Asperger综合征儿童的智力结构与临床症状

目的:探讨Asperger综合征(Asperger syndrome,AS)儿童的智力结构特点及其智力合成指数与其临床症状的相关关系.方法:采用国内修订韦氏儿童智力量表第4版(Wechsler Intelligence Scale for Children-Fourth Edition,WISC-Ⅳ)对27例符合美国精神障碍诊断与统计手册第4版的AS儿童和年龄、性别匹配的27名正常儿童进行测试,由AS儿童家长填写AS筛查量表以评估其临床症状.结果:AS组在总智商[(96.1±12.0) vs.(105.6±9.4)]、知觉推理指数[(100.4±13.6) vs.(108.9±l1.2)]、工作记忆指数[(92.3±10.0) vs.(97.9±9.9)]、加工速度指数[(92.2±l1.5)vs.(107.4±l2.8)]、认知效率指数[(90.8±9.3) vs.(102.3±10.6)]均低于正常对照组(均P＜0.05).分测验中AS组在积木[(9.7±3.4) vs.(12.3±2.6)]、背数[(7.9±1.9)vs.(9.0±1.9)]、译码[(8.2±2.2) vs.(11.3±3.0)]、符号检索[(9.2±2.6)vs.(1 1.6±2.5)]的得分低于对照组(P＜0.05).AS的智力合成指数与其临床症状未发现具有相关关系(r =0.34 ～0.63,均P＞0.05).结论:AS组智力水平在正常范围但低于正常对照组,AS儿童存在着一般认知能力高于认知效率的认知模式,AS儿童的智力合成指数与其临床症状的关系有待进一步研究.     

注意缺陷多动障碍及共患学习困难儿童大脑灰质、白质和全脑体积磁共振成像研究

目的:探讨注意缺陷多动障碍(ADHD)及共患学习困难(LD)儿童大脑灰质、白质和全脑体积的特点。方法:本研究共纳入符合美国精神障碍诊断与统计手册第4版(DSM-IV)之相应诊断标准的36例ADHD儿童,以及性别、年龄均匹配的36名正常对照。ADHD儿童中有18例共患LD(ADHD+LD组)、18例不共患LD(ADHD-LD组)。以中国儿童-韦氏智力测定量表(C-WISC)、利手问卷评定被试的智商和利手状况。以磁共振成像检查收集被试的大脑影像。采用基于体素的形态学测量(voxelbased morphometry,VBM)方法研究ADHD组与对照组脑结构的差异,同时分析共病LD患者大脑体积的特点。结果:与正常对照相比,ADHD儿童大脑灰质[(746.9±68.3)mm3vs.(790.5±72.2)mm3]和全脑[(1212.4±115.2)mm3vs.(1270.6±113.1)mm3]体积减小(P0.05),白质体积组间差异无统计学意义。与对照组相比,ADHD+LD组灰质[(731.1±69.5)mm3vs.(790.5±72.2)mm3]、白质[(435.2±51.1)mm3vs.(480.1±50.5)mm3]和全脑[(1166.3±112.3)mm3vs.(1270.6±113.1)mm3]体积减小(P0.05);与ADHD-LD相比,ADHD+LD组白质[(435.2±51.1)mm3vs.(495.7±55.7)mm3]和全脑[(1166.3±112.3)mm3vs.(1258.3±100.9)mm3]体积减小(P0.05);ADHD-LD和对照组大脑体积组间差异无统计学意义。结论:ADHD儿童存在灰质体积和全脑体积减小,共患LD会使ADHD儿童大脑体积更小,提示大脑体积异常可能参与LD和/或ADHD的发病机制以及ADHD共病LD的病理机制。     

儿童的教师权威认知与师生关系的关系

目的:探讨儿童的教师权威认知发展特点,以及与师生关系的相关性。方法:在北京市2所小学选取四、五、六年级儿童共460名,采用两难故事情境评估儿童的教师权威认知水平、教师权威认知量表测验儿童对教师各领域权威认同度、学生版师生关系量表测量儿童的师生关系程度。结果:10岁儿童的教师不良处理方法权威认知得分高于11岁组与12岁组[(10.7±3.1)vs.(9.5±2.9),(10.7±3.1)vs.(9.3±2.6);均P0.05],12岁儿童的教师情感权威认知得分低于10岁组与11岁组[(18.2±2.6)vs.(18.7±1.9),(18.2±2.6)vs.(18.9±1.7);均P0.05]。处于合理化过渡水平的儿童,对教师的不良处理方法权威认知得分低于低水平和自我发展定向水平[(9.4±3.0)vs.(10.3±2.9),(9.4±3.0)vs.(10.3±2.8);均P0.05]。儿童的教师规则和个人生活权威认知得分对师生亲密性[(β=0.20,P0.05)vs.(β=0.23,P0.001)]、支持性[(β=0.23,P0.001)vs.(β=0.17,P0.01)]、满意度[(β=0.30,P0.001)vs.(β=0.13,P0.05)]得分均有正向预测作用,对师生之间的冲突性得分有负向预测作用[(β=-0.24,P0.01)vs.(β=-0.11,P0.05)]。结论:儿童对教师的不良处理方法权威认同存在权威认知水平上的差异,对教师主观方面权威认同度随着年龄的增加而降低,教师客观方面权威认知对师生的亲密性、支持性与满意度的建立具有积极预测作用,对师生冲突具有负向预测作用。     

注意缺陷多动障碍儿童的工作记忆存储特征

目的:探讨注意缺陷多动障碍(ADHD)儿童工作记忆存储能力特征。方法:对26名符合美国精神障碍诊断与统计手册第4版(DSM-IV)诊断标准的ADHD儿童和39名年龄及性别与之匹配的正常儿童,进行中国修订-韦氏儿童智力量表(C-WISC)、背数测验变式、方块图敲击试验变式和Kaufman儿童能力评估成套测验的寻找位置和手动作分测验测试,测查言语工作记忆和视空间工作记忆存储能力。结果:ADHD组在10 s后背数测验[(5.5±1.3)vs.(6.8±1.5)]、倒背数字[(3.3±1.1)vs.(4.1±1.0)]、方块图敲击试验[(4.4±1.1)vs.(5.1±0.8)]、10 s后敲击试验[(3.4±1.3)vs.(4.1±1.1)]、手动作测试[(8.5±3.3)vs.(10.4±3.1)]得分均低于正常组(均P0.05),两组在顺序背数测试[(6.6±1.0)vs.(7.1±1.0)]和寻找位置测试[(10.3±2.8)vs.(11.5±2.8)]得分差异无统计学意义(均P0.05)。多重线性回归分析表明,10 s后背数测试(β=0.31)、方块图敲击测试(β=0.29)、10秒后敲击试验(β=0.24)的得分高低与是否患ADHD相关(P0.05)。结论:ADHD儿童可能存在语音环信息保持能力损害和空间序列性信息存储能力缺陷。     

注意缺陷多动障碍儿童的内隐视觉空间注意特点

目的:探讨注意缺陷多动障碍(ADHD)儿童被动和主动内隐视觉空间注意特点.方法:选取符合美国精神障碍诊断与统计手册第4版(DSM-Ⅳ)ADHD诊断标准的儿童25例,以及性别、年龄与之匹配的正常儿童18名.分别测试反映被动内隐视觉空间注意的pop-out视觉搜索任务及反映主动内隐视觉空间注意的线索-目标视觉搜索任务,比较两组反应时(RT)、正确率和个体内反应时标准差(ISD).结果:Pop-out视觉搜索任务中,ADHD儿童[(637.4±132.0) ms vs.(626.3±125.0) ms]和正常儿童[(635.5±131.1) ms vs.(626.6±138.5) ms]对左视野目标反应时均长于右视野(均P＜0.05),但是两组之间反应时、总体正确率差异无统计学意义(均P ＞0.05);正常儿童左视野正确率低于右视野[(92.3±9.4)％ vs.(94.5±8.1)％,P＜0.01],而ADHD儿童左右视野正确率差异无统计学意义[(91.9±7.4)％ vs.(90.7±7.5)％,P＞0.05],ADHD儿童ISD大于正常儿童[(185.4±48.0) ms vs.(137.5±36.7) ms,P＜0.01].线索-目标任务中,ADHD儿童和正常儿童对左视野的目标反应时均长于右视野[ADHD组,(641.1 ±94.2) ms vs.(629.1 ±83.1)ms;正常对照组,(626.3±128.6) ms vs.(614.9±133.1)ms;均P＜0.05],且线索提示有效目标反应时短于线索提示无效[ADHD组,(627.6±89.4) msvs.(654.3±84.6)ms,P＜0.01;正常对照组,(615.4±132.5) ms vs.(627.3 ±127.5) ms,P＜0.01];两组之间反应时和正确率差异无统计学意义,ADHD儿童ISD大于正常儿童[(200.1±46.8) ms vs.(147.8±32.8)ms,P=0.05].结论:与正常儿童相比,ADHD儿童无论是被动还是主动内隐视觉空间注意,其注意力状态均不稳定,波动性增大,注意力维持困难.     

MPC基因甲基化在迟发性运动障碍发病机制中的作用

目的:探讨线粒体丙酮酸载体(MPC)基因差异甲基化在迟发性运动障碍(TD)发病机制中可能的作用。方法:共纳入符合DSM-IV精神分裂症诊断标准伴发TD患者14例(TD组)、不伴TD患者14例(NTD组)、首发患者14例(FE组)及正常对照组14例(HC组),运用MassArray系统检测精神分裂症患者和正常对照的MPC基因启动子区CpG位点的甲基化程度。结果:精神分裂症组MPC2基因CpG182∶187∶195位点的甲基化水平高于正常对照组[(-1.38±0.21) vs.(-1.58±0.02)];FE组MPC1的CpG87∶90位点[(-1.29±0.25) vs.(-1.61±0.28)]与MPC2的CpG 37位点[(-1.55±0.13) vs.(-1.90±0.14)]的甲基化水平高于慢性精神分裂症组;慢性精神分裂症组MPC1基因CpG276位点的甲基化水平高于FE组[(-0.86±0.21) vs.(-1.34±0.56)];TD组MPC1基因的CpG87∶90位点上的甲基化水平高于NTD组[-1.41±0.18) vs.-1.80±0.23)](均P﹤0.05)。相关分析结果显示,CpG CpG87∶90位点与AIMS总分呈正相关(r=0.59,P0.01)。结论:本研究提示精神分裂症和抗精神病药物的作用可能影响着MPC基因甲基化的表达。MPC基因甲基化在精神分裂症伴TD患者中存在异常,提示其在TD的发病机制中可能起一定作用。     

2～3岁孤独谱系障碍儿童突显网络的磁共振研究

目的:探讨2~3岁孤独谱系障碍(ASD)与发育迟缓(DD)儿童突显网络的结构差异。方法:对46名符合美国精神障碍诊断和统计手册第4版(修订版)(DSM-Ⅳ-TR)诊断标准的ASD和39例年龄、性别及发育商匹配的DD儿童(对照组)进行磁共振(MRI)扫描,比较两组前扣带回、岛叶灰质体积和皮层厚度的差异,分析前扣带回与岛叶灰质体积的相关性。使用孤独症诊断访谈量表(修订版)(ADI-R)以及沟通及象征行为量表/发展概况表(CSBS-DP)评估两组儿童的临床症状,分析ASD临床症状与脑结构体积变化之间的相关性。结果:与对照组相比,ASD组左侧岛叶灰质体积、左尾部及左喙部扣带区灰质体积增大(均P<0.05)。两组儿童的前扣带回和岛叶皮层厚度差异均无统计学意义(均P>0.05)。分别以年龄和全脑体积为协变量后ASD组左侧岛叶灰质体积[(7.1±0.6)cm3vs.(6.7±0.8)cm3]、左尾部扣带区灰质体积[(1.9±0.4)cm3vs.(1.7±0.4)cm3]及左喙部扣带区灰质体积[(2.7±0.5)cm3vs.(2.3±0.6)cm3]差异仍有统计学意义(均P<0.05)。ADI-R及CSBS-DP评分与体积的相关分析表明,对照组“用物”分项的评分与右侧岛叶灰质体积(r=0.38,P<0.05)呈正相关,其他相关系数无统计学意义。结论:与智能匹配的发育迟缓儿童相比孤独谱系障碍儿童突显网络的重要节点可能存在体积异常。     

读写困难与听写困难儿童的言语和视知觉认知缺陷

目的:研究读写双困难儿童和听写困难儿童在认知能力方面的差异.方法:在本横断面研究中,运用多重比较评估法分别对21名读写困难学生、20名听写困难学生和26名生理年龄匹配的对照组学生进行语音意识测验、语素意识测验和视知觉能力测验.结果:读写双困难组儿童的语音意识测验、语素意识测验得分均低于对照组[(-0.85±2.05)vs.(0.69±1.78), (20.7±2.8)vs.(22.8±1.8);均P＜0.05];读写双困难组儿童的视知觉记忆能力和视动统合能力得分均低于对照组[(7.2±2.4)vs.(8.6±1.8),(13.6±4.4)vs.(17.5±4.7);均P＜0.05],听写困难组儿童的视知觉辨别能力和视知觉记忆能力得分低于对照组[(2.8±1.6)vs.(4.1±1.4),(7.3±2.4)vs.(8.6±1.8);均P＜0.05].结论:视觉辨别和视觉短时记忆等功能的损伤是听写困难儿童特异性的认知缺陷,而语音、语义功能缺损则是读写双重困难儿童的重要特征.     

艾滋病致孤儿童的同胞分离抚养方式与健康危险行为

目的:探讨艾滋病致孤儿童的同胞分离抚养方式与其健康危险行为的关系.方法:选取6～17岁有同胞的艾滋病致孤儿童(父母双亡)155人参与本研究,根据是否经历同胞分离抚养,把他们分为同胞分离组(n=96)和无同胞分离组(n=59);根据不同的抚养方式把他们分为艾滋病致孤儿童福利院组(n=97)、家庭式抚养所组(n=8)与家族抚养组(n=50).采用健康危险行为量表进行测评.结果:经历同胞分离抚养的艾滋病致孤儿童的“饮酒”[(1.6±0.7)vs.(1.4±0.5)]、“打人”[(1.5±0.8)vs.(1.3±0.6)]和“破坏公共财产”[(1.1±0.5)vs.(1.0±0.0)]得分高于无同胞分离抚养组(均P＜0.05).艾滋病致孤儿童福利院抚养组的“打人”得分高于家庭式抚养所和家族抚养组[(1.6±0.8)vs.(1.2±0.4),(1.2±0.4);P＜0.05].多元协方差分析结果显示,经历同胞分离抚养的艾滋病致孤儿童的“饮酒”和“想要或扬言要伤害他人的行为”[(1.2±0.5)vs.(1.1±0.2)]的得分高于无同胞分离抚养者(均P＜0.05).结论:经历同胞分离抚养的艾滋病致孤儿童可能比没经历同胞分离抚养的艾滋病致孤儿童表现出更多的健康危险行为.     

精神分裂症伴迟发性运动障碍患者静息态脑功能低频振幅研究

目的:采用低频振幅(ALFF)指标评估精神分裂症伴迟发性运动障碍(TD)患者静息态脑功能活动及其与TD临床症状之间的关系。方法:对32例精神分裂症伴TD的患者(TD组),31例精神分裂症不伴TD的患者(非TD组)和32名正常对照(正常对照组)进行静息态脑功能磁共振扫描。分别使用阳性症状与阴性症状量表(PANSS)、异常不自主运动量表(AIMS)及重复性成套神经心理状态测验(RBANS)评估精神症状、异常不自主运动严重程度及认知功能。使用单样本t检验和单因素方差分析及事后比较t检验进行ALFF组内统计和组间比较。运用Pearson相关分析研究感兴趣区ALFF信号值与TD临床特征的关系。结果:TD组PANSS阴性症状得分高于非TD组[(22±5)vs.(17±6),P0.01],视觉广度认知得分低于非TD组[(72±14)vs.(82±15),P0.01]。TD组在右侧枕上回和楔叶的ALFF信号值低于非TD组(P0.01,Alpha Sim校正)。相关分析显示TD组样本在右侧枕上回和楔叶的ALFF值与AIM S总分之间呈弱负相关(r=-0.38),视觉广度认知得分与AIM S总分之间也呈弱负相关(r=-0.44),均有统计学意义(P0.05)。结论:本研究提示精神分裂症伴TD患者在静息状态下存在脑自发性神经活动异常,以枕上回和楔叶较为显著,并可能与TD的临床症状相关。     

MRI in schizophrenia: basal ganglia and white matter T1 times

The T1 relaxation time of the basal ganglia (putamen, globus pallidus and head of caudate) and of the frontoparietal centrum semiovale was compared between 49 schizophrenic patients and 36 healthy controls. Previous reports of increased T1 time in the basal ganglia were not confirmed, and group differences were not detected within the white matter. Within patients T1 values could not be related to tardive dyskinesia or other clinical features. Normal variation seen in basal ganglia T1 times is described for the first time: lowest values occur in the globus pallidus and highest in the caudate, and values within the putamen increase rostrally.     

基于磁共振T1成像的帕金森病相关脑结构体积差异性分析

目的 应用3.0T磁共振T1成像分析帕金森病（PD）患者脑结构如尾状核、壳核、苍白球、中脑、背侧丘脑、海马、杏仁核体积的变化,探讨MRI体积测量在PD引起形态学改变的应用及在早期诊断上的意义。 方法 采用3.0T MRI对40例早中期PD患者和年龄匹配的32名正常人进行扫描,分别测量出全脑体积、双侧尾状核、双侧壳核、双侧苍白球、中脑、双侧背侧丘脑、双侧海马、双侧杏仁核的体积,对体积值标准化处理后,使用SPSS 22.0软件对数据进行统计学分析。 结果 比较早中期PD患者和正常对照组发现, PD患者的全脑、双侧尾状核、双侧海马、双侧杏仁核的标准化体积和正常人比较差异无显著性（P>0.05）;双侧壳核、双侧苍白球、双侧背侧丘脑、中脑标准化体积差异有显著性（P<0.05）。 结论 基于MRI测量尾状核、壳核、苍白球、中脑、背侧丘脑、海马与杏仁核的体积的变化能为PD的辅助诊断提供一定帮助。     

Striatopallidal regulation of affect in bipolar disorder

BACKGROUND: Evidence from the neuroimaging literature suggests that the basal ganglia plays an important role in the regulation of affect. This conclusion stems almost exclusively from group comparisons and it remains unclear whether previous findings can be confirmed from a longitudinal study of mood change. The aim of this study was to increase our understanding of the functional role of the basal ganglia and thalamus in relation to change in affect in patients with bipolar disorder. METHODS: Ten bipolar disorder subjects participated in a functional MRI study. We used a simple motor reaction time task to probe subcortical regions bilaterally. Subjects were scanned twice, once when their self-reported mood ratings indicated hypomania or euthymia and then again when they were in depressed states. RESULTS: Subjects in their euthymic or hypomanic states exhibited increased caudate activity bilaterally and the globus pallidus of the left hemisphere. Longitudinal analyses revealed a significant association between an increase in severity of depression and a decrease in activity in the external segment of the right globus pallidus. CONCLUSIONS: Our findings suggest that the globus pallidus is less responsive during a simple motor task in the depressed compared to the normal or euthymic states in patients with bipolar disorder. These results are consistent with current physiologic models of basal ganglia circuitry in which an increase in caudate activity results in an increase in inhibitory GABAergic outflow to the external globus pallidus and subsequent decrease in thalamocortical excitation and may underlie the clinical manifestations of depression in bipolar disorder. LIMITATIONS: The findings of this study need to be interpreted with caution as correlation coefficients may be overestimated in this small study sample.     

The pattern of neurodegeneration in Huntington's disease: a comparative study of cannabinoid, dopamine, adenosine and GABA(A) receptor alterations in the human basal ganglia in Huntington's disease

In order to investigate the sequence and pattern of neurodegeneration in Huntington's disease, the distribution and density of cannabinoid CB(1), dopamine D(1) and D(2), adenosine A(2a) and GABA(A) receptor changes were studied in the basal ganglia in early (grade 0), intermediate (grades 1, 2) and advanced (grade 3) neuropathological grades of Huntington's disease. The results showed a sequential pattern of receptor changes in the basal ganglia with increasing neuropathological grades of Huntington's disease. First, the very early stages of the disease (grade 0) were characterized by a major loss of cannabinoid CB(1), dopamine D(2) and adenosine A(2a) receptor binding in the caudate nucleus, putamen and globus pallidus externus and an increase in GABA(A) receptor binding in the globus pallidus externus. Second, intermediate neuropathological grades (grades 1, 2) showed a further marked decrease of CB(1) receptor binding in the caudate nucleus and putamen; this was associated with a loss of D(1) receptors in the caudate nucleus and putamen and a loss of both CB(1) and D(1) receptors in the substantia nigra. Finally, advanced grades of Huntington's disease showed an almost total loss of CB(1) receptors and the further depletion of D(1) receptors in the caudate nucleus, putamen and globus pallidus internus, and an increase in GABA(A) receptor binding in the globus pallidus internus.These findings suggest that there is a sequential but overlapping pattern of neurodegeneration of GABAergic striatal efferent projection neurons in increasing neuropathological grades of Huntington's disease. First, GABA/enkephalin striatopallidal neurons projecting to the globus pallidus externus are affected in the very early grades of the disease. Second, GABA/substance P striatonigral neurons projecting to the substantia nigra are involved at intermediate neuropathological grades. Finally, GABA/substance P striatopallidal neurons projecting to the globus pallidus internus are affected in the late grades of the disease. In addition, the finding that cannabinoid receptors are dramatically reduced in all regions of the basal ganglia in advance of other receptor changes in Huntington's disease suggests a possible role for cannabinoids in the progression of neurodegeneration in Huntington's disease.     

Distribution and binding parameters of GABAA receptors in the thalamic nuclei of Macaca mulatta and changes caused by lesioning in the globus pallidus and reticular thalamic nucleus

Ascending output from the basal ganglia to the primate motor thalamus is carried by GABAergic nigro- and pallido-thalamic pathways, which interact with intrinsic thalamic GABAergic systems represented in primates by local circuit neurons and axons of the reticular thalamic nucleus. Disease-triggered pathological processes in the basal ganglia can compromise any of these pathways either directly or indirectly, yet the effects of basal ganglia lesioning on its thalamic afferent-receiving territories has not been studied in primates. Two GABA(A) receptor ligands, [(3)H]muscimol and [(3)H]flunitrazepam, were used to study the distribution and binding properties of the receptor in intact monkeys, those with kainic acid lesions in the globus pallidus, and those with ibotenic acid lesions in the reticular nucleus using quantitative autoradiographic technique on cryostat sections of fresh frozen brain tissue. In control monkeys the binding affinities for [(3)H]muscimol averaged 50 nM in the thalamic nuclei and 86 nM in the basal ganglia while the binding densities varied (maximum density of binding sites [Bmax] range of 99.4-1000.1 fmol/mg of tissue). Binding affinities and Bmax values for [(3)H]flunitrazepam averaged 2.02 nM and 81-113 fmol/mg of tissue, respectively. Addition of 100-microM GABA increased average affinity to 1.35 nM whereas Bmax values increased anywhere from 1-50% in different nuclei. Zolpidem (100 nM) decreased binding by 68-80%. Bmax values for both ligands were decreased at the two survival times in both medial and lateral globus pallidus implying involvement of both nuclei in the lesion. Statistically significant, 40% decrease (P=0.055) of Bmax for [(3)H]muscimol was observed in the ventral anterior nucleus pars densicellularis (VAdc, the main pallidal projection territory in the thalamus) 1 week after globus pallidus lesioning and a 36% decrease (P=0.017) 4 months post-lesioning. In contrast, [(3)H]flunitrazepam Bmax values in the VAdc of the same animals were increased by 23% (P=0.021) at 1 week and 28% (P=0.005) 4 months postlesion, respectively. One week after the reticular nucleus lesioning, the binding densities of [(3)H]muscimol and [(3)H]flunitrazepam were decreased in the thalamic nuclei receiving projections from the lesioned reticular nucleus sector by approximately 50% (P<0.05) and 10-33% (P<0.05), respectively. The results suggest that different GABA(A) receptor subtypes are associated with different GABAergic systems in the thalamus which react differently to deafferentation.     

Initial observations on the distribution of cannabinoid receptor binding sites in the human adult basal ganglia using autoradiography.

The distribution of cannabinoid receptor binding sites has been studied in the basal ganglia of 3 human adults using the synthetic cannabinoid agonist [3H]CP55,940 and autoradiography. The [3H]CP55,940-specific labeling was found in the caudate, putamen, accumbens, substantia nigra pars reticulata, and globus pallidus. The binding was consistently higher in the medial over the lateral part of the globus pallidus.     

Neurotensin selectively facilitates glutamatergic transmission in globus pallidus

The tridecapeptide neurotensin has been demonstrated to modulate neurotransmission in a number of brain regions. There is evidence that neurotensin receptors exist in globus pallidus presynaptically and postsynaptically. Whole-cell patch-clamp recordings were used to investigate the modulatory effects of neurotensin on glutamate and GABA transmission in this basal ganglia nucleus in rats. Neurotensin at 1 microM significantly increased the frequency of glutamate receptor-mediated miniature excitatory postsynaptic currents. In contrast, neurotensin had no effect on GABA(A) receptor-mediated miniature inhibitory postsynaptic currents. The presynaptic facilitation of neurotensin on glutamatergic transmission could be mimicked by the C-terminal fragment, neurotensin (8-13), but not by the N-terminal fragment, neurotensin (1-8). The selective neurotensin type-1 receptor antagonist, SR48692 {2-[(1-(7-chloro-4-quinolinyl)-5-2(2,6-dimethoxyphenyl)pyrazol-3-yl)carbonylamino]-tricyclo(3.3.1.1.(3.7))-decan-2-carboxylic acid}, blocked this facilitatory effect of neurotensin, and which itself had no effect on miniature excitatory postsynaptic currents. The specific phospholipase C inhibitor, U73122 {1-[6-[[17beta-3-methoyyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione}, significantly inhibit neurotensin-induced facilitation on glutamate release. Taken together with the reported postsynaptic depolarization of neurotensin in globus pallidus, it is suggested that neurotensin excites the globus pallidus neurons by multiple mechanisms which may provide a rationale for further investigations into its involvement in motor disorders originating from the basal ganglia.     

Changes in subcortical structures in early- versus late-onset Alzheimer's disease

Patients with early-onset Alzheimer's disease (EOAD) are reported to be different from those with late-onset Alzheimer's disease (LOAD) in terms of neuropsychological and neuroimaging findings. In this study, we aimed to compare the longitudinal volume changes of 6 subcortical structures (the amygdala, hippocampus, thalamus, putamen, globus pallidus, and caudate nucleus) between patients with EOAD and LOAD for 3 years. We prospectively recruited 36 patients with probable Alzheimer's disease (14 EOAD, 22 LOAD) and 14 normal control subjects. We analyzed the volume of subcortical structures using an automatic surface-based method. At baseline, there were no differences in the volumes of subcortical structures between patients with EOAD and LOAD. However, over 3 years of longitudinal follow-up, patients with EOAD showed more rapid volumetric decline in the caudate, putamen, and thalamus than patients with LOAD, which is consistent with neuropsychological results. Our findings suggested that the cognitive reserve theory might be applicable to explain different decline rates of the volumes of the basal ganglia and thalamus according to onset age.     

Caudate nucleus hypointensity in the elderly is associated with markers of neurodegeneration on MRI

In this study we investigated patterns of hypointense basal ganglia on T2*-weighted magnetic resonance imaging (MRI) in 413 non-demented elderly (range: 70–82 years, mean 77 years; male/female: 177/239). In addition, we assessed associations between these patterns and age-related changes in the brain.Three patterns were noted: hypointensity limited to the globus pallidus (group I; n = 30; 7%), hypointensity of both globus pallidus and putamen (group II; n = 272; 66%), and hypointensity of globus pallidus, putamen and caudate nucleus (group III; n = 111; 27%). Group III demonstrated a higher volume of white matter hyperintensities, more atrophy, decreased whole brain magnetization transfer ratios and increased T2-values compared to groups I and II. No differences were observed between groups I and II.From this study we conclude that hypointensity of the caudate nucleus is associated with a higher load of age-related cerebral changes. These data suggest that hypointensity of the caudate nucleus could be a new biomarker of age-related changes in the brain.     

Role of individual basal ganglia nuclei in force amplitude generation

The basal ganglia-thalamo-cortical loop is an important neural circuit that regulates motor control. A key parameter that the nervous system regulates is the level of force to exert against an object during tasks such as grasping. Previous studies indicate that the basal ganglia do not exhibit increased activity with increasing amplitude of force, although these conclusions are based mainly on the putamen. The present study used functional magnetic resonance imaging to investigate which regions in the basal ganglia, thalamus, and motor cortex display increased activity when producing pinch-grip contractions of increasing force amplitude. We found that the internal portion of the globus pallidus (GPi) and subthalamic nucleus (STN) had a positive increase in percent signal change with increasing force, whereas the external portion of the globus pallidus, anterior putamen, posterior putamen, and caudate did not. In the thalamus we found that the ventral thalamic regions increase in percent signal change and activation volume with increasing force amplitude. The contralateral and ipsilateral primary motor/somatosensory (M1/S1) cortices had a positive increase in percent signal change and activation volume with increasing force amplitude, and the contralateral M1/S1 had a greater increase in percent signal change and activation volume than the ipsilateral side. We also found that deactivation did not change across force in the motor cortex and basal ganglia, but that the ipsilateral M1/S1 had greater deactivation than the contralateral M1/S1. Our findings provide direct evidence that GPi and STN regulate the amplitude of force output. These findings emphasize the heterogeneous role of individual nuclei of the basal ganglia in regulating specific parameters of motor output.