Ethanol reduces rCFB activation of left dorsolateral prefrontal cortex during a verbal fluency task

In a previous study in normal subjects (Wendt et al., 1994), using a reversing checkerboard as activation stimulus, we found that the coupling between local neuronal activity and regional cerebral blood flow was preserved following ethanol, and that a right-sided occipital activation response seen during sobriety became symmetrical during inebriation. In the present study we investigated if ethanol has a detrimental effect also on the activation of the left dorsolateral prefrontal cortex found in normals during verbal fluency. Measurements of regional cerebral blood flow in 20 healthy, young, male, right-handed volunteers during rest and verbal fluency were made during sobriety and inebriation (0.06% blood alcohol concentration) with a 1-week interval. We found a decrease in word production during inebriation. The normal activation within the frontotemporal part of the left dorsolateral prefrontal cortext was preserved during inebriation. The activation of this region seems thus to be robust to the effects of ethanol. During inebriation no activation response to the word fluency test was found in the anterior prefrontal part of the dorsolateral prefrontal cortex. This region is important for working, temporal, and short-term memory functions, processes that are affected by ethanol. Hemispheric functioning and specialization seem to be adversely affected by ethanol, regardless of which hemisphere is most involved while sober.     

Functional asymmetry of human prefrontal cortex: encoding and retrieval of verbally and nonverbally coded information

There are several views about the organization of memory functions in the human prefrontal cortex. One view assumes a process-specific brain lateralization according to different memory subprocesses, that is, encoding and retrieval. An alternative view emphasizes content-specific lateralization of brain systems involved in memory processes. This study addresses this apparent inconsistency between process- and content-specific lateralization of brain activity by investigating the effects of verbal and nonverbal encoding on prefrontal activations during encoding and retrieval of environmental novel sounds using fMRI. An intentional memory task was applied in which subjects were required either to judge the sounds' loudness (nonverbal encoding task) or to indicate whether or not a sound can be verbally described (verbal encoding task). Retrieval processes were examined in a subsequent yes/no recognition test. In the study phase the right posterior dorsolateral prefrontal cortex (PFC) was activated in both tasks. During verbal encoding additional activation of the left dorsolateral PFC was obtained. Retrieval-related fMRI activity varied as a function of encoding task: For the nonverbal task we detected an activation focus in the right posterior dorsolateral PFC whereas an activation in the left dorsolateral PFC was observed for the verbal task. These findings indicate that the right dorsolateral PFC is engaged in encoding of auditory information irrespective of encoding task. The lateralization of PFC activity during retrieval was shown to depend on the availability of verbal codes, with left hemispheric involvement for verbally and right hemispheric activation for nonverbally coded information.     

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.     

Frontal brain asymmetry in depression with comorbid anxiety: a neuropsychological investigation

The approach-withdrawal model posits that depression and anxiety are associated with a relative right asymmetry in frontal brain activity. Most studies have tested this model using measures of cortical brain activity such as electroencephalography. However, neuropsychological tasks that differentially use left versus right frontal cortical regions can also be used to test hypotheses from the model. In two independent samples (Study 1 and 2), the present study investigated the performance of currently depressed individuals with or without a comorbid anxiety disorder and healthy controls on neuropsychological tasks tapping primarily left (verbal fluency) or right (design fluency) frontal brain regions. Across both samples, results indicated that comorbid participants performed more poorly than depressed only and control participants on design fluency, while all groups showed equivalent performance on verbal fluency. Moreover, comorbid participants showed "asymmetrical" performance on these two tasks (i.e., poorer design [right frontal] relative to verbal [left frontal] fluency), whereas depressed only and control participants showed approximately symmetrical profiles of performance. Results from these two samples suggest an abnormal frontal asymmetry in neurocognitive performance driven primarily by right frontal dysfunction among anxious-depressed individuals and highlight the importance of considering comorbid anxiety when examining frontal brain functioning in depression.     

Developmental differences in prefrontal activation during working memory maintenance and manipulation for different memory loads

The ability to keep information active in working memory is one of the cornerstones of cognitive development. Prior studies have demonstrated that regions which are important for working memory performance in adults, such as dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), and superior parietal cortex, become increasingly engaged across school-aged development. The primary goal of the present functional MRI study was to investigate the involvement of these regions in the development of working memory manipulation relative to maintenance functions under different loads. We measured activation in DLPFC, VLPFC, and superior parietal cortex during the delay period of a verbal working memory task in 11-13-year-old children and young adults. We found evidence for age-related behavioral improvements in working memory and functional changes within DLPFC and VLPFC activation patterns. Although activation profiles of DLPFC and VLPFC were similar, group differences were most pronounced for right DLPFC. Consistent with prior studies, right DLPFC showed an interaction between age and condition (i.e. manipulation versus maintenance), specifically at the lower loads. This interaction was characterized by increased activation for manipulation relative to maintenance trials in adults compared to children. In contrast, we did not observe a significant age-dependent load sensitivity. These results suggest that age-related differences in the right DLPFC are specific to working memory manipulation and are not related to task difficulty and/or differences in short-term memory capacity.     

PET studies of encoding and retrieval: The HERA model

We review positron emission tomography (PET) studies whose results converge on the hemispheric encoding/retrieval asymmetry (HERA) model of the involvement of prefrontal cortical regions in the processes of human memory. The model holds that the left prefrontal cortex is differentially more involved in retrieval of information from semantic memory, and in simultaneously encoding novel aspects of the retrieved information into episodic memory, than is the right prefrontal cortex. The right prefrontal cortex, on the other hand, is differentially more involved in episodic memory retrieval than is the left prefrontal cortex. This general pattern holds for different kinds of information (e.g., verbal materials, pictures, faces) and a variety of conditions of encoding and retrieval.     

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.     

概化理论预算限制下最佳样本量估计

概化理论广泛应用于各种心理测评实践中。当有预算限制时,概化理论需要考虑如何设计一个测量可靠性相对较高且可行性也相对较强的测量程序,这就要求通过某些途径估计最佳样本量。拉格朗日乘法是概化理论预算限制下最佳样本量估计较为成熟的方法。探讨了概化理论预算限制下最佳样本量估计的一些影响因素,如受总预算舍入的影响等,也提出了一些后续改善的建议,如推导出拉格朗日乘法的统一公式等     

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.     

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。     

Seeing minds in others: Mind perception modulates low-level social-cognitive performance and relates to ventromedial prefrontal structures

In social interactions, we rely on nonverbal cues like gaze direction to understand the behavior of others. How we react to these cues is affected by whether they are believed to originate from an entity with a mind, capable of having internal states (i.e., mind perception). While prior work has established a set of neural regions linked to social-cognitive processes like mind perception, the degree to which activation within this network relates to performance in subsequent social-cognitive tasks remains unclear. In the current study, participants performed a mind perception task (i.e., judging the likelihood that faces, varying in physical human-likeness, have internal states) while event-related fMRI was collected. Afterwards, participants performed a social attention task outside the scanner, during which they were cued by the gaze of the same faces that they previously judged within the mind perception task. Parametric analyses of the fMRI data revealed that activity within ventromedial prefrontal cortex (vmPFC) was related to both mind ratings inside the scanner and gaze-cueing performance outside the scanner. In addition, other social brain regions were related to gaze-cueing performance, including frontal areas like the left insula, dorsolateral prefrontal cortex, and inferior frontal gyrus, as well as temporal areas like the left temporo-parietal junction and bilateral temporal gyri. The findings suggest that functions subserved by the vmPFC are relevant to both mind perception and social attention, implicating a role of vmPFC in the top-down modulation of low-level social-cognitive processes.     

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.     

rTMS stimulation on left DLPFC increases the correct recognition of memories for emotional target and distractor words

According to a recent hypothesis, the prefrontal cortex has been proposed as the site of emotional memory integration, because it is sensitive to the recognition of emotional contents. In the present research, we explored the role of the dorsolateral prefrontal cortex (DLPFC) in memory recognition processes for positive versus negative emotional stimuli when old (target) and new (distractor, either semantically related or unrelated to the target) stimuli were presented. The role of the DLPFC was analysed using an rTMS (repeated transcranial magnetic stimulation) paradigm that induced increased cortical activation of the left DLPFC. The subjects were required to perform a task that consisted of two experimental phases (i.e., an encoding and a recognition phase) in which the targets and the distractors were presented and recognition performance was measured. rTMS stimulation was provided over the left DLPFC during the recognition phase. We found that the rTMS stimulation affected the memory recognition of positive emotional material. Moreover, related and unrelated distractors were discarded better when they were positively valenced, and a more significant effect (i.e., increased performance) was produced in response to related distractors. This result suggests that the activation of the left DLPFC favours the memory recognition of positive emotional information, and that such activation is able to induce a more appropriate selective process to distinguish target from distractor stimuli in the presence of more complex processes (related distractors). The valence model of emotional cue processing may explain this increased performance by demonstrating the distinct role of the left hemisphere in the retrieval of positive emotional information.     

Contribution of NIRS to the study of prefrontal cortex for verbal fluency in aging

Healthy aging is characterized by a number of changes on brain structure and function. Several neuroimaging studies have shown an age-related reduction in hemispheric asymmetry on various cognitive tasks, a phenomenon captured by Cabeza (2002) in the Hemispheric Asymmetry Reduction in Older Adults (HAROLD) model. Although this phenomenon is supported by a range of neuroimaging data on memory and inhibitory processes, there is little evidence concerning changes in hemispheric asymmetry for language processing, and particularly word retrieval, which is assessed with verbal fluency task (VFT). This study aimed to investigate the age-related changes in cerebral oxygenation in the prefrontal cortex for both letter and category VFT, varying the complexity of the criteria (i.e., degree of productivity) and using near-infrared spectroscopy (NIRS). Sixteen younger and 16 older adults participated in this study. For both VF conditions, participants were instructed to pronounce as many nouns as possible as a function of high-productivity (e.g., “animals” or “L”) or low-productivity (e.g., “flowers” or “V”) criteria. Behavioral data (i.e., accuracy responses) showed comparable performance in younger and older adults for both VF conditions. However, NIRS data showed more reduced activation (i.e., significantly reduced increase in [O₂Hb] and reduced decrease in [HHb]) in older than younger adults for both VFT. In addition, a bilateral effect was found for both groups, suggesting that VFT requires both executive and language functions. The results are discussed in the context of the current theories of aging.     

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.     

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.     

The effect of bicephalic stimulation of the dorsolateral prefrontal cortex on the attentional bias for threat: A transcranial direct current stimulation study

Previous stimulation studies demonstrated that the dorsolateral prefrontal cortex (DLPFC) is involved in threat processing. According to a model of emotional processing, an unbalance between the two DLPFCs, with a hyperactivation of right frontal areas, is involved in the processing of negative emotions and genesis of anxiety. In the present study, we investigated the role of the right and left DLPFC in threat processing in healthy women who also completed the State-Trait Anxiety Inventory (STAI). We simultaneously modulated the activity of the right and left dorsolateral prefrontal cortex by applying bicephalic transcranial direct current stimulation (tDCS) before participants completed a modified version of the classic Posner task using threatening and nonthreatening stimuli as spatial cues. Anodal stimulation on the right DLPFC with a simultaneous cathodal stimulation over the left side induced a disengagement bias in individuals with low STAI scores and a facilitation bias in individuals with high STAI scores. Anodal stimulation on the left DLPFC with the simultaneous cathodal stimulation over the right side did not affect threat processing. The findings of the present study provided specific support to the hypothesis that unbalanced activation between left and right hemispheres with enhanced activation of the right DLPFC is critical in early top-down threat processing in healthy individuals.     

The role of spatial configuration in tests of working memory explored with functional neuroimaging

While the importance of the prefrontal cortex for "higher-order" cognitive functions is largely undisputed, no consensus has been reached regarding the fractionation of functions within this region. Several recent functional neuroimaging studies have suggested that the mid-ventrolateral frontal cortex may play an important role in various aspects of human memory. Thus, similar patterns of activation have been observed in this region during analogous spatial, verbal and visual span tasks. In the present study, however, activation was observed in a more dorsolateral region of the lateral frontal cortex during a modified version of the spatial span task, which differed only in the spatial configuration of the array employed. The results of a supplementary behavioral study, designed to investigate this effect further, suggest that in spatial memory tasks certain stimulus configurations may encourage subjects to adopt mnemonic strategies, which may depend upon dorsolateral, rather than ventrolateral, regions of the frontal cortex. These findings shed further light on the functional relationship between dorsal and ventral regions of the lateral frontal cortex and, more specifically, how the "executive" processes assumed to be dependent upon these regions might contribute to aspects of human memory.     

The contribution of the dorsolateral prefrontal cortex in full and divided encoding: a paired-pulse transcranial magnetic stimulation study

This research investigated the contribution of the dorsolateral prefrontal cortex (DLPFC) in the attentional resources in episodic encoding for both verbal and non-verbal material. Paired-pulse transcranial magnetic stimulations (TMS) were used to interfere transiently with either the left or right DLPFC during encoding under full attention (FA) or under divided attention (DA) in a recognition paradigm using words and random shapes. Participants recognized fewer items after TMS over the left DLPFC than over the right DLPFC during FA encoding. However, TMS over the left DLPFC did not impair performance when compared to sham condition. Conversely, participants produced fewer items after TMS over the right DLPFC in DA encoding compared to sham condition, but not compared to TMS over the left DLPFC. These effects were found for both words and random shapes. These results suggest that the right DLPFC play an important role in successful encoding with a concomitant task regardless of the type of material.