D-cycloserine normalizes long-term motor plasticity after transcranial magnetic intermittent theta-burst stimulation in major depressive disorder

ObjectivesMajor Depressive Disorder (MDD) is associated with glutamatergic alterations, including the N-methyl-D-aspartate receptor (NMDA-R). The NMDA-R plays an important role in synaptic plasticity, and individuals with MDD have been shown to have impairments in repetitive Transcranial Magnetic Stimulation (rTMS) motor plasticity. Here, we test whether D-cycloserine, a NMDA-R partial agonist, can rescue TMS motor plasticity in MDD.MethodsWe conducted randomized double-blind placebo-controlled crossover studies in healthy (n = 12) and MDD (n = 12) participants. We stimulated motor cortex using TMS intermittent theta burst stimulation (iTBS) with placebo or D-cycloserine (100 mg). Motor evoked potentials (MEPs) were sampled before and after iTBS. Stimulus response curves (SRC) were characterized at baseline, +90 minutes, and the following day.ResultsAcute iTBS MEP facilitation is reduced in MDD and is not rescued by D-cycloserine. After iTBS, SRCs shift to indicate sustained decrease in excitability in healthy participants, yet increased in excitability in MDD participants. D-cycloserine normalized SRC changes from baseline to the following day in MDD participants. In both healthy and MDD participants, D-cycloserine stabilized changes in SRC.ConclusionMDD is associated with alterations in motor plasticity that are rescued and stabilized by NMDA-R agonism.SignificanceAgonism of NMDA receptors rescues iTBS motor plasticity in MDD.     

Effect of repetitive transcranial magnetic stimulation combined with robot-assisted training on wrist muscle activation post-stroke

ObjectiveTo compare the effects of active assisted wrist extension training, using a robotic exoskeleton (RW), with simultaneous 5 Hz (rTMS + RW) or Sham rTMS (Sham rTMS + RW) over the ipsilesional extensor carpi radialis motor cortical representation, on voluntary wrist muscle activation following stroke.MethodsThe two training conditions were completed at least one week apart in 13 participants >1-year post-stroke. Voluntary wrist extensor muscle activation (motor unit (MU) recruitment thresholds and firing rate modulation in a ramp-hold handgrip task), ipsilesional corticospinal excitability (motor evoked potential [MEP] amplitude) and transcallosal inhibition were measured Pre- and Post-training.ResultsFor MUs active both Pre and Post training, greater reductions in recruitment thresholds were found Post rTMS + RW training (p = 0.0001) compared to Sham rTMS + RW (p = 0.16). MU firing rate modulation increased following both training conditions (p = 0.001). Ipsilesional MEPs were elicited Pre and Post in only 5/13 participants. No significant changes were seen in ipsilesional corticospinal excitability and transcallosal inhibition measures (p > 0.05).ConclusionsFollowing a single rTMS + RW session in people >1-year post-stroke, changes were found in voluntary muscle activation of wrist extensor muscles. Alterations in ipsilesional corticospinal or interhemispheric excitability were not detected.SignificanceThe effects of rTMS + RW on muscle activation warrant further investigation as post-stroke rehabilitation strategy.     

Postoperative navigated transcranial magnetic stimulation to predict motor recovery after surgery of tumors in motor eloquent areas

ObjectiveTo know whether motor deficits after tumor surgery are transient is reassuring for the patient and crucial for planning rehabilitation and adjuvant treatment. We analyze the value of postoperative MRI navigated transcranial magnetic stimulation (nTMS) compared to intraoperative MEP monitoring in predicting recovery of motor function.MethodsRetrospective series of nTMS mappings within 14 days after surgery for supratentorial tumors (09/2014–05/2018). All patients with motor deficits of Medical-Research-Council-Grade (MRCS) 0–4- were included.ResultsWe performed nTMS mapping on average 3.8 days after surgery and recorded nTMS MEP in 11 of 13 patients. Motor strength recovered to at least MRCS 4 within one month if postoperative nTMS elicited MEPs (positive predictive value 90.9%). If nTMS did not elicit MEPs, the patient did not recover (negative predictive value 100%). Intraoperative MEP and postoperative nTMS were equally predictive for long-term motor recovery. In cases of intraoperative MEP alteration/signal loss, but a positive postoperative nTMS mapping, 2/3 patients demonstrated a good motor recovery.ConclusionnTMS may predict long-term motor recovery of patients suffering from severe motor deficits directly after resection of tumors located in motor eloquent areas.SignificanceIn cases of intraoperative MEP alterations, postoperative nTMS may clarify the potential for motor recovery.     

Region-dependent bidirectional plasticity in M1 following quadripulse transcranial magnetic stimulation in the inferior parietal cortex

BackgroundThe ability to manipulate the excitability of the network between the inferior parietal lobule (IPL) and primary motor cortex (M1) may have clinical value.ObjectiveTo investigate the possibility of inducing long-lasting changes in M1 excitability by applying quadripulse transcranial magnetic stimulation (QPS) to the IPL, and to ascertain stimulus condition- and site-dependent differences in the effects.MethodsQPS was applied to M1, the primary somatosensory cortex (S1), the supramarginal gyrus (SMG) and angular gyrus (AG) IPL areas, with the inter-stimulus interval (ISI) in the train of pulses set to either 5 ms (QPS-5) or 50 ms (QPS-50). QPS was repeated at 0.2 Hz for 30 min, or not presented (sham condition). Excitability changes in the target site were examined by means of single-pulse transcranial magnetic stimulation (TMS).ResultsQPS-5 and QPS-50 at M1 increased and decreased M1 excitability, respectively. QPS at S1 induced no obvious change in M1 excitability. However, QPS at the SMG induced mainly suppressive effects in M1 for at least 30 min, regardless of the ISI length. Both QPS ISIs at the AG yielded significantly different MEP compared to those at the SMG. Thus, the direction of the plastic effect of QPS differed depending on the site, even under the same stimulation conditions.ConclusionsQPS at the IPL produced long-lasting changes in M1 excitability, which differed depending on the precise stimulation site within the IPL. These results raise the possibility of noninvasive induction of functional plasticity in M1 via input from the IPL.     

Atlas-informed computational processing pipeline for individual targeting of brain areas for therapeutic navigated transcranial magnetic stimulation

ObjectiveNavigated transcranial magnetic stimulation (nTMS) is targeted at different cortical sites for diagnostic, therapeutic, and neuroscientific purposes. Correct identification of the cortical target areas is important for achieving desired effects, but it is challenging when no direct responses arise upon target area stimulation. We aimed at utilizing atlas-based marking of cortical areas for nTMS targeting to present a convenient, rater-independent method for overlaying the individual target sites with brain anatomy.MethodsWe developed a pipeline, which fits a brain atlas to the individual brain and enables visualization of the target areas during the nTMS session. We applied the pipeline to our previous nTMS data, focusing on depression and schizophrenia patients. Furthermore, we included examples of Tourette syndrome and tinnitus therapies, as well as neurosurgical and motor mappings.ResultsIn depression and schizophrenia patients, the visually selected dorsolateral prefrontal cortex (DLPFC) targets were close to the border between atlas areas A9/46 and A8. In the other areas, the atlas-based areas were in agreement with the treatment targets.ConclusionsThe atlas-based target areas agreed well with the cortical targets selected by experts during the treatments.SignificanceOverlaying atlas information over the navigation view is a convenient and useful add-on for improving nTMS targeting.     

Improved object recognition memory using post-encoding repetitive transcranial magnetic stimulation

BackgroundBrain stimulation is known to affect canonical pathways and proteins involved in memory. However, there are conflicting results on the ability of brain stimulation to improve to memory, which may be due to variations in timing of stimulation.HypothesisWe hypothesized that repetitive transcranial magnetic stimulation (rTMS) given following a learning task and within the time period before retrieval could help improve memory.MethodsWe implanted male B6129SF2/J mice (n = 32) with a cranial attachment to secure the rTMS coil so that the mice could be given consistent stimulation to the frontal area whilst freely moving. Mice then underwent the object recognition test sampling phase and given treatment +3, +24, +48 h following the test. Treatment consisted of 10 min 10 Hz rTMS stimulation (TMS, n = 10), sham treatment (SHAM, n = 11) or a control group which did not do the behavior test or receive rTMS (CONTROL n = 11). At +72 h mice were tested for their exploration of the novel vs familiar object.ResultsAt 72-h's, only the mice which received rTMS had greater exploration of the novel object than the familiar object. We further show that promoting synaptic GluR2 and maintaining synaptic connections in the perirhinal cortex and hippocampal CA1 are important for this effect. In addition, we found evidence that these changes were linked to CAMKII and CREB pathways in hippocampal neurons.ConclusionBy linking the known biological effects of rTMS to memory pathways we provide evidence that rTMS is effective in improving memory when given during the consolidation and maintenance phases.     

Theta-burst versus 20 Hz repetitive transcranial magnetic stimulation in neuropathic pain: A head-to-head comparison

ObjectiveHigh-frequency repetitive transcranial magnetic stimulation (rTMS) has been shown to reduce neuropathic pain, but intermittent “theta-burst” stimulation (iTBS) could be a better alternative because of shorter duration and greater ability to induce cortical plasticity. Here we compared head-to-head the pain-relieving efficacy of the two modalities when applied daily for 5 days to patients with neuropathic pain.MethodsForty-six patients received 20 Hz-rTMS and/or iTBS protocols and 39 of them underwent the full two procedures in a random cross-over design. They rated pain intensity, sleep quality, fatigue and general health status daily during 5 consecutive weeks.ResultsPain relief during the month following stimulation was superior after 20 Hz-rTMS relative to iTBS (F(1,38) = 4.645; p = 0.037). Correlation between respective levels of maximal relief showed a significant deviation toward the 20 Hz-rTMS effect. A greater proportion of individuals responded to 20 Hz-rTMS (52% vs 32%, 95 %CI[0.095–3.27]; p = 0.06), and reports of fatigue significantly improved after 20 Hz-rTMS relative to iTBS (p = 0.01). General health and sleep quality scores did not differentiate both techniques.ConclusionsHigh-frequency rTMS appeared superior to iTBS for neuropathic pain relief.SignificanceAdequate matching between the oscillatory activity of motor cortex and that of rTMS may increase synaptic efficacy, thus enhancing functional connectivity of motor cortex with distant structures involved in pain regulation.     

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.     

Acute effects of spaced cathodal transcranial direct current stimulation in drug resistant focal epilepsies

ObjectiveTo evaluate the safety and temporal dynamic of the antiepileptic effect of spaced transcranial direct current stimulation (tDCS) in different focal epilepsies.MethodsCathodal tDCS with individual electrode placement was performed in 15 adults with drug resistant focal epilepsy. An amplitude of 2 mA was applied twice for 9 minutes, with an interstimulation interval of 20 minutes. Tolerability was assessed via the Comfort Rating Questionnaire and the frequency of interictal epileptiform discharges (IEDs) was sequentially compared between the 24 hours before and after tDCS.ResultsTDCS led to a significant reduction in the total number of IEDs/24 h by up to 68% (mean ± SD: −30.4 ± 21.1%, p = 0.001) as well as in seizure frequency (p = 0.041). The maximum IED reduction was observed between the 3rd and 21st hour after stimulation. Favorable clinical response was associated with structural etiology and clearly circumscribed epileptogenic foci but did not differ between frontal and temporal epilepsies. Overall, the tDCS treatment was well tolerated and did not lead to severe adverse events.ConclusionsThe spaced stimulation approach proved to be safe and well-tolerated in patients with drug-resistant unifocal epilepsies, leading to sustained IED and seizure frequency reduction.SignificanceSpaced tDCS induces mediate antiepileptic effects with promising therapeutic potential.     

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.     

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.     

Navigated repetitive transcranial magnetic stimulation improves the outcome of postsurgical paresis in glioma patients – A randomized,double-blinded trial

BackgroundNavigated repetitive transcranial magnetic stimulation (nrTMS) is effective therapy for stroke patients. Neurorehabilitation could be supported by low-frequency stimulation of the non-damaged hemisphere to reduce transcallosal inhibition.ObjectiveThe present study examines the effect of postoperative nrTMS therapy of the unaffected hemisphere in glioma patients suffering from acute surgery-related paresis of the upper extremity (UE) due to subcortical ischemia.MethodsWe performed a randomized, sham-controlled, double-blinded trial on patients suffering from acute surgery-related paresis of the UE after glioma resection. Patients were randomly assigned to receive either low frequency nrTMS (1 Hz, 15 min) or sham stimulation directly before physical therapy for 7 consecutive days. We performed primary and secondary outcome measures on day 1, on day 7, and at a 3-month follow-up (FU). The primary endpoint was the change in Fugl-Meyer Assessment (FMA) at FU compared to day 1 after surgery.ResultsCompared to the sham stimulation, nrTMS significantly improved outcomes between day 1 and FU based on the FMA (mean [95% CI] +31.9 [22.6, 41.3] vs. +4.2 [-4.1, 12.5]; P = .001) and the National Institutes of Health Stroke Scale (NIHSS) (−5.6 [-7.5, −3.6] vs. −2.4 [-3.6, −1.2]; P = .02). To achieve a minimal clinically important difference of 10 points on the FMA scale, the number needed to treat is 2.19.ConclusionThe present results show that patients suffering from acute surgery-related paresis of the UE due to subcortical ischemia after glioma resection significantly benefit from low-frequency nrTMS stimulation therapy of the unaffected hemisphere.Clinical trial registrationLocal institutional registration: 12/15; ClinicalTrials.gov number: NCT03982329     

Severe obstructive sleep apnea in patients with chronic obstructive pulmonary disease is associated with an increased prevalence of mild cognitive impairment

BackgroundChronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) are associated with mild cognitive impairment (MCI). However, this association is unclear. This study aimed to assess the prevalence of MCI in patients with overlap syndrome, determine whether OSA increases the risk of MCI in patients with COPD, and investigate the potential mechanisms for this association.MethodsParticipants with stable Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2–4 COPD and complaints of snoring in 2016–2018 were enrolled in this cross-sectional observational study. All were free of asthma, acute left-sided congestive heart failure, unstable coronary heart disease, uncontrolled hypertension, diabetes, encephalitis, and epilepsy. They underwent pulmonary function tests and overnight polysomnography and completed the Montreal Cognitive Assessment (MoCA). MCI was defined by an MoCA score of <23, while OSA was defined by an apnea-hypopnea index (AHI) of ≥15 per hour. The association between MCI, demographics, and comorbidities was tested by logistic regression analysis with adjustment for confounders. Sleep-disordered breathing measures were investigated as potential mechanisms underlying this relationship.ResultsMCI was significantly more common in patients with overlap syndrome than in those with COPD (40.6% [43/106] vs 24.6% [42/171]). After adjustment, severe OSA was an independent contributor to MCI (odds ratio, OR 2.27; 95% confidence interval, CI 1.12–4.62). Increased percent of night-time spent with oxygen saturation <90% (TSat₉₀) was associated with increased odds of MCI (odds ratio 4.75, 95% CI 2.73–11.13).ConclusionsMCI is more prevalent in overlap syndrome than in COPD. OSA may contribute to MCI in COPD. The mechanism may involve TSat₉₀.     

Cognitive deficits and rehabilitation mechanisms in mild traumatic brain injury patients revealed by EEG connectivity markers

ObjectiveTo explore the multiple specific biomarkers and cognitive compensatory mechanisms of mild traumatic brain injury (mTBI) patients at recovery stage.MethodsThe experiment was performed in two sections. In Section I, using event-related potential, event-related oscillation and spatial phase-synchronization, we explored neural dynamics in 24 volunteered healthy controls (HC) and 38 patients at least 6 months post-mTBI (19 with epidural hematoma, EDH; 19 with subdural hematoma, SDH) during a Go/NoGo task. In Section II, according to the neuropsychological scales, patients were divided into sub-groups to assess these electroencephalography (EEG) indicators in identifying different rehabilitation outcomes of mTBI.ResultsIn Section I, mean amplitudes of NoGo-P3 and P3d were decreased in mTBI patients relative to HC, and NoGo-theta power in the non-injured hemisphere was decreased in SDH patients only. In Section II, patients with chronic neuropsychological defects exhibited more serious impairments of intra-hemispheric connectivity, whereas inter-hemispheric centro-parietal and frontal connectivity were enhanced in response to lesions.ConclusionsEEG distinguished mTBI patients from healthy controls, and estimated different rehabilitation outcomes of mTBI. The centro-parietal and frontal connectivity are the main compensatory mechanism for the recovery of mTBI patients.SignificanceEEG measurements and network connectivity can track recovery process and mechanism of mTBI.     

Motor cortex transcranial direct current stimulation effects on knee osteoarthritis pain in elderly subjects with dysfunctional descending pain inhibitory system: A randomized controlled trial

BackgroundAlthough evidence has indicated a positive effect of transcranial direct current stimulation (tDCS) on reducing pain, few studies have focused on the elderly population with knee osteoarthritis (KOA).ObjectiveTo evaluate whether tDCS reduces KOA pain in elderly individuals with a dysfunctional descending pain inhibitory system (DPIS).MethodsIn a double-blind trial, individuals ≥ 60 years with KOA pain and a dysfunctional DPIS, we randomly assigned patients to receive 15 daily sessions of 2 mA tDCS over the primary motor cortex (anode) and contralateral supraorbital area (cathode) (M1-SO) for 20 min or sham tDCS. Change in pain perception indexed by the Brief Pain Inventory (BPI) at the end of intervention was the primary outcome. Secondary outcomes included: disability, quantitative sensory testing, pain pressure threshold and conditioned pain modulation (CPM). Subjects were followed-up for 2 months.ResultsOf the 104 enrolled subjects, with mean (SD) age of 73.9 (8.01) years and 88 (84.6%) female, 102 finished the trial. In the intention-to-treat analysis, the active tDCS group had a significantly greater reduction in BPI compared to the sham group (difference, 1.59; 95% CI, 0.95 to 2.23; P < 0.001; Cohen’s d, 0.58); and, also a significantly greater improvement in CPM-pressure in the knee (P = 0.01) and CPM-pain in the hand (P = 0.01). These effects were not sustained at follow-up. The intervention was well tolerated, with no severe adverse effects.ConclusionM1-SO tDCS is associated with a moderate effect size in reducing pain in elderly patients with KOA after 15 daily sessions of stimulation. This intervention has also shown to modulate the DPIS.     

Assessment of safety of self-controlled repetitive trans-vertebral magnetic stimulation

ObjectiveThe aim of this study was to assess safety issues of self-controlled repetitive trans-vertebral magnetic stimulation (rTVMS) in humans.MethodsWe investigated effects of self-controlled rTVMS (≤20 Hz, ≤90% intensity) on vital signs and subjective sensations in 1690 trials of 30 healthy volunteers and 12 patients with spinal cord disorders.ResultsHealthy volunteers and the patients received 4595 ± 2345, and 4450 ± 2304 pulses in one day, respectively. No serious adverse events were observed in any participants, and only minor events were seen as follows. While blood pressure was unaffected in the patients, the diastolic blood pressure increased slightly after rTVMS in healthy volunteers. The peripheral capillary oxygen saturation increased after rTVMS in healthy volunteers. “Pain” or “Discomfort” was reported in approximately 10% of trials in both participants groups. Degree of the evoked sensation positively correlated with stimulus intensity and was affected by the site of stimulation.ConclusionSelf-controlled rTVMS (≤20 Hz and ≤90% intensity) did not induce any serious adverse effects in healthy volunteers and patients with spinal cord disorders.SignificanceOur results indicate that rTVMS can be used safely in physiological investigations in healthy volunteers and also as treatment for neurological disorders.     

Probing EEG activity in the targeted cortex after focal transcranial electrical stimulation

BackgroundRecording electroencephalography (EEG) from the targeted cortex immediately before and after focal transcranial electrical stimulation (TES) remains a challenge.MethodsWe introduce a hybrid stimulation-recording approach where a single EEG electrode is inserted into the inner electrode of a double-ring montage for focal TES. The new combined electrode was placed at the C3 position of the EEG 10–20 system. Neuronal activity was recorded in two volunteers before and after 20 Hz alternating-current TES at peak-to-peak intensities of 1 and 2 mA. TES-induced electric field distributions were simulated with SIMNIBS software.ResultsUsing the hybrid stimulation-recording set-up, EEG activity was successfully recorded directly before and after TES. Simulations revealed comparable electrical fields in the stimulated cortex for the pseudomonopolar montage with and without embedded EEG electrode.ConclusionThe hybrid TES-EEG approach can be used to probe after-effects of focal TES on neuronal activity in the targeted cortex.     

Sleep modulates effective connectivity: A study using intracranial stimulation and recording

ObjectiveSleep is an active process with an important role in memory. Epilepsy patients often display a disturbed sleep architecture, with consequences on cognition. We aimed to investigate the effect of sleep on cortical networks’ organization.MethodsWe analyzed cortico-cortical evoked responses elicited by single pulse electrical stimulation (SPES) using intracranial depth electrodes in 25 patients with drug-resistant focal epilepsy explored using stereo-EEG. We applied the SPES protocol during wakefulness and NREM – N2 sleep. We analyzed 31,710 significant responses elicited by 799 stimulations covering most brain structures, epileptogenic or non-epileptogenic. We analyzed effective connectivity between structures using a graph-theory approach.ResultsSleep increases excitability in the brain, regardless of epileptogenicity. Local and distant connections are differently modulated by sleep, depending on the tissue epileptogenicity.In non-epileptogenic areas, frontal lobe connectivity is enhanced during sleep. There is increased connectivity between the hippocampus and temporal neocortex, while perisylvian structures are disconnected from the temporal lobe. In epileptogenic areas, we found a clear interhemispheric difference, with decreased connectivity in the right hemisphere during sleep.ConclusionsSleep modulates brain excitability and reconfigures functional brain networks, depending on tissue epileptogenicity.SignificanceWe found specific patterns of information flow during sleep in physiologic and pathologic structures, with possible implications for cognition.