Paired Acute Invasive/Non-invasive Stimulation (PAINS) study: A phase I/II randomized,sham-controlled crossover trial in chronic neuropathic pain

BackgroundDorsal root ganglion (DRG) stimulation, an invasive method of neuromodulation, and transcranial direct current stimulation (tDCS), a non-invasive method of altering cortical excitability, have both proven effective in relieving chronic pain.ObjectiveWe employed a randomized, sham-controlled crossover study design to investigate whether single-session tDCS would have an additive therapeutic effect alongside DRG stimulation (DRGS) in the treatment of chronic pain.MethodsSixteen neuropathic pain patients who were previously implanted with DRG stimulators were recruited. Baseline pain scores were established with DRGS-OFF. Pain scores were then recorded with DRGS-ON, after paired sham tDCS stimulation, and after paired active anodal tDCS (a-tDCS) stimulation. For active tDCS, patients were randomized to ‘MEG (magnetoencephalography) localized’ tDCS or contralateral motor cortex (M1) tDCS for 30 min. EEG recordings and evaluations of tDCS adverse effects were also collected.ResultsAll participants reported the interventions to be tolerable with no significant adverse effects during the session. Paired DRGS/active tDCS resulted in a significant reduction in pain scores compared to paired DRGS-ON/sham tDCS or DRGS alone. There was no difference in the additive effect of M1 vs. MEG-localized tDCS. Significant augmentation of beta activity was observed between DRGS-OFF and DRGS-ON conditions, as well as between paired DRGS-ON/sham tDCS and paired DRGS-ON/active tDCS.ConclusionOur results indicate that a single session of tDCS alongside DRGS is safe and can significantly reduce pain acutely in neuropathic pain patients. Paired invasive/non-invasive neuromodulation is a promising new treatment strategy for pain management and should be evaluated further to assess long-term benefits.     

Transcranial random noise stimulation is more effective than transcranial direct current stimulation for enhancing working memory in healthy individuals: Behavioural and electrophysiological evidence

BackgroundTranscranial direct current stimulation (tDCS) has been shown to improve working memory (WM) performance in healthy individuals, however effects tend to be modest and variable. Transcranial random noise stimulation (tRNS) can be delivered with a direct-current offset (DC-offset) to induce equal or even greater effects on cortical excitability than tDCS. To-date, no research has directly compared the effects of these techniques on WM performance or underlying neurophysiological activity.ObjectiveTo compare the effects of anodal tDCS, tRNS + DC-offset, or sham stimulation over the left dorsolateral prefrontal cortex (DLPFC) on WM performance and task-related EEG oscillatory activity in healthy adults.MethodsUsing a between-subjects design, 49 participants were allocated to receive either anodal tDCS (N = 16), high-frequency tRNS + DC-offset (N = 16), or sham stimulation (N = 17) to the left DLPFC. Changes in WM performance were assessed using the Sternberg WM task completed before and 5- and 25-min post-stimulation. Event-related synchronisation/desynchronisation (ERS/ERD) of oscillatory activity was analysed from EEG recorded during WM encoding and maintenance.ResultstRNS induced more pronounced and consistent enhancements in WM accuracy when compared to both tDCS and sham stimulation. Improvements in WM performance following tRNS were accompanied by increased theta ERS and diminished gamma ERD during WM encoding, which were significantly greater than those observed following anodal tDCS or sham stimulation.ConclusionsThese findings demonstrate the potential of tRNS + DC-offset to modulate cognitive and electrophysiological measures of WM and raise the possibility that tRNS + DC-offset may be more effective and reliable than tDCS for enhancing WM performance in healthy individuals.     

Transcranial Direct Current Stimulation for Treatment of Refractory Childhood Focal Epilepsy

BackgroundCathodal transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation method for suppressing regional cortical excitability. We examine the safety and antiepileptic efficacy of cathodal tDCS in children with refractory focal epilepsy. Although a prior cathodal tDCS trial in adults with epilepsy revealed EEG improvement, neither the antiepileptic potential nor the safety and tolerability of tDCS has been tested in children.MethodThe study consisted of three phases: 1) a 4-week pre-treatment monitoring period with vital sign measures, EEG, seizure diary, and baseline quality of life (QOL) questionnaire; 2) a single treatment with 1 mA cathodal tDCS for 20 min with cathode positioned over the seizure focus and anode on the contralateral shoulder; 3) follow-ups immediately after stimulation, and at 24, 48 h, and 4 weeks after tDCS with continued seizure diary and epileptic discharge counts on EEG; the QOL questionnaire was also repeated 4 weeks after stimulation. Patients were randomized to receive either single session active or sham tDCS 1 mA, 20 min.ResultsThirty six children (6–15 years) with focal epilepsy were enrolled, 27 in active and 9 in sham group. All patients tolerated tDCS well. No serious adverse events occurred. Active tDCS treatment was associated with significant reductions in epileptic discharge frequency immediately and 24 and 48 h after tDCS. Four weeks after treatment, a small (clinically negligible but statistically significant) decrease in seizure frequency was also detected.ConclusionA single session of cathodal tDCS improves epileptic EEG abnormalities for 48 h and is well-tolerated in children.     

Effects of anodal tDCS on lumbar propriospinal system in healthy subjects

ObjectiveIt has recently been shown that transcranial direct current stimulation (tDCS) (1) can modify lumbar spinal network excitability and (2) decreases cervical propriospinal system excitability. Thus the purpose of this series of experiments was to determine if anodal tDCS applied over the leg motor cortex area induces changes in lumbar propriospinal system excitability. To that end, the effects of anodal tDCS and sham tDCS on group I and group II propriospinal facilitation of quadriceps motoneurones were studied in healthy subjects.MethodsCommon peroneal nerve group I and group II quadriceps H-reflex facilitation was assessed in 15 healthy subjects in two randomised conditions: anodal tDCS condition and sham tDCS condition. Recordings were performed before, during and after the end of the cortical stimulation.ResultsCompared to sham, anodal tDCS decreases significantly CPN-induced group I and II quadriceps H-reflex facilitation during and also after the end of the cortical stimulation.ConclusionsAnodal tDCS induces (1) modulation of lumbar propriospinal system excitability (2) post-effects on spinal network.SignificanceThese results open a new vista to regulate propriospinal lumbar system excitability in patients and suggest that anodal tDCS would be interesting for neuro-rehabilitation of patients with central nervous system lesions.     

Kainic acid induced hippocampal seizures in rats: comparisons of acute and chronic seizures using intrahippocampal versus systemic injections

Hyppocampal epilepsy is a recently defined syndrome occurring in 65% of all temporal lobe epilepsies as defined by: 1) electrographic (EEG) onset in the hippocampus (HC) prior to EEG seizures elsewhere, 2) post-resection hippocampal sclerosis and mossy fiber synaptic reorganizations and 3) relief of typical complex partial seizures after surgical resection of the hyppocampus. We used intrahippocampal kainic acid injections V² in rats at different developmental ages (postnatal 7 through adult) to develop long term spontaneous HC EEG spikes, EEG seizures, and behavioral seizures. Split-screen video/EEG monitoring demonstrated that this intrahippocampal kainic acid model produced progressive development of: 1) ipsilateral interictal spikes, 2) later polyspike complexes, 3) bilaterally-asynchronous EEG spiking, 4) unilateral HC EEG seizure onsets with occasional secondarily generalized spread to apposite HC and motor cortex to elicit complex partial seizures, and 5) in all seizing rats there was mossy fiber synaptic reorganization, even when injected at age 7 days. These results indicate that the intrahippocampal kainic acid injection model is similar to human hippocampal epilepsy.Supported by NIH Grants NS 02808, NS 31655 (T.L.B.); K08 NS 1603 (G.W.M.); and Fogarty Fellowship TWO 4959 (J.P.L.).     

EEG oscillations and magnetically evoked motor potentials reflect motor system excitability in overlapping neuronal populations

ObjectiveTo understand the relationship between neuronal excitability reflected by transcranial magnetic stimulation (TMS) evoked motor potentials (MEPs) and spontaneous oscillation amplitude and phase.MethodsWe combined spontaneous EEG measurement with motor cortex TMS and recorded MEP amplitudes from abductor digiti minimi (ADM).ResultsMidrange-beta oscillations over the stimulated left motor cortex were, on average, weaker before large- than small-amplitude MEPs. The phase of occipital midrange-beta oscillations was related to the MEP amplitudes.ConclusionsThe present results support the view that MEP and Rolandic beta oscillation amplitudes are associated with motor cortical excitability. However, oscillations seen in EEG reflect the excitability of a large population of cortical neurons, and MEP amplitude is affected also by spinal excitability and action potential desynchronization. Thus, MEP and EEG oscillation amplitudes are not strongly correlated. In addition, even during rest, motor system excitability appears to be related to activity in occipital areas at frequency ranges associated with visuomotor processing.SignificanceThe ability of spontaneous oscillations and MEPs to inform us about cortical excitability is clarified. For example, it is suggested that oscillatory activity at non-motor sites might be related to motor system excitability at rest.     

Can individually targeted and optimized multi-channel tDCS outperform standard bipolar tDCS in stimulating the primary somatosensory cortex?

BackgroundTranscranial direct current stimulation (tDCS) has emerged as a non-invasive neuro-modulation technique. Most studies show that anodal tDCS increases cortical excitability, however, with variable outcomes. Previously, we have shown in computer simulations that our multi-channel tDCS (mc-tDCS) approach, the distributed constrained maximum intensity (D-CMI) method can potentially lead to better controlled tDCS results due to the improved directionality of the injected current at the target side for individually optimized D-CMI montages.ObjectiveIn this study, we test the application of the D-CMI approach in an experimental study to stimulate the somatosensory P20/N20 target source in Brodmann area 3b and compare it with standard bipolar tDCS and sham conditions.MethodsWe applied anodal D-CMI, the standard bipolar and D-CMI based Sham tDCS for 10 min to target the 20 ms post-stimulus somatosensory P20/N20 target brain source in Brodmann area 3b reconstructed using combined magnetoencephalography (MEG) and electroencephalography (EEG) source analysis in realistic head models with calibrated skull conductivity in a group-study with 13 subjects. Finger-stimulated somatosensory evoked fields (SEF) were recorded and the component at 20 ms post-stimulus (M20) was analyzed before and after the application of the three tDCS conditions in order to read out the stimulation effect on Brodmann area 3b.ResultsAnalysis of the finger stimulated SEF M20 peak before (baseline) and after tDCS shows a significant increase in source amplitude in Brodmann area 3b for D-CMI (6–16 min after tDCS), while no significant effects are found for standard bipolar (6–16 min after tDCS) and sham (6–16 min after tDCS) stimulation conditions. For the later time courses (16–26 and 27–37 min post-stimulation), we found a significant decrease in M20 peak source amplitude for standard bipolar and sham tDCS, while there was no effect for D-CMI.ConclusionOur results indicate that targeted and optimized, and thereby highly individualized, mc-tDCS can outperform standard bipolar stimulation and lead to better control over stimulation outcomes with, however, a considerable amount of additional work compared to standard bipolar tDCS.     

Corticospinal excitability enhancement with simultaneous transcranial near-infrared stimulation and anodal direct current stimulation of motor cortex

ObjectivesNon-invasive brain stimulation (NIBS) is beneficial to many neurological and psychiatric disorders by modulating neuroplasticity and cortical excitability. However, recent studies evidence that single type of NIBS such as transcranial direct current stimulation (tDCS) does not have meaningful clinical therapeutic responses due to their small effect size. Transcranial near-infrared stimulation (tNIRS) is a novel form of NIBS. Both tNIRS and tDCS implement its therapeutic effects by modulating cortical excitability but with different mechanisms. We hypothesized that simultaneous tNIRS and tDCS is superior to single stimulation, leading to a greater cortical excitability.MethodsSixteen healthy subjects participated in a double-blind, sham-controlled, cross-over designed study. Motor evoked potentials (MEPs) were used to measure motor cortex excitability. The changes of MEP were calculated and compared in the sham condition, tDCS stimulation condition, tNIRS condition and the simultaneous tNIRS and anodal tDCS condition.ResultstDCS alone and tNIRS alone both elicited higher MEP after stimulation, while the MEP amplitude in the simultaneous tNIRS and tDCS condition was significantly higher than either tNIRS alone or tDCS alone. The enhancement lasted up to at least 30 minutes after stimulation, indicating simultaneous 820 nm tNIRS with 2 mA anodal tDCS have a synergistic effect on cortical plasticity.ConclusionsSimultaneous application of tNIRS with tDCS produces a stronger cortical excitability effect.SignificanceThe simultaneous tNIRS and tDCS is a promising technology with exciting potential as a means of treatment, neuro-enhancement, or neuro-protection.     

Repetitive anodal transcranial direct current stimulation improves neurological recovery by preserving the neuroplasticity in an asphyxial rat model of cardiac arrest

BackgroundNon-shockable rhythms present an increasing proportion of out-of-hospital cardiac arrest (CA) patients, but are associated with poor prognosis and received limited therapeutic effect of targeted temperature management (TTM). Previous study showed repetitive anodal transcranial direct current stimulation (tDCS) improved neurological outcomes in animals with ventricular fibrillation. Here, we examine the effectiveness of tDCS on neurological recovery and the potential mechanisms in a rat model of asphyxial CA.MethodCardiopulmonary resuscitation was initiated after 5 min of untreated asphyxial CA. Animals were randomized to three experimental groups immediately after successful resuscitation (n = 12/group, 6 males): no-treatment control (NTC) group, TTM group, and tDCS group. Post resuscitation hemodynamics, quantitative electroencephalogram (EEG), neurological deficit score, and 96-h survival were evaluated. Brain tissues of additional animals undergoing same experimental procedure was harvested for enzyme-linked immunoassay-based quantification assays of neuroplasticity-related biomarkers and compared with the sham-operated rats (n = 6/group).ResultsWe observed that after resuscitation tDCS-treated animals exhibited significantly higher mean arterial pressure and left ventricular ejection fraction than NTC group and showed greatly improved EEG characteristics including weighted-permutation entropy and gamma band power, and neurologic deficit scores and 96-h survival rates compared to NTC and TTM groups. Furthermore, neuroplastic biomarkers including microtubule-associated protein 2, growth-associated protein 43, postsynaptic density protein 95 and synaptophysin, were significantly higher in tDCS group when compared with NTC and TTM groups.ConclusionIn this rat model of asphyxial CA, repetitive anodal tDCS commenced after resuscitation improved neurological recovery, and it may exert a neuroprotective effect by preserving the neuroplasticity.     

Spike patterns surrounding sleep and seizures localize the seizure-onset zone in focal epilepsy

Objective

Interictal spikes help localize seizure generators as part of surgical planning for drug-resistant epilepsy. However, there are often multiple spike populations whose frequencies change over time, influenced by brain state. Understanding state changes in spike rates will improve our ability to use spikes for surgical planning. Our goal was to determine the effect of sleep and seizures on interictal spikes, and to use sleep and seizure-related changes in spikes to localize the seizure-onset zone (SOZ).

Methods

We performed a retrospective analysis of intracranial electroencephalography (EEG) data from patients with focal epilepsy. We automatically detected interictal spikes and we classified different time periods as awake or asleep based on the ratio of alpha to delta power, with a secondary analysis using the recently published SleepSEEG algorithm. We analyzed spike rates surrounding sleep and seizures. We developed a model to localize the SOZ using state-dependent spike rates.

Results

We analyzed data from 101 patients (54 women, age range 16–69). The normalized alpha-delta power ratio accurately classified wake from sleep periods (area under the curve = .90). Spikes were more frequent in sleep than wakefulness and in the post-ictal compared to the pre-ictal state. Patients with temporal lobe epilepsy had a greater wake-to-sleep and pre- to post-ictal spike rate increase compared to patients with extra-temporal epilepsy. A machine-learning classifier incorporating state-dependent spike rates accurately identified the SOZ (area under the curve = .83). Spike rates tended to be higher and better localize the seizure-onset zone in non–rapid eye movement (NREM) sleep than in wake or REM sleep.

Significance

The change in spike rates surrounding sleep and seizures differs between temporal and extra-temporal lobe epilepsy. Spikes are more frequent and better localize the SOZ in sleep, particularly in NREM sleep. Quantitative analysis of spikes may provide useful ancillary data to localize the SOZ and improve surgical planning.     

Effects of multisite anodal transcranial direct current stimulation combined with cognitive stimulation in patients with Alzheimer's disease and its neurophysiological correlates: A double-blind randomized clinical trial

ObjectivesWe aimed to examine the effects of multisite anodal transcranial direct current stimulation (tDCS) combined with cognitive stimulation (CS) over 2 months on cognitive performance and brain activity, and the relationship between them, in patients with Alzheimer's disease (AD).MethodsPatients with AD were randomly assigned to an active tDCS+CS (n=18) or a sham tDCS+CS (n=18) group. Cognitive performance was assessed using the Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog) and brain activity using EEG (spectral power and coherence analysis) before and after the intervention. Multisite anodal tDCS (2 mA, 30 min) was applied over six brain regions [left and right dorsolateral prefrontal cortex (F3 and F4), Broca's area (F5), Wernicke's area (CP5), left and right somatosensory association cortex (P3 and P4)] for 24 sessions (three times a week). Both groups performed CS during tDCS.ResultsAnodal tDCS+CS delays cognitive decline (ADAS-cog change) to a greater extent than sham tDCS+CS (-3.4±1.1 vs. -1.7±0.4; p=.03). Bilateral EEG coherence at high and low frequencies was greater for the active tDCS+CS than sham+CS group for most electrode pairs assessed (p < .05). The post-intervention ADAS-cog change score was predictive for EEG coherence at different sites (R²=.59 to .68; p < .05) in the active but not in the sham tDCS+CS group.ConclusionAnodal tDCS+CS improved overall cognitive function and changed EEG brain activity compared to sham tDCS+CS. Changes in cognitive performance were associated with changes in EEG measures of brain activity. Anodal tDCS+CS appears to be a promising therapeutic strategy to modulate cortical activity and improve cognitive function in patients with AD.     

Interaction Between Simultaneously Applied Neuromodulatory Interventions in Humans

BackgroundTranscranial direct current stimulation (tDCS) is a neuromodulatory technique with the potential to enhance the efficacy of traditional therapies such as neuromuscular electrical stimulation (NMES). Yet, concurrent application of tDCS/NMES may also activate homeostatic mechanisms that block or reverse effects on corticomotor excitability. It is unknown how tDCS and NMES interact in the human primary motor cortex (M1) and whether effects are summative (increase corticomotor excitability beyond that of tDCS or NMES applied alone) or competitive (block or reduce corticomotor excitability effects of tDCS or NMES applied alone).ObjectiveTo investigate corticomotor excitability in response to NMES after concurrent application of tDCS protocols that enhance (anodal tDCS) or suppress (cathodal tDCS) excitability of M1.MethodsWe used transcranial magnetic stimulation (TMS) to examine corticomotor excitability before and after the concurrent application of: i) NMES with anodal tDCS; and ii) NMES with cathodal tDCS. Effects were contrasted to four control conditions: i) NMES alone, ii) anodal tDCS alone, iii) cathodal tDCS alone, and iv) sham stimulation.ResultsConcurrent application of two protocols that enhance excitability when applied alone (NMES and anodal tDCS) failed to induce summative effects on corticomotor excitability, as predicted by homeostatic plasticity mechanisms. Combined cathodal tDCS and NMES suppressed the enhanced excitation induced by NMES, an effect that might be explained by calcium dependent anti-gating models.ConclusionsThese novel findings highlight the complex mechanisms involved when two neuromodulatory techniques are combined and suggest that careful testing of combined interventions is necessary before application in clinical contexts.     

Behavioural and electrophysiological effects of tDCS to prefrontal cortex in patients with disorders of consciousness

ObjectivesLeft dorsolateral prefrontal cortex anodal transcranial direct current stimulation (tDCS) was applied in a group of patients with disorders of consciousness to determine the effects of modulation of spontaneous oscillatory brain activity.Methods12 patients in an unresponsive wakefulness syndrome (UWS) and 12 in a minimally conscious state (MCS) underwent 2-weeks active and 2-weeks sham tDCS. Neurophysiological assessment was performed with EEG power spectra and coherence analysis directly before and after each session.ResultsAn increase of power and coherence of the frontal and parietal alpha and beta frequency bands and significant clinical improvements were seen after the active tDCS in MCS patients. In contrast, UWS patients showed some local frontal changes in the slow frequencies. No treatment effect was observed after sham.ConclusionstDCS could induce changes in cortical EEG oscillations, modulating the travel of alpha and beta waves between anterior and posterior brain areas when some cognitive functions were preserved. This plays an important role in consciousness by integrating cognitive-emotional processing with the state of arousal. In unresponsive people, brain integration seems to be lost.SignificanceOur results further support the critical role of long-range fronto-parietal connections in consciousness and show the potential therapeutic utility of tDCS.     

Dysmorphic neurons as cellular source for phase-amplitude coupling in Focal Cortical Dysplasia Type II

ObjectiveReliable localization of the epileptogenic zone is necessary for successful epilepsy surgery. Neurophysiological biomarkers include ictal onsets and interictal spikes. Furthermore, the epileptic network shows oscillations with potential localization value and pathomechanistic implications. The cellular origin of such markers in invasive EEG in vivo remains to be clarified.MethodsIn the presented pilot study, surgical brain samples and invasive EEG recordings of seven patients with surgically treated Focal Cortical Dysplasia (FCD) type II were coregistered using a novel protocol. Dysmorphic neurons and balloon cells were immunohistochemically quantified. Evaluated markers included seizure onset, spikes, and oscillatory activity in delta, theta, gamma and ripple frequency bands, as well as sample entropy and phase-amplitude coupling between delta, theta, alpha and beta phase and gamma amplitude.ResultsCorrelations between histopathology and neurophysiology provided evidence for a contribution of dysmorphic neurons to interictal spikes, fast gamma activity and ripples. Furthermore, seizure onset and phase-amplitude coupling in areas with dysmorphic neurons suggests preserved connectivity is related to seizure initiation. Balloon cells showed no association.ConclusionsPhase-amplitude coupling, spikes, fast gamma and ripples are related to the density of dysmorphic neurons and localize the seizure onset zone.SignificanceThe results of our pilot study provide a new powerful tool to address the cellular source of abnormal neurophysiology signals to leverage current and novel biomarkers for the localization of epileptic activity in the human brain.     

Beta-band oscillations as a biomarker of gait recovery in spinal cord injury patients: A quantitative electroencephalography analysis

ObjectiveThe gait recovery in spinal cord injury (SCI) seems to be partially related to the reorganization of cerebral function; however, the neural mechanisms and the respective biomarkers are not well known. This study tested the hypothesis that enhanced beta-band oscillations may be a marker of compensatory neural plasticity during the recovery period in SCI. We tested this hypothesis at baseline in SCI subjects and also in response to cortical stimulation with transcranial direct current stimulation (tDCS) combined with robotic-assisted gait training (RAGT).MethodsIn this neurophysiological analysis of a randomized controlled trial, thirty-nine patients with incomplete SCI were included. They received 30 sessions of either active or sham anodal tDCS over the primary motor area for 20 min combined with RAGT. We analyzed the Electroencephalography (EEG) power spectrum and task-related power modulation of EEG oscillations, and their association with gait function indexed by Walk Index for Spinal Cord Injury (WISCI-II). Univariate and multivariate linear/logistic regression analyses were performed to identify the predictors of gait function and recovery.ResultsConsistent with our hypothesis, we found that in the sensorimotor area: (1) Anodal tDCS combined with RAGT can modulate high-beta EEG oscillations power and enhance gait recovery; (2) higher high-beta EEG oscillations power at baseline can predict baseline gait function; (3) high-beta EEG oscillations power at baseline can predict gait recovery – the higher power at baseline, the better gait recovery; (4) decreases in relative high-beta power and increases in beta power decrease during walking are associated with gait recovery.ConclusionsEnhanced EEG beta oscillations in the sensorimotor area in SCI subjects may be part of a compensatory mechanism to enhance local plasticity. Our results point to the direction that interventions enhancing local plasticity such as tDCS combined with robotic training also lead to an immediate increase in sensorimotor cortex activation, improvement in gait recovery, and subsequent decrease in high-beta power. These findings suggest that beta-band oscillations may be potential biomarkers of gait function and recovery in SCI.SignificanceThese findings are significant for rehabilitation in SCI patients, and as EEG is a portable, inexpensive, and easy-to-apply system, the clinical translation is feasible to follow better the recovery process and to help to individualize rehabilitation therapies of SCI patients.     

Cell type-specific excitability probed by optogenetic stimulation depends on the phase of the alpha oscillation

BackgroundAlpha oscillations have been proposed to provide phasic inhibition in the brain. Yet, pinging alpha oscillations with transcranial magnetic stimulation (TMS) to examine phase-dependent network excitability has resulted in conflicting findings. At the cellular level, such gating by the alpha oscillation remains poorly understood.ObjectiveWe examine how the excitability of pyramidal cells and presumed fast-spiking inhibitory interneurons depends on the phase of the alpha oscillation.MethodsOptogenetic stimulation pulses were administered at random phases of the alpha oscillation in the posterior parietal cortex (PPC) of two adult ferrets that expressed channelrhodopsin in pyramidal cells. Post-stimulation firing probability was calculated as a function of the stimulation phase of the alpha oscillation for both verum and sham stimulation.ResultsThe excitability of pyramidal cells depended on the alpha phase, in anticorrelation with their intrinsic phase preference; pyramidal cells were more responsive to optogenetic stimulation at the alpha phase with intrinsically low firing rates. In contrast, presumed fast-spiking inhibitory interneurons did not show such a phase dependency despite their stronger intrinsic phase preference.ConclusionsAlpha oscillations gate input to PPC in a phase-dependent manner such that low intrinsic activity was associated with higher responsiveness to input. This finding supports a model of cortical oscillation, in which internal processing and communication are limited to the depolarized half-cycle, whereas the other half-cycle serves as a signal detector for unexpected input. The functional role of different parts of the alpha cycle may vary across the cortex depending on local neuronal firing properties.     

Noninvasive transcranial direct current stimulation in a genetic absence model

The proposed area of onset for absence epilepsy characteristic of spontaneously occurring spike and slow-wave discharges (SWDs) in the genetic absence rat model is the subgranular layer of the somatosensory cortex. Modulation of the hyperexcitable cortical foci by bilateral transcranial direct current stimulation (tDCS) might change the expression of SWDs. The effects of cathodal and anodal tDCS as well as cumulative effects of different intensities of repeated cathodal stimulation on EEG and behavior were examined. Cathodal tDCS reduced the number of SWDs during stimulation and affected the mean duration after stimulation both in an intensity-dependent manner. Behavior was changed after the highest stimulation intensity. Spectral analyses of the EEG during stimulation revealed an increase in sub-delta and delta frequency ranges, suggesting that cortical cells were hyperpolarized. Cathodal tDCS might be an effective non-invasive tool to decrease cortical excitability, presumably in focal zone in this genetic model.     

Anodal transcranial direct current stimulation in chronic migraine and medication overuse headache: A pilot double-blind randomized sham-controlled trial

ObjectivesLittle evidence is available on the role of transcranial direct current stimulation (tDCS) in patients affected by chronic migraine (CM) and medication overuse headache (MOH). We aim to investigate the effects of tDCS in patients with CM and MOH as well as its role on brain activity.MethodsTwenty patients with CM and MOH were hospitalized for a 7-day detoxification treatment. Upon admission, patients were randomly assigned to anodal tDCS or sham stimulation delivered over the primary motor cortex contralateral to the prevalent migraine pain side every day for 5 days. Clinical data were recorded at baseline (T0), after 1 month (T2) and 6 months (T3). EEG recording was performed at T0, at the end of the tDCS/Sham treatment, and at T2.ResultsAt T2 and T3, we found a significant reduction in monthly migraine days (p = 0.001), which were more pronounced in the tDCS group when compared to the sham group (p = 0.016).At T2, we found a significant increase of alpha rhythm in occipital leads, which was significantly higher in tDCS group when compared to sham group.ConclusionstDCS showed adjuvant effects to detoxification in the management of patients with CM and MOH. The EEG recording showed a significant potentiation of alpha rhythm, which may represent a correlate of the underlying changes in cortico-thalamic connections.SignificanceThis study suggests a possible role for tDCS in the treatment of CM and MOH. The observed clinical improvement is coupled with a potentiation of EEG alpha rhythm.     

No effect of anodal tDCS on motor cortical excitability and no evidence for responders in a large double-blind placebo-controlled trial

BackgroundTranscranial direct current stimulation (tDCS) has emerged as a non-invasive brain stimulation technique. Most studies show that anodal tDCS increases cortical excitability. However, this effect has been found to be highly variable.ObjectiveTo test the effect of anodal tDCS on cortical excitability and the interaction effect of two participant-specific factors that may explain individual differences in sensitivity to anodal tDCS: the Brain Derived Neurotrophic Factor Val66Met polymorphism (BDNF genotype) and the latency difference between anterior-posterior and lateromedial TMS pulses (APLM latency).MethodsIn 62 healthy participants, cortical excitability over the left motor cortex was measured before and after anodal tDCS at 2 mA for 20 min in a pre-registered, double-blind, randomized, placebo-controlled trial with repeated measures.ResultsWe did not find a main effect of anodal tDCS, nor an interaction effect of the participant-specific predictors. Moreover, further analyses did not provide evidence for the existence of responders and non-responders.ConclusionThis study indicates that anodal tDCS at 2 mA for 20 min may not reliably affect cortical excitability.     

Interictal indices of temporal seizure origin

Two studies assessed the value of temporal lobe interictal electroencephalographic (EEG) spikes and delta in indicating side of temporal epileptogenesis. The first study determined laterality of spikes/delta in awake recordings of 56 patients whose seizures all began unilaterally as proven by (1) EEG-recorded seizures and (2) >90% improvement after lobectomy. Spikes of 52 (93%) and delta of 46 (82%) patients predominated or appeared exclusively ipsilateral to seizure origin. Neither predominated contralaterally in any patient. The second study investigated laterality of temporal seizures in a separate group of 156 patients with various side vs side spike or delta ratios on 1 to ≥4 awake recordings. Ninety-nine of 104 patients (95%) with temporal spikes on four or more awake recordings had most or all seizures ipsilateral to most spikes, including 79 of 80 (99%) of those with ≥3 side vs side spike ratios. Among the 120 patients with high (≥3) side vs side spike ratios, most or all seizures of 118 (98%) originated ipsilateral to most spikes. Predominant seizure origin also correlated with lateralized arrhythmic delta—from 90% ipsilateral seizures of those with one EEG with delta to 100% with ≥4 such EEGs. Data from these two studies using opposite directions of analysis (seizures ← spikes/delta and spikes/delta → seizures) demonstrate high correlations between laterality of interictal and ictal entities, particularly if temporal spikes clearly predominate on one side and if unilateral temporal delta activity persists over several recordings. Such correlations suggest that the awake interictal scalp EEG cannot be ignored when assessing laterality of temporal epileptogenesis.