The Role Of Interoception In Anxiety And The Underlying Neural Mechanisms

Interoception refers to the processing of the physiological signals arising from within the body,involving all major biological systems such as respiratory,cardiovascular,gastrointestinal,genitourinary,and immune systems.It is essential for maintaining bodily homeostasis,symptom perception,emotional experience,self-regulation,decision-making,and self-awareness.Conversely,disturbances in interoceptive processing have been observed in several psychological disorders such as anxiety disorders,depression and functional syndromes.Although considerable efforts have advanced our knowledge of interoception,the complex relationships between interoception and anxiety remain challenging to understand in scientific research and clinical practices.Throughout the past decades,insights into the brain regions moderating the relationships between interoception and anxiety have grown rapidly.In particular,a large body of research has consistently demonstrated the central role of the insula in both interoception and anxiety.However,the neural processes underlying the role of interoception in anxiety are still far from being clear.It was this current gap in the research on the relationships between interoception and anxiety that served as an inspiration for my Ph D studies,with the aim to investigate the role of interoception in anxiety by applying behavioral,functional magnetic resonance imaging(f MRI)and electroencephalography(EEG)methodologies.In this doctoral dissertation,we start with a general introduction into the definition of interoception and its important role in anxiety,highlighting the mind-body interactive processes in the experience of anxiety(chapter 1).Next we discuss the gaps based on the review of previous work on the role interoception in anxiety and the underlying neural substrates,and present the research plan for this thesis in chapter 2.To address these gaps,four thematically linked empirical studies including 6 experiments were conducted.In the first study,we investigated whether higher individual levels of anxiety correlate with higher interoceptive sensibility and interoceptive accuracy,and whether individual emotion regulation ability modulates the relationship between trait anxiety and interoceptive accuracy(chapter 3).We measured trait anxiety using State Trait Anxiety Inventory.Individual interoceptive sensibility was assessed using Body Perception Questionnaire,an instrument to evaluate autonomic reactivity and subjective experiences of body awareness.The Heartbeat Counting Task was used to assess interoceptive accuracy.An emotion regulation task was used to assess the individual levels of emotion regulation ability.As hypothesized,we observed a significant correlation of trait anxiety with interoceptive sensibility,but not with interoceptive accuracy.We also found that higher trait anxiety was associated with poorer emotion regulation ability.In addition,our data showed a moderating effect of emotion regulation ability on the relationship between trait anxiety and interoceptive accuracy,although the effect did not reach statistical significance.Furthermore,a significantly positive correlation between trait anxiety and interoceptive accuracy was only found in the low emotion regulation ability group but not in the high emotion regulation ability group.In chapter 4,given that recent accounts highlight the role of the insula in both interoception and the subjective experience of anxiety,the study 2 aimed at investigating the overlapping and different neural substrates of interoception and anxiety,as well as the relationships between interoception-related insular activity,interoceptive accuracy,and anxiety.This was done in two experiments using f MRI in a design in which volunteers focused their attention on their heartbeat,on anxious events or on external sound.In the study 2-a,one hundred fifty two healthy participants completed the f MRI task.The results showed that insula,middle cingulate cortex,and ventral medial prefrontal cortex were commonly activated during interoception and anxiety conditions.Uniquely activated regions involved in the interoceptive attention included cerebellum lobe and supramarginal gyrus,while the cuneus,parahippocampa gyrus,inferior frontal gyrus,superior frontal gyrus and middle frontal gyrus were uniquely activated during the anxiety attention condition.In the study 2-b,forty healthy volunteers were involved in the f MRI task and they also performed the Heartbeat Counting Task and State Trait Anxiety Inventory to measure interoceptive accuracy and anxiety levels,respectively.The results showed posterior,mid and anterior insular activity during cardiac interoception,whereas activation during the anxiety condition was only observed in the anterior insula.Activation of the anterior insula during cardiac interoception was positively correlated with state and trait anxiety levels,respectively.Moreover,the mid-insular activity during the cardiac attention condition not only related to individuals' interoceptive accuracy but also to their levels of state and trait anxiety,respectively.These findings confirm that there are common and distinct neural representations of interoceptive attention and experience of anxiety across the insular regions,and suggest that one's experience of anxiety appears to involve the interoceptive information and the mid-insula as a crucial link between cardiac interoception and anxiety.In chapter 5,we introduced the error-related negativity(ERN)as an event-related potential in the EEG observed within the first 100 ms after commission of an error,which has been suggested to relate to anxiety disorders.While the ERN has extensively been studied in tasks using exteroceptive stimuli,its relation to interoceptive stimuli is unknown.Since errors related to interoception might be particularly relevant for survival and anxiety,the study 3 aimed to explore the ERN for errors related to interoceptive sensations,to compare the interoceptive ERN with a commonly observed ERN related to exteroceptive,visual stimuli and to examine their associations with anxiety.We studied the ERNs using a respiratory forced choice reaction time task and a visual flanker task in 40 healthy volunteers during continuous 129 channel EEG recordings.In the respiratory task,participants received inspiratory occlusions of two different durations and indicated whether each occlusion was short or long.In the Flanker task,participants indicated the direction of arrowheads.Anxiety levels were assessed with the Anxiety Sensitivity Index.Comparable with the exteroceptive ERN,the interoceptive ERN was observed at fronto-central scalp positions after error commission in the occlusion task,but it peaked significantly earlier than the exteroceptive ERN.Mean amplitudes of the interoceptive ERN and exteroceptive ERN showed no significant difference and were not correlated.Moreover,higher levels of anxiety sensitivity were correlated with significantly greater amplitudes of the interoceptive ERN,but with lower amplitudes of the exteroceptive ERN.The present results firstly demonstrate an error-related negativity EEG-potential that is related to interoceptive sensations.This interoceptive ERN is not associated with a commonly observed ERN elicited by exteroceptive stimuli and is distinctly linked to higher levels of anxiety sensitivity.The interoceptive ERN might be a promising neural marker for future studies on interoceptive error processing and anxiety.In chapter 6,we induced the dyspnea as a prevalent interoceptive sensation and an aversive symptom in anxiety disorders.Considering the important role of interoceptive threat and unpredictability in anxiety and its reported relations to increased self-reports and electrophysiological responses of anxiety such as the startle probe N100 as well as the amplified threat sensitivity as reflected by greater error-related negativity(ERN),study 4 aimed to investigate whether unpredictable compared to predictable dyspnea would increase the anxiety and perception of dyspnea using high-density electroencephalography.Thirty-two healthy participants performed a respiratory forced choice reaction time task to elicit an interoceptive ERN during two conditions: an unpredictable and a predictable resistive load-induced dyspnea condition.Predictability was manipulated by pairing(predictable condition)or not pairing(unpredictable condition)dyspnea with a startle tone probe.Self-reports of dyspnea and affective state as well as the startle probe N100 and interoceptive ERN were measured.The results demonstrated greater dyspnea unpleasantness in the unpredictable compared to the predictable condition.Post-hoc analyses revealed that this was paralleled by greater anxiety,and greater amplitudes for the startle probe N100 and the interoceptive ERN during the unpredictable relative to the predictable condition,but only when the unpredictable condition was experienced in the first experimental block.Furthermore,higher trait-like anxiety sensitivity was associated with higher ratings for dyspnea unpleasantness in both the unpredictable and predictable conditions,but with higher experimental state anxiety ratings only in the unpredictable condition.These findings suggest that unpredictability increases anxiety levels,especially when upcoming dyspnea is particularly unpredictable,such as in early experimental phases.This effect seems related to increased perception of dyspnea.In summary,our findings demonstrate close relationships between interoceptive processes and anxiety and the modulation of this relationship by emotion regulation ability.Insular activity and interoceptive error-related negativity were identified as contributing neural mechanisms.Moreover,our results also suggest to take unpredictability into considerations when investigating the role of interoception in anxiety.We further discuss the theoretical and clinical implications of these findings in chapter 7.