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.

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.

Impaired Facilitatory Mechanisms of Auditory Attention After Damage of the Lateral Prefrontal Cortex.

There is growing evidence that auditory selective attention operates via distinct facilitatory and inhibitory mechanisms enabling selective enhancement and suppression of sound processing, respectively. The lateral prefrontal cortex (LPFC) plays a crucial role in the top-down control of selective attention. However, whether the LPFC controls facilitatory, inhibitory, or both attentional mechanisms is unclear. Facilitatory and inhibitory mechanisms were assessed, in patients with LPFC damage, by comparing event-related potentials (ERPs) to attended and ignored sounds with ERPs to these same sounds when attention was equally distributed to all sounds. In control subjects, we observed 2 late frontally distributed ERP components: a transient facilitatory component occurring from 150 to 250 ms after sound onset; and an inhibitory component onsetting at 250 ms. Only the facilitatory component was affected in patients with LPFC damage: this component was absent when attending to sounds delivered in the ear contralateral to the lesion, with the most prominent decreases observed over the damaged brain regions. These findings have 2 important implications: (i) they provide evidence for functionally distinct facilitatory and inhibitory mechanisms supporting late auditory selective attention; (ii) they show that the LPFC is involved in the control of the facilitatory mechanisms of auditory attention.

Damage to dorsolateral prefrontal cortex affects tradeoffs between honesty and self-interest.

Substantial correlational evidence suggests that prefrontal regions are critical to honest and dishonest behavior, but causal evidence specifying the nature of this involvement remains absent. We found that lesions of the human dorsolateral prefrontal cortex (DLPFC) decreased the effect of honesty concerns on behavior in economic games that pit honesty motives against self-interest, but did not affect decisions when honesty concerns were absent. These results point to a causal role for DLPFC in honest behavior.

Hemicraniectomy: a new model for human electrophysiology with high spatio-temporal resolution.

Human electrophysiological research is generally restricted to scalp EEG, magneto-encephalography, and intracranial electrophysiology. Here we examine a unique patient cohort that has undergone decompressive hemicraniectomy, a surgical procedure wherein a portion of the calvaria is removed for several months during which time the scalp overlies the brain without intervening bone. We quantify the differences in signals between electrodes over areas with no underlying skull and scalp EEG electrodes over the intact skull in the same subjects. Signals over the hemicraniectomy have enhanced amplitude and greater task-related power at higher frequencies (60-115 Hz) compared with signals over skull. We also provide evidence of a metric for trial-by-trial EMG/EEG coupling that is effective over the hemicraniectomy but not intact skull at frequencies >60 Hz. Taken together, these results provide evidence that the hemicraniectomy model provides a means for studying neural dynamics in humans with enhanced spatial and temporal resolution.

Prefrontal cortex is critical for contextual processing: evidence from brain lesions.

We investigated the role of prefrontal cortex (PFC) in local contextual processing using a combined event-related potentials and lesion approach. Local context was defined as the occurrence of a short predictive series of visual stimuli occurring before delivery of a target event. Targets were preceded by either randomized sequences of standards or by sequences including a three-stimulus predictive sequence signalling the occurrence of a subsequent target event. PFC lesioned patients were impaired in their ability to use local contextual information. The response time for controls revealed a larger benefit for predictable targets than for random targets relative to PFC patients. PFC patients had reduced amplitude of a context-dependent positivity and failed to generate the expected P3b latency shift between predictive and non-predictive targets. These findings show that PFC patients are unable to utilize predictive local context to guide behaviour, providing evidence for a critical role of PFC in local contextual processing.

No disillusions in auditory extinction: perceiving a melody comprised of unperceived notes.

The formation of coherent percepts requires grouping together spatio-temporally disparate sensory inputs. Two major questions arise: (1) is awareness necessary for this process; and (2) can non-conscious elements of the sensory input be grouped into a conscious percept? To address this question, we tested two patients suffering from severe left auditory extinction following right hemisphere damage. In extinction, patients are unaware of the presence of left side stimuli when they are presented simultaneously with right side stimuli. We used the 'scale illusion' to test whether extinguished tones on the left can be incorporated into the content of conscious awareness. In the scale illusion, healthy listeners obtain the illusion of distinct melodies, which are the result of grouping of information from both ears into illusory auditory streams. We show that the two patients were susceptible to the scale illusion while being consciously unaware of the stimuli presented on their left. This suggests that awareness is not necessary for auditory grouping and non-conscious elements can be incorporated into a conscious percept.

Orbitofrontal cortex and social behavior: integrating self-monitoring and emotion-cognition interactions.

The role of the orbitofrontal cortex in social behavior remains a puzzle. Various theories of the social functions of the orbitofrontal cortex focus on the role of this area in either emotional processing or its involvement in online monitoring of behavior (i.e., self-monitoring). The present research attempts to integrate these two theories by examining whether improving the self-monitoring of patients with orbitofrontal damage is associated with the generation of emotions needed to guide interpersonal behavior. Patients with orbitofrontal damage, patients with lateral prefrontal damage, and healthy controls took part in an interpersonal task. After completing the task, participants' self-monitoring was increased by showing them a videotape of their task performance. In comparison to healthy controls and patients with lateral prefrontal damage, orbitofrontal damage was associated with objectively inappropriate social behavior. Although patients with orbitofrontal damage were aware of social norms of intimacy, they were unaware that their task performance violated these norms. The embarrassment typically associated with inappropriate social behavior was elicited in these patients only after their self-monitoring increased from viewing their videotaped performance. These findings suggest that damage to the orbitofrontal cortex impairs self-insight that may preclude the generation of helpful emotional information. The results highlight the role of the orbitofrontal cortex in the interplay of self-monitoring and emotional processing and suggest avenues for neurorehabilitation of patients with social deficits subsequent to orbitofrontal damage.

The impact of orbital prefrontal cortex damage on emotional activation to unanticipated and anticipated acoustic startle stimuli.

Damage to the orbital prefrontal cortex has been implicated in selectively diminishing electrodermal autonomic nervous system responses to anticipated punishing stimuli (e.g., losing money; Bechara, Damasio, & Damasio, 2000), but not to unanticipated punishing stimuli (e.g., loud noises; Damasio, Tranel, & Damasio, 1990). We extended this research by examining the effects of orbitofrontal damage on emotional responses to unanticipated and anticipated acoustic startles and collecting a more extensive set of physiological measures, emotional facial behavior, and self-reported emotional experience. Consistent with previous research, patients showed intact physiology to an unanticipated startle but failed to show appropriate anticipatory cardiovascular responses (patients' heart rates decreased, controls' increased). In addition, patients displayed more surprise facial behavior and reported marginally more fear than did controls in response to the unanticipated startle. Thus, orbitofrontal damage may compromise the ability to anticipate physiologically the onset of aversive stimuli, despite intact or enhanced emotional responses when such stimuli occur unexpectedly.

The regulatory function of self-conscious emotion: insights from patients with orbitofrontal damage.

Although once considered disruptive, self-conscious emotions are now theorized to be fundamentally involved in the regulation of social behavior. The present study examined the social regulation function of self-conscious emotions by comparing healthy participants with a neuropsychological population--patients with orbitofrontal lesions--characterized by selective regulatory deficits. Orbitofrontal patients and healthy controls participated in a series of tasks designed to assess their social regulation and self-conscious emotions. Another task assessed the ability to infer others' emotional states, an appraisal process involved in self-conscious emotion. Consistent with the theory that self-conscious emotions are important for regulating social behavior, the findings show that deficient behavioral regulation is associated with inappropriate self-conscious emotions that reinforce maladaptive behavior. Additionally, deficient behavioral regulation is associated with impairments in interpreting the self-conscious emotions of others.