Differential effects of distraction during working memory on delay-period activity in the prefrontal cortex and the visual association cortex

Maintaining relevant information for later use is a critical aspect of working memory (WM). The lateral prefrontal cortex (PFC) and posterior sensory cortical areas appear to be important in supporting maintenance. However, the relative and unique contributions of these areas remain unclear. We have designed a WM paradigm with distraction to probe the contents of maintenance representations in these regions. During delayed recognition trials of faces, selective interference was evident behaviorally with face distraction leading to significantly worse performance than with scene distraction. Event-related fMRI of the human brain showed that maintenance activity in the lateral PFC, but not in visual association cortex (VAC), was selectively disrupted by face distraction. Additionally, the functional connectivity between the lateral PFC and the VAC was perturbed during these trials. We propose a hierarchical and distributed model of active maintenance in which the lateral PFC codes for abstracted mnemonic information, while sensory areas represent specific features of the memoranda. Furthermore, persistent coactivation between the PFC and sensory areas may be a mechanism by which information is actively maintained.     

Dissociable networks involved in spatial and temporal order source retrieval

Space and time are important components of our episodic memories. Without this information, we cannot determine the "where and when" of our recent memories, rendering it difficult to disambiguate individual episodes from each other. The neural underpinnings of spatial and temporal order memory in humans remain unclear, in part because of difficulties in disentangling the contributions of these two types of source information. To address this issue, we conducted an experiment in which participants first navigated a virtual city, experiencing unique routes in a specific temporal order and learning about the spatial layout of the city. Spatial and temporal order information were dissociated in our task such that learning one type of information did not facilitate the other behaviorally. This allowed us to then address the extent to which the two types of information involved functionally distinct or overlapping brain areas. During functional magnetic resonance imaging (fMRI), participants retrieved information about the relative distance of stores within the city (spatial task) and the temporal order of stores from each other (temporal task). Comparable hippocampal activity was observed during these two tasks, but greater prefrontal activity was seen during temporal order retrieval whereas greater parahippocampal activity was seen during spatial retrieval. We suggest that while the brain possesses dissociable networks for maintaining and representing spatial layout and temporal order components of episodic memory, this information may converge into a common representation for source memory in areas such as the hippocampus.     

Isolating the retrieval of imagined pictures during episodic memory: activation of the left precuneus and left prefrontal cortex

The posterior medial parietal cortex and the left prefrontal cortex have both been implicated in the recollection of past episodes. In order to clarify their functional significance, we performed this functional magnetic resonance imaging study, which employed event-related source memory and item recognition retrieval of words paired with corresponding imagined or viewed pictures. Our results suggest that episodic source memory is related to a functional network including the posterior precuneus and the left lateral prefrontal cortex. This network is activated during explicit retrieval of imagined pictures and results from the retrieval of item-context associations. This suggests that previously imagined pictures provide a context with which encoded words can be more strongly associated.     

Electrophysiological correlates of retrieval orientation in reality monitoring

Retrieval orientation describes the modulation in the processing of retrieval cues by the nature of the targeted material in memory. Retrieval orientation is usually investigated by analyzing the cortical responses to new (unstudied) material when different memory contents are targeted. This approach avoids confounding effects of retrieval success. We investigated the neural correlates of retrieval orientation in reality monitoring with event-related potentials (ERPs) and assessed the impact of retrieval accuracy on obtained ERP measures. Thirty-two subjects studied visually presented object names that were followed either by a picture of that object (perceived condition) or by the instruction to mentally generate such a picture (imagine condition). Subsequently, subjects had to identify object names of one study condition and reject object names of the second study condition together with newly presented object names. The data analysis showed that object names were more accurately identified when they had been presented in the perceived condition. Two topographically distinct ERP effects of retrieval orientation were revealed: From 600 to 1100 ms after stimulus representation, ERPs were more positive at frontal electrode sites when object names from the imagine condition were targeted. The analysis of response-locked ERP data revealed an additional effect at posterior electrode sites, with more negative ERPs shortly after response onset when items from the imagine condition were targeted. The ERP effect at frontal electrode sites, but not at posterior electrode sites was modulated by relative memory accuracy, with stronger effects in subjects who had lower memory accuracy for items of the imagine condition. The findings are suggestive for a contribution of frontal brain areas to retrieval orientation processes in reality monitoring and indicate that neural correlates of retrieval orientation can be modulated by retrieval effort, with stronger activation of these correlates with increasing task demands.     

Dissociable correlates of two classes of retrieval processing in prefrontal cortex

Although substantial evidence suggests that the prefrontal cortex (PFC) implements processes that are critical for accurate episodic memory judgments, the specific roles of different PFC subregions remain unclear. Here, we used event-related functional magnetic resonance imaging to distinguish between prefrontal activity related to operations that (1) influence processing of retrieval cues based on current task demands, or (2) are involved in monitoring the outputs of retrieval. Fourteen participants studied auditory words spoken by a male or female speaker and completed memory tests in which the stimuli were unstudied foil words and studied words spoken by either the same speaker at study, or the alternate speaker. On "general" test trials, participants were to determine whether each word was studied, regardless of the voice of the speaker, whereas on "specific" test trials, participants were to additionally distinguish between studied words that were spoken in the same voice or a different voice at study. Thus, on specific test trials, participants were explicitly required to attend to voice information in order to evaluate each test item. Anterior (right BA 10), dorsolateral prefrontal (right BA 46), and inferior frontal (bilateral BA 47/12) regions were more active during specific than during general trials. Activation in anterior and dorsolateral PFC was enhanced during specific test trials even in response to unstudied items, suggesting that activation in these regions was related to the differential processing of retrieval cues in the two tasks. In contrast, differences between specific and general test trials in inferior frontal regions (bilateral BA 47/12) were seen only for studied items, suggesting a role for these regions in post-retrieval monitoring processes. Results from this study are consistent with the idea that different PFC subregions implement distinct, but complementary processes that collectively support accurate episodic memory judgments.     

楔前叶/后扣带皮层在静息态功能网络中起关键节点作用的研究进展

已有文献报道指出一些脑区能够组成默认脑功能网络.不同的实验任务显示楔前叶/后扣带皮层与其他节点之间有更强的相互作用.功能连接分析发现楔前叶/后扣带皮层是默认脑功能网络中的一个关键区域.静息态默认脑功能网络是无尺度网络,具有小世界特性,楔前叶/后扣带皮层可能是该默认脑功能网络中一个重要的"集散节点".     

Working memory dysfunction in schizophrenia compared to healthy controls and patients with depression: evidence from event-related fMRI

Studies on working memory (WM) dysfunction in schizophrenia have reported several functionally aberrant brain areas including the lateral prefrontal cortex, superior temporal areas and the striatum. However, less is known about the relationship of WM-dysfunction, cerebral activation, task-accuracy and diagnostic specificity. Using a novel WM-task and event-related functional magnetic resonance imaging (fMRI), we studied healthy control subjects (n=17) and partially remitted, medicated inpatients meeting DSM-IV criteria for schizophrenia (n=19) and major depressive disorder (n=12). Due to the event-related technique, we excluded incorrectly performed trials, thus controlling for accuracy-related activation confounds. Compared with controls, patients with schizophrenia showed less activation in frontoparietal and subcortical regions at high cognitive load levels. Compared with patients with depression, schizophrenic patients showed less prefrontal activation in left inferior frontal cortex and right cerebellum. In patients with schizophrenia, a lack of deactivation of the superior temporal cortex was found compared to both healthy controls and patients with depression. Thus, we could not confirm previous findings of impaired lateral prefrontal activation during WM performance in schizophrenic patients after the exclusion of incorrectly performed or omitted trials in our functional analysis. However, superior temporal cortex dysfunction in patients with schizophrenia may be regarded as schizophrenia-specific finding in terms of psychiatric diagnosis specificity.     

工作记忆中整合物体和位置信息时的前额叶激活

目的：利用功能磁共振成像（fMRI）技术研究了情节缓存中信息整合过程的脑机制。方法：8名正常被试在MR扫描中执行工作记忆任务，“组合”（bound）条件下物体出现在外周某个位置，“未组合”（unbound）条件下，同时呈现一个位于中心的物体和一个在外周某个位置的十字，让被试将物体想象到十字所在位置，要求被试判断再次出现的物体是否在曾经见过的位置（“组合”条件）或曾经想象过的位置（“未组合”条件）。结果：“未组合”条件相对于知觉“组合”条件，在双侧额中回／额下回、顶叶和小脑等区域出现了显著激活；“组合”条件相对于”未组合”条件没有任何激活。结论：本研究表明前额叶皮层在没有知觉表征情况下建立新的整合表征中具有重要作用。现有研究已证明前额叶皮层在建构和保持整合信息中的作用，本文进一步的研究提示它可能是情节缓存中信息整合的神经基础。     

From perception to sentence comprehension: the convergence of auditory and visual information of language in the left inferior frontal cortex

We used functional magnetic resonance imaging (fMRI) to characterize cortical activation associated with sentence processing, thereby elucidating where in the brain auditory and visual inputs of words converge during sentence comprehension. Within one scanning session, subjects performed three types of tasks with different linguistic components from perception to sentence comprehension: nonword (N(AV); auditory and visual), phrase (P; either auditory or visual), and sentence (S; either auditory or visual) tasks. In a comparison of the P and N(AV) tasks, the angular and supramarginal gyri showed bilateral activation, whereas the inferior and middle frontal gyri showed left-lateralized activation. A comparison of the S and P tasks, together with a conjunction analysis, revealed a ventral region of the left inferior frontal gyrus (F3t/F3O), which was sentence-processing selective and modality-independent. These results unequivocally demonstrated that the left F3t/F3O is involved in the selection and integration of semantic information that are separable from lexico-semantic processing.     

The impact of affect and frequency on lexical decision: the role of the amygdala and inferior frontal cortex

The current study used event-related fMRI to examine BOLD responses associated with two factors that behaviorally determine speed of lexical decision: frequency and emotion. Thirteen healthy adults performed a visual lexical decision task, discriminating between words and orthographically and phonologically legal nonwords. The study involved a 2 (Frequency: high and low) x 3 (Emotional arousal: highly negative, mildly negative, and neutral words) design with word categories matched for number of letters and concreteness. There were significant main effects for both frequency and emotion in lexical decision reaction times but no significant interaction. Negative word lexical decisions were associated with increased activation in bilateral amygdala and middle temporal cortex as well as rostral anterior and posterior cingulate cortex. Low-frequency word lexical decisions, relative to high-frequency word lexical decisions, were associated with increased bilateral activity in inferior frontal cortex. Inferior frontal cortex activation was particularly low during lexical decision for high-frequency emotional words but significant for high-frequency neutral emotional words. We suggest that this is because the semantic representation of high-frequency emotional words may receive sufficient additional augmentation via the reciprocal activation from the amygdala such that selective augmentation by inferior frontal cortex to achieve lexical decision is unnecessary.     

Differential roles for left inferior frontal and superior temporal cortex in multimodal integration of action and language

Several studies indicate that both posterior superior temporal sulcus/middle temporal gyrus (pSTS/MTG) and left inferior frontal gyrus (LIFG) are involved in integrating information from different modalities. Here we investigated the respective roles of these two areas in integration of action and language information. We exploited the fact that the semantic relationship between language and different forms of action (i.e. co-speech gestures and pantomimes) is radically different. Speech and co-speech gestures are always produced together, and gestures are not unambiguously understood without speech. On the contrary, pantomimes are not necessarily produced together with speech and can be easily understood without speech. We presented speech together with these two types of communicative hand actions in matching or mismatching combinations to manipulate semantic integration load. Left and right pSTS/MTG were only involved in semantic integration of speech and pantomimes. Left IFG on the other hand was involved in integration of speech and co-speech gestures as well as of speech and pantomimes. Effective connectivity analyses showed that depending upon the semantic relationship between language and action, LIFG modulates activation levels in left pSTS.This suggests that integration in pSTS/MTG involves the matching of two input streams for which there is a relatively stable common object representation, whereas integration in LIFG is better characterized as the on-line construction of a new and unified representation of the input streams. In conclusion, pSTS/MTG and LIFG are differentially involved in multimodal integration, crucially depending upon the semantic relationship between the input streams.     

The precuneus/posterior cingulate cortex plays a pivotal role in the default mode network: Evidence from a partial correlation network analysis

Recent research has shown that intrinsic brain activity as observed by functional magnetic resonance imaging (fMRI) manifest itself as coherent signal changes in networks encompassing brain regions that span long-range neuronal pathways. One of these networks, the so called default mode network, has become the primary target in recent investigations to link intrinsic activity to cognition and how intrinsic signal changes may be altered in disease. In this study we assessed functional connectivity within the default mode network during both rest and a continuous working memory task on a region-by-region basis using partial correlation analysis, a data-driven method that provides insight into effective connectivity within neuronal networks. Prominent features of functional connectivity within the default mode network included an overall strong level of interaction between the precuneus/posterior cingulate region and the rest of the default mode network, as well as a high degree of interaction between the left and right medial temporal lobes combined with weak interactions between the medial temporal lobes and the rest of the default mode network. Additionally, we found support for strong interactions between the precuneus/posterior cingulate cortex and the left inferior parietal lobe as well as between the dorsal and ventral sections of the medial prefrontal cortex. The suggested pivotal role of the precuneus/posterior cingulate cortex in the default mode network is discussed.     

Human cortical EEG rhythms during long-term episodic memory task. A high-resolution EEG study of the HERA model

Many recent neuroimaging studies of episodic memory have indicated an asymmetry in prefrontal involvement, with the left prefrontal cortex more involved than the right in encoding, the right more than the left in retrieval (hemispheric encoding and retrieval asymmetry, or HERA model). In this electroencephalographic (EEG) high-resolution study, we studied brain rhythmicity during a visual episodic memory (recognition) task. The theta (4-6 Hz), alpha (6-12 Hz) and gamma (28-48 Hz) oscillations were investigated during a visuospatial long-term episodic memory task including an encoding (ENC) and retrieval (RET) phases. During the ENC phase, 25 figures representing interiors of buildings ("indoor") were randomly intermingled with 25 figures representing landscapes ("landscapes"). Subject's response was given at left ("indoor") or right ("landscapes") mouse button. During the RET phase (1 h later), 25 figures representing previously presented "indoor" pictures ("tests") were randomly intermingled with 25 figures representing novel "indoor" ("distractors"). Again, a mouse response was required. Theta and alpha EEG results showed no change of frontal rhythmicity. In contrast, the HERA prediction of asymmetry was fitted only by EEG gamma responses, but only in the posterior parietal areas. The ENC phase was associated with gamma EEG oscillations over left parietal cortex. Afterward, the RET phase was associated with gamma EEG oscillations predominantly over right parietal cortex. The predicted HERA asymmetry was thus observed in an unexpected location. This discrepancy may be due to the differential sensitivity of neuroimaging methods to selected components of cognitive processing. The strict relation between gamma response and perception suggests that retrieval processes of long-term memory deeply impinged upon sensory representation of the stored material.     

Spatial working memory deficits in obsessive compulsive disorder are associated with excessive engagement of the medial frontal cortex

Recent studies have shown that obsessive compulsive disorder (OCD) is associated with a specific deficit in spatial working memory, especially when task difficulty (i.e., working memory load) is high. It is not clear whether this deficit is associated with dysfunction of the brain system that subserves spatial working memory, or whether it is associated with a more generalized effect on executive functions. In contrast to studies in healthy volunteers and schizophrenia, spatial working memory in OCD has not been investigated before using functional neuroimaging techniques. We conducted a functional MRI study in 11 treatment-free female patients with OCD and 11 for sex-, age-, education-, and handedness pairwise-matched healthy controls in order to assess performance on a parametric spatial n-back task as well as the underlying neuronal substrate and its dynamics. Patients with OCD performed poorly at the highest level of task difficulty and engaged the same set of brain regions as the matched healthy controls. In this set, the effect of difficulty on magnitude of brain activity was the same in patients and in controls except for a region covering the anterior cingulate cortex. In this region activity was significantly elevated in patients with OCD at all levels of the parametric task. These findings do not provide evidence for a deficit of the spatial working memory system proper, but suggest that the abnormal performance pattern may be secondary to another aspect of executive dysfunctioning in OCD.     

Neural correlates of relational and item-specific encoding during working and long-term memory in schizophrenia

Successful long-term memory (LTM) depends upon effective control of information in working memory (WM), and there is evidence that both WM and LTM are impaired by schizophrenia. This study tests the hypothesis that LTM deficits in schizophrenia may result from impaired control of relational processing in WM due to dorsolateral prefrontal cortex (DLPFC) dysfunction. fMRI was performed on 19 healthy controls and 20 patients with schizophrenia during WM tasks emphasizing relational (reorder trials) versus item-specific (rehearse trials) processing. WM activity was also examined with respect to LTM recognition on a task administered outside the scanner. Receiver operator characteristic analysis assessed familiarity and recollection components of LTM. Patients showed a disproportionate familiarity deficit for reorder versus rehearse trials against a background of generalized LTM impairments. Relational processing during WM led to DLPFC activation in both groups. However, this activation was less focal in patients than in controls, and patients with more severe negative symptoms showed less of a DLPFC increase. fMRI analysis of subsequent recognition performance revealed a group by condition interaction. High LTM for reorder versus rehearse trials was associated with bilateral DLPFC activation in controls, but not in patients who activated the left middle temporal and inferior occipital gyrus. Results indicate that although patients can activate the DLPFC on a structured relational WM task, this activation is less focal and does not translate to high retrieval success, suggesting a disruption in the interaction between WM and LTM processes in schizophrenia.     

Establishing propositional truth-value in counterfactual and real-world contexts during sentence comprehension: differential sensitivity of the left and right inferior frontal gyri

What makes a proposition true or false has traditionally played an essential role in philosophical and linguistic theories of meaning. A comprehensive neurobiological theory of language must ultimately be able to explain the combined contributions of real-world truth-value and discourse context to sentence meaning. This fMRI study investigated the neural circuits that are sensitive to the propositional truth-value of sentences about counterfactual worlds, aiming to reveal differential hemispheric sensitivity of the inferior prefrontal gyri to counterfactual truth-value and real-world truth-value. Participants read true or false counterfactual conditional sentences (“If N.A.S.A. had not developed its Apollo Project, the first country to land on the moon would be Russia/America”) and real-world sentences (“Because N.A.S.A. developed its Apollo Project, the first country to land on the moon has been America/Russia”) that were matched on contextual constraint and truth-value. ROI analyses showed that whereas the left BA 47 showed similar activity increases to counterfactual false sentences and to real-world false sentences (compared to true sentences), the right BA 47 showed a larger increase for counterfactual false sentences. Moreover, whole-brain analyses revealed a distributed neural circuit for dealing with propositional truth-value. These results constitute the first evidence for hemispheric differences in processing counterfactual truth-value and real-world truth-value, and point toward additional right hemisphere involvement in counterfactual comprehension.     

Regional activation of the human medial temporal lobe during intentional encoding of objects and positions

The medial temporal lobe (MTL) consists of several regions thought to be involved in learning and memory. However, the degree of functional specialization among these regions remains unclear. Previous studies have demonstrated effects of both content and processing stage, but findings have been inconsistent. In particular, studies have suggested that the perirhinal cortex is more involved in object processing than spatial processing, while other regions such as the parahippocampal cortex have been implicated in spatial processing. In this study, functional magnetic resonance imaging (fMRI) optimized for the MTL region was used to probe MTL activation during intentional encoding of object identities or positions. A region of interest analysis showed that object encoding evoked stronger activation than position encoding in bilateral perirhinal cortex, temporopolar cortex, parahippocampal cortex, hippocampus and amygdala. Results also indicate an unexpected significant correlation in activation level between anterior and posterior portions in both the left parahippocampal cortex and left hippocampus. Exploratory analysis did not show any regional content effects during preparation and rehearsal stages. These results provide additional evidence for functional specialization within the MTL, but were less clear regarding the specific nature of content specificity in these regions.     

听觉剥夺幼鼠学习记忆能力及听皮质超微结构研究

摘要 目的：探讨听觉剥夺对幼鼠学习记忆的影响及听皮质细胞超微结构的变化。 方法：将36只SD幼鼠随机分为听觉剥夺组和正常对照组。听觉剥夺组在生后第7天用阿米卡星500mg/kg·d皮下注射,直到生后第16天,建立听觉剥夺模型。分别于生后第3周、5周、7周进行Morris 水迷宫测试,检测各组幼鼠的学习记忆能力。行为学测试完毕后,观察听皮质超微结构的变化。对照组只进行等容量生理盐水皮下注射。 结果：①定位航行实验：3周龄听觉剥夺组和对照组每天逃避潜伏期差异均无显著性意义（P值均＞0.05）;5周龄听觉剥夺组幼鼠自第2天起,每天的逃避潜伏期均较同龄对照组延长,差异有显著性意义（P值分别P＜0.05、P＜0.01、P＜0.01）;7周龄听觉剥夺组幼鼠每天逃避潜伏期均较同龄正常鼠延长,差异有显著性意义（P值分别P＜0.05、P＜0.01、P＜0.01、P＜0.01）。②空间探索实验：生后3周龄幼鼠听觉剥夺组及对照组在目标象限游泳时间及跨越平台次数差异无显著性意义（P＞0.05）;5周龄、7周龄听觉剥夺组在目标象限的游泳时间均短于正常对照组（P＜0.05、P＜0.01）,跨越平台次数较对照组减少,差异均有显著性意义（P值均＜0.05）。③对照组神经元形态完整,结构清晰,细胞器丰富;突触丰富,突触前膜、后膜结构及突触间隙清晰,突触囊泡多。听觉剥夺组神经元肿胀,细胞器明显减少;突触囊泡数量减少,突触前、后膜结构模糊不清,突触间隙融合。 结论：听觉剥夺幼鼠学习记忆能力下降,并与听皮质神经元及突触超微结构改变密切相关。     

Amygdala modulation of parahippocampal and frontal regions during emotionally influenced memory storage

Considerable evidence from both animal and human subject research supports the hypothesis that the amygdala, when activated by emotional arousal, modulates memory storage processes in other brain regions. By this hypothesis, changes in the functional interactions of the amygdala with other brain regions during emotional conditions should underlie, at least in part, enhanced memory for emotional material. Here we examined the influence of the human amygdala on other brain regions under emotional and nonemotional learning conditions using structural equation modeling (SEqM). Eleven male subjects received two PET scans for regional cerebral glucose metabolism-one scan while viewing a series of emotionally provocative (negative) film clips and a second scan while viewing a series of more emotionally neutral film clips. Enhanced activity in the right amygdala was related to enhanced memory for the emotional films. To identify potential candidate voxels for SEqM, the functional connectivity of the maximally activated voxel within the right amygdala was investigated using partial least squares. A subset of regions identified by this analysis showing differences functional connectivity with the amygdala between the emotional versus neutral film conditions were then submitted to SEqM, which revealed significantly increased amygdala influences on the ipsilateral parahippocampal gyrus and ventrolateral prefrontal cortex during the emotional relative to the neutral film viewing condition. These findings support the view that increased influences from the amygdala, presumably reflecting its memory-modulation function, occur during emotionally arousing learning situations.     

Cortical and limbic activation during viewing of high- versus low-calorie foods

Despite the high prevalence of obesity, eating disorders, and weight-related health problems in modernized cultures, the neural systems regulating human feeding remain poorly understood. Therefore, we applied functional magnetic resonance imaging (fMRI) to study the cerebral responses of 13 healthy normal-weight adult women as they viewed color photographs of food. The motivational salience of the stimuli was manipulated by presenting images from three categories: high-calorie foods, low-calorie foods, and nonedible dining-related utensils. Both food categories were associated with bilateral activation of the amygdala and ventromedial prefrontal cortex. High-calorie foods yielded significant activation within the medial and dorsolateral prefrontal cortex, thalamus, hypothalamus, corpus callosum, and cerebellum. Low-calorie foods yielded smaller regions of focal activation within medial orbitofrontal cortex; primary gustatory/somatosensory cortex; and superior, middle, and medial temporal regions. Findings suggest that the amygdala may be responsive to a general category of biologically relevant stimuli such as food, whereas separate ventromedial prefrontal systems may be activated depending on the perceived reward value or motivational salience of food stimuli.