Neuroanatomical substrates for the volitional regulation of heart rate

The control of physiological arousal can assist in the regulation of emotional state. A subset cortical and subcortical brain regions are implicated in autonomic control of bodily arousal during emotional behaviors. Here, we combined human functional neuroimaging with autonomic monitoring to identify neural mechanisms that support the volitional regulation of heart rate, a process that may be assisted by visual feedback. During functional magnetic resonance imaging (fMRI), 15 healthy adults performed an experimental task in which they were prompted voluntarily to increase or decrease cardiovascular arousal (heart rate) during true, false, or absent visual feedback. Participants achieved appropriate changes in heart rate, without significant modulation of respiratory rate, and were overall not influenced by the presence of visual feedback. Increased activity in right amygdala, striatum and brainstem occurred when participants attempted to increase heart rate. In contrast, activation of ventrolateral prefrontal and parietal cortices occurred when attempting to decrease heart rate. Biofeedback enhanced activity within occipito-temporal cortices, but there was no significant interaction with task conditions. Activity in regions including pregenual anterior cingulate and ventral striatum reflected the magnitude of successful task performance, which was negatively related to subclinical anxiety symptoms. Measured changes in respiration correlated with posterior insula activation and heart rate, at a more lenient threshold, change correlated with insula, caudate, and midbrain activity. Our findings highlight a set of brain regions, notably ventrolateral prefrontal cortex, supporting volitional control of cardiovascular arousal. These data are relevant to understanding neural substrates supporting interaction between intentional and interoceptive states related to anxiety, with implications for biofeedback interventions, e.g., real-time fMRI, that target emotional regulation

Flexibly adapting to emotional cues: Examining the functional and structural correlates of emotional reactivity and emotion control in healthy and depressed individuals

The ability of emotionally significant stimuli to bias our behaviour is an evolutionarily adaptive phenomenon. However, sometimes emotions become excessive, inappropriate, and even pathological, like in major depressive disorder (MDD). Emotional flexibility includes both the neural processes involved in reacting to, or representing, emotional significance, and those involved in controlling emotional reactivity. MDD represents a potentially distinct form of emotion (in)flexibility, and therefore offers a unique perspective for understanding both the integration of conflicting emotional cues and the neural regions involved in actively controlling emotional systems. The present investigation of emotional flexibility began by considering the functional neural correlates of competing socio-emotional cues and effortful emotion regulation in MDD using both negative and positive emotions. Study 1 revealed greater amygdala activity in MDD relative to control participants when negative cues were centrally presented and task-relevant. No significant between-group differences were observed in the amygdala for peripheral task-irrelevant negative distracters. However, controls demonstrated greater recruitment of the ventrolateral (vlPFC) and dorsomedial prefrontal cortices (dmPFC) implicated in emotion control. Conversely, attenuated amygdala activity for task-relevant and irrelevant positive cues was observed in depressed participants. In Study 2, effortful emotion regulation using strategies adapted from cognitive behaviour therapy (CBT) revealed greater activity in regions of the dorsal and lateral prefrontal cortices in both MDD and control participants when attempting to either down-regulate negative or up-regulate positive emotions. During the down-regulation of negative cues, only controls displayed a significant reduction of amygdala activity. In Study 3, an individual differences approach using multiple regression revealed that while greater amygdala-vmPFC structural connectivity was associated with low trait-anxiety, greater connectivity between amygdala and regions of occipitotemporal and parietal cortices was associated with high trait-anxiety. These findings are discussed with respect to current models of emotional reactivity and emotion control derived from studies of both healthy individuals and those with emotional disorders, particularly depression. The focus is on amygdala variability in differing contexts, the role of the vmPFC in the modulation of amygdala activity via learning processes, and the modulation of emotion by attention or cognitive control mechanisms initiated by regions of frontoparietal cortices

The Multi-Dimensional Contributions of Prefrontal Circuits to Emotion Regulation during Adulthood and Critical Stages of Development

The prefrontal cortex (PFC) plays a pivotal role in regulating our emotions. The importance of ventromedial regions in emotion regulation, including the ventral sector of the medial PFC, the medial sector of the orbital cortex and subgenual cingulate cortex, have been recognized for a long time. However, it is increasingly apparent that lateral and dorsal regions of the PFC, as well as neighbouring dorsal anterior cingulate cortex, also play a role. Defining the underlying psychological mechanisms by which these functionally distinct regions modulate emotions and the nature and extent of their interactions is a critical step towards better stratification of the symptoms of mood and anxiety disorders. It is also important to extend our understanding of these prefrontal circuits in development. Specifically, it is important to determine whether they exhibit differential sensitivity to perturbations by known risk factors such as stress and inflammation at distinct developmental epochs. This Special Issue brings together the most recent research in humans and other animals that addresses these important issues, and in doing so, highlights the value of the translational approach

The uncertain brain: a co-ordinate based meta-analysis of the neural signatures supporting uncertainty during different contexts

Uncertainty is often inevitable in everyday life and can be both stressful and exciting. Given its relevance to psychopathology and wellbeing, recent research has begun to address the brain basis of uncertainty. In the current review we examined whether there are discrete and shared neural signatures for different uncertain contexts. From the literature we identified three broad categories of uncertainty currently empirically studied using functional MRI (fMRI): basic threat and reward uncertainty, decision-making under uncertainty, and associative learning under uncertainty. We examined the neural basis of each category by using a coordinate based metaanalysis, where brain activation foci from previously published fMRI experiments were drawn together (1998-2017; 87 studies). The analyses revealed shared and discrete patterns of neural activation for uncertainty, such as the insula and amygdala, depending on the category. Such findings will have relevance for researchers attempting to conceptualise uncertainty, as well as clinical researchers examining the neural basis of uncertainty in relation to psychopathology

Temporal characteristics of the influence of punishment on perceptual decision making in the human brain

Perceptual decision making is the process by which information from sensory systems is combined and used to influence our behavior. In addition to the sensory input, this process can be affected by other factors, such as reward and punishment for correct and incorrect responses. To investigate the temporal dynamics of how monetary punishment influences perceptual decision making in humans, we collected electroencephalography (EEG) data during a perceptual categorization task whereby the punishment level for incorrect responses was parametrically manipulated across blocks of trials. Behaviorally, we observed improved accuracy for high relative to low punishment levels. Using multivariate linear discriminant analysis of the EEG, we identified multiple punishment-induced discriminating components with spatially distinct scalp topographies. Compared with components related to sensory evidence, components discriminating punishment levels appeared later in the trial, suggesting that punishment affects primarily late postsensory, decision-related processing. Crucially, the amplitude of these punishment components across participants was predictive of the size of the behavioral improvements induced by punishment. Finally, trial-by-trial changes in prestimulus oscillatory activity in the alpha and gamma bands were good predictors of the amplitude of these components. We discuss these findings in the context of increased motivation/attention, resulting from increases in punishment, which in turn yields improved decision-related processing

Investigation of Memory Related Cortical Thalamic Circuitry in the Human Brain

This dissertation examined the role of medial prefrontal cortex (mPFC) and the hippocampus (HC) in episodic memory, and provides a novel approach to identify the midline thalamus mediating mPFC-HC interactions in humans. The mPFC and HC are critical to the temporal organization of episodic memory, and these interactions are disrupted in several mental health and neurological disorders. In the first study, I provide evidence that the mPFC is involved in ordinal retrieval, and the HC is active in temporal context retrieval in remembering the order of when events happen. In the second study, I focus on the anatomical basis of the mPFC-HC interactions which is reliant on the midline thalamus. I review in detail the anatomy of the midline thalamus both in location, and connectivity profile with the rest of the brain comparing the extensive anatomical evidence in rodents with the available evidence in monkeys and humans. This section also elaborates on the role of the midline thalamus in memory, stress regulation, wakefulness, and feeding behavior, and how pathological markers along the midline thalamus are a vanguard of several neurological disorders including Alzheimer’s Disease, schizophrenia, depression, and drug addiction. Lastly, I devised a new approach to identify the midline thalamus in humans in vivo using diffusion weighted imaging, capitalizing on known fiber connections gleaned from non-human animals, focusing on connections between the midline thalamus and the mPFC, medial temporal lobe and the nucleus accumbens. The success of this approach is promising for translational imaging. Overall, this dissertation provides new evidence on 1) complementary functional roles of the mPFC and HC in sequence memory, 2) a cross-species anatomical framework for understanding the midline thalamus in humans and neurological disorders, and 3) a new method for non-invasive identification of the midline thalamus in humans in vivo. Thus, this dissertation provides a new fundamental understanding of mPFC-midline thalamic-HC circuit in humans and tools for its non-invasive study in human disease

Primate Ventromedial Prefrontal Cortex and the Physiological and Behavioural Dysfunction Characteristic of Mood and Anxiety Disorders

The heterogeneity intrinsic to the ventromedial prefrontal cortex (vmPFC) is evidenced in both its anatomy and implicated function: vmPFC subregions have roles in positive affect, negative affect and autonomic/endocrine regulation. Whether different subregions serve fundamentally different functions, or whether they perform similar computations on different inputs, remains unclear. Nevertheless, the role of the vmPFC in psychopathology is widely appreciated – in mood and anxiety disorders, over-activity within constituent regions of the vmPFC is consistently implicated in symptomatology, together with its normalisation following successful treatment. However, the precise locus of change varies between studies. The work presented in this thesis investigates the causal contributions of over-activity within two key subregions of the vmPFC – the subgenual anterior cingulate cortex (sgACC, area 25) and perigenual anterior cingulate cortex (pgACC, area 32) – in discrete dimensions of behaviour and physiology affected in psychiatric disorders. Specifically, the impact of over-activity is assessed on (i) baseline physiological function; (ii) the regulation of anticipatory, motivational and consummatory aspects of reward-related behaviour; and (iii) negative affect including fear learning, stress recovery and the intolerance of uncertainty. To provide further insight into the mechanism of action of antidepressants, the efficacy of selected treatments is tested on changes induced by over-activity of these regions. Beyond the direct relevance of the results presented here to psychiatric disorders and their treatment, the thesis aims to emphasise the importance of broader themes associated with the measurement and quantification of emotion in preclinical animal studies. First, a multi-faceted approach is utilised enabling quantification of both the autonomic and behavioural aspects of emotion. In so doing, the experiments maintain relevance to studies which assess these correlates in isolation, both in humans (which typically measure subjective responses and physiology) and in rodents (which frequently assess behaviour in isolation). The assessment of more than one dimension of emotion confers these studies with improved power to detect maladaptive changes. Second, the experiments described were conducted in the marmoset, a new-world primate. The extensive anatomical homology between marmoset and human prefrontal cortex facilitates the forward-translation of functional results. In combination with the appropriate assays, this renders marmosets as an invaluable species to study the causal contributions of vmPFC subregions to symptoms of psychiatric disorders. I believe that the results of these experiments provide important insights into the causal role primate vmPFC has in relation to the behavioural and physiological aspects of psychiatric symptomatology. Most importantly, I hope that they serve as the foundation for future work to further elucidate the neuropathological processes underlying mental disorders.MRC DTP Studentshi

The neural architecture of emotional intelligence.

Emotional Intelligence (EI) is a nebulous concept that permeates daily interpersonal communication. Despite prolific research into its benefits, EI subjective measurement is difficult, contributing to an enigmatic definition of its core constructs. However, neuroimaging research probing socioaffective brain mechanisms underlying putative EI constructs can add an objective perspective to existing models, thereby illuminating the nature of EI. Therefore, the primary aim of this dissertation is to identify brain networks underlying EI and examine how EI arises from the brain’s functional and structural neuroarchitecture. EI is first defined according to behavioral data, which suggests EI is made up of two core constructs: Empathy and Emotion Regulation (ER). The interaction of brain networks underlying Empathy and ER is then investigated using a novel neuroimaging analysis method: dynamic functional connectivity (dynFC). The results suggest efficient communication and (re)configuration between the CEN, DMN, SN underlie both ER and RME task dynamics, and that these temporal patterns relate to trait empathy and ER tendency. Given the demonstrated behavioral and neurobiological relationship between empathy and ER, our second aim is to examine each of these constructs individually through detailed experiments using a variety of neuroimaging methodologies. The dissertation concludes by proposing EI is an ability that arises from the effective, yet flexible communication between brain networks underlying Empathy and ER. The dissertation is divided into five chapters. Chapter I describes the foundational concept of EI as originally described by a variety of psychological figures and the lacuna that exists in terms of its neural correlates. Chapter II presents behavioral data that proposes EI is best predicted by Empathy and ER. Chapter III explores the dynamic relationship between brain networks underlying Empathy and ER, with the aim of elucidating their neurobiological associations, and investigate how such associations may combine to create EI. Chapter IV examines Empathy closely, by probing its neurobiological relationship to interoception and anxiety. Chapter V examines ER closely, by investigating whether gender plays a role in ER, and its neurobiological relationship to hormones. Chapter VI links the general findings from Chapters III, IV and V, and proposes an integrative neurocognitive EI model. The dissertation concludes by providing clinical and non-clinical applications for the model

Social and Affective Neuroscience of Everyday Human Interaction

This Open Access book presents the current state of the art knowledge on social and affective neuroscience based on empirical findings. This volume is divided into several sections first guiding the reader through important theoretical topics within affective neuroscience, social neuroscience and moral emotions, and clinical neuroscience. Each chapter addresses everyday social interactions and various aspects of social interactions from a different angle taking the reader on a diverse journey. The last section of the book is of methodological nature. Basic information is presented for the reader to learn about common methodologies used in neuroscience alongside advanced input to deepen the understanding and usability of these methods in social and affective neuroscience for more experienced readers