Local and distant cortical responses to single pulse intracranial stimulation in the human brain are differentially modulated by specific stimulation parameters

BackgroundElectrical neuromodulation via direct electrical stimulation (DES) is an increasingly common therapy for a wide variety of neuropsychiatric diseases. Unfortunately, therapeutic efficacy is inconsistent, likely due to our limited understanding of the relationship between the massive stimulation parameter space and brain tissue responses.ObjectiveTo better understand how different parameters induce varied neural responses, we systematically examined single pulse-induced cortico-cortico evoked potentials (CCEP) as a function of stimulation amplitude, duration, brain region, and whether grey or white matter was stimulated.MethodsWe measured voltage peak amplitudes and area under the curve (AUC) of intracranially recorded stimulation responses as a function of distance from the stimulation site, pulse width, current injected, location relative to grey and white matter, and brain region stimulated (N = 52, n = 719 stimulation sites).ResultsIncreasing stimulation pulse width increased responses near the stimulation location. Increasing stimulation amplitude (current) increased both evoked amplitudes and AUC nonlinearly. Locally (<15 mm), stimulation at the boundary between grey and white matter induced larger responses. In contrast, for distant sites (>15 mm), white matter stimulation consistently produced larger responses than stimulation in or near grey matter. The stimulation location-response curves followed different trends for cingulate, lateral frontal, and lateral temporal cortical stimulation.ConclusionThese results demonstrate that a stronger local response may require stimulation in the grey-white boundary while stimulation in the white matter could be needed for network activation. Thus, stimulation parameters tailored for a specific anatomical-functional outcome may be key to advancing neuromodulatory therapy.     

Dynamic of neurochemical alterations in striatum,hippocampus and cortex after the 6-OHDA mesostriatal lesion

Immediate neurochemical alterations produced by 6-OHDA could explain the general toxic pattern in the central nervous system. However, no evidences describe the effects of 6-OHDA on early changes of neurotransmitters in rats’ striatum, cortex and hippocampus. In our study, unilateral 6-OHDA injection into medial forebrain bundle (MFB) was used in rats, then five neurotransmitters were analyzed at 3, 6, 12, 24, 48 and 72 h, respectively. Results showed that 6-OHDA injection caused a sharp decline of striatal dopamine (DA) levels in the first 12 h followed by a further reduction between 12 and 48 h. However, striatal levels of homovanillic acid (HVA) were stable in the first 12 h and showed a marked reduction between 12 and 24 h. Striatal levels of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) decreased linearly for 72 h, whereas levels of norepinephrine (NE) showed a slight reduction in the first 48 h, and returned back to normal afterwards. Striatal HVA/DA ratio increased significantly in the first 12 h, but 5-HIAA/5-HT ratio showed a sharp increase between 12 and 72 h. Besides, neurochemical alterations were also found in hippocampus and cortex, and the correlations of neurotransmitters were analyzed. Our study indicated that NE system had little influence in the early phase of 6-OHDA injection, moreover, early neurochemical alterations were involved with striatum, hippocampus and cortex.     

牡丹皮饮片的有效期研究

目的：进行中药材有效期方法研究。方法选用易散失气味、易变色的牡丹皮饮片作为研究对象,通过经典恒温实验和留样观察实验,用紫外色谱法测定其有效成分丹皮酚含量。推导出牡丹皮饮片中丹皮酚含量变化规律。结果在经典恒温实验中,丹皮酚含量变化符合一级反应规律。牡丹皮在20℃贮存,丹皮酚含量变化速度常数K20℃=1.194＆#215;10-4、该批牡丹皮的有效期为226 d。经典恒温实验推导的结果与留样观察有效成分含量的变化结果基本一致。结论用经典恒温实验预测牡丹皮饮片有效期的方法可行,得出有效期结论可靠。     

Intact alternation performance in high lethality suicide attempters

Suicide attempters often perform poorly on tasks linked to ventral prefrontal cortical (VPFC) function. Object Alternation (OA) – a VPFC probe – has not been used in these studies. In this study, currently depressed medication-free past suicide attempters whose most severe attempt was of high (n=31) vs. low (n=64) lethality, 114 medication-free depressed non-attempters, and 86 non-patients completed a computerized OA task. Participants also completed comparison tasks assessing the discriminant validity of OA (Wisconsin Card Sort), its concurrent validity relative to tasks associated with past attempt status (computerized Stroop task, Buschke Selective Reminding Test), and its construct validity as a VPFC measure (Go-No Go and Iowa Gambling Task). Against expectations, high lethality suicide attempters – the majority of whom used non-violent methods in their attempts with some planning – outperformed other depressed groups on OA, with no group differences observed on Wisconsin Card Sort. Despite intact performance on OA, past attempters exhibited deficits on the Stroop and Buschke. OA performance was associated with performance on Go-No Go and Iowa Gambling, confirming that OA measures a similar construct. VPFC dysfunction may not be a characteristic of all suicide attempters, especially those who make more carefully planned, non-violent – though potentially lethal – attempts.     

Accelerated aging of selective brain structures in human immunodeficiency virus infection: a controlled,longitudinal magnetic resonance imaging study

Advances in treatment have transformed human immunodeficiency virus (HIV) infection from an inexorable march to severe morbidity and premature death to a manageable chronic condition, often marked by good health. Thus, infected individuals are living long enough that there is a potential for interaction with normal senescence effects on various organ systems, including the brain. To examine this interaction, the brains of 51 individuals with HIV infection and 65 uninfected controls were studied using 351 magnetic resonance imaging and a battery of neuropsychological tests collected 2 or more times over follow-up periods ranging from 6 months to 8 years. Brain tissue regions of interest showed expected age-related decrease in volume; cerebrospinal fluid-filled spaces showed increase in volume for both groups. Although HIV-infected individuals were in good general health, and free of clinically-detectable dementia, several brain regions supporting higher-order cognition and integration of functions showed acceleration of the normal aging trajectory, including neocortex, which extended from the frontal and temporal poles to the parietal lobe, and the thalamus. Beyond an anticipated increase in lateral ventricle and Sylvian fissure volumes and decrease in tissue volumes (specifically, the frontal and sensorimotor neocortices, thalamus, and hippocampus) with longer duration of illness, most regions also showed accelerated disease progression. This accelerated loss of cortical tissue may represent a risk factor for premature cognitive and motor compromise if not dementia. On a more promising note, HIV-infected patients with increasing CD4 counts exhibited slower expansion of Sylvian fissure volume and slower declines of frontal and temporoparietal cortices, insula, and hippocampus tissue volumes. Thus, attenuated shrinkage of these brain regions, likely with adequate pharmacologic treatment and control of further infection, has the potential of abating decline in associated higher-order functions, notably, explicit memory, executive functions, self-regulation, and visuospatial abilities.     

重复经颅磁刺激对急性缺血性卒中患者运动功能恢复的影响

目的 探讨高频(10 Hz)、低频(1 Hz)以及θ短阵快速脉冲模式(theta burst stimulation,TBS)重复经颅磁刺激(repetitive transcranial magnetic stimulation,rTMS)对急性期缺血性卒中偏瘫患者运动功能恢复的影响.方法 将72例急性缺血性卒中偏瘫患者采用随机数字表法随机分组,分别给予低频(18例)、高频(18例)、TBS(18例)rTMS或假刺激(对照组,18例),每天1次,连续治疗2周.所有入组患者在rTMS治疗前(第1 次治疗之前当天)和治疗后(最后1次治疗之后当天)应用Fugl-Meyer运动功能评分(Fugl-Meyer Assessment,FMA)和美国国立卫生研究院卒中量表(National Institutes of Health Stroke Scale,NIHSS)进行神经功能评价.结果 4组患者治疗后FMA和NIHSS评分均较治疗前出现显著改善(P均<0.05).高频组、低频组以及TBS组rTMS治疗后FMA和NIHSS评分均较对照组出现显著改善(P均<0.05),各治疗组间无显著性差异.结论 高频、低频和TBS rTMS均能改善急性缺血性卒中偏瘫患者的运动功能恢复,各治疗模式间无显著性差异.     

皮质类固醇性青光眼的诱因分析及防治

目的:探讨皮质类固醇性青光眼的发病原因及临床特点,提出做好防治的重要性。方法:回顾性分析1998年1月至2005年10月我科收治的34例类固醇性青光眼病人用药时间特点及临床表现、体征。结果:34例患者均为长期反复局部使用地塞米松复合制剂,用药时间6个月至5年,34例均为开角型青光眼。结论:皮质类固醇性青光眼发病取决所用激素剂型、剂量、用药时间及频度途径等。因此提高人们对该病的重视,加强药品销售管理,做好健康教育,避免长期滥用皮质类固醇药物是关健。