A novel tDCS sham approach based on model-driven controlled shunting

BackgroundTranscranial direct current stimulation (tDCS), a non-invasive brain stimulation technique able to transiently modulate brain activity, is surging as one of the most promising therapeutic solutions in many neurological and psychiatric disorders. However, profound limitations exist in current placebo (sham) protocols that limit single- and double-blinding, especially in non-naïve subjects.ObjectiveTo ensure better blinding and strengthen reliability of tDCS studies and trials, we tested a new optimization algorithm aimed at creating an “active” sham tDCS condition (ActiSham hereafter) capable of inducing the same scalp sensations perceived during real stimulation while preventing currents from reaching the cortex and cause changes in brain excitability.MethodsA novel model-based multielectrode technique — optimizing the location and currents of a set of small electrodes placed on the scalp — was used to control the relative amount of current delivered transcranially in real and placebo multichannel tDCS conditions. The presence, intensity and localization of scalp sensations during tDCS was evaluated by means of a specifically designed questionnaire administered to the participants. We compared blinding ratings by directly addressing subjects’ ability to discriminate across conditions for both traditional (Bifocal-tDCS and Sham, using sponge electrodes) and our novel multifocal approach (both real Multifocal-tDCS and ActiSham). Changes in corticospinal excitability were monitored based on Motor Evoked Potentials (MEPs) recorded via concurrent Transcranial Magnetic Stimulation (TMS) and electromyography (EMG).ResultsParticipants perceived Multifocal-tDCS and ActiSham similarly in terms of both localization and intensity of scalp sensations, whereas traditional Bifocal stimulation was rated as more painful and annoying compared to its Sham counterpart. Additionally, differences in scalp localization were reported for active/sham Bifocal-tDCS, with Sham tDCS inducing more widespread itching and burning sensations. As for MEPs amplitude, a main effect of stimulation was found when comparing Bifocal-Sham and ActiSham (F_(1,13) = 6.67, p = .023), with higher MEPs amplitudes after the application of Bifocal-Sham.ConclusionsCompared to traditional Bifocal-tDCS, ActiSham offers better participants’ blinding by inducing very similar scalp sensations to those of real Multifocal tDCS both in terms of intensity and localization, while not affecting corticospinal excitability.     

How structural and functional MRI can inform dual-site tACS parameters: A case study in a clinical population and its pragmatic implications

BackgroundAbnormalities in frontoparietal network (FPN) were observed in many neuropsychiatric diseases including substance use disorders. A growing number of studies are using dual-site-tACS with frontoparietal synchronization to engage this network. However, a computational pathway to inform and optimize parameter space for frontoparietal synchronization is still lacking. In this case study, in a group of participants with methamphetamine use disorders, we proposed a computational pathway to extract optimal electrode montage while accounting for stimulation intensity using structural and functional MRI.MethodsSixty methamphetamine users completed an fMRI drug cue-reactivity task. Four main steps were taken to define electrode montage and adjust stimulation intensity using 4x1 high-definition (HD) electrodes for a dual-site-tACS; (1) Frontal seed was defined based on the maximum electric fields (EF) predicted by simulation of HD montage over DLPFC (F3/F4 in EEG 10–10), (2) frontal seed-to-whole brain context-dependent correlation was calculated to determine connected regions to frontal seeds, (3) center of connected cluster in parietal cortex was selected as a location for placing the second set of HD electrodes to shape the informed montage, (4) individualized head models were used to determine optimal stimulation intensity considering underlying brain structure. The informed montage was compared to montages with large electrodes and classic frontoparietal HD montages (F3-P3/F4-P4) in terms of tACS-induced EF and ROI-to-ROI task-based/resting-state connectivity.ResultsCompared to the large electrodes, HD frontoparietal montages allow for a finer control of the spatial peak fields in the main nodes of the FPN at the cost of lower maximum EF (large-pad/HD: max EF[V/m] = 0.37/0.11, number of cortical sub-regions that EF exceeds 50% of the max = 77/13). For defining stimulation targets based on EF patterns, using group-level head models compared to a single standard head model results in comparable but significantly different seed locations (6.43 mm Euclidean distance between the locations of the frontal maximum EF in standard-space). As expected, significant task-based/resting-state connections were only found between frontal-parietal locations in the informed montage. Cue-induced craving score was correlated with frontoparietal connectivity only in the informed montage (r = ?0.24). Stimulation intensity in the informed montage, and not in the classic HD montage, needs 40% reduction in the parietal site to reduce the disparity in EF between stimulation sites.ConclusionThis study provides some empirical insights to montage and dose selection in dual-site-tACS using individual brain structures and functions and proposes a computational pathway to use head models and functional MRI to define (1) optimum electrode montage for targeting FPN in a context of interest (drug-cue-reactivity) and (2) proper transcranial stimulation intensity.     

不同波形低频率电刺激对小鼠海马电点燃癫痫的作用比较

目的观察比较不同脉冲波形的低频率电刺激对海马电点燃癫痫模型小鼠的作用差异。方法采用电点燃刺激法建立小鼠癫痫模型, 观察正弦波、单相方波、双相方波低频率电刺激对模型小鼠癫痫行为发作及后放电持续时间的影响, 并比较不同时间点给予正弦波低频率电刺激的抗癫痫作用。结果与对照组比较, 正弦波低频率电刺激30 s能降低小鼠海马电点燃癫痫发作等级(2.85 ± 0.27 vs 4.75 ±0.12, P < 0.05)、减少大发作概率(53.6% vs 96.5%, P < 0.01) 和缩短后放电持续时间[(16.22 ± 1.69) s vs (30.29 ± 1.12) s, P < 0.01], 而单相方波和双相方波低频率电刺激30 s没有明显的抗癫痫作用。常用的单相方波低频率电刺激15 min能降低小鼠海马电点燃发作等级(3.58 ± 0.16, P < 0.05)、减少大发作概率(66.7%, P < 0.01);但对海马后放电持续时间及大发作持续时间无影响(均 P>0.05)。此外, 电点燃刺激前预先给予或结束后3 s内给予正弦波低频率电刺激具有明显的抗癫痫作用( P < 0.05或 P < 0.01), 而电点燃刺激结束10 s给予正弦波低频率电刺激则无上述抗癫痫作用。 结论低频率电刺激抗癫痫作用受波形参数的影响, 其中正弦波低频率电刺激能有效抑制小鼠海马电点燃癫痫的发作。     

Utility of Deep Brain Stimulation Telemedicine for Patients With Movement Disorders During the COVID-19 Outbreak in China

ObjectiveTo explore the utility of deep brain stimulation (DBS) telemedicine in the management of patients with movement disorders from January 2019 to March 2020, covering the main period of the COVID-19 outbreak in China.Materials and MethodsWe obtained data from 40 hospitals around China that employed DBS tele-programming for their outpatients with Parkinson’s disease or dystonia from January 2019 to March 2020. Data were obtained on the number and nature of patients’ DBS health care service requests, reasons for their requests, the number of DBS telemedicine sessions subsequently completed, safety issues, and the patients’ satisfaction with the DBS tele-programing parameter adjustments made.ResultsThere were 909 DBS tele-programming health service requests (from 196 patients) completed during the study period. The results showed: 1) the number of DBS telemedicine sessions requested and the number of patients examined increased during the COVID-19 outbreak in February and March 2020 when compared with the monthly numbers in 2019; 2) the most common reason for the patients’ health service requests was poor symptom control; 3) the most common DBS tele-programming adjustment made was voltage change; 4) overall, most (89%) DBS tele-programming adjustment sessions were experienced by the patients as satisfactory; and 5) significant adverse events and unexpected treatment interruptions caused by connection failure or other hardware- or software-related problems did not occur.ConclusionsDBS telemedicine could have a unique role to play in maintaining the delivery of DBS treatment and medical care to outpatients with movement disorders during the COVID-19 pandemic.     

Proteases and their inhibitors as prognostic factors for high-grade serous ovarian cancer

Ovarian carcinoma is one of the most lethal malignancies, but only very few prognostic biomarkers are known. The degradome, comprising proteases, protease non-proteolytic homologues and inhibitors, have been involved in the prognosis of many cancer types, including ovarian carcinoma. The prognostic significance of the whole degradome family has not been specifically studied in high-grade serous ovarian cancer. A targeted DNA microarray known as the CLIP-CHIP microarray was used to identify potential prognostic factors in ten high-grade serous ovarian cancer women who had early recurrence (<1.6 years) or late/no recurrence after first line surgery and chemotherapy. In women with early recurrence, we identified seven upregulated genes (TMPRSS4, MASP1/3, SPC18, PSMB1, IGFBP2, CFI – encoding Complement Factor I – and MMP9) and one down-regulated gene (ADAM-10). Using immunohistochemistry, we evaluated the prognostic effect of these 8 candidate genes in an independent cohort of 112 high-grade serous ovarian cancer women. Outcomes were progression, defined according to CA-125 criteria, and death. Multivariate Cox proportional hazard regression models were done to estimate the associations between each protein and each outcome. High ADAM-10 expression (intensity of 2–3) was associated with a lower risk of progression (adjusted hazard ratio (HR): 0.51; 95% confidence interval (CI): 0.29-0.87). High complement factor I expression (intensity 2–3) was associated with a higher risk of progression (adjusted HR: 2.30, 95% CI: 1.17–4.53) and death (adjusted HR: 3.42; 95% CI: 1.72–6.79). Overall, we identified the prognostic value of two proteases, ADAM-10 and complement factor I, for high-grade serous ovarian cancer which could have clinical significance.     

Efficacy of percutaneous and transcutaneous tibial nerve stimulation in women with idiopathic overactive bladder: A prospective randomised controlled trial

BackgroundDifferent studies have reported the efficacy of percutaneous tibial nerve stimulation (PTNS) and transcutaneous tibial nerve stimulation (TTNS) in treating idiopathic overactive bladder (OAB). However, no study has compared the effectiveness of PTNS and TTNS added to bladder training (BT) in idiopathic OAB.ObjectiveTo compare the efficacy of PTNS and TTNS added to BT in women with idiopathic OAB.MethodsWe randomised 60 women with idiopathic OAB into 3 groups. Group 1 (n = 19) received BT, Group 2 (n = 19) received PTNS in addition to BT, and Group 3 (n = 20) received TTNS in addition to BT. PTNS and TTNS were performed 2 days a week, for 30 min a day, for a total of 12 sessions for 6 weeks. Patients were evaluated by incontinence severity (pad test), a 3-day voiding diary (frequency of voiding, incontinence episodes, nocturia and number of pads used), symptom severity, quality of life, treatment success (positive response rate), treatment satisfaction (Likert scale), discomfort level and preparation time for stimulation (sec).ResultsAt the end of treatment; severity of incontinence, frequency of voiding, incontinence episodes, nocturia, number of pads used, symptom severity and quality of life were significantly improved in Groups 2 and 3 versus Group 1 (P < 0.0167). Treatment success and treatment satisfaction were higher in Groups 2 and 3 than Group 1 (P < 0.001 and P < 0.0167, respectively). Level of discomfort was lower, treatment satisfaction was higher and preparation time for stimulation was shorter in Group 3 than Group 2 (P < 0.05).ConclusionBoth the PTNS plus BT and TTNS plus BT were more effective than BT alone in women with idiopathic OAB. These 2 tibial nerve stimulation methods had similar clinical efficacy but with slight differences: TTNS had shorter preparation time, less discomfort level and higher patient satisfaction than PTNS.     

Development of a core outcome set for venous leg ulceration (CoreVen) research evaluations (protocol)

BackgroundA venous leg ulcer is a chronic leg wound caused by poor venous blood circulation in the lower limbs. It is a recurring condition causing pain, malodour, reduced mobility, and depression. Randomised controlled trials evaluating treatments for venous leg ulcers provide important evidence to inform clinical decision-making. However, for findings to be useful, outcomes need to be clinically meaningful, consistently reported across trials, and fully reported. Research has identified the large number of outcomes reported in venous leg ulcer trials, impacting both synthesis of results, and clinical decision-making. To address this, a core outcome set will be developed. A core outcome set is an agreed standardised set of outcomes which should be, as a minimum, measured and reported in all trials which evaluate treatment effectiveness for a given indication. A core outcome set has the potential to reduce research waste, improve the utility of RCTs, reduce reporting bias, facilitate treatment comparisons across different sources of evidence and expedite the production of systematic reviews, meta-analyses and evidence-based clinical guidelines.AimThe aim of this project is to develop a core outcome set for research evaluating the effectiveness of interventions for treating venous leg ulceration.MethodsThrough a scoping review of the literature on venous leg ulceration, we will firstly identify a list of candidate outcome domains (broad categories in relation to what is being measured) from randomised controlled trials and qualitative research, and outcomes (specific methods in relation to what is being measured). In two further stages, we will use the resulting lists of outcome domains and outcomes to design two online surveys. A range of stakeholders will be invited to participate in the surveys and they will be asked to indicate which outcome domains and outcomes are most important and should be considered as core in future research reports.     

EEG power spectral density under Propofol and its association with burst suppression,a marker of cerebral fragility

ObjectiveUnder General Anesthesia (GA), age and Burst Suppression (BS) are associated with cognitive postoperative complications, yet how these parameters are related to per-operative EEG and hypnotic doses is unclear. In this prospective study, we address this question comparing age and BS occurrences with a new score (BP_TIVA) based on Propofol doses, EEG and alpha-band power spectral densities, evaluated for SEF₉₅ = 8–13 Hz.Methods59 patients (55 [34–67] yr, 67% female) undergoing neuroradiology or orthopedic surgery were included. Total IntraVenous Anesthesia was used for Propofol and analgesics infusion. Cerebral activity was monitored from a frontal electrodes montage EEG.ResultsBP_TIVA was inversely correlated with age (Pearson r = −0.78, p < 0.001), and was significantly lower (p < 0.001) when BS occurred during the GA first minutes (induction). Additionally, the age-free BP_TIVA score was better associated with BS at induction than age (AUC = 0.94 versus 0.82, p < 0.05).ConclusionWe designed BP_TIVA score based on hypnotics and EEG. It was correlated with age yet was better associated to BS occurring during GA induction, the latter being a cerebral fragility sign.SignificanceThis advocate for an approach based on evaluating the cerebral physiological age (« brain age ») to predict postoperative cognitive evolution.