei of Parkinson's patients, using a novel block-design stimulation paradigm.ResultsDBS significantly suppressed beta activity (13–35Hz) but the suppression effect appeared to gradually attenuate during a 6-month follow-up period after surgery (p = 0.002). However, beta suppression did not attenuate after repeated stimulation over several minutes (p > 0.110), suggesting that the changes in beta suppression may reflect a slow reconfiguration of neural pathways instead of habituation. Suppression of beta was also associated with clinical symptom improvement across subjects. Importantly, symptom-relevant features fell within the high beta band at month 1 but shifted to the low beta band at month 6, indicating that the high beta and the low beta oscillations may play different functional roles and respond differently to stimulation over the long-term treatment.ConclusionThese data may advance understanding of chronic DBS effects on beta oscillations and their association with clinical improvement, offering novel insights to the therapeutic mechanisms of DBS.     

Differentiating transcranial magnetic stimulation cortical and auditory responses via single pulse and paired pulse protocols: A TMS-EEG study

ObjectiveWe measured the neurophysiological responses of both active and sham transcranial magnetic stimulation (TMS) for both single pulse (SP) and paired pulse (PP; long interval cortical inhibition (LICI)) paradigms using TMS-EEG (electroencephalography).MethodsNineteen healthy subjects received active and sham (coil 90° tilted and touching the scalp) SP and PP TMS over the left dorsolateral prefrontal cortex (DLPFC). We measured excitability through SP TMS and inhibition (i.e., cortical inhibition (CI)) through PP TMS.ResultsCortical excitability indexed by area under the curve (AUC_(25-275ms)) was significantly higher in the active compared to sham stimulation (F(1,18) = 43.737, p < 0.001, η² = 0.708). Moreover, the amplitude of N100-P200 complex was significantly larger (F(1,18) = 9.118, p < 0.01, η² = 0.336) with active stimulation (10.38 ± 9.576 µV) compared to sham (4.295 ± 2.323 µV). Significant interaction effects were also observed between active and sham stimulation for both the SP and PP (i.e., LICI) cortical responses. Finally, only active stimulation (CI = 0.64 ± 0.23, p < 0.001) resulted in significant cortical inhibition.ConclusionThe significant differences between active and sham stimulation in both excitatory and inhibitory neurophysiological responses showed that active stimulation elicits responses from the cortex that are different from the non-specific effects of sham stimulation.SignificanceOur study reaffirms that TMS-EEG represents an effective tool to evaluate cortical neurophysiology with high fidelity.     

Excessive short-latency stretch reflexes in the calf muscles do not cause postural instability in patients with hereditary spastic paraplegia

ObjectiveTo identify the role of hyperexcitable short-latency stretch reflexes (SLRs) on balance control in people with hereditary spastic paraplegia (PwHSP).MethodsSixteen PwHSP with triceps surae spasticity and 9 healthy control subjects were subjected to toes-up support-surface perturbations. EMG data were recorded from gastrocnemius, soleus and tibialis anterior. Furthermore, center-of-mass trajectories were recorded.ResultsPwHSP were less able to withstand the perturbations. Triceps surae SLRs (40–80 ms post perturbation) in PwHSP were increased compared to healthy subjects. Furthermore, a sustained triceps surae EMG activity at 220–320 ms post perturbation was observed in PwHSP, whereas control subjects demonstrated suppression of triceps surae activity. Center of mass trajectories started to diverge between PwHSP and controls only after ∼500 ms, with greater excursions being observed in the PwHSP.ConclusionsThe present results confirm that balance control is impaired in PwHSP. However, the late instant of center of mass divergence argues against a direct, causative role of hyperexcitable SLRs in the triceps surae.SignificanceWe postulate that enhanced short-latency stretch reflexes of the triceps surae do not underlie poor balance control in PwHSP. Instead, we suggest the lack of suppression of later triceps surae activity to be the main cause.     

Ictal gamma-band interactions localize ictogenic nodes of the epileptic network in focal cortical dysplasia

ObjectiveEpilepsy surgery fails in > 30% of patients with focal cortical dysplasia (FCD). The seizure persistence after surgery can be attributed to the inability to precisely localize the tissue with an endogenous potential to generate seizures. In this study, we aimed to identify the critical components of the epileptic network that were actively involved in seizure genesis.MethodsThe directed transfer function was applied to intracranial EEG recordings and the effective connectivity was determined with a high temporal and frequency resolution. Pre-ictal network properties were compared with ictal epochs to identify regions actively generating ictal activity and discriminate them from the areas of propagation.ResultsAnalysis of 276 seizures from 30 patients revealed the existence of a seizure-related network reconfiguration in the gamma-band (25–170 Hz; p < 0.005) – ictogenic nodes. Unlike seizure onset zone, resecting the majority of ictogenic nodes correlated with favorable outcomes (p < 0.012).ConclusionThe prerequisite to successful epilepsy surgery is the accurate identification of brain areas from which seizures arise. We show that in FCD-related epilepsy, gamma-band network markers can reliably identify and distinguish ictogenic areas in macroelectrode recordings, improve intracranial EEG interpretation and better delineate the epileptogenic zone.SignificanceIctogenic nodes localize the critical parts of the epileptogenic tissue and increase the diagnostic yield of intracranial evaluation.     

Intermuscular coherence as biomarker for pallidal deep brain stimulation efficacy in dystonia

ObjectiveFinding a non-invasive biomarker for Globus Pallidus interna Deep Brain Stimulation (GPi-DBS) efficacy. Dystonia heterogeneity leads to a wide variety of clinical response to GPi-DBS, making it hard to predict GPi-DBS efficacy for individual patients.MethodsEEG-EMG recordings of twelve dystonia patients who received bilateral GPi-DBS took place pre- and 1 year post-surgery ON and OFF stimulation, during a rest, pinch, and flexion task. Dystonia severity was assessed using the BFMDRS and TWSTRS (pre- and post-surgery ON stimulation). Intermuscular coherence (IMC) and motorcortex corticomuscular coherence (CMC) were calculated. Low frequency (4–12 Hz) and beta band (13–30 Hz) peak coherences were studied.ResultsDystonia severity improved after 1 year GPi-DBS therapy (BFMDRS: 30%, median 7.8 (IQR 3–10), TWSTRS: 22%, median 6.8 (IQR 4–9)). 86% of IMC were above the 95% confidence limit. The highest IMC peak decreased significantly with GPi-DBS in the low frequency and beta band. Low frequency and beta band IMC correlated partly with dystonia severity and severity improvement. CMC generally were below the 95% confidence limit.ConclusionsPeak low frequency IMC functioned as biomarker for GPi-DBS efficacy, and partly correlated with dystonia severity.SignificanceIMC can function as biomarker. Confirmation in a larger study is needed for use in clinical practice.     

Quantitative electroencephalography characteristics of tilt-induced neurally-mediated syncope among youth

ObjectiveTo characterize the quantitative electroencephalographic (QEEG) patterns associated with tilt-induced syncope in youth.MethodsSeveral QEEG parameters were analyzed. Data were calculated for peak or nadir changes with syncope for amplitude-EEG, fast Fourier transform (FFT) power in several frequency ranges, 8–13 Hz/1–4 Hz frequency ratio, and FFT edge.ResultsChanges in QEEG parameters were present among all patients with tilt-induced syncope (n = 76). These changes included increases in the low frequency FFT power (1–4 Hz range), decreases in the power ratio (8–13 Hz/1–4 Hz) and decreases in the FFT edge (95%, 1–18 Hz). All patients had suppression of EEG amplitudes that closely followed loss of consciousness. Asymmetry indices demonstrated cerebral hemisphere lateralization at multiple periods during the evolution of syncope, but the side of lateralization did not differ from 0.5 probability.ConclusionsQEEG parameters can be used to characterize EEG changes associated with tilt-induced, neurally-mediated syncope.SignificanceQEEG may serve as a useful tool for the study of syncope neurophysiology, and the modeling of changes with syncope may improve our understanding of other neurologic disorders caused by defects in cerebral perfusion.     

Single stage epilepsy surgery in children and adolescents with focal cortical dysplasia type II – Prognostic value of the intraoperative electrocorticogram

ObjectiveTo evaluate prospectively the informative/prognostic value of epileptic discharges in the post-resection ECoGs of children with drug-resistant epilepsies and Focal Cortical Dysplasia type II (FCD-II).MethodsIncluded were consecutive patients with focal epilepsies and suspected FCD-II who were planned for single-stage epilepsy surgery based on non-invasive presurgical evaluation results. Intraoperative ECoGs were recorded using a 32-channel system with strip- and/or grid-electrodes. Spikes were defined as transients with a mainly negative component and duration of 20–70 ms. Fast activity was defined as rhythmic bursts of polyspikes >13 Hz. All ECoGs were analysed visually. The significance of both spikes and fast activity in the post-resection ECoG for seizure outcomes 24 months after surgery was evaluated.ResultsData from 18 patients (five girls) were analysed. 10/18 patients (55.6%) showed spikes in their post-resection ECoGs, five of them showed additional fast activity. 24 months after surgery, 12/18 patients (66.7%) were seizure-free. There was a significant correlation between unfavorable seizure outcomes and fast activity in the post-resection ECoGs (p = 0.009), whereas spikes alone were not predictive (p = 0.502).ConclusionEven when recorded with non-sophisticated techniques, presence of fast activity in post-resection ECoGs might be a valid negative outcome-predictor after surgery in paediatric patients with FCD-II associated drug-resistant epilepsies.SignificanceFast activity recorded with a relatively simple ECoG equipment seems also to have prognostic significance and by this might be an alternative to HFOs recorded with highly sophisticated and expensive technologies.     

Phase-amplitude coupling of ripple activities during seizure evolution with theta phase

ObjectiveHigh-frequency activities (HFAs) and phase-amplitude coupling (PAC) are key neurophysiological biomarkers for studying human epilepsy. We aimed to clarify and visualize how HFAs are modulated by the phase of low-frequency bands during seizures.MethodsWe used intracranial electrodes to record seizures of focal epilepsy (12 focal-to-bilateral tonic-clonic seizures and three focal-aware seizures in seven patients). The synchronization index, representing PAC, was used to analyze the coupling between the amplitude of ripples (80–250 Hz) and the phase of lower frequencies. We created a video in which the intracranial electrode contacts were scaled linearly to the power changes of ripple.ResultsThe main low frequency band modulating ictal-ripple activities was the θ band (4–8 Hz), and after completion of ictal-ripple burst, δ (1–4 Hz)-ripple PAC occurred. The ripple power increased simultaneously with rhythmic fluctuations from the seizure onset zone, and spread to other regions.ConclusionsRipple activities during seizure evolution were modulated by the θ phase. The PAC phenomenon was visualized as rhythmic fluctuations.SignificanceRipple power associated with seizure evolution increased and spread with fluctuations. The θ oscillations related to the fluctuations might represent the common neurophysiological processing involved in seizure generation.     

Engagement of cortico-cortical and cortico-subcortical networks in a patient with epileptic spasms: An integrated neurophysiological study

ObjectiveWe aimed to delineate the engagement of cortico-cortical and cortico-subcortical networks in the generation of epileptic spasms (ES) using integrated neurophysiological techniques.MethodsSeventeen-year-old male patient with intractable ES underwent chronic subdural electrode implantation for presurgical evaluation. Networks were evaluated in ictal periods using high-frequency oscillation (HFO) analysis and in interictal periods using magnetoencephalography (MEG) and simultaneous electroencephalography, and functional magnetic resonance imaging (EEG-fMRI). Cortico-cortical evoked potentials (CCEPs) were recorded to trace connections among the networks.ResultsIctal HFO revealed a network comprising multilobar cortical regions (frontal, parietal, and temporal), but sparing the positive motor area. Interictally, MEG and EEG-fMRI revealed spike-and-wave-related activation in these cortical regions. Analysis of CCEPs provided evidence of connectivity within the cortico-cortical network. Additionally, EEG-fMRI results indicate the involvement of subcortical structures, such as bilateral thalamus (predominantly right) and midbrain.ConclusionsIn this case study, integrated neurophysiological techniques provided converging evidence for the involvement of a cortico-cortical network (sparing the positive motor area) and a cortico-subcortical network in the generation of ES in the patient.SignificanceCortico-cortical and cortico-subcortical pathways, with the exception of the direct descending corticospinal pathway from the positive motor area, may play important roles in the generation of ES.     

Seizure onset location shapes dynamics of initiation

ObjectiveIctal electrographic patterns are widely thought to reflect underlying neural mechanisms of seizures. Here we studied the degree to which seizure patterns are consistent in a given patient, relate to particular brain regions and if two candidate biomarkers (high-frequency oscillations, HFOs; infraslow activity, ISA) and network activity, as assessed with cross-frequency interactions, can discriminate between seizure types.MethodsWe analyzed temporal changes in low and high frequency oscillations recorded during seizures, as well as phase-amplitude coupling (PAC) to monitor the interactions between delta/theta and ripple/fast ripple frequency bands at seizure onset.ResultsSeizures of multiple electrographic patterns were observed in a given patient and brain region. While there was an increase in HFO rate across different electrographic patterns, there are specific relationships between types of HFO activity and onset region. Similarly, changes in PAC dynamics were more closely related to seizure onset region than they were to electrographic patterns while ISA was a poor indicator for seizure onset.ConclusionsOur findings suggest that the onset region sculpts neurodynamics at seizure initiation and that unique features of the cytoarchitecture and/or connectivity of that region play a significant role in determining seizure mechanism.SignificanceTo learn how seizures are initiated, researchers would do well to consider other aspects of their manifestation, in addition to their electrographic patterns. Examination of onset pattern in conjunction with the interactions between different oscillatory frequencies in the context of different brain regions might be more informative and lead to more reliable clinical inference as well as novel therapeutic approaches.     

Relationship between high-frequency activity in the cortical sensory and the motor hand areas,and their myelin content

BackgroundThe human primary sensory (S1) and primary motor (M1) hand areas feature high-frequency neuronal responses. Electrical nerve stimulation evokes high-frequency oscillations (HFO) at around 650 Hz in the contralateral S1. Likewise, transcranial magnetic stimulation (TMS) of M1 can evoke a series of descending volleys in the corticospinal pathway that can be detected non-invasively with a paired-pulse TMS protocol, called short interval intracortical facilitation (SICF). SICF features several peaks of facilitation of motor evoked potentials in contralateral hand muscles, which are separated by inter-peak intervals resembling HFO rhythmicity.HypothesisIn this study, we tested the hypothesis that the individual expressions of HFO and SICF are tightly related to each other and to the regional myelin content in the sensorimotor cortex.MethodsIn 24 healthy volunteers, we recorded HFO and SICF, and, in a subgroup of 20 participants, we mapped the cortical myelin content using the ratio between the T1- and T2-weighted MRI signal as read-out.ResultsThe individual frequencies and magnitudes of HFO and SICF curves were tightly correlated: the intervals between the first and second peak of cortical HFO and SICF showed a positive linear relationship (r = 0.703, p < 0.001), while their amplitudes were inversely related (r = ?0.613, p = 0.001). The rhythmicity, but not the magnitude of the high-frequency responses, was related to the cortical myelin content: the higher the cortical myelin content, the shorter the inter-peak intervals of HFO and SICF.ConclusionThe results confirm a tight functional relationship between high-frequency responses in S1 (i.e., HFO) and M1 (i.e., as measured with SICF). They also establish a link between the degree of regional cortical myelination and the expression of high-frequency responses in the human sensorimotor cortex, giving further the opportunity to infer their generators.