非侵入性脑刺激应用于创伤后应激障碍和物质滥用障碍的记忆干预

记忆是进行思维、想象等高级心理活动的基础,是累积经验、促进个体生存的重要功能。然而,创伤后应激障碍和物质滥用障碍具有某种非适应性记忆过强的特征,不利于个体生存。因此,以病理性改变的记忆为靶点,通过削弱或更新非适应性记忆,可以达到缓解症状甚至治愈的目的。记忆并非是对经验的刻板记录,而是对经验不断更新整合的过程,因此记忆有被干预的可能。记忆的再次激活可能会诱发记忆消退和再巩固,这为记忆相关精神疾病的干预提供了思路和启发。非侵入性脑刺激（noninvasive brain stimulation,NIBS）技术作为一种时间、空间分辨率较高的无创神经调控技术,近年来开始被结合运用到记忆干预研究中。不同刺激参数的NIBS （如频率、极性,以及受刺激区域的初始神经激活状态）应用于特定大脑皮质区域,可以调节神经可塑性,增强或降低靶点脑区的兴奋性,从而削弱或增强行为表现,实现记忆消退增强或在再巩固时间窗内干预记忆。本文首先介绍了记忆相关的脑功能基础研究与局部脑区干预方案的理论联系,继而回顾了近年来NIBS与记忆干预相结合应用于创伤或物质滥用相关障碍的临床干预研究,为精神疾病临床诊疗提供理论依据和启发。     

创伤后应激障碍的经颅磁刺激研究进展

创伤后应激障碍会损伤记忆、注意和执行等认知功能,引起异常的脑活动及脑区间功能连接.尽管药物治疗和心理干预能够取得一定的治疗效果,但存在药物副作用和起效延迟等问题.经颅磁刺激作为新的创伤后应激障碍干预手段受到越来越多的关注.本文通过综述经颅磁刺激干预创伤后应激障碍以及调控认知功能和脑活动的相关研究,系统探讨了创伤后应激障碍干预中经颅磁刺激模式、刺激靶点和疗效评估等问题,并提出未来借助更有效的技术手段进行定位、建立全面有效的评估体系和结合新的记忆理论探索具有长期临床改善效果的干预方案.     

强迫症的生物学机制和治疗综述

强迫症是以具有反复强迫思维和强迫行为为特征的一种心理障碍疾病。该病严重影响人们的心理健康和日常生活,因而受到广泛的关注。强迫症病因比较复杂,受到多种因素的影响,家庭环境、社会氛围、个人受教育程度、智力水平及个体的身体素质、健康状况及个性特点等因素与强迫症的产生密切相关。对强迫症的生物学机制的研究主要集中在对相关基因的研究上,其中五羟色胺和多巴胺在强迫症中的作用机制相对来说研究的比较多,也比较成熟,近年来又发现谷氨酸通路和白细胞介素-10也与强迫症的发生有关。与此同时一些治疗强迫症的方法也涌现了出来,如药物治疗和心理治疗。本文拟从强迫症的概念、临床表现、影响因素、生物学机制及其治疗方法等方面的研究进行阐述,以期为今后的研究提供一些参考和依据。     

帕金森病伴抑郁患者DBS术后帕罗西汀治疗疗效观察

目的：研究丘脑底核（STN）脑深部电刺激（DBS）治疗帕金森病（PD）合并抑郁障碍术后服用帕罗西汀治疗的疗效。方法：将38例合并抑郁障碍的PD患者随机分为三组,行丘脑底核脑深部电极植入术,术后空白对照组不服用任何抗抑郁药物,药物治疗组服用帕罗西汀每日一次,每次20mg,安慰剂组服用安慰剂。术前一周,术后1个月、2个月和3个月进行随访和临床评价。结果：抑郁患者术后抑郁障碍症状如焦虑、绝望和激越症状也有不同程度好转,应用安慰剂后,患者术后抑郁障碍程度好转程度大于空白对照组（P〈0.05）,而应用帕罗西汀后术后3个月汉密尔顿抑郁量表评分（HAMD）下降程度显著低于空白对照组及安慰剂组（P〈0.05）。结论：表明STN-DBS术后PD患者的抑郁症状有所改善,辅助抗抑郁药物治疗效果更佳。     

深部脑刺激作用机制的探讨

深部脑刺激器（deep brain stimulator）,也经常被称为脑起搏器,是可植入人体设备,并连续不断地传送刺激脉冲到深部脑组织的特定区域,即所谓的深部脑刺激（deep brain stimulation,DBS）.迄今为止,深部脑刺激是治疗严重顽固抗药性运动障碍疾病（如帕金森病,原发性震颤及肌张力异常等）的最有效的外科治疗手段之一.此外,广大的科研工作者也不断地探索应用DBS治疗其他神经及精神异常（如,癫痫和强迫症）的新的临床应用.尽管应用DBS治疗运动障碍非常有效,并也迅速被探索性地应用到其他神经障碍治疗中,但其作用机制仍然不是十分清楚,成为学者们争论的热点.DBS治疗效果的作用机制通常有两种基本的观点：高频刺激抑制学说及高频刺激兴奋学说.基于最近发表的关于中枢神经系统内的高频刺激效应的资料、数据及相关评论,两种机制共存并发挥作用的DBS作用假说被提出,认为DBS通过施加高频刺激干扰并控制了核团病理性紊乱随机活动,同时施加兴奋性刺激到其他基底节的网络,以实现对帕金森病的治疗.     

丘脑底核高频和低频电刺激治疗帕金森病的临床效果评价

目的:观察和比较丘脑底核高频电刺激与低频电刺激治疗帕金森病(PD)的临床效果。方法:对入选的31名PD患者行双侧丘脑底核电刺激手术,术后1个月,在高频刺激条件下,进行UPDRS运动评分,同时对震颤、强直、运动迟缓、中轴症状进行评分;术后6个月,在关闭刺激、高频刺激和低频刺激三种刺激条件,同样进行相关评分。结果:术后1个月和术后6个月,除中轴症状外,UPDRS运动评分和震颤、强直、运动迟缓评分均较术前明显降低(P0.05)。术后6个月,HFS、LFS刺激条件下,UPDRS运动评分和震颤、强直、运动迟缓评分均较OFF降低(P0.05),但中轴症状评分无明显降低(P0.05)。术后6个月,LFS较HFS,各项评分均无明显差异。结论:丘脑底核高频和低频电刺激均能改善PD的运动功能,对震颤、强直和运动迟缓疗效明显,但对中轴症状均无明显治疗效果。     

A prospective study of delayed sleep phase syndrome in patients with severe resistant obsessive-compulsive disorder

There have been relatively few studies examining sleep in patients withobsessive-compulsive disorder (OCD) and these have produced contradictoryfindings. A recent retrospective study identified a possible association betweenOCD and a circadian rhythm sleep disorder known as delayed sleep phase syndrome(DSPS). Patients with this pattern of sleeping go to bed and get up much laterthan normal. They are unable to shift their sleep to an earlier time and,as a result, suffer considerable disruption to social and occupational functioning.In this study, we examined the sleep of patients with OCD prospectively. Weaimed to establish the frequency of DSPS in this population and any associatedclinical or demographic factors which might be implicated in its aetiology.     

A computational modelling approach to investigate different targets in deep brain stimulation for Parkinson’s disease

We investigated by a computational model of the basal ganglia the different network effects of deep brain stimulation (DBS) for Parkinson’s disease (PD) in different target sites in the subthalamic nucleus (STN), the globus pallidus pars interna (GPi), and the globus pallidus pars externa (GPe). A cellular-based model of the basal ganglia system (BGS), based on the model proposed by Rubin and Terman (J Comput Neurosci 16:211–235, 2004), was developed. The original Rubin and Terman model was able to reproduce both the physiological and pathological activities of STN, GPi, GPe and thalamo-cortical (TC) relay cells. In the present study, we introduced a representation of the direct pathway of the BGS, allowing a more complete framework to simulate DBS and to interpret its network effects in the BGS. Our results suggest that DBS in the STN could functionally restore the TC relay activity, while DBS in the GPe and in the GPi could functionally over-activate and inhibit it, respectively. Our results are consistent with the experimental and the clinical evidences on the network effects of DBS.     

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.     

New insights offered by a computational model of deep brain stimulation

Deep brain stimulation (DBS) is a standard neurosurgical procedure used to treat motor symptoms in about 5% of patients with Parkinson's disease (PD). Despite the indisputable success of this procedure, the biological mechanisms underlying the clinical benefits of DBS have not yet been fully elucidated. The paper starts with a brief review on the use of DBS to treat PD symptoms. The second section introduces a computational model based on the population density approach and the Izhikevich neuron model. We explain why this model is appropriate for investigating macroscopic network effects and exploring the physiological mechanisms which respond to this treatment strategy (i.e., DBS). Finally, we present new insights into the ways this computational model may help to elucidate the dynamic network effects produced in a cerebral structure when DBS is applied.     

Altered hippocampal morphology in unmedicated patients with major depressive illness

Despite converging evidence that major depressive illness is associated with both memory impairment and hippocampal pathology, findings vary widely across studies and it is not known whether these changes are regionally specific. In the present study we acquired brain MRIs (magnetic resonance images) from 31 unmedicated patients with MDD (major depressive disorder; mean age 39.2±11.9 years; 77% female) and 31 demographically comparable controls. Three-dimensional parametric mesh models were created to examine localized alterations of hippocampal morphology. Although global volumes did not differ between groups, statistical mapping results revealed that in MDD patients, more severe depressive symptoms were associated with greater left hippocampal atrophy, particularly in CA1 (cornu ammonis 1) subfields and the subiculum. However, previous treatment with atypical antipsychotics was associated with a trend towards larger left hippocampal volume. Our findings suggest effects of illness severity on hippocampal size, as well as a possible effect of past history of atypical antipsychotic treatment, which may reflect prolonged neuroprotective effects. This possibility awaits confirmation in longitudinal studies.     

丘脑底核脑深部电刺激治疗帕金森病的临床分析

目的:通过丘脑底核脑深部电刺激术治疗帕金森病,观察其肌肉僵直、静止性震颤、运动迟缓等症状的改善情况。方法:选取以丘脑底核为刺激靶点收治的帕金森病患者8例,对比手术前后患者肌强直、静止性震颤、运动迟缓等症状的改善情况,并进行UPDRS评分。结果:接受丘脑底核脑深部电刺激术治疗帕金森病6个月后,患者肌肉僵直、静止性震颤、运动迟缓等临床主症的改善上效果良好;与手术前相比,患者术后UPDRS评分均有所降低,差异具有统计学意义(P0.05);患者术后美多巴服用量显著减少,差异具有统计学意义(P0.05);患者术后没有产生永久性的并发症以及较明显的临床症状;但对大量油脂性渗出及典型面具性面容的治疗上未见明显疗效。结论:丘脑底核脑深部电刺激术治疗帕金森氏病,可以使帕金森病主要临床症状肌肉僵直、静止震颤及运动迟缓得到明显改善,显著减少美多巴服药量,具有安全可靠的疗效,对临床具有指导意义,值得临床推广应用。     

Deep brain stimulation amplitude alters posture shift velocity in Parkinson’s disease

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is now widely used to alleviate symptoms of Parkinson’s disease (PD). The specific aim of this study was to identify posture control measures that may be used to improve selection of DBS parameters in the clinic and this was carried out by changing the DBS stimulation amplitude. A dynamic posture shift paradigm was used to assess posture control in 4 PD STN-DBS subjects. Each subject was tested at 4 stimulation amplitude settings. Movements of the center of pressure and the position of the pelvis were monitored and several quantitative indices were calculated. The presence of any statistically significant changes in several normalized indices due to reduced/no stimulation was tested using the one-sample t test. The peak velocity and the average movement velocity during the initial and mid phases of movement towards the target posture were substantially reduced. These results may be explained in terms of increased akinesia and bradykinesia due to altered stimulation conditions. Thus, the dynamic posture shift paradigm may be an effective tool to quantitatively characterize the effects of DBS on posture control and should be further investigated as a tool for selection of DBS parameters in the clinic.