Daniel Tranel

Impairment of social and moral behavior related to early damage in human prefrontal cortex.

The long-term consequences of early prefrontal cortex lesions occurring before 16 months were investigated in two adults. As is the case when such damage occurs in adulthood, the two early-onset patients had severely impaired social behavior despite normal basic cognitive abilities, and showed insensitivity to future consequences of decisions, defective autonomic responses to punishment contingencies and failure to respond to behavioral interventions. Unlike adult-onset patients, however, the two patients had defective social and moral reasoning, suggesting that the acquisition of complex social conventions and moral rules had been impaired. Thus early-onset prefrontal damage resulted in a syndrome resembling psychopathy.

Double dissociation of conditioning and declarative knowledge relative to the amygdala and hippocampus in humans

A patient with selective bilateral damage to the amygdala did not acquire conditioned autonomic responses to visual or auditory stimuli but did acquire the declarative facts about which visual or auditory stimuli were paired with the unconditioned stimulus. By contrast, a patient with selective bilateral damage to the hippocampus failed to acquire the facts but did acquire the conditioning. Finally, a patient with bilateral damage to both amygdala and hippocampal formation acquired neither the conditioning nor the facts. These findings demonstrate a double dissociation of conditioning and declarative knowledge relative to the human amygdala and hippocampus.

Individuals with sociopathic behavior caused by frontal damage fail to respond autonomically to social stimuli.

Following damage to ventromedial frontal cortices, adults with previously normal personalities develop defects in decision-making and planning that are especially revealed in an abnormal social conduct. The defect repeatedly leads to negative personal consequences. The physiopathology of this disorder is an enigma. We propose that the defect is due to an inability to activate somatic states linked to punishment and reward, that were previously experienced in association with specific social situations, and that must be reactivated in connection with anticipated outcomes of response options. During the processing that follows the perception of a social event, the experience of certain anticipated outcomes of response options would be marked by the reactivation of an appropriate somatic state. Failure to reactivate pertinent somatic markers would deprive the individual of an automatic device to signal ultimately deleterious consequences relative to responses that might nevertheless bring immediate reward (or, alternatively, signal ultimately advantageous outcomes relative to responses that might bring immediate pain). As an example, activation of somatic markers would (1) force attention to future negative consequences, permitting conscious suppression of the responses leading to them and deliberate selection of biologically advantageous responses, and (2) trigger non-conscious inhibition of response states by engagement of subcortical neurotransmitter systems linked to appetitive behaviors. An investigation of this theory in patients with frontal damage reveals that their autonomic responses to socially meaningful stimuli are indeed abnormal, suggesting that such stimuli fail to activate somatic states at the most basic level. On the contrary, elementary unconditioned stimuli (e.g. a loud noise) produce normal autonomic responses.

The human amygdala in social judgment

Studies in animals have implicated the amygdala in emotional, and social, behaviours, especially those related to fear and aggression. Although lesion, and functional imaging, studies in humans have demonstrated the amygdalas participation in recognizing emotional facial expressions, its role in human social behaviour has remained unclear. We report here our investigation into the hypothesis that the human amygdala is required for accurate social judgments of other individuals on the basis of their facial appearance. We asked three subjects with complete bilateral amygdala damage to judge faces of unfamiliar people with respect to two attributes important in real-life social encounters: approachability and trustworthiness. All three subjects judged unfamiliar individuals to be more approachable and more trustworthy than did control subjects. The impairment was most striking for faces to which normal subjects assign the most negative ratings: unapproachable and untrustworthy looking individuals. Additional investigations revealed that the impairment does not extend to judging verbal descriptions of people. The amygdala appears to be an important component of the neural systems that help retrieve socially relevant knowledge on the basis of facial appearance.

A mechanism for impaired fear recognition after amygdala damage

Ten years ago, we reported that SM, a patient with rare bilateral amygdala damage, showed an intriguing impairment in her ability to recognize fear from facial expressions. Since then, the importance of the amygdala in processing information about facial emotions has been borne out by a number of lesion and functional imaging studies. Yet the mechanism by which amygdala damage compromises fear recognition has not been identified. Returning to patient SM, we now show that her impairment stems from an inability to make normal use of information from the eye region of faces when judging emotions, a defect we trace to a lack of spontaneous fixations on the eyes during free viewing of faces. Although SM fails to look normally at the eye region in all facial expressions, her selective impairment in recognizing fear is explained by the fact that the eyes are the most important feature for identifying this emotion. Notably, SMs recognition of fearful faces became entirely normal when she was instructed explicitly to look at the eyes. This finding provides a mechanism to explain the amygdalas role in fear recognition, and points to new approaches for the possible rehabilitation of patients with defective emotion perception.

Neural Systems Responding to Degrees of Uncertainty in Human Decision-Making

Much is known about how people make decisions under varying levels of probability (risk). Less is known about the neural basis of decision-making when probabilities are uncertain because of missing information (ambiguity). In decision theory, ambiguity about probabilities should not affect choices. Using functional brain imaging, we show that the level of ambiguity in choices correlates positively with activation in the amygdala and orbitofrontal cortex, and negatively with a striatal system. Moreover, striatal activity correlates positively with expected reward. Neurological subjects with orbitofrontal lesions were insensitive to the level of ambiguity and risk in behavioral choices. These data suggest a general neural circuit responding to degrees of uncertainty, contrary to decision theory.

Damage to the prefrontal cortex increases utilitarian moral judgements

The psychological and neurobiological processes underlying moral judgement have been the focus of many recent empirical studies. Of central interest is whether emotions play a causal role in moral judgement, and, in parallel, how emotion-related areas of the brain contribute to moral judgement. Here we show that six patients with focal bilateral damage to the ventromedial prefrontal cortex (VMPC), a brain region necessary for the normal generation of emotions and, in particular, social emotions, produce an abnormally ‘utilitarian’ pattern of judgements on moral dilemmas that pit compelling considerations of aggregate welfare against highly emotionally aversive behaviours (for example, having to sacrifice one person’s life to save a number of other lives). In contrast, the VMPC patients’ judgements were normal in other classes of moral dilemmas. These findings indicate that, for a selective set of moral dilemmas, the VMPC is critical for normal judgements of right and wrong. The findings support a necessary role for emotion in the generation of those judgements.

Cortical Systems for the Recognition of Emotion in Facial Expressions

This study is part of an effort to map neural systems involved in the processing of emotion, and it focuses on the possible cortical components of the process of recognizing facial expressions. We hypothesized that the cortical systems most responsible for the recognition of emotional facial expressions would draw on discrete regions of right higher-order sensory cortices and that the recognition of specific emotions would depend on partially distinct system subsets of such cortical regions. We tested these hypotheses using lesion analysis in 37 subjects with focal brain damage. Subjects were asked to recognize facial expressions of six basic emotions: happiness, surprise, fear, anger, disgust, and sadness. Data were analyzed with a novel technique, based on three-dimensional reconstruction of brain images, in which anatomical description of surface lesions and task performance scores were jointly mapped onto a standard brain-space. We found that all subjects recognized happy expressions normally but that some subjects were impaired in recognizing negative emotions, especially fear and sadness. The cortical surface regions that best correlated with impaired recognition of emotion were in the right inferior parietal cortex and in the right mesial anterior infracalcarine cortex. We did not find impairments in recognizing any emotion in subjects with lesions restricted to the left hemisphere. These data provide evidence for a neural system important to processing facial expressions of some emotions, involving discrete visual and somatosensory cortical sectors in right hemisphere.

Wisconsin Card Sorting Test Performance as a Measure of Frontal Lobe Damage

We examined the sensitivity and specificity of the Wisconsin Card Sorting Test (WCST) as a measure of frontal lobe damage in 91 subjects with stable focal brain lesions. Anatomical information about the location and extent of brain damage was obtained from MR and CT transparencies. No significant differences in WCST performance were found between subjects with frontal vs. nonfrontal damage. Some subjects with extensive frontal lobe damage performed well on the WCST, and some subjects with damage outside of the frontal lobes failed. The optimal cutoff scores for discriminating frontal from nonfrontal subjects correctly classified only 62% of the subjects. Further analysis of WCST performances associated with damage to various subregions of the frontal lobes also failed to reveal any reliable relationships. These findings indicate that performance on the WCST cannot be interpreted in isolation as an index of frontal lobe damage.

Neural systems behind word and concept retrieval

Using both the lesion method and functional imaging (positron emission tomography) in large cohorts of subjects investigated with the same experimental tasks, we tested the following hypotheses: (A) that the retrieval of words which denote concrete entities belonging to distinct conceptual categories depends upon partially segregated regions in higher-order cortices of the left temporal lobe; and (B) that the retrieval of conceptual knowledge pertaining to the same concrete entities also depends on partially segregated regions; however, those regions will be different from those postulated in hypothesis A, and located predominantly in the right hemisphere (the second hypothesis tested only with the lesion method). The analyses provide support for hypothesis A in that several regions outside the classical Broca and Wernicke language areas are involved in name retrieval of concrete entities, and that there is a partial segregation in the temporal lobe with respect to the conceptual category to which the entities belong, and partial support for hypothesis B in that retrieval of conceptual knowledge is partially segregated from name retrieval in the lesion study. Those regions identified here are seen as parts of flexible, multi-component systems serving concept and word retrieval for concrete entities belonging to different conceptual categories. By comparing different approaches the article also addresses a number of method issues that have surfaced in recent studies in this field.