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.     

Hemispheric Activation of Anterior and Inferior Prefrontal Cortex during Verbal Encoding and Recognition: A PET Study of Healthy Volunteers

Evidence of bilateral prefrontal activation during memory encoding and retrieval has increased attention given to anatomical subdivisions within the prefrontal cortex. The current study examined anterior and inferior aspects of the prefrontal cortex to determine their degree of functional and hemispheric overlap during encoding and recognition. Cerebral blood flow of 25 healthy volunteers was measured using PET ¹⁵O-water methods during four conditions: resting baseline, sequential finger movement, word encoding, and word recognition. Resting and motor images were averaged to provide a single reference that was subtracted from encoding and recognition using statistical parametric mapping (SPM96). Memory conditions were also subtracted from each other to identify differences in regional activity. Subjects performed well (86% correct) and had a slightly conservative response bias. Baseline subtraction from encoding revealed focal activation of left inferior prefrontal cortex (area 45) without significant contralateral activation. Recognition minus baseline subtraction produced a focal right anterior prefrontal activation (areas 9 and 10) that was not present in the left hemisphere. Bilateral effects were seen in area 45 during recognition. Subtraction of memory tasks from each other did not reveal any areas of greater activity during encoding. However, the recognition task produced greater activation in right area 9 extending into the anterior cingulate. Greater activity during recognition was also observed in left insula and bilateral visual integration areas. These results are discussed in relation to the prevailing model of prefrontal hemispheric asymmetry during episodic memory.     

A common functional brain network for autobiographical, episodic, and semantic memory retrieval

The objective of this study was to delineate a common functional network that underlies autobiographical, episodic, and semantic memory retrieval. We conducted an event-related fMRI study in which we utilized the same pictorial stimuli, but manipulated retrieval demands to extract autobiographical, episodic, or semantic memories. To assess this common network, we first examined the functional connectivity of regions identified by a previous analysis of task-related activity that were active across all three tasks. Three of these regions (left hippocampus, left lingual gyrus, and right caudate nucleus) appeared to share a common pattern of connectivity. This was confirmed in a subsequent functional connectivity analysis using these three regions as seeds. The results of this analysis showed that there was a pattern of functional connectivity that characterized all three seeds and that was common across the three retrieval conditions. Activity in inferior frontal and middle temporal cortex bilaterally, left temporoparietal junction, and anterior and posterior cingulate gyri was positively correlated with the seeds, whereas activity in posterior occipito-temporo-parietal regions was negatively correlated. These findings support the idea that a common neural network underlies the retrieval of declarative memories regardless of memory content. This proposed network consists of increased activity in regions that represent internal processes of memory retrieval and decreased activity in regions that mediate attention to external stimuli.     

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.     

Parahippocampal Activation during Successful Recognition of Words: A Self-Paced Event-Related fMRI Study

In this study, we investigated retrieval from verbal episodic memory using a self-paced event-related fMRI paradigm, similar to the designs typically used in behavioral studies of memory function. We tested the hypothesis that the medial temporal lobe (MTL) is involved in the actual recovery of verbal information (retrieval success) rather than in the attempt to retrieve information (retrieval attempt). To this end, we used a verbal recognition task, distinguishing correctly recognized words, correctly rejected words, and a low-level baseline condition. Directly contrasting correct recognition with correct rejection of words, we found activation in the left fusiform/parahippocampal gyrus, indicating that this region has a distinct role in the successful retrieval of verbal information. Furthermore, our results were in agreement with those of previous imaging studies that compared a fixed-paced verbal recognition task to a baseline condition, showing activation in bilateral inferior frontal cortex, left dorsolateral prefrontal cortex, left anterior insular cortex, and anterior cingulate. This demonstrates the applicability of a self-paced event-related design within imaging studies of memory function.     

The effect of word concreteness on recognition memory

Concrete words that are readily imagined are better remembered than abstract words. Theoretical explanations for this effect either claim a dual coding of concrete words in the form of both a verbal and a sensory code (dual-coding theory), or a more accessible semantic network for concrete words than for abstract words (context-availability theory). However, the neural mechanisms of improved memory for concrete versus abstract words are poorly understood. Here, we investigated the processing of concrete and abstract words during encoding and retrieval in a recognition memory task using event-related functional magnetic resonance imaging (fMRI). As predicted, memory performance was significantly better for concrete words than for abstract words. Abstract words elicited stronger activations of the left inferior frontal cortex both during encoding and recognition than did concrete words. Stronger activation of this area was also associated with successful encoding for both abstract and concrete words. Concrete words elicited stronger activations bilaterally in the posterior inferior parietal lobe during recognition. The left parietal activation was associated with correct identification of old stimuli. The anterior precuneus, left cerebellar hemisphere and the posterior and anterior cingulate cortex showed activations both for successful recognition of concrete words and for online processing of concrete words during encoding. Additionally, we observed a correlation across subjects between brain activity in the left anterior fusiform gyrus and hippocampus during recognition of learned words and the strength of the concreteness effect. These findings support the idea of specific brain processes for concrete words, which are reactivated during successful recognition.     

Incidental effects of emotional valence in single word processing: an fMRI study

The present study aimed at identifying the neural responses associated with the incidental processing of the emotional valence of single words using event-related functional magnetic resonance imaging (fMRI). Twenty right-handed participants performed a visual lexical decision task, discriminating between nouns and orthographically and phonologically legal nonwords. Positive, neutral and negative word categories were matched for frequency, number and frequency of orthographic neighbors, number of letters and imageability. Response times and accuracy data differed significantly between positive and neutral, and positive and negative words respectively, thus, replicating the findings of a pilot study. Words showed distributed, mainly left hemisphere activations, indicating involvement of a neural network responsible for semantic word knowledge. The neuroimaging data further revealed areas in left orbitofrontal gyrus and bilateral inferior frontal gyrus with greater activation to emotional than to neutral words. These brain regions are known to be involved in processing semantic and emotional information. Furthermore, distinct activations associated with positive words were observed in bilateral middle temporal and superior frontal gyrus, known to support semantic retrieval, and a distributed network, namely anterior and posterior cingulate gyrus, lingual gyrus and hippocampus when comparing positive and negative words. The latter areas were previously associated with explicit and not incidental processing of the emotional meaning of words and emotional memory retrieval. Thus, the results are discussed in relation to models of processing semantic and episodic emotional information.     

遗忘型轻度认知障碍患者默认网络改变:基于后扣带回的脑连接研究

目的 探讨遗忘型轻度认知障碍(aMCI)患者后扣带回(PCC)功能连接的变化。 方法 选取性别、年龄和教育程度相匹配的18例aMCI患者(aMCI组)和20名健康老年人(健康老年组)进行GRE-EPI序列的静息状态fMRI检查,以PCC作为种子点,与全脑其他区域进行基于体素的时间序列相关分析。 结果 aMCI组与PCC有显著连接的脑区包括双侧背外侧前额叶(DLPFC)、左侧内侧前额叶(MPFC)及左侧前扣带回(ACC)、双侧顶下小叶(IPL)、双侧颞中回和双侧楔前叶。健康老年组与PCC有显著连接的脑区包括双侧DLPFC、右侧MPFC及ACC、双侧IPL、双侧颞中回、双侧颞下回和双侧楔前叶。健康老年组较aMCI组在右侧额上回、额中回、额下回的盖部及三角部、MPFC及ACC、颞中回及左侧楔前叶连接增强;aMCI组多个脑区功能连接较健康老年组增强,主要包括左侧半球的扣带回中部、顶上小叶(SPL)、IPL、颞中回及右侧IPL。 结论 PCC是aMCI患者脑代谢最先降低的区域,aMCI的PCC与多个功能区的连接破坏是其情节记忆功能减退的生物学基础,而其连接增强提示功能代偿可能。     

The role of precuneus and left inferior frontal cortex during source memory episodic retrieval

The posterior medial parietal cortex and left prefrontal cortex (PFC) have both been implicated in the recollection of past episodes. In a previous study, we found the posterior precuneus and left lateral inferior frontal cortex to be activated during episodic source memory retrieval. This study further examines the role of posterior precuneal and left prefrontal activation during episodic source memory retrieval using a similar source memory paradigm but with longer latency between encoding and retrieval. Our results suggest that both the precuneus and the left inferior PFC are important for regeneration of rich episodic contextual associations and that the precuneus activates in tandem with the left inferior PFC during correct source retrieval. Further, results suggest that the left ventro-lateral frontal region/frontal operculum is involved in searching for task-relevant information (BA 47) and subsequent monitoring or scrutiny (BA 44/45) while regions in the dorsal inferior frontal cortex are important for information selection (BA 45/46).     

Similarities and differences in the neural correlates of episodic memory retrieval and working memory

Functional neuroimaging studies have shown that different cognitive functions activate overlapping brain regions. An activation overlap may occur because a region is involved in operations tapped by different cognitive functions or because the activated area comprises subregions differentially involved in each of the functions. To investigate these issues, we directly compared brain activity during episodic retrieval (ER) and working memory (WM) using event-related functional MRI (fMRI). ER was investigated with a word recognition test, and WM was investigated with a word delayed-response test. Two-phase trials distinguished between retrieval mode and cue-specific aspects of ER, as well as between encoding/maintenance and retrieval aspects of WM. The results revealed a common fronto-parieto-cerebellar network for ER and WM, as well as subregions differentially involved in each function. Specifically, there were two main findings. First, the results differentiated common and specific subregions within the prefrontal cortex: (i) left dorsolateral areas were recruited by both functions, possibly reflecting monitoring operations; (ii) bilateral anterior and ventrolateral areas were more activated during ER than during WM, possibly reflecting retrieval mode and cue-specific ER operations, respectively; and (iii) left posterior/ventral (Broca's area) and bilateral posterior/dorsal areas were more activated during WM than during ER, possibly reflecting phonological and generic WM operations, respectively. Second, hippocampal and parahippocampal regions were activated not only for ER but also for WM. This result suggests that indexing operations mediated by the medial temporal lobes apply to both long-term and short-term memory traces. Overall, our results show that direct cross-function comparisons are critical to understand the role of different brain regions in various cognitive functions.     

The representation of social interaction in episodic memory: a functional MRI study

The representation of social interaction in episodic memory is a critical factor for the successful navigation of social relationships. In general, it is important to separate episodic memory during social interaction from episodic memory during the self-generation of action events. Different cortical representations have been associated with social interaction vs. self-generated episodic memory. Here we clarified the cortical representation of the effect of context (social vs. solitary) on episodic memory by comparing it with the generation effect (self vs. other) on episodic memory. Each participant learned words while engaged in a sentence generation and a reading task, and subsequently each participant was scanned with functional magnetic resonance imaging (fMRI) while they performed a recognition task using the words that had been learned. The experiment was comprised of four conditions and we looked at two situations that involved a social context and non-social (solitary) context task. In the learning session before entering the MRI, two participants collaborated in a social context either generating (social-contextual self-generation condition: SS) or reading (social-contextual other-generation condition: SO) a sequence of sentences alternately to construct a meaningful story narrative. In the non-social context, the participants generated (non-social-contextual self-generation condition: NS) or read (non-social-contextual other-generation condition: NO) a sequence of sentences individually. The stimuli for the recognition session consisted of learned words and novel words. Activation for social context retrieval was identified in the right medial prefrontal cortex (mPFC), and activation for self-generated retrieval was identified in the left mPFC and the left middle cingulate cortex. These results indicate that dissociable regions within the medial prefrontal cortices contribute to the processes involved in the representation of social interaction, including social context and self-generation in the retrieval of episodic memory.     

Cerebellar contributions to episodic memory encoding as revealed by fMRI

Event-related functional Magnetic Resonance Imaging (fMRI) allows for the comparison of hemodynamic responses evoked by items that are remembered in a subsequent memory task vs. items that are forgotten. In this way, brain regions that assumingly contribute to successful memory encoding have been identified, including the left inferior prefrontal cortex (LIPC) and the medial temporal lobe. Although a cerebellar involvement in verbal working memory is well-established, a contribution of the cerebellum to episodic long-term encoding has only sporadically been described, and mechanisms underlying cerebellar memory effects are unclear. We conducted a typical incidental verbal memory fMRI experiment with three different encoding tasks varying the depth of semantic processing. Slice positioning allowed for the coverage of the entire cerebellum. We observed a significant subsequent memory effect within the superior and posterior right cerebellar hemisphere that was task independent. Additionally, we found a different area within the superior right cerebellum displaying a memory effect specifically for semantically processed words and a bilateral cerebellar activation specifically associated with encoding success only for a non-semantic task. Our results suggest that besides its known role in verbal working memory, the cerebellum contributes to episodic long-term encoding and should therefore be considered in future fMRI studies dealing with episodic memory.     

Dynamic neural networks supporting memory retrieval

How do separate neural networks interact to support complex cognitive processes such as remembrance of the personal past? Autobiographical memory (AM) retrieval recruits a consistent pattern of activation that potentially comprises multiple neural networks. However, it is unclear how such large-scale neural networks interact and are modulated by properties of the memory retrieval process. In the present functional MRI (fMRI) study, we combined independent component analysis (ICA) and dynamic causal modeling (DCM) to understand the neural networks supporting AM retrieval. ICA revealed four task-related components consistent with the previous literature: 1) medial prefrontal cortex (PFC) network, associated with self-referential processes, 2) medial temporal lobe (MTL) network, associated with memory, 3) frontoparietal network, associated with strategic search, and 4) cingulooperculum network, associated with goal maintenance. DCM analysis revealed that the medial PFC network drove activation within the system, consistent with the importance of this network to AM retrieval. Additionally, memory accessibility and recollection uniquely altered connectivity between these neural networks. Recollection modulated the influence of the medial PFC on the MTL network during elaboration, suggesting that greater connectivity among subsystems of the default network supports greater re-experience. In contrast, memory accessibility modulated the influence of frontoparietal and MTL networks on the medial PFC network, suggesting that ease of retrieval involves greater fluency among the multiple networks contributing to AM. These results show the integration between neural networks supporting AM retrieval and the modulation of network connectivity by behavior.     

Abnormal insula functional network is associated with episodic memory decline in amnestic mild cognitive impairment

Abnormalities of functional connectivity in the default mode network (DMN) recently have been reported in patients with amnestic mild cognitive impairment (aMCI), Alzheimer's disease (AD) or other psychiatric diseases. As such, these abnormalities may be epiphenomena instead of playing a causal role in AD progression. To date, few studies have investigated specific brain networks, which extend beyond the DMN involved in the early AD stages, especially in aMCI. The insula is one site affected by early pathological changes in AD and is a crucial hub of the human brain networks. Currently, we explored the contribution of the insula networks to cognitive performance in aMCI patients. Thirty aMCI and 26 cognitively normal (CN) subjects participated in this study. Intrinsic connectivity of the insula networks was measured, using the resting-state functional connectivity fMRI approach. We examined the differential connectivity of insula networks between groups, and the neural correlation between the altered insula networks connectivity and the cognitive performance in aMCI patients and CN subjects, respectively. Insula subregional volumes were also investigated. AMCI subjects, when compared to CN subjects, showed significantly reduced right posterior insula volumes, cognitive deficits and disrupted intrinsic connectivity of the insula networks. Specifically, decreased intrinsic connectivity was primarily located in the frontal-parietal network and the cingulo-opercular network, including the anterior prefrontal cortex (aPFC), anterior cingulate cortex, operculum, inferior parietal cortex and precuneus. Increased intrinsic connectivity was primarily situated in the visual-auditory pathway, which included the posterior superior temporal gyrus and middle occipital gyrus. Conjunction analysis was performed; and significantly decreased intrinsic connectivity in the overlapping regions of the anterior and posterior insula networks, including the bilateral aPFC, left dorsolateral prefrontal cortex, dorsomedial prefrontal cortex, and anterior temporal pole was found. Furthermore, the disrupted intrinsic connectivity was associated with episodic memory (EM) deficits in the aMCI patients and not in the CN subjects. These findings demonstrated that the functional integration of the insula networks plays an important role in the EM process. They provided new insight into the neural mechanism underlying the memory deficits in aMCI patients.     

Neural correlates of episodic retrieval success

Episodic memory retrieval involves multiple component processes, including those that occur when information is correctly remembered (retrieval success). The present study employed rapid-presentation event-related functional MRI that allowed different trial types with short intertrial intervals to be sorted such that the hemodynamic response associated with retrieval success could be extracted. Specifically, in an old/new episodic recognition task, hit trials (correctly recognized old items) and correct rejection trials (correctly rejected new items) were directly compared. The comparison revealed a mostly left-lateralized set of brain regions. Differential activation was most robust in left lateral parietal cortex and medial parietal cortex. Additional regions of differential activation included left anterior prefrontal cortex at or near Brodmann area 10, anterior insula, thalamus, anterior cingulate cortex, frontal cortex along inferior frontal gyrus, premotor cortex, and presupplementary motor area. These results suggest that left frontal and parietal regions modulate activity based on the successful retrieval of information from episodic memory. We discuss these findings in the context of several recent investigations that provide converging results as well as prior studies that have failed to detect these changes.     

Prefrontal hemodynamic activity predicts false memory--a near-infrared spectroscopy study

Evidence from lesion studies suggests an important role of the prefrontal cortex (PFC) in the reconstructive processes of episodic memory or memory distortion. Results from functional imaging studies imply PFC involvement during the illusionary recollection of non-experienced events. Here, we used a two-channel near-infrared spectroscopy (NIRS) system and conducted real-time monitoring of PFC hemodynamics, while subjects studied word lists and subsequently recognized unstudied items (false recognition). Bilateral increases in the oxygenated hemoglobin concentration ([oxy-Hb]) were observed during false recognition compared to true recognition, and a left PFC dominant increase of [oxy-Hb] was observed during encoding phases where subjects later claimed that they recognized unstudied words. Traces of semantic processing, reflected primarily in the left PFC activity, could eventually predict whether subjects falsely recognize non-experienced events.     

Acute tryptophan depletion reduces activation in the right hippocampus during encoding in an episodic memory task

Acute tryptophan depletion (ATD), a well-recognized method to lower central serotonin levels, was used to examine the effects of lower central serotonin levels on memory function in healthy males. Functional Magnetic Resonance Imaging (fMRI) was used to examine changes in brain activation during the encoding and the retrieval phase of a visual verbal episodic memory task. ATD led to more positively rated words in the encoding phase and to poorer recognition of these positively rated words in the retrieval phase. Furthermore, encoding was accompanied by enhanced brain activation in occipital, middle and superior frontal, anterior and posterior cingulate and striatal areas. Retrieval attempt was accompanied by enhanced activation in the cuneus, inferior occipital gyrus and inferior and middle frontal areas. Retrieval success was accompanied by activation in an extensive network including frontal, parietal, temporal, cingulate, striatal and cerebellar areas. In the encoding phase ATD attenuated activation in the right hippocampus and ATD did not affect brain activity in the retrieval phase. These results show that serotonin is important in long term memory processes, and that serotonin acts on the encoding phase and not on the retrieval phase.     

The role of the prefrontal cortex in recognition memory and memory for source: an fMRI study.

We employed fMRI to index neural activity in prefrontal cortex during tests of recognition and source memory. At study, subjects were presented with words displayed either to the left or right of fixation, and, depending on the side, performed one of two orienting tasks. The test phase consisted of a sequence of three 10-word blocks, displayed in central vision. For one block, subjects performed recognition judgements on a mixture of two old and eight new words (low density recognition). For another block, recognition judgements were performed on a mixture of eight old and two new words (high density recognition). In the remaining block, also consisting of eight old and two new items, the requirement was to judge whether each word had been presented at study on the left or the right. Relative to the low density condition, high density recognition was associated with increased activity in right and, to a lesser extent, left, anterior prefrontal cortex (BA 10), replicating the findings of two previous PET studies. Right anterior prefrontal activity did not show any further increase during the source task. Instead, greater activity was found, relative to high density recognition, in left BA 10, left inferior frontal gyrus (BA 45/47), and bilateral opercular cortices (BA 45/47). The findings are inconsistent with the proposal that activation of right anterior prefrontal cortex during memory retrieval reflects "postretrieval" processing demands, such demands being considerably greater for judgments of source than recognition. The findings provide further evidence that the left prefrontal cortex plays a role in episodic memory retrieval when the task explicitly requires recovery of contextual as well as item information.     

Recognition memory for studied words is determined by cortical activation differences at encoding but not during retrieval

Prior work has shown that when responses to incidentally encoded words are sorted, subsequently remembered words elicit greater left prefrontal BOLD signal change relative to forgotten words. Similarly, low-frequency words elicit greater activation than high-frequency words in the same left prefrontal regions, contributing to their better subsequent memorability. This study examined the relative contribution of encoding and retrieval processes to the correct recognition of target words. A mixture of high- and low-frequency words was incidentally encoded. Scanning was performed at encoding as well as during retrieval. During encoding, greater activation in the left prefrontal and anterior cingulate regions predicted a higher proportion of hits for low-frequency words. However, data acquired during recognition showed that word frequency did not modulate activation in any of the areas tracking successful recognition. This result demonstrates that under some circumstances, the recognition of studied words is determined purely by processes that are active during encoding. In contrast to the finding for hits, activation associated with correctly rejected foils was modulated by word frequency, being higher for high-frequency words in the left lateral parietal and anterior prefrontal regions. These findings were replicated in two further experiments, one in which the number of test items at recognition was doubled and another where encoding strength for high-frequency words was varied (once vs. 10 times). These results indicate that word frequency modulates activity in the left lateral parietal and anterior prefrontal regions contingent on whether the item involved is correctly recognized as a target or a foil. This observation is consistent with a dual process account of episodic memory.     

汉字情景记忆时皮层定位的fMRI研究

目的探讨用功能磁共振成像(fMRI)检测汉字情景记忆时皮层定位的价值及皮层定位的双侧不对称性.方法 10名健康右利手成人,以高频双字汉字作为刺激任务,行全脑fMRI,确定激活皮层的定位.结果汉字情景记忆时双侧多个脑区有激活,但两侧激活脑区不完全对称,编码加工时主要激活脑区为左侧纹外区和左侧颞叶梭状回,而提取加工时左侧顶叶楔前叶、左侧前额叶背外侧显著激活.结论汉字情景记忆时左右大脑半球激活区存在不对称性,fMRI可对此种功能皮层进行准确定位.