Sleep deprivation in depression stabilizing antidepressant effects by repetitive transcranial magnetic stimulation

Partial sleep deprivation (PSD) has a profound and rapid effect on depressed mood. However, the transient antidepressant effect of PSD - most patients relapse after one night of recovery sleep - is limiting the clinical use of this method. Using a controlled, balanced parallel design we studied, whether repetitive transcranial magnetic stimulation (rTMS) applied in the morning after PSD is able to prevent this relapse. 20 PSD responders were randomly assigned to receive either active or sham stimulation during the following 4 days after PSD. Active stimulation prolonged significantly (p < 0.001) the antidepressant effect of PSD up to 4 days. This finding indicates that rTMS is an efficacious method to prevent relapse after PSD.     

重复经颅磁刺激对创伤性颅脑损伤患者脑脊液中兴奋性氨基酸含量的影响

目的：探讨重复经颅磁刺激（rTMS）对急性颅脑损伤患者脑脊液中兴奋性氨基酸（EAA）含量的影响。方法：30例创伤性颅脑损伤（TBI）病人按格拉斯哥昏迷评分分为轻型组（rTMS3）、中型组（rTMS2）、重型组（rTMS1）,每组10例,各组病人分别随机分为rTMS对照亚组（A组）及治疗亚组（B组）,每亚组5例。于TBI后第15天行腰椎穿刺采集脑脊液,采用高效液相色谱法测定脑脊液中谷氨酸（ASP）及门冬氨酸（GLU）含量。结果：脑脊液ASP和GLU水平随着脑损伤程度的加重而升高,各rTMS治疗组与相应各对照组的EAA相比,rTMS治疗组EAA的水平均低于相应对照组。结论：rTMS可通过降低TBI后脑脊液EAA水平发挥脑保护作用。脑脊液EAA的含量变化可作为TBI严重程度的生化指标。     

重复经颅磁刺激对创伤性颅脑损伤患者脑脊液中兴奋性氨基酸 含量的影响

目的:探讨重复经颅磁刺激(rTMS)对急性颅脑损伤患者脑脊液中兴奋性氨基酸(EAA)含量的影响。方法:30例创伤性颅脑损伤(TBI)病人按格拉斯哥昏迷评分分为轻型组(rTMS3)、中型组(rTMS2)、重型组(rTMS1),每组10例,各组病人分别随机分为rTMS对照亚组(A组)及治疗亚组(B组),每亚组5例。于TBI后第15天行腰椎穿刺采集脑脊液,采用高效液相色谱法测定脑脊液中谷氨酸(ASP)及门冬氨酸(GLU)含量。结果:脑脊液ASP和GLU水平随着脑损伤程度的加重而升高,各rTMS治疗组与相应各对照组的EAA相比,rTMS治疗组EAA的水平均低于相应对照组。结论:rTMS可通过降低TBI后脑脊液EAA水平发挥脑保护作用。脑脊液EAA的含量变化可作为TBI严重程度的生化指标。     

Synthesis and monoamine transporter affinity of 3-aryl substituted trop-2-enes

A series of new 3-aryl-tropanes have been synthesized, and their affinities and selectivities were evaluated for monoamine transporters. (1RS)-3-(Fluoren-2-yl)-8-methyl-8-azabicyclo[3.2.1]oct-2-ene exhibited the highest affinity for the human serotonin transporter (IC₅₀ = 14.5 nM). It is also 52-fold and 230-fold selective over human dopamine and norepinephrine transporters, respectively.     

Comparison of the outcomes of repetitive transcranial magnetic stimulation to the ipsilateral and contralateral auditory cortex in unilateral tinnitus

Transcranial magnetic stimulation (TMS) is a noninvasive method of activating or deactivating focal areas of the human brain. Repetitive TMS (rTMS) applied over the temporoparietal cortex has been reported to show therapeutic effects on tinnitus. We compared the effects of 1?Hz rTMS delivered either contralaterally or ipsilaterally to the symptomatic ear in patients with unilateral tinnitus. Forty patients with asymmetric hearing loss and non-pulsatile tinnitus localized to poorer ear of 6 months in duration or greater who were refractory to medication were enrolled in this study. Patients were assigned randomly to one of two treatment groups: with 1?Hz stimulation applied the temporoparietal junction either ipsilaterally (n?=?21) or contralaterally (n?=?19) to the symptomatic ear. The patients were given 600 pulses per session daily for 5?d. Changes in the tinnitus handicap inventory (THI) and self-rating visual analog scores (VAS) for loudness, awareness and annoyance were analyzed before, immediately after and 1 month after treatment. There was no significant difference in the rate of patients with marked improvement between ipsilateral and contralateral stimulation groups. In addition, there were no significant differences in the amount of decreases in THI scores and VAS between the two groups immediately or 1 month after rTMS. Finally, significant decreases in THI scores and most VAS were observed 1 month after rTMS in both groups compared to pretreatment. Daily treatment with 1?Hz rTMS ipsilaterally and contralaterally to the side of tinnitus both had significant beneficial effects. The laterality of stimulation with 1?Hz rTMS is not the decisive factor in relieving symptoms.     

Effects of transcranial magnetic stimulation on oxidative stress in experimental autoimmune encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) reproduces a multiple sclerosis (MS)-like experimental model. The main objective was to evaluate the effect of extremely low-frequency electromagnetic fields (EL-EMF) application, like a paradigm of transcranial magnetic stimulation (TMS) in the development of EAE. Rats were injected with a single dose of 150?μg of myelin oligodendrocyte glycoprotein (MOG, fragment 35–55) to produce experimental MS. To assess the effect of TMS application in EAE, the rats were treated with TMS (60?Hz and 0.7?mT) for 2?h in the morning, once a day, 5 days a week, during 3 weeks. TMS was applied to the head. The effect of TMS on EAE was evaluated as motor symptoms and, oxidative and cell damage. The data showed that MOG induced motor symptoms as tail paralysis and limb paresis/paralysis, oxidative stress and cell death similar to MS when compared with control animals. Importantly, TMS application attenuated motor symptoms, oxidative and cell damage, whereas it increased antioxidant system. Our findings suggest that: (i) MOG reproduces an experimental model of MS characterised by oxidative and cell damage; and (ii) TMS application decreases oxidative stress and cell death induced by MOG.     

低频重复经颅磁刺激联合益生菌对脑卒中后抑郁患者认知和运动功能及肠道菌群的影响

目的 分析低频重复经颅磁刺激联合益生菌对脑卒中后抑郁患者认知、运动功能及肠道菌群的影响。 方法 选取我院2016年12月至2019年2月收治的110例脑卒中后抑郁患者进行研究,按随机数字表法分为观察组与对照组,各55例。两组患者均给予低频重复经颅磁刺激治疗,观察组患者进一步联合益生菌治疗。治疗4周后比较两组患者抑郁、认知功能、运动功能、肠道菌群及不良反应发生情况。 结果 治疗后观察组患者肠道双歧杆菌数量[(9.59±0.73)lg copies/g vs(7.56±0.54)lg copies/g]和乳杆菌数量[(9.53±0.68)lg copies/g vs(7.84±0.56)lg copies/g]高于对照组,而肠球菌数量[(7.86±0.63)lg copies/g vs(9.81±0.52)lg copies/g]与大肠埃希菌数量[(7.64±0.37)lg copies/g vs(9.16±0.48)lg copies/g]低于对照组,差异有统计学意义(均P0.05)。 结论 低频重复经颅磁刺激联合益生菌治疗可有效改善脑卒中后抑郁患者认知、运动功能及其肠道菌群和抑郁状态,安全性较高。     

Norepinephrine transporter (NET) knock-out upregulates dopamine and serotonin transporters in the mouse brain

The noradrenaline, serotonin and dopamine transporters are three main transporters, which are the target of the antidepressant drugs. In the present study we demonstrate that the life-long deletion of the noradrenaline transporter (NET) induced up-regulation of two other monoamine transporters, dopamine and serotonin (DAT and SERT, respectively). An increase in the binding of [³H]paroxetine to the SERT and [³H]GBR12935 to the DAT was observed in various brain regions of NET-KO mice, without alterations of mRNA encoding these transporters, as measured by in situ hybridization. This important finding impacts the interpretation of previous data indicating the supersensitizity of NET-KO mice for psychostimulants or stronger effect of citalopram in behavioral tests. While using the NET-KO mice in various psychopharmacological studies is very important, one has to be aware that these mice lack NET from the earliest period of their existence, thus compensatory alterations do take place and have to be considered when it comes to interpretation of the obtained results.     

Effect of transcranial magnetic stimulation on treatment effect and immune function

To explore the effect of transcranial stimulation on the therapeutic effect and immune function of patients with post-stroke depression (PSD). Methods Selection in September 2020–April 2021 on the diagnosis of 70 patients with PSD as the research object, 35 patients were randomly divided into control group and intervention group and control group given conventional treatment, the intervention group in the control group on the basis of the application of transcranial magnetic stimulation treatment, compare the curative effect of two groups of patients after the treatment cycle and the effects on the immune function. Results After treatment, the levels of DA, NE, 5-HT in 2 groups were significantly increased, and those in the observation group were significantly higher than those in the control group (P < 0.05). After 8 weeks of treatment, serum Gly content in 2 groups was significantly increased and Glu content was significantly decreased compared with before treatment. Compared with the control group, serum Gly content in observation group was significantly increased and Glu content was significantly decreased after treatment (P < 0.05). After 8 weeks of treatment, the contents of IL-1β, IL-6 and TNF-α in serum of 2 groups were significantly decreased, compared with the control group, the contents of IL-1β, IL-6 and TNF-α in serum of observation group were significantly decreased (P < 0.05); Before treatment, there was no significant difference in PHQ-9 score and MBI score between the two groups (P > 0.05). After 8 weeks of treatment, PHQ-9 score and MBI score in the two groups were better than before treatment, and the observation group was better than the control group (P < 0.05). Conclusion Transcranial magnetic stimulation therapy can not only effectively promote the synthesis and release of monoamine neurotransmitters in patients with post-stroke depression, regulate the inhibitory/excitatory amino acid neurotransmitters, reduce inflammatory response, improve the clinical treatment effect and enhance the immune function of PSD patients, which has clinical application value.     

重复经颅磁刺激联合低剂量氟西汀对CUMS抑郁小鼠的影响*

目的:探讨重复经颅磁刺激(rTMS)联合低剂量氟西汀对慢性不可预知轻度压力(CUMS)抑郁小鼠的影响及其交互作用。方法:取42只雄性BALB/c小鼠随机分为正常对照组(Control,7只)和抑郁症模型组(Model,35只),Model组小鼠给予限制塑料管内、鼠笼倾斜、不筑巢、拥挤环境、明暗颠倒、白噪声等6种刺激,每种刺激随机且不同时出现2次,共刺激4周建立CUMS模型。随后35只Model组鼠随机分为CUMS组(8只)、氟西汀组(Fluoxetine,9只)、rTMS组(9只)和rTMS+Fluoxetine组(9只)。Fluoxetine组给予腹腔注射氟西汀5 mg/(kg·d),rTMS组给予10 Hz频率刺激,rTMS+Fluoxetine组给予腹腔注射氟西汀5 mg/(kg·d)和10 Hz频率刺激,Control和CUMS模型组给予相同体积生理盐水腹腔注射和伪刺激,各组均连续干预4周,随后进行行为学实验,最后运用析因设计方差分析方法分析Fluoxetine与rTMS的交互作用。结果:与Control组比,CUMS组小鼠强迫游泳实验中不动时间显著升高(P＜0.05),蔗糖实验中糖喜好程度、旷场实验中心运动次数和体重变化率均显著下降(P＜0.05)。与CUMS组比,rTMS组、Fluoxetine组和rTMS+Fluoxetine组抑郁症小鼠强迫游泳实验中不动时间显著降低(P＜0.01)、蔗糖实验中糖喜好程度和旷场实验中心运动次数显著升高(P＜0.05),其中rTMS+Fluoxetine组联合应用效果更显著(P＜0.05),但体重变化率仅rTMS+Fluoxetine组有变化(P＜0.05)。结论:重复经颅磁刺激和/或氟西汀均能不同程度的改善CUMS小鼠抑郁状态,其中联合应用的干预作用优于单独使用氟西汀或rTMS的效果,且有交互作用。     

Listening to speech recruits specific tongue motor synergies as revealed by transcranial magnetic stimulation and tissue-Doppler ultrasound imaging

The activation of listener''s motor system during speech processing was first demonstrated by the enhancement of electromyographic tongue potentials as evoked by single-pulse transcranial magnetic stimulation (TMS) over tongue motor cortex. This technique is, however, technically challenging and enables only a rather coarse measurement of this motor mirroring. Here, we applied TMS to listeners’ tongue motor area in association with ultrasound tissue Doppler imaging to describe fine-grained tongue kinematic synergies evoked by passive listening to speech. Subjects listened to syllables requiring different patterns of dorso-ventral and antero-posterior movements (/ki/, /ko/, /ti/, /to/). Results show that passive listening to speech sounds evokes a pattern of motor synergies mirroring those occurring during speech production. Moreover, mirror motor synergies were more evident in those subjects showing good performances in discriminating speech in noise demonstrating a role of the speech-related mirror system in feed-forward processing the speaker''s ongoing motor plan.     

Efficacy and safety of deep transcranial magnetic stimulation for major depression: a prospective multicenter randomized controlled trial

Major depressive disorder (MDD) is a prevalent and disabling condition, and many patients do not respond to available treatments. Deep transcranial magnetic stimulation (dTMS) is a new technology allowing non-surgical stimulation of relatively deep brain areas. This is the first double-blind randomized controlled multicenter study evaluating the efficacy and safety of dTMS in MDD. We recruited 212 MDD outpatients, aged 22–68 years, who had either failed one to four antidepressant trials or not tolerated at least two antidepressant treatments during the current episode. They were randomly assigned to monotherapy with active or sham dTMS. Twenty sessions of dTMS (18 Hz over the prefrontal cortex) were applied during 4 weeks acutely, and then biweekly for 12 weeks. Primary and secondary efficacy endpoints were the change in the Hamilton Depression Rating Scale (HDRS-21) score and response/remission rates at week 5, respectively. dTMS induced a 6.39 point improvement in HDRS-21 scores, while a 3.28 point improvement was observed in the sham group (p+0.008), resulting in a 0.76 effect size. Response and remission rates were higher in the dTMS than in the sham group (response: 38.4 vs. 21.4%, p+0.013; remission: 32.6 vs. 14.6%, p+0.005). These differences between active and sham treatment were stable during the 12-week maintenance phase. dTMS was associated with few and minor side effects apart from one seizure in a patient where a protocol violation occurred. These results suggest that dTMS constitutes a novel intervention in MDD, which is efficacious and safe in patients not responding to antidepressant medications, and whose effect remains stable over 3 months of maintenance treatment.     

经颅磁刺激参数与结构要件的影响分析

为了进一步探索经颅磁刺激工作机理并改进或研制出新的经颅磁刺激激励源.本文从经颅磁刺激的原理推导出了磁场、感应电流及激励源原理电路电流的表达式,利用大脑-线圈和大脑-线圈-铁芯两种经颅磁刺激模型分析影响因素与头模型各组织的磁场和感应电流分布.对比分析表明电流的性质,线圈半径,线圈激励特性与铁芯对感应电流分布与电磁场分布有着本质的影响.对经颅磁刺激参数及结构要件的研究与分析可用于指导刺激线圈参数及激励源电路参数的设置,以及探索新的激励源制作.     

Modulation of learning and hippocampal, neuronal plasticity by repetitive transcranial magnetic stimulation (rTMS)

The influence of high-frequency repetitive transcranial magnetic stimulation (rTMS) on learning process in mice and on neuronal excitability of the hippocampal tissue obtained from stimulated animals were investigated. While the stimulation with rTMS at higher frequency (15 Hz) improved animals' performance in novel object recognition test (NOR), lower frequency (1 and 8 Hz) impaired the memory. The effect was observed when evaluated immediately after rTMS exposure and declined with time. In parallel to the results of behavioral test, there was a significant enhancement of the synaptic efficiency expressed as of the long-term potentiation (LTP) recorded from hippocampal slices prepared from the animals exposed to 15 Hz rTMS. The stimulation with 1 and 8 Hz had no influence on the magnitude of LTP. Our results demonstrate that rTMS modifies mechanisms involved in memory formation. The effects of rTMS in vivo are preserved and expressed in the hippocampus tested in vitro.     

Inhibition of vesicular uptake of monoamines by hyperforin

Hyperforin is the major active ingredient of Hypericum perforatum (St John's Wort), a traditional antidepressant medication. This study evaluated its inhibitory effects on the synaptic uptake of monoamines in rat forebrain homogenates, comparing the nature of the inhibition at synaptic and vesicular monoamine transporters. A hyperforin-rich extract inhibited with equal potencies the sodium-dependent uptake of the monoamine neurotransmitters serotonin [5-HT], dopamine [DA] and norepinephrine [NE] into rat brain synaptosomes. Hyperforin inhibited the uptake of all three monoamines noncompetitively, in marked contrast with the competitive inhibition exerted by fluoxetine, GBR12909 or desipramine on the uptake of these monoamines. Hyperforin had no inhibitory effect on the binding of [3H]paroxetine, [3H]GBR12935 and [3H]nisoxetine to membrane presynaptic transporters for 5-HT, DA and NE, respectively. The apparent presynaptic inhibition of monoamine uptake could reflect a "reserpine-like mechanism" by which hyperforin induced release of neurotransmitters from synaptic vesicles into the cytoplasm. Thus, we assessed the effects of hyperforin on the vesicular monoamine transporter. Hyperforin inhibited with equal potencies the uptake of the three tritiated monoamines to rat brain synaptic vesicles. Similarly to the synaptosomal uptake, the vesicular uptake was also noncompetitively inhibited by hyperforin. Notably, hyperforin did not affect the direct binding on [3H]dihydrotetrabenazine, a selective vesicular monoamine transporter ligand, to rat forebrain membranes. Our results support the notion that hyperforin interferes with the storage of monoamines in synaptic vesicles, rather than being a selective inhibitor of either synaptic membrane or vesicular monoamine transporters.     

Specificity of endogenous substrates for types A and B monoamine oxidase in rat striatum

Abstract: Studies were designed to evaluate specificity of the transmitter amines serotonin (5-hydroxytryptamine, 5-HT) and dopamine (DA), as well as the trace amines p -tyramine ( p -TA) and β -phenylethylamine (PEA) for types A and B monoamine oxidase (MAO) in rat striatum. 5-HT was found to be a specific substrate for the type A enzyme. However, the specificity of PEA for the type B enzyme was found to be concentration-dependent. When low concentrations of PEA and 5-HT were used to measure type B and type A activities, respectively, both clorgyline and deprenyl were highly selective for the sensitive form of MAO in vivo. However, as the concentration of PEA was increased, the type B inhibitor deprenyl became less effective in preventing deamination of PEA. Conversely, the type A inhibitor clorgyline became more effective in this regard. Kinetic analysis following selective in vivo inhibition showed PEA deamination by both forms of MAO with a 13-fold greater affinity for the type B enzyme. In vivo dose-response curves obtained with the common substrates DA and p -TA showed approximately 20% deamination by the B enzyme. Kinetic values for DA and p -TA deamination in in vivo -treated tissue possessing only type A or type B MAO activity, revealed a 2.5-fold greater affinity for the type A enzyme. These studies show the importance of concentration on substrate specificity in striatal tissue. The results obtained characterize the common substrate properties of DA and p -TA as well as of PEA in rat striatum. In addition, the presence of regional specificity for 5-HT deamination by only type A MAO is demonstrated.     

Prediction of lower limb motor outcomes based on transcranial magnetic stimulation findings in patients with an infarct of the anterior cerebral artery

Abstract

The aim was to investigate the relationship between transcranial magnetic stimulation (TMS) at the early stage of stroke and 6-month motor outcome for patients with anterior cerebral artery territory infarct. Patients were classified into TMS(+) and TMS(?) groups. At the 6-month evaluation, lower limb motor function for the TMS(+) group was significantly better than those for the TMS(?) group. Thus, early TMS evaluation is useful for predicting recovery of lower limb motor function in patients experiencing this type of stroke.     

Reduction in cortical parvalbumin expression due to intermittent theta‐burst stimulation correlates with maturation of the perineuronal nets in young rats

We recently showed that intermittent theta‐burst stimulation (iTBS) using transcranial magnetic stimulation strongly reduces the number of rat neocortical interneurons expressing glutamic acid decarboxylase 67 kDa (GAD67) and parvalbumin (PV), indicating changed activity of fast‐spiking (FS) interneurons. In advance of in vitro studies intended to characterize changes in electrical properties of FS interneurons under these conditions, we tested whether the iTBS effect is age‐dependent. Conscious Sprague‐Dawley rats aged between 28 and 90 days received three blocks of iTBS at 15 min intervals. We found that iTBS‐related reduction in PV+ cells was absent up to an age of 32 days, then gradually increased, and approached a maximum of about 40% reduction at an age of about 40 days. The relative number of cells expressing PV (PV+, 8–9%) did not change with age in sham‐controls and also the increase in cortical c‐Fos expression induced by iTBS was not principally age‐dependent. However, a prominent growth of the perineuronal nets, typically surrounding the PV+ cells, exactly paralleled the increase in the iTBS effect. Based on these findings, we conclude that the functional development of the inhibitory network of PV+ interneurons with regard to intracortical synaptic connectivity is not sufficiently matured in rats younger than 35d to enable activity‐dependent modifications during iTBS. Outgrowth of the perineuronal nets and associated maturation of excitatory cortical inputs, as is characteristic for the critical cortical period, may take place before PV+ interneurons can be sufficiently activated via repetitive transcranial magnetic stimulation, allowing plastic changes of molecular phenotype and likely also synaptic plasticity. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 75: 1–11, 2015