Polarity-specific high-definition transcranial direct current stimulation of the anterior and posterior default mode network improves remote memory retrieval

BackgroundPrevious studies show that activity in the posterior default mode network (pDMN), including the posterior cingulate cortex and the precuneus, is correlated with the success of long-term episodic memory retrieval. However, the role of the anterior DMN (aDMN) including the medial prefrontal cortex is still unclear. Some studies show that activating the medial prefrontal cortex improves memory retrieval while other studies show deactivation of the medial prefrontal cortex in successful retrieval of episodic memories, suggesting a possible functional dissociation between the aDMN and pDMN.ObjectiveIn the current study, we aim to causally explore this probable dissociation using high-definition transcranial direct current stimulation (HD-tDCS).MethodsWe perform a randomised double-blinded two-visit placebo-controlled study with 84 healthy young adults. During Visit 1 they learn 75 Swahili-English word-associations. Seven days later, they randomly receive either anodal, cathodal or sham HD-tDCS targeting the pDMN or aDMN while they recall what they have previously learned.ResultsWe demonstrate that anodal stimulation of the pDMN and cathodal stimulation of the aDMN, equally improve the percentage of Swahili-English word-associations recalled 7 days after learning.ConclusionsModulating the activity in the aDMN and pDMN causally affect memory retrieval performance. HD-tDCS of the aDMN and pDMN shows that anodal stimulation of the pDMN and cathodal stimulation of the aDMN increases memory retrieval performance one week after the learning phase. Given consistent evidence, it is highly likely that we are increasing the activity in the pDMN with anodal pDMN stimulation. However, it is not clear if cathodal HD-tDCS targetting aDMN works via decoupling from the pDMN or via indirectly disinhibit pDMN.     

Should we start integrating genetic data in decision-making on device-aided therapies in Parkinson disease? A point of view

Parkinson disease (PD) is a complex heterogeneous neurodegenerative disorder. Association studies have revealed numerous genetic risk loci and variants, and about 5–10% suffer from a monogenic form. Because the presentation and course of PD is unique to each patient, personalized symptomatic treatment should ideally be offered to treat the most disabling motor and non-motor symptoms. Indeed, clinical milestones and treatment complications that appear during disease progression are influenced by the genetic imprint. With recent advances in PD, more patients live longer to become eligible for device-aided therapies, such as apomorphine continuous subcutaneous infusion, levodopa duodenal gel infusion, and deep brain stimulation surgery, each with its own inclusion and exclusion criteria, advantages and disadvantages. Because genetic variants influence the expression of particular clinical profiles, factors for better or worse outcomes for device-aided therapies may then be proactively identified. For example, mutations in PRKN, LRRK2 and GBA express phenotypes that favor suitability for different device therapies, although with marked differences in the therapeutic window; whereas multiplications of SNCA express phenotypes that make them less desirable for device therapies.     

Effects of transcranial direct current stimulation on experimental pain perception: A systematic review and meta-analysis

ObjectiveMany studies have examined the effectiveness of transcranial direct current stimulation (tDCS) on human pain perception in both healthy populations and pain patients. Nevertheless, studies have yielded conflicting results, likely due to differences in stimulation parameters, experimental paradigms, and outcome measures. Human experimental pain models that utilize indices of pain in response to well-controlled noxious stimuli can avoid many confounds present in clinical data. This study aimed to assess the robustness of tDCS effects on experimental pain perception among healthy populations.MethodsWe conducted three meta-analyses that analyzed tDCS effects on ratings of perceived pain intensity to suprathreshold noxious stimuli, pain threshold and tolerance.ResultsThe meta-analyses showed a statically significant tDCS effect on attenuating pain-intensity ratings to suprathreshold noxious stimuli. In contrast, tDCS effects on pain threshold and pain tolerance were statistically non-significant. Moderator analysis further suggested that stimulation parameters (active electrode size and current density) and experimental pain modality moderated the effectiveness of tDCS in attenuating pain-intensity ratings.ConclusionThe effectiveness of tDCS on attenuating experimental pain perception depends on both stimulation parameters of tDCS and the modality of experimental pain.SignificanceThis study provides some theoretical basis for the application of tDCS in pain management.     

Temporal interference stimulation targets deep brain regions by modulating neural oscillations

BackgroundTemporal interference (TI) stimulation of the brain generates amplitude-modulated electric fields oscillating in the kHz range with the goal of non-invasive targeted deep brain stimulation. Yet, the current intensities required in human (sensitivity) to modulate deep brain activity and if superficial brain region are spared (selectivity) at these intensities remains unclear.ObjectiveWe developed an experimentally constrained theory for TI sensitivity to kHz electric field given the attenuation by membrane low-pass filtering property, and for TI selectivity to deep structures given the distribution of modulated and unmodulated electric fields in brain.MethodsThe electric field threshold to modulate carbachol-induced gamma oscillations in rat hippocampal slices was determined for unmodulated 0.05–2 kHz sine waveforms, and 5 Hz amplitude-modulated waveforms with 0.1–2 kHz carrier frequencies. The neuronal effects are replicated with a computational network model to explore the underlying mechanisms, and then coupled to a validated current-flow model of the human head.ResultsAmplitude-modulated electric fields are stronger in deep brain regions, while unmodulated electric fields are maximal at the cortical regions. Both experiment and model confirmed the hypothesis that spatial selectivity of temporal interference stimulation depends on the phasic modulation of neural oscillations only in deep brain regions. Adaptation mechanism (e.g. GABA_b) enhanced sensitivity to amplitude modulated waveform in contrast to unmodulated kHz and produced selectivity in modulating gamma oscillation (i.e. Higher gamma modulation in amplitude modulated vs unmodulated kHz stimulation). Selection of carrier frequency strongly affected sensitivity to amplitude modulation stimulation. Amplitude modulated stimulation with 100 Hz carrier frequency required ∼5 V/m (corresponding to ∼13 mA at the scalp surface), whereas, 1 kHz carrier frequency ∼60 V/m (∼160 mA) and 2 kHz carrier frequency ∼80 V/m (∼220 mA) to significantly modulate gamma oscillation. Sensitivity is increased (scalp current required decreased) for theoretical neuronal membranes with faster time constants.ConclusionThe TI sensitivity (current required at the scalp) depends on the neuronal membrane time-constant (e.g. axons) approaching the kHz carrier frequency. TI selectivity is governed by network adaption (e.g. GABA_b) that is faster than the amplitude-modulation frequency. Thus, we show neuronal and network oscillations time-constants determine the scalp current required and the selectivity achievable with TI in humans.     

Phase-dependent offline enhancement of human motor memory

BackgroundSkill learning engages offline activity in the primary motor cortex (M1). Sensorimotor cortical activity oscillates between excitatory trough and inhibitory peak phases of the mu (8–12 Hz) rhythm. We recently showed that these mu phases influence the magnitude and direction of neuroplasticity induction within M1. However, the contribution of M1 activity during mu peak and trough phases to human skill learning has not been investigated.ObjectiveTo evaluate the effects of phase-dependent TMS during mu peak and trough phases on offline learning of a newly-acquired motor skill.MethodsOn Day 1, three groups of healthy adults practiced an explicit motor sequence learning task with their non-dominant left hand. After practice, phase-dependent TMS was applied to the right M1 during either mu peak or mu trough phases. The third group received sham TMS during random mu phases. On Day 2, all subjects were re-tested on the same task to evaluate offline learning.ResultsSubjects who received phase-dependent TMS during mu trough phases showed increased offline skill learning compared to those who received phase-dependent TMS during mu peak phases or sham TMS during random mu phases. Additionally, phase-dependent TMS during mu trough phases elicited stronger whole-brain broadband oscillatory power responses than phase-dependent TMS during mu peak phases.ConclusionsWe conclude that sensorimotor mu trough phases reflect brief windows of opportunity during which TMS can strengthen newly-acquired skill memories.     

Could non-HDL-cholesterol be a better marker of atherogenic dyslipidemia in obstructive sleep apnea?

Background/objectiveObstructive sleep apnea (OSA) is independently associated with dyslipidemia, a surrogate marker of atherosclerosis. Low-density lipoprotein (LDL)-cholesterol is accepted as a major independent risk factor for cardiovascular disease. However, non-high-density lipoprotein (HDL)-cholesterol is a better marker of atherogenic dyslipidemia and recommended as a target of lipid lowering therapy. We aimed to assess the prevalence of atherogenic dyslipidemia, and relationship between OSA severity and serum LDL-cholesterol and non-HDL cholesterol levels in OSA patients.MethodsWe retrospectively evaluated treatment naïve 2361 subjects admitted to the sleep laboratory of a university hospital for polysomnography. All subjects’ lipid profile including total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, and non-HDL-cholesterol were measured.ResultsOut of 2361 patients (mean age 49.6 ± 11.9 years; 68.9% male, apnea-hypopnea index 36.6 ± 28.4/h), 185 (7.8%) had no OSA and 2176 (92.2%) had OSA. Atherogenic dyslipidemia prevalence was high (57–66%) in OSA patients, and especially increased in severe OSA compared to other groups (p < 0.05). Though total and LDL-cholesterol did not differ between those with and without OSA, non-HDL-cholesterol (p = 0.020), and triglycerides (p = 0.001) were higher and HDL-cholesterol levels (p = 0.018) were lower in OSA patients than non-OSA. Non-HDL-cholesterol was significantly correlated with OSA severity (p < 0.001) and hypoxia parameters (p < 0.01), whereas LDL-cholesterol showed no correlation.ConclusionsAtherogenic dyslipidemia is highly prevalent and non-HDL-cholesterol levels are significantly increased, predominantly in severe OSA patients. Non-HDL-cholesterol but not LDL-cholesterol, is significantly correlated with OSA severity and hypoxia parameters. Therefore, it could be better to use non-HDL-cholesterol, which is a guideline recommended target of lipid therapy, as a marker of atherosclerotic cardiovascular risk in OSA patients.     

Two forms of short-interval intracortical inhibition in human motor cortex

BackgroundPulses of transcranial magnetic stimulation (TMS) with a predominantly anterior-posterior (AP) or posterior-anterior (PA) current direction over the primary motor cortex appear to activate distinct excitatory inputs to corticospinal neurons. In contrast, very few reports have examined whether the inhibitory neurons responsible for short-interval intracortical inhibition (SICI) are sensitive to TMS current direction.ObjectivesTo investigate whether SICI evaluated with AP and PA conditioning stimuli (CS_PA and CS_AP) activate different inhibitory pathways. SICI was always assessed using a PA-oriented test stimulus (TS_PA).MethodsUsing two superimposed TMS coils, CS_PA and CS_AP were applied at interstimulus intervals (ISI) of 1–5 ms before a TS_PA, and at a range of different intensities. Using a triple stimulation design, we then tested whether SICI at ISI of 3 ms using opposite directions of CS (SICI_CSPA3 and SICI_CSAP3) interacted differently with three other forms of inhibition, including SICI at ISI of 2 ms (SICI_CSPA2), cerebellum-motor cortex inhibition (CBI 5 ms) and short-latency afferent inhibition (SAI 22 ms). Finally, we compared the effect of tonic and phasic voluntary contraction on SICI_CSPA3 and SICI_CSAP3.ResultsCS_AP produced little SICI at ISIs = 1 and 2 ms. However, at ISI = 3 ms, both CS_AP and CS_PA were equally effective at the same percent of maximum stimulator output. Despite this apparent similarity, combining SICI_CSPA3 or SICI_CSAP3 with other forms of inhibition led to quite different results: SICI_CSPA3 interacted in complex ways with CBI, SAI and SICI_CSPA2, whereas the effect of SICI_CSAP3 appeared to be quite independent of them. Although SICI_CSPA and SICI_CSAP were both reduced by the same amount during voluntary tonic contraction compared with rest, in a simple reaction time task SICI_CSAP was disinhibited much earlier following the imperative signal than SICI_CSPA.ConclusionsSICI_CSPA appears to activate a different inhibitory pathway to that activated by SICI_CSAP. The difference is behaviourally relevant since the pathways are controlled differently during volitional contraction. The results may explain some previous pathological data and open the possibility of testing whether these pathways are differentially recruited in a range of tasks.     

Thalamic deep brain stimulation for Tourette Syndrome: A naturalistic trial with brief randomized,double-blinded sham-controlled periods

BackgroundThere is still a lack of controlled studies to prove efficacy of thalamic deep brain stimulation for Tourette's Syndrome.ObjectivesIn this controlled trial, we investigated the course of tic severity, comorbidities and quality of life during thalamic stimulation and whether changes in tic severity can be assigned to ongoing compared to sham stimulation.MethodsWe included eight adult patients with medically refractory Tourette's syndrome. Bilateral electrodes were implanted in the centromedian-parafascicular-complex and the nucleus ventro-oralis internus. Tic severity, quality of life and comorbidities were assessed before surgery as well as six and twelve months after. Short randomized, double-blinded sham-controlled crossover sequences with either active or sham stimulation were implemented at both six- and twelve-months’ assessments. The primary outcome measurement was the difference in the Yale Global Tic Severity Scale tic score between active and sham stimulation. Adverse events were systematically surveyed for all patients to evaluate safety.ResultsActive stimulation resulted in significantly higher tic reductions than sham stimulation (F = 79.5; p = 0.001). Overall quality of life and comorbidities improved significantly in the open-label-phase. Over the course of the trial two severe adverse events occurred that were resolved without sequelae.ConclusionOur results provide evidence that thalamic stimulation is effective in improving tic severity and overall quality of life. Crucially, the reduction of tic severity was primarily driven by active stimulation. Further research may focus on improving stimulation protocols and refining patient selection to improve efficacy and safety of deep brain stimulation for Tourette's Syndrome.     

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.     

延续护理在2型糖尿病患者中的应用效果及并发症发生率影响观察

目的:研究对2型糖尿病患者实施延续护理的效果。方法:选取2018年1月~2018年12月在某院治疗后出院的2型糖尿病患者120例展开研究,按护理施差异分为两组,对照组常规护理,观察组在常规护理基础上实施延续护理,对比分析护理效果、护理后并发症发生率以及生活质量改善情况。结果:经护理后观察组血糖各指标均明显低于对照组(P<0.05);观察组发生率21.6%,对照组发生率41.6%(P<0.05);护理后观察组生活质量各项评分均明显高于对照组(P<0.05)。结论:对2型糖尿病患者实施延续护理效果显著,值得推广。