Damage To Orbitofrontal Cortex Research Articles

Orbitofrontal cortex governs working memory for temporal order

How do we think about time? Converging lesion and neuroimaging evidence indicates that orbitofrontal cortex (OFC) supports the encoding and retrieval of temporal context in long-term memory1, which may contribute to confabulation in individuals with OFC damage2. Here, we reveal that OFC damage diminishes working memory for temporal order, that is, the ability to disentangle the relative recency of events as they unfold. OFC lesions reduced working memory for temporal order but not spatial position, and individual deficits were commensurate with lesion size. Comparable effects were absent in patients with lesions restricted to lateral prefrontal cortex (PFC). Based on these findings, we propose that OFC supports understanding of the order of events. Well-documented behavioral changes in individuals with OFC damage2 may relate to impaired temporal-order understanding.

Bridging across functional models: The OFC as a value-making neural network.

Many functions have been attributed to the orbitofrontal cortex (OFC)-some classical roles, such as signaling the value of action outcomes, being challenged by more recent ones, such as signaling the position of a trial within a task space. In this paper, we propose a unifying neural network architecture, whose function is to generate a value from a set of attributes attached to a particular object. Our model reverses the logic of perceptual choice models, by considering values as outputs of (and not inputs to) the neural network. In doing so, the model explains why univariate value signals have been observed in both likeability rating and economic choice tasks, while the features associated with a particular task trial can be decoded using multivariate analysis. Moreover, simulations show that a globally positive correlation with subjective value at the population level can coexist with a variety of correlation coefficients at the single-unit level, bridging typical observations made in human neuroimaging and monkey electrophysiology studies of OFC activity. To better explain binary choice, we equipped the neural network with recurrent feedback connections that enable simultaneous coding of values associated with currently attended and previously considered objects. Simulations of this augmented model show that virtual lesions produce systematically intransitive preferences, as observed in patients with damage to the OFC. Thus, our neural network model is sufficiently general and flexible to account for a core set of observations and make specific predictions about both OFC activity during value judgment and behavioral consequence of OFC damage. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Chapter 1 - The neuroscience of emotional disorders

Emotions can be defined as states elicited by rewards or punishments, and indeed the neurology of emotional disorders can be understood in terms of this foundation. The orbitofrontal cortex in humans and other primates is a critical area in emotion processing, determining the value of stimuli and whether they are rewarding or nonrewarding. The cortical processing that occurs before the orbitofrontal cortex primarily involves defining the identity of stimuli, i.e., "what" is present and not reward value. There is evidence that this holds true for taste, visual, somatosensory, and olfactory stimuli. The human medial orbitofrontal cortex is important in processing many different types of reward, and the lateral orbitofrontal cortex in processing nonreward and punishment. Humans with damage to the orbitofrontal cortex have an impaired ability to identify facial and voice expressions of emotions, and impaired subjective experience of emotion. They can have an altered personality and be impulsive because they are impaired at processing failures to receive expected rewards and at processing punishments. In humans, the role of the amygdala in the processing of emotions is reduced because of the great evolutionary development of the orbitofrontal cortex: amygdala damage has much less effect on emotion than does orbitofrontal cortex damage. The orbitofrontal cortex projects reward value information to the anterior cingulate cortex, which is involved in learning those actions required to obtain rewards and avoid punishments. The cingulate cortex thus provides an output route for emotional behavior. In depression, the medial orbitofrontal cortex has decreased connectivity and sensitivity to reward, and the lateral orbitofrontal cortex has increased connectivity and sensitivity to nonreward. The orbitofrontal cortex has major projections to the anterior cingulate cortex, including its subcommissural region, and the anterior cingulate cortex is also implicated in depression.

Rapid Rule-Based Reward Reversal and the Lateral Orbitofrontal Cortex.

Humans and other primates can reverse their choice of stimuli in one trial when the rewards delivered by the stimuli change or reverse. Rapidly changing our behavior when the rewards change is important for many types of behavior, including emotional and social behavior. It is shown in a one-trial rule-based Go-NoGo deterministic visual discrimination reversal task to obtain points, that the human right lateral orbitofrontal cortex and adjoining inferior frontal gyrus is activated on reversal trials, when an expected reward is not obtained, and the non-reward allows the human to switch choices based on a rule. This reward reversal goes beyond model-free reinforcement learning. This functionality of the right lateral orbitofrontal cortex shown here in very rapid, one-trial, rule-based changes in human behavior when a reward is not received is related to the emotional and social changes that follow orbitofrontal cortex damage, and to depression in which this non-reward system is oversensitive and over-connected.

Preservation of Interference Effects in Working Memory After Orbitofrontal Damage.

Orbitofrontal cortex (OFC) is implicated in multiple cognitive processes, including inhibitory control, context memory, recency judgment, and choice behavior. Despite an emerging understanding of the role of OFC in memory and executive control, its necessity for core working memory (WM) operations remains undefined. Here, we assessed the impact of OFC damage on interference effects in WM using a Recent Probes task based on the Sternberg item-recognition task (1966). Subjects were asked to memorize a set of letters and then indicate whether a probe letter was presented in a particular set. Four conditions were created according to the forthcoming response (“yes”/“no”) and the recency of the probe (presented in the previous trial set or not). We compared behavioral and electroencephalography (EEG) responses between healthy subjects (n = 14) and patients with bilateral OFC damage (n = 14). Both groups had the same recency pattern of slower reaction time (RT) when the probe was presented in the previous trial but not in the current one, reflecting the proactive interference (PI). The within-group electrophysiological results showed no condition difference during letter encoding and maintenance. In contrast, event-related potentials (ERPs) to probes showed distinct within-group condition effects, and condition by group effects. The response and recency effects for controls occurred within the same time window (300–500 ms after probe onset) and were observed in two distinct spatial groups including right centro-posterior and left frontal electrodes. Both clusters showed ERP differences elicited by the response effect, and one cluster was also sensitive to the recency manipulation. Condition differences for the OFC group involved two different clusters, encompassing only left hemisphere electrodes and occurring during two consecutive time windows (345–463 ms and 565–710 ms). Both clusters were sensitive to the response effect, but no recency effect was found despite the behavioral recency effect. Although the groups had different electrophysiological responses, the maintenance of letters in WM, the evaluation of the context of the probe, and the decision to accept or reject a probed letter were preserved in OFC patients. The results suggest that neural reorganization may contribute to intact recency judgment and response after OFC damage.

Patients with basal ganglia damage show preserved learning in an economic game

Both basal ganglia (BG) and orbitofrontal cortex (OFC) have been widely implicated in social and non-social decision-making. However, unlike OFC damage, BG pathology is not typically associated with disturbances in social functioning. Here we studied the behavior of patients with focal lesions to either BG or OFC in a multi-strategy competitive game known to engage these regions. We find that whereas OFC patients are significantly impaired, BG patients show intact learning in the economic game. By contrast, when information about the strategic context is absent, both cohorts are significantly impaired. Computational modeling further shows a preserved ability in BG patients to learn by anticipating and responding to the behavior of others using the strategic context. These results suggest that apparently divergent findings on BG contribution to social decision-making may instead reflect a model where higher-order learning processes are dissociable from trial-and-error learning, and can be preserved despite BG damage.

Impairment in judgement of the moral emotion guilt following orbitofrontal cortex damage

Although neuroimaging studies have provided evidence for an association between moral emotions and the orbitofrontal cortex, studies on patients with focal lesions using experimental probes of moral emotions are scarce. Here, we addressed this topic by presenting a moral emotion judgement task to patients with focal brain damage. Four judgement tasks in a simple pairwise choice paradigm were given to 72 patients with cerebrovascular disease. These tasks consisted of a perceptual line judgement task as a control task; the objects' preference task as a basic preference judgement task; and two types of moral emotion judgement task, an anger task and a guilt task. A multiple linear regression analysis was performed on each set of task performance scores to take into account potential confounders. Performance on the guilt emotion judgement task negatively correlated with the orbitofrontal cortex damage, but not with the other variables. Results for the other judgement tasks did not reach statistical significance. The close association between orbitofrontal cortex damage and a decrease in guilt emotion judgement consistency might suggest that the orbitofrontal cortex plays a key role in the sense of guilt, a hallmark of morality.

「人となり」における大脳内側面・底面（眼窩面）の役割

「人となり」における大脳内側面・底面（眼窩面）の役割

The role of the orbitofrontal cortex in regulation of interpersonal space: evidence from frontal lesion and frontotemporal dementia patients.

Interpersonal distance is central to communication and complex social behaviors but the neural correlates of interpersonal distance preferences are not defined. Previous studies suggest that damage to the orbitofrontal cortex (OFC) is associated with impaired interpersonal behavior. To examine whether the OFC is critical for maintaining appropriate interpersonal distance, we tested two groups of patients with OFC damage: Patients with OFC lesions and patients with behavioral variant frontotemporal dementia. These two groups were compared to healthy controls and to patients with lesions restricted to the dorsolateral prefrontal cortex. Only patients with OFC damage showed abnormal interpersonal distance preferences, which were significantly different from both controls and patients with dorsolateral prefrontal damage. The comfortable distances these patients chose with strangers were significantly closer than the other groups and resembled distances normally used with close others. These results shed light on the role of the OFC in regulating social behavior and may serve as a simple diagnostic tool for dementia or lesion patients.

Specialized areas for value updating and goal selection in the primate orbitofrontal cortex.

The macaque orbitofrontal cortex (OFC) is essential for selecting goals based on current, updated values of expected reward outcomes. As monkeys consume a given type of reward to satiety, its value diminishes, and OFC damage impairs the ability to shift goal choices away from devalued outcomes. To examine the contributions of OFC's components to goal selection, we reversibly inactivated either its anterior (area 11) or posterior (area 13) parts. We found that neurons in area 13 must be active during the selective satiation procedure to enable the updating of outcome valuations. After this updating has occurred, however, area 13 is not needed to select goals based on this knowledge. In contrast, neurons in area 11 do not need to be active during the value-updating process. Instead, inactivation of this area during choices causes an impairment. These findings demonstrate selective and complementary specializations within the OFC.

Lateral orbitofrontal cortex links social impressions to political choices.

Recent studies of political behavior suggest that voting decisions can be influenced substantially by "first-impression" social attributions based on physical appearance. Separate lines of research have implicated the orbitofrontal cortex (OFC) in the judgment of social traits on the one hand and economic decision-making on the other, making this region a plausible candidate for linking social attributions to voting decisions. Here, we asked whether OFC lesions in humans disrupted the ability to judge traits of political candidates or affected how these judgments influenced voting decisions. Seven patients with lateral OFC damage, 18 patients with frontal damage sparing the lateral OFC, and 53 matched healthy participants took part in a simulated election paradigm, in which they voted for real-life (but unknown) candidates based only on photographs of their faces. Consistent with previous work, attributions of "competence" and "attractiveness" based on candidate appearance predicted voting behavior in the healthy control group. Frontal damage did not affect substantially the ability to make competence or attractiveness judgments, but patients with damage to the lateral OFC differed from other groups in how they applied this information when voting. Only attractiveness ratings had any predictive power for voting choices after lateral OFC damage, whereas other frontal patients and healthy controls relied on information about both competence and attractiveness in making their choice. An intact lateral OFC may not be necessary for judgment of social traits based on physical appearance, but it seems to be crucial in applying this information in political decision-making.

Anodal tDCS targeting the right orbitofrontal cortex enhances facial expression recognition.

The orbitofrontal cortex (OFC) has been implicated in the capacity to accurately recognise facial expressions. The aim of the current study was to determine if anodal transcranial direct current stimulation (tDCS) targeting the right OFC in healthy adults would enhance facial expression recognition, compared with a sham condition. Across two counterbalanced sessions of tDCS (i.e. anodal and sham), 20 undergraduate participants (18 female) completed a facial expression labelling task comprising angry, disgusted, fearful, happy, sad and neutral expressions, and a control (social judgement) task comprising the same expressions. Responses on the labelling task were scored for accuracy, median reaction time and overall efficiency (i.e. combined accuracy and reaction time). Anodal tDCS targeting the right OFC enhanced facial expression recognition, reflected in greater efficiency and speed of recognition across emotions, relative to the sham condition. In contrast, there was no effect of tDCS to responses on the control task. This is the first study to demonstrate that anodal tDCS targeting the right OFC boosts facial expression recognition. This finding provides a solid foundation for future research to examine the efficacy of this technique as a means to treat facial expression recognition deficits, particularly in individuals with OFC damage or dysfunction.

The nature of facial expression recognition deficits following orbitofrontal cortex damage.

Orbitofrontal cortex (OFC) damage has been associated with facial expression recognition deficits in some, but not all, previous studies. The pattern of performance of a group of patients with OFC damage was assessed across a series of facial expression recognition tasks. We aimed to determine whether some tasks were more sensitive at detecting deficits than others. Seven patients with damage to the OFC, 6 control patients with frontal lesions that spared the OFC, and a group of healthy controls completed a series of facial expression recognition tasks including 2 labeling tasks and 2 matching tasks. The OFC patient group demonstrated impaired labeling of negative facial expressions (i.e., anger, disgust, fear, and sadness) shown for a short time (500 ms) relative to the comparison groups. When facial expressions were shown for a longer time (5,000 ms), the OFC patient group's performance did not differ significantly from either comparison group. The OFC patient group was impaired when matching subtle, low intensity negative facial expressions, but not when matching high intensity, prototypical facial expressions. The pattern of performance across tasks revealed that only certain facial expression recognition tasks appear to be sufficiently sensitive to detect deficits in patients with OFC damage. These findings have important implications for the assessment of facial expression recognition difficulties in patients with OFC damage and more broadly, for special populations.

Taste and odour-induced taste perception following unilateral lesions to the anteromedial temporal lobe and the orbitofrontal cortex

Odour-induced tastes occur when smelling certain odours (e.g., sweet-smelling vanilla) and may represent a universal form of synaesthesia. If odour-induced tastes are perceptually akin to tastes generated by stimulating taste receptors on the tongue, as perceptual data imply, then these two forms of gustatory experience may also share common processing resources in the brain. In this study, we examine this hypothesis for two secondary gustatory processing areas—the orbitofrontal cortex (OFC) and amygdala. We compared nine patients with anteromedial temporal lobe (AMTL) resections that included the amygdala, and three patients with OFC damage, to a healthy comparison group (n = 42), on tests of olfactory, gustatory, and odour-induced taste perception. While AMTL patients had a range of generally small taste impairments, they were unimpaired on tests of odour-induced taste perception. Two of the three OFC cases had impairments in taste hedonics and discrimination. The case with the most profound gustatory deficit was also mildly impaired on tests of odour-induced taste perception. The OFC findings are consistent with overlaps in circuits supporting taste and odour-induced taste perception, especially those responsible for more perceptual aspects of processing.

Beyond Reversal: A Critical Role for Human Orbitofrontal Cortex in Flexible Learning from Probabilistic Feedback

Damage to the orbitofrontal cortex (OFC) has been linked to impaired reinforcement processing and maladaptive behavior in changing environments across species. Flexible stimulus-outcome learning, canonically captured by reversal learning tasks, has been shown to rely critically on OFC in rats, monkeys, and humans. However, the precise role of OFC in this learning remains unclear. Furthermore, whether other frontal regions also contribute has not been definitively established, particularly in humans. In the present study, a reversal learning task with probabilistic feedback was administered to 39 patients with focal lesions affecting various sectors of the frontal lobes and to 51 healthy, demographically matched control subjects. Standard groupwise comparisons were supplemented with voxel-based lesion-symptom mapping to identify regions within the frontal lobes critical for task performance. Learning in this dynamic stimulus-reinforcement environment was considered both in terms of overall performance and at the trial-by-trial level. In this challenging, probabilistic context, OFC damage disrupted both initial and reversal learning. Trial-by-trial performance patterns suggest that OFC plays a critical role in interpreting feedback from a particular trial within the broader context of the outcome history across trials rather than in simply suppressing preexisting stimulus-outcome associations. The findings show that OFC, and not other prefrontal regions, plays a necessary role in flexible stimulus-reinforcement learning in humans.

The role of the orbitofrontal cortex in affective theory of mind deficits in criminal offenders with psychopathic tendencies

Individuals with psychopathy show impaired emotional and social behavior, such as lack of emotional responsiveness to others and deficient empathy. However, there are controversies regarding these individuals theory of mind (ToM) abilities and the neuroanatomical basis of their aberrant social behavior. The present study tested the hypothesis that impairment in the emotional aspects of ToM (affective ToM) rather than general ToM abilities may account for the impaired social behavior observed in psychopathy and that this pattern of performance may be associated with orbitofrontal cortex (OFC) dysfunction. To assess the emotional and cognitive aspects of ToM we used a task that examines affective versus cognitive ToM processing in separate conditions. ToM abilities of criminal offender diagnosed with antisocial personality disorder with high psychopathy features were compared to that of participants with localized lesions in the OFC or dorsolateral, participants with non-frontal lesions, and healthy control subjects. Individuals with psychopathy and those with OFC lesions were impaired on the ‘affective ToM’ conditions but not in cognitive ToM conditions, compared to the control groups. It was concluded that the pattern of mentalizing impairments in psychopathy resembles remarkably that seen in participants with lesions of the frontal lobe, particularly with OFC damage, providing support for the notion of amygdala–OFC dysfunction in psychopathy.

Construct Validity of the Iowa Gambling Task

The Iowa Gambling Task (IGT) was created to assess real-world decision making in a laboratory setting and has been applied to various clinical populations (i.e., substance abuse, schizophrenia, pathological gamblers) outside those with orbitofrontal cortex damage, for whom it was originally developed. The current review provides a critical examination of lesion, functional neuroimaging, developmental, and clinical studies in order to examine the construct validity of the IGT. The preponderance of evidence provides support for the use of the IGT to detect decision making deficits in clinical populations, in the context of a more comprehensive evaluation. The review includes a discussion of three critical issues affecting the validity of the IGT, as it has recently become available as a clinical instrument: the lack of a concise definition as to what aspect of decision making the IGT measures, the lack of data regarding reliability of the IGT, and the influence of personality and state mood on IGT performance.

The role of the orbitofrontal cortex in human discrimination learning

Several lines of evidence implicate the prefrontal cortex in learning but there is little evidence from studies of human lesion patients to demonstrate the critical role of this structure. To this end, we tested patients with lesions of the frontal lobe (n=36) and healthy controls (n=35) on two learning tasks: the weather prediction task (WPT), and an eight-pair concurrent visual discrimination task (‘Choose’). Performance of both tasks was previously shown to be disrupted in patients with Parkinson's disease; the Choose deficit was only present when patients were medicated. Patients with damage to the orbitofrontal cortex (OFC) were significantly impaired on Choose, compared to both healthy controls and non-OFC lesion patients. The OFC lesion patients showed a mild deficit on the first 50 trials of the WPT, compared to the control subjects but not non-OFC lesion patients. The selective deficit in the OFC patients on Choose performance could not be attributed to the larger lesion size in this group, and the deficit was not correlated with the volume of damage to adjacent prefrontal subregions (e.g. anterior cingulate cortex). These data support the notion that the OFC play a role in normal discrimination learning, and suggest qualitative similarities in learning performance of patients with OFC damage and medicated PD patients.

Dysfunctions of Medial and Lateral Orbitofrontal Cortex in Psychopathy

Psychopathy is a developmental disorder marked by emotional hypo-responsiveness and an increased risk for instrumental and reactive aggression. In this paper, it will be argued that the developmental origins of psychopathy do not lie in orbitofrontal cortex (OFC) dysfunction. This is because the key functional impairments seen in psychopathy are associated with amygdala damage, not with OFC damage. However, it will be argued that the role played by the integrated functioning of the amygdala and medial OFC in stimulus-reinforcement learning and decision making is disrupted in psychopathy. Impaired learning of stimulus-reinforcement associations and representation of reinforcement expectations are thought to underlie the impairments in socialization and appropriate decision making seen in psychopathy. It is suggested that the impairment in the role of medial OFC in prediction error signaling and the detection of contingency change may underlie the impairments in flexible behavioral change seen in psychopathy.

Neural Encoding in the Orbitofrontal Cortex Related to Goal‐Directed Behavior

Research using laboratory animals, alongside clinical studies of human patients, support a role for the orbitofrontal cortex (OFC) in adaptive decision-making and goal-directed behavior. The functions of OFC neurons within this domain have been studied extensively in both rats and primates. Electrophysiological recordings during performance of relevant behavioral tasks provide a coherent portrait of OFC encoding that is reward related. OFC neurons represent associative relationships between events, encoding information that is predictive of outcome value. That encoding can be understood as a neural basis for deficits seen after OFC damage in the use of outcome expectancy to guide performance. There is less agreement, however, on whether OFC itself plays a role in translating information on outcome expectancy into the actual guidance of overt behavioral responding. New findings indicate that rat OFC neurons prominently encode additional task-related information and events related to goal-directed action. This encoding can occur in populations of OFC neurons that are independent of the OFC neurons representing reward value. The significance of this emerging evidence may require studies that address the larger scale network through which OFC integrates expected outcome information with behavioral control.