Orbitofrontal Cortex Patients Research Articles

Altered hierarchical auditory predictive processing after lesions to the orbitofrontal cortex.

Orbitofrontal cortex (OFC) is classically linked to inhibitory control, emotion regulation, and reward processing. Recent perspectives propose that the OFC also generates predictions about perceptual events, actions, and their outcomes. We tested the role of the OFC in detecting violations of prediction at two levels of abstraction (i.e., hierarchical predictive processing) by studying the event-related potentials (ERPs) of patients with focal OFC lesions (n = 12) and healthy controls (n = 14) while they detected deviant sequences of tones in a local-global paradigm. The structural regularities of the tones were controlled at two hierarchical levels by rules defined at a local (i.e., between tones within sequences) and at a global (i.e., between sequences) level. In OFC patients, ERPs elicited by standard tones were unaffected at both local and global levels compared to controls. However, patients showed an attenuated mismatch negativity (MMN) and P3a to local prediction violation, as well as a diminished MMN followed by a delayed P3a to the combined local and global level prediction violation. The subsequent P3b component to conditions involving violations of prediction at the level of global rules was preserved in the OFC group. Comparable effects were absent in patients with lesions restricted to the lateral PFC, which lends a degree of anatomical specificity to the altered predictive processing resulting from OFC lesion. Overall, the altered magnitudes and time courses of MMN/P3a responses after lesions to the OFC indicate that the neural correlates of detection of auditory regularity violation are impacted at two hierarchical levels of rule abstraction.

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.

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.

Orbito-frontal Cortex is Necessary for Temporal Context Memory

Lesion and neuroimaging studies suggest that orbito-frontal cortex (OFC) supports temporal aspects of episodic memory. However, it is unclear whether OFC contributes to the encoding and/or retrieval of temporal context and whether it is selective for temporal relative to nontemporal (spatial) context memory. We addressed this issue with two complimentary studies: functional magnetic resonance imaging to measure OFC activity associated with successful temporal and spatial context memory during encoding and retrieval in healthy young participants, and a neuropsychological investigation to measure changes in spatial and temporal context memory in OFC lesion patients. Imaging results revealed that OFC contributed to encoding and retrieval of associations between objects and their temporal but not their spatial contexts. Consistent with this, OFC patients exhibited impairments in temporal but not spatial source memory accuracy. These results suggest that OFC plays a critical role in the formation and subsequent retrieval of temporal context.

Orbito-frontal lesions cause impairment during late but not early emotional prosodic processing

The orbitofrontal cortex (OFC) is functionally linked to a variety of cognitive and emotional functions. In particular, lesions of the human OFC lead to large-scale changes in social and emotional behavior. For example, patients with OFC lesions are reported to suffer from deficits in affective decision-making, including impaired emotional face and voice expression recognition (e.g., Hornak et al., 1996, 2003). However, previous studies have failed to acknowledge that emotional processing is a multistage process. Thus, different stages of emotional processing (e.g., early vs. late) in the same patient group could be affected in a qualitatively different manner. The present study investigated this possibility and tested implicit emotional speech processing in an ERP experiment followed by an explicit behavioral emotional recognition task. OFC patients listened to vocal emotional expressions of anger, fear, disgust, and happiness compared to a neutral baseline spoken either with or without lexical content. In line with previous evidence (Paulmann & Kotz, 2008b), both patients and healthy controls differentiate emotional and neutral prosody within 200 ms (P200). However, the recognition of emotional vocal expressions is impaired in OFC patients as compared to healthy controls. The current data serve as first evidence that emotional prosody processing is impaired only at a late, and not at an early processing stage in OFC patients.

The effect of orbitofrontal lesions on the error-related negativity

Current theories of orbitofrontal cortex (OFC) function suggest that this region should participate in the generation of error-related signals associated with the outcomes of actions. We investigated the impact of lesions to OFC on the error-related negativity (ERN), an electrophysiological marker of performance monitoring. Four OFC patients and eight control subjects participated in a manual Stroop task while brain electrical activity was recorded. We found that the ERN was attenuated in the patient group. Three of the patients also had impaired error correction performance, but all showed normal post-error slowing. These findings suggest OFC involvement in monitoring and evaluation of ongoing 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.

The Role of Orbitofrontal Cortex in Decision Making

Clinical accounts of the effects of damage to orbitofrontal cortex (OFC) have provided important clues about the functions of this region in humans. Patients with OFC injury can demonstrate relatively isolated difficulties with decision making, and the development of laboratory tasks that captured these difficulties was an important advance. However, much of the work to date has been limited by the use of a single, complex decision-making task and by a narrow focus on risky decisions. A fuller understanding of the neural basis of decision making requires identification of the simpler components that underlie this complex behavior. Here, I review evidence that OFC lesions disrupt reversal learning in humans, as in animals, and show that this deficit in reversal learning is an important mechanism underlying the difficulties of such patients in the Iowa gambling task. Reversal learning, in turn, can be decomposed into simpler processes: a failure to rapidly learn from negative feedback may be the critical difficulty for OFC patients. OFC damage can also affect forms of decision making that do not require trial-by-trial learning. Preference judgment is a simple form of decision making that requires comparing the relative value of options. Humans with OFC lesions are more inconsistent in their choices, even in very simple preference judgment tasks. These results are broadly consistent with the view that OFC is critically involved in representing the relative value of stimuli, but also raise the possibility that this region plays distinct roles in reinforcement learning and value-based judgment.

Impulsivity, time perception, emotion and reinforcement sensitivity in patients with orbitofrontal cortex lesions.

Damage to the orbitofrontal cortex (OFC) in humans has been associated with disinhibited or socially inappropriate behaviour and emotional changes. Some of the changes may be related to difficulty in responding correctly to rewards and punishers, in that these patients have difficulty in learning to correct their choice of a visual stimulus when it is no longer associated with reward. We extend this fundamental approach by investigating the relationship between frontal dysfunction and impulsive behaviour, the behavioural, emotional and personality changes seen in patients with prefrontal cortex damage, and thus in addition illuminate the cognitive and biological processes that are impaired in impulsive people. OFC patients (n = 23) performed more impulsively on both self-report and cognitive/behavioural tests of impulsivity, reported more inappropriate 'frontal' behaviours, and performed worse on a stimulus-reinforcement association reversal task, than non-OFC prefrontal cortex lesion control (n = 20) and normal control (n = 39) participants. Further, OFC patients experienced more subjective anger than non-OFC and normal participants, and less subjective happiness than normals; and had a faster subjective sense of time (overestimated and underproduced time intervals) than normal controls, while non-OFC patients did not differ from normals. Finally, both OFC and non-OFC patients were less open to experience than normal participants. There were no differences between OFC patients, non-OFC lesion patients and normal controls on all other personality traits, most notably extraversion. In a spatial working memory task, the non-OFC group, most of whom had dorsolateral prefrontal cortex lesions, were impaired in that they repeatedly returned to previously chosen empty locations ('within errors'), whereas OFC patients were not impaired on this measure. Thus there is a dissociation between the effects of OFC damage which does not affect this measure of spatial working memory but does affect impulsive and inappropriate behaviour, reversal, personality, time perception and emotion; and dorsolateral prefrontal cortex damage which does affect this measure of spatial working memory, but not impulsive and inappropriate behaviour, reversal, personality, time perception and emotion. The effects of OFC damage on impulsive and related behaviours described here have implications for understanding impulsive behaviour.

Long- and short-range reward expectancy in the primate orbitofrontal cortex.

The orbitofrontal cortex (OFC) is important in motivation and emotion. We previously reported reward expectancy-related delay activities during a delayed reaction time task in primate OFC neurons. To further investigate the significance of the OFC in motivational operations, we examined pre-instruction, baseline activities of OFC neurons in relation to reward expectancy during the delayed reaction time task. In this task, an instruction cue indicated whether reward would be present or absent in the trial. Each set of four consecutive trials constituted one block within which three different kinds of rewards and one trial with no reward were given in a fixed order that differed from the monkey's reward preference. We identified two types of OFC neurons with reward expectancy-related pre-instruction activities: Step-type neurons showed stepwise changes (increase or decrease) in pre-instruction activity toward the trial with a particular outcome, which usually was the most or least attractive within a block; Pref-type neurons showed pre-instruction activity changes according to the monkey's preference for each trial's outcome. We propose that Step-type and Pref-type neurons are related to long-range and short-range reward expectancies of a particular outcome, respectively. The OFC is considered to play important roles in goal-directed behaviour by adjusting the motivational level toward a certain (current or future) outcome of a particular motivational significance based on the two kinds of reward expectancy processes. Impairments in goal-directed behaviour by OFC patients may be caused by a lack of long-range expectancy or by a deficit in compromising between short-range and long-range expectancies.