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Social network size has been associated with complex socio-cognitive processes (e.g., memory, perspective taking). Supporting this idea, recent neuroimaging studies in healthy adults have reported a relationship between social network size and brain volumes in regions related to memory and social cognition (e.g., hippocampus, amygdala). Lesion-deficit studies in neurological patients are rare and have been inconclusive due to differences in participant sampling and measurement. The present study uses a multiple case study approach. We investigated patients with focal damage to the hippocampus and/or amygdala (two neural structures thought to be critical for social networks), and examined the patients' social network size, loneliness, and life satisfaction relative to a non-injured comparison group. Patients with amygdalar damage had smaller social networks and reported higher levels of loneliness and lower life satisfaction, on average, than comparison participants. Patients with damage to the hippocampus reported more friends than the comparison participants, but did not differ in their ratings of loneliness or life satisfaction. This lesion study offers new evidence that the amygdala is critical for social networks, life satisfaction, and reduced loneliness., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Research on changes in personality and behavior following brain damage has focused largely on negative outcomes, such as increased irritability, moodiness, and social inappropriateness. However, clinical observations suggest that some patients may actually show positive personality and behavioral changes following a neurological event. In the current work, we investigated neuroanatomical correlates of positive personality and behavioral changes following a discrete neurological event (e.g., stroke, benign tumor resection). Patients (N = 97) were rated by a well-known family member or friend on five domains of personality and behavior: social behavior, irascibility, hypo-emotionality, distress, and executive functioning. Ratings were acquired during the chronic epoch of recovery, when psychological status was stabilized. We identified patients who showed positive changes in personality and behavior in one or more domains of functioning. Lesion analyses indicated that positive changes in personality and behavior were most consistently related to damage to the bilateral frontal polar regions and the right anterior dorsolateral prefrontal region. These findings support the conclusion that improvements in personality and behavior can occur after a neurological event, and that such changes have systematic neuroanatomical correlates. Patients who showed positive changes in personality and behavior following a neurological event were rated as having more disturbed functioning prior to the event. Our study may be taken as preliminary evidence that improvements in personality and behavior following a neurological event may involve dampening of (premorbidly) more extreme expressions of emotion., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Studies of individuals with focal brain damage have long been used to expand understanding of the neural basis of psychopathology. However, most previous studies were conducted using small sample sizes and relatively coarse methods for measuring psychopathology or mapping brain-behavior relationships. Here, we examined the factor structure and neural correlates of psychopathology in 232 individuals with focal brain damage, using their responses to the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF). Factor analysis and voxel-based lesion symptom mapping were used to examine the structure and neural correlates of psychopathology in this sample. Consistent with existing MMPI-2-RF literature, separate internalizing, externalizing, and psychotic symptom dimensions were found. In addition, a somatic dimension likely reflecting neurological symptoms was identified. Damage to the medial temporal lobe, including the hippocampus, was associated with scales related to both internalizing problems and psychoticism. Damage to the medial temporal lobe and orbitofrontal cortex was associated with both a general distrust of others and beliefs that one is being personally targeted by others. These findings provide evidence for the critical role of dysfunction in specific frontal and temporal regions in the development of psychopathology., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Implicit moral evaluations-spontaneous, unintentional judgments about the moral status of actions or persons-are thought to play a pivotal role in moral experience, suggesting a need for research to model these moral evaluations in clinical populations. Prior research reveals that the ventromedial prefrontal cortex (vmPFC) is a critical area underpinning affect and morality, and patients with vmPFC lesions show abnormalities in moral judgment and moral behavior. We use indirect measurement and multinomial modeling to understand differences in implicit moral evaluations among patients with vmPFC lesions. Our model quantifies multiple processes of moral judgment: implicit moral evaluations in response to distracting moral transgressions (Unintentional Judgment), accurate moral judgments about target actions (Intentional Judgment), and a directional tendency to judge actions as morally wrong (Response Bias). Compared to individuals with non-vmPFC brain damage and neurologically healthy comparisons, patients with vmPFC lesions showed a dual deficit in processes of moral judgment. First, patients with vmPFC lesions showed reduced Unintentional Judgment about moral transgressions, but not about non-moral negative affective distracters. Second, patients with vmPFC lesions showed reduced Intentional Judgment about target actions. These findings highlight the utility of a formal modeling approach in moral psychology, revealing a dual deficit in multiple component processes of moral judgment among patients with vmPFC lesions., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Temporal lobe epilepsy (TLE) can be associated with a marked impairment of autobiographical memory. This is occasionally its presenting feature. We describe two individuals with severe epilepsy-associated autobiographical memory loss. Both MB and PT were reassured initially that their memory was intact on the basis of standard neuropsychological tests. Both have written detailed accounts of their symptoms. The key neuropsychological features of their cases are the relative normality of performance on standard memory tests, with preservation of semantic memory for impersonal information, in contrast to a profound amnesia for salient autobiographical episodes and an impoverishment of imaginative scene construction. First person accounts from these individuals illustrate the importance of autobiographical memory in sustaining a coherent sense of self, informing interpersonal relationships and supporting future thinking and problem-solving. These cases contribute to the growing evidence for a distinctive pattern of autobiographical memory loss associated with TLE, and indicate that it can take a severe form affecting both personal semantics and episodic recollection. Defining the phase of memory processing most relevant to this form of amnesia, and the roles of physiological and structural pathology, requires further research. The paper's title refers to the introspective 'void' highlighted by both MB and PT in their reports - in PT's words: 'My primary symptom is the void that is my past'., (Copyright © 2017. Published by Elsevier Ltd.)

People listen to music because it is pleasurable. However, there are individual differences in the reward value of music. At the extreme low end of this continuum, individuals who derive no pleasure from music are said to have 'musical anhedonia.' Cases of acquired musical anhedonia following focal brain damage are rare, with only a handful having been reported in the scientific literature. Here, we surveyed a large sample of patients with focal brain damage to identify the frequency, specificity, and neural correlates of acquired musical anhedonia. Participants completed the Musical anhedonia Questionnaire and the Barcelona Music Reward Questionnaire (Mas-Herrero et al., 2013) to assess changes in musical enjoyment and reward following brain injury. Neuroanatomical data were analyzed with a proportional MAP-3 method to create voxelwise lesion proportion difference maps. No clear or consistent neuroanatomical correlates of musical anhedonia were identified. One patient with damage to the right-hemisphere putamen and internal capsule displayed specific and severe acquired musical anhedonia. These findings indicate that acquired musical anhedonia is very uncommon, a result which is consistent with the fact that only a small number of such cases have been reported in the literature. This rarity could have positive implications for the therapeutic potentialities of music in patients with severe neurological disorders., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Word learning has been proposed to rely on unique brain regions including the temporal lobes, and the left temporal lobe appears to be especially important. In order to investigate the role of the left temporal lobe in word learning under different conditions, we tested whether patients with left temporal lobectomies (N=6) could learn novel words using two distinct formats. Previous research has shown that word learning in contrastive fast mapping conditions may rely on different neural substrates than explicit encoding conditions (Sharon et al., 2011). In the current investigation, we used a previously reported word learning task that implemented two distinct study formats (Warren and Duff, 2014): a contrastive fast mapping condition in which a picture of a novel item was displayed beside a picture of a familiar item while the novel item's name was presented aurally ("Click on the numbat."); and an explicit encoding (i.e., control) condition in which a picture of a novel item was displayed while its name was presented aurally ("This is a numbat."). After a delay, learning of the novel words was evaluated with memory tests including three-alternative forced-choice recognition, free recall, cued recall, and familiarity ratings. During the fast-mapping study condition both the left temporal lobectomy and healthy comparison groups performed well, but at test only the comparison group showed evidence of novel word learning. Our findings indicate that unilateral resection of the left temporal lobe including the hippocampus and temporal pole can severely impair word learning, and that fast-mapping study conditions do not promote subsequent word learning in temporal lobectomy populations., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Converging evidence points to a neural network that supports a range of abilities including remembering the past, thinking about the future, and introspecting about oneself and others. Neuroimaging studies find hippocampal activation during event construction tasks, and patients with hippocampal amnesia are impaired in their ability to (re)construct events of the past and the future. Neuroimaging studies of constructed experiences similarly implicate the medial prefrontal cortex (mPFC), but it remains unknown whether the mPFC is critical for such processes. The current study compares performance of five patients with bilateral mPFC damage, six patients with bilateral hippocampal damage, and demographically matched comparison participants on an event construction task. Participants were given a neutral cue word and asked to (re)construct events across four time conditions: real past, imagined past, imagined present, and future. These event narratives were analyzed for the number of internal and external details to quantify the extent of episodic (re)experiencing. Given the literature on the involvement of the mPFC in self-referential processing, we also analyzed the event narratives for self-references. The patients with mPFC damage did not differ from healthy comparison participants in their ability to construct highly detailed episodic events across time periods but displayed disruptions in their incorporation of the self. Patients with hippocampal damage showed the opposite pattern; they were impaired in their ability to construct highly detailed episodic events across time periods but not in their incorporation of the self. The results suggest differential contributions of hippocampus and medial prefrontal cortex to the distributed neural network for various forms of self-projection., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Reciprocal trust is a crucial component of cooperative, mutually beneficial social relationships. Previous research using tasks that require judging and developing interpersonal trust has suggested that the insula may be an important brain region underlying these processes (King-Casas et al., 2008). Here, using a neuropsychological approach, we investigated the role of the insula in reciprocal trust during the Trust Game (TG), an interpersonal economic exchange. Consistent with previous research, we found that neurologically normal adults reciprocate trust in kind, i.e., they increase trust in response to increases from their partners, and decrease trust in response to decreases. In contrast, individuals with damage to the insula displayed abnormal expressions of trust. Specifically, these individuals behaved benevolently (expressing misplaced trust) when playing the role of investor, and malevolently (violating their partner's trust) when playing the role of the trustee. Our findings lend further support to the idea that the insula is important for expressing normal interpersonal trust, perhaps because the insula helps to recognize risk during decision-making and to identify social norm violations., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: This study aimed to extend previous work on decision-making deficits in anorexia nervosa (AN) by using a longitudinal design to examine decision-making before and after weight restoration., Methods: Participants were 22 women with AN and 20 healthy comparison participants who completed the Iowa Gambling Task (IGT). Decision-making was assessed both before and after weight restoration in a subset of 14 AN patients. Self-report and interview assessments were used to measure psychological correlates of decision-making performance including depression, anxiety, and eating disorder symptoms, and magnetic resonance imaging (MRI) scans were conducted to explore associations between brain volume in the orbitofrontal cortex (OFC) and decision-making in individuals with AN., Results: Currently ill AN patients performed worse on the IGT compared to the control group. Although decision-making performance did not improve significantly with weight restoration in the full AN sample, AN patients who were poor performers at baseline did improve task performance with weight-restoration. When actively ill, lower body mass index (BMI) and decreased left medial OFC volume were significantly associated with worse IGT performance, and these associations were no longer significant after weight restoration., Conclusions: Findings suggest that decision-making deficits in AN in the acute phase of illness are associated with low weight and decreased left medial OFC volume, but increases in brain volume and BMI may not have been sufficient to improve decision-making in all patients. Findings contribute to a model for understanding how some patients may sustain self-starvation, and future work should examine whether decision-making deficits predict relapse., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Counterfactual feelings of regret occur when people make comparisons between an actual outcome and a better outcome that would have occurred under a different choice. We investigated the choices of individuals with damage to the ventral medial prefrontal cortex (VMPFC) and the lateral orbital frontal cortex (LOFC) to see whether their emotional responses were sensitive to regret. Participants made choices between gambles, each with monetary outcomes. After every choice, subjects learned the consequences of both gambles and rated their emotional response to the outcome. Normal subjects and lesion control subjects tended to make better choices and reported post-decision emotions that were sensitive to regret comparisons. VMPFC patients tended to make worse choices, and, contrary to our predictions, they reported emotions that were sensitive to regret comparisons. In contrast, LOFC patients made better choices, but reported emotional reactions that were insensitive to regret comparisons. We suggest the VMPFC is involved in the association between choices and anticipated emotions that guide future choices, while the LOFC is involved in experienced emotions that follow choices, emotions that may signal the need for behavioral change., (© 2013 Elsevier Ltd. All rights reserved.)

During conversation, interactants draw on their shared communicative context and history ("common ground") to help decide what to say next, tailoring utterances based on their knowledge of what the listener knows. The use of common ground draws on an understanding of the thoughts and feelings of others to create and update a model of what is known by the other person, employing cognitive processes such as theory of mind. We tested the hypothesis that the ventromedial prefrontal cortex (vmPFC), a neural region involved in processing and interpreting social and emotional information, would be critical for the development and use of common ground. We studied seven patients with bilateral vmPFC damage and seven age-, sex-, and education-matched healthy comparison participants, each interacting with a familiar partner. Across 24 trials, participants verbally directed their partners how to arrange a set of 12 abstract tangram cards. Our hypothesis was not supported: the vmPFC and healthy comparison groups showed similar development and use of common ground, evident in reduction in time and words used to describe the cards, similar increases in the use of definite references (e.g., the horse), and comparable use of verbal play (playful language) in their interactions. These results argue against the idea that the vmPFC is critical for the development and use of common ground in social interaction. We propose that a cognitive and neuroanatomical bifurcation in theory of mind processes may explain this outcome. The vmPFC may be important for affective theory of mind (the ability to understand another's feelings); however, the development and use of common ground in social interaction may place higher demands on the ability to understand another's knowledge, or cognitive theory of mind, which may not require the vmPFC., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Markets are mechanisms of social exchange, intended to facilitate trading. However, the question remains as to whether markets would help or hurt individuals with decision-makings deficits, as is frequently encountered in the case of cognitive aging. Essential for predicting future gains and losses in monetary and social domains, the striatal nuclei in the brain undergo structural, neurochemical, and functional decline with age. We correlated the efficacy of market mechanisms with dorsal striatal decline in an aging population, by using market based trading in the context of the 2008 U.S. Presidential Elections (primary cycle). Impaired decision-makers displayed higher prediction error (difference between their prediction and actual outcome). Lower in vivo caudate volume was also associated with higher prediction error. Importantly, market-based trading protected older adults with lower caudate volume to a greater extent from their own poorly calibrated predictions. Counterintuitive to the traditional public perception of the market as a fickle, risky proposition where vulnerable traders are most surely to be burned, we suggest that market-based mechanisms protect individuals with brain-based decision-making vulnerabilities., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Decision-making is a complex process that requires the orchestration of multiple neural systems. For example, decision-making is believed to involve areas of the brain involved in emotion (e.g., amygdala, ventromedial prefrontal cortex) and memory (e.g., hippocampus, dorsolateral prefrontal cortex). In this article, we will present findings related to the amygdala's role in decision-making, and differentiate the contributions of the amygdala from those of other structurally and functionally connected neural regions. Decades of research have shown that the amygdala is involved in associating a stimulus with its emotional value. This tradition has been extended in newer work, which has shown that the amygdala is especially important for decision-making, by triggering autonomic responses to emotional stimuli, including monetary reward and punishment. Patients with amygdala damage lack these autonomic responses to reward and punishment, and consequently, cannot utilize "somatic marker" type cues to guide future decision-making. Studies using laboratory decision-making tests have found deficient decision-making in patients with bilateral amygdala damage, which resembles their real-world difficulties with decision-making. Additionally, we have found evidence for an interaction between sex and laterality of amygdala functioning, such that unilateral damage to the right amygdala results in greater deficits in decision-making and social behavior in men, while left amygdala damage seems to be more detrimental for women. We have posited that the amygdala is part of an "impulsive," habit type system that triggers emotional responses to immediate outcomes., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

The human amygdala is known to be involved in processing social, emotional, and reward-related information. Previous reports have indicated that the amygdala is involved in extracting trustworthiness information from faces. Interestingly, functional neuroimaging research using economic tasks that presumably require developing and/or expressing interpersonal trust, such as the Trust Game (TG), have not routinely identified involvement of the amygdala. The present study sought to explore the role of the amygdala in developing and expressing interpersonal trust, via a multi-round, multiplayer economic exchange, a version of the TG, in a large sample of participants with focal brain damage. Participants with unilateral damage to the amygdala displayed increased benevolent behavior in the TG, and specifically, they tended to increase trust in response to betrayals. On the other hand, neurologically normal adults tended to repay trust in kind, i.e., they decreased interpersonal trust in response to betrayals or increased trust in response to increases from others. Comparison participants, with brain damage that does not include the amygdala, ventromedial prefrontal or insular cortices, tended to behave ambivalently to the expressed trust or betrayal of others. Our data suggest that the amygdala is necessary for developing and expressing normal interpersonal trust. This increased tendency to behave benevolently in response to defections from others may be related to the abnormal social behavior observed in this group. Moreover, increased benevolence may increase the likelihood or opportunity to be taken advantage of by others., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

As we learn new information about the social and moral behaviors of other people, we form and update character judgments of them, and this can profoundly influence how we regard and act towards others. In the study reported here, we capitalized on two interesting neurological patient populations where this process of complex "moral updating" may go awry: patients with bilateral damage to ventromedial prefrontal cortex (vmPFC) and patients with bilateral damage to hippocampus (HC). We predicted that vmPFC patients, who have impaired emotion processing, would exhibit reduced moral updating, and we also investigated how moral updating might be affected by severe declarative memory impairment in HC patients. The vmPFC, HC, and brain-damaged comparison (BDC) participants made moral judgments about unfamiliar persons before and after exposure to social scenarios depicting the persons engaged in morally good, bad, or neutral behaviors. In line with our prediction, the vmPFC group showed the least amount of change in moral judgments, and interestingly, the HC group showed the most amount of change. These results suggest that the vmPFC and hippocampus play critical but complementary roles in updating moral character judgments about others: the vmPFC may attribute emotional salience to moral information, whereas the hippocampus may provide necessary contextual information from which to make appropriate character judgments., (2010 Elsevier Ltd. All rights reserved.)

The ability to produce appropriate physiological and psychological responses to stressful situations depends on accurate recognition and appraisal of such situations. Such ability is also important for proper emotion regulation. A number of studies have suggested that the medial prefrontal cortex (mPFC) plays a significant role in emotion regulation, as well as in the control of physiological endpoints of emotion regulation such as the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS). Further, recent work has suggested that men and women may differ in these mechanisms of neural control of emotion regulation. Here, we examined the role of the human mPFC in self-report, ANS, and HPA stress reactivity by testing a group of participants with damage to this region (9 women and 9 men), a brain damaged comparison group (6 women and 6 men), and healthy comparison participants (27 women and 27 men) on an orthostatic challenge and the Trier Social Stress Test (TSST). The mPFC participants showed heightened self-reported stress in response to the TSST. In women, mPFC damage led to an increased cortisol response to the TSST. By contrast, in men, greater volume of mPFC damage was correlated with a decreased cortisol response. Finally, men with mPFC damage showed altered autonomic control of the heart (higher heart rate and lower high frequency heart rate variability) during an orthostatic challenge. These findings support the idea that the mPFC is involved in the regulation of physiological and psychological responses to stress and that this regulation may differ between men and women.

Previous studies have reported conflicting evidence concerning the contribution of declarative memory to advantageous decision-making on the Iowa Gambling Task (IGT). One study, in which the measurement of psychophysiology during the task necessitated a 10-s delay between card selections, found that six participants with amnesia due to hippocampal damage failed to develop a preference for advantageous decks over disadvantageous decks [Gutbrod, K., Krouzel, C., Hofer, H., Muri, R., Perrig, W., & Ptak, R. (2006). Decision-making in amnesia: Do advantageous decisions require conscious knowledge of previous behavioural choices? Neuropsychologia, 44(8), 1315-1324]. However, a single-case study (where psychophysiology was not measured and no delay between card selections occurred) showed that an amnesic patient developed normal preference for advantageous decks [Turnbull, O. H., & Evans, C. E. (2006). Preserved complex emotion-based learning in amnesia. Neuropsychologia, 44(2), 300-306]. We sought to resolve these discrepant findings by examining IGT performances in five patients with profound amnesia (WMS-III General Memory Index M=63) and bilateral hippocampal damage caused by anoxia (n=4) or herpes simplex encephalitis (n=1). In one administration of the IGT, psychophysiology measurements were utilized and a 6-s delay was interposed between card selections. In a second administration, no delay between card selections was interposed. While age-, sex-, and education-matched healthy comparison participants showed significant learning with a gradual preference for advantageous decks in both conditions, amnesic patients, irrespective of IGT administration condition and extent of medial temporal lobe damage, failed to develop this preference. These findings strongly discount the possibility that the delay between card selections explains why amnesic participants fail to learn in the IGT, and suggest instead a significant role for medial temporal lobe declarative memory systems in the type of complex decision-making tapped by the IGT.

Objective: Based upon Damasio's "convergence zone" model of semantic memory, we predicted that epilepsy surgical patients with anterior temporal lobe (TL) seizure onset would exhibit a pattern of category-specific naming and recognition deficits not observed in patients with seizures arising elsewhere., Methods: We assessed epilepsy patients with unilateral seizure onset of anterior TL or other origin (n=22), pre- or post-operatively, using a set of category-specific items and a conventional measure of visual naming (Boston Naming Test: BNT)., Results: Category-specific naming deficits were exhibited by patients with dominant anterior TL seizure onset/resection for famous faces and animals, while category-specific recognition deficits for these same categories were exhibited by patients with nondominant anterior TL onset/resection. Patients with other seizure onset did not exhibit category-specific deficits. Naming and recognition deficits were frequently not detected by the BNT, which samples only a limited range of stimuli., Interpretation: Consistent with the "convergence zone" framework, results suggest that the nondominant anterior TL plays a major role in binding sensory information into conceptual percepts for certain stimuli, while dominant TL regions function to provide a link to verbal labels for these percepts. Although observed category-specific deficits were striking, they were often missed by the BNT, suggesting that they are more prevalent than recognized in both pre- and post-surgical epilepsy patients. Systematic investigation of these deficits could lead to more refined models of semantic memory, aid in the localization of seizures, and contribute to modifications in surgical technique and patient selection in epilepsy surgery to improve neurocognitive outcome.

The prefrontal region of the brain, including the ventromedial sector which supports reasoning and decision-making, may undergo disproportionate aging in some older persons, but the empirical evidence is decidedly mixed. To help resolve this, we tested 80 neurologically and psychiatrically healthy Younger (aged 26-55) and Older (aged 56-85) adults on a "Gambling Task", which provides a close analog to real-world decision-making by factoring in reward, punishment, and unpredictability, yielding a sensitive index of ventromedial prefrontal function. A subset of the Older group manifested a decision-making impairment on the Gambling Task, in spite of otherwise intact cognitive functioning. This finding raises the possibility of disproportionate aging of the ventromedial prefrontal cortex in these individuals. Our finding has important societal and public policy implications (e.g., choosing medical care, allocating personal wealth), and may also help explain why many older individuals are targeted by and susceptible to fraudulent advertising.

Bilateral damage to the human amygdala impairs recognition of negatively valenced emotions from facial expressions, but it is unclear if this finding generalizes to richer visual stimuli that contain cues in addition to faces. We investigated this issue in 4 subjects with bilateral amygdala damage, 23 with unilateral amygdala damage, 22 brain-damaged controls and 16 normal individuals. Subjects were shown two blocks of complex social scenes; all stimuli in the two blocks were identical, except that the first block had all facial expressions in the image erased. While control subjects were more accurate in recognizing emotions when facial expressions were present, subjects with bilateral amygdala damage did not show the same benefit for negative emotions, often performing equivalently across the two conditions. Most striking, subjects with bilateral amygdala damage were more accurate in recognizing scenes showing anger with faces erased than with faces present, an effect resulting in part from highly abnormal recognition of certain angry facial expressions. All four subjects with bilateral amygdala damage were impaired in recognizing angry faces shown in isolation, and frequently mistook expressions of anger for smiles, a mistake never made by any control subject. Bilateral amygdala damage thus disproportionately impairs recognition of certain emotions from complex visual stimuli when subjects utilize information from facial expressions.

The neural correlates of naming stimuli presented through the auditory modality have scarcely been studied. Using a PET experiment in 10 normal subjects, we began to address this issue by testing the hypothesis that naming animals from their characteristic sounds will engage bilateral primary auditory and auditory association cortices, bilateral early visual association cortices, left inferotemporal (IT) cortices, and left frontal operculum. Subjects listened to characteristic animal sounds (e.g. a rooster crowing), and named the animals making the sounds. When contrasted with a baseline task that involved saying up/down to the direction of pitch change in tone sequences, the naming task produced activation in mesial occipital cortices, the left ventral IT region, and the left frontal operculum. We interpret the activation in visual association cortices to reflect the process of retrieving conceptual knowledge (e.g. physical structure) pertinent to the animals being named, as in visual images. The left IT activation is interpreted to reflect activation of a mediation system for word retrieval, that operates to link conceptual knowledge retrieval to word production, and whose triggering is independent of the sensory modality in which a stimulus is presented., (Copyright 2002 Elsevier Science Ltd.)

Recent functional imaging studies of topographical learning point to the participation of a large network of cortical and subcortical regions. Nevertheless, areas which are crucial remain poorly specified due to the absence of group studies of subjects with focal lesions distributed throughout the brain. We assessed the ability of 127 subjects with stable, focal lesions to learn a complex real-life route, a critical aspect of topographical functioning. Results indicated that impairment in route learning was highly associated with damage to medial occipital and posterior parahippocampal cortices in either hemisphere, the right hippocampus, and the right inferotemporal region. Impairment was seen among 86% of the subjects with damage to any these regions, in contrast to impairment among 31% of subjects with lesions in other regions. The importance of medial occipitotemporal cortices bilaterally and right inferotemporal cortex likely reflects the critical role of the ability to quickly and accurately perceive and learn multiple topographical scenes. The importance of the right (and probably left) posterior parahippocampal gyrus and of the right hippocampus likely reflects their critical, distinctive roles forming an integrated representation of the extended topographical environment (i.e., the appearance of places and spatial relationships between specific places), and consolidating that representation into multifaceted contextual knowledge of the environment.

Bilateral damage to the amygdala in a variety of animal species can impair emotional reactions to stimuli in several sensory modalities. Such damage in humans impairs visual recognition of emotion in facial expressions, but possible impairments in modalities other than vision have not been sufficiently explored. We examined two subjects with complete bilateral amygdala damage, and seven with unilateral amygdala damage, on a standardized task of emotional prosody recognition. The data were compared to those from 15 brain-damaged and from 14 normal control subjects. One of the bilateral amygdala subjects, whose lesions were restricted to the amygdala, was entirely normal in recognizing emotion in prosody on all tasks, the other, whose damage included substantial lesions also in extra-amygdalar structures, especially in right hemisphere, was normal on most, albeit not all, measures of emotional prosody recognition. We suggest that the human amygdala's role in recognizing emotion in prosody may not be as critical as it is for facial expressions, and that extra-amygdalar structures in right hemisphere may be more important for recognizing emotional prosody. It remains possible that recognition of emotion in classes of auditory stimuli other than prosody will require the amygdala.

Several studies have shown that cortical damage, especially to the right hemisphere and to frontal lobes, may attenuate skin conductance responses selectively to psychologically significant stimuli. We tested this hypothesis in 32 patients with frontal lesions, verified by computer assisted tomography and magnetic resonance imaging, and 45 healthy controls. Patients and controls were given a protocol which included a rest period, a series of innocuous tones, and a reaction time task. Patients were given a second protocol in which they viewed slides with positive and negative emotional content and neutral slides. Results showed attenuated electrodermal activity (EDA) during task instructions and smaller skin conductance responses to reaction-time stimuli in patients compared to controls but few differences under passive conditions or in orienting responses to simple tones. Patients with lateral prefrontal and paraventricular lesions were especially low in EDA in the reaction time task, and those with right and bilateral lesions in the cingulate gyrus and/or frontal operculum had attenuated EDA in both protocols. We conclude that the effects of certain frontal lesions are on the psychological response to significance which is indexed by EDA rather than directly on EDA per se.

Findings from several case studies have shown that bilateral amygdala damage impairs recognition of emotions in facial expressions, especially fear. However, one study did not find such an impairment, and, in general, comparison across studies has been made difficult because of the different stimuli and tasks employed. In a collaborative study to facilitate such comparisons, we report here the recognition of emotional facial expressions in nine subjects with bilateral amygdala damage, using a sensitive and quantitative assessment. Compared to controls, the subjects as a group were significantly impaired in recognizing fear, although individual performances ranged from severely impaired to essentially normal. Most subjects were impaired on several negative emotions in addition to fear, but no subject was impaired in recognizing happy expressions. An analysis of response consistency showed that impaired recognition of fear could not be attributed simply to mistaking fear for another emotion. While it remains unclear why some subjects with amygdala damage included here are not impaired on our task, the results overall are consistent with the idea that the amygdala plays an important role in triggering knowledge related to threat and danger signaled by facial expressions.

Category-related effects in the retrieval of conceptual and lexical knowledge for concrete entities have been well documented in lesion studies, and also with functional imaging and electrophysiological approaches. For example, brain-damaged subjects may be impaired in the ability to recognize or to name animals but not tools, or the opposite pattern may obtain. One reason for these dissociations is that different patterns of defects tend to be caused by distinct lesion profiles, suggesting a relative tendency for certain neural systems to be involved in category-related knowledge. But we and others have also hypothesized that a variety of traits of concrete entities co-determine category-related dissociations. Such traits ('factors') include homomorphy (similarity of form), familiarity, value to perceiver, manipulability, characteristic motion, characteristic sensory modality of transaction (vision, touch, hearing), and typical age of acquisition. It is our view that the mix of factors relative to different conceptual categories plays a key role in the neuroanatomical distribution of records for those different categories, and is thus behind the systematic correlations between certain retrieval defects and damage to certain neural systems [12, 52]. In this study, we operationalized these factors and analyzed their intercorrelations. Stimuli were slides of 215 items from the conceptual categories of animals, fruits/vegetables, tools/utensils, vehicles, and musical instruments. The factors were operationalized on the basis of ratings obtained from 227 normal control subjects and on the basis of computer analyses of the digitized outlines of the stimuli. Principal components analysis revealed that 81% of the variability across items could be accounted for by three components: Component 1 (practically useful, common items): high value to perceiver, tactile mode of transaction, high familiarity, low age of acquisition; Component 2 (homomorphic, non-manipulable items): high homomorphy, low characteristic motion and manipulability; Component 3 (items with characteristic sound): hearing mode of transaction, highly distinctive sounds. In another analysis, we found that the categories of animals versus tools/utensils differed significantly on the factors of homomorphy, familiarity, value, manipulability, characteristic motion, and touch. The factor structure we identified in this study may help explain category-related performance defects in brain-damaged subjects. The results lend support to our proposal that systematic differences in physical characteristics and contextual specification of concrete entities constitute a driving force behind the regionalization of neural systems related to the acquisition and retrieval of conceptual and lexical knowledge.

Both clinical reports and systematic neuropsychological studies have shown that patients with damage to selected brain sites develop defects in the retrieval of conceptual knowledge for various concrete entities, leading to the hypothesis that the retrieval of knowledge for entities from different conceptual categories depends on partially segregated large-scale neural systems. To test this hypothesis, 116 subjects with focal, unilateral lesions to various sectors of the telencephalon, and 55 matched controls, were studied with a procedure which required the visual recognition of entities from three categories--unique persons, non-unique animals and non-unique tools. Defective recognition of persons was associated with maximal lesion overlap in right temporal polar region; defective recognition of animals was associated with maximal lesion overlap in right mesial occipital/ventral temporal region and also in left mesial occipital region; and defective recognition of tools was associated with maximal lesion overlap in the occipital-temporal-parietal junction of the left hemisphere. The findings support the hypothesis that the normal retrieval of knowledge for concrete entities from different conceptual domains depends on partially segregated neural systems. These sites may operate as catalysts for the retrieval of the multidimensional aspects of knowledge which are necessary and sufficient for the mental representation of a concept of a given entity.

In vivo occipital asymmetry (OA) measurements have been used to infer functional asymmetries such as language dominance. We investigated the degree of correlation between OA measurements derived by the same rater from different scans of the same subject. We used magnetic resonance (MR) and computerized axial tomography (CT) to study correlations between MR:MR, CT:CT and CT:MR. The highest intrasubject correlation was for MR:MR (r = 0.79). The CT:CT value was similar (r = 0.78) and the CT:MR correlation was slightly lower (r = 0.72). The findings indicate that the reliability of occipital asymmetry measurements is modest at best, setting a low ceiling on the valid use of this variable to infer other indexes.

The role of the human amygdala in cross-modal associations was investigated in two subjects: SM-046, who had bilateral damage circumscribed to the amygdala; and the patient known as Boswell, whose damage in both temporal lobes includes the amygdala and surrounding cortices. Neither subject was impaired on Tactile-Visual or Visual-Tactile cross-modal tasks using the Arc-Circle test, suggesting that the amygdala is not involved in cross-modal associations involving perceptually "equivalent" basic stimulus properties. On the other hand, the results are compatible with the amygdala's involvement in higher-order associations between exteroceptive sensory data and interoceptive data concerned with correlated somatic states.

Several lines of evidence have suggested that the amygdala is a crucial component of the anatomical network that mediates the skin conductance orienting response (SCOR). In this study, the electrodermal activity of a patient whose entire amygdaloid complex had been destroyed bilaterally, and of 7 age- and gender-matched controls, was recorded under the same experimental conditions. The results indicate unequivocally that the subject could generate normal skin conductance and SCORs, in response to stimuli of different sensory modalities and configurations. This suggests that the amygdala is not a necessary component of the neural network underlying SCORs and that there are alternate neural units and pathways that link sensory cortices to autonomic effectors.