The familiarity to the subject of any potential stimuli presents one of the major difficulties fo... more The familiarity to the subject of any potential stimuli presents one of the major difficulties for the investigation of the self; the separation of effects resulting from familiarity from self-effects being extremely problematic. The aim of this study was thus to investigate the neural distinction between self and familiarity by combining two sets of fMRI data with a meta-analysis. In the first fMRI experiment, regions responding to self/ familiarity were investigated using the subject's own name and names of familiar others. These effects were confirmed and extended in a second fMRI experiment using the subject's own name and a stranger's name, as spoken by familiar and unfamiliar voices. Finally, a meta-analysis of self-and familiarity-related studies was conducted. Neural activity in the anterior brain regions, such as the anterior cingulate (ACC) and anterior insula (AI), was found to be specific for self-specific stimuli. In contrast, posterior brain regions, such as the posterior cingulate, were activated by familiar stimuli. Finally, the distinction between anterior and posterior regions for self and familiarity was confirmed by meta-analytic data. This study demonstrates a clear anterior-posterior cortical partition between self-specificity and familiarity.
Research in humans and animals has shown that negative childhood experiences (NCE) can have long-... more Research in humans and animals has shown that negative childhood experiences (NCE) can have long-term effects on the structure and function of the brain. Alterations have been noted in grey and white matter, in the brain's resting state, on the glutamatergic system, and on neural and behavioural responses to aversive stimuli. These effects can be linked to psychiatric disorder such as depression and anxiety disorders that are influenced by excessive exposure to early life stressors. The aim of the current study was to investigate the effect of NCEs on these systems. Resting state functional MRI (rsfMRI), aversion task fMRI, glutamate magnetic resonance spectroscopy (MRS), and diffusion magnetic resonance imaging (dMRI) were combined with the Childhood Trauma Questionnaire (CTQ) in healthy subjects to examine the impact of NCEs on the brain. Low CTQ scores, a measure of NCEs, were related to higher resting state glutamate levels and higher resting state entropy in the medial pref...
Alexithymia relates to difficulties recognizing and describing emotions. It has been linked to su... more Alexithymia relates to difficulties recognizing and describing emotions. It has been linked to subjectively increased interoceptive awareness (IA) and to psychiatric illnesses such as major depressive disorder (MDD) and somatization. MDD in turn is characterized by aberrant emotion processing and IA on the subjective as well as on the neural level. However, a link between neural activity in response to IA and alexithymic traits in health and depression remains unclear. A well-established fMRI task was used to investigate neural activity during IA (heartbeat counting) and exteroceptive awareness (tone counting) in non-psychiatric controls (NC) and MDD. Firstly, comparing MDD and NC, a linear relationship between IA-related activity and scores of the Toronto Alexithymia Scale (TAS) was investigated through whole-brain regression. Secondly, NC were divided by median-split of TAS scores into groups showing low (NC-low) or high (NC-high) alexithymia. MDD and NC-high showed equally high T...
Interoceptive awareness is defined as the awareness of stimuli originating inside one's own body ... more 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).
Communication between cortical and subcortical regions is integral to a wide range of psychologic... more 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 in vivo 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.
Objective: The Beck Depression Inventory (BDI) is probably the most widely used depression scale.... more Objective: The Beck Depression Inventory (BDI) is probably the most widely used depression scale. It has been suggested that it contains a two-factor structure measuring cognitive-affective (i.e. psychological) and somatic-vegetative depressive symptoms. In this study we aim to evaluate these factors by probing for their neural correlates. Methods: Neural responses evoked by emotional perception, relative to an emotional judgment task, were measured using functional magnetic resonance imaging (fMRI) in 20 medication-free patients with severe MDD. Psychological and somatic-vegetative symptoms were evaluated with the BDI. Results: Psychological symptoms correlated with signal changes in the dorsomedial and right ventrolateral prefrontal cortex, while somatic-vegetative symptoms correlated with signal changes in the pre-genual anterior cingulate cortex. Conclusions: These preliminary findings demonstrate segregated neural representation of psychological and somatic-vegetative symptoms of MDD in different cortical regions. Thus, our results indicate that the two-factor structure of the BDI is related to distinct neural correlates.
The resting brain shows high neural activity in various regions, the default-mode network, chief ... more The resting brain shows high neural activity in various regions, the default-mode network, chief among them the cortical midline structures (CMS). The psychological correlate of high resting state neural activity in CMS remains however unclear though speculatively it has been associated with processing of internally-oriented self-relatedness. We used functional MRI to examine internally-oriented self-relatedness during the resting state period. This was indirectly done by letting subjects perceive emotional pictures followed by a fixation cross; the very same pictures were then rated subjectively according to their degree of self-relatedness in a postscanning session. This allowed us to correlate the picture ratings of self-relatedness with signal changes in the subsequent resting state period, i.e. fixation period. The emotional pictures' degree of self-relatedness parametrically modulated subsequent resting state signal changes in various CMS, including ventro-and dorsomedial prefrontal cortex and posterior cingulate cortex. This modulation could be distinguished from effects of emotion dimensions (e.g. valence, intensity) and evoked effects of selfrelatedness during the stimulus period itself the latter being observed rather in subcortical regions, e.g. amygdala, ventral striatum, and tectum. In sum, our findings suggest that resting state neural activity in CMS is parametrically and specifically modulated by the preceding stimulus's degree of self-relatedness. This lends further support to the presumed involvement of these regions in processing internally-oriented self-relatedness as distinguished from externally-oriented self-relatedness.
Studies using functional magnetic resonance imaging (fMRI) show predominant negative blood oxygen... more Studies using functional magnetic resonance imaging (fMRI) show predominant negative blood oxygenation level-dependent (BOLD) responses (NBRs) in regions of the default-mode network such as the pregenual anterior cingulate cortex, the ventromedial prefrontal cortex, and the posterior cingulate cortex. Patients with major depressive disorder (MDD) show emotional-cognitive disturbances, which have been associated with alterations within the default-mode network. However, it remains unclear whether these default-mode network alterations are related to abnormalities in NBRs. We therefore investigated neural activity in the default-mode network during different emotional tasks in patients with MDD in an event-related fMRI design. MDD patients showed significantly reduced NBRs in several regions of the default-mode network. Decreased NBRs in MDD patients correlated with depression severity and feelings of hopelessness. In sum, our findings demonstrate that default-mode network NBRs are reduced in MDD and modulate these patients' abnormally negative emotions.
The perception of aversive stimuli is essential for human survival and depends largely on environ... more The perception of aversive stimuli is essential for human survival and depends largely on environmental context. Although aversive brain processing has been shown to involve the sensorimotor cortex, the neural and biochemical mechanisms underlying the interaction between two independent aversive cues are unclear. Based on previous work indicating ventromedial prefrontal cortex (vmPFC) involvement in the mediation of context-dependent emotional effects, we hypothesized a central role for the vmPFC in modulating sensorimotor cortex activity using a GABAergic mechanism during an aversive-aversive stimulus interaction. This approach revealed differential activations within the aversion-related network (eg, sensorimotor cortex, midcingulate, and insula) for the aversive-aversive, when compared with the aversive-neutral, interaction. Individual differences in sensorimotor cortex signal changes during the aversiveaversive interaction were predicted by GABA A receptors in both vmPFC and sensorimotor cortex. Together, these results demonstrate the central role of GABA in mediating context-dependent effects in aversion-related processing.
Emotions are frequently characterized by distinct dimensions such as valence, intensity, and reco... more Emotions are frequently characterized by distinct dimensions such as valence, intensity, and recognition. However, the exact neural representation of these dimensions in different prefrontal cortical regions remains unclear. One of the problems in revealing prefrontal cortical representation is that the very same regions are also involved in cognitive functions associated with emotion processing. We therefore conducted an fMRI study involving the viewing of emotional pictures (using the International Affective Picture System; IAPS) and controlled for associated cognitive processing like judgment and preceding attention. Functional activation was correlated with subjective post-scanning ratings of valence, intensity, and recognition. Valence significantly correlated with the functional response in ventromedial prefrontal cortex (VMPFC) and dorsolateral prefrontal cortex (DLPFC), intensity with activation in ventrolateral prefrontal cortex (VLPFC) and dorsomedial prefrontal cortex (DMPFC), and recognition with the functional response in perigenual anterior cingulate cortex (PACC). In conclusion, our results indicate segregated neural representation of the different emotion dimensions in different prefrontal cortical regions.
The insula has been identified as a key region involved in interoceptive awareness. Whilst imagin... more The insula has been identified as a key region involved in interoceptive awareness. Whilst imaging studies have investigated the neural activation patterns in this region involved in intero-and exteroceptive awareness, the underlying biochemical mechanisms still remain unclear.
Self-referential processing involves a complex set of cognitive functions, posing challenges to d... more Self-referential processing involves a complex set of cognitive functions, posing challenges to delineating its independent neural correlates. While self-referential processing has been considered functionally intertwined with episodic memory, the present study explores their overlap and dissociability. Standard tasks for self-referential processing and episodic memory were combined into a single fMRI experiment. Contrasting the effects of self-relatedness and retrieval success allowed for the two processes to be delineated. Stimuli judged as self-referential specifically activated the posterior cingulate/anterior precuneus, the medial prefrontal cortex, and an inferior division of the inferior parietal lobule. In contrast, episodic memory retrieval specifically involved the posterior precuneus, the right anterior prefrontal cortex, and a superior division of the inferior parietal lobule (extending into superior parietal lobule). Overlapping activations were found in intermediate zones in the precuneus and the inferior parietal lobule, but not in the prefrontal cortex. While our data show common networks for both processes in the medial and lateral parietal cortex, three functional differentiations were also observed: (1) an anterior-posterior differentiation within the medial parietal cortex; (2) a medial-anterolateral differentiation within the prefrontal cortex; and, (3) an inferiorsuperior differentiation within the lateral parietal cortex for self-referential processing versus episodic memory retrieval.
Sexual activity involves excitement with high arousal and pleasure as typical features of emotion... more Sexual activity involves excitement with high arousal and pleasure as typical features of emotions. Brain activations specifically related to erotic feelings and those related to general emotional processing are therefore hard to disentangle. Using fMRI in 21 healthy subjects (11 males and 10 females), we investigated regions that show activations specifically related to the viewing of sexually intense pictures while controlling for general emotional arousal (GEA) or pleasure. Activations in the ventral striatum and hypothalamus were found to be modulated by the stimulus' specific sexual intensity (SSI) while activations in the anterior cingulate cortex were associated with an interaction between sexual intensity and emotional valence. In contrast, activation in other regions like the dorsomedial prefrontal cortex, the mediodorsal thalamus and the amygdala was associated only with a general emotional component during sexual arousal. No differences were found in these effects when comparing females and males. Our findings demonstrate for the first time neural differentiation between emotional and sexual components in the neural network underlying sexual arousal.
h i g h l i g h t s • Provide an overview of factors to consider when planning multi-modal imagin... more 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.
The familiarity to the subject of any potential stimuli presents one of the major difficulties fo... more The familiarity to the subject of any potential stimuli presents one of the major difficulties for the investigation of the self; the separation of effects resulting from familiarity from self‐effects being extremely problematic. The aim of this study was thus to investigate the neural distinction between self and familiarity by combining two sets of fMRI data with a meta‐analysis. In the first fMRI experiment, regions responding to self/familiarity were investigated using the subject's own name and names of familiar others. These effects were confirmed and extended in a second fMRI experiment using the subject's own name and a stranger's name, as spoken by familiar and unfamiliar voices. Finally, a meta‐analysis of self‐ and familiarity‐related studies was conducted. Neural activity in the anterior brain regions, such as the anterior cingulate (ACC) and anterior insula (AI), was found to be specific for self‐specific stimuli. In contrast, posterior brain regions, such a...
Patients with major depressive disorder (MDD) often show a tendency to strongly introspect and re... more Patients with major depressive disorder (MDD) often show a tendency to strongly introspect and reflect upon their self, which has been described as increased self‐focus. Although subcortical‐cortical midline structures have been associated with reflection and introspection of oneself in healthy subjects, the neural correlates of the abnormally increased attribution of negative emotions to oneself, i.e. negative self‐attribution, as hallmark of the increased self‐focus in MDD remain unclear. The aim of the study was, therefore, to investigate the neural correlates during judgment of self‐relatedness of positive and negative emotional stimuli thereby testing for emotional self‐attribution. Using fMRI, we investigated 27 acute MDD patients and compared them with 25 healthy subjects employing a paradigm that focused on judgment of self‐relatedness when compared with mere perception of the very same emotional stimuli. Behaviourally, patients with MDD showed significantly higher degrees o...
The ability to detect and respond appropriately to aversive stimuli is essential for all organism... more The ability to detect and respond appropriately to aversive stimuli is essential for all organisms, from fruit flies to humans. This suggests the existence of a core neural network which mediates aversion-related processing. Human imaging studies on aversion have highlighted the involvement of various cortical regions, such as the prefrontal cortex, while animal studies have focused largely on subcortical regions like the periaqueductal gray and hypothalamus. However, whether and how these regions form a core neural network of aversion remains unclear. To help determine this, a translational cross-species investigation in humans (i.e., meta-analysis) and other animals (i.e., systematic review of functional neuroanatomy) was performed. Our results highlighted the recruitment of the anterior cingulate cortex, the anterior insula, and the amygdala as well as other subcortical (e.g., thalamus, midbrain) and cortical (e.g., orbitofrontal) regions in both animals and humans. Importantly, involvement of these regions remained independent of sensory modality. This study provides evidence for a core neural network mediating aversion in both animals and humans. This not only contributes to our understanding of the trans-species neural correlates of aversion but may also carry important implications for psychiatric disorders where abnormal aversive behavior can often be observed.
The current study investigated the immediate neurophysiological effects of different types of mas... more The current study investigated the immediate neurophysiological effects of different types of massage in healthy adults using functional magnetic resonance imaging (fMRI). Much attention has been given to the default mode network, a set of brain regions showing greater activity in the resting state. These regions (i.e. insula, posterior and anterior cingulate, inferior parietal and medial prefrontal cortices) have been postulated to be involved in the neural correlates of consciousness, specifically in arousal and awareness. We posit that massage would modulate these same regions given the benefits and pleasant affective properties of touch. To this end, healthy participants were randomly assigned to one of four conditions: 1. Swedish massage, 2. reflexology, 3. massage with an object or 4. a resting control condition. The right foot was massaged while each participant performed a cognitive association task in the scanner. We found that the Swedish massage treatment activated the subgenual anterior and retrosplenial/posterior cingulate cortices. This increased blood oxygen level dependent (BOLD) signal was maintained only in the former brain region during performance of the cognitive task. Interestingly, the reflexology massage condition selectively affected the retrosplenial/posterior cingulate in the resting state, whereas massage with the object augmented the BOLD response in this region during the cognitive task performance. These findings should have implications for better understanding how alternative treatments might affect resting state neural activity and could ultimately be important for devising new targets in the management of mood disorders.
The familiarity to the subject of any potential stimuli presents one of the major difficulties fo... more The familiarity to the subject of any potential stimuli presents one of the major difficulties for the investigation of the self; the separation of effects resulting from familiarity from self-effects being extremely problematic. The aim of this study was thus to investigate the neural distinction between self and familiarity by combining two sets of fMRI data with a meta-analysis. In the first fMRI experiment, regions responding to self/ familiarity were investigated using the subject's own name and names of familiar others. These effects were confirmed and extended in a second fMRI experiment using the subject's own name and a stranger's name, as spoken by familiar and unfamiliar voices. Finally, a meta-analysis of self-and familiarity-related studies was conducted. Neural activity in the anterior brain regions, such as the anterior cingulate (ACC) and anterior insula (AI), was found to be specific for self-specific stimuli. In contrast, posterior brain regions, such as the posterior cingulate, were activated by familiar stimuli. Finally, the distinction between anterior and posterior regions for self and familiarity was confirmed by meta-analytic data. This study demonstrates a clear anterior-posterior cortical partition between self-specificity and familiarity.
Research in humans and animals has shown that negative childhood experiences (NCE) can have long-... more Research in humans and animals has shown that negative childhood experiences (NCE) can have long-term effects on the structure and function of the brain. Alterations have been noted in grey and white matter, in the brain's resting state, on the glutamatergic system, and on neural and behavioural responses to aversive stimuli. These effects can be linked to psychiatric disorder such as depression and anxiety disorders that are influenced by excessive exposure to early life stressors. The aim of the current study was to investigate the effect of NCEs on these systems. Resting state functional MRI (rsfMRI), aversion task fMRI, glutamate magnetic resonance spectroscopy (MRS), and diffusion magnetic resonance imaging (dMRI) were combined with the Childhood Trauma Questionnaire (CTQ) in healthy subjects to examine the impact of NCEs on the brain. Low CTQ scores, a measure of NCEs, were related to higher resting state glutamate levels and higher resting state entropy in the medial pref...
Alexithymia relates to difficulties recognizing and describing emotions. It has been linked to su... more Alexithymia relates to difficulties recognizing and describing emotions. It has been linked to subjectively increased interoceptive awareness (IA) and to psychiatric illnesses such as major depressive disorder (MDD) and somatization. MDD in turn is characterized by aberrant emotion processing and IA on the subjective as well as on the neural level. However, a link between neural activity in response to IA and alexithymic traits in health and depression remains unclear. A well-established fMRI task was used to investigate neural activity during IA (heartbeat counting) and exteroceptive awareness (tone counting) in non-psychiatric controls (NC) and MDD. Firstly, comparing MDD and NC, a linear relationship between IA-related activity and scores of the Toronto Alexithymia Scale (TAS) was investigated through whole-brain regression. Secondly, NC were divided by median-split of TAS scores into groups showing low (NC-low) or high (NC-high) alexithymia. MDD and NC-high showed equally high T...
Interoceptive awareness is defined as the awareness of stimuli originating inside one's own body ... more 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).
Communication between cortical and subcortical regions is integral to a wide range of psychologic... more 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 in vivo 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.
Objective: The Beck Depression Inventory (BDI) is probably the most widely used depression scale.... more Objective: The Beck Depression Inventory (BDI) is probably the most widely used depression scale. It has been suggested that it contains a two-factor structure measuring cognitive-affective (i.e. psychological) and somatic-vegetative depressive symptoms. In this study we aim to evaluate these factors by probing for their neural correlates. Methods: Neural responses evoked by emotional perception, relative to an emotional judgment task, were measured using functional magnetic resonance imaging (fMRI) in 20 medication-free patients with severe MDD. Psychological and somatic-vegetative symptoms were evaluated with the BDI. Results: Psychological symptoms correlated with signal changes in the dorsomedial and right ventrolateral prefrontal cortex, while somatic-vegetative symptoms correlated with signal changes in the pre-genual anterior cingulate cortex. Conclusions: These preliminary findings demonstrate segregated neural representation of psychological and somatic-vegetative symptoms of MDD in different cortical regions. Thus, our results indicate that the two-factor structure of the BDI is related to distinct neural correlates.
The resting brain shows high neural activity in various regions, the default-mode network, chief ... more The resting brain shows high neural activity in various regions, the default-mode network, chief among them the cortical midline structures (CMS). The psychological correlate of high resting state neural activity in CMS remains however unclear though speculatively it has been associated with processing of internally-oriented self-relatedness. We used functional MRI to examine internally-oriented self-relatedness during the resting state period. This was indirectly done by letting subjects perceive emotional pictures followed by a fixation cross; the very same pictures were then rated subjectively according to their degree of self-relatedness in a postscanning session. This allowed us to correlate the picture ratings of self-relatedness with signal changes in the subsequent resting state period, i.e. fixation period. The emotional pictures' degree of self-relatedness parametrically modulated subsequent resting state signal changes in various CMS, including ventro-and dorsomedial prefrontal cortex and posterior cingulate cortex. This modulation could be distinguished from effects of emotion dimensions (e.g. valence, intensity) and evoked effects of selfrelatedness during the stimulus period itself the latter being observed rather in subcortical regions, e.g. amygdala, ventral striatum, and tectum. In sum, our findings suggest that resting state neural activity in CMS is parametrically and specifically modulated by the preceding stimulus's degree of self-relatedness. This lends further support to the presumed involvement of these regions in processing internally-oriented self-relatedness as distinguished from externally-oriented self-relatedness.
Studies using functional magnetic resonance imaging (fMRI) show predominant negative blood oxygen... more Studies using functional magnetic resonance imaging (fMRI) show predominant negative blood oxygenation level-dependent (BOLD) responses (NBRs) in regions of the default-mode network such as the pregenual anterior cingulate cortex, the ventromedial prefrontal cortex, and the posterior cingulate cortex. Patients with major depressive disorder (MDD) show emotional-cognitive disturbances, which have been associated with alterations within the default-mode network. However, it remains unclear whether these default-mode network alterations are related to abnormalities in NBRs. We therefore investigated neural activity in the default-mode network during different emotional tasks in patients with MDD in an event-related fMRI design. MDD patients showed significantly reduced NBRs in several regions of the default-mode network. Decreased NBRs in MDD patients correlated with depression severity and feelings of hopelessness. In sum, our findings demonstrate that default-mode network NBRs are reduced in MDD and modulate these patients' abnormally negative emotions.
The perception of aversive stimuli is essential for human survival and depends largely on environ... more The perception of aversive stimuli is essential for human survival and depends largely on environmental context. Although aversive brain processing has been shown to involve the sensorimotor cortex, the neural and biochemical mechanisms underlying the interaction between two independent aversive cues are unclear. Based on previous work indicating ventromedial prefrontal cortex (vmPFC) involvement in the mediation of context-dependent emotional effects, we hypothesized a central role for the vmPFC in modulating sensorimotor cortex activity using a GABAergic mechanism during an aversive-aversive stimulus interaction. This approach revealed differential activations within the aversion-related network (eg, sensorimotor cortex, midcingulate, and insula) for the aversive-aversive, when compared with the aversive-neutral, interaction. Individual differences in sensorimotor cortex signal changes during the aversiveaversive interaction were predicted by GABA A receptors in both vmPFC and sensorimotor cortex. Together, these results demonstrate the central role of GABA in mediating context-dependent effects in aversion-related processing.
Emotions are frequently characterized by distinct dimensions such as valence, intensity, and reco... more Emotions are frequently characterized by distinct dimensions such as valence, intensity, and recognition. However, the exact neural representation of these dimensions in different prefrontal cortical regions remains unclear. One of the problems in revealing prefrontal cortical representation is that the very same regions are also involved in cognitive functions associated with emotion processing. We therefore conducted an fMRI study involving the viewing of emotional pictures (using the International Affective Picture System; IAPS) and controlled for associated cognitive processing like judgment and preceding attention. Functional activation was correlated with subjective post-scanning ratings of valence, intensity, and recognition. Valence significantly correlated with the functional response in ventromedial prefrontal cortex (VMPFC) and dorsolateral prefrontal cortex (DLPFC), intensity with activation in ventrolateral prefrontal cortex (VLPFC) and dorsomedial prefrontal cortex (DMPFC), and recognition with the functional response in perigenual anterior cingulate cortex (PACC). In conclusion, our results indicate segregated neural representation of the different emotion dimensions in different prefrontal cortical regions.
The insula has been identified as a key region involved in interoceptive awareness. Whilst imagin... more The insula has been identified as a key region involved in interoceptive awareness. Whilst imaging studies have investigated the neural activation patterns in this region involved in intero-and exteroceptive awareness, the underlying biochemical mechanisms still remain unclear.
Self-referential processing involves a complex set of cognitive functions, posing challenges to d... more Self-referential processing involves a complex set of cognitive functions, posing challenges to delineating its independent neural correlates. While self-referential processing has been considered functionally intertwined with episodic memory, the present study explores their overlap and dissociability. Standard tasks for self-referential processing and episodic memory were combined into a single fMRI experiment. Contrasting the effects of self-relatedness and retrieval success allowed for the two processes to be delineated. Stimuli judged as self-referential specifically activated the posterior cingulate/anterior precuneus, the medial prefrontal cortex, and an inferior division of the inferior parietal lobule. In contrast, episodic memory retrieval specifically involved the posterior precuneus, the right anterior prefrontal cortex, and a superior division of the inferior parietal lobule (extending into superior parietal lobule). Overlapping activations were found in intermediate zones in the precuneus and the inferior parietal lobule, but not in the prefrontal cortex. While our data show common networks for both processes in the medial and lateral parietal cortex, three functional differentiations were also observed: (1) an anterior-posterior differentiation within the medial parietal cortex; (2) a medial-anterolateral differentiation within the prefrontal cortex; and, (3) an inferiorsuperior differentiation within the lateral parietal cortex for self-referential processing versus episodic memory retrieval.
Sexual activity involves excitement with high arousal and pleasure as typical features of emotion... more Sexual activity involves excitement with high arousal and pleasure as typical features of emotions. Brain activations specifically related to erotic feelings and those related to general emotional processing are therefore hard to disentangle. Using fMRI in 21 healthy subjects (11 males and 10 females), we investigated regions that show activations specifically related to the viewing of sexually intense pictures while controlling for general emotional arousal (GEA) or pleasure. Activations in the ventral striatum and hypothalamus were found to be modulated by the stimulus' specific sexual intensity (SSI) while activations in the anterior cingulate cortex were associated with an interaction between sexual intensity and emotional valence. In contrast, activation in other regions like the dorsomedial prefrontal cortex, the mediodorsal thalamus and the amygdala was associated only with a general emotional component during sexual arousal. No differences were found in these effects when comparing females and males. Our findings demonstrate for the first time neural differentiation between emotional and sexual components in the neural network underlying sexual arousal.
h i g h l i g h t s • Provide an overview of factors to consider when planning multi-modal imagin... more 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.
The familiarity to the subject of any potential stimuli presents one of the major difficulties fo... more The familiarity to the subject of any potential stimuli presents one of the major difficulties for the investigation of the self; the separation of effects resulting from familiarity from self‐effects being extremely problematic. The aim of this study was thus to investigate the neural distinction between self and familiarity by combining two sets of fMRI data with a meta‐analysis. In the first fMRI experiment, regions responding to self/familiarity were investigated using the subject's own name and names of familiar others. These effects were confirmed and extended in a second fMRI experiment using the subject's own name and a stranger's name, as spoken by familiar and unfamiliar voices. Finally, a meta‐analysis of self‐ and familiarity‐related studies was conducted. Neural activity in the anterior brain regions, such as the anterior cingulate (ACC) and anterior insula (AI), was found to be specific for self‐specific stimuli. In contrast, posterior brain regions, such a...
Patients with major depressive disorder (MDD) often show a tendency to strongly introspect and re... more Patients with major depressive disorder (MDD) often show a tendency to strongly introspect and reflect upon their self, which has been described as increased self‐focus. Although subcortical‐cortical midline structures have been associated with reflection and introspection of oneself in healthy subjects, the neural correlates of the abnormally increased attribution of negative emotions to oneself, i.e. negative self‐attribution, as hallmark of the increased self‐focus in MDD remain unclear. The aim of the study was, therefore, to investigate the neural correlates during judgment of self‐relatedness of positive and negative emotional stimuli thereby testing for emotional self‐attribution. Using fMRI, we investigated 27 acute MDD patients and compared them with 25 healthy subjects employing a paradigm that focused on judgment of self‐relatedness when compared with mere perception of the very same emotional stimuli. Behaviourally, patients with MDD showed significantly higher degrees o...
The ability to detect and respond appropriately to aversive stimuli is essential for all organism... more The ability to detect and respond appropriately to aversive stimuli is essential for all organisms, from fruit flies to humans. This suggests the existence of a core neural network which mediates aversion-related processing. Human imaging studies on aversion have highlighted the involvement of various cortical regions, such as the prefrontal cortex, while animal studies have focused largely on subcortical regions like the periaqueductal gray and hypothalamus. However, whether and how these regions form a core neural network of aversion remains unclear. To help determine this, a translational cross-species investigation in humans (i.e., meta-analysis) and other animals (i.e., systematic review of functional neuroanatomy) was performed. Our results highlighted the recruitment of the anterior cingulate cortex, the anterior insula, and the amygdala as well as other subcortical (e.g., thalamus, midbrain) and cortical (e.g., orbitofrontal) regions in both animals and humans. Importantly, involvement of these regions remained independent of sensory modality. This study provides evidence for a core neural network mediating aversion in both animals and humans. This not only contributes to our understanding of the trans-species neural correlates of aversion but may also carry important implications for psychiatric disorders where abnormal aversive behavior can often be observed.
The current study investigated the immediate neurophysiological effects of different types of mas... more The current study investigated the immediate neurophysiological effects of different types of massage in healthy adults using functional magnetic resonance imaging (fMRI). Much attention has been given to the default mode network, a set of brain regions showing greater activity in the resting state. These regions (i.e. insula, posterior and anterior cingulate, inferior parietal and medial prefrontal cortices) have been postulated to be involved in the neural correlates of consciousness, specifically in arousal and awareness. We posit that massage would modulate these same regions given the benefits and pleasant affective properties of touch. To this end, healthy participants were randomly assigned to one of four conditions: 1. Swedish massage, 2. reflexology, 3. massage with an object or 4. a resting control condition. The right foot was massaged while each participant performed a cognitive association task in the scanner. We found that the Swedish massage treatment activated the subgenual anterior and retrosplenial/posterior cingulate cortices. This increased blood oxygen level dependent (BOLD) signal was maintained only in the former brain region during performance of the cognitive task. Interestingly, the reflexology massage condition selectively affected the retrosplenial/posterior cingulate in the resting state, whereas massage with the object augmented the BOLD response in this region during the cognitive task performance. These findings should have implications for better understanding how alternative treatments might affect resting state neural activity and could ultimately be important for devising new targets in the management of mood disorders.
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Papers by Georg Northoff