Stimulus-driven reorienting in the ventral frontoparietal attention network: the role of emotional content

Activity in the human temporoparietal junction (TPJ) and inferior frontal gyrus (IFG) is hypothesized to underlie stimulus-driven, or “bottom-up” attention reorienting. Demanding tasks require focused attention, and as task difficulty increases, activity suppression in the ventral network correlates positively with task performance, an effect thought to reflect the gating of irrelevant cues. However, activation in these structures is elicited by a range of stimulus features and task demands that vary across multiple characteristics, complicating the interpretation of the functional role of this pathway. Consideration of several current studies suggests that, in addition to task difficulty, the motivational relevance or emotional intensity of distractor stimuli may supersede ongoing task priority, and evoke ventral network activation. Support for this possibility is offered from a review of recent reports, and the import of this perspective for models of attention reorienting is discussed

Mental Imagery in the Regulation of Differential Fear Conditioning: A Multimodal Investigation Involving Self-Report, Psychophysiology, and Brain Imaging

Mental imagery is a common component in a range of emotion regulation techniques. However, the effectiveness and neural mechanisms of regulation via mental imagery are underexplored due to a lack of studies targeting mental imagery specifically. This discrepancy results in uncertainty regarding the mechanism of regulation in existing paradigms. Biased competition for attentional resources presents a plausible model by which a mental imagery-based distracter can downregulate response to an emotional stimulus. If visualizing an imagined distracter effectively regulates emotional response, the inclusion of mental imagery components in other techniques represents a potential confound. To address this discrepancy, this dissertation investigates the effectiveness and neural correlates of mental imagery in the regulation of differentially conditioned fear. Results of this investigation indicate that mental imagery-based regulation is comparably effective to object-based distraction, but requires a greater investment of cognitive resources to perform. Furthermore, while neural mechanisms of this regulation are consistent with biased competition, mental imagery-based distraction demonstrates notable differences in neural correlates from those identified in object-based distraction. In conclusion, mental imagery represents both a distinct and effective technique in emotion regulation

Functional Source Separation for EEG-fMRI Fusion: Application to Steady-State Visual Evoked Potentials

Neurorobotics is one of the most ambitious fields in robotics, driving integration of interdisciplinary data and knowledge. One of the most productive areas of interdisciplinary research in this area has been the implementation of biologically-inspired mechanisms in the development of autonomous systems. Specifically, enabling such systems to display adaptive behavior such as learning from good and bad outcomes, has been achieved by quantifying and understanding the neural mechanisms of the brain networks mediating adaptive behaviors in humans and animals. For example, associative learning from aversive or dangerous outcomes is crucial for an autonomous system, to avoid dangerous situations in the future. A body of neuroscience research has suggested that the neurocomputations in the human brain during associative learning involve re-shaping of sensory responses. The nature of these adaptive changes in sensory processing during learning however are not yet well enough understood to be readily implemented into on-board algorithms for robotics application. Toward this overall goal, we record the simultaneous electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI), characterizing one candidate mechanism, i.e., large-scale brain oscillations. The present report examines the use of Functional Source Separation (FSS) as an optimization step in EEG-fMRI fusion that harnesses timing information to constrain the solutions that satisfy physiological assumptions. We applied this approach to the voxel-wise correlation of steady-state visual evoked potential (ssVEP) amplitude and blood oxygen level-dependent imaging (BOLD), across both time series. The results showed the benefit of FSS for the extraction of robust ssVEP signals during simultaneous EEG-fMRI recordings. Applied to data from a 3-phase aversive conditioning paradigm, the correlation maps across the three phases (habituation, acquisition, extinction) show converging results, notably major overlapping areas in both primary and extended visual cortical regions, including calcarine sulcus, lingual cortex, and cuneus. In addition, during the acquisition phase when aversive learning occurs, we observed additional correlations between ssVEP and BOLD in the anterior cingulate cortex (ACC) as well as the precuneus and superior temporal gyrus

Neural mechanisms of visual awareness and their modulation by social threat

The human brain can extract an enormous wealth of visual information from our surroundings. However, only a fraction of this immense data set ever becomes available to the observer’s awareness. How and why certain information is selected for awareness are questions under active investigation. Following two introductory chapters, this thesis contains six inter-related experimental chapters, through which I will explore two key outstanding questions in this field, using bistable perceptual paradigms to study conscious and non-conscious visual processing in healthy human volunteers. The first major theme focuses on adding new insight into the brain regions and networks that facilitate transfer between non-conscious and conscious modes of visual processing. In Chapters 3 and 4 I will use fMRI, both in task-related and resting-state conditions, to delineate areas, and their interactions (in terms of effective connectivity), which are relevant for transition between different conscious perceptual experiences. In Chapter 5 I will focus on one specific region in the proposed perceptual transition-related network (the frontal eye field) and explore its causal role in access to awareness using repetitive TMS. The second key question explored in this thesis is how social cues in the visual environment influence non-conscious visual processing as well as transition to conscious vision. In Chapter 6 I will study behavioural effects of non-conscious social cues from faces, and the relationship of these effects to focal brain anatomy. Based on finding slower perceptuomotor performance when non-conscious faces contain threatening cues in Chapter 6, I hypothesise that a defensive freezing response is engaged in such situations. The final two experimental chapters will explore the correlates of putative human freezing in the context of non-conscious social threat: using fMRI and psychophysiological measurements to study effects on perceptual transition in Chapter 7, and relating TMS-induced motor-evoked potentials and concurrent psychophysiological measurements to non-conscious perceptuomotor performance in Chapter 8. Taken together, the presented findings shed new light on the network of brain regions involved in transition between non-conscious and conscious modes of visual processing. In addition, they uncover novel mechanisms through which socially relevant visual cues shape our awareness of the visual world, with particular emphasis on the engagement of defensive responses by socially threatening stimuli. The concluding chapter discusses the implications of these findings and explores relevant avenues for future work

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 spatial logic of fear

Peripersonal space (PPS) is the multimodal sensorimotor representation of the space surrounding the body. This thesis investigates how PPS is modulated by emotional faces, which represent particularly salient cue in our environment. Study 1 shows that looming neutral, joyful, and angry faces gradually facilitate motor responses to tactile stimuli. Conversely, looming fearful faces show no such effect. Also, at the closest position in PPS, multisensory response facilitation is lower for fearful than neutral faces. Study 2a addresses the hypothesis that fearful faces promote a redirection of attention towards the peripheral space. In line with this, it shows that motor responses to tactile stimuli are facilitated when a looming fearful face is associated with the appearance of a visual element presented in the periphery, rather than close to the face. Also, this effect is found in near space and not in far space. This result suggests that a near looming fearful face elicits a redirection of attention to the peripheral space. Such effect is not found for neutral, joyful, or angry faces (Study 2b). Study 3 shows that the redirection of attention in PPS by fearful faces is accompanied by a modulation of the electrophysiological signal associated with face processing (N170). Finally, Study 4 shows that the skin conductance response to looming fearful, but not joyful or neutral faces, is modulated by the distance of the face from participants’ body, being maximal in the near space. Together these studies show that, at variance with other emotions, fearful faces shift attention to other portions of space - than that of the face - where the threat may be located. It is argued that this fear-evoked redirection of attention may enhance the defensive function of PPS, when most needed, i.e., when the source of threat is nearby, but its location remains unknown

Diagnostic information use to understand brain mechanisms of facial expression categorization

Proficient categorization of facial expressions is crucial for normal social interaction. Neurophysiological, behavioural, event-related potential, lesion and functional neuroimaging techniques can be used to investigate the underlying brain mechanisms supporting this seemingly effortless process, and the associated arrangement of bilateral networks. These brain areas exhibit consistent and replicable activation patterns, and can be broadly defined to include visual (occipital and temporal), limbic (amygdala) and prefrontal (orbitofrontal) regions. Together, these areas support early perceptual processing, the formation of detailed representations and subsequent recognition of expressive faces. Despite the critical role of facial expressions in social communication and extensive work in this area, it is still not known how the brain decodes nonverbal signals in terms of expression-specific features. For these reasons, this thesis investigates the role of these so-called diagnostic facial features at three significant stages in expression recognition; the spatiotemporal inputs to the visual system, the dynamic integration of features in higher visual (occipitotemporal) areas, and early sensitivity to features in V1. In Chapter 1, the basic emotion categories are presented, along with the brain regions that are activated by these expressions. In line with this, the current cognitive theory of face processing reviews functional and anatomical dissociations within the distributed neural “face network”. Chapter 1 also introduces the way in which we measure and use diagnostic information to derive brain sensitivity to specific facial features, and how this is a useful tool by which to understand spatial and temporal organisation of expression recognition in the brain. In relation to this, hierarchical, bottom-up neural processing is discussed along with high-level, top-down facilitatory mechanisms. Chapter 2 describes an eye-movement study that reveals inputs to the visual system via fixations reflect diagnostic information use. Inputs to the visual system dictate the information distributed to cognitive systems during the seamless and rapid categorization of expressive faces. How we perform eye-movements during this task informs how task-driven and stimulus-driven mechanisms interact to guide the extraction of information supporting recognition. We recorded eye movements of observers who categorized the six basic categories of facial expressions. We use a measure of task-relevant information (diagnosticity) to discuss oculomotor behaviour, with focus on two findings. Firstly, fixated regions reveal expression differences. Secondly, by examining fixation sequences, the intersection of fixations with diagnostic information increases in a sequence of fixations. This suggests a top-down drive to acquire task-relevant information, with different functional roles for first and final fixations. A combination of psychophysical studies of visual recognition together with the EEG (electroencephalogram) signal is used to infer the dynamics of feature extraction and use during the recognition of facial expressions in Chapter 3. The results reveal a process that integrates visual information over about 50 milliseconds prior to the face-sensitive N170 event-related potential, starting at the eye region, and proceeding gradually towards lower regions. The finding that informative features for recognition are not processed simultaneously but in an orderly progression over a short time period is instructive for understanding the processes involved in visual recognition, and in particular the integration of bottom-up and top-down processes. In Chapter 4 we use fMRI to investigate the task-dependent activation to diagnostic features in early visual areas, suggesting top-down mechanisms as V1 traditionally exhibits only simple response properties. Chapter 3 revealed that diagnostic features modulate the temporal dynamics of brain signals in higher visual areas. Within the hierarchical visual system however, it is not known if an early (V1/V2/V3) sensitivity to diagnostic information contributes to categorical facial judgements, conceivably driven by top-down signals triggered in visual processing. Using retinotopic mapping, we reveal task-dependent information extraction within the earliest cortical representation (V1) of two features known to be differentially necessary for face recognition tasks (eyes and mouth). This strategic encoding of face images is beyond typical V1 properties and suggests a top-down influence of task extending down to the earliest retinotopic stages of visual processing. The significance of these data is discussed in the context of the cortical face network and bidirectional processing in the visual system. The visual cognition of facial expression processing is concerned with the interactive processing of bottom-up sensory-driven information and top-down mechanisms to relate visual input to categorical judgements. The three experiments presented in this thesis are summarized in Chapter 5 in relation to how diagnostic features can be used to explore such processing in the human brain leading to proficient facial expression categorization

Anxiety and how to control it: the functional role of the bed nucleus of the stria terminalis.

Anxiety disorders afflict up to one third of the population. Research to date has primarily focused on the amygdala, however, new perspectives suggest that a tiny basal forebrain region known as the bed nucleus of the stria terminalis (BNST) may hold key insights into understanding and treating anxiety disorders. Therefore, my first aim was to empirically investigate the importance and influence of the BNST in anxiety processing. Using fearful faces and human screams as aversive stimuli, two threat conditions were created: one in which threats were certain and predictable (fear) and another in which threats were uncertain and unpredictable (anxiety). Results indicated that the amygdala showed preferential engagement during fear and displayed functional connectivity with regions involved in stimulus processing and motor response. By contrast, the BNST preferentially responded during anxiety and exhibited functional connectivity with prefrontal regions underlying interoception and rumination. Together, this suggests that the amygdala and BNST play distinct but complementary roles during threat processing, with the BNST specializing in the detection of potential threats to promote hypervigilant monitoring. A primary mechanism of impaired functioning in anxiety disorders is emotion dysregulation, and has been another key focus in research. However, most emotion regulation (ER) paradigms use explicitly cued pictorial stimuli (negative scenes or faces) that induce disgust, when anxiety, by definition, is a sustained response to uncertain or unpredictable prospective threats. Therefore, my second aim was to specifically investigate anxiety regulation. 30 participants underwent high-resolution fMRI (1.5 mm3) while performing a novel task — a hybrid of the previous task and a canonical ER task – in order to: 1) investigate whether the BNST can be downregulated during uncertain anticipation, and 2) characterize the prefrontal regulatory mechanisms. Results showed that anxiety regulation was associated with pronounced BNST downregulation, enhanced activation of prefrontal regions (right middle frontal gyrus [rMFG], right inferior frontal gyrus [rIFG]), and increased connectivity between the rIFG and BNST while simultaneously decreasing connectivity among attentional circuits. These results provide the first evidence that the BNST can be volitionally downregulated and further suggest that anxiety regulation modulates higher-order attentional systems to putatively reduce vigilance

Attention to pain! A neurocognitive perspective on attentional modulation of pain in neuroimaging studies

Several studies have used neuroimaging techniques to investigate brain correlates of the attentional modulation of pain. Although these studies have advanced the knowledge in the field, important confounding factors such as imprecise theoretical definitions of attention, incomplete operationalization of the construct under exam, and limitations of techniques relying on measuring regional changes in cerebral blood flow have hampered the potential relevance of the conclusions. Here, we first provide an overview of the major theories of attention and of attention in the study of pain to bridge theory and experimental results. We conclude that load and motivational/affective theories are particularly relevant to study the attentional modulation of pain and should be carefully integrated in functional neuroimaging studies. Then, we summarize previous findings and discuss the possible neural correlates of the attentional modulation of pain. We discuss whether classical functional neuroimaging techniques are suitable to measure the effect of a fluctuating process like attention, and in which circumstances functional neuroimaging can be reliably used to measure the attentional modulation of pain. Finally, we argue that the analysis of brain networks and spontaneous oscillations may be a crucial future development in the study of attentional modulation of pain, and why the interplay between attention and pain, as examined so far, may rely on neural mechanisms shared with other sensory modalities

Understanding the relationship between chronic pain and emotional disorders

Although frequent coexistence of chronic pain and emotional disorders is well documented, exact mechanisms of comorbidity are not fully understood. The overarching aim of this thesis was to advance our knowledge of the mechanisms that link chronic pain and emotional disorders. Results of the literature review suggest that nosologically different conditions might coexist if they share common transdiagnostic risk factors that predispose individuals to several disorders. Using this transdiagnostic approach, a theoretical model explaining the relationships between different risk factors and how they might contribute to comorbidity between chronic pain and emotional disorders has been developed. According to the proposed model, one of the most fundamental transdiagnostic risk factors associated with both conditions is uncontrollable stress. It does not cause chronic pain or emotional disorders directly but promotes development of other risk factors, such as helplessness, negative affectivity, hypersensitivity to pain, dysregulation of stress response, and cognitive deficits. Importantly, these risk factors are not disorder specific. They equally predispose individuals to depression, anxiety, and chronic pain. Development of a specific disorder is determined by the influence of environmental and biological moderators that transform pre-existing risk factors into specific disorders. Considering that the sequence of pathological processes leading to psychopathology and/or chronic pain starts from the experience of uncontrollable stress, it is important to identify neural mechanisms that could mediate its effects. There is evidence suggesting that the frontal pole comprising of the rostromedial prefrontal cortex (rmPFC) and rostrolateral prefrontal cortex (rlPFC) plays an essential role in evaluation of controllability. Dysfunction of this area may increase the sense of uncontrollability, thereby promoting development of transdiagnostic risk factors. Both subregions of the frontal pole are parts of the neural networks that perform higher-order processing and modulation of nociceptive and emotional reactions. Thus, increased sensitivity to pain and heightened negative affect in patients with chronic pain disorders might be mediated by impaired interaction of the rmPFC and rlPFC with low-level nociceptive and emotional circuits. To test this hypothesis, resting-state functional and effective connectivity of the rmPFC and rlPFC was investigated in two chronic pain conditions: chronic low back pain (CLBP) and osteoarthritis (OA). Functional connectivity (FC) of the rmPFC and rlPFC in CLBP. CLBP patients displayed decreased FC of the rmPFC with retrosplenial cortex (RSC), posterior part of the ventral pallidum (VP), and mediodorsal (MD) thalamus. Diminished interaction with these regions may hinder retrieval of positive episodic memories of control and attribution of positive outcomes to personal actions. This may negatively influence patients’ belief about their ability to cope with stress, increase the sense of perceived uncontrollability. CLBP patients also showed reduced FC of the rmPFC with the medial pulvinar nucleus of the thalamus, midbrain reticular formation, and periaqueductal grey. These structures are parts of the ascending reticular activating system (ARAS) that regulates the level of arousal in the central nervous system. Reduced modulation of the arousal system by the rmPFC may result in development of a hyperarousal state and amplification of nociceptive and emotional responses leading to hyperalgesia and increased negative affectivity. There was no difference in FC of the rlPFC between CLBP patients and healthy controls. Effective connectivity analysis in CLBP. Causal interactions between the rmPFC, stress-related brainstem structures (dorsal raphe nucleus, ventral and dorsal periaqueductal grey), and memory systems (ventral striatum, hippocampus, amygdala) were investigated using the spectral dynamic causal modelling (spDCM). Consistent with the results of the FC analysis in CLBP, the spDCM also found altered interaction between the rmPFC and memory systems. Specifically, patients showed weaker connectivity of the rmPFC with hippocampus and stronger connectivity with the amygdala. Such pattern of connectivity may lead to inaccurate evaluation of the probability of control based on past experiences, overgeneralization and impaired extinction of fears. Patients also demonstrated hyperactivation of the dorsal raphe nucleus, ventral and dorsal periaqueductal grey (parts of the ARAS) that may contribute to hyperalgesia and increased negative affectivity. Functional connectivity of the rmPFC and rlPFC in OA. In this study FC of the rmPFC and rlPFC was compared between patients with shorter duration of OA (7 years), and healthy volunteers. Only patients with longer duration of OA showed increased negative FC of the rmPFC with multiple brainstem nuclei, such as the parabrachial complex, locus coeruleus, dorsal and median raphe nuclei, ventral tegmental area, midbrain reticular formation, and periaqueductal grey, that together comprise the ARAS. Negative FC between the rmPFC and ARAS may reflect increased compensatory inhibition of the activating system by the rmPFC in attempts to suppress pain-induced arousal and negative affect. Despite longer duration of pain, patients did not show signs of hyperalgesia or emotional distress. Perhaps, effective suppression of the brainstem arousal system demonstrated by OA patients was due to preserved connectivity between the rmPFC and memory systems. Both groups of OA patients also showed reduced FC of the rlPFC with the multiple demand network that may contribute to development of another transdiagnostic risk factor, i.e., cognitive deficit. Results of all three studies presented in this thesis suggest that chronic stress may cause development of transdiagnostic risk factors such as negative affectivity and hyperalgesia via hyperactivation of the brainstem arousal system that augments nociceptive and emotional responses. Impaired regulation of the arousal system by the rmPFC, which evaluates controllability of the stress based on previous experiences, may contribute to hyperactivation of the ARAS. Reduced interaction between the rmPFC and memory systems may obstruct retrieval and utilization of positive memories of control, thereby increasing the sense of uncontrollability, facilitating hyperarousal, and contributing to development of transdiagnostic risk factors. In contrast, preserved connectivity between the rmPFC and memory systems may oppose the negative effects of chronic stress and help patients to maintain a belief that they are capable of coping with the stress