Jorge Moll

Human fronto–mesolimbic networks guide decisions about charitable donation

Humans often sacrifice material benefits to endorse or to oppose societal causes based on moral beliefs. Charitable donation behavior, which has been the target of recent experimental economics studies, is an outstanding contemporary manifestation of this ability. Yet the neural bases of this unique aspect of human altruism, which extends beyond interpersonal interactions, remain obscure. In this article, we use functional magnetic resonance imaging while participants anonymously donated to or opposed real charitable organizations related to major societal causes. We show that the mesolimbic reward system is engaged by donations in the same way as when monetary rewards are obtained. Furthermore, medial orbitofrontal–subgenual and lateral orbitofrontal areas, which also play key roles in more primitive mechanisms of social attachment and aversion, specifically mediate decisions to donate or to oppose societal causes. Remarkably, more anterior sectors of the prefrontal cortex are distinctively recruited when altruistic choices prevail over selfish material interests.

The neural basis of human moral cognition

Moral cognitive neuroscience is an emerging field of research that focuses on the neural basis of uniquely human forms of social cognition and behaviour. Recent functional imaging and clinical evidence indicates that a remarkably consistent network of brain regions is involved in moral cognition. These findings are fostering new interpretations of social behavioural impairments in patients with brain dysfunction, and require new approaches to enable us to understand the complex links between individuals and society. Here, we propose a cognitive neuroscience view of how cultural and context-dependent knowledge, semantic social knowledge and motivational states can be integrated to explain complex aspects of human moral cognition.

Social concepts are represented in the superior anterior temporal cortex

Social concepts such as “tactless” or “honorable” enable us to describe our own as well as others social behaviors. The prevailing view is that this abstract social semantic knowledge is mainly subserved by the same medial prefrontal regions that are considered essential for mental state attribution and self-reflection. Nevertheless, neurodegeneration of the anterior temporal cortex typically leads to impairments of social behavior as well as general conceptual knowledge. By using functional MRI, we demonstrate that the anterior temporal lobe represents abstract social semantic knowledge in agreement with this patient evidence. The bilateral superior anterior temporal lobes (Brodmanns area 38) are selectively activated when participants judge the meaning relatedness of social concepts (e.g., honor–brave) as compared with concepts describing general animal functions (e.g., nutritious–useful). Remarkably, only activity in the superior anterior temporal cortex, but not the medial prefrontal cortex, correlates with the richness of detail with which social concepts describe social behavior. Furthermore, this anterior temporal lobe activation is independent of emotional valence, whereas medial prefrontal regions show enhanced activation for positive social concepts. Our results demonstrate that the superior anterior temporal cortex plays a key role in social cognition by providing abstract conceptual knowledge of social behaviors. We further speculate that these abstract conceptual representations can be associated with different contexts of social actions and emotions through integration with frontolimbic circuits to enable flexible evaluations of social behavior.

The Neural Basis of Human Social Values: Evidence from Functional MRI

Social values are composed of social concepts (e.g., generosity) and context-dependent moral sentiments (e.g., pride). The neural basis of this intricate cognitive architecture has not been investigated thus far. Here, we used functional magnetic resonance imaging while subjects imagined their own actions toward another person (self-agency) which either conformed or were counter to a social value and were associated with pride or guilt, respectively. Imagined actions of another person toward the subjects (other-agency) in accordance with or counter to a value were associated with gratitude or indignation/anger. As hypothesized, superior anterior temporal lobe (aTL) activity increased with conceptual detail in all conditions. During self-agency, activity in the anterior ventromedial prefrontal cortex correlated with pride and guilt, whereas activity in the subgenual cingulate solely correlated with guilt. In contrast, indignation/anger activated lateral orbitofrontal-insular cortices. Pride and gratitude additionally evoked mesolimbic and basal forebrain activations. Our results demonstrate that social values emerge from coactivation of stable abstract social conceptual representations in the superior aTL and context-dependent moral sentiments encoded in fronto-mesolimbic regions. This neural architecture may provide the basis of our ability to communicate about the meaning of social values across cultural contexts without limiting our flexibility to adapt their emotional interpretation.

The self as a moral agent: Linking the neural bases of social agency and moral sensitivity

Abstract The human brain is inherently able to understand the world in moral ways, endowing most of us with an intuitive sense of fairness, concern for others, and observance of cultural norms. We have argued that this moral sensitivity ability depends on a sophisticated integration of cognitive, emotional, and motivational mechanisms, which are modulated by individual experience in different cultural milieus. Different lines of investigation on agency and morality have pointed to overlapping neural systems. Therefore, understanding the relationships between morality and agency may provide key insights into the mechanisms underlying human behavior in several clinical and societal settings. We used functional MRI to investigate the contribution of agency and of specific moral emotions to brain activation using action scripts. Results showed that emotionally neutral agency recruited neural networks previously associated with agency, intentionality and moral cognition, encompassing ventral and subgenual sectors of the medial prefrontal cortex (PFC), insula, anterior temporal cortex and superior temporal sulcus (STS). Compared to emotionally neutral agency, different categories of moral emotions led to distinct activation patterns: (1) prosocial emotions (guilt, embarrassment, compassion) activated the anterior medial PFC and STS, with (2) empathic emotions (guilt and compassion) additionally recruiting the mesolimbic pathway; (3) other-critical emotions (disgust and indignation) were associated with activation of the amygdala—parahippocampal and fusiform areas. These findings indicate that agency related to norm-abiding social behaviors of emotionally neutral scripts share neural substrates both with the “default mode” of brain function and with the moral sensitivity network. Additional activation in specific components of this network is elicited by different classes of moral emotions, in agreement with recent integrative models of moral cognition and emotion.

Social conceptual impairments in frontotemporal lobar degeneration with right anterior temporal hypometabolism

Inappropriate social behaviours are early and distinctive symptoms of the temporal and frontal variants of frontotemporal lobar degeneration (FTLD). Knowledge of social behaviour is essential for appropriate social conduct. It is unknown, however, in what way this knowledge is degraded in FTLD. In a recent functional MRI study, we have identified a right-lateralized superior anterior temporal lobe (aTL) region showing selective activation for social concepts (i.e. concepts describing social behaviour: e.g. polite, stingy) as compared with concepts describing less socially relevant animal behaviour (animal function concepts: e.g. trainable, nutritious). In a further fMRI study, superior aTL activation was independent of the context of actions and feelings associated with these social concepts. Here, we investigated whether the right superior sector of the aTL is necessary for context-independent knowledge of social concepts. We assessed neuronal glucose uptake using 18-fluoro-deoxy-glucose-positron emission tomography (FDG-PET) and a novel semantic discrimination task which probed knowledge of social and animal function concepts in patients with FTLD (n = 29) and corticobasal syndrome (n = 18). FTLD and corticobasal syndrome groups performed equally poorly on animal function concepts but FTLD patients showed more pronounced impairments on social concepts than corticobasal syndrome patients. FTLD patients with right superior aTL hypometabolism, as determined on individual ROI analyses, were significantly more impaired on social concepts than on animal function concepts. FTLD patients with selective impairments for social concepts, as determined on individual neuropsychological profiles, showed higher levels of inappropriate social behaviours (disinhibition) and demonstrated more pronounced hypometabolism in the right superior aTL, the left temporal pole and the right lateral orbitofrontal and dorsomedial prefrontal cortex as compared with FTLD patients showing selective impairments of animal function concepts. Combining both FTLD subgroup analyses, based on anatomical and neuropsychological criteria, by using inclusive masks, revealed the right superior aTL as associated with selective impairments of social concepts in both analyses. These results corroborate the hypothesis that the right aTL is necessary for representing conceptual social knowledge. Further, we provide first evidence for the potential importance of conceptual social knowledge impairments as contributing to behavioural symptoms of FTLD.

A psychological and neuroanatomical model of obsessive-compulsive disorder.

Imaging, surgical, and lesion studies suggest that the prefrontal cortex (orbitofrontal and anterior cingulate cortexes), basal ganglia, and thalamus are involved in the pathogenesis of obsessive-compulsive disorder (OCD). On the basis of these findings several models of OCD have been developed, but have had difficulty fully integrating the psychological and neuroanatomical findings of OCD. Recent research in the field of cognitive neuroscience on the normal function of these brain areas demonstrates the role of the orbitofrontal cortex in reward, the anterior cingulate cortex in error detection, the basal ganglia in affecting the threshold for activation of motor and behavioral programs, and the prefrontal cortex in storing memories of behavioral sequences (called structured event complexes or SECs). The authors propose that the initiation of these SECs can be accompanied by anxiety that is relieved with completion of the SEC, and that a deficit in this process could be responsible for many of the symptoms of OCD. Specifically, the anxiety can form the basis of an obsession, and a compulsion can be an attempt to receive relief from the anxiety by repeating parts of, or an entire, SEC. The authors discuss empiric support for, and specific experimental predictions of, this model. The authors believe that this model explains the specific symptoms, and integrates the psychology and neuroanatomy of OCD better than previous models.

No effect of DC brain polarization on verbal fluency in patients with advanced frontotemporal dementia.

Direct Current (DC) brain polarization can alter the activity of cortical neurons and the excitability of the human cortex (Wassermann and Grafman, 2005). We recently reported that surface-anodal DC current applied to the left prefrontal area enhances verbal fluency in healthy subjects (Iyer et al., 2005). Frontotemporal dementia (FTD) comprises a set of disorders affecting the frontal and/or the anterior temporal lobes of the brain that present with behavioral and cognitive symptoms (Lund/Manchester, 1994), including impaired verbal fluency (the ability to generate words within a specific category) (Perri et al., 2005), which depends substantially on prefrontal cortex function (Stuss et al., 1998). To date, no effective treatment for the cognitive deficits in FTD has been found (Huey et al., 2006). Using letter-cued verbal fluency as the primary therapeutic outcome, we undertook a double-blinded, controlled trial of DC polarization in FTD. n nThe 10 patients were clinically diagnosed with FTD by published criteria (Lund/Manchester, 1994). Nine had predominantly behavioral, and one language, symptoms. At initial evaluation, the patients had a mean age of 61.3 years (range 46 to 80 years), a mean duration of illness of 3.4 years (range 1.2 to 6 years), and a mean total Mattis Dementia Rating Scale 2 of 109.3 points (range 45 to 131). The patients were taking the following CNS-active medications: Cholinesterase-inhibitors (6 patients), memantine (5 patients), antidepressants (2 patients), atypical antipsychotic medications (2 patients), benzodiazepines (1 patient). We applied 2 mA current through 25 cm2 electrodes (80 μC/cm2) for 40 min in the patients. As in our pilot study in healthy subjects (Iyer et al., 2005), the anode was placed at the F3 International 10-20 electrode position and the cathode over the right supraorbital area. The current was delivered by a Phoresor® II Auto Model PM850 iontophoresis device. In a double-blind, sham-controlled design each patient received separate sessions of active and sham treatment in a randomized and counterbalanced order. In the active condition, the current (2 mA) was delivered for 20 min before and 20 min after the start of testing (40 min). In the sham condition, the device delivered 10 seconds of very low current (0.1 mA) and was then shut off. The device was set by an investigator who neither interacted with the patients nor took part in the analysis of the data. Two target letters, matched for word frequency, were used before and after treatment in each session in a counterbalanced order. A secondary outcome was total score on the Neuropsychiatric Inventory (Cummings et al., 1994), a measure of behavioral symptoms, covering the 24 hours before and after each treatment. n nActive polarization produced no improvement in verbal fluency relative to sham (Mean change: 1.4 ± 1.9 vs. 1.3 ± 2.9 words, paired t = −0.10, p = 0.93). There was a significant effect of treatment, independent of type (before treatment: 5.1 ± 5.1 words, after treatment: 6.5 ± 5.6 words, paired t = 2.55, p = 0.02), apparently related to practice (Figure 1). This is similar in magnitude to the practice effect observed in normal control subjects given repeated administrations of a verbal fluency task (Lemay et al., 2004). There was no significant effect of treatment on the Neuropsychiatric Inventory scores. n n n nFigure 1 n nDifference in letter-cued verbal fluencies before and after sham and actual treatment. Bars represent the 90th and 10th, and boxes the 75th and 25th, percentiles. Center line is the median. n n n nUsing a treatment that produced significant improvement in verbal fluency in healthy subjects and in a pilot study with FTD patients, we were unable to produce any measurable benefit in FTD. There are several possible reasons for this. First, less current could be reaching the frontal cortex in FTD patients compared to normal controls due to shunting through the increased CSF space left by brain atrophy. Second, depletion of neurons may leave the affected cortex incapable of responding to polarization. Third, some of the more severely affected patients had difficulty cooperating the task and staying in set. A less severely affected patient group might have responded. We do not currently have data to support or refute these theories. While the results from this small trial were negative, there is enough evidence for DC polarizations ability to modulate and enhance local cortical function (Wassermann and Grafman, 2005) to warrant further trials in neurobehavioral disorders.

Increased amygdala response to shame in remitted major depressive disorder.

Proneness to self-blaming moral emotions such as shame and guilt is increased in major depressive disorder (MDD), and may play an important role in vulnerability even after symptoms have subsided. Social psychologists have argued that shame-proneness is relevant for depression vulnerability and is distinct from guilt. Shame depends on the imagined critical perception of others, whereas guilt results from one’s own judgement. The neuroanatomy of shame in MDD is unknown. Using fMRI, we compared 21 participants with MDD remitted from symptoms with no current co-morbid axis-I disorders, and 18 control participants with no personal or family history of MDD. The MDD group exhibited higher activation of the right amygdala and posterior insula for shame relative to guilt (SPM8). This neural difference was observed despite equal levels of rated negative emotional valence and frequencies of induced shame and guilt experience across groups. These same results were found in the medication-free MDD subgroup (Nu200a=u200a15). Increased amygdala and posterior insula activations, known to be related to sensory perception of emotional stimuli, distinguish shame from guilt responses in remitted MDD. People with MDD thus exhibit changes in the neural response to shame after symptoms have subsided. This supports the hypothesis that shame and guilt play at least partly distinct roles in vulnerability to MDD. Shame-induction may be a more sensitive probe of residual amygdala hypersensitivity in MDD compared with facial emotion-evoked responses previously found to normalize on remission.

White Matter Tract Damage in the Behavioral Variant of Frontotemporal and Corticobasal Dementia Syndromes

The phenotypes of the behavioral variant of frontotemporal dementia and the corticobasal syndrome present considerable clinical and anatomical overlap. The respective patterns of white matter damage in these syndromes have not been directly contrasted. Beyond cortical involvement, damage to white matter pathways may critically contribute to both common and specific symptoms in both conditions. Here we assessed patients with the behavioral variant of frontotemporal dementia and corticobasal syndrome with whole-brain diffusion tensor imaging to identify the white matter networks underlying these pathologies. Twenty patients with the behavioral variant of frontotemporal dementia, 19 with corticobasal syndrome, and 15 healthy controls were enrolled in the study. Differences in tract integrity between (i) patients and controls, and (ii) patients with the corticobasal syndrome and the behavioral variant of frontotemporal dementia were assessed with whole brain tract-based spatial statistics and analyses of regions of interest. Behavioral variant of frontotemporal dementia and the corticobasal syndrome shared a pattern of bilaterally decreased white matter integrity in the anterior commissure, genu and body of the corpus callosum, corona radiata and in the long intrahemispheric association pathways. Patients with the behavioral variant of frontotemporal dementia showed greater damage to the uncinate fasciculus, genu of corpus callosum and forceps minor. In contrast, corticobasal syndrome patients had greater damage to the midbody of the corpus callosum and perirolandic corona radiata. Whereas several compact white matter pathways were damaged in both the behavioral variant of frontotemporal dementia and corticobasal syndrome, the distribution and degree of white matter damage differed between them. These findings concur with the distinctive clinical manifestations of these conditions and may improve the in vivo neuroanatomical and diagnostic characterization of these disorders.