健康人脑空间工作记忆的脑功能磁共振研究

目的 通过功能磁共振成像(unctional magnetic resonance imaging, fMRI)技术研究健康人脑空间工作记忆的功能脑区.方法 10名右利手健康志愿者进行空间工作记忆任务的同时进行fMRI扫描,实验采用组块设计和SPM99软件进行数据分析和脑功能区定位.结果 大脑皮质所激活的主要脑区有双侧顶叶(BA7/40,BA:Brodmann area,布鲁德曼分区),双侧额叶(BA6/9/47),双侧枕颞交界处(BA19/37);被激活的大脑皮质下结构有右侧尾状核、左侧丘脑和左侧中脑黑质;双侧小脑也均被显著激活(P<0.001).结论 人脑处理空间工作记忆信息是由大脑皮质下结构及小脑与大脑皮质共同完成的.     

颞叶癫痫患者执行功能的功能磁共振研究

目的 探讨颞叶癫痫(temporal lobe epilepsy ,TLE)患者执行功能的脑功能状态及激活模式.方法 应用注意网络测试(attentional networks test,ANT)软件,对12例TLE患者及12名健康受试者进行执行功能行为学测试;应用组块式功能磁共振(functional magnetic resonance imaging ,fMRI)扫描,使用统计参数图(Statistical Parametric Mapping 2,SPM 2)软件分析fMRI数据.结果 与健康受试组比较,TLE患者组执行功能反应时间(RT)较慢[患者组:(158.9±50.2)ms;健康受试组:(112.4±28.3)ms, t=2.63,P<0.05].健康受试组执行功能fMRI显示激活脑区右侧半球偏侧化,位于右扣带回后部、颞下回、前额叶、海马、顶叶及左颞中回.TLE患者组右侧前额叶和右额叶 (激活体素:53,34 voxel P<0.01)等靠近中线脑区激活体素较小.健康受试组存在与反应时间正、负相关脑区(P<0.001),TLE组则仅存与反应时间正相关脑区(P<0.001).结论 TLE患者存在执行功能障碍,与上述脑区激活功能低下和失调控有关,这些脑区可能是TLE患者执行功能损害的形态学基础.     

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。     

首发精神分裂症患者治疗前后脑功能磁共振成像的研究

目的 利用功能磁共振成像(fMRI)探讨首发精神分裂症患者利培酮治疗前后认知功能激发图像的特点。方法 18例首发精神分裂症患者治疗前进行倒背数字作业的fMRI检查,经利培酮[(3.8±0.9)mg/d]治疗(57±9)d后复查fMRI(16例)。用阳性和阴性症状量表(PANSS)及治疗中需处理的不良反应症状量表评价精神症状的严重程度及不良反应。结果 (1)利培酮治疗后的PANSS减分率为(50±22)％,有效率为72％。(2)治疗前倒背数字作业激活范围较广泛,包括额叶、顶叶及颞叶等脑区。(3)左侧额上回治疗前激活脑区计数为4,治疗后计数为12,治疗前后激活脑区计数的差异有非常显著性(P=0.009);左侧额叶腹外侧面治疗前激活平均体积为(15±38)个体素,治疗后激活平均体积为(67±76)个体素,治疗前后的差异有显著性(P=0.046)。结论 首发精神分裂症患者在发病初期就存在工作记忆缺陷,这种缺陷可能与左侧额上回及额下回激活低下有关,利培酮治疗可改善患者的工作记忆缺陷。     

戒断期海洛因依赖者额叶认知功能的功能磁共振成像研究

目的 研究戒断期海洛因依赖者(AHD)的脑认知功能.方法 采用3.0 T磁共振成像系统,对30例AHD(AHD组)和18名健康对照者(对照组)在完成Go/NoGo任务时行全脑功能磁共振成像(fMRI)扫描,记录反应时间(RT).结果 (1)RT:AHD组在完成Go/NoGo任务时的RT[(394±34)ms]长于对照组[(374±26)ms;P<0.05].(2)fMRI:对照组在完成Go/NoGo任务时,诱发激活双侧前额叶内侧回、前扣带回以及双侧额下回等脑区;AHD组全脑活动普遍低,仅有双侧额上回和左侧额中回激活.两组间比较,AHD组激活显著低于对照组的区域主要位于在双侧额内侧回、前扣带回、额下回及双侧颞叶等脑区(P<0.005).结论 戒断期海洛因依赖者反应抑制功能障碍仍然存在,促进其认知功能的恢复可能成为戒毒、抗复吸的有效策略.     

认知矫正治疗前后慢性精神分裂症患者功能磁共振成像的对照研究

目的 探讨认知矫正治疗对精神分裂症患者工作记忆相关脑区活动的影响.方法 对10例病情稳定的慢性精神分裂症患者进行为期6个月的认知矫正治疗,分别于治疗前后进行韦克斯勒记忆量表(WMS)测查及功能磁共振成像(fMRI)测量.结果 (1)WMS测查:治疗后再认[(8.11±4.34)分]和再生[(10.22±3.35)分]以及Benton错误[(3.75±2.92)分]均较治疗前[分别为(5.78±2.95)分、(8.56±3.21)分和(8.00±6.28)分]改善,均P＜0.05.(2)fMRI:治疗前后的反应时和正确率比较,差异无统计学意义(P＞0.05).治疗后在高负荷条件下,背侧前额叶皮质(DLPFC)区域(Brodmann46区)的激活范围(x,y,z=-51,36,15;k=40,t=7.21)小于治疗前的激活范围(x,y,z=-48,24,24,k=154,t=12.72),治疗前后DLPFC区域激活(x,y,z=-24,36,18,k=12,t=3.75)的差异有统计学意义(P＜0.005);在低负荷条件下,治疗前后DLPFC区域激活的差异无统计学意义(P＞0.05).结论 认知矫正治疗能改善精神分裂症患者工作记忆相关脑区的活动.     

前额叶损伤患者的视-空间工作记忆改变

目的 探讨前额叶不同亚区损伤患者的视-空间工作记忆障碍.方法 将20例前额叶不同亚区损伤患者以及20名与其人口学资料相匹配的健康人作为被试,采用视觉面孔和视觉空间的延迟匹配任务对上述2组进行视-空间工作记忆测试.结果 与健康对照组(72.9%±6.1%)相比,前额叶腹侧(ventral prefrontal cortex,VPFC)损伤的患者视觉客体工作记忆的正确率(46.4%±11.4%)明显下降,差异有统计学意义(U=1.00,P<0.01);而前额叶背外侧(dorsolateral prefrontal cortex,DLPFC)损伤的患者在视觉客体(50.4%±15.1%)和视觉空间(72.6%±18.6%)工作记忆均有明显损伤,与对照组(72.9%±6.1%、89.4%±10.1%)比较差异均有统计学意义(U=-20.5、59.5,均P<0.01).对左、右前额叶损伤的2组患者进行分析,结果表明2组患者在视觉客体和空间工作记忆正确率的比较差异均无统计学意义.对前额叶亚区进行左右侧比较,2组VPFC患者在视觉客体和视觉空间工作记忆差异均无统计学意义;左侧DLPFC损伤组和右侧DLPFC损伤组在视觉客体工作记忆正确率和视觉面孔工作记忆正确率方面,差异均无统计学意义.结论 前额叶是工作记忆加工的重要脑区,其不仅参与了视觉客体的工作记忆加工过程,同时参与了视觉空间的工作记忆加工,而且对于前额叶不同亚区在视-空间工作记忆加工过程中还存在分离.     

静息状态功能磁共振成像观察轻度阿尔茨海默病后扣带回功能连通性的变化

目的 利用静息状态功能磁共振成像(fMRI)研究阿尔茨海默病(AD)早期后扣带回相关的静息脑网络连通性是如何变化的.方法 运用fMRI研究了16例轻度AD患者和16名健康对照者在静息状态后扣带回的功能连通性.与后扣带回有功能连通性的脑区是通过检测低频波动信号的时程相关性获得的.应用通用的SPM2图像统计软件计算组间和组内连通性差异,激活区阈值设置:P<0.01(校正),像素范围>5.利用SPM2软件随机效应分析t检验(经校正P<0.01,t=2.47,像素范围>5),比较患者组和对照组连通性激活的脑区.结果 与后扣带回有功能连通性减弱的脑区包括前额叶中线区、楔前叶、双侧视皮质、双侧颞下回、左侧海马、右侧丘脑、右侧额叶背外侧区;偏左侧化的连通性增高的脑区包括前额叶中线区、左侧颞下回、左侧基底节区、双侧额叶背外侧区及左侧中央前区.结论 与后扣带回相关的静息状态脑网络连通性减低与AD早期情节记忆损害和高级视觉功能损害有关系,轻度AD保留着功能连接的重塑性以便维持脑功能.静息fMRI是一种探索AD脑功能机制的适宜方法.     

正常人汉字工作记忆功能磁共振脑激活区改变的研究

目的探讨正常人汉字任务下脑激活区的改变。方法对40例正常人进行汉字工作记忆功能磁共振扫描。结果汉字工作记忆任务下,编码、保持及提取期均有额叶、楔前叶、楔叶、边缘叶及扣带回的正向激活,且有侧脑室及脑脊液在编码及保持期的正向激活和在提取期的负向激活。除共同激活脑区外,编码期所有激活脑区均为正向激活,保持期正向激活脑区有中央前回、杏仁核、上后扣带皮层(BA 31),负向激活脑区有颞中回、顶叶、角回,提取期正向激活脑区有尾状核。结论汉字任务下,脑激活区的改变除皮层及皮层下结构,还有侧脑室及脑脊液的激活。     

睡眠剥夺影响数字记忆的功能磁共振成像研究

研究背景长时间连续作业易导致大脑疲劳,已有证据显示脑疲劳对作业者认知功能和行为反应能力具有严重损害作用,因此揭示连续作业和睡眠剥夺对认知功能影响的机制,有助于对抗连续作业所致疲劳,提高连续作业能力。本研究通过分析睡眠剥夺前后功能磁共振成像(fMRI)特点,探讨睡眠剥夺影响学习记忆的神经机制。方法共6例健康男性志愿者接受48h睡眠剥夺,采用组块设计方法评价睡眠剥夺前后数字记忆功能变化,fMRI比较数字记忆编码、维持和提取阶段各脑区的激活特点。结果睡眠剥夺48h,受试者对4～7个0～9数字记忆的错误率并未增加(均P>0.05);对4～6个0～9数字记忆的反应时间与睡眠剥夺前无明显差异(均P>0.05),仅7个0～9数字记忆的反应时间增加(P=0.005)。睡眠剥夺后激活减弱的脑区在数字记忆试验编码阶段为左侧海马旁回Brodmann30区、颞上回Brodmann42区、岛叶Brodmann41区和额叶Brodmann6区;在维持阶段分别为左侧颞上回Brodmann38区、颞中回Brodmann21区、海马旁回和杏仁核Brodmann30区、额中回Brodmann47区、豆状核和丘脑,以及右侧豆状核、左侧扣带后回Brodmann30区、右侧扣带后回Brodmann30区、双侧扣带回Brodmann24区、双侧额中回和额内侧回Brodmann6区;提取阶段包括双侧海马、右侧杏仁核和顶下小叶Brodmann40区、左侧楔前叶Brodmann19区和丘脑。结论在数字记忆的不同阶段,机体通过激活不同的脑区来维持清醒状态,48h睡眠剥夺后参与数字记忆的大脑皮质及皮质下结构广泛受损。     

Activity in human medial temporal lobe associated with encoding process in spatial working memory revealed by magnetoencephalography

Animal studies have suggested that working memory may be affected after lesions in the medial temporal lobe, although this assumption has not been corroborated by neuropsychological studies in humans. However, very recently, several functional neuroimaging studies in humans have successfully observed activation of the medial temporal lobe during working memory tasks. The main aim of this study was to investigate the contribution of the medial temporal lobe to the encoding process in spatial working memory. To address this issue we registered the neuromagnetic brain patterns of eight adult volunteers while they performed a spatial working memory task and more perceptual task using identical stimuli. After a initial phase (between 200 and 400 ms) without differences in activation, the medial temporal lobe showed a sustained activity, more evident in the right hemisphere, lasting up to 800 ms during the encoding stage of the spatial working memory task, while the activation in the perceptual task terminated earlier (approximately 400 ms after stimulus onset). The finding of a continued activation of the medial temporal lobe strongly suggests the contribution of this brain region to encoding operations in working memory.     

Frontal and parietal activity after sleep deprivation is dependent on task difficulty and can be predicted by the fMRI response after normal sleep

Sleep disturbance in neurological and psychiatric disorders is common and associated with diminished cognitive functioning. Whilst these deficits can be localised predominantly to frontal and parietal regions, there have been reported inconsistencies which may be due to differences in the difficulty and type of task. In the present study we examined the effects of sleep deprivation (SD) whilst parametrically varying working memory load using an n-back task. 20 right-handed males performed the n-back task after a night of normal sleep (RW: rested wakefulness) and after approximately 31 h of SD. Comparison of load responsive cerebral activation identified two clusters where the parametric response was altered after SD. In the right ventrolateral prefrontal cortex activity was reduced at the most difficult working memory load, whereas in the right inferior parietal lobe activity was increased at the simplest working memory load. The strength of activation in both of these regions during RW predicted the response of those same regions to SD. While the ability to predict signal change has previously been demonstrated using behavioural measures, to our knowledge this is the first study to show that the neuronal effects of SD can be predicted based upon activation during a normal rested condition.     

Partial withdrawal of levothyroxine treated disease leads to brain activations and effects on performance in a working memory task: A pilot study

Hypothyroidism is associated with memory impairments. The present study aimed to evaluate the effects of partial withdrawal of levothyroxine on working memory tasks and brain function. Fifteen subjects under long‐term levothyroxine substitution as a result of complete hypothyroidism participated in the present study. Functional magnetic resonance imaging (MRI) was performed using a working memory task (n‐back task) and neuropsychological tests were performed before and 52‐54 days after the induction of subclinical hypothyroidism by reducing the pretest levothyroxine dosage by 30%. Reaction time of subjects under partial levothyroxine withdrawal was significantly longer and less accurate with respect to solving the working memory tasks. Functional MRI revealed significant activation changes after medication withdrawal in the cerebellum, insula, parietal, frontal, temporal and occipital lobes, lingual gyrus, and the cuneus. Partial withdrawal of levothyroxine may lead to deficits in a working memory task and to an activation of brain areas associated with working memory ability.     

Is the parietal lobe necessary for recollection in humans?

An intriguing puzzle in cognitive neuroscience over recent years has been the common observation of parietal lobe activation in functional neuroimaging studies during the performance of human memory tasks. These findings have surprised scientists and clinicians because they challenge decades of established thinking that the parietal lobe does not support memory function. However, direct empirical investigation of whether circumscribed parietal lobe lesions might indeed be associated with human memory impairment has been lacking. Here we confirm using functional magnetic resonance imaging that significant parietal lobe activation is observed in healthy volunteers during a task assessing recollection of the context in which events previously occurred. However, patients with parietal lobe lesions that overlap closely with the regions activated in the healthy volunteers nevertheless exhibit normal performance on the same recollection task. Thus, although the processes subserved by the human parietal lobe appear to be recruited to support memory function, they are not a necessary requirement for accurate remembering to occur.     

Medial temporal and prefrontal contributions to working memory tasks with novel and familiar stimuli.

Lesions of parahippocampal structures impair performance of delayed matching tasks in nonhuman primates, suggesting a role for these structures in the maintenance of items in working memory and short-term stimulus matching. However, most human functional imaging studies have not shown medial temporal activation during working memory tasks and have primarily focused on functional magnetic resonance imaging (fMRI) signal intensity changes in the prefrontal and posterior parietal cortex. The goal of this study was to test the hypothesis that the difference between the human and nonhuman primate data results from the use of highly familiar stimuli in human working memory studies and trial-unique stimuli in nonhuman primate studies. We used fMRI to examine prefrontal and temporal lobe activation during performance of a working memory (two-back) task, using blocks of novel and highly familiar complex pictures. Performance of the working memory task with novel complex pictures resulted in greater signal change within medial temporal lobe structures than performance of the task with familiar complex pictures. In contrast, the working memory task with highly familiar stimuli resulted in greater prefrontal activation. These results are consistent without hypothesis that the medial temporal lobe is recruited for the short-term maintenance of information that has no prior representation in the brain, whereas the prefrontal cortex is important for monitoring familiar stimuli that have a high degree of interference. A second set of tasks examined stimulus matching. Subjects performed a target-matching task, during which they identified a single target presented in blocks of novel or familiar stimuli. The results provide evidence of hippocampal and parahippocampal recruitment in the target-matching task with familiar stimuli. These results are consistent with prior animal studies and suggest that prefrontal regions may be important for the monitoring and matching of familiar stimuli which have a high potential for interference, whereas medial temporal regions may become proportionally more important for matching and maintenance of novel stimuli.     

Neural correlates of working memory for sign language

Eight, early bilingual, sign language interpreters participated in a PET study, which compared working memory for Swedish Sign Language (SSL) with working memory for audiovisual Swedish speech. The interaction between language modality and memory task was manipulated in a within-subjects design. Overall, the results show a previously undocumented, language modality-specific working memory neural architecture for SSL, which relies on a network of bilateral temporal, bilateral parietal and left premotor activation. In addition, differential activation in the right cerebellum was found for the two language modalities. Similarities across language modality are found in Broca's area for all tasks and in the anterior left inferior frontal lobe for semantic retrieval. The bilateral parietal activation pattern for sign language bears similarity to neural activity during, e.g., nonverbal visuospatial tasks, and it is argued that this may reflect generation of a virtual spatial array. Aspects of the data suggesting an age of acquisition effect are also considered. Furthermore, it is discussed why the pattern of parietal activation cannot be explained by factors relating to perception, production or recoding of signs, or to task difficulty. The results are generally compatible with Wilson's [Psychon. Bull. Rev. 8 (2001) 44] account of working memory.     

Different hemispheric specializations for pitch and audioverbal working memory

Critical times of involvement of areas important to working memory were examined both with pitch and audioverbal N-back tasks using single-pulse transcranial magnetic stimulation (TMS). TMS was administered to 12 healthy participants over dorsolateral prefrontal and inferior parietal regions in each hemisphere at four different times after stimulus onset (250, 450, 650, and 850 ms). For the pitch N-back task, interference with working memory, as evidenced by a significant increase in reaction time, was observed with TMS over the right hemisphere regions. In contrast, for the audioverbal N-back task, TMS resulted in significantly increased reaction time only for left inferior parietal TMS delivered 450 ms after stimulus onset. These results imply different hemispheric specializations for pitch and audioverbal working memory.     

Frontal-parietal activation differences observed before the execution of remembered saccades: an event-related potentials study

Healthy subjects performed saccadic eye movements in one memory (MEM) and two delay tasks (delay, DEL and modified delay, M-DEL) while we recorded scalp event-related potentials (ERPs) from 25 electrode sites. In the MEM task the subjects were instructed to retain in memory the location of a visual target for a delay of 1-6 s and then perform a remembered saccade at the go signal. In the DEL task the target remained on until movement completion and in the M-DEL task the target, that was visible during the delay period, disappeared synchronously with the go signal. A reduction in response latency and an increase in the percentage of dysmetric movements were observed for the MEM task compared to the two delay tasks. An increased ERP activity at the central-frontal electrode sites compared to the parietal sites was significant only for the MEM task early on during the delay period (500-1000 ms). During the period preceding the onset of the saccade, a parietal increase of activity was observed for all tasks. Furthermore the activity was smaller for the frontal compared to the parietal areas only for the memory task thus indicating a near reversal of the previous pattern of activity observed during the early delay period. This specific activation pattern of frontal and parietal areas, observed for the MEM task only, requires further investigation focusing on the temporal pattern of activation of large brain areas involved in working memory processing.     

A cross-sectional and follow-up functional MRI study with a working memory task in adolescent anorexia nervosa

Structural and functional brain abnormalities have been described in anorexia nervosa (AN). The objective of this study was to examine whether there is abnormal regional brain activation during a working memory task not associated with any emotional stimuli in adolescent patients with anorexia and to detect possible changes after weight recovery. Fourteen children and adolescents (age range 11–18 years) consecutively admitted with DSM-IV diagnosis of AN and fourteen control subjects of similar age were assessed by means of psychopathological scales and functional magnetic resonance imaging (fMRI) during a working memory task. After seven months of treatment and weight recovery, nine AN patients were reassessed. Before treatment, the AN group showed significantly higher activation than controls in temporal and parietal areas and especially in the temporal superior gyrus during performance of the cognitive task. Control subjects did not show greater activation than AN patients in any region. A negative correlation was found between brain activation and body mass index and a positive correlation between activation and depressive symptomatology. At follow-up after weight recovery, AN patients showed a decrease in brain activation in these areas and did not present differences with respect to controls. These results show that adolescent AN patients showed hyperactivation in the parietal and especially the temporal lobe during a working memory task, suggesting that they must make an additional effort to perform at normal levels. This activation correlated with clinical variables. In these young patients, differences with respect to controls disappeared after weight recovery.     

精神分裂症患者基于事件前瞻记忆缺陷的功能磁共振成像特点

目的应用功能磁共振成像(fMRI)技术探讨精神分裂症基于事件前瞻记忆缺陷的生物学基础及神经机制。方法采取横断面病例对照研究方法,共招募20名健康志愿者(对照组)和20例精神分裂症患者(观察组)入组,以双重任务前瞻记忆实验范式作为刺激任务,同时应用阳性与阴性症状量表和阴性症状评定量表评定精神症状严重程度,采用锥体外系不良反应量表评定锥体外系不良反应严重程度。应用Matlab2011b,SPM8软件对影像学数据进行预处理及统计分析。采用独立样本t检验分析比较两组的脑区激活情况,设定激活差异显著水平为P<0.005(未校正)。选取前瞻记忆主要激活脑区,应用REST1.8软件提取激活脑区的血氧水平依赖性信号强度,采用Pearson相关分析探究脑区激活强度的相关因素。结果预处理中发现,观察组2例被试者有明显的头部运动(移动>2.5 mm,转动>2.5°),剔除图像分析,最后观察组18例,对照组20例被试者的图像数据进入统计分析。相对于健康志愿者,精神分裂症患者在执行前瞻记忆任务时的正确率较低且反应时更长[(83.40±15.33)%比(94.30±10.94)%,(870.54±156.70)ms比(757.33±187.44)ms;均P<0.05]。进行中任务的反应时与阴性症状量表评分呈正相关(r=0.494,P=0.037),前瞻记忆任务的正确率与智商呈正相关(r=0.558,P=0.016),前瞻记忆任务的反应时与氯丙嗪等效剂量呈正相关(r=0.492,P=0.038)。fMRI扫描显示精神分裂症患者右额中回、双侧顶下小叶(角回、缘上回)、右前扣带回以及右楔前叶脑区激活明显低于健康志愿者(均P<0.005)。右缘上回(r=-0.589,P=0.010)、左角回(r=-0.593,P=0.010)、右楔前叶(r=-0.590,P=0.010)的激活程度与氯丙嗪等效剂量呈负相关。右前扣带回(r=-0.537,P=0.021)、右额中回(r=-0.501,P=0.034)的激活程度与进行中任务的反应时呈负相关。结论前瞻记忆需要消耗认知资源。精神分裂症患者存在显著的基于事件前瞻记忆缺陷,其缺陷机制可能与额中回、顶下小叶(缘上回、角回)、前扣带回以及楔前叶功能紊乱有关。