Sliding-window analysis tracks fluctuations in amygdala functional connectivity associated with physiological arousal and vigilance during fear conditioning

We evaluated whether sliding-window analysis can reveal functionally relevant brain network dynamics during a well-established fear conditioning paradigm. To this end, we tested if fMRI fluctuations in amygdala functional connectivity (FC) can be related to task-induced changes in physiological arousal and vigilance, as reflected in the skin conductance level (SCL). Thirty-two healthy individuals participated in the study. For the sliding-window analysis we used windows that were shifted by one volume at a time. Amygdala FC was calculated for each of these windows. Simultaneously acquired SCL time series were averaged over time frames that corresponded to the sliding-window FC analysis, which were subsequently associated with the whole-brain seed-based amygdala sliding-window FC using the GLM. Surrogate time series were generated to test whether connectivity dynamics could have occurred by chance. In addition, results were contrasted against static amygdala FC and sliding-window FC of the primary visual cortex, which was chosen as a control seed, while a physio-physiological interaction (PPI) was performed as cross-validation. During periods of increased SCL, the left amygdala became more strongly coupled with the bilateral insula and medial prefrontal cortex, core areas of the salience network. The sliding-window analysis yielded a connectivity pattern that was unlikely to have occurred by chance, was spatially distinct from static amygdala FC and from sliding-window FC of the primary visual cortex, but was highly comparable to that of the PPI analysis. We conclude that sliding-window analysis can reveal functionally relevant fluctuations in connectivity in the context of an externally cued task

Using Movies to Probe the Neurobiology of Anxiety

Over the past century, research has helped us build a fundamental understanding of the neurobiological underpinnings of anxiety. Specifically, anxiety engages a broad range of cortico-subcortical neural circuitry. Core to this is a ‘defensive response network’ which includes an amygdala-prefrontal circuit that is hypothesized to drive attentional amplification of threat-relevant stimuli in the environment. In order to help prepare the body for defensive behaviors to threat, anxiety also engages peripheral physiological systems. However, our theoretical frameworks of the neurobiology of anxiety are built mostly on the foundations of tightly-controlled experiments, such as task-based fMRI. Whether these findings generalize to more naturalistic settings is unknown. To address this shortcoming, movie-watching paradigms offer an effective tool at the intersection of tightly controlled and entirely naturalistic experiments. Particularly, using suspenseful movies presents a novel and effective means to induce and study anxiety. In this thesis, I demonstrate the potential of movie-watching paradigms in the study of how trait and state anxiety impact the ‘defensive response network’ in the brain, as well as peripheral physiology. The key findings reveal that trait anxiety is associated with differing amygdala-prefrontal responses to suspenseful movies; specific trait anxiety symptoms are linked to altered states of anxiety during suspenseful movies; and states of anxiety during movies impact brain-body communication. Notably, my results frequently diverged from those of conventional task-based experiments. Taken together, the insights gathered from this thesis underscore the utility of movie-watching paradigms for a more nuanced understanding of how anxiety impacts the brain and peripheral physiology. These outcomes provide compelling evidence that further integration of naturalistic methods will be beneficial in the study of the neurobiology of anxiety

Space and Value in the Primate Amygdala and Basal Forebrain

A stimulus predicting reinforcement can trigger emotional responses, such as arousal, as well as cognitive ones, such as increasing attention towards that stimulus. Neuroscientists have long appreciated that the amygdala mediates spatially non-specific emotional responses, but it remains unclear whether the amygdala links motivational and spatial representations in a way that may be important for the emotional-guidance of attention. To test whether amygdala neurons encode spatial and motivational information, we presented reward-predictive cues in different spatial configurations while assessing whether these cues influenced spatial attention. Cue configuration and predicted reward magnitude modulated amygdala neural activity in a coordinated fashion. Moreover, fluctuations in activity were correlated with trial-to-trial variability in spatial attention. Thus the amygdala integrates spatial and motivational information, which may influence the spatial allocation of cognitive resources. When surveying the environment, animals must be acutely aware of associations between stimuli and aversive outcomes in addition to those resulting in appetitive outcomes. This involves attending to appetitive stimuli in order to obtain positive outcomes, and aversive stimuli in order to avoid negative outcomes. While we first demonstrated that amygdala might play a role in influencing spatial attention towards appetitive stimuli, it is unclear whether the activity of individual amygdala neurons are modulated in a similar way by aversive stimuli that also attract attention. Recording from amygdala neurons while monkeys allocated attention both towards appetitive and aversive stimuli revealed that firing rates reflected where attention was allocated irrespective of valence. We also found that amygdala neurons preferentially encode appetitive and aversive stimuli relative to those of little motivational significance in a conditioning paradigm where spatial characteristics were irrelevant. Thus, amygdala neurons respond with respect to the motivational significance of stimuli, which is tied to spatial attention in contexts involving multiple stimuli. While the amygdala might be involved in guiding attention towards motivationally significant stimuli, this process is likely dependent on its interactions with anatomically linked brain areas. The basal forebrain is a candidate brain area for interacting with the amygdala in influencing emotionally-guided attention given its anatomical connectivity and influence over attentional processes. Here, we analyzed data from amygdala and basal forebrain neurons recorded while spatial attention was captured by appetitive and aversive stimuli. Neurons in the basal forebrain were spatial selective for appetitive and aversive stimuli much like the amygdala. We also found that the timing of value signals differed across brain areas in a manner dependent on the spatial configuration of stimuli. Together, these results demonstrate how the amygdala and basal forebrain may participate in coordinating cognitive and emotional processes and are suggestive of how dysfunction within this pathway might contribute to disorders where emotionally-guided attention is impaired

Simultaneous pupillometry and functional Magnetic Resonance Imaging (fMRI) for the detection of stress-related endophenotypes

Mental diseases constitute a core health challenge of the 21st century. To date, diagnostics in psychiatry have been primarily based on subjective self-reports, largely bypassing the biological underpinnings and phenotypic heterogeneity of psychiatric disorders. As an effort to implement a more biologically valid classification of mental disorders, recent initiatives like the Research Domain Criteria (RDoC) project aim to identify endophenotypes that reflect transdiagnostic core mechanisms of psychiatric disorders. Stress is known to play a fundamental role in the development of mood and anxiety disorders. One key system involved in the physiological response to stress is the brainstem?s noradrenergic (NA) arousal center located in the locus coeruleus (LC), and previous studies indicate that pupil size provides an indirect index for activity of the LC-NA system. In order to investigate the relationship between spontaneous drifts in autonomic arousal and global brain activity in healthy human subjects, we first determined the fMRI correlates of spontaneous pupil fluctuations during the resting state. We found that pupil dilations are strongly coupled to activation of the dorsal anterior cingulate cortex (dACC) and bilateral insula (salience network [SN]). To assess whether this link between the pupil and the SN would also extend to emotional arousal, we next investigated the neural correlates of reward anticipation-induced pupil dilations in healthy subjects. Here, we could show that a cue signaling the possibility to receive a monetary reward evoked strong pupil dilations, the magnitude of which predicted response time to a target cue. Again, pupil dilations were strongly linked to SN activation. Furthermore, our results suggest that pupillometry is helpful to dissect different phases of reward anticipation and associated brain activity, disentangling reward prediction, arousal modulation and attentionrelated processes. These observations led us to the conclusion that the SN modulates arousal levels to optimize task performance, that is, to counteract drowsiness/ transitions to sleep during the resting state and to facilitate reward-directed behaviors in the reward anticipation task. Taken together, pupillometry appears to provide a reliable index for activity of the SN, a core network related to psychiatric disorders, making it a promising tool for the detection of stress-related endophenotypes

Simultaneous pupillometry and functional Magnetic Resonance Imaging (fMRI) for the detection of stress-related endophenotypes

Mental diseases constitute a core health challenge of the 21st century. To date, diagnostics in psychiatry have been primarily based on subjective self-reports, largely bypassing the biological underpinnings and phenotypic heterogeneity of psychiatric disorders. As an effort to implement a more biologically valid classification of mental disorders, recent initiatives like the Research Domain Criteria (RDoC) project aim to identify endophenotypes that reflect transdiagnostic core mechanisms of psychiatric disorders. Stress is known to play a fundamental role in the development of mood and anxiety disorders. One key system involved in the physiological response to stress is the brainstem’s noradrenergic (NA) arousal center located in the locus coeruleus (LC), and previous studies indicate that pupil size provides an indirect index for activity of the LC-NA system. In order to investigate the relationship between spontaneous drifts in autonomic arousal and global brain activity in healthy human subjects, we first determined the fMRI correlates of spontaneous pupil fluctuations during the resting state. We found that pupil dilations are strongly coupled to activation of the dorsal anterior cingulate cortex (dACC) and bilateral insula (salience network [SN]). To assess whether this link between the pupil and the SN would also extend to emotional arousal, we next investigated the neural correlates of reward anticipation-induced pupil dilations in healthy subjects. Here, we could show that a cue signaling the possibility to receive a monetary reward evoked strong pupil dilations, the magnitude of which predicted response time to a target cue. Again, pupil dilations were strongly linked to SN activation. Furthermore, our results suggest that pupillometry is helpful to dissect different phases of reward anticipation and associated brain activity, disentangling reward prediction, arousal modulation and attentionrelated processes. These observations led us to the conclusion that the SN modulates arousal levels to optimize task performance, that is, to counteract drowsiness/ transitions to sleep during the resting state and to facilitate reward-directed behaviors in the reward anticipation task. Taken together, pupillometry appears to provide a reliable index for activity of the SN, a core network related to psychiatric disorders, making it a promising tool for the detection of stress-related endophenotypes

A multicomponential examination of tennis players’ emotional responses to music

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.The principal aim of this research programme was to examine multiple components of competitive tennis players’ emotional responses to pre-performance music. To this end, four objectives were defined: First, to develop a grounded theory (Glaser & Strauss, 1967) of players’ use of music to manipulate emotional state; second, to examine the impact of altering music tempo and intensity on players’ affective and behavioural responses; third, to identify neural origins for these phenomena; and fourth, to elucidate the role of motoneuron excitability in behavioural responses observed. These objectives were realised in four interrelated studies. First, 14 players provided quantitative and qualitative interview, questionnaire, and diary data to detail their use of personally emotive music; a grounded theory and associated model were consequently developed to facilitate future research and practice. Participants used music to attain five broad emotional states, including psyched-up; this was associated with faster tempi and louder intensities (volumes). Study 2 was conceived to examine the effects of manipulating these variables on 54 players’ affective and behavioural states, using measures based on Russell’s (1980) affective circumplex and reaction times (RTs). Faster tempi elicited higher valence and arousal, loud intensity yielded higher arousal and shorter RTs; and higher arousal was associated with shorter RTs. Functional magnetic resonance imaging was utilised in Study 3 to identify neural bases for 12 participants’ emotional responses to the same music manipulations; emotion-processing, visuomotor and sensorimotor structures were activated under high-arousal conditions. Transcranial magnetic stimulation and electromyography were used in Study 4 to investigate changes in 10 participants’ corticospinal excitability as a result of listening to purposively selected music; optimised music elicited higher arousal and reduced corticospinal response latencies. The foremost contribution of this thesis is to show that music variables may be carefully selected and/or manipulated to maximise performance-facilitating emotional responses to music in tennis

Neuroscience

Exposure to violence during childhood can lead to functional changes in brain regions that are important for emotion expression and regulation, which may increase susceptibility to internalizing disorders in adulthood. Specifically, childhood violence exposure can disrupt the functional connectivity among brain regions that include the prefrontal cortex (PFC), hippocampus, and amygdala. Together, these regions are important for modulating autonomic responses to stress. However, it is unclear to what extent changes in brain connectivity relate to autonomic stress reactivity and how the relationship between brain connectivity and autonomic responses to stress varies with childhood violence exposure. Thus, the present study examined whether stress-induced changes in autonomic responses (e.g., heart rate, skin conductance level (SCL)) varied with amygdala-, hippocampus-, and ventromedial prefrontal cortex (vmPFC)-whole brain resting-state functional connectivity (rsFC) as a function of violence exposure. Two hundred and ninety-seven participants completed two resting-state functional magnetic resonance imaging scans prior to (pre-stress) and after (post-stress) a psychosocial stress task. Heart rate and SCL were recorded during each scan. Post-stress heart rate varied negatively with post-stress amygdala-inferior parietal lobule rsFC and positively with post-stress hippocampus-anterior cingulate cortex rsFC among those exposed to high, but not low, levels of violence. Results from the present study suggest that post-stress fronto-limbic and parieto-limbic rsFC modulates heart rate and may underlie differences in the stress response among those exposed to high levels of violence.U19 DP002664/DP/NCCDPHP CDC HHSUnited States/U48 DP000046/DP/NCCDPHP CDC HHSUnited States/U19 DP002665/DP/NCCDPHP CDC HHSUnited States/U48 DP000057/DP/NCCDPHP CDC HHSUnited States/U19 DP002663/DP/NCCDPHP CDC HHSUnited States/U48 DP000056/DP/NCCDPHP CDC HHSUnited States/R01 MH098348/MH/NIMH NIH HHSUnited States

Fluctuations of attention network activation during the resting state reflect fluctuations in subjective attentional state.

peer reviewe

A multicomponential examination of tennis players’ emotional responses to music

The principal aim of this research programme was to examine multiple components of competitive tennis players’ emotional responses to pre-performance music. To this end, four objectives were defined: First, to develop a grounded theory (Glaser & Strauss, 1967) of players’ use of music to manipulate emotional state; second, to examine the impact of altering music tempo and intensity on players’ affective and behavioural responses; third, to identify neural origins for these phenomena; and fourth, to elucidate the role of motoneuron excitability in behavioural responses observed. These objectives were realised in four interrelated studies. First, 14 players provided quantitative and qualitative interview, questionnaire, and diary data to detail their use of personally emotive music; a grounded theory and associated model were consequently developed to facilitate future research and practice. Participants used music to attain five broad emotional states, including psyched-up; this was associated with faster tempi and louder intensities (volumes). Study 2 was conceived to examine the effects of manipulating these variables on 54 players’ affective and behavioural states, using measures based on Russell’s (1980) affective circumplex and reaction times (RTs). Faster tempi elicited higher valence and arousal, loud intensity yielded higher arousal and shorter RTs; and higher arousal was associated with shorter RTs. Functional magnetic resonance imaging was utilised in Study 3 to identify neural bases for 12 participants’ emotional responses to the same music manipulations; emotion-processing, visuomotor and sensorimotor structures were activated under high-arousal conditions. Transcranial magnetic stimulation and electromyography were used in Study 4 to investigate changes in 10 participants’ corticospinal excitability as a result of listening to purposively selected music; optimised music elicited higher arousal and reduced corticospinal response latencies. The foremost contribution of this thesis is to show that music variables may be carefully selected and/or manipulated to maximise performance-facilitating emotional responses to music in tennis.EThOS - Electronic Theses Online ServiceGBUnited Kingdo