持续短阵快速脉冲刺激前额叶皮质对视空间注意功能的调控机制

目的:探讨持续短阵快速脉冲刺激背外侧前额叶皮质对视空间注意功能的调控机制.方法:选取志愿受试者40人参加本实验,男女各半,全部为右利手.采用持续短阵快速脉冲经颅磁刺激(cTBS,TMS)背外侧前额叶皮质(DLPFC)后进行注意网络测试(ANT),所有受试者均按照随机顺序进行真/假刺激左佑侧背外侧前额叶脑区.结果:持续短阵快速脉冲经颅磁刺激施加于前额叶时,不同提示和刺激类型的平均反应时均无明显改变.右侧额叶抑制,警觉和执行功能受损(P＜0.05);左侧额叶抑制,反而出现警觉和执行功能增强(P＜005).结论:背外侧前额叶皮质主要与警觉和执行功能有关,具有明显的右侧半球优势.在双侧大脑半球同源脑区间,视空间注意认知过程存在竞争性抑制.     

单侧后顶叶皮质过度活动对空间定向功能的影响

摘要 目的：探讨单侧后顶叶皮质的过度活动是否会造成对侧同源脑区的功能抑制并影响空间定向功能。 方法：按照一定的入选标准选取健康受试者30人,采用兴奋性间歇性短阵快速脉冲刺激,随机对左/右侧后顶叶皮质进行真/假刺激,结合注意网络测试系统评定受试者视空间注意功能的变化。 结果：间歇性短阵快速脉冲刺激右侧后顶叶皮质,可以提高警觉及定向功能（P＜0.05）;刺激左侧后顶叶皮质,定向功能受损（P＜0.05）。 结论：右侧后顶叶是空间定向活动的关键脑区,左侧后顶叶过度活动可以导致右侧后顶叶功能抑制。建立双侧半球间新的竞争性平衡,对实现单侧后顶叶损害空间定向功能的康复具有重要意义。     

脑额顶网络损害患者视空间注意功能障碍的研究

目的 探讨额顶网络损害患者视空间注意网络的解剖和功能定位及其相互影响.方法 采用注意网络测试任务,对13例局灶性额叶损害和12例顶叶损害患者进行网络效率测试,并与30例正常对照组的注意网络测试结果相比较.结果 额顶网络损害患者不同提示和刺激类型的平均反应时间均明显比正常对照组慢(P＜0.05);警觉和定向网络效率及其比率也均明显受损(P＜0.01).额叶损害患者执行网络效率及其比率与正常对照组比较明显受损(P＜0.01),而顶叶损害患者没有受损,反而网络效率比率还增强(P＜0.01).结论 额顶网络与警觉和定向网络功能有关,而执行控制网络主要与额叶活动有关,并且注意网络测试是研究视觉注意认知过程的有效任务和工具.

Abstract：

Objective To probe deficits in visuospatial attention using an attention network test (ANT) in patients with frontoparietal network lesions. Methods The ANT was used to measure the alertness, orienting and executive control abilities of 25 patients with local brain lesions, including 13 with frontal and 12 with parietal damage. Their results were compared with those of health adults. Results During ANT tasks, the patients' responses were significantly slower on each cue and target condition than controls', and showed deficits in their alerting and orienting networks. The efficiency of executive control was impaired in patients with frontal lesions, but increased with parietal lesions. Conclusions These findings suggest that the frontoparietal network is involved in alerting and orienting, but the executive control function may be selectively associated with the frontal lobe. ANT is an efficienttool for studying visual attention and cognition.     

后顶叶皮质调控视空间注意功能的经颅磁刺激研究

目的探讨后顶叶皮质与视空间注意功能的关联性及其调控机制。 方法选取志愿受试者40例参加本实验，所有受试者均按照随机顺序对左、右侧后顶叶进行真、假刺激。于刺激前和每次刺激后(刺激后)对40例受试者进行神经行为学评价和注意网络测试，并对所获得的数据进行分析。 结果刺激前、后，受试者各项行为学评价差异均无统计学意义（P&rt;0.05）。右侧真刺激与假刺激比较，空间提示状态下平均RT明显延长，差异具有统计学意义（t=2.648,P<0.05）；且右侧真刺激时与左侧真刺激时空间提示状态下的平均RT比较，差异有统计学意义（t=3.689,P<0.01）。右侧PPC真刺激后，警觉网络效率（t=2.843,P<0.01）及其比率（t=2.841,P<0.01）明显降低，而左侧PPC真刺激后，警觉网络效率（t=2.324,P<0.05）及其比率（t=2.225,P<0.05）明显增强，且左侧与右侧真刺激后警觉网络效率及其比率比较，差异均也有统计学意义（P<0.05）；定向网络——右侧PPC真刺激后，定向网络效率（t=5.535,P<0.01）及其比率（t=5.245,P<0.01）明显降低，左侧与右侧真刺激后定向网络效率及其比率比较，差异均也有统计学意义（P<0.05）。 结论后顶叶皮质主要与定向和警觉功能有关，具有明显的右侧半球优势。在双侧大脑半球同源脑区间，视空间注意认知过程存在竞争性抑制。     

经颅直流电刺激对脑卒中视觉空间忽略患者视运动探查功能的影响

摘要 目的：观察阳极经颅直流电刺激作用于右侧后顶叶皮质对右侧脑卒中后左侧视觉空间忽略患者视运动探查功能表现的影响。 方法：研究纳入20例右侧脑卒中后左侧视觉空间忽略患者,分为治疗组和对照组：治疗组（n=10）行经颅直流电刺激联合常规康复治疗;对照组（n=10）行常规康复治疗。治疗前、治疗后予以不同注意需求的视运动探查任务评估：单纯搜索目标（线段删除）、对不同搜索目标进行不同标记（缺口探查）、从干扰刺激中搜索目标（星星删除）。 结果：治疗组线段删除得分较治疗前有改善,左侧缺口圆判断错误率、星星删除遗漏率有所减低,且差异均有显著性意义（P＜0.05）;而对照组较基线水平相比差异无显著性意义（P＞0.05）;治疗后两组间线段删除、缺口探查未标记目标百分比及左侧缺口率差异有显著性意义（P＜0.05）,但星星删除差异无显著性意义（P＞0.05）。 结论：阳极经颅直流电刺激作用于右侧后顶叶皮质对不同注意加工需求的视运动探查任务影响不同,经颅直流电刺激对单纯目标搜索功能的改善和以目标物自身为参考框架成分加工的改善有促进作用。     

经颅磁刺激对健康受试者舌骨上肌群运动诱发电位的影响

目的研究短阵快速脉冲经颅磁刺激（TBS）对舌骨上肌群运动皮质兴奋性的影响,进一步探讨双侧大脑半球运动皮质对舌骨上肌群的调控机制。 方法选取健康受试者24例,采用持续短阵快速脉冲经颅磁刺激（cTBS）刺激受试者左侧舌骨上肌群运动皮质,采用间隔短阵快速脉冲经颅磁刺激(iTBS)刺激受试者右侧舌骨上肌群运动皮质,记录刺激前及刺激后即刻、15min、30min双侧舌骨上肌群的运动诱发电位（MEP）,用重复测量方差分析方法分析刺激前、后不同时间点双侧舌骨上肌群MEP波幅的变化。 结果刺激前,左右两侧舌骨上肌群MEP波幅分别为（375.29±176.09）μV和（368.17±149.02）μV,分别与同侧刺激后即刻、刺激后15min和刺激后30min舌骨上肌群MEP波幅比较,差异均有统计学意义（P<0.05）。 结论iTBS可兴奋右侧舌骨上肌群运动皮质,并能逆转左侧相应皮质被cTBS预处理的抑制效应。TBS可以影响两侧大脑半球舌骨上肌群运动皮质的兴奋性,对脑卒中后吞咽障碍患者的康复具有重要指导意义。     

经颅磁刺激抑制健康人初级运动皮质后双侧中央前回精细分区的脑有效连接变化

目的观察经颅磁刺激抑制右侧初级运动皮质(M1)后双侧中央前回精细分区有效连接变化情况。方法选取21例健康志愿者纳入本研究,于持续短阵脉冲刺激(cTBS)干预前、后分别行静息态功能磁共振(rs-fMRI)检查,参照中科院自动化研究所制订的脑图谱对受试者双侧中央前回进行精细分区,选用Granger因果分析观察受试者双侧中央前回有效连接变化情况。结果经cTBS抑制右侧M1区后受试者双侧中央前回各亚区有效连接呈显著变化,右上肢功能区对左上肢、左头面部功能区的有效连接减弱,左上肢功能区对右侧头面部及右上肢功能区的有效连接增强。结论经cTBS抑制右侧M1区后,受试者双侧M1区上肢功能区的有效连接变化反映了半球间交互抑制,同时M1躯干功能区也发生了与上肢功能区方向相反的有效连接改变。     

高频重复经颅磁刺激治疗遗忘型轻度认知障碍的局部一致性研究

目的 通过局部一致性(ReHo)分析方法探究高频重复经颅磁刺激(rTMS)治疗遗忘型轻度认知障碍(aMCI)的脑功能影像机制。 方法 采用随机对照的研究方法,将25例aMCI患者分为观察组（13例）和对照组（12例）,观察组行经颅磁刺激治疗,刺激部位为左侧前额叶背外侧区（DLPFC）,频率10 Hz,80% RMT,每次400个脉冲,5次/周,共治疗4周;对照组仅将磁刺激线圈垂直置于颅骨表面行假经颅磁刺激治疗,其余仪器设备、刺激位点、强度及频率等与观察组相同。分别于治疗前和治疗4周后（治疗后）,采用中文版蒙特利尔认知评估量表(MoCA)对2组患者进行认知功能评估,并行静息态功能性磁共振成像（fMRI）数据采集,比较治疗前后aMCI患者大脑ReHo值的变化。 结果 观察组患者经4周rTMS治疗后的MoCA评分较组内治疗前和对照组治疗后明显提高(P<0.05 )。fMRI检测结果显示,与组内治疗前相比,观察组治疗后右侧额中回脑区的ReHo值显著增加(P<0.05 ),而对照组治疗后右侧额中回和左侧楔前叶脑区的ReHo值显著降低(P<0.05 )。 结论 高频rTMS可以提高aMCI患者的认知功能,使认知相关脑区神经元间的自发活动更趋于同步化。     

θ节律串刺激对视觉空间注意的行为学及事件相关电位研究

目的:研究持续性θ节律串刺激(cTBS)对视觉空间注意障碍的作用机制.方法:将30例正常受试者随机分为实验组(刺激组)和对照组(假刺激组),两组经过TBS刺激后进行事件相关电位(ERP)实验,实验范式为“提示一靶”,包括范围提示和汉字提示,范围提示为“大”圈和“小”圈,汉字提示为“大”字和“小”字.TBS刺激参数频率为30Hz,刺激强度为刺激器输出的50％,刺激部位为受试者右侧大脑的顶叶后部(P4),刺激脉冲801串,刺激间隔100ms.结果:实验组和对照组在汉字提示和范围提示时,反应时表现出提示等级效应(P＜0.05).实验组与对照组比较,在汉字提示下P1、P2波幅明显低于对照组(P＜0.05),在范围提示下PO4部位的P1、N1、N2波幅明显低于对照组(P＜0.05).实验组汉字提示与范围提示比较,范围提示时P1、P2、N2波幅更大(P＜0.05);对照组汉字提示与范围提示比较,范围提示时P1、N1、P2波幅更大(P＜0.05).结论:对右侧顶后叶皮质(PPC)进行抑制性cTBS刺激,能够影响大脑皮质神经元兴奋性活动,尤其会影响对左侧靶目标的识别及加工.     

经颅直流电刺激对最小意识状态患者脑功能网络的即刻效应研究

目的:探讨经颅直流电刺激(tDCS)对最小意识状态(MCS)患者静息态脑功能网络功能连接强度(FCS)的影响。方法:纳入11例符合MCS诊断标准的患者,其中男9例,女2例;脑外伤10例,脑出血1例;平均年龄37.27±8.36岁,平均病程3.36±0.12个月。所有患者入组前均给予1次静息态功能性磁共振(rs-f MRI)扫描,随后固定tDCS的电极,阳极固定在左侧前额叶背外侧区,阴极固定在眶上区,并按照下列顺序进行研究。首先给予单次安慰tDCS刺激(20min),单次安慰刺激完成后进行第2次rs-f MRI扫描,然后给予单次真tDCS刺激(20min),单次真tDCS刺激结束后进行第3次rs-f MRI扫描,每次给予rs-f MRI评估同时应用昏迷恢复量表修订版(CRS-R)进行测评。结果:与治疗前比较,单次安慰tDCS治疗后各静息态脑功能网络功能连接强度差异无显著性意义(P0.05);单次真tDCS治疗后听觉网路(右侧颞下回)、额顶网络(左侧角回及颞叶后部)的功能连接强度(FCS)显著增强(P0.05)。单次真tDCS与单次安慰tDCS比较,默认网络(右侧楔前叶)、额顶网络(右侧角回、右侧中央后回)、感觉运动网络(双侧辅助运动区)功能连接强度显著增强(P0.05)。结论:经颅直流电刺激对静息态脑功能连接产生显著影响,双侧大脑半球感觉运动网络、左侧额顶网络功能、意识水平相关的默认网络关键节点(右侧楔前叶)功能连接强度增强,可能是这种干预促进患者意识水平恢复的神经机制。     

The activation of attentional networks

Alerting, orienting, and executive control are widely thought to be relatively independent aspects of attention that are linked to separable brain regions. However, neuroimaging studies have yet to examine evidence for the anatomical separability of these three aspects of attention in the same subjects performing the same task. The attention network test (ANT) examines the effects of cues and targets within a single reaction time task to provide a means of exploring the efficiency of the alerting, orienting, and executive control networks involved in attention. It also provides an opportunity to examine the brain activity of these three networks as they operate in a single integrated task. We used event-related functional magnetic resonance imaging (fMRI) to explore the brain areas involved in the three attention systems targeted by the ANT. The alerting contrast showed strong thalamic involvement and activation of anterior and posterior cortical sites. As expected, the orienting contrast activated parietal sites and frontal eye fields. The executive control network contrast showed activation of the anterior cingulate along with several other brain areas. With some exceptions, activation patterns of these three networks within this single task are consistent with previous fMRI studies that have been studied in separate tasks. Overall, the fMRI results suggest that the functional contrasts within this single task differentially activate three separable anatomical networks related to the components of attention.     

rTMS evidence of different delay and decision processes in a fronto-parietal neuronal network activated during spatial working memory

The existence of a specific and widely distributed network for spatial working memory (WM) in humans, involving the posterior parietal cortex and the prefrontal cortex, is supported by a number of neuroimaging studies. We used a repetitive transcranial magnetic stimulation (rTMS) approach to investigate the temporal dynamics and the reciprocal interactions of the different areas of the parieto-frontal network in normal subjects performing a spatial WM task, with the aim to compare neural activity of the different areas in the delay and decision phases of the task. Trains of rTMS at 25 Hz were delivered over the posterior parietal cortex (PPC), the premotor cortex (SFG) and the dorsolateral prefrontal cortex (DLPFC) of the right hemisphere alternatively during the two phases. We found a pattern of interference of TMS during the delay phase for both parietal and DLPFC sites of stimulation, with no effect observed for the SFG site. When rTMS trains were applied during the decision phase, an interference was observed selectively for DLPFC. The present study shows the existence of a parallel processing in the parieto-frontal network of spatial WM during the delay phase. Furthermore, it provides new evidence of the critical role of the DLPFC during both the delay and the decision phases. We suggest that in DLPFC, two different networks coexist: A local neural network subserving the decisional processes and a second neural population functionally interconnected with the PPC and activated when a certain spatial information has to be kept in memory, available to use.     

活体小鼠后顶叶皮质神经元双光子成像与空间定向机制

目的:结合双光子显微镜和Morris水迷宫探讨右侧顶叶皮质在空间认知功能中的作用机制.方法:选用C57BL/6J小鼠18只,随机分为正常对照组和右侧顶叶损毁组,用直流电损害小鼠的后顶叶皮质,正常对照组未做任何处理.在双光子显微镜下观测小鼠活体内右侧顶叶皮质神经元活动,Morris水迷宫评价小鼠的空间认知功能.结果:在双光子显微镜下,损毁组小鼠较正常组右侧顶叶皮质功能神经细胞明显减少,神经元跨膜电位明显减弱.在水迷宫空间任务中,损毁组小鼠空间学习能力及空间探索功能也均明显减弱.结论:双光子显微镜可在活体动物直接观察神经元活动;正常右侧后顶叶功能神经元活动是空间定向认知的关键.     

The effect of gender on planning: An fMRI study using the Tower of London task

Since the introduction of brain mapping, evidences of functional gender differences have been corroborating previous behavioral and neuropsychological results showing a sex-specific brain organization. We investigated gender differences in brain activation during the performance of the Tower of London (TOL) task which is a standardized test to assess executive functions. Eighteen healthy subjects (9 females and 9 males) underwent fMRI scanning while solving a series of TOL problems with different levels of difficulty. Data were analyzed by modeling both genders and difficulty task load. Task-elicited brain activations comprised a bilateral fronto-parietal network, common to both genders; within this network, females activated more than males in dorsolateral prefrontal cortex (DLPFC) and right parietal cortex, whereas males showed higher activity in precuneus. A prominent parietal activity was found at low level of difficulty while, with heavier task demand, several frontal regions and subcortical structures were recruited. Our results suggest peculiar gender strategies, with males relying more on visuospatial abilities and females on executive processing.     

The role of the dorsolateral prefrontal cortex in random number generation: a study with positron emission tomography

Random number generation (RNG) engages a number of executive processes. We used positron emission tomography (PET) to measure regional cerebral blood flow (rCBF) in six volunteers who performed RNG and a control counting (COUNT) task at six rates paced by a tone. This provided a systematic variation of difficulty of RNG. Relative to COUNT, RNG was associated with significant activation of the left dorsolateral prefrontal cortex (DLPFC), the anterior cingulate, the superior parietal cortex bilaterally, the right inferior frontal cortex, and the left and right cerebellar hemispheres. Faster rates of RNG were associated with a significant decrease in regional cerebral blood flow (rCBF) in the left and right DLPFC and the right superior parietal cortex. rCBF in the left DLPFC was significantly and negatively associated with count score 1, a measure of habitual counting during RNG. These results are discussed in relation to the network modulation model of RNG developed on the basis of our previous studies using transcranial magnetic stimulation and dual task paradigms. This suggests that during RNG, suppression of habitual counting is achieved through the modulatory (inhibitory) influence of the left DLPFC over a number associative network distributed in the superior temporal cortex. At faster rates of RNG the synchronization demands of paced RNG result in the breakdown of this modulatory influence, which is evident from decreased rCBF in the left DLPFC and increased habitual counting at faster rates.     

Continuous theta-burst stimulation (cTBS) over the lateral prefrontal cortex alters reinforcement learning bias

The prefrontal cortex is known to play a key role in higher-order cognitive functions. Recently, we showed that this brain region is active in reinforcement learning, during which subjects constantly have to integrate trial outcomes in order to optimize performance. To further elucidate the role of the dorsolateral prefrontal cortex (DLPFC) in reinforcement learning, we applied continuous theta-burst stimulation (cTBS) either to the left or right DLPFC, or to the vertex as a control region, respectively, prior to the performance of a probabilistic learning task in an fMRI environment. While there was no influence of cTBS on learning performance per se, we observed a stimulation-dependent modulation of reward vs. punishment sensitivity: Left-hemispherical DLPFC stimulation led to a more reward-guided performance, while right-hemispherical cTBS induced a more avoidance-guided behavior. FMRI results showed enhanced prediction error coding in the ventral striatum in subjects stimulated over the left as compared to the right DLPFC. Both behavioral and imaging results are in line with recent findings that left, but not right-hemispherical stimulation can trigger a release of dopamine in the ventral striatum, which has been suggested to increase the relative impact of rewards rather than punishment on behavior.     

Cerebral correlates of alerting, orienting and reorienting of visuospatial attention: an event-related fMRI study

The identification of brain systems contributing to different aspects of visuospatial attention is of both clinical and theoretical interest. Cued target detection tasks provide a simple means to dissociate attentional subcomponents, such as alerting, orienting or reorienting of attention. Event-related functional magnetic resonance imaging (fMRI) was used to study neural correlates of these distinct attentional processes. Volunteers were scanned while performing a centrally cued target detection task. Four different types of trials (no cue, neutral cue, valid cue and invalid cue trials) with targets appearing either in the right or left hemifield were randomly intermixed. Behaviourally, the data provided evidence for alerting, spatial orienting and reorienting of attention. Neurally, the alerting effect was seen in bilaterally increased extrastriatal blood oxygenation level-dependent (BOLD) activity in neutral as compared to no cue trials. Neural correlates of spatial orienting were seen in anterior cingulate cortex, which was more active during valid as compared to neutral cue trials. Neural correlates of reorienting of attention, that is, higher BOLD activity to invalid as compared to validly cued trials were evident in several brain regions including left and right intraparietal sulcus, right temporo-parietal junction and middle frontal gyrus bilaterally. The data suggest that frontal and parietal regions are specifically involved in reorienting rather than orienting attention to a spatial position. Alerting effects were seen in extrastriate regions which suggest that increased phasic alertness results in a top-down modulation of neural activity in visual processing areas.     

The link between visual exploration and neuronal activity: a multi-modal study combining eye tracking, functional magnetic resonance imaging and transcranial magnetic stimulation

In the present multi-modal study we aimed to investigate the role of visual exploration in relation to the neuronal activity and performance during visuospatial processing. To this end, event related functional magnetic resonance imaging er-fMRI was combined with simultaneous eye tracking recording and transcranial magnetic stimulation (TMS). Two groups of twenty healthy subjects each performed an angle discrimination task with different levels of difficulty during er-fMRI. The number of fixations as a measure of visual exploration effort was chosen to predict blood oxygen level-dependent (BOLD) signal changes using the general linear model (GLM). Without TMS, a positive linear relationship between the visual exploration effort and the BOLD signal was found in a bilateral fronto-parietal cortical network, indicating that these regions reflect the increased number of fixations and the higher brain activity due to higher task demands. Furthermore, the relationship found between the number of fixations and the performance demonstrates the relevance of visual exploration for visuospatial task solving. In the TMS group, offline theta bursts TMS (TBS) was applied over the right posterior parietal cortex (PPC) before the fMRI experiment started. Compared to controls, TBS led to a reduced correlation between visual exploration and BOLD signal change in regions of the fronto-parietal network of the right hemisphere, indicating a disruption of the network. In contrast, an increased correlation was found in regions of the left hemisphere, suggesting an intent to compensate functionality of the disturbed areas. TBS led to fewer fixations and faster response time while keeping accuracy at the same level, indicating that subjects explored more than actually needed.     

The left parietal and premotor cortices: motor attention and selection

It is well established that the premotor cortex has a central role in the selection of movements. The role of parts of the parietal cortex in movement control has proved more difficult to describe but appears to be related to the preparation and the redirection of movements and movement intentions. We have referred to some of these processes as motor attention. It has been known since the time of William James that covert motor attention can be directed to an upcoming movement just as visuospatial attention can be directed to a location in space. While some parietal regions, particularly in the right hemisphere, are concerned with covert orienting and the redirecting of covert orienting it may be useful to consider other parietal regions, in the anterior inferior parietal lobule and in the posterior superior parietal lobule, particularly in the left hemisphere, as contributing to motor attention. Such parts of the parietal lobe are activated in neuroimaging experiments when subjects covertly prepare movements or switch intended movements. Lesions or transcranial magnetic stimulation (TMS) affect the redirecting of motor attention. The difficulties apraxic patients experience when sequencing movements may partly be due to an inability to redirect motor attention from one movement to another. The role of the premotor cortex in selecting movements is also lateralized to the left hemisphere. Damage to left hemisphere movement selection mechanisms may also contribute to apraxia. If, however, it remains intact after a stroke then the premotor cortex may contribute to the recovery of arm movements. A group of patients with unilateral left hemisphere lesions and impaired movements in the contralateral right hand was studied. Functional magnetic resonance imaging showed that in some cases the premotor cortex in the intact hemisphere was more active when the stroke-affected hand was used. TMS in the same area in the same patients had the most disruptive effect on movements. In summary, patterns of motor impairment and recovery seen after strokes can partly be explained with reference to the roles of the parietal and premotor cortices in motor attention and selection.