首发精神分裂症患者听感觉门控P50及认知功能的相关性研究

目的 探讨首发精神分裂症患者听感觉门控P50与威斯康星卡片分类测验之间的相关性.方法 采用配对听觉条件、测试刺激范式及威斯康星卡片分类测验对51名首发精神分裂症患者和51名健康常人进行检测,并进行相关性分析.结果 患者组听感觉门控P50抑制明显高于对照组(P<0.01);威斯康星卡片分类测验结果显示,患者组完成分类数和正确分类数显著低于对照组,而错误数和持续错误数显著高于对照组(P<0.01);患者组听感觉门控P50抑制与威斯康星卡片分类测验指标间无相关性.结论 首发精神分裂症患者存在认知功能损害与额叶功能缺陷,反映出可能存在不同的神经发生机制.     

精神分裂症患者健康一级亲属P50感觉门控对照研究

目的 探讨精神分裂症患者健康一级亲属不同诱发模式P50感觉门控的临床特征.方法 应用条件-测试刺激模式和刺激序列模式检测精神分裂症患者健康一级亲属、精神分裂症患者和健康自愿者（对照组）的脑听觉诱发电位P50,计算P50抑制率,比较3组间的差异性.结果 条件-测试刺激模式中,亲属组T-P50波幅显著低于患者组、高于对照组（P＜0.05）,P50抑制显著强于患者组、弱于对照组（P＜0.05）;刺激序列模式中,亲属组、对照组P50波幅显著低于患者组（P＜0.05）,P50抑制显著强于患者组（P＜0.05）,亲属组与对照组比较差异无显著性（P＞0.05）.结论 精神分裂症患者健康一级亲属两种诱发模式P50感觉门控功能表现不一致,可能具有不同的中枢神经机制.     

未经治疗的首发精神分裂症患者脑灰质非对称性改变:基于VBM的MRI结构研究

目的:采用核磁共振成像及优化的基于体素形态学研究(voxel based morphometry,VBM)新技术分析未经治疗的首发精神分裂症患者的脑结构非对称性改变。方法:对符合DSM-IV精神分裂症诊断标准,同时未经药物治疗的首发精神分裂症住院患者以及正常志愿者各20例进行核磁共振扫描脑结构成像及基于VBM的脑非对称性分析。结果:病例组较正常对照显示出明显的正常非对称性减低甚至反转的改变。正常右利手左半球优势区域如额上回、颞中回、扣带回、眶回、尾状核头以及丘脑的非对称性下降;中央后回非对称性反转;海马及海马旁回的右大于左的非对称性增加。结论:脑非对称性在未用药物治疗的首发精神分裂症患者中有明显的异常改变,提示精神分裂症患者存在原发的脑结构非对称性异常,脑非对称性紊乱的存在反映了神经异常发育与精神分裂症的发病的关联。精神分裂症患者存在的脑结构非对称性异常可能构成了精神分裂症的神经生物学表征。     

未用药精神分裂症患者在面孔识别任务的fMRI研究

目的应用功能磁共振成像研究（fMRI）对比未用药精神分裂症组和对照组在进行面孔识别工作记忆时（中性面孔作为记忆内容）脑激活区的差异。方法本研究对10名符合ICD-10、DSM-Ⅳ精神分裂症偏执型未用药患者（病例组）和10名年龄、性别和教育程度相匹配的健康人进行面孔识别功能成像,所有研究对象均为右利手,经常规MR检查除外脑部外伤等器质性疾患,应用磁共振BOLD成像技术比较两组在进行面孔识别任务时各脑区激活程度的差异。结果在面孔识别任务时病例组较对照组脑部激活降低的区域：两侧梭状回、两侧枕中回、两侧扣带回、两侧额中回和额下回、两侧小脑、左额上回、左顶上叶、右顶下叶和左侧丘脑。结论梭状回是分裂症患者面孔识别认知功能受损的主要部位,同时,两侧额叶（VLFPC、DLFPC）、扣带回、小脑和左丘脑等激活程度降低也说明分裂症患者这些脑区信息加工过程受损。     

无症状反流性食管炎患者静息期功能性磁共振成像脑区活动特征分析

目的探讨无症状反流性食管炎患者静息期功能性磁共振成像脑区活动特征。方法选择食管炎患者共28例,包括无症状(研究组)和有症状(对照组)患者各14例,在静息期进行功能性磁共振成像(f MRI)扫描,观察并比较两组脑区活动特征。结果两组在静息期f ALFF值均存在显著高于全脑平均值的脑区。当zf ALFF的差异阈值=2.1103时,可见研究组患者在右侧中央沟盖、右侧颞上回、右侧颞横回、右侧中央后回较对照组患者f ALFFz值明显减低(P0.01),峰值点Talairach空间坐标为(45,-4,11),激活体素个数为121,峰激活强度为2.1799。结论无症状反流性食管炎患者静息期功能性磁共振成像脑区活动出现特殊变化,内脏感觉敏感性变化在无症状反流性食管炎患者发病中起着重要作用。     

重复伤害性电刺激下大鼠脑功能性磁共振成像的变化

目的:观察重复伤害性电刺激下大鼠脑功能磁共振成像的变化.方法:健康清洁级SD大鼠24只,麻醉后行4个相同时间段的左前爪重复伤害性电刺激(分别为A、B、C、D,刺激间期为10 min);刺激期间予脑功能磁共振成像扫描,用统计参数法行图像分析不同时间段伤害性电刺激下脑功能成像的变化.结果:不同时间段刺激鼠左前爪激活数目情况:D时间段的总的激活数目显著低于A、B、C时间段,差异有统计学意义(P＜0.05);C时间段总的激活数目显著低于A、B时间段,差异有统计学意义(P＜ 0.05).A、B、C、D时间段伤害性电刺激大鼠均存在明显的局部脑区的血氧水平依赖(blood-oxygenation level-dependent,BOLD)信号的强烈变化,主要激活脑区包括:伏膈核(accumbens nucleus,Acb)、右侧初级感觉皮质(primary somatosensory cortex,SI)、右侧腹后外侧丘脑核(ventral posterolateral thalamic nucleus,VPL)及后扣带回皮质(retrosplenial granular cortex,RSG);在重复伤害性电刺激后,中枢对电刺激引起的躯体感觉传导通路及加工网络的BOLD信号响应减弱.结论:重复伤害性电刺激后,大鼠脑功能成像显示激活脑区数目减少,伏膈核、右侧S1、VPL、RSG脑区激活体素减小,可能与中枢对伤害性刺激的调制有关.     

首发精神分裂症患者威斯康星卡片分类测验中的脑功能障碍研究

目的:探讨首发未服药精神分裂症患者进行威斯康星卡片分类测验(WCST)操作时的脑功能状态特点。方法:20名健康受试者(对照组)和20名首发未服药精神分裂症患者(患者组)操作WCST和颜色卡片分类测验(CCST)时进行脑功能磁共振成像(fMRI),比较2组激活脑区的激活体积。结果:对照组WCST和CCST功能图像相减获得的脑活动功能图像显示,激活主要分布在双侧前额叶,尤其是背外侧部以及顶叶后下部皮质和前扣带回。患者组WCST操作成绩较对照组差,有显著性差异(P<0.01)。与对照组相比,患者组的左侧前额叶背外侧部、左前扣带回皮质激活低下,左顶叶后下部皮质激活增加(P<0.01或0.05)。结论:双侧前额叶,尤其是背外侧部,以及顶叶后下部皮质和前扣带回皮质参与WCST操作的高级认知过程。精神分裂症患者在未治疗前就存在执行功能缺陷,其前额叶和扣带回功能低下,可能与患者执行功能障碍相关;后顶叶皮质功能亢进,可能对前额叶功能低下有补偿作用。     

精神分裂症海马前后亚区结构改变的磁共振成像研究

目的通过人脑结构磁共振成像探讨精神分裂症患者前、后海马结构的改变,以及认知障碍病理生理机制。材料与方法选取符合纳入标准的精神分裂症患者72例和健康人群74名。比较海马、前海马和后海马体积的组间差异(将年龄和性别作为协变量),进一步将存在差异的脑区的体积值与认知得分进行相关分析。结果 (1)患病组两侧海马、前海马、后海马体积均显著小于对照组(P0.05);(2)患病组后海马体积与言语学习能力正相关,右侧前海马体积与推理/问题解决能力正相关。结论精神分裂症患者前后海马体积萎缩模式为理解精神分裂症患者认知障碍病理生理机制提供新的依据。     

男性精神分裂症患者前额叶和丘脑质子波谱分析

目的 探讨男性精神分裂症患者前额叶、丘脑的氢质子磁共振波谱(1H-MRS)的特点.方法 以26例7 d内未使用抗精神病药物及影响脑内乙酰胆碱神经递质药物的男性精神分裂症患者为研究组,以28名正常人为对照组.在入组24 h内两组采用多体素1H-MRS检测前额叶和丘脑生化代谢物N-乙酰基天门冬氨酸(NAA)、胆碱复合物(Cho)与肌酸复合物(Cr),完成NAA/Cr值、Cho/Cr值和NAA/(Cho+Cr)值的计算.结果 与对照组相比,研究组左侧前额叶及左、右侧丘脑NAA/Cr值(分别为1.40±0.34、1.45±0.31和1.51±0.32)均低于对照组(分别为1.69±0.31、1.69±0.23和1.70±0.28),差异有统计学意义(P均<0.05).Cho/Cr值和NAA/(Cho+Cr)值两组间比较差异无统计学意义.结论 男性精神分裂症患者的1H-MRS与正常人存在差异,左侧前额叶及丘脑同时存在神经元的功能和(或)结构异常.     

首发重性抑郁障碍患者治疗前后面部表情认知的脑功能磁共振研究

目的用功能磁共振手段对首发未用药的重性抑郁障碍(MDD)患者治疗前后面部表情认知时脑功能活动的变化进行研究。方法对21例MDD患者分别在治疗前后进行脑功能磁共振扫描,比较MDD患者治疗前后进行面部表情认知时的脑激活区域差异。结果与治疗前相比,治疗后MDD患者在进行悲伤表情认知时激活显著减弱的脑区有:两侧额叶中央前回、两侧额中回、左侧顶叶中央后回和左侧扣带回;激活显著增强的脑区有:两侧顶上小叶和左侧枕中回。与治疗前相比,治疗后MDD患者在进行愉快表情认知时激活显著减弱的脑区有:左侧额中回、右侧扣带回和右侧海马旁回;激活显著增强的脑区有:右侧额下回和左侧枕叶梭状回。结论治疗前后MDD患者在进行悲伤或愉快表情认知时存在脑区激活的动态变化,说明MDD患者存在多个脑区的脑功能异常,并且这种异常能在有效的抗抑郁治疗后随着症状缓解而改善,抑郁症患者的脑功能异常可能在抑郁症的发病机制中发挥重要作用。     

The neural networks underlying auditory sensory gating

One of the most consistent electrophysiological deficits reported in the schizophrenia literature is the failure to inhibit, or properly gate, the neuronal response to the second stimulus of an identical pair (i.e., sensory gating). Although animal and invasive human studies have consistently implicated the auditory cortex, prefrontal cortex and hippocampus in mediating the sensory gating response, localized activation in these structures has not always been reported during non-invasive imaging modalities. In the current experiment, event-related FMRI and a variant of the traditional gating paradigm were utilized to examine how the gating network differentially responded to the processing of pairs of identical and non-identical tones. Two single-tone conditions were also presented so that they could be used to estimate the HRF for paired stimuli, reconstructed based on actual hemodynamic responses, to serve as a control non-gating condition. Results supported an emerging theory that the gating response for both paired-tone conditions was primarily mediated by auditory and prefrontal cortex, with potential contributions from the thalamus. Results also indicated that the left auditory cortex may play a preferential role in determining the stimuli that should be inhibited (gated) or receive further processing due to novelty of information. In contrast, there was no evidence of hippocampal involvement, suggesting that future work is needed to determine what role it may play in the gating response.     

首发和慢性精神分裂症幻听患者的扩散张量成像研究

目的:探索首发和慢性精神分裂症幻听患者是否存在听觉、语言及记忆/边缘系统网络的相关白质纤维异常。方法:纳入21例首发和12例慢性精神分裂症幻听患者及人口学参量匹配的26例健康对照。收集所有研究对象的DTI数据,采用基于纤维束的空间统计分析方法比较两组患者和对照组间的白质纤维差异。结果:与对照组相比,首发精神分裂症幻听患者在胼胝体、上纵束、下额枕束、钩束、扣带束、外囊及内囊前肢区域部分各向异性(FA)显著降低,径向扩散张量(RD)显著升高。慢性精神分裂症幻听患者表现出比首发患者更广泛的白质损害,且除FA和RD的改变外,部分脑区还表现出轴向扩散张量(AD)的升高。结论:精神分裂症幻听患者存在连接语言、听觉和记忆/边缘系统网络的多种白质纤维异常。慢性精神分裂症幻听患者与首发患者相比可能表现出更严重的神经退行性改变。     

Evidence for a frontal cortex role in both auditory and somatosensory habituation: a MEG study

Auditory and somatosensory responses to paired stimuli were investigated for commonality of frontal activation that may be associated with gating using magnetoencephalography (MEG). A paired stimulus paradigm for each sensory evoked study tested right and left hemispheres independently in ten normal controls. MR-FOCUSS, a current density technique, imaged simultaneously active cortical sources. Each subject showed source localization, in the primary auditory or somatosensory cortex, for the respective stimuli following both the first (S1) and second (S2) impulses. Gating ratios for the auditory M50 response, equivalent to the P50 in EEG, were 0.54+/-0.24 and 0.63+/-0.52 for the right and left hemispheres. Somatosensory gating ratios were evaluated for early and late latencies as the pulse duration elicits extended response. Early gating ratios for right and left hemispheres were 0.69+/-0.21 and 0.69+/-0.41 while late ratios were 0.81+/-0.41 and 0.80+/-0.48. Regions of activation in the frontal cortex, beyond the primary auditory or somatosensory cortex, were mapped within 25 ms of peak S1 latencies in 9/10 subjects during auditory stimulus and in 10/10 subjects for somatosensory stimulus. Similar frontal activations were mapped within 25 ms of peak S2 latencies for 75% of auditory responses and for 100% of somatosensory responses. Comparison between modalities showed similar frontal region activations for 17/20 S1 responses and for 13/20 S2 responses. MEG offers a technique for evaluating cross modality gating. The results suggest similar frontal sources are simultaneously active during auditory and somatosensory habituation.     

Generators of the intracranial P50 response in auditory sensory gating

Clarification of the cortical mechanisms underlying auditory sensory gating may advance our understanding of brain dysfunctions associated with schizophrenia. To this end, data from nine epilepsy patients who participated in an auditory paired-click paradigm during pre-surgical evaluation and had grids of electrodes covering temporal and frontal lobe were analyzed. A distributed source localization approach was applied to the intracranial P50 response and the Gating Difference Wave obtained by subtracting the response to the second stimuli from the response to the first stimuli. Source reconstruction of the P50 showed that the main generators of the response were localized in the temporal lobes. The analysis also suggested that the maximum neuronal activity contributing to the amplitude reduction in the P50 time range (phenomenon of auditory sensory gating) is localized at the frontal lobe. Present findings suggest that while the temporal lobe is the main generator of the P50 component, the frontal lobe seems to be a substantial contributor to the process of sensory gating as observed from scalp recordings.     

Spatiotemporal signatures of an abnormal auditory system in stuttering

People who stutter (PWS) can reduce their stuttering rates under masking noise and altered auditory feedback; such a response can be attributed to altered auditory input, which suggests that abnormal speech processing in PWS results from abnormal processing of auditory input. However, the details of this abnormal processing of basic auditory information remain unclear. In order to characterize such abnormalities, we examined the functional and structural changes in the auditory cortices of PWS by using a 306-channel magnetoencephalography system to assess auditory sensory gating (P50m suppression) and tonotopic organization. Additionally, we employed voxel-based morphometry to compare cortical gray matter (GM) volumes on structural MR images. PWS exhibited impaired left auditory sensory gating. The tonotopic organization in the right hemisphere of PWS is expanded compared with that of the controls. Furthermore, PWS showed a significant increase in the GM volume of the right superior temporal gyrus, consistent with the right tonotopic expansion. Accordingly, we suggest that PWS have impaired left auditory sensory gating during basic auditory input processing and that some error signals in the auditory cortex could result in abnormal speech processing. Functional and structural reorganization of the right auditory cortex appears to be a compensatory mechanism for impaired left auditory cortex function in PWS.     

The selective alpha7 nicotinic acetylcholine receptor agonist PNU-282987 [N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-4-chlorobenzamide hydrochloride] enhances GABAergic synaptic activity in brain slices and restores auditory gating deficits in anesthetized rats

Schizophrenic patients are thought to have an impaired ability to process sensory information. This deficit leads to disrupted auditory gating measured electrophysiologically as a reduced suppression of the second of paired auditoryevoked responses (P50) and is proposed to be associated with decreased function and/or expression of the homomeric alpha7 nicotinic acetylcholine receptor (nAChR). Here, we provide evidence that N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-4-chlorobenzamide hydrochloride (PNU-282987), a novel selective agonist of the alpha7 nAChR, evoked whole-cell currents from cultured rat hippocampal neurons that were sensitive to the selective alpha7 nAChR antagonist methyllycaconitine (MLA) and enhanced GABAergic synaptic activity when applied to hippocampal slices. Amphetamine-induced sensory gating deficit, determined by auditory-evoked potentials in hippocampal CA3 region, was restored by systemic administration of PNU-282987 in chloral hydrate-anesthetized rats. Auditory gating of rat reticular thalamic neurons was also disrupted by amphetamine; however, PNU-282987 normalized gating deficit only in a subset of tested neurons (6 of 11). Furthermore, PNU-282987 improved the inherent hippocampal gating deficit occurring in a subpopulation of anesthetized rats, and enhanced amphetamine-induced hippocampal oscillation. We propose that the alpha7 nAChR agonist PNU-282987, via modulating/enhancing hippocampal GABAergic neurotransmission, improves auditory gating and enhances hippocampal oscillatory activity. These results provide further support for the concept that drugs that selectively activate alpha7 nAChRs may offer a novel, potential pharmacotherapy in treatment of schizophrenia.     

强迫症和精神分裂症患者的听及视信息加工过程中感觉性脑诱发电位特征比较

背景应用脑诱发电位技术比较强迫症和精神分裂症患者在听及视信息加工过程中感觉性脑诱发电位特征,是否可发现一些异常的生物学指标.目的观察强迫症和精神分裂症患者感觉性脑诱发电位长潜伏期及听觉脑诱发电位的变化特征,并与健康人相比较.设计随机抽样法,病例对照研究.地点和对象病例组为宁波市康宁医院门诊和住院患者,对照组均为身心健康的志愿者.干预利用意大利百胜公司GalileoSirius电生理仪对36例强迫症和36例精神分裂症患者用33例正常对照组进行了短声、闪光刺激,完成听觉脑诱发电位、视觉脑诱发电位.主要观察指标观察主波出现率,各波的波幅和潜伏期.结果发现与正常对照组相比,强迫症和精神分裂症患者无论在听觉诱发电位(auditory evoked potentials AEP),还是在视觉诱发电位(vi-sual evoked potentials VEP)中,其P3波出现率明显减少(x2=12.73,P＜0.01;x2=13.13,P＜0.01);其中VEP/P3出现率精神分裂症与强迫症相比更为减少(x2=34.62,P＜0.01).强迫症和精神分裂症患者的AEP/P2波呈双峰率现象均增高(x2=4.17,P＜0.05).强迫症、精神分裂症和正常对照组三组在相比,在AEP中潜伏期N1、P2波延长(F=6.95,P＜0.01;F=6.45,P＜0.01),波幅N1波下降(F=3.55,P＜0.05);VEP中P2潜伏期延长(F=6.16,P＜0.01),波幅P2,P3波均有改变(F=7.96,P＜0.01;F=12.06,P＜001).结论强迫症和精神分裂症患者在听、视信息加工过程均有不同程度的异常,以精神分裂症为重,其异常指标与其发病机制和症状有关,值得关注.     

宽叶缬草对局灶性脑缺血后海马区C-Fos,C-Jun表达的实验研究

INTRODUCTIONStrokeisoneofthemostcommoncauseofdeathanddisablinganeurologicdisorderinChina．RecentresearchshowedthatChinesetraditionalmedicinecouldimprovetheoutcome，butthemecha－nismwasstillunclear犤１－３犦．Valerianofficinalsvar．latifolia（VOL）isoneofthemedicineinShennongjia，Hubeiprovince，whichcouldeliminateoxygen－derivedfreeradidicals，protectvascularendothe－lialcellsandinhibitproliferationofsmoothmusclecells．Thisex－perimentselectreversiblemiddlecerebralarteryocclusion（MCAO…