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

An insula hierarchical network architecture for active interoceptive inference

In the brain, the insular cortex receives a vast amount of interoceptive information, ascending through deep brain structures, from multiple visceral organs. The unique hierarchical and modular architecture of the insula suggests specialization for processing interoceptive afferents. Yet, the biological significance of the insula's neuroanatomical architecture, in relation to deep brain structures, remains obscure. In this opinion piece, we propose the Insula Hierarchical Modular Adaptive Interoception Control (IMAC) model to suggest that insula modules (granular, dysgranular and agranular), forming parallel networks with the prefrontal cortex and striatum, are specialized to form higher order interoceptive representations. These interoceptive representations are recruited in a context-dependent manner to support habitual, model-based and exploratory control of visceral organs and physiological processes. We discuss how insula interoceptive representations may give rise to conscious feelings that best explain lower order deep brain interoceptive representations, and how the insula may serve to defend the body and mind against pathological depression

Functional Alterations in Cerebellar Functional Connectivity in Anxiety Disorders

Adolescents with anxiety disorders exhibit excessive emotional and somatic arousal. Neuroimaging studies have shown abnormal cerebral cortical activation and connectivity in this patient population. The specific role of cerebellar output circuitry, specifically the dentate nuclei (DN), in adolescent anxiety disorders remains largely unexplored. Resting-state functional connectivity analyses have parcellated the DN, the major output nuclei of the cerebellum, into three functional territories (FTs) that include default-mode, salience-motor, and visual networks. The objective of this study was to understand whether FTs of the DN are implicated in adolescent anxiety disorders. Forty-one adolescents (mean age 15.19 ± 0.82, 26 females) with one or more anxiety disorders and 55 age- and gender-matched healthy controls completed resting-state fMRI scans and a self-report survey on anxiety symptoms. Seed-to-voxel functional connectivity analyses were performed using the FTs from DN parcellation. Brain connectivity metrics were then correlated with State-Trait Anxiety Inventory (STAI) measures within each group. Adolescents with an anxiety disorder showed significant hyperconnectivity between salience-motor DN FT and cerebral cortical salience-motor regions compared to controls. Salience-motor FT connectivity with cerebral cortical sensorimotor regions was significantly correlated with STAI-trait scores in HC (R2 = 0.41). Here, we report DN functional connectivity differences in adolescents diagnosed with anxiety, as well as in HC with variable degrees of anxiety traits. These observations highlight the relevance of DN as a potential clinical and sub-clinical marker of anxiety

Neuronal basis of emotion processing and regulation in conduct disorder

Emotion regulation, a key component of healthy development, has been shown to be deficient in several psychiatric conditions, including conduct disorder. Conduct disorder is a neuropsychiatric disorder of childhood and adolescence characterized by severe aggressive behavior and violation of societal norms. It is highly prevalent and results in substantial economic costs and negative social consequences. Neuroimaging evidence has revealed brain activity alterations in several regions, including prefrontal, temporal, and limbic cortex (amygdala, insula, and cingulate gyrus). While the neuronal basis of emotion processing in conduct disorder has been intensely investigated, the brain correlates of implicit and explicit emotion regulation remain unclear. The main aim of this dissertation was to extend current knowledge by investigating the neuronal mechanisms of emotion regulation in children and adolescents with conduct disorder. First, we conducted a meta-analysis in order to identify the neuronal correlates of emotion processing in adolescents with aggressive behavior. We then developed an affective Stroop task designed to investigate the interplay between emotion and cognition in a paediatric population, and validated it in healthy young adults. We then employed the task to study the neuronal characteristics of implicit emotion-cognition interaction in children and adolescents with conduct disorder. Finally, we investigated explicit emotion regulation by cognitive reappraisal (i.e., reinterpretation of the meaning of an emotional stimulus) in conduct disorder. We here present findings on altered brain function during tasks assessing implicit and explicit emotion regulation in adolescents with conduct disorder that are in agreement with behaviorally observed deficits. Our meta-analysis on emotion processing in conduct disorder summarized previous literature indicating prefrontal and limbic brain structure and function alterations. The results from our study employing the affective Stroop task in healthy adults validated the usefulness of our task design and replicated previous findings suggesting that emotion significantly impacts cognition on a behavioral and neuronal level. Using the affective Stroop and cognitive reappraisal tasks in adolescents with conduct disorder revealed neuronal alterations within prefrontal and limbic regions, brain areas implicated in both emotion and cognition. Overall, the results of this dissertation provide novel evidence on the neuronal basis of emotion regulation deficits in conduct disorder. Future studies shall further investigate emotion regulation in specific subgroups of conduct disorder, for example those with psychopathic traits or high levels of anxiety with the ultimate goal of influencing the child’s immediate environment and society as a whole

The Association of Cognitive Function with Autonomic-Cardiovascular Reactivity to and Recovery From Stress

The contribution of stress in the development of chronic and terminal disease has garnered significant interest in contemporary research. The current study aims to look at how performance in domains of cognitive function may affect autonomic-cardiovascular reactivity and recovery to psychologically stressful tasks as such reactions, over time, may contribute to the development of cardiovascular disease. The current study analyzed data from 209 healthy middle-age adults. This included four neuropsychological tests utilized here to represent abilities in four different cognitive domains: response inhibition, mental flexibility, verbal memory, and nonverbal memory. The participants were also introduced to three psychologically stressful tasks while blood pressure, heart rate, and spectral components of heart rate variability measurements were taken during the tasks and the post-task recovery period. Results showed no significant relationship between blood pressure reactivity or recovery and cognitive function. No significant relationship was found between heart rate variability reactivity and cognitive function. Results showed no significant relationship between blood pressure reactivity or recovery and cognitive function. No significant relationship was found between heart rate variability reactivity and cognitive function. However, superior performance in response inhibition was significantly positively associated with both LF-HRV (p = .04) and HF-HRV (p = .02) in the immediate recovery phase and HF-HRV (p = .02) in the delayed recovery phase. Such findings suggest that greater response inhibition abilities may contribute to greater vagally induced recovery from stressful tasks. Such a response can be considered healthy and likely acts as a protective factor against the development of cardiovascular disease

Neuronal and behavioural pain processing

In our study “Neuronal and Behavioural Pain Processing: A Comparison Between a Strong Brand and a Generic Medication Placebo using the Example of Aspirin vs. 1A Pharma”, we investigated the expectation effects associated with brands by labelling two different placebo interventions. We tested the hypothesis, whether a strong brand can influence the impact of an inert substance. We studied the potential differences between the two placebos on a behavioural and neural level inducing the stimulus with noxious heat pain using Medoc. The research objective was to unveil, whether recipients can be influenced through expectations, verbal suggestions and the brand itself. We applied a two by two design with two identical placebo interventions that differed in their labelling. One group was told that they will receive 500 mg of “Aspirin” (original brand), while the other group was told that they will receive a popular ASA generic (“1A Pharma”). At the beginning, we established the individual pain levels of each subject with the numeric rating scale. Then we measured pain intensities before and after the intervention. The intervention was the administration of the placebo. We investigated behavioural as well as neural differences and looked for corresponding activated brain regions using functional magnetic resonance imaging (fMRI). Those participants, who were administered the original brand in the placebo intervention, showed a decrease in pain intensity. The generic group did not show any significant pain decrease. At the neuronal level, during the native condition, we observed activations of the anterior insula in both groups. After the intervention, the participants showed activations of the dorsomedial prefrontal cortex. The direct comparison of the two placebo conditions – the branded placebo vs. the generic – showed higher activations for the bilateral dorsolateral and dorsomedial prefrontal cortex. During the anticipation phase we observed activations of hippocampal, parahippocampal and adjacent brain areas for the generic group, only. These results suggest that only the original brand appears to evoke a behavioural response measured in terms of pain reduction. On a neuronal level, the activations were significant for the original brand only. Comparing the two placebo interventions, expectations seem to be significantly enhanced by the trusted brand, which appears to boost the placebo effect. Our results suggest that the underlying neural mechanisms of this placebo response are based on fronto-cortical neural networks

Evidence for a Large-Scale Brain System Supporting Allostasis and Interoception in Humans

Large-scale intrinsic brain systems have been identified for exteroceptive senses (e.g., sight, hearing, touch). We introduce an analogous system for representing sensations from within the body, called interoception, and demonstrate its relation to regulating peripheral systems in the body, called allostasis. Employing the recently introduced Embodied Predictive Interoception Coding (EPIC) model, we used tract-tracing studies of macaque monkeys, followed by two intrinsic functional magnetic resonance imaging samples (N = 280 and N = 270) to evaluate the existence of an intrinsic allostatic/interoceptive system in the human brain. Another sample (N = 41) allowed us to evaluate the convergent validity of the hypothesized allostatic/interoceptive system by showing that individuals with stronger connectivity between system hubs performed better on an implicit index of interoceptive ability related to autonomic fluctuations. Implications include insights for the brain’s functional architecture, dissolving the artificial boundary between mind and body, and unifying mental and physical illness