Long-term prophylactic efficacy of transcranial direct current stimulation in chronic migraine. A randomised,patient-assessor blinded,sham-controlled trial

ObjectiveTo assess the prophylactic effect of anodal tDCS of the left motor cortex in patients with resistant chronic migraine (CM) and its long-term maintenance.MethodsIn a patient-assessor blinded, sham-controlled trial, 36 patients were randomized to receive anodal tDCS (active group, n = 18) or sham tDCS (sham group, n = 18). The studied population was characterized by a previous failure of at least 3 classes of preventive drugs and a mean duration of migraine history of 26 years. The tDCS procedure consisted of an induction phase of 5 consecutive daily sessions (week 1) followed by a maintenance phase of 1 weekly session during the next 4 weeks and two bimonthly sessions in the next month, for a total of 11 sessions during 2 months. Anodal tDCS was delivered at 2 mA intensity for 20 min over the left motor cortex. The primary endpoint was the reduction in the monthly number of migraine attacks from baseline to each period of follow-up (months 1, 2, 3, 5) between the active and sham groups.ResultsThe monthly number of migraine attacks expressed as the percentage of reduction from baseline was significantly reduced in the active versus the sham group, from the end of first month (?21% ± 22 vs. ?2% ±25, p = 0.019) to the end of follow-up (3-month post-treatment) (?32% ± 33 vs. ?6% ±39, p = 0.011). At this time, the rate of responders, defined as a reduction of the monthly number of migraine attacks ≥30% from baseline, was significantly higher in the active group than in the sham group (50% vs. 14%, p = 0.043).ConclusionOur results show a marked prophylactic effect of anodal tDCS of the left motor cortex in resistant CM extending several months after the stimulation period, and suggest that this neuromodulatory approach may be part of the prophylactic alternatives available for CM.     

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.     

Comparison between conventional and HD-tDCS of the right inferior frontal gyrus in children and adolescents with ADHD

ObjectiveTo investigate whether the effects of HD-tDCS and conventional tDCS of the right IFG are superior to the effects of sham stimulation for the improvement of working memory performance in ADHD.Methods15 ADHD patients between 10 and 16 years underwent three tDCS sessions in which conventional, HD and sham tDCS of the right IFG were applied. In all sessions a 2-back working memory task was solved and EEG was recorded. Baseline data were assessed from 15 age matched healthy controls.ResultsIn ADHD patients, increased positive values of P300 and N200 mean amplitudes were found after conventional and HD-tDCS. Thus, both components were more in resemblance to ERPs in healthy controls. Behavioral performance was not generally influenced by tDCS but effects of HD-tDCS depended on individual hyperactive/impulsive symptom load. The rate of responders for HD-tDCS was equivalent to the responder rate for conventional tDCS.ConclusionsERP data indicate that HD-tDCS is equally suitable as conventional tDCS for the recruitment of the right IFG in the context of working memory processing.SignificanceHD-tDCS of the right IFG is a promising approach for neuromodulation in ADHD but further research is necessary to develop adaptations that produce reliable behavioral benefits.     

Early transcranial direct current stimulation with modified constraint-induced movement therapy for motor and functional upper limb recovery in hospitalized patients with stroke: A randomized,multicentre, double-blind,clinical trial

BackgroundConstraint-induced movement therapy (CIMT) and transcranial direct current stimulation (tDCS) are used to reduce interhemispheric imbalance after stroke, which is why the combination of these therapies has been used for neurological recovery, but not in the acute phase.ObjectivesTo evaluate the effectiveness of combining active or sham bihemispheric tDCS with modified CIMT (mCIMT) for the recovery of the Upper Limb (UL) in hospitalized patients with acute and subacute stroke.MethodsThis randomized controlled, double-blind, placebo-controlled, parallel group clinical trial was executed between September 2018 to March 2021 recruited 70 patients. The patients were randomized to one of two groups to receive treatment for 7 consecutive days, which included 20 min of active or sham bihemispheric tDCS daily (anodal ipsilesional and cathodal contralesional), with an mCIMT protocol. The primary outcome was the difference in the evolution of motor and functional upper limb recovery with assessment on days 0, 5, 7, 10 and 90. The secondary outcomes were independence in activities of daily living (ADL) and quality of life.ResultsThe active group presented a statistically significant gap compared to the simulated group throughout the trend in the scores of the FMA (motor function and joint pain) and WMFT (functional ability and weight to box) (p < 0.05) and showed a minimal clinically important difference (FMA: difference between groups of 4.9 points [CI: 0.007- 9.799]; WMFT: difference between groups of 6.54 points [CI: 1.10-14.15]). In the secondary outcomes, there was a significant difference between the groups in ADL independence (Functional Independence Measure: difference of 8.63 [CI: 1.37-18.64]) and perceived recovery of quality of life evaluated at 90 days (p = 0.0176).ConclusionsCombining mCIMT with bihemispheric tDCS in patients hospitalized with acute-subacute stroke allows us to maximize the motor and functional recovery of the paretic upper limb in the early stages and independence in ADL, maintaining the effects over time.     

Valproate but not levetiracetam slows the EEG alpha peak frequency – A pharmaco-EEG study

ObjectiveStudies of the effect of valproate (VPA) on the background EEG have shown varying results. Therefore, we compared the effect of VPA and levetiracetam (LEV) on the EEG alpha peak frequency (APF).MethodsWe retrospectively examined the APF in resting-state EEG of patients undergoing inpatient video-EEG monitoring (VEM) during withdrawal of VPA or LEV. We assessed APF trends by computing linear fits across individual patients’ APF as a function of consecutive days, and correlated the APF and daily antiseizure medication (ASM) doses on a single-patient and group level.ResultsThe APF in the VPA-group significantly increased over days with falling VPA doses (p = 0.005, n = 13), but did not change significantly in the LEV-group (p = 0.47, n = 18). APF correlated negatively with daily ASM doses in the VPA-group (average of r = −0.74 ± 0.12 across patients, p = 0.0039), but not in the LEV-group (average of r = −0.17 ± 0.18 across patients, p = 0.4072).ConclusionsOur results suggest that VPA treatment slows the APF. This APF reduction correlates with the daily dose of VPA and is not present in LEV treatment.SignificanceOur study identifies a VPA-related slowing of the APF even in patients without electroencephalographic or overt clinical signs of encephalopathy.     

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.     

Characterization of EEG-based functional brain networks in myotonic dystrophy type 1

ObjectiveIn the autosomal dominant, multisystem, chronic progressive disease myotonic dystrophy type 1 (DM1), cognitive deficits may originate from disrupted functional brain networks. We aimed to use network analysis of resting-state electro-encephalography (EEG) recordings of patients with DM1 and matched unaffected controls to investigate changes in network organization in large-scale functional brain networks and correlations with cognitive deficits.MethodsIn this cross-sectional study, 28 adult patients with genetically confirmed DM1 and 26 age-, sex- and education-matched unaffected controls underwent resting-state EEG and neuropsychological assessment. We calculated the Phase Lag Index (PLI) to determine EEG frequency-dependent functional connectivity between brain regions. Functional brain networks were characterized by applying concepts from graph theory and compared between-groups. Network topology was evaluated using the minimum spanning tree (MST). We evaluated correlations between network metrics and neuropsychological tests that showed statistically significant between-group differences.ResultsFunctional connectivity estimated as whole-brain median PLI for DM1 patients versus healthy controls was higher in theta band (0.141 [0.050] versus 0.125 [0.018], p = 0.029), and lower in the upper alpha band (0.154 [0.048] versus 0.182 [0.073], p = 0.038), respectively. Functional MST-constructed networks in DM1 patients were significantly dissimilar from healthy controls in the delta, (p = 0.009); theta, (p = 0.009); lower alpha, (p = 0.036); and upper alpha, (p = 0.008) bands. In evaluation of local MST network measures, trends toward networks with higher global integration in the theta band and lower global integration in the upper alpha band were observed. Compared to unaffected controls, DM1 patients performed worse on tests of attention, motor function, executive function and visuospatial memory. Visuospatial memory correlated with the global median PLI in the upper alpha band; the Stroop interference test correlated with betweenness centrality in this band.ConclusionThis study supports the hypothesis that brain changes in DM1 give rise to disrupted functional network organization, as modelled with EEG-based networks. Further study may help unravel the relations with clinical brain-related DM1 symptoms.SignificanceEEG network analysis has potential to help understand brain related DM1 phenotypes.FundingThis work was supported by the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement n° 305697 (OPTIMISTIC) and the Marigold Foundation.     

Parsing the antidepressant effects of non-invasive brain stimulation and pharmacotherapy: A symptom clustering approach on ELECT-TDCS

BackgroundTranscranial direct current stimulation (tDCS) presents small antidepressant efficacy at group level and considerable inter-individual variability of response. Its heterogeneous effects bring the need to investigate whether specific groups of patients submitted to tDCS could present comparable or larger improvement compared to pharmacotherapy. Aggregate measurements might be insufficient to address its effects.Objective/Hypothesis: To determine the efficacy of tDCS, compared to pharmacotherapy and placebo, in depressive symptom clusters.MethodsData from ELECT-TDCS (Escitalopram versus Electrical Direct-Current Therapy for Treating Depression Clinical Study, ClinicalTrials.gov, NCT01894815), in which antidepressant-free, depressed patients were randomized to receive 22 bifrontal tDCS (2 mA, 30 min) sessions (n = 94), escitalopram 20 mg/day (n = 91), or placebo (n = 60) over 10 weeks. Agglomerative hierarchical clustering identified “sleep/insomnia”, “core depressive”, “guilt/anxiety”, and “atypical” clusters that were the dependent measure. Trajectories were estimated using linear mixed regression models. Effect sizes are expressed in raw HAM-D units. P-values were adjusted for multiple comparisons.ResultsFor core depressive symptoms, escitalopram was superior to tDCS (ES = −0.56; CI_95% = -0.94 to −0.17, p = .009), which was superior to placebo (ES = 0.49; CI_95% = 0.06 to 0.92, p = .042). TDCS but not escitalopram was superior to placebo in sleep/insomnia symptoms (ES = 0.87; CI_95% = 0.22 to 1.52, p = .015). Escitalopram but not tDCS was superior to placebo in guilt/anxiety symptoms (ES = 1.66; CI_95% = 0.58 to 2.75, p = .006). No active intervention was superior to placebo for atypical symptoms.ConclusionsPharmacotherapy and non-invasive brain stimulation produce distinct effects in depressive symptoms. TDCS or escitalopram could be chosen according to specific clusters of symptoms for a bigger response.Trial registrationClinicalTrials.gov, NCT01894815     

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.     

Self-administered transcranial direct current stimulation for pain in older adults with knee osteoarthritis: A randomized controlled study

BackgroundKnee osteoarthritis (OA) is a leading cause of pain in older adults. Previous studies indicated clinic-based transcranial direct current stimulation (tDCS) was effective to reduce pain in various populations, but no published studies have reported the efficacy of home-based self-administered tDCS in older adults with knee OA using a randomized clinical study.ObjectiveThe purpose of this study was to evaluate the efficacy and feasibility of tDCS on clinical pain intensity in adults with knee OA pain.MethodsOne hundred twenty participants aged 50–85 years with knee OA pain were randomly assigned to receive fifteen daily sessions of 2 mA tDCS for 20 min (n = 60) or sham tDCS (n = 60) over 3 weeks with remote supervision via telehealth. Clinical pain intensity was measured by the Numeric Rating Scale and Western Ontario and McMaster Universities Osteoarthritis Index. Also, we collected data on the tDCS experience via a questionnaire.ResultsParticipants (68% female) had a mean age of 66 years. Active tDCS significantly reduced pain intensity compared to sham tDCS after completion of the fifteen daily sessions (Cohen's d = 1.20; p-value < 0.0001). Participants showed high levels of satisfaction with their tDCS experience, and there have been no adverse events.ConclusionWe demonstrated that home-based self-administered tDCS was feasible and reduced clinical pain intensity in older adults with knee OA, which can increase its accessibility. Future studies with multi-site randomized controlled trials are needed to validate our findings.Trial registrationClinicalTrials.gov Identifier NCT04016272.     

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.     

Abnormal patterns of corticomuscular and intermuscular coherence in childhood dystonia

ObjectiveSensorimotor processing is abnormal in Idiopathic/Genetic dystonias, but poorly studied in Acquired dystonias. Beta-Corticomuscular coherence (CMC) quantifies coupling between oscillatory electroencephalogram (EEG) and electromyogram (EMG) activity and is modulated by sensory stimuli. We test the hypothesis that sensory modulation of CMC and intermuscular coherence (IMC) is abnormal in Idiopathic/Genetic and Acquired dystonias.MethodsParticipants: 11 children with Acquired dystonia, 5 with Idiopathic/Genetic dystonia, 13 controls (12–18 years). CMC and IMC were recorded during a grasp task, with mechanical perturbations provided by an electromechanical tapper. Coherence patterns pre- and post-stimulus were compared across groups.ResultsBeta-CMC increased post-stimulus in Controls and Acquired dystonia (p = 0.001 and p = 0.010, respectively), but not in Idiopathic/Genetic dystonia (p = 0.799). The modulation differed between groups, being larger in both Controls and Acquired dystonia compared with Idiopathic/Genetic dystonia (p = 0.003 and p = 0.022). Beta-IMC increased significantly post-stimulus in Controls (p = 0.004), but not in dystonia. Prominent 4–12 Hz IMC was seen in all dystonia patients and correlated with severity (rho = 0.618).ConclusionIdiopathic/Genetic and Acquired dystonia share an abnormal low-frequency IMC. In contrast, sensory modulation of beta-CMC differed between the two groups.SignificanceThe findings suggest that sensorimotor processing is abnormal in Acquired as well as Idiopathic/Genetic dystonia, but that the nature of the abnormality differs.     

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.     

Source imaging of seizure onset predicts surgical outcome in pediatric epilepsy

ObjectiveTo assess whether ictal electric source imaging (ESI) on low-density scalp EEG can approximate the seizure onset zone (SOZ) location and predict surgical outcome in children with refractory epilepsy undergoing surgery.MethodsWe examined 35 children with refractory epilepsy. We dichotomized surgical outcome into seizure- and non-seizure-free. We identified ictal onsets recorded with scalp and intracranial EEG and localized them using equivalent current dipoles and standardized low-resolution magnetic tomography (sLORETA). We estimated the localization accuracy of scalp EEG as distance of scalp dipoles from intracranial dipoles. We also calculated the distances of scalp dipoles from resection, as well as their resection percentage and compared between seizure-free and non-seizure-free patients. We built receiver operating characteristic curves to test whether resection percentage predicted outcome.ResultsResection distance was lower in seizure-free patients for both dipoles (p = 0.006) and sLORETA (p = 0.04). Resection percentage predicted outcome with a sensitivity of 57.1% (95% CI, 34–78.2%), a specificity of 85.7% (95% CI, 57.2–98.2%) and an accuracy of 68.6% (95% CI, 50.7–83.5%) (p = 0.01).ConclusionIctal ESI performed on low-density scalp EEG can delineate the SOZ and predict outcome.SignificanceSuch an application may increase the number of children who are referred for epilepsy surgery and improve their outcome.     

Machine learning for predicting levetiracetam treatment response in temporal lobe epilepsy

ObjectiveTo determine the predictive power for seizure-freedom of 19-channels EEG, measured both before and after three months the initiation of the use of Levetiracetam (LEV), in a cohort of people after a new diagnosis of temporal-lobe epilepsy (TLE) using a machine-learning approach.MethodsTwenty-three individuals with TLE were examined. We dichotomized clinical outcome into seizure-free (SF) and non-seizure-free (NSF) after two years of LEV. EEG effective power in different frequency bands was compared using baseline EEG (T0) and the EEG after three months of LEV therapy (T1) between SF and NSF patients. Partial Least Square (PLS) analysis was used to test and validate the prediction of the model for clinical outcome.ResultsA total of 152 features were extracted from the EEG recordings. When considering only the features calculated at T1, a predictive power for seizure-freedom (AUC = 0.750) was obtained. When employing both T0 and T1 features, an AUC = 0.800 was obtained.ConclusionsThis study provides a proof-of-concept pipeline for predicting the clinical response to anti-seizure medications in people with epilepsy.SignificanceFuture studies may benefit from the pipeline proposed in this study in order to develop a model that can match each patient to the most effective anti-seizure medication.     

Measuring the effects of first antiepileptic medication in Temporal Lobe Epilepsy: Predictive value of quantitative-EEG analysis

ObjectiveTo determine the quantitative EEG responses in a population of drug-naïve patients with Temporal Lobe Epilepsy (TLE) after Levetiracetam (LEV) initiation as first antiepileptic drug (AED). We hypothesized that the outcome of AED treatment can be predicted from EEG data in patients with TLE.MethodsTwenty-three patients with TLE and twenty-five healthy controls were examined. Clinical outcome was dichotomized into seizure-free (SF) and non-seizure-free (NSF) after two years of LEV. EEG parameters were compared between healthy controls and patients with TLE at baseline (EEG^pre) and after three months of AED therapy (EEG^pre-post) and between SF and NSF patients. Receiver Operating Characteristic curves models were built to test whether EEG parameters predicted outcome.ResultsAED therapy induces an increase in EEG power for Alpha (p = 0.06) and a decrease in Theta (p < 0.05). Connectivity values were lower in SF compared to NSF patients (p < 0.001). Quantitative EEG predicted outcome after LEV treatment with an estimated accuracy varying from 65.2% to 91.3% (area under the curve [AUC] = 0.56–0.93) for EEG^pre and from 69.9% to 86.9% (AUC = 0.69–0.94) for EEG^pre-post.ConclusionsAED therapy induces EEG modifications in TLE patients, and such modifications are predictive of clinical outcome.SignificanceQuantitative EEG may help understanding the effect of AEDs in the central nervous system and offer new prognostic biomarkers for patients with epilepsy.     

Antidepressant effects of tDCS are associated with prefrontal gray matter volumes at baseline: Evidence from the ELECT-TDCS trial

BackgroundTranscranial direct current stimulation (tDCS) is a promising intervention for major depression. However, its clinical effects are heterogeneous. We investigated, in a subsample of the randomized, clinical trial Escitalopram versus Electrical Direct Current Therapy for Depression Study (ELECT-TDCS), whether the volumes of left and right prefrontal cortex (PFC) and anterior cingulate cortex (ACC) were associated with prefrontal tDCS response.MethodsBaseline structural T1 weighted MRI data were analyzed from 52 patients (15 males). Patients were randomized to the following conditions: escitalopram 20 mg/day, bifrontal tDCS (2 mA, 30min, 22 sessions), or placebo. Antidepressant outcomes were assessed over a treatment period of 10 weeks. Voxel-based gray matter volumes of PFC and ACC were determined using state-of-the-art parcellation approaches.ResultsAccording to our a priori hypothesis, in the left dorsal PFC, larger gray matter volumes were associated with depression improvement in the tDCS group (n = 15) compared to sham (n = 21) (Cohen's d = 0.3, 95% confidence interval [0.01; 0.6], p = 0.04). Neither right PFC nor ACC volumes were associated with depression improvement. Exploratory analyses of distinct PFC subregions were performed, but no area was associated with tDCS response after correction for multiple comparisons.ConclusionLeft PFC baseline gray matter volume was associated with tDCS antidepressant effects. This brain region and its subdivisions should be investigated further as a potential neurobiological predictor for prefrontal tDCS treatment in depression and might be correlated with tDCS antidepressant mechanisms of action.     

Repeated stimulation of the dorsolateral-prefrontal cortex improves executive dysfunctions and craving in drug addiction: A randomized,double-blind,parallel-group study

BackgroundAccording to the neurocognitive model of addiction, the development and maintenance of drug addiction is associated with cognitive control deficits, as well as decreased activity of prefrontal regions, especially the dorsolateral prefrontal cortex (DLPFC). This study investigated how improving executive functions (EFs) impacts methamphetamine-use disorder, which has been less explored compared to craving, but might be a central aspect for the therapeutic efficacy of DLPFC stimulation in drug addiction.MethodsWe assessed the efficacy of 10 repeated sessions of transcranial direct current stimulation (tDCS) over the DLPFC on executive dysfunctions in methamphetamine-use disorder, and its association with craving alterations. 39 of 50 initially recruited individuals with methamphetamine-use disorder who were in the abstinent-course treatment were randomly assigned to “active” and “sham” stimulation groups in a randomized, double-blind parallel-group study. They received active (2 mA, 20 min) or sham tDCS for 10 sessions over 5 weeks. Performance on major EF tasks (e.g., working memory, inhibitory control, cognitive flexibility, and risk-taking behaviour) and craving were measured before, immediately after, and 1 month following the intervention. Participants reported abstinence from drug consumption throughout the experiment, verified by regular urine tests during the course of the study up to the follow-up measurement.ResultsThe group which received active DLPFC tDCS showed significantly improved task performance across all EFs immediately after and 1 month following the intervention, when compared to both pre-stimulation baseline and individuals who received sham tDCS. Similarly, a significant reduction in craving was observed immediately after and 1 month following the intervention in the active, but not sham stimulation group. A significant correlation between cognitive control improvement and craving reduction was found as well.ConclusionsImprovement of cognitive control functions is closely associated with reduced craving. Repeated DLPFC stimulation in order to improve executive control could be a promising approach for therapeutic interventions in drug addiction. However, the observed findings require further confirmation by studies that measure relapse/consumption of the respective substances over longer follow-up measurements.     

High-amplitude fast activity in EEG: An early diagnostic marker in children with beta-propeller protein-associated neurodegeneration (BPAN)

ObjectiveThe early diagnosis of beta-propeller protein-associated neurodegeneration (BPAN) before distinct brain magnetic resonance imaging (MRI) findings of iron deposition occur remains challenging. This study examined whether children with BPAN have characteristic high-amplitude (>50 μV) fast activity (HAFA) on electroencephalography (EEG).MethodsWe conducted a retrospective analysis of EEG performed during childhood in five patients with BPAN. We also examined 143 EEGs from 59 patients with different etiologies, including epilepsy (n = 33), acute encephalopathy (n = 6), neurodevelopmental disorders (n = 5), non-epileptic events (n = 4), and others (n = 11). Trained electroencephalographers reviewed all of the EEGs. When excessive fast activity was observed, the amplitude, frequency, and locality were assessed.ResultsAll five patients with BPAN underwent initial EEGs at 12–21 months old, and diffuse continuous HAFA (range 20–50 Hz) was observed on both awake and sleep EEGs. In the awake records, there was no clear posterior dominant rhythm in 4 of the 5 patients. Although 28% of the 143 EEGs had continuous excessive fast activity, mainly in the sleep records, only two (1.4%) exhibited HAFA when asleep, and their awake EEGs had clear posterior dominant rhythm.ConclusionsThe EEGs of children with BPAN showed diffuse HAFA continuously when both awake and asleep, which is uncommon in children with other etiologies.SignificanceThis study provides an important clue for the early diagnosis of BPAN.     

Weak DCS causes a relatively strong cumulative boost of synaptic plasticity with spaced learning

BackgroundElectric fields generated during direct current stimulation (DCS) are known to modulate activity-dependent synaptic plasticity in-vitro. This provides a mechanistic explanation for the lasting behavioral effects observed with transcranial direct current stimulation (tDCS) in human learning experiments. However, previous in-vitro synaptic plasticity experiments show relatively small effects despite using strong fields compared to what is expected with conventional tDCS in humans (20 V/m vs. 1 V/m). There is therefore a need to improve the effectiveness of tDCS at realistic field intensities. Here we leverage the observation that effects of learning are known to accumulate over multiple bouts of learning, known as spaced learning.HypothesisWe propose that effects of DCS on synaptic long-term potentiation (LTP) accumulate over time in a spaced learning paradigm, thus revealing effects at more realistic field intensities.MethodsWe leverage a standard model for spaced learning by inducing LTP with repeated bouts of theta burst stimulation (TBS) in hippocampal slice preparations. We studied the cumulative effects of DCS paired with TBS at various intensities applied during the induction of LTP in the CA1 region of rat hippocampal slices.ResultsAs predicted, DCS applied during repeated bouts of theta burst stimulation (TBS) resulted in an increase of LTP. This spaced learning effect is saturated quickly with strong TBS protocols and stronger fields. In contrast, weaker TBS and the weakest electric fields of 2.5 V/m resulted in the strongest relative efficacies (12% boost in LTP per 1 V/m applied).ConclusionsWeak DCS causes a relatively strong cumulative effect of spaced learning on synaptic plasticity. Staturarion may have masked stronger effects sizes in previous in-vitro studies. Relative effect sizes of DCS are now closer in line with human tDCS experiments.