Interoceptive Awareness and the Insula – Application of Neuroimaging Techniques in Psychotherapy

Interoceptive awareness is defined as the awareness of stimuli originating inside one’s own body such as the heartbeat. The emergence of new brain imaging techniques like functional magnetic resonance imaging (fMRI) or magnetic resonance spectroscopy (MRS) has increased our knowledge of neural substrates underlying interoceptive awareness. In particular, the bilateral brain structure of the insula has been identified as a key region involved in interoceptive processes in healthy populations. In line with prominent theories of human emotion, the insula has an important function in connecting interoceptive awareness with affective experience. This connection hinging on the insula between interoception and emotional processing is suggestive of an involvement of the insula in mood disorders such as major depressive disorder (MDD). Multilayered deficits in the insula cortex of depressed individuals such as abnormal function, biochemistry, and anatomy support this hypothesis. The aim of the present article is a) to describe the importance of the insula for the interplay between interoception and emotional processing and b) how this might be figured into psychotherapeutic treatment of depressed patients using new imaging techniques like real-time fMRI. The article begins with a brief introduction about neuroanatomical settings of the insula (I. Introduction–Neuroanatomical background of the insula). Afterwards, early behavioral studies to investigate interoceptive awareness are described (II. A step Back–First attempts to investigate interoceptive awareness), followed by a description of more recent imaging studies outlining neural mechanisms underlying interoceptive awareness and emotional processing in the insula (III. The insula as key region involved in functional interoception and emotion.) Throughout, the article addresses the question of why the investigation of individuals suffering from depression might provide novel insights into the neural underpinnings of interoceptive awareness and its link to abnormal behavior (IV. Why study interoceptive awareness in depressed participants?). Following the description of a selected study that combines for the first time functional results of interoception (using fMRI) with biochemical results of the insula (using MRS) (V. Neuroimaging in interoceptive awareness combining fMRI and MRS – A specific study), the article concludes with a perspective outlining the potential for using imaging techniques like real-time fMRI to enhance neural activity in the insula during interoceptive awareness. This approach potentially leads to faster recovery in depressed patients and might be the first therapeutic application of functional imaging in psychiatry (VI. Perspectives: Neurofeedback in major depression using real-time fMRI)

Interoception in insula subregions as a possible state marker for depression - an exploratory fMRI study investigating healthy, depressed and remitted participants

Background: Interoceptive awareness (iA), the awareness of stimuli originating inside the body, plays an important role in human emotions and psychopathology. The insula is particularly involved in neural processes underlying iA. However, iA-related neural activity in the insula during the acute state of major depressive disorder (MDD) and in remission from depression has not been explored. Methods: A well-established fMRI paradigm for studying (iA; heartbeat counting) and exteroceptive awareness (eA; tone counting) was used. Study participants formed three independent groups: patients suffering from MDD, patients in remission from MDD or healthy controls. Task-induced neural activity in three functional subdivisions of the insula was compared between these groups. Results: Depressed participants showed neural hypo-responses during iA in anterior insula regions, as compared to both healthy and remitted participants. The right dorsal anterior insula showed the strongest response to iA across all participant groups. In depressed participants there was no differentiation between different stimuli types in this region (i.e., between iA, eA and noTask). Healthy and remitted participants in contrast showed clear activity differences. Conclusions: This is the first study comparing iA and eA-related activity in the insula in depressed participants to that in healthy and remitted individuals. The preliminary results suggest that these groups differ in there being hypo- responses across insula regions in the depressed participants, whilst non- psychiatric participants and patients in remission from MDD show the same neural activity during iA in insula subregions implying a possible state marker for MDD. The lack of activity differences between different stimulus types in the depressed group may account for their symptoms of altered external and internal focus

Anticipatory feelings: Neural correlates and linguistic markers

This review introduces anticipatory feelings (AF) as a new construct related to the process of anticipation and prediction of future events. AF, defined as the state of awareness of physiological and neurocognitive changes that occur within an oganism in the form of a process of adapting to future events, are an important component of anticipation and expectancy. They encompass bodily-related interoceptive and affective components and are influenced by intrapersonal and dispositional factors, such as optimism, hope, pessimism, or worry. In the present review, we consider evidence from animal and human research, including neuroimaging studies, to characterize the brain structures and brain networks involved in AF. The majority of studies reviewed revealed three brain regions involved in future oriented feelings: 1) the insula; 2) the ventromedial prefrontal cortex (vmPFC); and 3) the amygdala. Moreover, these brain regions were confirmed by a meta-analysis, using a platform for large-scale, automated synthesis of fMRI data. Finally, by adopting a neurolinguistic and a big data approach, we illustrate how AF are expressed in language

Untersuchungen neuraler und neurochemischer Mechanismen

Interoceptive awareness, the awareness of stimuli originating inside the body, plays an important role in theories of human emotions. Pushed forward by the emergence of new brain imaging techniques, our understanding of the neural substrates underlying interoceptive awareness continues to increase. The insula, a bilateral brain structure located within the Sylvian fissure, has been identified as a key region involved in interoceptive awareness in neurotypical individuals. Emotional functions in turn have been associated with interoceptive awareness and with activity during rest in cortical midline structures, whose anterior parts are functionally connected with insula activity. That said, this dual association of emotions with activity during rest and interoception remains to be investigated. In addition, to date, little has been established regarding the biochemical underpinnings of interoceptive awareness. Similarly, its role in affective disorders like major depression has been suggested but remains unclear. In order to investigate these points, imaging techniques including functional magnetic resonance imaging (fMRI), positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) were combined in studies on healthy, depressed and remitted participants. A well established fMRI paradigm to investigate neural activity during intero- and exteroceptive awareness (heartbeat counting and external tone counting) as well as during rest was used in combination with behavioural tests. Firstly, it was shown that neural activity in anterior cortical midline regions during rest, rather than during interoceptive awareness, is associated with emotional scores in a group of healthy participants. In a second study, it was shown that neural activity in the insula during rest is abnormally processed in depressed patients. Moreover, activity during rest was decoupled from perception of one’s own body in the depressed group as well as positively related to depression severity. Thirdly, it was shown that group differences between healthy, depressed and remitted participants occurred particularly in the dorsal anterior part of the insula during interoceptive awareness. This region showed hypo-responsiveness in depressed participants, which normalized after remission. In addition, the depressed group showed no differential activity in this region between rest and intero-/exteroceptive awareness. Finally, biochemical investigations in healthy participants in the areas of interest (insula and cortical midline structures) revealed that i) the inhibitory neurotransmitter GABA within cortical midline structures is an important influencing factor in the differential processing of intero- and exteroceptive awareness and ii) GABA modulates neural activity induced by specifically interoceptive awareness in the insula, with this link not seen in cortical midline structures. Moreover, both GABA and neural signal changes during interoceptive awareness were related here to the degree of depressed affect. Taken together, the results presented in this work provide on the one hand initial biochemical links to neural processes induced by interoceptive awareness in the insula as well as neural processes induced by exteroceptive awareness in cortical midline regions. On the other hand, they provide valuable information about the interconnections between rest, and intero- and exteroceptive awareness in combination with behaviour (emotions and body perception). By investigating individuals suffering from depression, novel insights into the neural underpinnings of interoceptive awareness and its link to abnormal behaviour was provided.Die Fähigkeit, körperliche Vorgänge wahrzunehmen, wird als interozeptive Aufmerksamkeit bezeichnet und spielt eine wichtige Rolle in Theorien menschlicher Emotionsverarbeitung. Moderne, bildgebende Verfahren haben sich zu einem populären Instrument der neurowissenschaftlichen Forschung entwickelt und dazu beigetragen, unser Verständnis der zu Grunde liegenden neuronalen Substrate interozeptiver Aufmerksamkeit ständig zu erweitern. Vor allem die Insula, eine in der Tiefe der Sylvischen Furche gelegene bilaterale Hirnstruktur, ist in aktuellen Forschungsarbeiten zur interozeptiven Aufmerksamkeit in den Mittelpunkt gerückt. Emotionsverarbeitung wiederum steht in engem Zusammenhang mit interozeptiver Aufmerksamkeit sowie mit neuronaler Ruheaktivität in den kortikalen Mittellinienstrukturen, deren anteriore Bereiche funktionell mit neuronaler Aktivität in der Insula gekoppelt sind. Allerdings bleibt diese zweifache Assoziation von Emotionen - zum einen mit neuronaler Ruheaktivität und zum anderen mit Interozeption - Gegenstand aktueller Forschung. Darüber hinaus ist zur Zeit wenig bekannt über die biochemischen Grundlagen der interozeptiven Aufmerksamkeit. Ebenso bleibt die Rolle bei affektiven Erkrankungen wie der Major Depression unklar. Um diese Zusammenhänge zu untersuchen, wurden bildgebende Verfahren wie die funktionelle Magnetresonanztomographie (fMRT), Positronen-Emissions- Tomographie (PET) und Magnetresonanzspektroskopie (MRS) angewandt. Es wurden hierfür sowohl gesunde Probanden als auch Patienten mit Major Depression und remittierte Patienten (nach Abklingen der depressiven Symptomatik) rekrutiert. Die neuronale Aktivität während intero- und exterozeptiver Aufmerksamkeit (durch internes Zählen des eigenen Herzschlages und eines extern applizierten Tones) sowie während einer Ruhebedingung wurde mittels eines etablierten fMRT- Paradigmas untersucht und mit behavioralen Tests kombiniert. Zunächst konnte in einer Gruppe von gesunden Probanden gezeigt werden, dass behaviorale Werte der Emotionsverarbeitung mit neuronaler Ruheaktivität in anterioren kortikalen Mittellinienstrukturen korreliert waren und nicht mit interozeptiver Aufmerksamkeit. In einer zweiten Studie wiesen depressive Patienten im Vergleich zu einer gesunden Probandengruppe eine abnorme neuronale Ruheaktivität in der Insula auf. Zudem zeigten depressive Patienten keine Korrelation zwischen neuronaler Ruheaktivität in der Insula und Körperwahrnehmung, so wie es in der gesunden Gruppe zu beobachten war. Die abweichende Ruheaktivität war außerdem mit der Depressionsschwere assoziiert. In einer dritten Studie konnte dargelegt werden, dass Gruppenunterschiede zwischen gesunden, depressiven sowie remittierten Probanden vor allem im dorsalen anterioren Teil der Insula während interozeptiver Aufmerksamkeit auftraten. Depressive Patienten wiesen hier neuronale Hypoaktivierung auf, welche sich nach Abklingen der Symptomatik normalisierte. Darüber hinaus fanden sich in der depressiven Gruppe keine Aktivitätsunterschiede zwischen den verschiedenen Bedingungen (intero- und exterozeptive Aufmerksamkeit sowie Ruhebedingung). Zum Schluss zeigten biochemische Untersuchungen in den hier primär untersuchten Gehirnbereichen (Insula und kortikale Mittellinenstrukturen) gesunder Probanden, dass i) der inhibitorische Neurotransmitter GABA eine wichtige Rolle in kortikalen Mittellinenstrukturen bei der differentiellen Verarbeitung von intero- und exterozeptiver Aufmerksamkeit spielt und ii) dass GABA die neuronale interozeptive Aktivität in der Insula moduliert, welches nicht in kortikalen Mittellinienstrukturen beobachtet wurde. GABA und neuronale Signalveränderungen während interozeptiver Aufmerksamkeit korrelierten außerdem mit behavioralen Depressionswerten. Zusammenfassend kann gesagt werden, dass die hier vorgestellten Ergebnisse erste biochemische Grundlagen interozeptiver Aufmerksamkeit in der Insula sowie exterozeptiver Aufmerksamkeit in kortikalen Mittellienenstrukturen aufzeigen. Darüber hinaus liefern die Ergebnisse wertvolle Informationen über die Verbindungen zwischen Ruheaktivität und intero-/ exterozeptiver Aufmerksamkeit in Kombination mit Verhaltensvariablen (Emotionen und Körperwahrnehmung). Die Untersuchung depressiver Patienten liefert neue Einblicke in neuronale Grundlagen interozeptiver Aufmerksamkeit in Verbindung mit Verhaltensauffälligkeiten

Stress and alterations in the pain matrix: A biopsychosocial perspective on back pain and its prevention and treatment

The genesis of chronic pain is explained by a biopsychosocial model. It hypothesizes an interdependency between environmental and genetic factors provoking aberrant long-term changes in biological and psychological regulatory systems. Physiological effects of psychological and physical stressors may play a crucial role in these maladaptive processes. Specifically, long-term demands on the stress response system may moderate central pain processing and influence descending serotonergic and noradrenergic signals from the brainstem, regulating nociceptive processing at the spinal level. However, the underlying mechanisms of this pathophysiological interplay still remain unclear. This paper aims to shed light on possible pathways between physical (exercise) and psychological stress and the potential neurobiological consequences in the genesis and treatment of chronic pain, highlighting evolving concepts and promising research directions in the treatment of chronic pain. Two treatment forms (exercise and mindfulness-based stress reduction as exemplary therapies), their interaction, and the dose-response will be discussed in more detail, which might pave the way to a better understanding of alterations in the pain matrix and help to develop future prevention and therapeutic concepts.ISSN:1660-4601ISSN:1661-782

Basic Neuroscience How to investigate neuro-biochemical relationships on a regional level in humans? Methodological considerations for combining functional with biochemical imaging

h i g h l i g h t s • Provide an overview of factors to consider when planning multi-modal imaging studies. • Discuss technical and methodological issues for hypothesis generation. • Discuss issues of specificity that arise in multi-modal imaging. a r t i c l e i n f o a b s t r a c t There is an increasing interest in combining different imaging modalities to investigate the relationship between neural and biochemical activity. More specifically, imaging techniques like MRS and PET that allow for biochemical measurement are combined with techniques like fMRI and EEG that measure neural activity in different states. Such combination of neural and biochemical measures raises not only technical issues, such as merging the different data sets, but also several methodological issues. These methodological issues -ranging from hypothesis generation and hypothesis-guided use of technical facilities to target measures and experimental measures -are the focus of this paper. We discuss the various methodological problems and issues raised by the combination of different imaging methodologies in order to investigate neuro-biochemical relationships on a regional level in humans. For example, the choice of transmitter and scan type is discussed, along with approaches to allow the establishment of particular specificities (such as regional or biochemical) to in turn make results fully interpretable. An algorithm that can be used as a form of checklist for designing such multimodal studies is presented. The paper concludes that while several methodological and technical caveats needs to be overcome and addressed, multimodal imaging of the neuro-biochemical relationship provides an important tool to better understand the physiological mechanisms of the human brain

Glutamate Concentration in the Medial Prefrontal Cortex Predicts Resting-State Cortical-Subcortical Functional Connectivity in Humans

<div><p>Communication between cortical and subcortical regions is integral to a wide range of psychological processes and has been implicated in a number of psychiatric conditions. Studies in animals have provided insight into the biochemical and connectivity processes underlying such communication. However, to date no experiments that link these factors in humans <i>in vivo</i> have been carried out. To investigate the role of glutamate in individual differences in communication between the cortex – specifically the medial prefrontal cortex (mPFC) – and subcortical regions in humans, a combination of resting-state fMRI, DTI and MRS was performed. The subcortical target regions were the nucleus accumbens (NAc), dorsomedial thalamus (DMT), and periaqueductal grey (PAG). It was found that functional connectivity between the mPFC and each of the NAc and DMT was positively correlated with mPFC glutamate concentrations, whilst functional connectivity between the mPFC and PAG was negatively correlated with glutamate concentration. The correlations involving mPFC glutamate and FC between the mPFC and each of the DMT and PAG were mirrored by correlations with structural connectivity, providing evidence that the glutamatergic relationship may, in part, be due to direct connectivity. These results are in agreement with existing results from animal studies and may have relevance for MDD and schizophrenia.</p> </div