The role of frontopolar cortex in subgoal processing during working memory

Neuroimaging studies have implicated the anterior-most or frontopolar regions of prefrontal cortex (FP-PFC, e.g., Brodmann's Area 10) as playing a central role in higher cognitive functions such as planning, problem solving, reasoning, and episodic memory retrieval. The current functional magnetic resonance imaging (fMRI) study tested the hypothesis that FP-PFC subserves processes related to the monitoring and management of subgoals, while maintaining information in working memory (WM). Subjects were scanned while performing two variants of a simple delayed response WM task. In the control WM condition, subjects monitored for the presence of a specific concrete probe word (LIME) occurring following a specific abstract cue word (FATE). In the subgoal WM condition, subjects monitored for the presence of any concrete probe word immediately following any abstract cue word. Thus, the task required semantic classification of the probe word (the subgoal task), while the cue was simultaneously maintained in WM, so that both pieces of information could be integrated into a target determination. In a second control condition, subjects performed abstract/concrete semantic classification without WM demands. A region within right FP-PFC was identified which showed significant activation during the subgoal WM condition, but no activity in either of the two control conditions. However, this FP-PFC region was not modulated by direct manipulation of active maintenance demands. In contrast, left dorsolateral PFC was affected by active maintenance demands, but the effect did not interact with the presence of a subgoal task. Finally, left ventral PFC regions showed activation in response to semantic classification, but were not affected by WM demands. These results suggest a triple dissociation of function within PFC regions, and further indicate that FP-PFC is selectively engaged by the requirement to monitor and integrate subgoals during WM tasks.     

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.     

Working memory component processes: Isolating BOLD signal changes

The chronology of the component processes subserving working memory (WM) and hemodynamic response lags has hindered the use of fMRI for exploring neural substrates of WM. In the present study, however, participants completed full trials that involved encoding two or six letters, maintaining the memory set over a delay, and then deciding whether a probe was in the memory set or not. Additionally, they completed encode-only, encode-and-maintain, and encode-and-decide partial trials intermixed with the full trials. The inclusion of partial trials allowed for the isolation of BOLD signal changes to the different trial periods. The results showed that only lateral and medial prefrontal cortex regions differentially responded to the 2- and 6-letter memory sets over the trial periods, showing greater activation to 6-letter sets during the encode and maintain trial periods. Thus, the data showed the differential involvement of PFC in the encoding and maintenance of supra- and sub-capacity memory sets and show the efficacy of using fMRI partial trial methods to study WM component processes.     

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.     

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.     

Maintenance versus manipulation in verbal working memory revisited: an fMRI study

Working memory (WM) is the ability to keep a limited amount of information "on line" for immediate use during short intervals. Verbal WM has been hypothesized to consist of neuroanatomically segregated components, i.e., maintenance (storage, rehearsal, and matching) and manipulation (reordering or updating), corresponding to ventrolateral and dorsolateral prefrontal cortex. Previous imaging studies of maintenance vs manipulation processes in WM have produced inconsistent results, which may have been due to methodological issues such as low statistical power and the use of insertion (subtraction) designs. In the present functional magnetic resonance imaging study we used parametric versions of both a prototypical maintenance task (Sternberg) and a prototypical manipulation task (n-letter back task) in 21 healthy subjects. Increased signal correlated with load common for both tasks was found in bilateral dorsolateral and anterior prefrontal, left ventrolateral prefrontal, and bilateral parietal regions. Workload x task interactions were found in bilateral dorsolateral prefrontal cortex for manipulation vs maintenance, but also for responding vs encoding (storage) in the maintenance task. Therefore, our data support a functional rather than a neuroanatomical distinction between maintenance and manipulation, given our finding that these tasks differentially activate virtually identical systems.     

Age-related changes in neural activity during performance matched working memory manipulation

A long-standing assumption in the cognitive aging literature is that performance on working memory (WM) tasks involving serial recall is relatively unaffected by aging, whereas tasks that require the rearrangement of items prior to recall are more age-sensitive. Previous neuroimaging studies of WM have found age-related increases in neural activity in frontoparietal brain regions during simple maintenance tasks, but few have examined whether there are age-related differences that are specific to rearranging WM items. In the current study, older and younger adults' brain activity was monitored using functional magnetic resonance imaging (fMRI) as they performed WM tasks involving either maintenance or manipulation (letter–number sequencing). The paradigm was developed so that performance was equivalent across age groups in both tasks, and the manipulation condition was not more difficult than the maintenance condition. In younger adults, manipulation-related increases in activation occurred within a very focal set of regions within the canonical brain WM network, including left posterior prefrontal cortex and bilateral inferior parietal cortex. In contrast, older adults showed a much wider extent of manipulation-related activation within this WM network, with significantly increased activity relative to younger adults found within bilateral PFC. The results suggest that activation and age-differences in lateral PFC engagement during WM manipulation conditions may reflect strategy use and controlled processing demands rather than reflect the act of manipulation per se.     

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.     

Cortical capacity constraints for visual working memory: dissociation of fMRI load effects in a fronto-parietal network

Working memory (WM) capacity limitations and their neurophysiological correlates are of special relevance for the understanding of higher cognitive functions. Evidence from behavioral studies suggests that restricted attentional resources contribute to these capacity limitations. In an event-related functional magnetic resonance imaging (fMRI) study, we probed the capacity of the human visual WM system for up to four complex nonnatural objects using a delayed discrimination task. A number of prefrontal and parietal areas bilaterally showed increased blood oxygen level-dependent activity, relative to baseline, throughout the task when more than one object had to be held in memory. Monotonic increases in response to memory load were observed bilaterally in the dorsolateral prefrontal cortex (DLPFC) and the presupplementary motor area (pre-SMA). Conversely, activity in the frontal eye fields (FEFs) and in areas along the intraparietal sulcus (IPS) peaked when subjects had to maintain only two or three objects and decreased in the highest load condition. This dissociation of memory load effects on cortical activity suggests that the cognitive operations subserved by the IPS and FEF, which are most likely related to attention, fail to support visual WM when the capacity limit is approached. The correlation of brain activity with performance implies that only the operations performed by the DLPFC and pre-SMA, which support an integrated representation of visual information, helped subjects to maintain a reasonable level of performance in the highest load condition. These results indicate that at least two distinct cortical subsystems are recruited for visual WM, and that their interplay changes when the capacity limit is reached.     

A face to remember: emotional expression modulates prefrontal activity during memory formation

Emotion can exert a modulatory role on episodic memory. Several studies have shown that negative stimuli (e.g., words, pictures) are better remembered than neutral ones. Although facial expressions are powerful emotional stimuli and have been shown to influence perception and attention processes, little is known about their effect on memory. We used functional magnetic resonance imaging (fMRI) in humans to investigate the effects of expression (happy, neutral, and fearful) on prefrontal cortex (PFC) activity during the encoding of faces, using a subsequent memory effect paradigm. Our results show that activity in right PFC predicted memory for faces, regardless of expression, while a homotopic region in the left hemisphere was associated with successful encoding only for faces with an emotional expression. These findings are consistent with the proposed role of right dorsolateral PFC in successful encoding of nonverbal material, but also suggest that left DLPFC may be a site where integration of memory and emotional processes occurs. This study sheds new light on the current controversy regarding the hemispheric lateralization of PFC in memory encoding.     

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.     

A functional neuroimaging study of motivation and executive function

Executive functions, such as working memory, must intersect with functions that determine value for the organism. Functional imaging work in humans and single-unit recordings in non-human primates provide evidence that PFC might integrate motivational context with working memory. With functional magnetic resonance imaging (fMRI), we addressed the question of motivation and working memory, using a trial-related design in an object-working memory task. The design permitted the analysis of BOLD signal at separate stages, corresponding to encoding, maintenance, and retrieval. Subjects were motivated by a financial incentive during the task, such that they could gain a high or a low reward. The two different levels of reward also entailed greater or lesser risk of losing money for incorrect responses. In the high, relative to the low, reward condition, subjects shifted response bias, and showed a trend to greater sensitivity. We found main effects in fMRI BOLD signal for reward, which overlapped with BOLD effects for maintenance of information, in the right superior frontal sulcus and bilateral intraparietal sulcus. We also found an interaction between reward and retrieval from working memory in the right dorsolateral prefrontal cortex. Main effects of load and reward occurred in adjacent regions of the ventrolateral PFC during retrieval. The data demonstrate that when subjects perform a simple working memory task, financial incentives motivate performance and interact with some of the same neural networks that process various stages of working memory. Areas of overlap and interaction may integrate information about value, or they may represent a general effect of motivation increasing neural effort.     

Neural system for updating object working memory from different sources: sensory stimuli or long-term memory

Working memory (WM) is the active maintenance of currently relevant information so that it is available for use. A crucial component of WM is the ability to update the contents when new information becomes more relevant than previously maintained information. New information can come from different sources, including from sensory stimuli (SS) or from long-term memory (LTM). Updating WM may involve a single neural system regardless of source, distinct systems for each source, or a common network with additional regions involved specifically in sensory or LTM processes. The current series of experiments indicates that a single fronto-parietal network (including supplementary motor area, parietal, left inferior frontal junction, middle frontal gyrus) is active in updating WM regardless of the source of information. Bilateral cuneus was more active during updating WM from LTM than updating from SS, but the activity in this region was attributable to recalling information from LTM regardless of whether that information was to be entered into WM for future use or not. No regions were found to be more active during updating from SS than updating from LTM. Functional connectivity analysis revealed that different regions within this common update network were differentially more correlated with visual processing regions when participants updated from SS, and more correlated with LTM processing regions when participants updated from the contents of LTM. These results suggest that a single neural mechanism is responsible for controlling the contents of WM regardless of whether that information originates from a sensory stimulus or from LTM. This network of regions involved in updating WM interacts with the rest of the brain differently depending on the source of newly relevant information.     

Working memory effects on semantic processing: priming differences in pars orbitalis

Both working memory (WM) and controlled (attention-mediated) semantic processing functions have been thought to operate as limited capacity systems, but the possible link between these processes has not been investigated. We found that increased WM load attenuated semantic priming (i.e., reduced the response time advantage for semantically primed relative to unprimed items) and changed fMRI signal intensities in brain regions usually associated with both WM (dorsolateral prefrontal cortex) and controlled semantic retrieval (inferior frontal gyrus [IFG], pars orbitalis). fMRI signal changes in dorsolateral prefrontal cortex were negatively correlated with signal changes in pars orbitalis. The findings suggest that controlled semantic processing and working memory share neural system resources.     

Quantification of serotonin transporter availability with [11C]MADAM--a comparison between the ECAT HRRT and HR systems

The five-factor model organizes personality traits into five factors: Neuroticism, Extraversion, Openness to Experience, Agreeableness, and Conscientiousness. Measures of these personality traits predict people's behaviors and important outcomes of their lives. Therefore, understanding the neural correlates of these personality traits is important. This study assessed the relationships between white matter (WM) integrity and personality traits among 51 healthy participants using diffusion tensor imaging (DTI) and the revised NEO Personality Inventory (NEO-PI-R). Neuroticism correlated positively while Openness and Agreeableness correlated negatively with DTI mean diffusivity (MD) in the corona radiata and superior longitudinal fasciculus, tracts that interconnect prefrontal cortex (PFC), parietal cortex, and subcortical structures. Furthermore, Neuroticism correlated positively with MD in the anterior cingulum and uncinate fasciculus, tracts interconnecting PFC and amygdala. Openness correlated negatively with MD of WM adjacent to the dorsolateral PFC in both hemispheres. These findings suggest that greater Neuroticism associates with worse integrity of WM interconnecting extensive cortical and subcortical structures including the PFC and amygdala and that greater Openness associates with better integrity of WM interconnecting extensive cortical and subcortical structures including the dorsolateral PFC.     

"Sculpting the response space"--an account of left prefrontal activation at encoding

Left lateral prefrontal cortex (PFC) is consistently activated in neuroimaging studies of memory encoding. Its role, however, remains unclear. We describe two functional magnetic resonance imaging (fMRI) studies addressing this question. In the first we used a blocked experimental design to explore the effect of repeated encoding of word paired associates. Initial presentation of word pairs was associated with left ventrolateral PFC activation that attenuated with subsequent presentations of the same lists. When well-learned lists were presented with word pairs rearranged, a left PFC activation, greater than that associated with the initial presentation, was observed. In a second experiment, the formation of these associative relationships was explored using an event-related design. Two types of word pairs were presented: closely related (e.g., King...Queen) and distantly related (e.g., Net...Ship). The same region of left PFC was differentially sensitive to these two event-types, showing a greater response for distantly related pairs. We suggest that left PFC activity, at memory encoding, reflects operations necessary to the formation of meaningful associations in the service of optimal learning. A crucial feature of such associative processing lies in selecting appropriate, and inhibiting inappropriate, semantic attributes of the study material.     

Identifying regional activity associated with temporally separated components of working memory using event-related functional MRI

This study describes the neural circuitry underlying temporally separated components of working memory (WM) performance-stimulus encoding, maintenance of information during a delay, and the response to a probe. While other studies have applied event-related fMRI to separate epochs of WM tasks, this study differs in that it employs a methodology that does not make any a priori assumptions about the shape of the hemodynamic response (HDR). This is important because no one model of the HDR is valid across the range of activated brain regions and stimulus types. Systematic modeling inaccuracies may lead to the misattribution of activity to adjacent events. Twelve healthy subjects performed a numerical version of the Sternberg Item Recognition Paradigm adapted for rapid presentation event-related fMRI. This paradigm emphasized maintenance rather than manipulative WM processes and used a subcapacity WM load. WM trials with different delay lengths were compared to fixation. The HDR of the entire WM trial for each trial type was estimated using a finite impulse response (FIR). Regional activity associated with the Encode, Delay, and Probe epochs was identified using contrasts that were based on the FIR estimates and by examining the HDRs. Each epoch was associated with a distinct but overlapping pattern of regional activity. Activation of the dorsolateral prefrontal cortex, thalamus, and basal ganglia was exclusively associated with the probe. This suggests that frontostriatal neural circuitry participates in selecting an appropriate response based on the contents of WM.     

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.     

Dissociable effects of arousal and valence on prefrontal activity indexing emotional evaluation and subsequent memory: an event-related fMRI study

Prefrontal cortex (PFC) activity associated with emotional evaluation and subsequent memory was investigated with event-related functional MRI (fMRI). Participants were scanned while rating the pleasantness of emotionally positive, negative, and neutral pictures, and memory for the pictures was tested after scanning. Emotional evaluation was measured by comparing activity during the picture rating task relative to baseline, and successful encoding was measured by comparing activity for subsequently remembered versus forgotten pictures (Dm effect). The effect of arousal on these measures was indicated by greater activity for both positive and negative pictures than for neutral ones, and the effect of valence was indicated by differences in activity between positive and negative pictures. The study yielded three main results. First, consistent with the valence hypothesis, specific regions in left dorsolateral PFC were more activated for positive than for negative picture evaluation, whereas regions in right ventrolateral PFC showed the converse pattern. Second, dorsomedial PFC activity was sensitive to emotional arousal, whereas ventromedial PFC activity was sensitive to positive valence, consistent with evidence linking these regions, respectively, to emotional processing and self-awareness or appetitive behavior. Finally, successful encoding (Dm) activity in left ventrolateral and dorsolateral PFC was greater for arousing than for neutral pictures. This finding suggests that the enhancing effect of emotion on memory formation is partly due to an augmentation of PFC-mediated strategic, semantic, and working memory operations. These results underscore the critical role of PFC in emotional evaluation and memory, and disentangle the effects of arousal and valence across PFC regions associated with different cognitive functions.     

Spatiotemporal characteristics of hemodynamic changes in the human lateral prefrontal cortex during working memory tasks

The prefrontal cortex (PFC) is widely believed to subserve mental manipulation and monitoring processes ascribed to the central executive (CE) of working memory (WM). We attempted to examine and localize the CE by functional imaging of the frontal cortex during tasks designed to require the CE. Using near-infrared spectroscopy, we studied the spatiotemporal dynamics of oxygenated hemoglobin (oxy-Hb), an indicator of changes in regional cerebral blood flow, in both sides of lateral PFC during WM intensive tasks. In most participants, increases in oxy-Hb were localized within one subdivison during performance of the n-back task, whereas oxy-Hb increased more diffusely during the random number generation (RNG) task. Activation of the ventrolateral PFC (VLPFC) was prominent in the n-back task; both sustained and transient dynamics were observed. Transient dynamics means that oxy-Hb first increases but then decreases to less than 50% of the peak value or below the baseline level before the end of the task. For the RNG task sustained activity was also observed in the dorsolateral PFC (DLPFC), especially in the right hemisphere. However, details of patterns of activation varied across participants: subdivisions commonly activated during performance of the two tasks were the bilateral VLPFCs, either side of the VLPFC, and either side of the DLPFC in 4, 2, and 4 of the 12 participants, respectively. The remaining 2 of the 12 participants had no regions commonly activated by these tasks. These results suggest that although the PFC is implicated in the CE, there is no stereotyped anatomical PFC substrate for the CE.