首发精神分裂症患者倒背数字作业的fMEI研究

目的利用功能磁共振成像(fMRI)探讨首发精神分裂症患者倒背数字作业激发图像的特点.方法 36例符合ICD-10诊断标准的(首发)精神分裂症患者及18名健康志愿者进行以倒背数字作业(backward digit span task, BDST)作为刺激模式、采用组块(block)设计的fMRI检查,经工作站处理后获功能图像.用阳性和阴性症状量表(PANSS)评价精神分裂症患者精神症状的严重程度. 结果 (1)健康志愿者与精神分裂症患者激活脑区的范围均较广泛,健康志愿者的左侧额上回、双侧额中回、左侧额下回、左侧中央前回、左侧顶上小叶、左侧缘上回、左侧颞下回及左侧枕颞外侧回等脑区均有明显激活.两组激活的脑区在额叶、颞叶、顶叶、枕叶及扣带回的分布,以及各脑区内部分布的差异均没有显著性(P>0.05).(2)健康志愿者与精神分裂症患者激活计数左侧额上回分别为16和11,左侧额下回分别为15和12,左侧中央前回分别为16和17,左侧颞下回分别为14和12,左侧顶上小叶分别为14和14,左侧缘上回分别为14和7,左侧枕颞外侧回分别为14和7,右侧中央前回分别为13和7,右侧枕颞外侧回分别为11和8,两组上述部位激活计数的差异均有显著性(P均＜0.05).(3)健康志愿者与精神分裂症患者左侧额叶背外侧的激活平均体积分别为(362±296)个体素和(79±101)个体素,差异有非常显著性(P=0.001);右侧顶叶后下部的激活平均体积分别为(448±273)个体素和(193±236)个体素,差异有显著性(P=0.039). 结论早期精神分裂症患者可能存在工作记忆缺陷,包括激活信息的保持及执行控制过程,激活信息的保持缺陷可能与左侧额叶腹外侧及顶叶后下部的功能低下有关,而执行控制缺陷可能与左侧额叶背外侧的功能低下有关.     

健康人倒背数字作业的脑功能磁共振成像研究

目的　利用功能磁共振成像(functionalmagneticresonanceimaging ,fMRI)技术探讨倒背数字作业认知功能的脑功能定位。方法　1 8名健康志愿者完成以倒背数字作业(backwarddigitspantask ,BDST)作为刺激模式、采用组块设计(block)的fMRI检查,经工作站处理后获功能图像。结果　健康志愿者的左侧额上回、额中回、额下回、中央前回、顶上小叶、缘上回、颞下回、枕颞外侧回及右侧额中回等脑区均有明显激活。结论　左侧额叶腹外侧及左侧项叶后下部可能参与工作记忆对语言材料激活信息的保持,而双侧额叶背外侧可能参与工作记忆对语言材料激活信息的执行控制。     

首发精神分裂症患者的功能磁共振初步研究

目的 利用血氧水平依赖性(blood oxygenation level-dependent,BOLD)功能磁共振成像(functional magnetic resonance imaging,fMRI)技术探讨首发精神分裂症患者治疗前后认知功能激发图像的特点。方法 13例首发精神分裂症患者入组,用利培酮或氯丙嗪治疗后9例患者复查fMRI。以词语流畅性作业(verbal fluency task,VF)作为任务,采用Block设计,用梯度回波-平面回波成像(GRE-EPI)序列采集数据,经工作站处理后获功能图像。结果 (1)VF激活受试者的额叶(前额叶)、顶叶及颞叶皮层;(2)复查的9例受试者中,7例激活增强,2例激活减弱;(3)治疗后激活增强的7例受试者的双侧额上、中、下回激活有增加趋势,而双侧颞上、中、下回激活有减少趋势(P>0.05);但左额叶背外侧面治疗后的激活明显强于治疗前(P=0.032)。结论 BOLD-fMRI可用于研究人脑的高级认知功能。首发精神分裂症患者治疗前后脑功能图像有明显变化,提示认知缺陷症状是可以治疗的。     

偏执型精神分裂症患者Stroop操作的功能磁共振研究

目的利用功能磁共振显像(fMRI)技术探讨精神分裂症患者注意障碍的脑功能基础。方法对14例精神分裂症患者(患者组)和16名正常人(对照组)检测Stroop测验刺激下的fMRI。结果(1)激活脑区计数(个)：Stroopl刺激下,患者组左侧额下回(11/3)、左侧颞上回(6/8)、左侧颞下回(6/8)脑区激活计数均多于对照组(分别为6/10、1/15、1/15),差异有统计学意义(P＜0.05)；Stroop2刺激下,患者组左侧前扣带皮质(ACC,4/10)、右侧额中回脑区激活计数(4/10)均少于对照组(分别为12/4、14/2),差异有统计学意义(P＜0.05),患者组左额上回激活计数(9/5)多于对照组(3/ 13),差异有统计学意义(P＜0.05)。(2)激活脑区体积(体素)：Stroop1刺激下,患者组右侧前额叶背外侧区(DLPFC,256±579)、左侧ACC(18±59)激活体积小于对照组(分别为298±597、67±87),差异有统计学意义(P＜0.05)；Stroop2刺激下,患者组两侧DLPFC(分别为73±190、80±245)、左侧ACC(17±28)激活体积小于对照组(分别为425±800、414±703、76±98),差异有统计学意义(P＜0.05)。结论精神分裂症患者的注意障碍可能与前额叶、ACC、颞叶神经回路功能障碍密切相关。     

血管性认知功能损害患者工作记忆和计算能力的fMRI研究

目的研究血管性认知功能损害(vascular cognitive impairment,VCI)患者在执行工作记忆和计算任务时,其功能磁共振(functional magnetic resonance imaging,fMRI)的信号激活脑区强度同正常人进行比较是否存在区别,明确VCI患者脑功能区信号变化特点,为VCI提供影像学诊断依据。方法采用简明精神状态检查(mini-mental state examination,MMSE)进行智能评定。利用功能磁共振成像技术,对25例VCI患者和15例对照组患者进行倒背数字作业,计算能力测验,对脑激活功能区进行分析,利用SPM2软件对图像数据进行处理。结果 VCI患者倒背数字作业时,双侧额中回、海马及颞上回激活脑区像素值显著减少(P<0.05);在计算能力测试方面,双侧额中回、海马、颞上回以及左侧角回、缘上回激活脑区像素值也显著减少(P<0.05)。结论在执行工作记忆和计算任务时,VCI患者存在特定激活脑区信号的减弱,通过对fMRI信号的侦测,可以为VCI的早期诊断提供影像学依据。     

正常人词语流畅性作业的脑功能磁共振成像研究

目的 利用功能磁共振成像(fMRI)技术探讨词语流畅性作业的脑功能定位。方法对18名健康志愿者进行词语流畅性作业的fMRI检查,fMRI用梯度回波-平面回波成像序列采集数据,经工作站处理后获功能图像。结果 经Fisher精确检验法,健康志愿者的双侧额上回、双侧额中回、右侧额下回及右侧扣带回的激活脑区计数,与理想激活脑区计数的差异均无显著性(P>0.05),其余脑区激活计数的差异均有显著性(P<0.05)。结论 双侧额叶背外侧及右侧额叶腹外侧可能参与长时记忆的提取过程,其中额叶背外侧可能参与核查及管理工作,而额叶腹外侧可能参与搜寻特异目标的过程。     

慢性失眠患者数字工作记忆的功能磁共振研究

目的 探讨慢性失眠患者数字工作记忆神经网络连接的改变.方法 采用组块设计方法,分别对40例慢性失眠患者(失眠组)及50例正常睡眠者(对照组)进行数字工作记忆状态下功能磁共振扫描,比较两组受试者在数字工作记忆中反应时间及正确率以及编码、维持、提取阶段脑区激活强度的改变.结果 失眠组与对照组数字工作记忆正确率的比较差异无统计学意义(P＞0.05),失眠组反应时间明显增加,差异有统计学意义(P＜0.01).慢性失眠患者在数字工作记忆编码期激活强度增强的脑区为左侧壳核、豆状核、顶下小叶及右侧尾状核、右枕叶;维持期激活强度增强的脑区为右侧额叶,左侧额叶及额叶内侧面,而左侧额上回激活强度有所下降;提取期激活强度增强的脑区为右额下回及右顶下缘角回,而激活轻度下降的脑区则有左内侧额上回、左岛叶、左后扣带回、左颞上回、左额上回及右颞叶、右后扣带回.结论 慢性失眠患者在数字工作记忆的各阶段,脑区激活强度较健康人有所改变:大脑皮质和皮质下结构广泛受损,即其神经网络连接发生明显改变.     

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.     

首发未治疗的精神分裂症患者低频振幅研究

目的:探讨首发未治疗的精神分裂症患者低频振幅(ALFF)改变及其与临床症状的关系。方法:对69例首次发病未治疗的精神分裂症患者(患者组)及74名健康对照者(对照组)进行静息态功能磁共振(fMRI)扫描获取ALFF值;采用阳性和阴性症状量表(PANSS)评估患者的临床症状,分析ALFF与临床症状的关系。结果:与对照组相比,患者组右颞中回、右脑岛、右尾状核、右额上回、右顶下小叶、左顶上回ALFF值明显增高,右楔叶ALFF值明显降低(高斯随机场矫正,体素P0.001;团块P0.05),患者组右额上回ALFF值与PANSS阳性症状分(多重比较矫正,r=0.30,P0.05)及总分(多重比较矫正,r=0.34,P0.05)呈正相关。结论:首发精神分裂症患者部分脑区脑功能活动异常,且异常活动脑区可能与临床症状相关。     

首发抑郁症患者字母工作记忆fMRI研究

目的探讨首发抑郁症患者字母工作记忆的脑激活特征。方法12例首发抑郁症患者与12名健康对照配对进行字母工作记忆任务的功能磁共振成像(fMRI)。以AFNI软件对fMRI数据进行定位与定量分析。结果①两组任务执行正确率均大于75%,患者组字母工作记忆2-back任务正确率低于对照组[(0.79±0.04)%vs(0.83±0.03)%,t=4.69,P<0.05];②两组字母工作记忆激活的感兴趣脑区(ROI)均为左侧Broca区BA44/45、双侧前额叶腹侧BA9/46、顶叶后部BA7/40、前运动区BA6及辅助运动区(SMA)BA6/8(P<0.05);③患者组在右侧与左侧BA9/46、右侧与左侧BA6及左侧Broca区的激活强度分别为:1.38%、1.69%、1.21%、1.32%及0.52%,低于对照组的2.42%、3.53%、2.95%、3.51%及1.62%(P<0.05)。结论首发抑郁症患者存在字母工作记忆损害,而语音环路的双侧BA9/46、BA6与左侧Broca区激活减弱可能为其病理机制之一。     

Treatment Considerations in Anticonvulsant Monotherapy

Summary: The long-standing practice of polypharmacy in treating epilepsy is giving way to use of monotherapy. Monotherapy can improve seizure control as well as reduce the risk of serious idiosyncratic reactions, dose-related side effects, and complex drug interactions. Monotherapy also offers improved compliance and cost-effectiveness. The basis of monotherapy is accurate diagnosis and assessment of the patient's seizure type(s), followed by selection of a single appropriate anticonvulsant drug. Many patients currently treated with multiple anticonvulsants can be successfully converted to monotherapy with a carefully monitored program in which troublesome and redundant drugs are gradually withdrawn from the therapeutic regimen.     

Dextromethorphan: Cellular Effects Reducing Neuronal Hyperactivity

Summary: Dextromethorphan is a dextrorotary morphinan without affinity for opioid receptors, commonly used as an antitussive medication. During the past 5 years, interest in the compound and its demethylated derivative, dextrorphan, has been revived because additional neuroprotective and an-tiepileptic properties were found in in vitro studies, animal experiments, and a few clinical cases. Both morphinans are able to inhibit N -methyl-D-aspartate (NMDA) receptor channels and voltage-operated calcium and sodium channels with different potencies. The inhibition of the NMDA receptor is believed to be the predominant mechanism of action responsible for the anticonvulsant and neuroprotective properties of the compounds.     

Pediatric Epilepsy Surgery

Summary: The use of implantable arrays of epidural electrodes has made it possible to carry out extraoperative electrocorticography (ECoG) and functional localization in the awake child. This has permitted cortical excisions that are determined by criteria similar to those obtained during surgical procedures performed under local anesthesia in adults. In addition, the method also permits simultaneous ECoG and video monitoring during the child's symptomatic seizures, providing additional important localizing information that is impractical to obtain in operations under local anesthesia. We report our experience with 75 children, ages 5 months to 15 years, whom we have managed with epidural electrode arrays. The method of extraoperative ECoG is described and illustrative cases are presented to demonstrate its feasibility and utility in children. In addition, we call attention to gliomas as a common cause of chronic focal seizures in children. Of 49 children undergoing resection and followed for from 1 to 14 years (mean of 5.8 years), 32 (65%) are either seizure free or have had a significant reduction in seizure frequency that has unambiguously improved their quality of life. The results are analyzed further by relating the surgical outcome to each of the pathologic entities that caused the seizures. This analysis reveals the variety of neurological conditions that commonly cause intractable focal seizure disorder in children and distinguishes those pathologic entities in which the seizure disorder is apt to respond to surgical intervention from those that will not.     

Un nouveau cadre conceptuel de travail pour une psychiatrie revisitée ? Introduction à deux articles de E. Kandel

In two articles which appeared in the American Journal of Psychiatry and that were subsequently translated for Évolution Psychiatrique, E. Kandel examines the bases for a reinterpreted psychiatry that is prepared to confront the major challenge of the 3rd millenium: that of insight into the mind and brain. This requires a major reorganization of the discipline, which involves a reinvestment of the scientific approach and a critical  assessment of the data provided by psychoanalytical psychiatry and cognitive neurosciences. Seven concepts have therefore been proposed for interactive re-examination: consciousness, the unconscious, memory, emotion, development, desire, impulse. The dynamic relations existing between genetics and the environment allow one to see how evolutions are possible from actions at different levels, both psychotherapeutic and pharmacological. Imaging and other techniques provide additional objective information to the process of human interaction which remains the basis of psychiatry. A common framework for psychiatry and the neurosciences, a reconsideration and renewal of the psychoanalytical approach are both possible and necessary.     

Opioids and the developing organism: A comprehensive bibliography, 1984–1988

A comprehensive bibliography of the literature concerned with opioids and the developing organism for 1984-1988 is presented. Utilized with companion papers (Neurosci. Biobehav. Rev. 6:439-479; 1982; 8:387-403; 1984), these articles cover the clinical and laboratory references beginning in 1875. For the years 1984, 1985, 1986, 1987, and 1988, a total of 877 citations were recorded. A series of indexes accompanies the citations in order to make the literature more accessible. These indexes are divided into clinical and laboratory topics, and subdivided into such topics as the type of opioid explored and the general area of biological interest (e.g., physiology).     

La biologie et le futur de la psychanalyse : un nouveau cadre conceptuel de travail pour une psychiatrie revisitée

The American Journal of Psychiatry has received a number of letters in response to my earlier “Framework” article (1). Some of these are reprinted elsewhere in this issue, and I have answered them briefly there. However, one issue raised by some letters deserves a more detailed answer, and that relates to whether biology is at all relevant to psychoanalysis. To my mind, this issue is so central to the future of psychoanalysis that it cannot be addressed with a brief comment. I therefore have written this article in an attempt to outline the importance of biology for the future of psychoanalysis.     

Facteurs de risque environnementaux à la schizophrénie

Schizophrenia is currently a major concern, its prevalence being estimated at around 1% and its social consequences being severe. The elucidation of the pathophysiology of the disease is difficult due to the great variability of clinical expressions, the instability of the clinical symptoms during the evolution and the absence of reliable biological markers. The existence of a familial aggregation in schizophrenia is well known, the risk of presenting the disease for first-degree relatives of patients being 5 to 10 times higher than the risk observed in the general population. The genetic component was further confirmed by twin and adoption studies. Although the concordance for the disease is higher (40 to 70%) among monozygotic twins as compared with dizygotic twins (15%) it does not reach 100%, which implies that environmental factors modulate the effects of the genotype. However, the role of these factors and especially their interaction with genetic factors remain unclear but the implications of some specific environmental factors are well documented by recent research data. The current literature on sex differences in schizophrenia is consistent. Several studies have suggested that male and female patients may differ in age at the onset and expression of clinical symptoms. Complications during pregnancy or birth-giving may increase the risk of developing schizophrenia later in life. The major complications are oxygen deprivation during pregnancy, bleeding, maternal malnutrition or infection (exposure to influenza, for example). A low birth weight is associated with an increased risk of schizophrenia. Psychoses are more common among people living in an urban environment and among those born during winter months. Schizophrenia is probably more prevalent in people who are living promiscuously, are subject to toxic abuse, poor nutrition and stress but here more precise data are needed. Moreover, immigrants have a higher risk of developing psychotic disorders. In addition, head traumas are associated with an increased risk of schizophrenia. Though they are contentious, some studies suggest that substance abuse (cannabis use in European countries) is related to the development of schizophrenia, especially in people with genetic vulnerability. Moreover, substance misuse may worsen the symptoms. If the environment is sufficiently stressful, people with a high genetic vulnerability will develop some degree of mental illness, including schizophrenia. Conversely, a less stressful or a protective environment may decrease the risk of its onset in persons with a predisposition to schizophrenia.     

Introduction: Goals

Summary: Epilepsy is characterized by recurrent seizures. Many epilepsies with focal seizures as well as convulsive generalized seizures respond satisfactorily to antiepileptic drugs (AEDs) that reduce repetitive firing (e.g., phenytoin, carbamazepine, and valproate) or that augment GABA_A-mediated inhibition (e.g., phenobarbital and benzodiazepines). A number of drugs presently under development, such as NMDA receptor antagonists, loreclezole, losigamone, meth-ysticine, and dextromethorphan, are promising in acute animal models of otherwise drug-resistant convulsant activity. As a result of recent studies in both experimental models and surgically resected human epileptic brain, the prospects for development of AEDs have significantly improved. Several new AEDs recently have reached the commercial market or are in experimental or clinical trials. A comparative presentation of the standing of the new AEDs with respect to their efficacy and side effects is necessary, but still very difficult. Because initial experience with new AEDs is restricted to populations with severe drug-resistant epilepsy, the crucial question whether potential new AEDs can alter prognosis is not yet definitively answered. There is a clear need to compare the effects of standard AEDs and new AEDs in naive patients and over longer follow-up periods. Moreover, because of the strong desire to develop antiepileptic therapy that directly treats the primary etiology of a given epileptic syndrome , or modifies the neurobiological processes that cause recurrent seizures, better experimental epilepsy models for chronic epilepsy and further clinical studies are necessary to increase the knowledge on the pathophysiology of distinct epileptic syndromes. In this respect, studies on the differences between responders and nonresponders to a given AED treatment are extremely valuable.