Mid-ventrolateral Prefrontal Cortex Research Articles

Evidence of a Causal Role for mid-Ventrolateral Prefrontal Cortex Based Functional Networks in Retrieving High-Fidelity Memory

Functional neuroimaging studies have implicated regions of both ventrolateral prefrontal cortex (VLPFC) and angular gyrus in processes associated with retrieving goal-relevant information, which increases the fidelity and richness of long-term memory (LTM). To further investigate the roles of these cortical regions as nodes in functional networks with memory regions of the medial temporal lobe (MTL), we used fMRI-guided, 1 Hz repetitive transcranial magnetic stimulation (rTMS) to perturb normal neuronal function. The aim was to test the causal roles of left mid-VLPFC and left angular gyrus (AG) in MTL-VLPFC-parietal networks that have been associated with high-fidelity memory retrieval. rTMS treatments were administered immediately before blocks in an old/new recognition test, which was based on a mnemonic similarity task requiring discrimination of previously studied pictures of common objects. Capability for mnemonic discrimination was evaluated after each of three conditions: placebo control (rTMS at somatosensory cortex), mid-VLPFC target (rTMS at left pars triangularis) and parietal target (rTMS at left AG). The results showed the effect of rTMS perturbation of mid-VLPFC diminished subsequent discrimination-based memory performance, relative to placebo control, and no significant effect of perturbation of AG. These findings show a causal role for functional networks with left mid-VLPFC in high-fidelity retrieval.

Theta-burst modulation of mid-ventrolateral prefrontal cortex affects salience coding in the human ventral tegmental area

In the context of hedonic (over-)eating the ventral tegmental area (VTA) as a core part of the dopaminergic reward system plays a central role in coding incentive salience of high-caloric food. In the present study, we used functional magnetic resonance imaging (fMRI) to investigate whether transcranial magnetic theta-burst stimulation (TBS) over the right mid-ventrolateral prefrontal cortex (mid-VLPFC) can induce modulation of calorie-sensitive brain activation in the VTA. The prefrontal location for TBS had been predetermined by seed-based resting-state fMRI with a functionally defined portion of the VTA serving as seed region obtained from an independent second fMRI experiment. In a sample of 15 healthy male participants, modulation of calorie-sensitive VTA activation did not significantly differ between the two TBS protocols. Comparisons with baseline revealed that both TBS protocols significantly affected calorie-sensitive neural processing of the mid-VLPFC in a rather similar way. In the VTA significant modulation of calorie-sensitive activation was observed after continuous TBS, whereas the modulatory effect of intermittent TBS was less reliable but also associated with a decrease of activation for high-caloric food images. Neurostimulation of right mid-VLPFC is suggestive as a main entry point of downstream signal changes for high- and low-caloric food cues that could enforce a shift in valuating stimuli of initially different incentive salience.

Neural coupling between contralesional motor and frontoparietal networks correlates with motor ability in individuals with chronic stroke

Movement is traditionally viewed as a process that involves motor brain regions. However, movement also implicates non-motor regions such as prefrontal and parietal cortex, regions whose integrity may thus be important for motor recovery after stroke. Importantly, focal brain damage can affect neural functioning within and between distinct brain networks implicated in the damage. The aim of this study is to investigate how resting state connectivity (rs-connectivity) within and between motor and frontoparietal networks are affected post-stroke in correlation with motor outcome. Twenty-seven participants with chronic stroke with unilateral upper limb deficits underwent motor assessments and magnetic resonance imaging. Participants completed the Chedoke-McMaster Stroke Assessment as a measure of arm (CMSA-Arm) and hand (CMSA-Hand) impairment and the Action Research Arm Test (ARAT) as a measure of motor function. We used a seed-based rs-connectivity approach defining the motor (seed=contralesional primary motor cortex (M1)) and frontoparietal (seed=contralesional dorsolateral prefrontal cortex (DLPFC)) networks. We analyzed the rs-connectivity within each network (intra-network connectivity) and between both networks (inter-network connectivity), and performed correlations between: a) intra-network connectivity and motor assessment scores; b) inter-network connectivity and motor assessment scores. We found: a) Participants with high rs-connectivity within the motor network (between M1 and supplementary motor area) have higher CMSA-Hand stage (z=3.62, p=0.003) and higher ARAT score (z=3.41, p=0.02). Rs-connectivity within the motor network was not significantly correlated with CMSA-Arm stage (z=1.83, p>0.05); b) Participants with high rs-connectivity within the frontoparietal network (between DLPFC and mid-ventrolateral prefrontal cortex) have higher CMSA-Hand stage (z=3.64, p=0.01). Rs-connectivity within the frontoparietal network was not significantly correlated with CMSA-Arm stage (z=0.93, p=0.03) or ARAT score (z=2.53, p=0.05); and c) Participants with high rs-connectivity between motor and frontoparietal networks have higher CMSA-Hand stage (rs=0.54, p=0.01) and higher ARAT score (rs=0.54, p=0.009). Rs-connectivity between the motor and frontoparietal networks was not significantly correlated with CMSA-Arm stage (rs=0.34, p=0.13). Taken together, the connectivity within and between the motor and frontoparietal networks correlate with motor outcome post-stroke. The integrity of these regions may be important for an individual's motor outcome. Motor-frontoparietal connectivity may be a potential biomarker of motor recovery post-stroke.

Reduced Cortical Thickness in the Temporal Pole, Insula, and Pars Triangularis in Patients with Panic Disorder.

PurposeRecent neuroimaging findings have revealed that paralimbic and prefrontal regions are involved in panic disorder (PD). However, no imaging studies have compared differences in cortical thickness between patients with PD and healthy control (HC) subjects.Materials and MethodsForty-seven right-handed patients with PD who met the diagnostic criteria in the Diagnostic and Statistical Manual of Mental Disorders-4th edition-text revision, and 30 HC subjects were enrolled. We used the FreeSurfer software package for estimating the cortical thickness of regions of interest, including the temporal pole, insula, and pars triangularis (mid-ventrolateral prefrontal cortex).ResultsCortical thickness of the temporal pole (p=0.033, right), insula (p=0.017, left), and pars triangularis (p=0.008, left; p=0.025, right) in patients with PD was significantly lower, compared with HC subjects (Benjamini-Hochberg false discovery rate correction). Exploratory analysis revealed a significant negative correlation between the cortical thickness of the right temporal pole and Beck Depression Inventory scores (r=-0.333, p=0.027) in patients with PD and positive correlations between the cortical thickness of the left pars triangularis and Panic Disorder Severity Scale (r=0.429, p=0.004), Anxiety Sensitivity Index-Revised (r=0.380, p=0.011), and Beck Anxiety Inventory (r=0.421, p=0.004) scores using Pearson's correlation.ConclusionOurs study is the first to demonstrate cortical thickness reduction in the temporal pole, insula, and pars triangularis in patients with PD, compared with the HC subjects. These findings suggest that reduced cortical thickness could play an important role in the pathophysiology of PD.

How the brain detects invariance and inhibits variance during category induction

A stepwise category-learning task was designed to examine brain activation associated with invariance detection and variance inhibition during category induction (CI). Three stimuli were displayed sequentially and participants were asked to learn the target category based on the invariant feature among stimuli. The processes of invariance detection and variance inhibition were necessary during certain events; however, these processes were not required for other events. Functional magnetic resonance imaging (fMRI) results indicated that the processes of detecting invariant features and inhibiting variant features were associated with significant activation in the left prefrontal cortex, including the left superior frontal gyrus, middle frontal gyrus, and mid-ventrolateral prefrontal cortex, as well as other regions (e.g., bilateral parietal cortex and putamen). These findings confirmed the important role of the fronto-parietal network and striatum in the invariance detection of category learning.

Neural Correlates of Direct and Indirect Suppression of Autobiographical Memories.

Research indicates that there are two possible mechanisms by which particular target memories can be intentionally forgotten. Direct suppression, which involves the suppression of the unwanted memory directly, and is dependent on a fronto-hippocampal modulatory process, and, memory substitution, which includes directing one’s attention to an alternative memory in order to prevent the unwanted memory from coming to mind, and involves engaging the caudal prefrontal cortex (cPFC) and the mid-ventrolateral prefrontal cortex (VLPFC) regions. Research to date, however, has investigated the neural basis of memory suppression of relatively simple information. The aim of the current study was to use fMRI to identify the neural mechanisms associated with the suppression of autobiographical memories. In the present study, 22 participants generated memories in response to a series of cue words. In a second session, participants learnt these cue-memory pairings, and were subsequently presented with a cue word and asked either to recall (think) or to suppress (no-think) the associated memory, or to think of an alternative memory in order to suppress the original memory (memory-substitution). Our findings demonstrated successful forgetting effects in the no-think and memory substitution conditions. Although we found no activation in the dorsolateral prefrontal cortex, there was reduced hippocampal activation during direct suppression. In the memory substitution condition, however, we failed to find increased activation in the cPFC and VLPFC regions. Our findings suggest that the suppression of autobiographical memories may rely on different neural mechanisms to those established for other types of material in memory.

Selective memory retrieval of auditory what and auditory where involves the ventrolateral prefrontal cortex

There is evidence from the visual, verbal, and tactile memory domains that the midventrolateral prefrontal cortex plays a critical role in the top-down modulation of activity within posterior cortical areas for the selective retrieval of specific aspects of a memorized experience, a functional process often referred to as active controlled retrieval. In the present functional neuroimaging study, we explore the neural bases of active retrieval for auditory nonverbal information, about which almost nothing is known. Human participants were scanned with functional magnetic resonance imaging (fMRI) in a task in which they were presented with short melodies from different locations in a simulated virtual acoustic environment within the scanner and were then instructed to retrieve selectively either the particular melody presented or its location. There were significant activity increases specifically within the midventrolateral prefrontal region during the selective retrieval of nonverbal auditory information. During the selective retrieval of information from auditory memory, the right midventrolateral prefrontal region increased its interaction with the auditory temporal region and the inferior parietal lobule in the right hemisphere. These findings provide evidence that the midventrolateral prefrontal cortical region interacts with specific posterior cortical areas in the human cerebral cortex for the selective retrieval of object and location features of an auditory memory experience.

Development of active control within working memory

This study aimed to compare children’s performance on two mnemonic functions that engage the lateral prefrontal cortex. Brain imaging studies in adults have shown that the mid-ventrolateral prefrontal cortex is specifically involved in active controlled retrieval, and the mid-dorsolateral prefrontal cortex is specifically involved in monitoring mnemonic information (Petrides, 2005). Eighty-two children aged from 6 years, 8 months to 8 years, 7 months were tested. They showed equivalent success rates in active retrieval and monitoring with color and shape information. However, children were slower in monitoring than in active retrieval in color trials. The results demonstrate that the specialized contributions of the lateral prefrontal cortex emerge conjointly during childhood giving children multiple tools to exert an active control within memory.

Opposing Mechanisms Support the Voluntary Forgetting of Unwanted Memories

SummaryReminders of the past can trigger the recollection of events that one would rather forget. Here, using fMRI, we demonstrate two distinct neural mechanisms that foster the intentional forgetting of such unwanted memories. Both mechanisms impair long-term retention by limiting momentary awareness of the memories, yet they operate in opposite ways. One mechanism, direct suppression, disengages episodic retrieval through the systemic inhibition of hippocampal processing that originates from right dorsolateral prefrontal cortex (PFC). The opposite mechanism, thought substitution, instead engages retrieval processes to occupy the limited focus of awareness with a substitute memory. It is mediated by interactions between left caudal and midventrolateral PFC that support the selective retrieval of substitutes in the context of prepotent, unwanted memories. These findings suggest that we are not at the mercy of passive forgetting; rather, our memories can be shaped by two opposite mechanisms of mnemonic control.

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.

Functional and anatomical organization of lateral prefrontal cortex for memory

Event Abstract Back to Event Functional and anatomical organization of lateral prefrontal cortex for memory Michael Petrides1, 2* 1 Montreal Neurological Institute, Cognitive Neuroscience Unit, Canada 2 McGill University, Department of Psychology, Canada The lateral prefrontal cortex consists of many areas that differ in terms of their architectonic structure and their inputs from and outputs to other cortical and subcortical brain regions. There is considerable evidence that the mid-dorsolateral prefrontal cortex (areas 46 and 9/46) is part of a wider fronto-parietal network critical for working memory processing. In the past, evidence was provided for the critical role of the mid-dorsolateral prefrontal cortex in the monitoring of information in working memory, but the role of the posterior parietal cortex has proven elusive. Recent research with functional magnetic resonance imaging has now provided evidence that the posterior parietal cortex plays a critical role in the manipulation of information during working memory processing. In contrast to the mid-dorsolateral prefrontal cortex, the mid-ventrolateral prefrontal cortex (areas 45 and 47/12) plays a critical role in controlled memory retrieval. The evidence has been obtained primarily from functional neuroimaging studies with normal human subjects that provide information about engagement of a cortical area in a cognitive process but no information on the neural computations performed. We have therefore examined the activity of single neurons in macaque monkeys during the performance of a controlled retrieval task identical to a task used in functional neuroimaging studies with humans. This task required the retrieval of a particular dimension from a recent multimodal memory experience. This research demonstrated the existence of neurons in this part of the prefrontal cortex that appear to code the isolation of specific information from an event in memory: their firing is a function of current information in memory and retrieval instruction. Thus, the mid-dorsolateral prefrontal cortex (areas 46 and 9/46) is specialized in the tracking of events that occupy working memory and works in concert with posterior parietal cortex for the manipulation of information in working memory, while the mid-ventrolateral prefrontal region (areas 45 and 47/12) is selectively involved in the active controlled retrieval of information memory. Conference: 41st European Brain and Behaviour Society Meeting, Rhodes Island, Greece, 13 Sep - 18 Sep, 2009. Presentation Type: Oral Presentation Topic: Plenary lectures Citation: Petrides M (2009). Functional and anatomical organization of lateral prefrontal cortex for memory. Conference Abstract: 41st European Brain and Behaviour Society Meeting. doi: 10.3389/conf.neuro.08.2009.09.007 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 04 Jun 2009; Published Online: 04 Jun 2009. * Correspondence: Michael Petrides, Montreal Neurological Institute, Cognitive Neuroscience Unit, Montréal, Canada, michael.petrides@mcgill.ca Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Michael Petrides Google Michael Petrides Google Scholar Michael Petrides PubMed Michael Petrides Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

When Learning and Remembering Compete: A Functional MRI Study

Recent functional neuroimaging evidence suggests a bottleneck between learning new information and remembering old information. In two behavioral experiments and one functional MRI (fMRI) experiment, we tested the hypothesis that learning and remembering compete when both processes happen within a brief period of time. In the first behavioral experiment, participants intentionally remembered old words displayed in the foreground, while incidentally learning new scenes displayed in the background. In line with a memory competition, we found that remembering old information was associated with impaired learning of new information. We replicated this finding in a subsequent fMRI experiment, which showed that this behavioral effect was coupled with a suppression of learning-related activity in visual and medial temporal areas. Moreover, the fMRI experiment provided evidence that left mid-ventrolateral prefrontal cortex is involved in resolving the memory competition, possibly by facilitating rapid switching between learning and remembering. Critically, a follow-up behavioral experiment in which the background scenes were replaced with a visual target detection task provided indications that the competition between learning and remembering was not merely due to attention. This study not only provides novel insight into our capacity to learn and remember, but also clarifies the neural mechanisms underlying flexible behavior.

Neural correlates of access to short-term memory

Behavioral research has led to the view that items in short-term memory can be parsed into two categories: a single item in the focus of attention that is available for immediate cognitive processing and a small set of other items that are in a heightened state of activation but require retrieval for further use. We examined this distinction by using an item-recognition task. The results show that the item in the focus of attention is represented by increased activation in inferior temporal representational cortices relative to other information in short-term memory. Functional connectivity analyses suggest that activation of these inferior temporal regions is maintained via frontal- and posterior-parietal contributions. By contrast, other items in short-term memory demand retrieval mechanisms that are represented by increased activation in the medial temporal lobe and left mid-ventrolateral prefrontal cortex. These results show that there are two distinctly different sorts of access to information in short-term memory, and that access by retrieval operations makes use of neural machinery similar to that used in long-term memory retrieval.

Waiting to retrieve: possible implications for brain function

There is evidence that the mid-ventrolateral prefrontal cortex is involved in control processing necessary for the active retrieval of mnemonic information when retrieval cannot be triggered automatically by unique/constant associations within memory. We hypothesized that this process is initiated as soon as an instructional cue to retrieve a particular aspect of an encoded stimulus is presented prior to the appearance of the test stimulus that prompts the subjects' response. To test this hypothesis, we provided the subjects with a delay period following the presentation of the instructional cue. Across delays, the subjects took longer to respond during the active retrieval compared with the automatic retrieval trials. Importantly, for both trial types, delays of up to 300 ms improved the subjects' reaction times during the test period by an average of 101 ms. Retrieval mechanisms, therefore, are initiated early during the post-instruction delay period prior to the presentation of the test stimulus needed for the decision.

Left mid‐ventrolateral prefrontal cortex: underlying principles of function

There is a growing body of evidence indicating that the mid-ventrolateral prefrontal cortex in the left hemisphere is involved in some aspect of controlled verbal memory retrieval. Its precise role, however, remains unclear. We tested the hypothesis that when stimuli in memory are related to each other in multiple ways, and therefore familiarity, strong constant stimulus-stimulus links or contextual cues are not sufficient for successful retrieval, control processing emanating from the mid-ventrolateral prefrontal cortex is required to disambiguate and select the appropriate information among memory traces. We refer to this type of retrieval as active retrieval to distinguish it from automatic retrieval which depends on the simple reactivation of memory traces. Normal human subjects were scanned with functional magnetic resonance imaging while they performed three memory tasks that varied in their demands on active retrieval of verbal information. As the demands on active retrieval increased, there was an increase in the activity within the mid-ventrolateral prefrontal cortex, bilaterally, but with more prominent activity in the left hemisphere. These activity increases correlated with activity in the posterior temporal region which, in the left hemisphere, is involved in language processing. No significant activity increases were observed in any other prefrontal region. Furthermore, for the retrieval of well-learned verbally cued conditional motor associations, there were no activity increases in the mid-ventrolateral prefrontal cortex. The present findings provide strong support for the hypothesis that the mid-ventrolateral prefrontal cortex, particularly in the left hemisphere, plays a major role in the active retrieval of information from verbal memory.

Ventrolateral Prefrontal Neuronal Activity Related to Active Controlled Memory Retrieval in Nonhuman Primates

It is controversial whether monkeys, like human subjects, can recall, upon instruction, specific information about an event in memory. We therefore tested macaque monkeys on a task that was originally developed to study such active controlled memory retrieval in human subjects and we were able to demonstrate that monkeys, like human subjects, can retrieve, upon command, specific components of previously encoded events. Furthermore, following earlier functional neuroimaging work with human subjects showing the mid-ventrolateral prefrontal cortex to be involved in such active controlled retrieval, we recorded single-neuron activity within this region of the monkey brain while the monkeys performed the active retrieval task. Neuronal responses were related to the retrieval and the decision whether the retrieved information was the instructed one. These findings demonstrate, for the first time, an impressive capacity by macaque monkeys for controlled memory retrieval and, in addition, provide neurophysiological evidence about the role of the mid-ventrolateral prefrontal cortex in such controlled retrieval.

The engagement of mid-ventrolateral prefrontal cortex and posterior brain regions in intentional cognitive activity

It is now widely recognized that cognitive processes are carried out by a distributed network of brain areas, some of which are involved in perceptual processing of a stimulus, whilst others are involved in cognitive control processes required to carry out certain tasks. In this study, differential contributions of higher visual areas and of an area involved in cognitive control processes were investigated in a task requiring participants to simply look at a stimulus or to look with the intention of remembering. Varying the extent to which intentional cognitive processes were required and the stimulus material in this task allowed the analysis of "top-down" and "bottom-up" influences on these areas, respectively. Significant increases in the mid-ventrolateral prefrontal cortex (mid-VLPFC) were only observed when the stimuli were viewed with an intention in mind, irrespective of the stimulus type. In contrast, activity in the parahippocampal place area and the fusiform face area, was only modulated in conditions requiring intentional control when stimuli were presented that also elicited activity in these regions during passive viewing. These findings help to clarify the complimentary role that the mid-VLPFC and posterior higher visual areas play in controlled and relatively automatic memory processing.

Heschl's Gyrus, Posterior Superior Temporal Gyrus, and Mid-Ventrolateral Prefrontal Cortex Have Different Roles in the Detection of Acoustic Changes

A part of the auditory system automatically detects changes in the acoustic environment. This preattentional process has been studied extensively, yet its cerebral origins have not been determined with sufficient accuracy to allow comparison to established anatomical and functional parcellations. Here we used event-related functional MRI and EEG in a parametric experimental design to determine the cortical areas in individual brains that participate in the detection of acoustic changes. Our results suggest that automatic change processing consists of at least three stages: initial detection in the primary auditory cortex, detailed analysis in the posterior superior temporal gyrus and planum temporale, and judgment of sufficient novelty for the allocation of attentional resources in the mid-ventrolateral prefrontal cortex.

Modulation of prefrontal cortex activation by emotional words in recognition memory

We employed event-related functional magnetic resonance imaging to examine emotional valence effects on verbal recognition memory. Using a yes/no recognition task, we focussed on prefrontal cortex responses to positive, negative and neutral words. Behavioral data confirmed enhanced processing of emotional items and functional magnetic resonance imaging revealed different subregions in the prefrontal cortex supporting retrieval of emotional words. Activations in the right mid-ventrolateral prefrontal cortex correlated with the correct retrieval conditions for negative words, whereas the right ventromedial and orbitofrontal prefrontal cortex showed enhanced responses to positive words. Additionally, differences between old and new items mainly affected bilateral orbitofrontal regions when processing positive words. The results are discussed in terms of higher monitoring demands owing to familiarity-based recognition bias for emotional words.

Dissociable contributions of the mid-ventrolateral frontal cortex and the medial temporal lobe system to human memory

Although the prefrontal cortex and regions of the medial temporal lobe are commonly co-activated in neuroimaging studies, their precise respective contributions to human memory remain unclear. In this event-related fMRI study, conditions requiring volunteers to simply look at pictures of abstract art were compared with conditions in which they were explicitly instructed to remember similar stimuli for later recognition. Looking, with no explicit instruction to remember, was associated with significant increases in signal intensity in the medial temporal lobe in 19 of the 20 volunteers scanned, but not in a region of the mid-ventrolateral prefrontal cortex that has previously been implicated in memory encoding and retrieval. Behavioral data collected outside the scanner on the same task revealed that recognition of these stimuli was, however, above chance. When the task instructions were changed to encourage the volunteers to remember the stimuli, significant increases in signal intensity were observed bilaterally, in the mid-ventrolateral frontal cortex, but there was no concomitant increase within the medial temporal lobe region. Moreover, behavioral data collected outside the scanner confirmed that recognition of these stimuli was significantly improved relative to the ‘just look’ trials. These results suggest that the mid-ventrolateral frontal cortex and the medial temporal lobe region make dissociable contributions to human memory that correspond closely to ‘top–down’ and ‘bottom–up’ notions of cognitive control, respectively.