Complex negative emotions induced by electrical stimulation of the human hypothalamus

BackgroundStimulation of the ventromedial hypothalamic region in animals has been reported to cause attack behavior labeled as sham-rage without offering information about the internal affective state of the animal being stimulated.ObjectiveTo examine the causal effect of electrical stimulation near the ventromedial region of the human hypothalamus on the human subjective experience and map the electrophysiological connectivity of the hypothalamus with other brain regions.MethodsWe examined a patient (Subject S20_150) with intracranial electrodes implanted across 170 brain regions, including the hypothalamus. We combined direct electrical stimulation with tractography, cortico-cortical evoked potentials (CCEP), and functional connectivity using resting state intracranial electroencephalography (EEG).ResultsRecordings in the hypothalamus did not reveal any epileptic abnormalities. Electrical stimulations near the ventromedial hypothalamus induced profound shame, sadness, and fear but not rage or anger. When repeated single-pulse stimulations were delivered to the hypothalamus, significant responses were evoked in the amygdala, hippocampus, ventromedial-prefrontal and orbitofrontal cortices, anterior cingulate, as well as ventral-anterior and dorsal-posterior insula. The time to first peak of these evoked responses varied and earliest propagations correlated best with the measures of resting-state EEG connectivity and structural connectivity.ConclusionThis patient's case offers details about the affective state induced by the stimulation of the human hypothalamus and provides causal evidence relevant to current theories of emotion. The complexity of affective state induced by the stimulation of the hypothalamus and the profile of hypothalamic electrophysiological connectivity suggest that the hypothalamus and its connected structures ought to be seen as causally important for human affective experience.     

Localized connectivity in depression: A meta-analysis of resting state functional imaging studies

Resting-state fMRI studies investigating the pathophysiology of depression have identified prominent abnormalities in large-scale brain networks. However, it is unclear if localized dysfunction of specialized brain regions contribute to network-level abnormalities. We employed a meta-analytical procedure and reviewed studies conducted in China investigating changes in regional homogeneity (ReHo), a measure of localized intraregional connectivity, from resting-state fMRI in depression. Exploiting the statistical power gained from pooled analysis, we also investigated the effects of age, gender, illness duration and treatment on ReHo. The medial prefrontal cortex (MPFC) showed the most robust and reliable increase in ReHo in depression, with greater abnormality in medication-free patients with multiple episodes. Brain networks that relate to this region have been identified previously to show aberrant connectivity in depression, and we propose that the localized neuronal inefficiency of MPFC exists alongside wider network level disruptions involving this region.     

抑郁症大鼠模型海马区及前额叶组织BDNF因子、Trkb蛋白表达的实验研究

目的:观察抑郁症大鼠模型脑组织不同部位神经营养因子水平的变化及抗抑郁药物使用后改变。方法:将成年SD大鼠30只分为正常对照组、模型对照组、药物干预组,每组10只,雌雄对半;正常组正常养殖,模型组采用慢性不可预知应激结合孤养方式制备抑郁模型大鼠4周。药物干预组采用模型组造模过程4周后给予药物(氟西汀)给入,自实验开始之后每周观察大鼠体重、糖水消耗、旷场实验指标的变化,最后采用荧光定量PCR法观察大鼠脑部BDNF因子及Trkb的表达。结果:与正常对照组大鼠相比,模型组大鼠体重增加缓慢、糖水消耗减少、旷场试验各项指标较正常组间差异具有统计学意义;荧光定量PCR结果显示:模型组较对照组各脑区BDNF及Trkb受体表达减少,药物干预组脑区BDNF及Trkb受体表达显著高于模型对照组。结论:脑部BDNF因子及Trkb的表达在抑郁症发生与治疗中有所改变。     

抑郁症患者与不明原因胸痛的关联性探讨

目的:分析抑郁症与不明原因胸痛间的关联性及其可能机制,为临床疾病的治疗提供参考依据。方法:纳入2012年6月至2014年5月四川省南充精神卫生中心精神科收治的不明原因胸痛患者35例,作为观察组,另选取35例来院进行常规体检的健康志愿者作为对照组,比较两组的抑郁量表评分、抑郁症发生率、血清C反应蛋白(CRP)、白细胞介素6(IL-6)、五羟色胺(5-HT)及外周血中的CD4+、CD8+含量。结果:与对照组比较,观察组的CRP、IL-6、5-HT、CD4+均低于对照组;且观察组的CD8+、抑郁症发生率(31.43%)、轻中度抑郁及重度抑郁患者比例均高于对照组水平,组间对比差异显著(P<0.05)。结论:抑郁症与不明原因胸痛存在一定相关性,推断可能与CRP、5-HT、IL-6等细胞因子有关,也可能与免疫抑制过程有关,在临床诊治中需引起重视。     

Cumulative experiences with life adversity: Identifying critical levels for targeting prevention efforts

This paper aims to assess the role of individual types and cumulative life adversity for understanding depressive symptomatology and aggressive behavior. Data were collected in 2011 as part of the Teen Life Online and in Schools Study from 916 ethnically-diverse students from 12 middle, K–8, 6–12 and high schools in the Midwest United States. Youth reported an average of 4.1 non-victimization adversities and chronic stressors in their lifetimes. There was a linear relationship between number of adversities and depression and aggression scores. Youth reporting the highest number of adversities (7 or more) had significantly higher depression and aggression scores than youth reporting any other number of adversities suggesting exposure at this level is a critical tipping point for mental health concerns. Findings underscore an urgent need to support youth as they attempt to negotiate, manage, and cope with adversity in their social worlds.     

Structural brain correlates of serum and epigenetic markers of inflammation in major depressive disorder

Inflammatory processes are implicated in the aetiology of Major Depressive Disorder (MDD); however, the relationship between peripheral inflammation, brain structure and depression remains unclear, partly due to complexities around the use of acute/phasic inflammatory biomarkers.Here, we report the first large-scale study of both serological and methylomic signatures of CRP (considered to represent acute and chronic measures of inflammation respectively) and their associations with depression status/symptoms, and structural neuroimaging phenotypes (T1 and diffusion MRI) in a large community-based sample (Generation Scotland; N_{MDD cases} = 271, N_controls = 609).Serum CRP was associated with overall MDD severity, and specifically with current somatic symptoms- general interest (β = 0.145, P_FDR = 6 × 10⁻⁴) and energy levels (β = 0.101, P_FDR = 0.027), along with reduced entorhinal cortex thickness (β = −0.095, P_FDR = 0.037). DNAm CRP was significantly associated with reduced global grey matter/cortical volume and widespread reductions in integrity of 16/24 white matter tracts (with greatest regional effects in the external and internal capsules, β_FA= −0.12 to −0.14). In general, the methylation-based measures showed stronger associations with imaging metrics than serum-based CRP measures (βaverage = −0.15 versus βaverage = 0.01 respectively).These findings provide evidence for central effects of peripheral inflammation from both serological and epigenetic markers of inflammation, including in brain regions previously implicated in depression. This suggests that these imaging measures may be involved in the relationship between peripheral inflammation and somatic/depressive symptoms. Notably, greater effects on brain morphology were seen for methylation-based rather than serum-based measures of inflammation, indicating the importance of such measures for future studies.     

Multimodal multi-center analysis of electroconvulsive therapy effects in depression: Brainwide gray matter increase without functional changes

BackgroundElectroconvulsive therapy (ECT) is an effective treatment for severe depression and induces gray matter (GM) increases in the brain. Small-scale studies suggest that ECT also leads to changes in brain functioning, but findings are inconsistent. In this study, we investigated the influence of ECT on changes in both brain structure and function and their relation to clinical improvement using multicenter neuroimaging data from the Global ECT-MRI Research Collaboration (GEMRIC).MethodsWe analyzed T1-weighted structural magnetic resonance imaging (MRI) and functional resting-state MRI data of 88 individuals (49 male) with depressive episodes before and within one week after ECT. We performed voxel-based morphometry on the structural data and calculated fractional amplitudes of low-frequency fluctuations, regional homogeneity, degree centrality, functional connectomics, and hippocampus connectivity for the functional data in both unimodal and multimodal analyses. Longitudinal effects in the ECT group were compared to repeated measures of healthy controls (n = 27).ResultsWide-spread increases in GM volume were found in patients following ECT. In contrast, no changes in any of the functional measures were observed, and there were no significant differences in structural or functional changes between ECT responders and non-responders. Multimodal analysis revealed that volume increases in the striatum, supplementary motor area and fusiform gyrus were associated with local changes in brain function.ConclusionThese results confirm wide-spread increases in GM volume, but suggest that this is not accompanied by functional changes or associated with clinical response. Instead, focal changes in brain function appear related to individual differences in brain volume increases.     

舌三针为主治疗脑卒中后吞咽功能障碍的临床研究

目的观察舌三针为主治疗脑卒中后吞咽功能障碍的临床疗效及其对脑神经机制的影响。方法将130例脑卒中后吞咽功能障碍患者随机分为治疗组和对照组,每组65例。对照组采用康复训练配合低频脉冲电刺激治疗,治疗组在对照组基础上采用舌三针治疗。观察两组治疗前后吞咽功能(洼田饮水试验评分)、精神状态[汉密尔顿焦虑量表(HAMA)评分、汉密尔顿抑郁量表(HAMD)评分]及表面肌电图各项指标[平均振幅值(AEMG)、持续时间(t)]的变化情况。结果两组治疗后洼田饮水试验评分、HAMA评分及HAMD评分与同组治疗前比较,差异均具有统计学意义(P<0.05)。治疗组治疗后洼田饮水试验评分、HAMA评分及HAMD评分与对照组比较,差异均具有统计学意义(P<0.05)。两组治疗后空吞咽时及吞咽5 mL水时sEMG各项指标(颏下肌群及舌骨下肌群的AEMG和t)与同组治疗前比较,差异均具有统计学意义(P<0.05)。治疗组治疗后空吞咽时及吞咽5 mL水时sEMG各项指标与对照组比较,差异均具有统计学意义(P<0.05)。治疗组治疗后误吸及肺部感染的发生率分别为16.1%和17.7%,对照组分别为36.2%和32.8%,两组比较差异均具有统计学意义(P<0.05)。结论舌三针配合康复训练及低频脉冲电刺激能有效改善脑卒中患者的吞咽功能。