睡眠剥夺对健康人注意力的影响

目的探讨睡眠剥夺对健康人注意力的影响。方法对10名健康青年男性志愿者进行32h(第1d8:00～第2d16:00)睡眠剥夺,并在睡眠剥夺前、后各17h和32h分别进行4次持续性操作任务(CPT)、选择性注意力(Stroop测验)的测试。结果在CPT和Stroop试验测试中,睡眠剥夺后2次测试的反应时间显著长于睡眠剥夺前,错误率显著高于睡眠剥夺前(均P<0.05),睡眠剥夺后第2次测试平均反应时间和错误率较第1次测试显著增加(均P<0.05)。结论健康人睡眠剥夺后注意力明显下降,并且睡眠剥夺时间越长越明显。     

功能磁共振成像研究睡眠剥夺36小时对健康男性工作记忆的影响

目的 利用功能磁共振成像(functional magnetic resonance imaging,fMRI)技术研究睡眠剥夺36 h对健康男性工作记忆的影响及可能机制.方法 10名健康男性受试者连续36 h睡眠剥夺,睡眠剥夺前后分别接受工作记忆任务测试,同时进行fMRI扫描.fMRI扫描采用2项工作记忆任务,收集获得的行为学结果和fMRI图像,用SPM2软件进行图像分析.比较睡眠剥夺前后工作记忆任务测试及fMRI扫描结果.结果 剥夺后LTR任务的反应时间为(866±102)ms,比剥夺前[(754±91)ms]明显延长(t=2.59,P<0.01),准确率为84.78%±8.71%,比剥夺前(95.31%±3.56%)明显降低(t=3.52,P<0.01);剥夺后PLUS任务的反应时间为(848±94)ms,比剥夺前[(756±79),ms]明显延长(t=2.37,P<0.05),准确率为84.22%±9.66%,比剥夺前(95.70%±4.72%)明显降低(t=3.38,P<0.01);剥夺前在额顶叶、前扣带回和丘脑等工作记忆相关性脑区被激活.PLUS任务较LTR任务激活脑区范围更广,强度更显著.剥夺后顶叶激活降低,前额叶和丘脑的激活增强.结论 睡眠剥夺能够导致工作记忆能力受损.fMRI显示睡眠剥夺后完成工作记忆任务时,在相应脑区顶叶激活降低,前额叶和丘脑激活增强,这可能是睡眠剥夺导致认知功能损害的机制之一.     

注意缺陷/多动障碍工作记忆的bold-功能磁共振成像研究

目的应用bold-功能磁共振成像(bold-fMRI)技术来研究注意缺陷/多动障碍(AD/HD)患者的工作记忆。并探讨使用哌醋甲酯1个月治疗前后AD/HD患者的脑部激活的改变情况。方法利用倒数n刺激模式(n-back)对7例AD/HD(注意缺陷为主型)和7名正常人进行blod-fMRI检查,对照研究AD/HD患者在工作记忆时涉及的各脑区的激活情况。结果AD/HD组治疗后的1-back任务较治疗前1-back任务在右额下回和右额中回激活明显,二者有显著性差异(P<0.05);AD/HD组在治疗后的2-back任务较治疗前2-back任务在左额下回和左顶叶后下部激活明显(P<0.05)。正常组的1-back任务与患者组治疗前的1-back任务比较没有显著性差异,正常组的2-back任务与患者组治疗前2-back任务比较在左额下回和左顶叶后下部激活明显(P<0.05)。结论AD/HD障碍患者存在执行功能方面的缺陷,AD/HD患者的语义性工作记忆缺损可能与前额叶和顶叶的功能缺陷有关。     

精神分裂症患者的工作记忆损伤研究

目的 探讨精神分裂症患者和正常人之间空间、语音及面孔工作记忆的差异.方法 分别对44名精神分裂症患者和40名健康成年人进行空间、语音及面孔工作记忆测试,比较两组任务成绩及反应时间的差异.结果 患者在进行空间工作记忆和面孔工作记忆任务时,准确率明显低于对照组,空间工作记忆(患者组:86.12+12.4%,对照组:91.63+6.18%,P1=0.014),面孔工作记忆(患者组:63.01+9.04%,对照组:69.14+9.24%,P2=0.003),而进行语音工作记忆任务时,两组准确率无统计学差异(P=0.42)患者在进行三项工作记忆测试时,耗时均较对照组长(P<0.05).结论 患者工作记忆损伤存在不均衡性,可能与精神分裂症损伤的脑区不同有关.     

注意缺陷多动障碍患儿工作记忆功能的近红外光谱成像研究北大核心CSCD

目的 初步探讨注意缺陷多动障碍（attention deficit hyperactivity disorder,ADHD）患儿执行工作记忆任务过程中前额叶皮质的激活特点.方法 选用n-back范式为工作记忆功能的心理学任务,应用功能性近红外光谱成像技术（functional near-infrared spectroscopy,fNIRS）检测12例ADHD患儿（ADHD组）和年龄、性别相匹配的13例健康儿童（对照组）在执行n-back任务时前额叶皮质氧合血红蛋白浓度的变化,同步记录行为学数据（按键正确的次数）.采用t检验对2组氧合血红蛋白浓度变化平均值和按键正确的次数进行比较.结果（1）0-back任务和1-back任务期间ADHD组较对照组按键正确次数低（0-back：t=-2.222,P=0.043;1-back：t=-3.276,P=0.005）.（2）0-back任务期间,对照组和ADHD组全部52个通道氧合血红蛋白浓度变化差异无统计学意义;在1-back任务期间,ADHD组[（0.022±0.040）mmol/（L·mm）]第18通道的氧合血红蛋白浓度变化弱于对照组[（0.085±0.040） mmol/（L·mm）;t=3.88,P〈0.05].结论 ADHD患儿在执行工作记忆任务过程中左侧背外侧前额叶激活减弱.     

偏头痛患者工作记忆能力初步研究

采用N-back神经心理学测试方法对诊断明确的23例偏头痛患者进行工作记忆能力评价,并与性别、年龄、受教育程度和神经心理学量表评分等相匹配的25例正常对照者进行比较。结果显示,与正常对照组相比,偏头痛组患者处理工作记忆初级任务时,准确率较高(t=2.627,P=0.017),但反应时间延长(t=1.483,P=0.012);而两组受试者处理高级任务时准确率和反应时间差异均无统计学意义(1-back:准确率t=1.399、P=0.387,反应时间t=1.069、P=0.335;2-back:准确率t=0.016、P=0.209,反应时间t=3.736、P=0.777)。表明偏头痛患者工作记忆能力总体上与正常人群大致相同。     

细胞型朊蛋白介导的海马神经元轴突延伸障碍可能参与睡眠剥夺后认知障碍

目的 研究快速眼动睡眠剥夺后大鼠空间记忆功能和海马细胞型朊蛋白(cellular prion protein,PrPC)表达的变化及沉默细胞型朊蛋白对体外培养的海马神经元轴突延伸的影响,探讨睡眠剥夺后认知功能变化的机制.方法 成年SD大鼠按体重大小排序,完全随机法分为3组,分别为正常笼养对照组、水槽对照组、睡眠剥夺组.采用改良多平台睡眠剥夺法进行连续72 h快速眼动睡眠剥夺.采用Moms水迷宫评估空间记忆.用蛋白质印迹法检测睡眠剥夺后各组大鼠海马PrPC表达的变化.使用原代培养的海马神经元,用RNA干扰技术沉默PrPC,观察神经元轴突延伸的变化.结果 大鼠睡眠剥夺后空间记忆受损,睡眠剥夺组穿越平台次数(3.17±0.95)较笼养对照组(7.17±0.95)和水槽对照组(6.50 ±0.62)明显减少(Z =2.026 6,Z=2.026 6,P＜0.05),平台接近平均值(mm)睡眠剥夺组(711.74 ±33.99)较笼养对照组(592.32±31.31)和水槽对照组(580.86±11.36)明显增大(Z=-2.001 6,Z=-2.482 0,P＜0.05).睡眠剥夺后海马PrPC的表达睡眠剥夺组(0.33±0.10)较笼养对照组(1.01±0.33)和水槽对照组(0.96±0.27)明显下调(Z =2.152 9,Z=2.152 9,P＜0.05).沉默PrPC导致原代培养的海马神经元轴突延伸障碍,感染组神经元(326.28±12.53)与未感染组(555.00±30.43)和感染阴性对照组(558.70±23.10)比较,轴突长度(μm)明显变短(Z =4.768 4,Z=4.877 0,P＜0.05).结论 睡眠剥夺后PrPC介导的海马新生神经元轴突延伸障碍可能是睡眠剥夺后认知障碍发生的潜在机制之一.     

睡眠剥夺对抑郁模型大鼠及正常大鼠行为的影响

目的 分析睡眠剥夺对抑郁模型大鼠及正常大鼠行为的不同影响.方法 实验动物为2～3月龄Sprague Dawley(SD)雄性大鼠,取24只随机分为:(A)正常对照组、(B)正常+大平台对照组、(C)正常+睡眠剥夺组,每组8只.另48只大鼠用21 d慢性不预见性应激制造抑郁模型.将造模成功者随机分为:(D)抑郁+睡眠剥夺组、(E)抑郁+大平台对照组.前三组在第0天和第3天检测大鼠自发活动.后两组在第0天、第21天和第24天检测大鼠自发活动.观察快眼动睡眠剥夺作用下正常大鼠和抑郁模型大鼠自发活动总路程、中央路程和休息时间的变化.结果 抑郁模型大鼠睡眠剥夺后与抑郁+大平台组大鼠相比较,总路程和休息时间显著增加,差异具有统计学意义(P＜0.05),中央路程之间差异无统计学意义(P＞0.05).抑郁模型大鼠睡眠剥夺后与睡眠剥夺前相比,总路程、中央路程均显著增加,差异具有统计学意义(P＜0.05);慢性应激抑郁模型大鼠在大平台水环境处理前后自发活动无明显变化,差异无统计学意义(P＞0.05).正常大鼠睡眠剥夺后与正常+大平台对照组比,自发活动总路程增加,差异具有统计学意义(P＜0.05),自发活动中央路程及休息时间无明显变化,差异无统计学意义(P＞0.05);正常大鼠经大平台水环境处理后,自发活动总路程、自发活动中央路程及自发活动休息时间均较正常对照组无明显变化,差异无统计学意义(P＞0.05).结论 睡眠剥夺后正常大鼠出现焦虑样行为改变,而对抑郁模型大鼠可以缓解其抑郁样行为.     

剥夺睡眠脑电图对儿童精神运动性癫痫的诊断价值及其影响因素

目的 研究剥夺睡眠脑电图(EEG)对儿童精神运动性癫痫的诊断价值及其影响因素.方法 对110例常规EEG检查阴性的精神运动性癫痫患儿进行剥夺睡眠EEG检查;比较剥夺睡眠EEG检查阳性与阴性患儿的有关临床资料;并对有关指标作多因素Logistic回归分析.结果 睡眠剥夺EEG检查阳性62例(56.4％)、阴性48例(43.6％).与睡眠剥夺EEG阴性组相比,阳性组有缺氧窒息史的比率显著增高,有发作诱因的比率和癫痫的发作频率明显降低,发作时间明显延长(P ＜0.05 ～0.01).多因素Logistic回归分析显示,发作诱因、发作频率和发作时间是影响睡眠剥夺EEG阳性率的相关因素(P ＜0.05～0.001).结论 剥夺睡眠EEG可提高儿童精神运动性癫痫的诊断率,癫痫的发作诱因、发作频率和发作时间均为影响其阳性率的因素.     

睡眠剥夺对大鼠海马和皮质IL-1βmRNA表达的影响

目的:研究完全睡眠剥夺对大鼠海马和皮质IL-1βmRNA表达的影响。方法:将大鼠放入1转／分钟转笼中,制作经历不同持续时间的完全睡眠剥夺(TSD)模型。30只大鼠随机分为5小组:对照组(正常对照CC组,环境对照 TC组)和睡眠剥夺组[TSD6h组,TSD1d组,TSD3d组(n=6只)]。采用RT-PCR方法检测大鼠海马和皮质IL- 1βmRNA表达。结果:大鼠海马区,TSD6h组和TSD1d组IL-1βmRNA的表达明显高于对照组,TSD3d组更为明显;皮质区TSD3d组表达也明显增多。结论:完全睡眠剥夺大鼠海马和皮质IL-1βmRNA表达增高,且随时间的延长而逐趋明显。睡眠短期剥夺IL-1βmRNA表达增高可能对脑细胞具有应激性保护作用,而长期剥夺后IL-1β持续增高可能对神经元有损伤作用。     

Motor excitability and motor behaviour after modafinil ingestion – a double-blind placebo-controlled cross-over trial

Summary. Modafinil is a novel vigilance-enhancing agent. We were interested if modafinil would also enhance motor excitability and improve motor performance and attention in healthy subjects.Ten volunteers received either a single oral dose of placebo or 200mg modafinil. A randomized double-blind crossover design was used. Transcranial magnetic stimulation was employed to test intracortical inhibition, intracortical facilitation, the cortical silent period and to obtain stimulus-response curves. In addition, M responses and F waves were recorded. Reaction time tasks, the nine-hole-peg test and the d2 attention test were also applied. These studies were performed prior to and 3 and 24 hours after drug ingestion.Modafinil did not change excitatory or inhibitory properties in the motor cortex. It did not alter corticospinal excitability and alpha motoneuronal excitability. In the modafinil group and in the placebo group, performance of the nine-hole-peg test and the d2 test improved to a similar extend over time. Thus, this study does not demonstrate significant differences between a single dose of modafinil and placebo in healthy subjects.     

Double-blind, placebo-controlled study of modafinil for fatigue and cognition in schizophrenia patients treated with psychotropic medications

OBJECTIVE: To assess the effects of modafinil on fatigue, symptoms, attention, working memory, and executive functioning in schizophrenia patients treated with psychotropic medications. METHOD: Twenty-four patients with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder (10 men and 14 women) were randomly assigned to modafinil up to 200 mg a day (N = 13) or placebo (N = 11) as an adjunct therapy in an 8-week, double-blind, placebo-controlled study. Data were collected from May 18, 2001 to September 11, 2003. RESULTS: Four subjects terminated the study early, including one because of worsening of psychosis during the first week taking modafinil. In the modafinil (N = 10) and placebo (N = 10) groups, fatigue improved significantly over time (p < .01), but there were no differences between groups on changes in fatigue, positive and negative symptoms, or cognition. CONCLUSION: Fatigue improved in both groups, and there were no differences between groups on changes in fatigue, symptoms, attention, working memory, or executive functioning. Lack of differences between groups may be due to small sample size or possible regression to the mean in the placebo group.     

Effects of buspirone and alprazolam on the cognitive performance of normal elderly subjects

OBJECTIVE: To increase understanding of the potential in elderly persons for disability related to behavioral side effects of anxiolytic medications, cognitive and psychomotor effects of clinical doses of buspirone and a popular intermediate-acting benzodiazepine, alprazolam, were examined in carefully screened, healthy elderly subjects. METHOD: Sixty subjects recruited through community organizations and newspaper advertisements and screened on the basis of history, physical examination, and laboratory studies were randomly assigned to one of three drug treatment groups. After 2 days of washout placebo, subjects were given 0.25 mg t.i.d. of alprazolam, 5 mg t.i.d. of buspirone, or placebo three times a day for a total of 14 days in a double-blind design. Behavioral assessments were completed beginning 1 hour after ingestion of medication on the second washout placebo day, day 1 of the treatment period, and day 14 of the treatment period. Tests included the continuous performance test, recall memory for word lists, digit-symbol substitution, retention of pictorial stimuli over 1 hour, the Profile of Mood States, and subjective ratings of mental status. RESULTS: Buspirone did not affect reaction time, vigilance, psychomotor speed, or memory function. Alprazolam had minimal effects on vigilance, psychomotor speed, and memory on the first treatment day and had no effects after repeated doses. CONCLUSIONS: Buspirone did not produce behavioral side effects that could lead to disability, and alprazolam had minimal side effects. Because the patients were carefully screened, it is unclear whether these medications in the doses used would have more side effects in less healthy elderly patients.     

Amphetamine, psychosis, and cognition in the schizophrenia spectrum

We previously reported that subjects with a schizophrenia spectrum personality disorder (ie, an odd cluster personality disorder), of which the prototype is schizotypal personality disorder, show cognitive impairment in circumscribed areas (working memory) compared with healthy control subjects, and that amphetamine administration improves working memory in subjects with schizotypal personality disorder. In this larger series, we wanted to determine whether amphetamine treatment ameliorates working memory impairment using three groups: subjects with a schizophrenia spectrum personality disorder (ie, schizotypal, paranoid, or schizoid personality disorder), other (subjects with nonschizophrenia spectrum) personality disorder, and healthy volunteers. We hypothesized that amphetamine treatment would improve cognitive function in domains in which subjects with schizophrenia spectrum personality disorder show impairment compared with healthy volunteers and the other personality disorder group. Overall, amphetamine treatment did not improve performance in any task compared with placebo, and there was no group by drug interaction in the total sample. However, when the sample was restricted to the subjects who showed impairment at baseline, amphetamine treatment improved visuospatial working memory. In the total patient sample, amphetamine treatment reduced negative symptoms, whereas positive symptoms remained unchanged. Amphetamine treatment improves working memory in those subjects with cognitive impairment at baseline, most of whom meet criteria for a schizophrenia spectrum disorder.     

Apomorphine effects on episodic memory in young healthy volunteers

RATIONALE: Dopamine (DA) modulates working memory. However, the relation between DA systems and episodic (declarative) memory is less established. Frontal lobe DA function may be involved. We were interested in assessing whether apomorphine (Apo), a drug used extensively in clinical research as a probe of DA function, has an effect on episodic memory test performance in healthy volunteers. OBJECTIVE: To investigate the effect of a presynaptic dose of Apo on episodic memory tests and on other tests thought to be sensitive to frontal lobe functions. METHODS: Twenty healthy subjects were treated with Apo HCl (5 microg/kg sc) or placebo (10 subjects/group) in a randomized, double blind parallel group design and performance on a battery of cognitive tests was assessed. RESULTS: Apomorphine significantly impaired performance on tests of source recognition (d.f.=19, p=0.05) and item recognition memory (d.f.=19, p<0.05), and memory interference (d.f.=19, p<0.010). No significant change was found on other tests (Go/no-Go Test, Categorized Words, Stroop, Trail Making Test, and verbal fluency). CONCLUSION: Findings in this small sample of subjects suggest that dopaminergic transmission affects episodic memory functions.     

Pharmacological modulation of prefrontal cortical activity during a working memory task in young and older humans: a PET study with physostigmine

OBJECTIVE: Age-associated cholinergic dysfunction may contribute to the cognitive decline observed during aging, including a decline in working memory. The current study was designed to determine how healthy aging influences the neural response to working memory before and during pharmacological potentiation of the cholinergic system. METHOD: In 13 young and 13 older healthy volunteers, regional cerebral blood flow (rCBF) was measured by using [15O]H2O and positron emission tomography across 10 scans that alternated between a working-memory-for-faces task and rest. In all subjects, the first two scans were obtained during intravenous saline infusion. Seven young and eight older subjects then received intravenous infusion of physostigmine, a cholinesterase inhibitor, and the remaining six young and five older subjects continued to receive saline. RESULTS: In the placebo condition, task-specific rCBF increases in prefrontal regions were observed in the right middle and inferior frontal cortices in young subjects and in more anterior and ventral prefrontal regions in older individuals. Physostigmine during the working memory task significantly improved performance in both age groups. The right prefrontal regions that were selectively recruited in each age group during the placebo condition showed significantly lower rCBF during physostigmine administration. CONCLUSIONS: Cholinergic enhancement does not affect structurally defined cortical regions but rather modulates neural activity in functionally defined regions, that is, in task-related prefrontal cortical areas that are selectively and distinctively recruited in young and older subjects.     

Neuropsychological performance in schizotypal personality disorder: importance of working memory

BACKGROUND: Cognitive deficits consistently have been reported in schizophrenia patients and in patients with schizotypal personality disorder. For this study, the authors wanted to identify which of the domains of cognitive impairment represent "core" deficits of schizophrenia, comparing subjects with schizotypal personality disorder to two comparison groups: healthy volunteers and patients with personality disorders unrelated to schizophrenia. METHOD: Three groups completed a neuropsychological battery: patients with DSM-III-R schizotypal personality disorder (N=82); patients with DSM-III-R personality disorders unrelated to schizophrenia (i.e., a personality disorder other than schizotypal, schizoid, or paranoid [N=44]); and healthy volunteers (N=63). The battery included the California Verbal Learning Test, Trailmaking Test parts A and B, the Dot test of working memory, the Stroop Color and Word Test, the Paced Auditory Serial Addition Test, the WMS visual reproduction test, and the WAIS-R vocabulary and block design. RESULTS: Normative standards for performance that controlled for age, gender, and education were created from the scores of the healthy volunteers. Overall, schizotypal personality disorder patients performed significantly worse than the healthy volunteers and those with personality disorders unrelated to schizophrenia. Specifically, patients with schizotypal personality disorder demonstrated impaired performance on the Paced Auditory Serial Addition Test, WMS visual reproduction test, Dot test, and California Verbal Learning Test. In addition, in a regression analysis, performance on the Paced Auditory Serial Addition Test demonstrated the largest effect size. Indeed, it accounted for unique variance above and beyond all other cognitive measures, since controlling for Paced Auditory Serial Addition Test performance abolished group differences across all other measures. CONCLUSIONS: Patients with schizotypal personality disorder demonstrated moderate cognitive impairment compared with healthy volunteers (significant for seven out of 11 measures). These differences reached statistical significance for tasks of working memory, episodic memory, and delayed recall. Working memory performance accounted for the group differences. This study supports the view that working memory represents a core deficit of schizophrenia spectrum disorders.     

Interaction of negative olfactory stimulation and working memory in schizophrenia patients: development and evaluation of a behavioral neuroimaging task

Negative affect plays a crucial role in the psychopathology of schizophrenia. Although it is known that negative emotion has a strong effect on cognitive performance, this interaction has mainly been studied in healthy volunteers. Hence, working memory was assessed in 24 schizophrenia patients and 24 matched comparison subjects with a 0-back/2-back continuous performance test. Simultaneously, negative emotion was induced by olfactory stimulation. Although subjective ratings confirmed that stimulation with a negative odor was associated with a significant increase in negative affect in patients and healthy volunteers, working memory performance was affected differentially in healthy volunteers and schizophrenia patients. Whilst a similar trend of a reduced behavioral performance during negative odor stimulation was observed in patients, only controls demonstrated a significantly higher response time and a reduced number of correct reactions during higher working memory demands (2-back). Patients, on the other hand, revealed an increase in false alarms during both conditions. The present data indicate a differential effect of negative mood induction on working memory performance in schizophrenia patients and healthy subjects.     

Two weeks of transdermal estradiol treatment in postmenopausal elderly women and its effect on memory and mood: verbal memory changes are associated with the treatment induced estradiol levels.

The present randomized double blind study investigated the effects of a 2 week transdermal estradiol treatment on memory performance in 38 healthy elderly women. Cognitive performance was tested at baseline and after 2 weeks of estradiol or placebo treatment using verbal, semantic, and spatial memory tests as well as a mental rotation task and the Stroop. Initial results showed no differences after treatment between placebo or estradiol treated subjects. However, within treatment group analysis revealed that estradiol treated subjects who reached higher estradiol levels (larger than 29 pg/ml) performed significantly better after treatment in the delayed recall of the paired associate test (verbal memory) than subjects who reached lower estradiol levels (P < 0.05). A nonsignificant trend was observed for the immediate recall condition (P < 0.10). These findings were strengthened by correlations between treatment-induced estradiol levels and changes in verbal memory performance. In addition, there was an association between estradiol levels and mood changes. However mood changes were not significantly associated with changes in verbal memory performance (P > 0.20). The present study supports the idea that estradiol replacement has specific effects on verbal memory in healthy postmenopausal women, with delayed recall being more affected. It suggests that these effects can occur relatively rapidly, and that there may be a dose response relationship of estradiol to memory enhancement. Furthermore, the fact that these results were obtained in women who had been menopausal for an average of 17 years before entering the study indicates that the brain maintains a sensitivity for estrogens even after years of low estradiol plasma concentrations.