Age-Related Changes in Neural Activation During Working Memory Performance

Changes in frontal lobe functions are a typical part of aging of the brain. There are age-related declines in working memory performance, a skill requiring frontal lobe activation. This study examined neural activation, using [15 O] water positron emission tomography (PET) methodology, during performance on two verbal working memory tasks in younger and older participants. The results demonstrated the typical areas of activation associated with working memory performance (e.g., dorsolateral prefrontal cortex and inferior parietal cortex) in both groups. However, the younger participants utilized the right dorsolateral prefrontal cortex and anterior cingulate gyrus significantly more than the older participants. In turn, the older participants used the left dorsolateral prefrontal cortex significantly more than the younger participants and maintained material-specific lateralization in their pattern of activation. These findings are consistent with a previous report of different age-related patterns of frontal activation during working memory.     

工作记忆的保持与操控：腹侧和背侧额叶皮层的特异性功能磁共振成像活动

为了进行大样本的老化与记忆的功能磁共振成像(fMRI)研究, 研究者设计了言语工作记忆的方案, 并且对一组健康青年人进行了施测。字母的呈现方式主要为两种条件: (i) 保持, 要求被试记住呈现的字母并且能够在4秒的间隔后保持; (ii) 操控, 被试需要将呈现的字母按字母表的顺序进行转换, 并且记住新的顺序。不管是用全脑分析, 还是用预先定义的感兴趣区域的分析方法, 对fMRI数据的分析表明本方案诱发了可靠的额叶皮层的激活, 且操控条件则引发了更为广泛的激活。背外侧和腹内侧前额叶的激活也表现出了不同特点, 操控引发了更多的背外侧前额叶激活。一些皮下区域也得到了激活, 特别是以前发现与工作记忆任务相关的一些区域。这说明该工作记忆研究方案适合探索额叶功能的与年龄相关的改变。     

Domain-dependent activation during spatial and nonspatial auditory working memory

Visual system has been proposed to be divided into two, the ventral and dorsal, processing streams. The ventral pathway is thought to be involved in object identification whereas the dorsal pathway processes information regarding the spatial locations of objects and the spatial relationships among objects. Several studies on working memory (WM) processing have further suggested that there is a dissociable domain-dependent functional organization within the prefrontal cortex for processing of spatial and nonspatial visual information. Also the auditory system is proposed to be organized into two domain-specific processing streams, similar to that seen in the visual system. Recent studies on auditory WM have further suggested that maintenance of nonspatial and spatial auditory information activates a distributed neural network including temporal, parietal, and frontal regions but the magnitude of activation within these activated areas shows a different functional topography depending on the type of information being maintained. The dorsal prefrontal cortex, specifically an area of the superior frontal sulcus (SFS), has been shown to exhibit greater activity for spatial than for nonspatial auditory tasks. Conversely, ventral frontal regions have been shown to be more recruited by nonspatial than by spatial auditory tasks. It has also been shown that the magnitude of this dissociation is dependent on the cognitive operations required during WM processing. Moreover, there is evidence that within the nonspatial domain in the ventral prefrontal cortex, there is an across-modality dissociation during maintenance of visual and auditory information. Taken together, human neuroimaging results on both visual and auditory sensory systems support the idea that the prefrontal cortex is organized according to the type of information being maintained in WM.     

Investigating virtual reality navigation in amnestic mild cognitive impairment using fMRI

Spatial navigation requires a well-established network of brain regions, including the hippocampus, caudate nucleus, and retrosplenial cortex. Amnestic Mild Cognitive Impairment (aMCI) is a condition with predominantly memory impairment, conferring a high predictive risk factor for dementia. aMCI is associated with hippocampal atrophy and subtle deficits in spatial navigation. We present the first use of a functional Magnetic Resonance Imaging (fMRI) navigation task in aMCI, using a virtual reality analog of the Radial Arm Maze. Compared with controls, aMCI patients showed reduced activity in the hippocampus bilaterally, retrosplenial cortex, and left dorsolateral prefrontal cortex. Reduced activation in key areas for successful navigation, as well as additional regions, was found alongside relatively normal task performance. Results also revealed increased activity in the right dorsolateral prefrontal cortex in aMCI patients, which may reflect compensation for reduced activations elsewhere. These data support suggestions that fMRI spatial navigation tasks may be useful for staging of progression in MCI.     

Interference resolution: Insights from a meta-analysis of neuroimaging tasks

A quantitative meta-analysis was performed on 47 neuroimaging studies involving tasks purported to require the resolution of interference. The tasks included the Stroop, flanker, go/no-go, stimulus-response compatibility, Simon, and stop signal tasks. Peak density-based analyses of these combined tasks reveal that the anterior cingulate cortex, dorsolateral prefrontal cortex, inferior frontal gyrus, posterior parietal cortex, and anterior insula may be important sites for the detection and/or resolution of interference. Individual task analyses reveal differential patterns of activation among the tasks. We propose that the drawing of distinctions among the processing stages at which interference may be resolved may explain regional activation differences. Our analyses suggest that resolution processes acting upon stimulus encoding, response selection, and response execution may recruit different neural regions.     

Manipulation of frontal brain asymmetry by cognitive tasks

The purpose of the present study was to evaluate whether verbal fluency tasks may specifically induce relatively greater left than right hemispheric activation in the dorsolateral prefrontal cortex. The effectiveness of the manipulation was evaluated by EEG, which was recorded during performance of the verbal fluency task and during two control conditions, i.e., a baseline condition without cognitive demands, and a mental arithmetic task, respectively. The results demonstrate that the desired effect can only be achieved in individuals with good performance on the verbal fluency task. Good and poor performers do not only differ in lateral asymmetry, but also in the most affected region within the prefrontal cortex. Whereas good performers show relatively increased activation in the cortical region and hemisphere putatively most specialized for this kind of task (i.e., the left dorsolateral frontal cortex), poor performers show a marked shift of frontopolar asymmetry to the right.     

Residual differences in language processing in compensated dyslexics revealed in simple word reading tasks

Using regional cerebral blood flow as an index of cerebral activity we studied dyslexic and control subjects during simple word reading tasks. The groups were pre-tested for reading skill and the dyslexic group had a lower reading performance but could read and comprehend standard texts. The aim was to elucidate differences in the cerebral activation pattern during reading. The tasks were simple enough that performance differences between the groups could be excluded. We found specific differences between the two groups that were dependent on the language task. When the visual route for language information was used, minor qualitative differences were found between the groups pertaining to the dominant hemisphere. Increasing the complexity of the task by using pseudowords activated the left frontal region more in the dyslexic group than in the control group. A similar effect was seen in a minor region in extrastriate lateral occipital cortex (BA 19). This finding indicates that the dyslexics used areas in these regions that the controls did not. On the other hand, the dyslexics activated less in the right angular gyrus, right dorsolateral prefrontal cortex, and in the right pallidum. Reading skill correlated with the level of activity in the right frontal cortex. We conclude, that cerebral activation pattern elicited by reading is different in dyslexics compared to controls in spite of an almost complete functional compensation.     

Maintenance versus manipulation of information held in working memory: an event-related fMRI study.

One model of the functional organization of lateral prefrontal cortex (PFC) in primates posits that this region is organized in a dorsal/ventral fashion subserving spatial and object working memory, respectively. Alternatively, it has been proposed that a dorsal/ventral subdivision of lateral PFC instead reflects the type of processing performed upon information held in working memory. We tested this hypothesis using an event-related fMRI method that can discriminate among functional changes occurring during temporally separated behavioral subcomponents of a single trial. Subjects performed a delayed-response task with two types of trials in which they were required to: (1) retain a sequence of letters across the delay period (maintenance) or (2) reorder the sequence into alphabetical order across the delay period (manipulation). In each subject, activity during the delay period was found in both dorsolateral and ventrolateral PFC in both types of trials. However, dorsolateral PFC activity was greater in manipulation trials. These findings are consistent with the processing model of the functional organization of working memory in PFC.     

Trait anxiety and the neural efficiency of manipulation in working memory

The present study investigates the effects of trait anxiety on the neural efficiency of working memory component functions (manipulation vs. maintenance) in the absence of threat-related stimuli. For the manipulation of affectively neutral verbal information held in working memory, high- and low-anxious individuals (N = 46) did not differ in their behavioral performance, yet trait anxiety was positively related to the neural effort expended on task processing, as measured by BOLD signal changes in fMRI. Higher levels of anxiety were associated with stronger activation in two regions implicated in the goal-directed control of attention--that is, right dorsolateral prefrontal cortex (DLPFC) and left inferior frontal sulcus--and with stronger deactivation in a region assigned to the brain's default-mode network--that is, rostral-ventral anterior cingulate cortex. Furthermore, anxiety was associated with a stronger functional coupling of right DLPFC with ventrolateral prefrontal cortex. We interpret our findings as reflecting reduced processing efficiency in high-anxious individuals and point out the need to consider measures of functional integration in addition to measures of regional activation strength when investigating individual differences in neural efficiency. With respect to the functions of working memory, we conclude that anxiety specifically impairs the processing efficiency of (control-demanding) manipulation processes (as opposed to mere maintenance). Notably, this study contributes to an accumulating body of evidence showing that anxiety also affects cognitive processing in the absence of threat-related stimuli.     

The mid-ventrolateral prefrontal cortex and active mnemonic retrieval

The role of the mid-ventrolateral prefrontal cortex in memory retrieval is examined and compared with the role of the mid-dorsolateral prefrontal cortex in the monitoring of information in memory. It has been argued that the mid-ventrolateral prefrontal cortex (areas 47/12 and 45) is involved in the active retrieval of information from posterior cortical association areas. Active retrieval is required when stimuli in memory do not bear stable relations to each other and therefore retrieval cannot be automatically driven by strong, stable, and unambiguous stimulus or context relations. Data from functional activation studies with normal human subjects are presented that have demonstrated specific changes in activity within the mid-ventrolateral region of the frontal cortex in relation to the active retrieval of information from memory. By contrast, increases in activity in the mid-dorsolateral region of the frontal cortex occur when the performance of the tasks requires monitoring of information in memory.     

客体与空间工作记忆的分离：来自皮层慢电位的证据

利用128导事件相关电位技术,采用延迟匹配任务的实验范式,测查了16名正常被试在完成客体任务和空间任务时的皮层慢电位（slow cortical potentials,简称sp成分）,实验发现：在后部脑区,客体工作记忆与空间工作记忆在慢波活动的时间上存在分离,空间任务更早的诱发出负sp成分,并且空间任务激活更多的后部脑区;左下前额叶在客体工作记忆任务与空间工作记忆任务中都有激活,并且激活强度不存在显著差异;背侧前额叶主要负责客体信息的保持与复述,但左右背侧前额叶的激活强度存在不对称性。     

Neurophysiology and neuroanatomy of reflexive and voluntary saccades in non-human primates

A multitude of cognitive functions can easily be tested by a number of relatively simple saccadic eye movement tasks. This approach has been employed extensively with patient populations to investigate the functional deficits associated with psychiatric disorders. Neurophysiological studies in non-human primates performing the same tasks have begun to provide us with insights into the neural mechanisms underlying many cognitive functions. Here, we review studies that have investigated single neuron activity in the superior colliculus (see glossary), frontal eye field, supplementary eye field, dorsolateral prefrontal cortex, anterior cingulate (see glossary) cortex and lateral intraparietal area associated with the performance of visually guided saccades, anti-saccades and memory-guided saccades in awake behaving monkeys.     

Neurophysiology and neuroanatomy of reflexive and voluntary saccades in non-human primates

A multitude of cognitive functions can easily be tested by a number of relatively simple saccadic eye movement tasks. This approach has been employed extensively with patient populations to investigate the functional deficits associated with psychiatric disorders. Neurophysiological studies in non-human primates performing the same tasks have begun to provide us with insights into the neural mechanisms underlying many cognitive functions. Here, we review studies that have investigated single neuron activity in the superior colliculus (see glossary), frontal eye field, supplementary eye field, dorsolateral prefrontal cortex, anterior cingulate (see glossary) cortex and lateral intraparietal area associated with the performance of visually guided saccades, anti-saccades and memory-guided saccades in awake behaving monkeys.     

Right-hemispheric cortical contributions to language ability in healthy adults

In this study we investigated the correlation between individual linguistic ability based on performance levels and their engagement of typical and atypical language areas in the brain. Eighteen healthy subjects between 21 and 64 years participated in language ability tests, and subsequent functional MRI scans measuring brain activity in response to a sentence completion and a word fluency task. Performance in both reading and high-level language tests correlated positively with increased right-hemispheric activation in the inferior frontal gyrus (specifically Brodmann area 47), the dorsolateral prefrontal cortex (DLPFC), and the medial temporal gyrus (Brodmann area 21). In contrast, we found a negative correlation between performance and left-hemispheric DLPFC activation.Our findings indicate that the right lateral frontal and right temporal regions positively modulate aspects of language ability.     

Domain specificity in the primate prefrontal cortex

Experimental studies in nonhuman primates and functional imaging studies in humans have underlined the critical role played by the prefrontal cortex (PFC) in working memory. However, the precise organization of the frontal lobes with respect to the different types of information operated upon is a point of controversy, and several models of functional organizations have been proposed. One model, developed by Goldman-Rakic and colleagues, postulates a modular organization of working memory based on the type of information processing (the domain specificity hypothesis). Evidence to date has focused on the encoding of the locations of visual objects by the dorsolateral PFC, whereas the ventrolateral PFC is suggested to be involved in processing the features and identity of objects. In this model, domain should refer to any sensory modality that registers information relevant to that domain—for example, there would be visual and auditory input to a spatial information processing region and a feature analysis system. In support of this model, recent studies have described pathways from the posterior and anterior auditory association cortex that target dorsolateral spatial-processing regions and ventrolateral object-processing regions, respectively. In addition, physiological recordings from the ventrolateral PFC indicate that some cells in this region are responsive to the features of complex sounds. Finally, recordings in adjacent ventrolateral prefrontal regions have shown that the features of somatosensory stimuli can be discriminated and encoded by ventrolateral prefrontal neurons. These discoveries argue that two domains, differing with respect to the type of information being processed, and not with respect to the sensory modality of the information, are specifically localized to discrete regions of the PFC and embody the domain specificity hypothesis, first proposed by Patricia Goldman-Rakic.     

Neural mechanisms of interference control underlie the relationship between fluid intelligence and working memory span

Fluid intelligence (gF) and working memory (WM) span predict success in demanding cognitive situations. Recent studies show that much of the variance in gF and WM span is shared, suggesting common neural mechanisms. This study provides a direct investigation of the degree to which shared variance in gF and WM span can be explained by neural mechanisms of interference control. The authors measured performance and functional magnetic resonance imaging activity in 102 participants during the n-back WM task, focusing on the selective activation effects associated with high-interference lure trials. Brain activity on these trials was correlated with gF, WM span, and task performance in core brain regions linked to WM and executive control, including bilateral dorsolateral prefrontal cortex (middle frontal gyrus; BA9) and parietal cortex (inferior parietal cortex; BA 40/7). Interference-related performance and interference-related activity accounted for a significant proportion of the shared variance in gF and WM span. Path analyses indicate that interference control activity may affect gF through a common set of processes that also influence WM span. These results suggest that individual differences in interference-control mechanisms are important for understanding the relationship between gF and WM span.     

The neural basis of updating: Distinguishing substitution processes from other concurrent processes

Sörqvist, P. & Sætrevik, B. (2010). The neural basis of updating: Distinguishing substitution processes from other concurrent processes. Scandinavian Journal of Psychology, 51, 357–362. Most previous studies of updating processes have not been able to contrast processes of substituting items in memory with other concurrent processes. In the present investigation, we used a new task called “number updating” and an fMRI protocol to contrast the activation of trials that require item substitution (adding a new item to the working memory representation and suppressing an old item) with trials that involve no substitution (discarding the new item). Trials that require item substitution activated the dorsolateral prefrontal cortex, the posterior medial frontal cortex and the parietal lobes, areas typically seen activated for working memory tasks in general. Trials that do not require substitution activated the anterior medial frontal cortex. Studies examining executive functions have associated this area with cognitive conflict, and may represent suppression of the substitution processes.     

The neural regions sustaining episodic encoding and recognition of objects

In this functional MRI experiment, encoding of objects was associated with activation in left ventrolateral prefrontal/insular and right dorsolateral prefrontal and fusiform regions as well as in the left putamen. By contrast, correct recognition of previously learned objects (R judgments) produced activation in left superior frontal, bilateral inferior frontal, and right cerebellar regions, whereas correct rejection of distractor objects (N judgments) was associated with activation in bilateral prefrontal and anterior cingulate cortices, in right parietal and cerebellar regions, in the left putamen, and in the right caudate nucleus. The R minus N comparison showed activation in the left lateral prefrontal cortex and in bilateral cingulate cortices and precunei, while the N minus R comparison did not reveal any positive signal change. These results support the view that similar regions of the frontal lobe are involved in episodic encoding and retrieval processes, and that the successful episodic retrieval of newly learned objects is mainly based on a frontoparietal network.     

Working and long-term memory deficits in schizophrenia: is there a common prefrontal mechanism?

This study tested the hypothesis that dorsolateral prefrontal cortex deficits contribute to both working memory and long-term memory disturbances in schizophrenia. It also examined whether such deficits were more severe for verbal than nonverbal stimuli. Functional magnetic resonance imaging was used to assess cortical activation during performance of verbal and nonverbal versions of a working memory task and both encoding and recognition tasks in 38 individuals with schizophrenia and 48 healthy controls. Performance of both working memory and long-term memory tasks revealed disturbed dorsolateral prefrontal cortex activation in schizophrenia, although medial temporal deficits were also present. Some evidence was found for more severe cognitive and functional deficits with verbal than nonverbal stimuli, although these results were mixed.