The mid-ventrolateral prefrontal cortex: insights into its role in memory retrieval

Although it is widely known that the prefrontal cortex plays a role in memory, the specific contribution of particular prefrontal regions in mnemonic functions remains controversial. The present investigation examined whether the mid-ventrolateral prefrontal cortex is selectively involved in active memory retrieval in situations in which mnemonic traces are embedded in ambiguous relations and automatic recollection cannot lead to successful retrieval. Thirteen subjects participated in this event-related functional magnetic resonance imaging experiment. Throughout the scanning session, trials belonging to an experimental and a control condition were administered in a pseudorandom fashion. During the encoding phase of any particular trial, subjects were presented with a stimulus-complex that was a combination of a face and a spatial location on the screen. In the experimental active retrieval condition, a question cue following the encoding phase instructed the subjects to retrieve selectively one of the two aspects of the encoded stimulus-complex, i.e. the face or the location. In the control condition, the question cue that followed the encoding phase instructed the subjects simply to recall the initially presented stimulus-complex, so as to be able to make a decision during the test phase based on simple stimulus familiarity. The comparison of the signal obtained during the retrieval phase of these two conditions yielded an increase in activity selective to the right mid-ventrolateral prefrontal region. These results therefore establish a specific link between the mid-ventrolateral prefrontal cortex and active retrieval mechanisms.     

Proactive and reactive cognitive control rely on flexible use of the ventrolateral prefrontal cortex

The role of ventral versus dorsolateral prefrontal regions in instantiating proactive and reactive cognitive control remains actively debated, with few studies parsing cue versus probe‐related activity. Rapid sampling (460 ms), long cue–probe delays, and advanced analytic techniques (deconvolution) were therefore used to quantify the magnitude and variability of neural responses during the AX Continuous Performance Test (AX‐CPT; N = 46) in humans. Behavioral results indicated slower reaction times during reactive cognitive control (AY trials) in conjunction with decreased accuracy and increased variability for proactive cognitive control (BX trials). The anterior insula/ventrolateral prefrontal cortex (aI/VLPFC) was commonly activated across comparisons of both proactive and reactive cognitive control. In contrast, activity within the dorsomedial and dorsolateral prefrontal cortex was limited to reactive cognitive control. The instantiation of proactive cognitive control during the probe period was also associated with sparse neural activation relative to baseline, potentially as a result of the high degree of neural and behavioral variability observed across individuals. Specifically, the variability of the hemodynamic response function (HRF) within motor circuitry increased after the presentation of B relative to A cues (i.e., late in HRF) and persisted throughout the B probe period. Finally, increased activation of right aI/VLPFC during the cue period was associated with decreased motor circuit activity during BX probes, suggesting a possible role for the aI/VLPFC in proactive suppression of neural responses. Considered collectively, current results highlight the flexible role of the VLPFC in implementing cognitive control during the AX‐CPT task but suggest large individual differences in proactive cognitive control strategies.     

Ventrolateral prefrontal cortex and the effects of task demand context on facial affect appraisal in schizophrenia

Schizophrenia patients display impaired performance and brain activity during facial affect recognition. These impairments may reflect stimulus-driven perceptual decrements and evaluative processing abnormalities. We differentiated these two processes by contrasting responses to identical stimuli presented under different contexts. Seventeen healthy controls and 16 schizophrenia patients performed an fMRI facial affect detection task. Subjects identified an affective target presented amongst foils of differing emotions. We hypothesized that targeting affiliative emotions (happiness, sadness) would create a task demand context distinct from that generated when targeting threat emotions (anger, fear). We compared affiliative foil stimuli within a congruent affiliative context with identical stimuli presented in an incongruent threat context. Threat foils were analysed in the same manner. Controls activated right orbitofrontal cortex (OFC)/ventrolateral prefrontal cortex (VLPFC) more to affiliative foils in threat contexts than to identical stimuli within affiliative contexts. Patients displayed reduced OFC/VLPFC activation to all foils, and no activation modulation by context. This lack of context modulation coincided with a 2-fold decrement in foil detection efficiency. Task demands produce contextual effects during facial affective processing in regions activated during affect evaluation. In schizophrenia, reduced modulation of OFC/VLPFC by context coupled with reduced behavioural efficiency suggests impaired ventral prefrontal control mechanisms that optimize affective appraisal.     

Dysfunctional involvement of emotion and reward brain regions on social decision making in excess weight adolescents

Obese adolescents suffer negative social experiences, but no studies have examined whether obesity is associated with dysfunction of the social brain or whether social brain abnormalities relate to disadvantageous traits and social decisions. We aimed at mapping functional activation differences in the brain circuitry of social decision making in adolescents with excess versus normal weight, and at examining whether these separate patterns correlate with reward/punishment sensitivity, disordered eating features, and behavioral decisions. In this fMRI study, 80 adolescents aged 12 to 18 years old were classified in two groups based on age adjusted body mass index (BMI) percentiles: normal weight (n = 44, BMI percentiles 5th–84th) and excess weight (n = 36, BMI percentile ≥ 85th). Participants were scanned while performing a social decision‐making task (ultimatum game) in which they chose to “accept” or “reject” offers to split monetary stakes made by another peer. Offers varied in fairness (Fair vs. Unfair) but in all cases “accepting” meant both players win the money, whereas “rejecting” meant both lose it. We showed that adolescents with excess weight compared to controls display significantly decreased activation of anterior insula, anterior cingulate, and midbrain during decisions about Unfair versus Fair offers. Moreover, excess weight subjects show lower sensitivity to reward and more maturity fears, which correlate with insula activation. Indeed, blunted insula activation accounted for the relationship between maturity fears and acceptance of unfair offers. Excess weight adolescents have diminished activation of brain regions essential for affective tracking of social decision making, which accounts for the association between maturity fears and social decisions. Hum Brain Mapp, 36:–237, 2015. © 2014 Wiley Periodicals, Inc .     

Involvement of rostral prefrontal cortex in selection between stimulus-oriented and stimulus-independent thought

We used functional magnetic resonance imaging to investigate brain activity while healthy subjects performed three different tasks, each of which alternated between: (i) phases relying on stimulus-oriented thought (i.e. cognitive processes provoked by incoming sensory information); and (ii) phases relying on stimulus-independent thought (i.e. cognitive processes that were not related to any information in the immediate sensory environment). Within each task, the two phases were matched as closely as possible. In all three tasks, lateral rostral prefrontal cortex was transiently activated by a switch between stimulus-oriented and stimulus-independent thought (regardless of the direction of the switch). Medial rostral prefrontal cortex consistently exhibited sustained activity for stimulus-oriented vs. stimulus-independent thought. These results suggest the involvement of rostral prefrontal cortex in selection between stimulus-oriented and stimulus-independent cognitive processes.     

Acquired self‐control of insula cortex modulates emotion recognition and brain network connectivity in schizophrenia

Real‐time functional magnetic resonance imaging (rtfMRI) is a novel technique that has allowed subjects to achieve self‐regulation of circumscribed brain regions. Despite its anticipated therapeutic benefits, there is no report on successful application of this technique in psychiatric populations. The objectives of the present study were to train schizophrenia patients to achieve volitional control of bilateral anterior insula cortex on multiple days, and to explore the effect of learned self‐regulation on face emotion recognition (an extensively studied deficit in schizophrenia) and on brain network connectivity. Nine patients with schizophrenia were trained to regulate the hemodynamic response in bilateral anterior insula with contingent rtfMRI neurofeedback, through a 2‐weeks training. At the end of the training stage, patients performed a face emotion recognition task to explore behavioral effects of learned self‐regulation. A learning effect in self‐regulation was found for bilateral anterior insula, which persisted through the training. Following successful self‐regulation, patients recognized disgust faces more accurately and happy faces less accurately. Improvements in disgust recognition were correlated with levels of self‐activation of right insula. RtfMRI training led to an increase in the number of the incoming and outgoing effective connections of the anterior insula. This study shows for the first time that patients with schizophrenia can learn volitional brain regulation by rtfMRI feedback training leading to changes in the perception of emotions and modulations of the brain network connectivity. These findings open the door for further studies of rtfMRI in severely ill psychiatric populations, and possible therapeutic applications. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

Cerebral plasticity and recovery of function after childhood prefrontal cortex damage

Objective: Recovery of function after early brain injury depends upon both reparative and compensatory processes that are minimally understood. Using functional magnetic resonance imaging (fMRI), this study investigated the reorganization of hemispheric brain activity of a 24 year old male who suffered right prefrontal cortex damage at 7 years of age related to ruptured arteriovenous malformation. His pattern of recovery has been examined and tracked over the past 17 years and evolved from initial significant impairments in executive, spatial and attentional abilities from the brain lesion to remarkable recovery of function.

Methods: High field fMRI studies were completed with experimental cognitive tasks sensitive to right prefrontal functions, including visuospatial relational reasoning, spatial working memory, go no-go, emotional face recognition, and coin calculation. Results were compared to a matched control group for total hemispheric activity patterns.

Results: Analyses revealed that on fMRI activation tasks where the patient scored similar to controls, he activated a broader network of bilateral cortical regions than controls. On tasks where he scored lower than controls, there was under-activation of prefrontal cortical regions in comparison to controls.

Conclusion: Recovery of function after prefrontal cortex damage in childhood can occur and be associated with significant functional reorganization of hemispheric activity patterns (i.e. developmental cerebral plasticity). Although not all tasks showed recovery to the same extent in this case, those tasks with the most robust recovery entailed compensatory activation of additional cortical regions on fMRI. Further studies are needed to confirm and extend these findings.     

Location and spatial profile of category-specific regions in human extrastriate cortex

Subjects were scanned in a single functional MRI (fMRI) experiment that enabled us to localize cortical regions in each subject in the occipital and temporal lobes that responded significantly in a variety of contrasts: faces>objects, body parts>objects, scenes>objects, objects>scrambled objects, and moving>stationary stimuli. The resulting activation maps were co-registered across subjects using spherical surface coordinates [Fischl et al., Hum Brain Mapp 1999;8:272-284] to produce a "percentage overlap map" indicating the percentage of subjects who showed a significant response for each contrast at each point on the surface. Prominent among the overlapping activations in these contrasts were the fusiform face area (FFA), extrastriate body area (EBA), parahippocampal place area (PPA), lateral occipital complex (LOC), and MT+/V5; only a few other areas responded consistently across subjects in these contrasts. Another analysis showed that the spatial profile of the selective response drops off quite sharply outside the standard borders of the FFA and PPA (less so for the EBA and MT+/V5), indicating that these regions are not simply peaks of very broad selectivities spanning centimeters of cortex, but fairly discrete regions of cortex with distinctive functional profiles. The data also yielded a surprise that challenges our understanding of the function of area MT+: a higher response to body parts than to objects. The anatomical consistency of each of our functionally defined regions across subjects and the spatial sharpness of their activation profiles within subjects highlight the fact that these regions constitute replicable and distinctive landmarks in the functional organization of the human brain.     

Selective activation of the ventrolateral prefrontal cortex in the human brain during active retrieval processing

The present study examined the role of the prefrontal cortex in retrieval processing using functional magnetic resonance imaging in human subjects. Ten healthy subjects were scanned while they performed a task that required retrieval of specific aspects of visual information. In order to examine brain activity specifically associated with retrieval, we designed a task that had retrieval and control conditions that were perfectly matched in terms of depth of encoding, decision making and postretrieval monitoring and differed only in terms of whether retrieval was required. In the retrieval condition, based on an instructional cue, the subjects had to retrieve either the particular stimulus that was previously presented or its location. In the control condition, the cue did not instruct retrieval but shared with the instructional cues the function of alerting the subjects of the impending test phase. The comparison of activity between the retrieval and control conditions demonstrated a significant and selective increase in activity related to retrieval processes within the ventrolateral prefrontal cortical region, more specifically within area 47/12. These activity increases were bilateral but stronger in the right hemisphere. The present study by strictly controlling the level of encoding, postretrieval monitoring, and decision making has demonstrated a specific increase in the ventrolateral prefrontal region that could be clearly related to active retrieval processing, i.e. the active selection of particular stored visual representations.     

Real time fMRI feedback of the anterior cingulate and posterior insular cortex in the processing of pain

Self‐regulation of brain activation using real‐time functional magnetic resonance imaging has been used to train subjects to modulate activation in various brain areas and has been associated with behavioral changes such as altered pain perception. The aim of this study was to assess the comparability of upregulation versus downregulation of activation in the rostral anterior cingulate cortex (rACC) and left posterior insula (pInsL) and its effect on pain intensity and unpleasantness. In a first study, we trained 10 healthy subjects to separately upregulate and downregulate the blood oxygenation level‐dependent response in the rACC or pInsL (six trials on 4 days) in response to painful electrical stimulation. The participants learned to significantly downregulate activation in pInsL and rACC and upregulate pInsL but not rACC. Success in the modulation of one region and direction of the modulation was not significantly correlated with success in another condition, indicating that the ability to control pain‐related brain activation is site‐specific. Less covariation between the areas in response to the nociceptive stimulus was positively correlated with learning success. Upregulation or downregulation of either region was unrelated to pain intensity or unpleasantness; however, our subjects did not learn rACC upregulation, which might be important for pain control. A significant increase in pain unpleasantness was found during upregulation of pInsL when covariation with the rACC was low. These initial results suggest that the state of the network involved in the processing of pain needs to be considered in the modulation of pain‐evoked activation and its behavioral effects. Hum Brain Mapp 35:5784–5798, 2014. © 2014 Wiley Periodicals, Inc.     

Functional connectivity between parietal and frontal brain regions and intelligence in young children: The Generation R study

It has been shown in adults that individual differences in intelligence are related to the integrity of the interaction between parietal and frontal brain regions. Since connectivity between distant brain regions strengthens during childhood, it is unclear when in the course of development this relationship emerges. Thus, the goal of this study was to determine whether parietal‐frontal functional connectivity is associated with intelligence in young children. We performed independent component analyses on resting‐state fMRI data of 115 children (6–8 years old) to select seed and target regions for a seed/target region correlation analysis. We found that higher nonverbal intelligence was associated with increased functional connectivity between right parietal and right frontal regions, and between right parietal and dorsal anterior cingulate regions. The association between intelligence and functional connectivity between certain brain regions was stronger in girls than boys. In conclusion, we found that connectivity between the parietal and frontal lobes is critically involved in intelligence in young children. Hum Brain Mapp 34:3299–3307, 2013. © 2012 Wiley Periodicals, Inc.     

Emotion regulation in spider phobia: role of the medial prefrontal cortex

Phobic responses are strong emotional reactions towards phobic objects, which can be described as a deficit in the automatic regulation of emotions. Difficulties in the voluntary cognitive control of these emotions suggest a further phobia-specific deficit in effortful emotion regulation mechanisms. The actual study is based on this emotion regulation conceptualization of specific phobias. The aim is to investigate the neural correlates of these two emotion regulation deficits in spider phobics. Sixteen spider phobic females participated in a functional magnetic resonance imaging (fMRI) study in which they were asked to voluntarily up- and down-regulate their emotions elicited by spider and generally aversive pictures with a reappraisal strategy. In line with the hypothesis concerning an automatic emotion regulation deficit, increased activity in the insula and reduced activity in the ventromedial prefrontal cortex was observed. Furthermore, phobia-specific effortful regulation within phobics was associated with altered activity in medial prefrontal cortex areas. Altogether, these results suggest that spider phobic subjects are indeed characterized by a deficit in the automatic as well as the effortful regulation of emotions elicited by phobic compared with aversive stimuli. These two forms of phobic emotion regulation deficits are associated with altered activity in different medial prefrontal cortex subregions.     

Distinct regions of medial rostral prefrontal cortex supporting social and nonsocial functions

While some recent neuroimaging studies have implicated medialrostral prefrontal cortex (MPFC) in ‘mentalizing’and self-reflection, others have implicated this region in attentiontowards perceptual vs self-generated information. In order toreconcile these seemingly contradictory findings, we used fMRIto investigate MPFC activity related to these two functionsin a factorial design. Participants performed two separate tasks,each of which alternated between ‘stimulus-oriented phases’(SO), where participants attended to task-relevant perceptualinformation, and ‘stimulus-independent phases’ (SI),where participants performed the same tasks in the absence ofsuch information. In half of the blocks (‘mentalizingcondition’), participants were instructed that they wereperforming these tasks in collaboration with an experimenter;in other blocks (‘non-mentalizing condition’), participantswere instructed that the experimenter was not involved. In fact,the tasks were identical in these conditions. Neuroimaging datarevealed adjacent but clearly distinct regions of activationwithin MPFC related to (i) mentalizing vs non-mentalizing conditions(relatively caudal/superior) and (ii) SO vs SI attention (relativelyrostral/inferior). These results generalized from one task tothe other, suggesting a new axis of functional organizationwithin MPFC.     

Differential responses of the dorsomedial prefrontal cortex and right posterior superior temporal sulcus to spontaneous mentalizing

Previous research suggests a role of the dorsomedial prefrontal cortex (dmPFC) in metacognitive representation of social information, while the right posterior superior temporal sulcus (pSTS) has been linked to social perception. This study targeted these functional roles in the context of spontaneous mentalizing. An animated shapes task was presented to 46 subjects during functional magnetic resonance imaging. Stimuli consisted of video clips depicting animated shapes whose movement patterns prompt spontaneous mentalizing or simple intention attribution. Based on their differential response during spontaneous mentalizing, both regions were characterized with respect to their task‐dependent connectivity profiles and their associations with autistic traits. Functional network analyses revealed highly localized coupling of the right pSTS with visual areas in the lateral occipital cortex, while the dmPFC showed extensive coupling with instances of large‐scale control networks and temporal areas including the right pSTS. Autistic traits were related to mentalizing‐specific activation of the dmPFC and to the strength of connectivity between the dmPFC and posterior temporal regions. These results are in good agreement with the hypothesized roles of the dmPFC and right pSTS for metacognitive representation and perception‐based processing of social information, respectively, and further inform their implication in social behavior linked to autism. Hum Brain Mapp 38:3791–3803, 2017. © 2017 Wiley Periodicals, Inc.     

Functional dissociation of the left and right fusiform gyrus in self-face recognition

It is well known that the fusiform gyrus is engaged in face perception, such as the processes of face familiarity and identity. However, the functional role of the fusiform gyrus in face processing related to high-level social cognition remains unclear. The current study assessed the functional role of individually defined fusiform face area (FFA) in the processing of self-face physical properties and self-face identity. We used functional magnetic resonance imaging to monitor neural responses to rapidly presented face stimuli drawn from morph continua between self-face (Morph 100%) and a gender-matched friend's face (Morph 0%) in a face recognition task. Contrasting Morph 100% versus Morph 60% that differed in self-face physical properties but were both recognized as the self uncovered neural activity sensitive to self-face physical properties in the left FFA. Contrasting Morphs 50% that were recognized as the self versus a friend on different trials revealed neural modulations associated with self-face identity in the right FFA. Moreover, the right FFA activity correlated with the frequency of recognizing Morphs 50% as the self. Our results provide evidence for functional dissociations of the left and right FFAs in the representations of self-face physical properties and self-face identity.     

Anterior prefrontal cortex and the recollection of contextual information

Recollective memory can involve the retrieval of many different kinds of contextual information, including where and when an event took place, as well as our thoughts and feelings at the time. The brain regions associated with this ability were examined in an event-related fMRI experiment, where participants made decisions about words or famous faces which were presented either on the left or right of a monitor screen. Subsequently, the studied words and faces were again presented and participants underwent fMRI brain scanning while recollecting either which of the decisions they had made on each item ("task memory"), or whether it had been presented on the left or right of the screen ("position memory"). A functional dissociation was observed within anterior prefrontal cortex (principally Brodmann's area 10), with activation in lateral regions associated with remembering either type of information (relative to baseline), and a medial anterior PFC region showing significantly greater activation during the "task memory" conditions. These results suggest different roles for lateral and medial anterior prefrontal cortex in recollection.     

Activity in medial prefrontal cortex during cognitive evaluation of threatening stimuli as a function of personality style

Cognitive evaluation of emotional stimuli involves a network of brain regions including the medial prefrontal cortex (mPFC). However, threatening stimuli may be perceived with differential salience in different individuals. The goal of our study was to evaluate how different personality styles are associated with differential modulation of brain activity during explicit recognition of fearful and angry facial expressions. Twenty-eight healthy subjects underwent fMRI. Based on a cognitivist model, subjects were categorized according to how they attribute salience to emotional stimuli and how they regulate their emotional activation. We compared 14 phobic prone (PP) subjects, whose identity is more centered on the inner experience ("inward") and around control of environmental threat, and 14 eating disorders prone (EDP) subjects, whose identity is more centered on external referential contexts ("outward") and much less around control of threatening stimuli. During fMRI subjects either matched the identity of one of two angry and fearful faces to that of a simultaneously presented target face or identified the expression of a target face by choosing one of two simultaneously presented linguistic labels. The fMRI results indicated that PP subjects had greater mPFC activation when compared with EDP subjects during cognitive labeling of threatening stimuli. Activity in the mPFC also correlated with personality style scores. These results demonstrate that PP subjects recruit greater neuronal resources in mPFC whose activity is associated with cognitive aspects that are closely intertwined with emotional processing. These findings are consistent with the contention that cognitive evaluation and salience of emotional stimuli are associated with different personality styles.     

Attention and working memory: a dynamical model of neuronal activity in the prefrontal cortex

Cognitive behaviour requires complex context-dependent mapping between sensory stimuli and actions. The same stimulus can lead to different behaviours depending on the situation, or the same behaviour may be elicited by different cueing stimuli. Neurons in the primate prefrontal cortex show task-specific firing activity during working memory delay periods. These neurons provide a neural substrate for mapping stimulus and response in a flexible, context- or rule-dependent, fashion. We describe here an integrate-and-fire network model to explain and investigate the different types of working-memory-related neuronal activity observed. The model contains different populations (or pools) of neurons (as found neurophysiologically) in attractor networks which respond in the delay period to the stimulus object, the stimulus position ('sensory pools'), to combinations of the stimulus sensory properties (e.g. the object identity or object location) and the response ('intermediate pools'), and to the response required (left or right) ('premotor pools'). The pools are arranged hierarchically, are linked by associative synaptic connections, and have global inhibition through inhibitory interneurons to implement competition. It is shown that a biasing attentional input to define the current rule applied to the intermediate pools enables the system to select the correct response in what is a biased competition model of attention. The integrate-and-fire model not only produces realistic spiking dynamicals very similar to the neuronal data but also shows how dopamine could weaken and shorten the persistent neuronal activity in the delay period; and allows us to predict more response errors when dopamine is elevated because there is less different activity in the different pools of competing neurons, resulting in more conflict.     

Dysfunctional connectivity in posterior brain regions involved in cognitive control in schizophrenia: A preliminary fMRI study

Cognitive control, the ability to use goal-directed information to guide behaviour, is impaired in schizophrenia, and mainly related to dysfunctions within the fronto-posterior brain network. However, cognitive control is a broad cognitive function encompassing distinct sub-processes that, until now, studies have failed to separate and relate to specific brain regions. The goal of this preliminary fMRI study is to investigate the functional specialization of posterior brain regions, and their functional interaction with lateral prefrontal cortex (LPFC) regions, in schizophrenia. Fourteen healthy participants and 15 matched schizophrenic patients participated in this fMRI study. We used a task paradigm that differentiates two cognitive control sub-processes according to the temporal framing of information, namely the control of immediate context (present cues) vs. temporal episode (past instructions). We found that areas activated during contextual and episodic controls were in dorsal posterior regions and that activations did not significantly differ between schizophrenic patients and healthy participants. However, while processing contextual signals, patients with schizophrenia failed to show decreased connectivity between caudal LPFC and areas located in ventral posterior regions. The absence of group difference in the functional specialization of posterior regions is difficult to interpret due to our small sample size. One interpretation for our connectivity results is that patients present an inefficient extinction of posterior regions involved in attention shifting by prefrontal areas involved in the top-down control of contextual signals. Further studies with larger sample sizes will be needed to ascertain those observations.     

Lesions of the orbital prefrontal cortex impair the formation of attentional set in rats

In rats, reversal learning impairments are commonly reported after lesions of the orbital prefrontal cortex (OFC), in contrast to the effect of lesions of the medial prefrontal cortex, which impair attentional set-shifting. Comparable dissociations have also been reported in humans, monkeys and mice. However, these two manifestations of behavioural flexibility may share common cognitive processes. The present study tested the hypothesis that lesions of the OFC (an area that integrates expected and actual outcomes to signal which cues in the environment predict reward) would impair the formation of attentional set as well as impairing reversal learning. We compared the performance of lesioned and control rats on two set-shifting tasks. The first task we used, 'the 4ID task', had no reversal stages, but multiple intradimensional acquisitions before the extradimensional shift stage, to assess set-formation as well as set-shifting. The second task was the standard intradimensional/extradimensional '7-stage task', which includes reversal learning stages after each compound acquisition. Compared with controls, lesioned rats were slower to form attentional set on the 4ID task. When they did form a set, they required more trials to complete the extradimensional shift stage. On the 7-stage task, we replicated our previous finding of impaired reversal learning and reduced shift-costs. We interpret these findings as reflecting a single deficit in identifying relevant cues after unexpected outcomes, which supports recent models of OFC function. Our findings challenge the assumption that the contribution of the OFC to behavioural flexibility is limited to reversal learning.