vmPFC Damage Research Articles

Impaired awareness of action-outcome contingency and causality during healthy ageing and following ventromedial prefrontal cortex lesions

Detecting causal relationships between actions and their outcomes is fundamental to guiding goal-directed behaviour. The ventromedial prefrontal cortex (vmPFC) has been extensively implicated in computing these environmental contingencies, via animal lesion models and human neuroimaging. However, whether the vmPFC is critical for contingency learning, and whether it can occur without subjective awareness of those contingencies, has not been established. To address this, we measured response adaption to contingency and subjective awareness of action-outcome relationships in individuals with vmPFC lesions and healthy elderly subjects. We showed that in both vmPFC damage and ageing, successful behavioural adaptation to variations in action-outcome contingencies was maintained, but subjective awareness of these contingencies was reduced. These results highlight two contexts where performance and awareness have been dissociated, and show that learning response-outcome contingencies to guide behaviour can occur without subjective awareness. Preserved responding in the vmPFC group suggests that this region is not critical for computing action-outcome contingencies to guide behaviour. In contrast, our findings highlight a critical role for the vmPFC in supporting awareness, or metacognitive ability, during learning. We further advance the hypothesis that responding to changing environmental contingencies, whilst simultaneously maintaining conscious awareness of those statistical regularities, is a form of dual-tasking that is impaired in ageing due to reduced prefrontal function.

Episodic future thinking following vmPFC damage: Impaired event construction, maintenance, or narration?

Functional neuroimaging and lesion studies show that the ventromedial prefrontal cortex (vmPFC) is implicated in episodic future thinking (EFT), yet its role remains unclear. In this study, we sought to (a) confirm recent findings of impaired EFT in patients with lesions to the vmPFC (vmPFC patients) using a new task, and (b) investigate the influence of nonepisodic mechanisms, namely, narrative construction and working memory maintenance, on vmPFC patients' EFT performance. vmPFC patients and healthy participants imagined future events using pictures as cues, described pictures, or described pictures while maintaining them in working memory after an observation phase. Compared with the controls, vmPFC patients produced less specific reports across all conditions, as indicated by fewer internal (episodic) but a similar number of external (semantic) details. However, controlling for description and working memory performance did not eliminate group differences in EFT. Moreover, vmPFC damage reduced the proportion of internal-to-total details for EFT only. These results indicate that EFT problems in vmPFC patients are not merely the reflection of problems in maintaining in working memory and narrating events, but, more likely, of an impairment upstream, in creating novel events. (PsycINFO Database Record

Hippocampal Damage Increases Deontological Responses during Moral Decision Making.

Complex moral decision making is associated with the ventromedial prefrontal cortex (vmPFC) in humans, and damage to this region significantly increases the frequency of utilitarian judgments. Since the vmPFC has strong anatomical and functional links with the hippocampus, here we asked how patients with selective bilateral hippocampal damage would derive moral decisions on a classic moral dilemmas paradigm. We found that the patients approved of the utilitarian options significantly less often than control participants, favoring instead deontological responses—rejecting actions that harm even one person. Thus, patients with hippocampal damage have a strikingly opposite approach to moral decision making than vmPFC-lesioned patients. Skin-conductance data collected during the task showed increased emotional arousal in the hippocampal-damaged patients and they stated that their moral decisions were based on emotional instinct. By contrast, control participants made moral decisions based on the integration of an adverse emotional response to harming others, visualization of the consequences of one's action, and the rational re-evaluation of future benefits. This integration may be disturbed in patients with either hippocampal or vmPFC damage. Hippocampal lesions decreased the ability to visualize a scenario and its future consequences, which seemed to render the adverse emotional response overwhelmingly dominant. In patients with vmPFC damage, visualization might also be reduced alongside an inability to detect the adverse emotional response, leaving only the utilitarian option open. Overall, these results provide insights into the processes involved in moral decision making and highlight the complementary roles played by two closely connected brain regions.SIGNIFICANCE STATEMENT The ventromedial prefrontal cortex (vmPFC) is closely associated with the ability to make complex moral judgements. When this area is damaged, patients become more utilitarian (the ends justify the means) and have decreased emotional arousal during moral decision making. The vmPFC is closely connected with another brain region—the hippocampus. In this study we found that patients with selective bilateral hippocampal damage show a strikingly opposite response pattern to those with vmPFC damage when making moral judgements. They rejected harmful actions of any kind (thus their responses were deontological) and showed increased emotional arousal. These results provide new insights into the processes involved in moral decision making and highlight the complementary roles played by two closely connected brain regions.

Ventromedial prefrontal cortex generates pre-stimulus theta coherence desynchronization: A schema instantiation hypothesis

The ventral medial prefrontal cortex (vmPFC) has long been implicated in monitoring of memory veracity, and more recently also in memory schema functions. In our model of strategic retrieval the two are related. We have proposed that the vmPFC has two schema-dependent functions: (i) to establish context-relevant templates against which the output of memory systems can be compared; (ii) to mediate automatic decision monitoring processes to ensure that only those responses that meet the criterion are enacted. Electroencephalogram (EEG) data were used to provide evidence that vmPFC supports both functions, and that schema instantiation informs monitoring. Participants viewed pictures of acquaintances, along with those of famous and nonfamous people, and were asked to respond positively only to pictures of individuals they had met (personal familiarity). The Self serves as a super-ordinate cognitive schema, facilitating accurate endorsement of acquaintances and exclusion of non-personal but familiar faces. For the present report we focused on pre-cue tonic oscillatory activity. Controls demonstrated theta coherence desynchronization between medial prefrontal areas, inferotemporal and lateral temporal cortices. These oscillatory coherence patterns were significantly reduced in patients with vmPFC damage, especially in those with clinical histories of spontaneous confabulation. Importantly, these pre-stimulus cortico-cortical desynchronizations predicted post-cue automatic memory activation, as indexed by a familiarity modulation of the face-sensitive posterior cortical N170. Pre-cue desynchronization also predicted early post-cue frontal positive modulation (P230) and response accuracy. The data are consistent with a schema instantiation model that suggests the vmPFC biases posterior neocortical long-term memory representations that enhance automatic memory cue processing and informs frontally-mediated rapid memory monitoring (P230). Damage to these structures can lead to inaccurate, context-irrelevant activation of schemas. These, in turn, impair monitoring signals and can lead to confabulation when memory control processes are also deficient.

Ventromedial prefrontal damage reduces mind-wandering and biases its temporal focus.

Mind-wandering, an ubiquitous expression of humans' mental life, reflects a drift of attention away from the current task towards self-generated thoughts, and has been associated with activity in the brain default network. To date, however, little is understood about the contribution of individual nodes of this network to mind-wandering. Here, we investigated whether the ventromedial prefrontal cortex (vmPFC) is critically involved in mind-wandering, by studying the propensity to mind-wander in patients with lesion to the vmPFC (vmPFC patients), control patients with lesions not involving the vmPFC, and healthy individuals. Participants performed three tasks varying in cognitive demands while their thoughts were periodically sampled, and a self-report scale of daydreaming in daily life. vmPFC patients exhibited reduced mind-wandering rates across tasks, and claimed less frequent daydreaming, than both healthy and brain-damaged controls. vmPFC damage reduced off-task thoughts related to the future, while it promoted those about the present. These results indicate that vmPFC critically supports mind-wandering, possibly by helping to construct future-related scenarios and thoughts that have the potential to draw attention inward, away from the ongoing tasks.

Emotion recognition deficits associated with ventromedial prefrontal cortex lesions are improved by gaze manipulation

Facial emotion recognition is a critical aspect of human communication. Since abnormalities in facial emotion recognition are associated with social and affective impairment in a variety of psychiatric and neurological conditions, identifying the neural substrates and psychological processes underlying facial emotion recognition will help advance basic and translational research on social-affective function. Ventromedial prefrontal cortex (vmPFC) has recently been implicated in deploying visual attention to the eyes of emotional faces, although there is mixed evidence regarding the importance of this brain region for recognition accuracy. In the present study of neurological patients with vmPFC damage, we used an emotion recognition task with morphed facial expressions of varying intensities to determine (1) whether vmPFC is essential for emotion recognition accuracy, and (2) whether instructed attention to the eyes of faces would be sufficient to improve any accuracy deficits. We found that vmPFC lesion patients are impaired, relative to neurologically healthy adults, at recognizing moderate intensity expressions of anger and that recognition accuracy can be improved by providing instructions of where to fixate. These results suggest that vmPFC may be important for the recognition of facial emotion through a role in guiding visual attention to emotionally salient regions of faces.

A boost of confidence: The role of the ventromedial prefrontal cortex in memory, decision-making, and schemas

The ventromedial prefrontal cortex (vmPFC) has been implicated in a wide array of functions across multiple domains. In this review, we focus on the vmPFC's involvement in mediating strategic aspects of memory retrieval, memory-related schema functions, and decision-making. We suggest that vmPFC generates a confidence signal that informs decisions and memory-guided behaviour. Confidence is central to these seemingly diverse functions: (1) Strategic retrieval: lesions to the vmPFC impair an early, automatic, and intuitive monitoring process (“feeling of rightness”; FOR) often associated with confabulation (spontaneous reporting of erroneous memories). Critically, confabulators typically demonstrate high levels of confidence in their false memories, suggesting that faulty monitoring following vmPFC damage may lead to indiscriminate confidence signals. (2) Memory schemas: the vmPFC is critically involved in instantiating and maintaining contextually relevant schemas, broadly defined as higher level knowledge structures that encapsulate lower level representational elements. The correspondence between memory retrieval cues and these activated schemas leads to FOR monitoring. Stronger, more elaborate schemas produce stronger FOR and influence confidence in the veracity of memory candidates. (3) Finally, we review evidence on the vmPFC's role in decision-making, extending this role to decision-making during memory retrieval. During non-mnemonic and mnemonic decision-making the vmPFC automatically encodes confidence. Confidence signal in the vmPFC is revealed as a non-linear relationship between a first-order monitoring assessment and second-order action or choice. Attempting to integrate the multiple functions of the vmPFC, we propose a posterior-anterior organizational principle for this region. More posterior vmPFC regions are involved in earlier, automatic, subjective, and contextually sensitive functions, while more anterior regions are involved in controlled actions based on these earlier functions. Confidence signals reflect the non-linear relationship between first-order, posterior-mediated and second-order, anterior-mediated processes and are represented along the entire axis.

Role of orbitofrontal cortex in reward sensitivity: evidence from human lesions

BackgroundAn emerging hypothesis from cognitive neuroscience is that the ventromedial prefrontal cortex (vmPFC) is central to the evaluation and expectation of reward. However, there is scant evidence that lesions in this region alter reward processing. Rather, patients with damage in vmPFC have shown many conflicting effects with respect to motivation and affect. We aimed to specifically examine incentivisation by reward after damage to human vmPFC. MethodsWe selected a group of 19 patients with highly focal medial frontal lesions, from a database of 453 patients with subarachnoid haemorrhage, and 32 age-matched healthy controls. We directly tested for sensitivity to incentives using eye movements. Lesions included anterior cingulate, vmPFC, and medial orbitofrontal cortex. The task required participants to make saccadic eye movements to a target while avoiding a distractor, to obtain speed-related rewards. Crucially, before each eye movement, participants heard a reward cue indicating the maximum reward available. We examined the effect of the incentive cue on subsequent saccade velocity, and how this motivational effect was altered by medial frontal damage. FindingsIn healthy people, mean peak saccadic velocity was modulated by the incentive (from 458 degrees per s [SE 15] to 489 [17], p=0·0011), allowing a parametric measure of reward sensitivity. As a group, patients with medial frontal damage had significantly reduced effects of reward on invigorating saccadic velocity (from 443 degrees per s [SE 16] to 459 [19], p=0·038) and autonomic (pupil) responses (z-score traces significantly differed after 653 ms, p<0·05) compared with controls. However at the individual level, some patients showed the opposite effect, with abnormally strong incentivisation effects (3 SD above controls). Voxel-based lesion mapping demonstrated that within the lesion group, increased sensitivity to rewards correlated with damage to vmPFC subregions (144 voxels=1·15 cm3 whole-brain corrected). Lesions to vmPFC were also associated with clinical apathy (p=0·027 in region of interest) suggesting that apathy associated with prefrontal damage is reduced by vmPFC damage. InterpretationThis study found that, although medial frontal lesions could generally reduce reward sensitivity, damage to key subregions paradoxically were protective of this effect. Changes in reward sensitivity caused by altered representation of reward value might be a central link between various facets of behavioural changes seen after medial frontal damage. The results suggest a direct, mechanistic role for prefrontal reward computation in clinical motivation syndromes. FundingWellcome Trust.

Impaired Valuation Leads to Increased Apathy Following Ventromedial Prefrontal Cortex Damage.

Apathy is defined by reduced goal-directed behavior, and is common in patients with damage to the ventromedial prefrontal cortex (vmPFC). Separately, in neuroeconomics research, the vmPFC has been shown to play a role in reward processing-namely, in "stimulus valuation," or the computation of the subjective reward value of a stimulus. Here, we used a sample of patients with focal brain lesions (N = 93) and matched healthy controls (N = 21) to determine whether the association between vmPFC damage and increased apathy is driven by impaired valuation. An auction task was used to measure valuation, and apathy was assessed via caregiver ratings of patients' day-to-day behavior. Lesion-symptom mapping identified the locus of impaired valuation in the vmPFC, and patients with damage to this region demonstrated increased apathy relative to patients with damage to dorsomedial prefrontal cortex (dmPFC), patients with damage to other brain regions, and healthy controls. Critically, the association between vmPFC damage and apathy was mediated by impaired valuation, with no effect as a function of dmPFC damage. Our results implicate a valuation-based mechanism underlying the relationship between vmPFC integrity and apathy, bridging findings from both the clinical literature and neuroeconomics research.

Investigating the Neural Correlates of Schemas: Ventromedial Prefrontal Cortex Is Necessary for Normal Schematic Influence on Memory.

In the human brain, new memories are strongly influenced by existing knowledge of relevant context (sometimes called "schemas"). Schemas can benefit memory by expediting learning and increasing capacity in familiar contexts, but these benefits may simultaneously reduce episode-specific memory. Here we show that damage to the human ventromedial prefrontal cortex (vmPFC) reduced the influence of existing knowledge on new memories. Our findings suggest that the vmPFC plays a key role in schematic memory processes by integrating previous experiences and contextual information to influence memory. These findings provide novel insight into the brain regions necessary for normal schematic memory and enhance our understanding of the brain networks supporting memory processes.

Effects of penetrating traumatic brain injury on event segmentation and memory

Penetrating traumatic brain injury (pTBI) is associated with deficits in cognitive tasks including comprehension and memory, and also with impairments in tasks of daily living. In naturalistic settings, one important component of cognitive task performance is event segmentation, the ability to parse the ongoing stream of behavior into meaningful units. Event segmentation ability is associated with memory performance and with action control, but is not well assessed by standard neuropsychological assessments or laboratory tasks. Here, we measured event segmentation and memory in a sample of 123 male military veterans aged 59–81 who had suffered a traumatic brain injury as young men, and 34 demographically similar controls. Participants watched movies of everyday activities and segmented them to identify fine-grained or coarse-grained events, and then completed tests of recognition memory for pictures from the movies and of memory for the temporal order of actions in the movies. Lesion location and volume were assessed with computed tomography (CT) imaging. Patients with traumatic brain injury were impaired on event segmentation. Those with larger lesions had larger impairments for fine segmentation and also impairments for both memory measures. Further, the degree of memory impairment was statistically mediated by the degree of event segmentation impairment. There was some evidence that lesions to the ventromedial prefrontal cortex (vmPFC) selectively impaired coarse segmentation; however, lesions outside of a priori regions of interest also were associated with impaired segmentation. One possibility is that the effect of vmPFC damage reflects the role of prefrontal event knowledge representations in ongoing comprehension. These results suggest that assessment of naturalistic event comprehension can be a valuable component of cognitive assessment in cases of traumatic brain injury, and that interventions aimed at event segmentation could be clinically helpful.

Memory, Decision-Making, and the Ventromedial Prefrontal Cortex (vmPFC): The Roles of Subcallosal and Posterior Orbitofrontal Cortices in Monitoring and Control Processes.

The ventromedial prefrontal cortex (vmPFC) prominently and separately features in neurobiological models of decision-making (e.g., value-encoding) and of memory (e.g., automatic veracity-monitoring). Recent decision-making models propose value judgments that inherently comprise of second-order confidence estimates. These demonstrate quadratic relationships with first-order judgments and are automatically encoded in vmPFC activity. Memory studies use Quantity-Accuracy Profiles to capture similar first-order and second-order meta-mnemonic processes, suggesting convergence across domains. Patients with PFC damage answered general knowledge questionnaires under 2 conditions. During forcedreport, they chose an answer and rated the probability of it being correct (first-order "monitoring"). During free report, they could choose to volunteer or withhold their previous answers (second-order "control") to maximize performance. We found quadratic relationships between first-order and second-order meta-mnemonic processes; voxel-based lesion-symptom mapping demonstrated that vmPFC damage diminished that relationship. Furthermore, damage to subcallosal vmPFC was specifically associated with impaired monitoring and additional damage to posterior orbitofrontal cortex led to deficient control. In decision-making, these regions typically support valuation and choice, respectively. Persistent spontaneous confabulation (false memory production) confirmed the clinical relevance of these dissociations. Compared with patients with no confabulation history, patients who currently confabulate were impaired on both monitoring and control, whereas former confabulators demonstrated impaired monitoring but intact control.

Sex-related functional asymmetry of the ventromedial prefrontal cortex in regard to decision-making under risk and ambiguity

Previous work has provided preliminary indication of sex-related functional asymmetry of the ventromedial prefrontal cortex (vmPFC) in social and emotional functions and complex decision-making. Findings have been inconsistent, and based on small numbers of patients. Given the rarity of these neurological cases, replicable results across studies are important to build evidence for sex-related functional asymmetry of the vmPFC. Here we used a sample of sixteen neurological patients with unilateral damage to the left or right vmPFC and examined differences between men and women on a task that probed decision-making under risk or decision-making under ambiguity. We found that men with right-hemisphere vmPFC damage and women with left-hemisphere vmPFC damage demonstrated significantly reduced aversion to risk and ambiguity. Men with damage to the left vmPFC and women with damage to the right vmPFC showed aversion to risk and ambiguity comparable to participants with left or right-sided brain damage outside the vmPFC, and to comparison participants without brain damage. Our results add to previous findings of sex-related functional asymmetry of the vmPFC in decision-making. Our study also replicates findings of no observable behavioral differences between men and women without neurological damage on tests of decision-making. This pattern of neurobiological divergence but behavioral convergence between men and women may reflect a complex interplay of neuroendocrine, developmental, and psychosocial factors.

Susceptibility to social pressure following ventromedial prefrontal cortex damage.

Social pressure influences human behavior including risk taking, but the psychological and neural underpinnings of this process are not well understood. We used the human lesion method to probe the role of ventromedial prefrontal cortex (vmPFC) in resisting adverse social pressure in the presence of risk. Thirty-seven participants (11 with vmPFC damage, 12 with brain damage outside the vmPFC and 14 without brain damage) were tested in driving simulator scenarios requiring left-turn decisions across oncoming traffic with varying time gaps between the oncoming vehicles. Social pressure was applied by a virtual driver who honked aggressively from behind. Participants with vmPFC damage were more likely to select smaller and potentially unsafe gaps under social pressure, while gap selection by the comparison groups did not change under social pressure. Participants with vmPFC damage also showed prolonged elevated skin conductance responses (SCR) under social pressure. Comparison groups showed similar initial elevated SCR, which then declined prior to making left-turn decisions. The findings suggest that the vmPFC plays an important role in resisting explicit and immediately present social pressure with potentially negative consequences. The vmPFC appears to contribute to the regulation of emotional responses and the modulation of decision making to optimize long-term outcomes.

Damage to the Ventromedial Prefrontal Cortex Impairs Learning from Observed Outcomes.

Individuals learn both from the outcomes of their own internally generated actions (“experiential learning”) and from the observation of the consequences of externally generated actions (“observational learning”). While neuroscience research has focused principally on the neural mechanisms by which brain structures such as the ventromedial prefrontal cortex (vmPFC) support experiential learning, relatively less is known regarding how learning proceeds through passive observation. We explored the necessity of the vmPFC for observational learning by testing a group of patients with damage to the vmPFC as well as demographically matched normal comparison and brain-damaged comparison groups—and a single patient with bilateral dorsal prefrontal damage—using several value-learning tasks that required learning from direct experience, observational learning, or both. We found a specific impairment in observational learning in patients with vmPFC damage manifest in the reduced influence of previously observed rewards on current choices, despite a relatively intact capacity for experiential learning. The current study provides evidence that the vmPFC plays a critical role in observational learning, suggests that there are dissociable neural circuits for experiential and observational learning, and offers an important new extension of how the vmPFC contributes to learning and memory.

Altered Communicative Decisions following Ventromedial Prefrontal Lesions

Damage to the human ventromedial prefrontal cortex (vmPFC) leads to profound changes in everyday social interactions [1, 2]. Yet, in the lab, vmPFC patients show surprising proficiency in reasoning about other agents [3-8]. These conflicting observations suggest that what vmPFC patients lack in everyday social interactions might be the ability to guide their decisions with knowledge about a social partner [9-13], despite preserved access to that knowledge [2, 14]. Quantification of socially relevant decisions during live interaction with different partners offers the possibility of testing this hypothesis. Eight patients with vmPFC damage, eight patients with brain damage elsewhere, and 15 healthy participants were asked to communicate non-verbally with two different addressees, an adult or a child, in an experimentally controlled interactive setting [15, 16]. In reality, a confederate blindly performed the role of both adult and child addressee, with matched performance and response times, such that the two addressees differed only in terms of the communicator's beliefs. Patients with vmPFC damage were able-and motivated-to generate communicatively effective behaviors. However, unlike patient and healthy controls, vmPFC patients failed to adjust their communicative decisions to the presumed abilities of their addressee. These findings indicate that the human vmPFC is necessarily involved in social interactions, insofar as those interactions need to be tailored toward knowledge about a social partner. In this perspective, the known contribution of this region to disparate domains like value-based decision-making[17-19], schema-based memory-processing [20-22], and person-specific mentalizing [11-13] might be instances of decisions based on contingently updated conceptual knowledge.

A neuropsychological investigation of decisional certainty

The certainty that one feels following a decision increases decision-making efficiency, but can also result in decreased decision accuracy. In the current study, a neuropsychological approach was used to examine the impact of damage to the ventromedial prefrontal cortex (vmPFC) on core psychological processes promoting decision certainty: selective exposure, overconfidence, and decisiveness. Given previous research demonstrating that vmPFC damage disrupts the generation of negative emotional (somatic) states that have been associated with selective exposure and overconfidence, it was hypothesized that damage to the vmPFC would disrupt engagement in selective exposure, decrease overconfidence, and increase indecision. Individuals with vmPFC damage exhibited increased indecision, but contrary to our hypothesis, engaged in similar levels of selective exposure and overconfidence as the comparison groups. These results indicate that indecision may be an important psychological mechanism involved in decision-making impairments associated with vmPFC injury. The results also suggest that the vmPFC may not be critical for selective exposure or overconfidence, which provides support for a recent “desirability” account of selective exposure.

Use of reported speech in the communicative interactions of individuals with ventromedial prefrontal cortex damage

Reported speech (RS) is a pervasive discourse practice in which speakers represent, or re-enact, words, thoughts, or feelings from other times and/or places, and it is thought to reflect and create emotional connections among interlocutors. The current study examines the role of the ventromedial prefrontal cortex (vmPFC), a neural structure critical for social, emotional, and interpersonal behavior, in the use of reported speech. In the communicative interactions of six individuals with vmPFC damage and six healthy comparison participants, each interacting with a clinician, we compared the frequency and use of reported speech. Contrary to our predictions, the vmPFC participants did not differ from healthy participants in the frequency or use of reported speech. These results suggest that the vmPFC does not make critical contributions to the use of reported speech in conversation and furthers our understanding of neural and cognitive underpinnings of reported speech and language use.

Ventromedial prefrontal cortex damage alters resting blood flow to the bed nucleus of stria terminalis

The ventromedial prefrontal cortex (vmPFC) plays a key role in modulating emotional responses, yet the precise neural mechanisms underlying this function remain unclear. vmPFC interacts with a number of subcortical structures involved in affective processing, including the amygdala, hypothalamus, periaqueductal gray, ventral striatum, and bed nucleus of stria terminalis (BNST). While a previous study of non-human primates shows that vmPFC lesions reduce BNST activity and anxious behavior, no such causal evidence exists in humans. In this study, we used a novel application of magnetic resonance imaging (MRI) in neurosurgical patients with focal, bilateral vmPFC damage to determine whether vmPFC is indeed critical for modulating BNST function in humans. Relative to neurologically healthy subjects, who exhibited robust rest-state functional connectivity between vmPFC and BNST, the vmPFC lesion patients had significantly lower resting-state perfusion of the right BNST. No such perfusion differences were observed for the amygdala, striatum, hypothalamus, or periaqueductal gray. This study thus provides unique data on the relationship between vmPFC and BNST, suggesting that vmPFC serves to promote BNST activity in humans. This finding is relevant for neural circuitry models of mood and anxiety disorders.

Schema representation in patients with ventromedial PFC lesions.

Human neuroimaging and animal studies have recently implicated the ventromedial prefrontal cortex (vmPFC) in memory schema, particularly in facilitating new encoding by existing schemas. In humans, the most conspicuous memory disorder following vmPFC damage is confabulation; strategic retrieval models suggest that aberrant schema activation or reinstatement plays a role in confabulation. This raises the possibility that beyond its role in schema-supported memory encoding, the vmPFC is also implicated in schema reinstatement itself. If that is the case, vmPFC lesions should lead to impaired schema-based operations, even on tasks that do not involve memory acquisition. To test this prediction, ten patients with vmPFC damage, four with present or prior confabulation, and a group of twelve matched healthy controls made speeded yes/no decisions as to whether words were closely related to a schema (a visit to the doctor). Ten minutes later, they repeated the task for a new schema (going to bed) with some words related to the first schema included as lures. Last, they rated the degree to which stimuli were related to the second schema. All four vmPFC patients with present or prior confabulation were impaired in rejecting lures and in classifying stimulus belongingness to the schema, even when they were not lures. Nonconfabulating patients performed comparably to healthy adults with high accuracy, comparable reaction times, and similar ratings. These results show for the first time that damage to the human vmPFC, when associated with confabulation, leads to deficient schema reinstatement, which is likely a prerequisite for schema-mediated memory integration.