Concept: Ventromedial prefrontal cortex
Misophonia is an affective sound-processing disorder characterized by the experience of strong negative emotions (anger and anxiety) in response to everyday sounds, such as those generated by other people eating, drinking, chewing, and breathing [1-8]. The commonplace nature of these sounds (often referred to as “trigger sounds”) makes misophonia a devastating disorder for sufferers and their families, and yet nothing is known about the underlying mechanism. Using functional and structural MRI coupled with physiological measurements, we demonstrate that misophonic subjects show specific trigger-sound-related responses in brain and body. Specifically, fMRI showed that in misophonic subjects, trigger sounds elicit greatly exaggerated blood-oxygen-level-dependent (BOLD) responses in the anterior insular cortex (AIC), a core hub of the "salience network" that is critical for perception of interoceptive signals and emotion processing. Trigger sounds in misophonics were associated with abnormal functional connectivity between AIC and a network of regions responsible for the processing and regulation of emotions, including ventromedial prefrontal cortex (vmPFC), posteromedial cortex (PMC), hippocampus, and amygdala. Trigger sounds elicited heightened heart rate (HR) and galvanic skin response (GSR) in misophonic subjects, which were mediated by AIC activity. Questionnaire analysis showed that misophonic subjects perceived their bodies differently: they scored higher on interoceptive sensibility than controls, consistent with abnormal functioning of AIC. Finally, brain structural measurements implied greater myelination within vmPFC in misophonic individuals. Overall, our results show that misophonia is a disorder in which abnormal salience is attributed to particular sounds based on the abnormal activation and functional connectivity of AIC.
High-level cognitive and emotional experience arises from brain activity, but the specific brain substrates for religious and spiritual euphoria remain unclear. We demonstrate using fMRI scans in 19 devout Mormons that a recognizable feeling central to their devotional practice was reproducibly associated with activation in nucleus accumbens, ventromedial prefrontal cortex, and frontal attentional regions. Nucleus accumbens activation preceded peak spiritual feelings by 1-3 seconds and was replicated in 4 separate tasks. Attentional activation in the anterior cingulate and frontal eye fields was greater in the right hemisphere. The association of abstract ideas and brain reward circuitry may interact with frontal attentional and emotive salience processing, suggesting a mechanism whereby doctrinal concepts may come to be intrinsically rewarding and motivate behavior in religious individuals.
The ability to infer intentions of other agents, called theory of mind (ToM), confers strong advantages for individuals in social situations. Here, we show that ToM can also be maladaptive when people interact with complex modern institutions like financial markets. We tested participants who were investing in an experimental bubble market, a situation in which the price of an asset is much higher than its underlying fundamental value. We describe a mechanism by which social signals computed in the dorsomedial prefrontal cortex affect value computations in ventromedial prefrontal cortex, thereby increasing an individual’s propensity to ‘ride’ financial bubbles and lose money. These regions compute a financial metric that signals variations in order flow intensity, prompting inference about other traders' intentions. Our results suggest that incorporating inferences about the intentions of others when making value judgments in a complex financial market could lead to the formation of market bubbles.
- Proceedings of the National Academy of Sciences of the United States of America
- Published over 7 years ago
Placebo analgesia is often conceptualized as a reward mechanism. However, by targeting only negative experiences, such as pain, placebo research may tell only half the story. We compared placebo improvement of painful touch (analgesia) with placebo improvement of pleasant touch (hyperhedonia) using functional MRI and a crossover design. Somatosensory processing was decreased during placebo analgesia and increased during placebo hyperhedonia. Both placebo responses were associated with similar patterns of activation increase in circuitry involved in emotion appraisal, including the pregenual anterior cingulate, medial orbitofrontal cortex, amygdala, accumbens, and midbrain structures. Importantly, placebo-induced coupling between the ventromedial prefrontal cortex and periaqueductal gray correlated with somatosensory decreases to painful touch and somatosensory increases to pleasant touch. These findings suggest that placebo analgesia and hyperhedonia are mediated by activation of shared emotion appraisal neurocircuitry, which down- or up-regulates early sensory processing, depending on whether the expectation is reduced pain or increased pleasure.
Memory dysfunction is a key symptom of age-related dementia. Although recent studies have suggested positive effects of electrical stimulation for memory enhancement, its potential targets remain largely unknown. In this study, we hypothesized that spatially targeted deep brain stimulation of ventromedial prefrontal cortex enhanced memory functions in a middle-aged rat model. Our results show that acute stimulation enhanced the short-, but not the long-term memory in the novel-object recognition task. Interestingly, after chronic high-frequency stimulation, both the short- and long-term memories were robustly improved in the novel-object recognition test and Morris water-maze spatial task compared to sham. Our results also demonstrated that chronic ventromedial prefrontal cortex high-frequency stimulation upregulated neurogenesis-associated genes along with enhanced hippocampal cell proliferation. Importantly, these memory behaviors were strongly correlated with the hippocampal neurogenesis. Overall, these findings suggest that chronic ventromedial prefrontal cortex high-frequency stimulation may serve as a novel effective therapeutic target for dementia-related disorders.
Beliefs profoundly affect people’s lives, but their cognitive and neural pathways are poorly understood. Although previous research has identified the ventromedial prefrontal cortex (vmPFC) as critical to representing religious beliefs, the means by which vmPFC enables religious belief is uncertain. We hypothesized that the vmPFC represents diverse religious beliefs and that a vmPFC lesion would be associated with religious fundamentalism, or the narrowing of religious beliefs. To test this prediction, we assessed religious adherence with a widely-used religious fundamentalism scale in a large sample of 119 patients with penetrating traumatic brain injury (pTBI). If the vmPFC is crucial to modulating diverse personal religious beliefs, we predicted that pTBI patients with lesions to the vmPFC would exhibit greater fundamentalism, and that this would be modulated by cognitive flexibility and trait openness. Instead, we found that participants with dorsolateral prefrontal cortex (dlPFC) lesions have fundamentalist beliefs similar to patients with vmPFC lesions and that the effect of a dlPFC lesion on fundamentalism was significantly mediated by decreased cognitive flexibility and openness. These findings indicate that cognitive flexibility and openness are necessary for flexible and adaptive religious commitment, and that such diversity of religious thought is dependent on dlPFC functionality.
Whole-brain voxel-based unbiased resting state functional connectivity was analysed in 418 subjects with autism and 509 matched typically developing individuals. We identified a key system in the middle temporal gyrus/superior temporal sulcus region that has reduced cortical functional connectivity (and increased with the medial thalamus), which is implicated in face expression processing involved in social behaviour. This system has reduced functional connectivity with the ventromedial prefrontal cortex, which is implicated in emotion and social communication. The middle temporal gyrus system is also implicated in theory of mind processing. We also identified in autism a second key system in the precuneus/superior parietal lobule region with reduced functional connectivity, which is implicated in spatial functions including of oneself, and of the spatial environment. It is proposed that these two types of functionality, face expression-related, and of one’s self and the environment, are important components of the computations involved in theory of mind, whether of oneself or of others, and that reduced connectivity within and between these regions may make a major contribution to the symptoms of autism.
Important decisions are often made under stressful circumstances that might compromise self-regulatory behavior. Yet the neural mechanisms by which stress influences self-control choices are unclear. We investigated these mechanisms in human participants who faced self-control dilemmas over food reward while undergoing fMRI following stress. We found that stress increased the influence of immediately rewarding taste attributes on choice and reduced self-control. This choice pattern was accompanied by increased functional connectivity between ventromedial prefrontal cortex (vmPFC) and amygdala and striatal regions encoding tastiness. Furthermore, stress was associated with reduced connectivity between the vmPFC and dorsolateral prefrontal cortex regions linked to self-control success. Notably, alterations in connectivity pathways could be dissociated by their differential relationships with cortisol and perceived stress. Our results indicate that stress may compromise self-control decisions by both enhancing the impact of immediately rewarding attributes and reducing the efficacy of regions promoting behaviors that are consistent with long-term goals.
Individuals' risk attitudes are known to guide choices about uncertain options. However, in the presence of others' decisions, these choices can be swayed and manifest as riskier or safer behavior than one would express alone. To test the mechanisms underlying effective social ‘nudges’ in human decision-making, we used functional neuroimaging and a task in which participants made choices about gambles alone and after observing others' selections. Against three alternative explanations, we found that observing others' choices of gambles increased the subjective value (utility) of those gambles for the observer. This ‘other-conferred utility’ was encoded in ventromedial prefrontal cortex, and these neural signals predicted conformity. We further identified a parametric interaction with individual risk preferences in anterior cingulate cortex and insula. These data provide a neuromechanistic account of how information from others is integrated with individual preferences that may explain preference-congruent susceptibility to social signals of safety and risk.
Self-esteem is shaped by the appraisals we receive from others. Here, we characterize neural and computational mechanisms underlying this form of social influence. We introduce a computational model that captures fluctuations in self-esteem engendered by prediction errors that quantify the difference between expected and received social feedback. Using functional MRI, we show these social prediction errors correlate with activity in ventral striatum/subgenual anterior cingulate cortex, while updates in self-esteem resulting from these errors co-varied with activity in ventromedial prefrontal cortex (vmPFC). We linked computational parameters to psychiatric symptoms using canonical correlation analysis to identify an ‘interpersonal vulnerability’ dimension. Vulnerability modulated the expression of prediction error responses in anterior insula and insula-vmPFC connectivity during self-esteem updates. Our findings indicate that updating of self-evaluative beliefs relies on learning mechanisms akin to those used in learning about others. Enhanced insula-vmPFC connectivity during updating of those beliefs may represent a marker for psychiatric vulnerability.