The synchronization of the human cortical working memory network

A verbal reasoning problem at the intersection of verbal working memory, problem-solving, and language comprehension was examined using event-related fMRI to distinguish differences in the differential timing of the response of the various cortical regions that compose the working memory network. Problems were developed such that the process demand as well as the timing of the manipulation of the contents of working memory (i.e., a demanding computation) was varied. Activation was observed in several regions including the dorsolateral prefrontal cortex, the inferior frontal gyrus, and the parietal lobe. Examination of the MR amplitude response revealed that the regions do not all activate simultaneously; instead, their activation time courses reveal differential responses that correspond to their theoretical processing role in the problem-solving task. The coordination of cortical area responses reveals how the various cortical regions synchronize and collaborate in order to accomplish a given cognitive function.     

功能磁共振观察反应抑制功能老化

目的 应用fMRI探讨反应抑制功能老化的神经功能特点。方法 对正常青年组及老年组（各25名）行停止信号任务fMRI扫描,使用SPM 8软件处理数据,以组间差异脑激活区作为反应抑制功能老化相关脑区,对各区信号强度与行为学数据 行相关性分析。结果 fMRI脑激活区（P<0.01,FDR校正）在青年组激活以额、顶叶为主,老年组激活区左侧化分布略明显;老年组较青年组在双侧前额中回、左侧额下回、右侧顶下小叶及尾状核头、前扣带回有强激活区。相关性分析显示,青年组右侧前额中回与SSRT呈正相关,左侧额中回、左侧额中/下回与SSRT呈负相关;老年组前扣带回、左侧额中回、左侧额中/下回与SSRT均呈正相关。结论 老年人反应抑制功能老化,依赖更多脑区进行功能代偿,主要依赖左侧额中/下回进行补充代偿和前扣带回进行重建代偿。     

精神分裂症空间工作记忆任务的fMRI研究

目的采用fMRI技术探讨精神分裂症患者空间工作记忆损害的神经机制。方法收集18例精神分裂症患者和18名正常受试者进行空间n-back任务的fMRI扫描。采用SPM 8进行数据预处理和统计分析,单样本t-检验用于分析两组各自脑激活结果,双样本t-检验用于工作记忆相关脑激活的组间比较。采用FDR方法进行多重比较校正。利用SPSS 17.0软件对工作记忆任务中的行为学结果 (正确率和反应时间)进行组间比较。结果与对照组相比,精神分裂症患者空间工作记忆任务反应时间延长(882.00±50.31)ms,正确率下降(83.60±2.90)%(P0.05)。精神分裂症患者在n-back空间工作记忆任务时所激活的脑区分布与对照组基本一致,主要包括双侧前额皮层、颞顶叶皮层及部分基底核团。但组间比较显示精神分裂症患者多个脑区激活强度及范围明显增加,包括双侧前额皮层背外侧、双侧后顶叶皮层、右侧中央前回、左侧颞中回、右扣带回和双侧小脑(FDR校正,P0.05)。结论执行空间工作记忆任务时精神分裂症患者脑区激活增加,但行为学表现下降,提示患者脑区活动效率低下,可能是工作记忆能力损害的神经基础。     

Cognitive control in the posterior frontolateral cortex: evidence from common activations in task coordination, interference control, and working memory

Cognitive control has often been associated with activations of middorsolateral prefrontal cortex. However, recent evidence highlights the importance of a more posterior frontolateral region around the junction of the inferior frontal sulcus and the inferior precentral sulcus (the inferior frontal junction area, IFJ). In the present experiment, we investigated the involvement of the IFJ in a task-switching paradigm, a manual Stroop task, and a verbal n-back task in a within-session within-group design. After computing contrasts for the individual tasks, the resulting z maps were overlaid to identify areas commonly activated by these tasks. Common activations were found in the IFJ, in the pre-SMA extending into mesial BA 8, in the middle frontal gyrus bordering the inferior frontal sulcus, in the anterior insula, and in parietal and thalamic regions. These results indicate the existence of a network of prefrontal, parietal, and subcortical regions mediating cognitive control in task coordination, interference control, and working memory. In particular, the results provide evidence for the assumption that, in the frontolateral cortex, not only the middorsolateral region but also the IFJ plays an important role in cognitive control.     

Cognitive effects of nicotine in humans: an fMRI study

To elucidate the neural correlates of cognitive effects of nicotine, we examined behavioral performance and blood oxygenation level-dependent regional brain activity, using functional magnetic resonance imaging, during a parametric "n-back" task in healthy nonsmoking males after the administration of nicotine (12 microg/kg body weight) or saline. Nicotine, compared to placebo, improved accuracy (P = 0.008) in all active conditions (2%-11%), and had a load-specific effect on latency (P = 0.004; 43.78% decrease at the highest memory load). Within a network of parietal and frontal areas activated by the task (P < 0.05, corrected at the voxel level), nicotine produced an increased response (P < 0.05; uncorrected within the regions of interest) in the anterior cingulate, superior frontal cortex, and superior parietal cortex. It also produced an increased response in the midbrain tectum in all active conditions and in the parahippocampal gyrus, cerebellum, and medial occipital lobe during rest (P = 0.05; uncorrected). The present observations point to altered neuronal activity in a distributed neural network associated with on-line task monitoring and attention and arousal systems as underlying nicotine-related enhancement of attention and working memory in human subjects.     

Multistable representation of speech forms: a functional MRI study of verbal transformations

We used functional magnetic resonance imaging (fMRI) to localize the brain areas involved in the imagery analogue of the verbal transformation effect, that is, the perceptual changes that occur when a speech form is cycled in rapid and continuous mental repetition. Two conditions were contrasted: a baseline condition involving the simple mental repetition of speech sequences, and a verbal transformation condition involving the mental repetition of the same items with an active search for verbal transformation. Our results reveal a predominantly left-lateralized network of cerebral regions activated by the verbal transformation task, similar to the neural network involved in verbal working memory: the left inferior frontal gyrus, the left supramarginal gyrus, the left superior temporal gyrus, the anterior part of the right cingulate cortex, and the cerebellar cortex, bilaterally. Our results strongly suggest that the imagery analogue of the verbal transformation effect, which requires percept analysis, form interpretation, and attentional maintenance of verbal material, relies on a working memory module sharing common components of speech perception and speech production systems.     

Males and females differ in brain activation during cognitive tasks

To examine the effect of gender on regional brain activity, we utilized functional magnetic resonance imaging (fMRI) during a motor task and three cognitive tasks; a word generation task, a spatial attention task, and a working memory task in healthy male (n = 23) and female (n = 10) volunteers. Functional data were examined for group differences both in the number of pixels activated, and the blood-oxygen-level-dependent (BOLD) magnitude during each task. Males had a significantly greater mean activation than females in the working memory task with a greater number of pixels being activated in the right superior parietal gyrus and right inferior occipital gyrus, and a greater BOLD magnitude occurring in the left inferior parietal lobe. However, despite these fMRI changes, there were no significant differences between males and females on cognitive performance of the task. In contrast, in the spatial attention task, men performed better at this task than women, but there were no significant functional differences between the two groups. In the word generation task, there were no external measures of performance, but in the functional measurements, males had a significantly greater mean activation than females, where males had a significantly greater BOLD signal magnitude in the left and right dorsolateral prefrontal cortex, the right inferior parietal lobe, and the cingulate. In neither of the motor tasks (right or left hand) did males and females perform differently. Our fMRI findings during the motor tasks were a greater mean BOLD signal magnitude in males in the right hand motor task, compared to females where males had an increased BOLD signal magnitude in the right inferior parietal gyrus and in the left inferior frontal gyrus. In conclusion, these results demonstrate differential patterns of activation in males and females during a variety of cognitive tasks, even though performance in these tasks may not vary, and also that variability in performance may not be reflected in differences in brain activation. These results suggest that in functional imaging studies in clinical populations it may be sensible to examine each sex independently until this effect is more fully understood.     

Load- and practice-dependent increases in cerebro-cerebellar activation in verbal working memory: an fMRI study

Load-dependent and practice-related changes in neocortical and cerebellar structures involved in verbal working memory (VWM) were investigated using functional MRI (fMRI) and a two alternative forced choice Sternberg paradigm. Using working memory loads ranging from 2 to 6 letters, regions exhibiting linear and quadratic trends in load-dependent activations were identified. Behaviorally, reaction time measurements revealed significant linear increases with increasing memory load, and significant decreases with increased task practice. Brain activations indicated a preponderance of linear load-dependent responses in both superior (lobule VI/Crus I) and inferior (lobule VIIB/VIIIA) cerebellar hemispheres, as well as in areas of neocortex including left precentral (BA 6), inferior frontal (BA 47), parahippocampal (BA 35), inferior parietal (BA 40), cingulate (BA 32), and right inferior and middle frontal (BA 46/47) regions. Fewer voxels exhibited quadratic without linear trends with the most prominent of these activations located in left inferior parietal (BA 40), precuneus, and parahippocampal regions. Analysis of load x session interactions revealed that right inferior cerebellar and left inferior parietal activations increased with practice, as did the correlations between activation in each region with reaction time, suggesting that changes in this cerebro-cerebellar network underlie practice-related increases in efficiency of VWM performance. These results replicate and extend our previous findings of fMRI activation in the cerebellum during VWM, and demonstrate predominately linear increases in cerebro-cerebellar activation with increasing memory load as well as changes in network function with increased task proficiency.     

Specific versus nonspecific brain activity in a parametric N-back task

In this study functional magnetic resonance imaging (fMRI) was used to examine cerebral activity patterns in relation to increasing mental load of a working memory task. Aim of the experiment was to distinguish nonspecific task-related processes from specific workload processes analytically. Twelve healthy volunteers engaged in a spatial n-back task with four levels. FMRI data were acquired with the 3D-PRESTO pulse sequence. Analysis entailed a two-step multiple regression algorithm, which was specifically designed to measure and separate load-sensitive and load-insensitive activity simultaneously, while preserving the original high spatial resolution of the fMRI signal. Load-sensitive and load-insensitive activity was found in both dorsolateral-prefrontal and parietal cortex, predominantly bilaterally, and in the anterior cingulate. As expected, the left primary sensorimotor cortex showed predominantly load-insensitive activity. Load-sensitive activity reflects specific working memory functions, such as temporary retention and manipulation of information, while load-insensitive activity reflects supportive functions, such as visual orientation, perception, encoding, and response selection and execution. Good performance was correlated with a large area of load-sensitive activity in anterior cingulate, and with a small area of load-insensitive activity in the right parietal cortex. The findings indicate that nonspecific and specific working memory processes colocalize and are represented in multiple frontal and parietal regions. Implication of this analytical strategy for application in research on psychiatric disorders is discussed.     

Cerebrocerebellar networks during articulatory rehearsal and verbal working memory tasks

Converging evidence has implicated the cerebellum in verbal working memory. The current fMRI study sought to further characterize cerebrocerebellar participation in this cognitive process by revealing regions of activation common to a verbal working task and an articulatory control task, as well as regions that are uniquely activated by working memory. Consistent with our model's predictions, load-dependent activations were observed in Broca's area (BA 44/6) and the superior cerebellar hemisphere (VI/CrusI) for both working memory and motoric rehearsal. In contrast, activations unique to verbal working memory were found in the inferior parietal lobule (BA 40) and the right inferior cerebellum hemisphere (VIIB). These findings provide evidence for two cerebrocerebellar networks for verbal working memory: a frontal/superior cerebellar articulatory control system and a parietal/inferior cerebellar phonological storage system.     

Neuroanatomic overlap of working memory and spatial attention networks: a functional MRI comparison within subjects

Frontal and posterior parietal activations have been reported in numerous studies of working memory and visuospatial attention. To directly compare the brain regions engaged by these two cognitive functions, the same set of subjects consecutively participated in tasks of working memory and spatial attention while undergoing functional MRI (fMRI). The working memory task required the subject to maintain an on-line representation of foveally displayed letters against a background of distracters. The spatial attention task required the subject to shift visual attention covertly in response to a centrally presented directional cue. The spatial attention task had no working memory requirement, and the working memory task had no covert spatial attention requirement. Subjects' ability to maintain central fixation was confirmed outside the MRI scanner using infrared oculography. According to cognitive conjunction analysis, the set of activations common to both tasks included the intraparietal sulcus, ventral precentral sulcus, supplementary motor area, frontal eye fields, thalamus, cerebellum, left temporal neocortex, and right insula. Double-subtraction analyses yielded additional activations attributable to verbal working memory in premotor cortex, left inferior prefrontal cortex, right inferior parietal lobule, precuneus, and right cerebellum. Additional activations attributable to covert spatial attention included the occipitotemporal junction and extrastriate cortex. The use of two different tasks in the same set of subjects allowed us to provide an unequivocal demonstration that the neural networks subserving spatial attention and working memory intersect at several frontoparietal sites. These findings support the view that major cognitive domains are represented by partially overlapping large-scale neural networks. The presence of this overlap also suggests that spatial attention and working memory share common cognitive features related to the dynamic shifting of attentional resources.     

汉语及图片语义加工机制的fMRI研究

目的利用功能磁共振成像(fMRI)技术探讨汉字及图片语义加工的脑机制。方法对13名正常青年受试者进行视觉方式呈现汉字及图片语义辨别任务的fMRI扫描,采用AFNI软件进行数据分析和脑功能区活动图像。结果fMRI显示两种任务均激活了左侧顶下小叶、额中回、额下回、右侧小脑及双侧梭状回、舌回、枕中回、枕下回、辅助运动区。其中左侧顶下小叶、额中回及双侧枕中回、梭状回在图片语义辨别任务激活明显强于汉字任务,有显著性差异(P<0.05)。结论汉字及图片语义的脑加工均存在偏侧化现象,图片语义的脑处理有更多的脑活动参与完成。     

功能磁共振成像观察2型糖尿病患者工作记忆

目的 通过功能磁共振成像技术对2型糖尿病患者的工作记忆进行研究,探讨2型糖尿病患者工作记忆的受损状况.方法 采用1-back组块设计,对16例2型糖尿病患者及13名正常对照受试者,进行词语及客体工作记忆任务的fMRI检查,对反应时间、正确率及脑激活图进行分析.结果 2型糖尿病组患者的正确反应时间、正确率与对照组相比差异无统计学意义(P>0.05).与对照组相比,2型糖尿病组在词语工作记忆时,左侧额叶、左侧顶叶及海马旁回等脑区激活显著减弱(P<0.05),客体工作记忆时,右侧额叶、左侧顶叶及双侧枕叶等脑区激活减弱(P<0.05).结论 2型糖尿病患者存在词语及客体工作记忆损害,经典激活脑区存在损害.     

Load response functions in the human spatial working memory circuit during location memory updating

Previous studies have emphasized that the dorsolateral prefrontal cortex is important for manipulating information in working memory, although activations in other frontal and parietal areas are commonly observed under the same conditions. We conducted an fMRI experiment to examine brain responses as a parametric function of memory updating, which is considered as an elemental process in working memory. In a variant spatial delayed-response task, human subjects performed updating operations over a 9-second delay period, during which they mentally transform the location of a memorized target in a 4 by 4 grid according to 3 to 12 instruction cues. Activity increased monotonically with increasing updating load in numerous cortical and subcortical regions including the rostrodorsal premotor (rdPM), lateral precentral sulcus, lateral prefrontal, posterior associative, striatal and cerebellar areas. The rdPM and superior parietal were particularly sensitive to the updating manipulation. There were several main findings. First, updating spatial working memory involved mostly the same cortical and subcortical regions that were activated during maintenance of spatial information. Second, the updating load response functions of regions in the spatial working memory circuit showed a strong linear component. However, none shows significant increases in activity from 9 to 12 updating operations. Third, activity in the right rdPM and anterior inferior frontal gyrus correlated positively with working memory performance in the high updating load condition. Our findings suggest that updating and maintenance of spatial information may share similar processes and that the rostrodorsal premotor cortex and anterior inferior frontal gyrus may be important for the success of tracking spatial information in working memory.     

Working memory load modulates the auditory "What" and "Where" neural networks

Working memory for sound identity (What) and sound location (Where) has been associated with increased neural activity in ventral and dorsal brain regions, respectively. To further ascertain this domain specificity, we measured fMRI signals during an n-back (n=1, 2) working memory task for sound identity or location, where stimuli selected randomly from three semantic categories (human, animal, and music) were presented at three possible virtual locations. Accuracy and reaction times were comparable in both "What" and "Where" tasks, albeit worse for the 2-back than for the 1-back condition. The analysis of fMRI data revealed greater activity in ventral and dorsal brain regions during sound identity and sound location, respectively. More importantly, there was an interaction between task and working memory load in the inferior parietal lobule (IPL). Within the right IPL, there were two sub-regions modulated differentially by working memory load: an anterior ventromedial region modulated by location load and a posterior dorsolateral region modulated by category load. These specific changes in neural activity as a function of working memory load reveal domain-specificity within the parietal cortex.     

Neurodevelopmental changes in verbal working memory load-dependency: an fMRI investigation

Development of working memory (WM) aptitude parallels structural changes in the frontal–parietal association cortices important for performance within this cognitive domain. The cerebellum has been proposed to function in support of the postulated phonological loop component of verbal WM, and along with frontal and parietal cortices, has been shown to exhibit linear WM load-dependent activation in adults. It is not known if these kinds of WM load-dependent relationships exist for cerebro-cerebellar networks in developmental populations, and whether there are age-related changes in the nature of load-dependency between childhood, adolescence, and adulthood. The present study used fMRI and a verbal Sternberg WM task with three load levels to investigate developmental changes in WM load-dependent cerebro-cerebellar activation in a sample of 30 children, adolescents, and young adults between the ages of 7 and 28. The neural substrates of linear load-dependency were found to change with age. Among adolescents and adults, frontal, parietal and cerebellar regions showed linear load-dependency, or increasing activation under conditions of increasing WM load. In contrast, children recruited only left ventral prefrontal cortex in response to increasing WM load. These results demonstrate that, while children, adolescents, and young adults activate similar cerebro-cerebellar verbal working memory networks, the extent to which they rely on parietal and cerebellar regions in response to increasing task difficulty changes significantly between childhood and adolescence.     

Involvement of the cerebellar cortex and nuclei in verbal and visuospatial working memory: a 7 T fMRI study

The first aim of the present study was to extend previous findings of similar cerebellar cortical areas being involved in verbal and spatial n-back working memory to the level of the cerebellar nuclei. The second aim was to investigate whether different areas of the cerebellar cortex and nuclei contribute to different working memory tasks (n-back vs. Sternberg tasks). Young and healthy subjects participated in two functional magnetic resonance imaging (fMRI) studies using a 7 T MR scanner with its increased signal-to-noise ratio. One group of subjects (n=21) performed an abstract and a verbal version of an n-back task contrasting a 2-back and 0-back condition. Another group of subjects (n=23) performed an abstract and a verbal version of a Sternberg task contrasting a high load and a low load condition. A block design was used. For image processing of the dentate nuclei, a recently developed region of interest (ROI) driven normalization method of the dentate nuclei was applied (Diedrichsen et al., 2011). Whereas activated areas of the cerebellar cortex and dentate nuclei were not significantly different comparing the abstract and verbal versions of the n-back task, activation in the abstract and verbal Sternberg tasks was significantly different. In both n-back tasks activation was most prominent at the border of lobules VI and Crus I, within lobule VII, and within the more caudal parts of the dentate nucleus bilaterally. In Sternberg tasks the most prominent activations were found in lobule VI extending into Crus I on the right. In the verbal Sternberg task activation was significantly larger within right lobule VI compared to the abstract Sternberg task and compared to the verbal n-back task. Activations of rostral parts of the dentate were most prominent in the verbal Sternberg task, whereas activation of caudal parts predominated in the abstract Sternberg task. On the one hand, the lack of difference between abstract and verbal n-back tasks and the lack of significant lateralization suggest a more general contribution of the cerebellum to working memory regardless of the modality. On the other hand, the focus of activation in right lobule VI in the verbal Sternberg task suggests specific cerebellar contributions to verbal working memory. The verbal Sternberg task emphasizes maintenance of stimuli via phonological rehearsal, whereas central executive demands prevail in n-back tasks. Based on the model of working memory by Baddeley and Hitch (1974), the present results show that different regions of the cerebellum support functions of the central executive system and one of the subsidiary systems, the phonological loop.     

Dissociation of cortical regions modulated by both working memory load and sleep deprivation and by sleep deprivation alone

Working memory is an important mental capacity that is compromised following sleep deprivation (SD). To understand how working memory load interacts with state to influence brain activation in load-sensitive regions, and the extent to which SD-related changes are common across different loads, we used fMRI to study twelve healthy subjects following 24 h of SD using a verbal n-back task with three load levels. Performance decline was observed by way of reduced accuracy and slower response times following SD. The left prefrontal region and thalamus showed load dependent activity modulation that interacted with state. The right parietal and anterior medial frontal regions showed load dependent changes in activity as well as an effect of state. The anterior cingulate and occipital regions showed activation that displayed state effects that were independent of working memory load. These findings represent a step toward identifying how different brain regions exhibit varying vulnerability to the deleterious effects of SD on working memory.     

Functional connectivity in an fMRI working memory task in high-functioning autism

An fMRI study was used to measure the brain activation of a group of adults with high-functioning autism compared to a Full Scale and Verbal IQ and age-matched control group during an n-back working memory task with letters. The behavioral results showed comparable performance, but the fMRI results suggested that the normal controls might use verbal codes to perform the task, while the adults with autism might use visual codes. The control group demonstrated more activation in the left than the right parietal regions, whereas the autism group showed more right lateralized activation in the prefrontal and parietal regions. The autism group also had more activation than the control group in the posterior regions including inferior temporal and occipital regions. The analysis of functional connectivity yielded similar patterns for the two groups with different hemispheric correlations. The temporal profile of the activity in the prefrontal regions was more correlated with the left parietal regions for the control group, whereas it was more correlated with the right parietal regions for the autism group.     

Executive Function in Chronic Pain Patients and Healthy Controls: Different Cortical Activation During Response Inhibition in Fibromyalgia

The primary symptom of fibromyalgia (FM) is chronic, widespread pain; however, patients report additional symptoms including decreased concentration and memory. Performance-based deficits are seen mainly in tests of working memory and executive function. Neural correlates of executive function were investigated in 18 FM patients and 14 age-matched healthy controls during a simple Go/No-Go task (response inhibition) while they underwent functional magnetic resonance imaging (fMRI). Performance was not different between FM and healthy control, in either reaction time or accuracy. However, fMRI revealed that FM patients had lower activation in the right premotor cortex, supplementary motor area, midcingulate cortex, putamen and, after controlling for anxiety, in the right insular cortex and right inferior frontal gyrus. A hyperactivation in FM patients was seen in the right inferior temporal gyrus/fusiform gyrus. Despite the same reaction times and accuracy, FM patients show less brain activation in cortical structures in the inhibition network (specifically in areas involved in response selection/motor preparation) and the attention network along with increased activation in brain areas not normally part of the inhibition network. We hypothesize that response inhibition and pain perception may rely on partially overlapping networks, and that in chronic pain patients, resources taken up by pain processing may not be available for executive functioning tasks such as response inhibition. Compensatory cortical plasticity may be required to achieve performance on a par with control groups.

Perspective

Neural activation (fMRI) during response inhibition was measured in fibromyalgia patients and controls. FM patients show lower activation in the inhibition and attention networks and increased activation in other areas. Inhibition and pain perception may use overlapping networks: resources taken up by pain processing may be unavailable for other processes.