Anatomy and computational modeling of networks underlying cognitive-emotional interaction

The classical dichotomy between cognition and emotion equated the first with rationality or logic and the second with irrational behaviors. The idea that cognition and emotion are separable, antagonistic forces competing for dominance of mind has been hard to displace despite abundant evidence to the contrary. For instance, it is now known that a pathological absence of emotion leads to profound impairment of decision making. Behavioral observations of this kind are corroborated at the mechanistic level: neuroanatomical studies reveal that brain areas typically described as underlying either cognitive or emotional processes are linked in ways that imply complex interactions that do not resemble a simple mutual antagonism. Instead, physiological studies and network simulations suggest that top-down signals from prefrontal cortex realize "cognitive control" in part by either suppressing or promoting emotional responses controlled by the amygdala, in a way that facilitates adaptation to changing task demands. Behavioral, anatomical, and physiological data suggest that emotion and cognition are equal partners in enabling a continuum or matrix of flexible behaviors that are subserved by multiple brain regions acting in concert. Here we focus on neuroanatomical data that highlight circuitry that structures cognitive-emotional interactions by directly or indirectly linking prefrontal areas with the amygdala. We also present an initial computational circuit model, based on anatomical, physiological, and behavioral data to explicitly frame the learning and performance mechanisms by which cognition and emotion interact to achieve flexible behavior.R01 MH057414 - NIMH NIH HHS; R01 NS024760 - NINDS NIH HH

Neural Dynamics of Autistic Behaviors: Cognitive, Emotional, and Timing Substrates

What brain mechanisms underlie autism and how do they give rise to autistic behavioral symptoms? This article describes a neural model, called the iSTART model, which proposes how cognitive, emotional, timing, and motor processes may interact together to create and perpetuate autistic symptoms. These model processes were originally developed to explain data concerning how the brain controls normal behaviors. The iSTART model shows how autistic behavioral symptoms may arise from prescribed breakdowns in these brain processes.Air Force Office of Scientific Research (F49620-01-1-0397); Office of Naval Research (N00014-01-1-0624

The role of the cerebellum in unconsciuos and conscious processing of emotions: a review

Studies from the past three decades have demonstrated that there is cerebellar involvement in the emotional domain. Emotional processing in humans requires both unconscious and conscious mechanisms. A significant amount of evidence indicates that the cerebellum is one of the cerebral structures that subserve emotional processing, although conflicting data have been reported on its function in unconscious and conscious mechanisms. This review discusses the available clinical, neuroimaging and neurophysiological data on this issue. We also propose a model in which the cerebellum acts as a mediator between the internal state and external environment for the unconscious and conscious levels of emotional processing

Capacity and tendency: A neuroscientific framework for the study of emotion regulation.

It is widely accepted that the ability to effectively regulate one's emotions is a cornerstone of physical and mental health. As such, it should come as no surprise that the number of neuroimaging studies focused on emotion regulation and associated processes has increased exponentially in the past decade. To date, neuroimaging research on this topic has examined two distinct but complementary features of emotion regulation - the capacity to effectively utilize a strategy to regulate emotion and to a lesser extent, the tendency to choose to regulate. However, theoretical accounts of emotion regulation have only recently begun to distinguish capacity from tendency. In the present review, we provide a novel framework for conceptualizing these two intertwined, yet distinct, facets of emotion regulation. First we characterize brain regions that support emotion generation and are thus targeted by emotion regulation. Next, we synthesize findings from the dozens of neuroimaging studies that have examined emotion regulation capacity, focusing in particular on the most commonly studied emotion regulation strategy - reappraisal. Finally, we discuss emerging neuroimaging research examining state and trait regulatory tendencies. We conclude by integrating findings from neuroimaging research on emotion regulation capacity and tendency and suggest ways that this integrated model can inform basic and translational neuroscientific research on emotion regulation

Does gaze direction modulate facial expression processing in children with autism spectrum disorder?

Two experiments investigated whether children with autism spectrum disorder (ASD) integrate relevant communicative signals, such as gaze direction, when decoding a facial expression. In Experiment 1, typically developing children (9–14 years old; n = 14) were faster at detecting a facial expression accompanying a gaze direction with a congruent motivational tendency (i.e., an avoidant facial expression with averted eye gaze) than those with an incongruent motivational tendency. Children with ASD (9–14 years old; n = 14) were not affected by the gaze direction of facial stimuli. This finding was replicated in Experiment 2, which presented only the eye region of the face to typically developing children (n = 10) and children with ASD (n = 10). These results demonstrated that children with ASD do not encode and/or integrate multiple communicative signals based on their affective or motivational tendency

Atypical eye contact in autism: Models, mechanisms and development

An atypical pattern of eye contact behaviour is one of the most significant symptoms of Autism Spectrum Disorder (ASD). Recent empirical advances have revealed the developmental, cognitive and neural basis of atypical eye contact behaviour in ASD. We review different models and advance a new ‘fast-track modulator model’. Specifically, we propose that atypical eye contact processing in ASD originates in the lack of influence from a subcortical face and eye contact detection route, which is hypothesized to modulate eye contact processing and guide its emergent specialization during development

The emotional gatekeeper: a computational model of attentional selection and suppression through the pathway from the amygdala to the inhibitory thalamic reticular nucleus

In a complex environment that contains both opportunities and threats, it is important for an organism to flexibly direct attention based on current events and prior plans. The amygdala, the hub of the brain's emotional system, is involved in forming and signaling affective associations between stimuli and their consequences. The inhibitory thalamic reticular nucleus (TRN) is a hub of the attentional system that gates thalamo-cortical signaling. In the primate brain, a recently discovered pathway from the amygdala sends robust projections to TRN. Here we used computational modeling to demonstrate how the amygdala-TRN pathway, embedded in a wider neural circuit, can mediate selective attention guided by emotions. Our Emotional Gatekeeper model demonstrates how this circuit enables focused top-down, and flexible bottom-up, allocation of attention. The model suggests that the amygdala-TRN projection can serve as a unique mechanism for emotion-guided selection of signals sent to cortex for further processing. This inhibitory selection mechanism can mediate a powerful affective 'framing' effect that may lead to biased decision-making in highly charged emotional situations. The model also supports the idea that the amygdala can serve as a relevance detection system. Further, the model demonstrates how abnormal top-down drive and dysregulated local inhibition in the amygdala and in the cortex can contribute to the attentional symptoms that accompany several neuropsychiatric disorders.R01MH057414 - NIMH NIH HHS; R01 MH057414 - NIMH NIH HHS; R01 MH101209 - NIMH NIH HHS; R01NS024760 - NINDS NIH HHS; R01MH101209 - NIMH NIH HHS; R01 NS024760 - NINDS NIH HH

Preliminary Evidence That CD38 Moderates the Association of Neuroticism on Amygdala-Subgenual Cingulate Connectivity.

CD38 genetic variation has been associated with autism spectrum disorders and social anxiety disorder, which may result from CD38's regulation of oxytocin secretion. Converging evidence has found that the rs3796863 A-allele contributes to increased social sensitivity compared to the CC genotype. The current study examined the moderating role of CD38 genetic variants (rs3796863 and rs6449182) that have been associated with enhanced (or reduced) social sensitivity on neural activation related to neuroticism, which is commonly elevated in individuals with social anxiety and depression. Adults (n = 72) with varying levels of social anxiety and depression provided biological samples for DNA extraction, completed a measure of neuroticism, and participated in a standardized emotion processing task (affect matching) while undergoing fMRI. A significant interaction effect was found for rs3796863 x neuroticism that predicted right amygdala-subgenual anterior cingulate cortex (sgACC) functional connectivity. Simple slopes analyses showed a positive association between neuroticism and right amygdala-sgACC connectivity among rs3796863 A-allele carriers. Findings suggest that the more socially sensitive rs3796863 A-allele may partially explain the relationship between a known risk factor (i.e. neuroticism) and promising biomarker (i.e. amygdala-sgACC connectivity) in the development and maintenance of social anxiety and depression

Sleep-amount differentially affects fear-processing neural circuitry in pediatric anxiety: A preliminary fMRI investigation.

Insufficient sleep, as well as the incidence of anxiety disorders, both peak during adolescence. While both conditions present perturbations in fear-processing-related neurocircuitry, it is unknown whether these neurofunctional alterations directly link anxiety and compromised sleep in adolescents. Fourteen anxious adolescents (AAs) and 19 healthy adolescents (HAs) were compared on a measure of sleep amount and neural responses to negatively valenced faces during fMRI. Group differences in neural response to negative faces emerged in the dorsal anterior cingulate cortex (dACC) and the hippocampus. In both regions, correlation of sleep amount with BOLD activation was positive in AAs, but negative in HAs. Follow-up psychophysiological interaction (PPI) analyses indicated positive connectivity between dACC and dorsomedial prefrontal cortex, and between hippocampus and insula. This connectivity was correlated negatively with sleep amount in AAs, but positively in HAs. In conclusion, the presence of clinical anxiety modulated the effects of sleep-amount on neural reactivity to negative faces differently among this group of adolescents, which may contribute to different clinical significance and outcomes of sleep disturbances in healthy adolescents and patients with anxiety disorders

Sensory sensitivity as a link between concussive traumatic brain injury and PTSD.

Traumatic brain injury (TBI) is one of the most common injuries to military personnel, a population often exposed to stressful stimuli and emotional trauma. Changes in sensory processing after TBI might contribute to TBI-post traumatic stress disorder (PTSD) comorbidity. Combining an animal model of TBI with an animal model of emotional trauma, we reveal an interaction between auditory sensitivity after TBI and fear conditioning where 75 dB white noise alone evokes a phonophobia-like phenotype and when paired with footshocks, fear is robustly enhanced. TBI reduced neuronal activity in the hippocampus but increased activity in the ipsilateral lateral amygdala (LA) when exposed to white noise. The white noise effect in LA was driven by increased activity in neurons projecting from ipsilateral auditory thalamus (medial geniculate nucleus). These data suggest that altered sensory processing within subcortical sensory-emotional circuitry after TBI results in neutral stimuli adopting aversive properties with a corresponding impact on facilitating trauma memories and may contribute to TBI-PTSD comorbidity