Prefrontal Contributions to Executive Control: fMRI Evidence for Functional Distinctions within Lateral Prefrontal Cortex

The prefrontal cortex (PFC) plays a fundamental role in internally guided behavior. Although it is generally accepted that PFC subserves working memory and executive control operations, it remains unclear whether the subregions within lateral PFC support distinct executive control processes. An event-related fMRI study was implemented to test the hypothesis that ventrolateral and dorsolateral PFC are functionally distinct, as well as to assess whether functional specialization exists within ventrolateral PFC. Participants performed two executive control tasks that differed in the types of control processes required. During rote rehearsal, participants covertly rehearsed three words in the order presented, thus requiring phonological access and maintenance. During elaborative rehearsal, participants made semantic comparisons between three words held in working memory, reordering them from least to most desirable. Thus, in addition to maintenance, elaborative rehearsal required goal-relevant coding of items in working memory ("monitoring") and selection from among the items to implement their reordering. Results revealed that left posterior ventrolateral PFC was active during performance of both tasks, whereas right dorsolateral PFC was differentially engaged during elaborative rehearsal. The temporal characteristics of the hemodynamic responses further suggested that dorsolateral activation lagged ventrolateral activation. Finally, differential activation patterns were observed within left ventrolateral PFC, distinguishing between posterior and anterior regions. These data suggest that anatomically separable subregions within lateral PFC may be functionally distinct and are consistent with models that posit a hierarchical relationship between dorsolateral and ventrolateral regions such that the former monitors and selects goal-relevant representations being maintained by the latter.     

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).     

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.     

Functional network in the prefrontal cortex during episodic memory retrieval

A recent consistent finding in neuroimaging studies of human memory is that the prefrontal cortex (PFC) is activated during episodic memory retrieval. To date, however, there has been no direct evidence to explain how activity in the right and left PFC and in the anterior and posterior PFC are functionally interconnected. The goal of the present study was to obtain such evidence by event-related functional magnetic resonance imaging (MRI) and the functional connectivity method. Subjects were first asked to try to remember a series of associate-word lists outside the MRI scanner in preparation for a later recognition test. In the MRI scanning phase, they were asked to make recognition judgments in regard to old words, semantically related lure words, and unrelated new words. The analysis of functional connectivity revealed that the posterior PFC in each hemisphere had strong functional interconnections with the contralateral posterior PFC, whereas the anterior PFC in each hemisphere had only weak functional interconnections with the contralateral anterior PFC. No strong functional interconnections were found between the anterior and posterior PFC in either hemisphere. These findings support the hypothesis of an associative contribution of the bilateral posterior PFC to episodic memory retrieval and a dissociative contribution of the bilateral anterior PFC.     

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.     

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 role of the right anterior prefrontal cortex in episodic retrieval

Regional brain activity was measured with H(2) (15)O PET while participants attempted to complete word-stem and word-fragment retrieval cues with previously studied words. The retrieval cue manipulation was employed to gain control over the monitoring operations associated with evaluating the episodic status of alternative cue completions. These operations were more constrained for fragments, which had fewer possible completions than each corresponding stem. In one condition (zero target), during the scanning interval none of the cues could be completed with studied items, whereas in another condition (high target), 80% of cues belonged to studied items. Relative to baseline tasks, right anterior prefrontal activity was greater for stems than for fragments in the zero target condition. The target density manipulation did not modulate right anterior prefrontal activity, but was associated with increased activity in right dorsolateral prefrontal cortex. These findings are consistent with the proposal that the right anterior prefrontal cortex supports monitoring operations during episodic retrieval tasks. In addition, the findings add to evidence suggesting that the dorsolateral and anterior right prefrontal cortex make functionally distinct contributions to episodic retrieval.     

Neuroimaging a single thought: dorsolateral PFC activity associated with refreshing just-activated information.

Neuroimaging studies of human working memory (WM) show conflicting results regarding whether dorsolateral prefrontal cortex (PFC) contributes to maintaining information in consciousness or is recruited primarily when information must be manipulated. Using functional magnetic resonance imaging (fMRI), we looked at a minimal maintenance process--thinking back to a single, just-seen stimulus (refreshing). We found greater activity in left dorsolateral PFC (BA9) when participants refreshed a word compared to reading a word once or a second time. Furthermore, recognition memory was subsequently more accurate and faster for items that had been refreshed, demonstrating that a single thought that maintains activation can have consequences for long-term memory. Our fMRI results call into question any class of models of the functional organization of PFC and WM that associates simple and/or maintenance processes only with ventrolateral PFC or that associates dorsolateral PFC only with more complex processes such as manipulation.     

Hippocampal activations during encoding and retrieval in a verbal working memory paradigm

Though the hippocampus has been associated with encoding and retrieval processes in episodic memory, the precise nature of its involvement in working memory has yet to be determined. This functional magnetic resonance imaging (fMRI) study employed a verbal working memory paradigm that allows for the within-subject comparison of functional activations during encoding, maintenance, and retrieval. In each trial, participants were shown 5 target words and, after an 8 s delay, a series of probe words. Probe words consisted of target matches, phonetically or semantically related foils, or foils unrelated to the target words. Both the left and right hippocampi showed higher mean activation amplitudes during encoding than maintenance. In contrast, the right dorsolateral prefrontal cortex (DLPFC) showed greater activation during maintenance than encoding. Both hippocampal and DLPFC regions were more active during retrieval than maintenance. Furthermore, an analysis of retrieval activation separated by probe type showed a trend toward greater bilateral hippocampal activation for probes related (both semantically and phonetically) to the target than for unrelated probes and still greater activation for target matches. This pattern suggests that there may be roles for the hippocampus and DLPFC in working memory that change as function of information processing stage. Additionally, the trend towards increased involvement of the hippocampus with the increase in relatedness of the probe stimuli to the information maintained is interpreted to be consistent with the role of the hippocampus in recollection-based retrieval in long-term memory and may indicate that this role extends to working memory processes.     

Dorsolateral prefrontal cortex involvement in memory post-retrieval monitoring revealed in both item and associative recognition tests

Post-retrieval monitoring is a process that contributes to episodic memory retrieval by allowing people to evaluate the relevance of retrieved information in relation to the task requirements. Previous studies have suggested that post-retrieval monitoring is supported by the dorsolateral prefrontal cortex (DLPFC). In this study, we used functional magnetic resonance imaging (fMRI) to evaluate involvement of the DLPFC in post-retrieval monitoring in two different recognition tests (item recognition and associative recognition). The item recognition memory test required subjects to make old/new judgments and the associative recognition memory test required them to make intact/rearranged judgments. Because the post-retrieval monitoring demand increases during old (hits) relative to new (correct rejections) item recognition trials, and also during rearranged (correct rejections) relative to intact (hits) associative recognition trials, we evaluated the brain activation associated with the interaction of Memory test (item versus associative) by Recognition trial (hit versus correct rejection). As expected, the DLPFC was activated in this interaction as well as for both old relative to new item recognition trials and rearranged relative to intact associative recognition trials. This study provides strong evidence that DLPFC activation supports post-retrieval monitoring across different types of recognition tasks.     

Retrieval of relational information: a role for the left inferior prefrontal cortex

Neuroimaging studies have implicated different areas of prefrontal cortex and medial temporal lobe structures (MTL) in episodic retrieval tasks. However, the role of specific regions in particular aspects of episodic memory is still unclear. In this experiment we studied changes in regional cerebral blood flow (rCBF) associated with relational and nonrelational retrieval of studied pairs of words. For relational retrieval, a list of either studied or rearranged pairs was presented and subjects (n = 8) were asked to indicate whether pairs had appeared on the study list. Under the nonrelational retrieval condition they indicated whether one or both words of the pair had appeared on the study list. As compared to the baseline condition (looking at a cross-mark), increased rCBF was observed in the left inferior prefrontal cortex (LIPFC) for both studied pairs and rearranged pairs under the relational retrieval condition. Under the nonrelational condition, an increase was observed in right inferior frontal gyrus. The MTL showed a trend for increased rCBF in the rearranged-pair condition. This increase was probably associated with the encoding that accompanies retrieval of novel stimuli. Results suggest that the lateralized activation of prefrontal cortex observed in episodic memory tasks may be related to the degree of relational processing involved. The LIPFC appears to be associated with relational retrieval and the right prefrontal cortex with nonrelational retrieval.     

Probability effects on the neural correlates of retrieval success: an fMRI study

Event-related fMRI was employed to investigate the influence of the relative probability of old and new test items on the neural correlates of recognition memory. Twelve subjects undertook three study-test cycles, each consisting of an identical study phase in which a series of words was encoded in an incidental task, followed by a test phase in which yes/no recognition judgments were made to a mixture of studied (old) and unstudied (new) words. The ratio of old to new words differed in each test phase, and was either 25:75, 50:50, or 75:25. In lateral inferior and medial parietal cortex, and the posterior cingulate, greater activity was elicited by correctly classified old than new items independently of old:new ratio. By contrast, in other regions, including anterior, dorsolateral, and ventrolateral prefrontal cortex, differences in the activity elicited by old and new items varied according to old:new ratio, demonstrating in some cases a complete crossover interaction. The results suggest that differential activity elicited by old and new test items is likely to support successful recognition in only a subset of the regions identified in previous studies as exhibiting such differences. In other regions, most notably prefrontal cortex, differences in the activity elicited by old and new items appear to reflect processes that are contingent upon, rather than in support of, successful recognition.     

Neural mechanisms of semantic interference and false recognition in short-term memory

Decades of research using the Deese-Roediger-McDermott (DRM) paradigm have demonstrated that episodic memory is vulnerable to semantic distortion, and neuroimaging investigations of this phenomenon have shown dissociations between the neural mechanisms subserving true and false retrieval from long-term memory. Recently, false short-term memories have also been demonstrated, with false recognition of items related in meaning to memoranda encoded less than 5s earlier. Semantic interference is also evident in short-term memory, such that correct rejection of related lures is slowed relative to correct rejection of unrelated lures. The present research constitutes the first fMRI investigation of false recognition and semantic interference in short-term memory using a short-term DRM paradigm in which participants retained 4 semantic associates over a short 4-s filled retention interval. Results showed increased activation in the left mid-ventrolateral prefrontal cortex (BA45) associated with semantic interference, and significant correlations between these increases and behavioral measures of interference across subjects. Furthermore, increases in dorsolateral PFC occurred when related lures were correctly rejected versus falsely remembered. Compared with false recognition, true recognition was associated with increases in left fusiform gyrus, a finding consistent with the notion that increased perceptual processing may distinguish true from false recognition over both short and long retention intervals. Findings are discussed in relation to current models of interference resolution in short-term memory, and suggest that false short-term recognition occurs as a consequence of the failure of frontally mediated cognitive control processes which adjudicate semantic familiarity in support of accurate mnemonic retrieval.     

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.     

The effects of aging on material-independent and material-dependent neural correlates of contextual binding

Previous behavioral research suggests that older adults exhibit impairments in source memory across a multitude of stimuli and associated details, possibly due to a deficit in contextual binding. However, it is unclear whether this binding deficit results from alterations in processes that are material-independent, processes that are specific to particular materials, or some combination of the two. We used event-related fMRI to investigate the effect of aging on contextual binding and associated neural activity for words and objects. Behavioral data showed similar age-related deficits in source memory accuracy for both words and objects. Imaging results revealed that young and older adults recruited similar networks of regions in support of contextual binding, independent of material, including the lateral prefrontal cortex (PFC) and hippocampus. Material-dependent binding effects were also present for both groups in ventrolateral prefrontal and parahippocampal cortices for words and objects, respectively. Older adults showed smaller material-independent contextual binding effects in frontal regions, namely the left dorsolateral PFC, and larger binding effects in the hippocampus. Further, age-related declines in object processing effects in extrastriate regions correlated with poorer source accuracy for objects. Collectively, these results suggest that age-related source memory deficits may be primarily due to changes in material-independent contextual binding processes. However, these impairments may be further impacted by impoverished item representations in material-specific processing regions.     

Semantic processing of Chinese in left inferior prefrontal cortex studied with reversible words

This study utilized fast event-related fMRI with reversible words to examine the role of left inferior prefrontal cortex (PFC) in semantic processing of Chinese. As a special linguistic phenomenon in Chinese, a reversible word is a two-character word (AB) that, when read from right to left (BA), opposite to the normal left to right reading direction, is also a real word. The two words, AB and BA, can have very different meanings. Fourteen native Chinese saw a reversible word (BA) and were asked to read it backward silently to obtain the meaning of AB, defined as the target meaning. They then saw two test words and decided which of the two was semantically related to the target meaning. Activity in a subregion of BA47 was found to be modulated by the extent to which irrelevant semantic activation of the distractor word BA interfered with semantic retrieval of the target word AB. This finding demonstrated the involvement of the left inferior PFC in the control processes of semantic retrieval in Chinese. In addition, comparing conditions using reversible with that using nonreversible words, we found evidence suggesting a semantic/phonological functional subdivision in left inferior PFC, consistent with that in English.     

Parietal activation during retrieval of abstract and concrete auditory information

Successful memory retrieval has been associated with a neural circuit that involves prefrontal, precuneus, and posterior parietal regions. Specifically, these regions are active during recognition memory tests when items correctly identified as "old" are compared with items correctly identified as "new." Yet, as nearly all previous fMRI studies have used visual stimuli, it is unclear whether activations in posterior regions are specifically associated with memory retrieval or if they reflect visuospatial processing. We focus on the status of parietal activations during recognition performance by testing memory for abstract and concrete nouns presented in the auditory modality with eyes closed. Successful retrieval of both concrete and abstract words was associated with increased activation in left inferior parietal regions (BA 40), similar to those observed with visual stimuli. These results demonstrate that activations in the posterior parietal cortex during retrieval cannot be attributed to bottom-up visuospatial processes but instead have a more direct relationship to memory retrieval processes.     

Task constraints modulate activation in right ventral lateral prefrontal cortex

Lesion data suggest that right prefrontal cortex (PFC) plays a critical role in open-ended problem solving. To test this hypothesis, we scanned fifteen normal subjects with fMRI as they completed three types of anagram problems varying in the level of constraints placed on the search space. On unconstrained trials, they rearranged letters to generate solutions (e.g., Can you make a "Word with ZJAZ?"). On semantically constrained trials, they rearranged letters to generate solutions within particular semantic categories (e.g., Can you make a type of "Music with ZJAZ?"). On baseline trials, they rearranged letters to make specific words (e.g., Can you make the word "JAZZ with ZJAZ?"). As predicted, the critical comparison of unconstrained vs. semantically constrained trials revealed significant activation in right ventral lateral PFC, as well as left superior frontal gyrus, frontopolar cortex, right superior parietal lobe, right post central gyrus, and the occipital-parietal sulcus. Furthermore, activation in right ventral lateral PFC (BA 47) increased as the constraints placed on the anagram search space were reduced. We argue that the activation in right ventral lateral PFC is related to hypothesis generation in unconstrained settings, whereas activation in other structures is related to additional processes linked to anagram problems such as semantic retrieval, semantic categorization, and cognitive monitoring. These results extend the lesion data and imaging studies by demonstrating that a relative absence of constraints on the solution space is sufficient to engage right ventral lateral PFC in hypothesis generation tasks.     

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.     

A systematic investigation of the functional neuroanatomy of auditory and visual phonological processing

Neuroimaging studies of auditory and visual phonological processing have revealed activation of the left inferior and middle frontal gyri. However, because of task differences in these studies (e.g., consonant discrimination versus rhyming), the extent to which this frontal activity is due to modality-specific linguistic processes or to more general task demands involved in the comparison and storage of stimuli remains unclear. An fMRI experiment investigated the functional neuroanatomical basis of phonological processing in discrimination and rhyming tasks across auditory and visual modalities. Participants made either "same/different" judgments on the final consonant or rhyme judgments on auditorily or visually presented pairs of words and pseudowords. Control tasks included "same/different" judgments on pairs of single tones or false fonts and on the final member in pairs of sequences of tones or false fonts. Although some regions produced expected modality-specific activation (i.e., left superior temporal gyrus in auditory tasks, and right lingual gyrus in visual tasks), several regions were active across modalities and tasks, including posterior inferior frontal gyrus (BA 44). Greater articulatory recoding demands for processing of pseudowords resulted in increased activation for pseudowords relative to other conditions in this frontal region. Task-specific frontal activation was observed for auditory pseudoword final consonant discrimination, likely due to increased working memory demands of selection (ventrolateral prefrontal cortex) and monitoring (mid-dorsolateral prefrontal cortex). Thus, the current study provides a systematic comparison of phonological tasks across modalities, with patterns of activation corresponding to the cognitive demands of performing phonological judgments on spoken and written stimuli.