@article{HuangIvYueetal.2015, author = {Huang, Zirui and Iv, Henry (Hap) Davis and Yue, Qiang and Wiebking, Christine and Duncan, Niall W. and Zhang, Jianfeng and Wagner, Nils-Frederic and Wolff, Annemarie and Northoff, Georg}, title = {Increase in glutamate/glutamine concentration in the medial prefrontal cortex during mental imagery: A combined functional mrs and fMRI study}, series = {Human brain mapping : a journal devoted to functional neuroanatomy and neuroimaging}, volume = {36}, journal = {Human brain mapping : a journal devoted to functional neuroanatomy and neuroimaging}, number = {8}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {1065-9471}, doi = {10.1002/hbm.22841}, pages = {3204 -- 3212}, year = {2015}, abstract = {Recent functional magnetic resonance spectroscopy (fMRS) studies have shown changes in glutamate/glutamine (Glx) concentrations between resting-state and active-task conditions. However, the types of task used have been limited to sensory paradigms, and the regions from which Glx concentrations have been measured limited to sensory ones. This leaves open the question as to whether the same effect can be seen in higher-order brain regions during cognitive tasks. Cortical midline structures, especially the medial prefrontal cortex (MPFC), have been suggested to be involved in various such cognitive tasks. We, therefore set out to use fMRS to investigate the dynamics of Glx concentrations in the MPFC between resting-state and mental imagery task conditions. The auditory cortex was used as a control region. In addition, functional magnetic resonance imaging was used to explore task-related neural activity changes. The mental imagery task consisted of imagining swimming and was applied to a large sample of healthy participants (n=46). The participants were all competitive swimmers, ensuring proficiency in mental-swimming. Glx concentrations in the MPFC increased during the imagery task, as compared to resting-state periods preceding and following the task. These increases mirror BOLD activity changes in the same region during the task. No changes in either Glx concentrations or BOLD activity were seen in the auditory cortex. These findings contribute to our understanding of the biochemical basis of generating or manipulating mental representations and the MPFC's role in this. Hum Brain Mapp 36:3204-3212, 2015. (c) 2015 Wiley Periodicals, Inc.}, language = {en} } @article{WiebkingdeGreckDuncanetal.2015, author = {Wiebking, Christine and de Greck, Moritz and Duncan, Niall W. and Tempelmann, Claus and Bajbouj, Malek and Northoff, Georg}, title = {Interoception in insula subregions as a possible state marker for depression}, series = {Frontiers in behavioral neuroscience}, journal = {Frontiers in behavioral neuroscience}, number = {9}, publisher = {Frontiers Research Foundation}, address = {Lausanne}, issn = {1662-5153}, doi = {10.3389/fnbeh.2015.00082}, pages = {14}, year = {2015}, abstract = {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.}, language = {en} } @article{WiebkingdeGreckDuncanetal.2015, author = {Wiebking, Christine and de Greck, Moritz and Duncan, Niall W. and Tempelmann, Claus and Bajbouj, Malek and Northoff, Georg}, title = {Interoception in insula subregions as a possible state marker for depression - an exploratory fMRI study investigating healthy, depressed and remitted participants}, series = {Frontiers in behavioral neuroscience}, volume = {9}, journal = {Frontiers in behavioral neuroscience}, publisher = {Frontiers Research Foundation}, address = {Lausanne}, issn = {1662-5153}, doi = {10.3389/fnbeh.2015.00082}, pages = {33}, year = {2015}, abstract = {Background: Interoceptive awareness, 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 interoceptive awareness (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 healthy 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.}, language = {en} } @article{DuncanHayesWiebkingetal.2015, author = {Duncan, Niall W. and Hayes, Dave J. and Wiebking, Christine and Tiret, Brice and Pietruska, Karin and Chen, David Q. and Rainville, Pierre and Marjanska, Malgorzata and Ayad, Omar and Doyon, Julien and Hodaie, Mojgan and Northoff, Georg}, title = {Negative childhood experiences alter a prefrontal-insular-motor cortical network in healthy adults: A preliminary multimodal rsfMRI-fMRI-MRS-dMRI study}, series = {Human brain mapping : a journal devoted to functional neuroanatomy and neuroimaging}, volume = {36}, journal = {Human brain mapping : a journal devoted to functional neuroanatomy and neuroimaging}, number = {11}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {1065-9471}, doi = {10.1002/hbm.22941}, pages = {4622 -- 4637}, year = {2015}, abstract = {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 prefrontal cortex (mPFC). CTQ scores, mPFC glutamate and entropy, correlated with neural BOLD responses to the anticipation of aversive stimuli in regions throughout the aversion-related network, with strong correlations between all measures in the motor cortex and left insula. Structural connectivity strength, measured using mean fractional anisotropy, between the mPFC and left insula correlated to aversion-related signal changes in the motor cortex. These findings highlight the impact of NCEs on multiple inter-related brain systems. In particular, they highlight the role of a prefrontal-insular-motor cortical network in the processing and responsivity to aversive stimuli and its potential adaptability by NCEs. Hum Brain Mapp 36:4622-4637, 2015. (c) 2015 Wiley Periodicals, Inc.}, language = {en} } @article{WiebkingNorthoff2015, author = {Wiebking, Christine and Northoff, Georg}, title = {Neural activity during interoceptive awareness and its associations with alexithymia}, series = {Frontiers in psychology}, volume = {6}, journal = {Frontiers in psychology}, number = {589}, publisher = {Frontiers Research Foundation}, issn = {1664-1078}, doi = {10.3389/fpsyg.2015.00589}, year = {2015}, abstract = {Objective: 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. Methods: 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 TAS scores. Subsequently, IA-related neural activity was compared on a whole-brain level between the three independent samples (MDD, NC-low, NC-high). Results: Whole-brain regressions between MDD and NC revealed neural differences during IA as a function of TAS-DD (subscale difficulty describing feelings) in the supragenual anterior cingulate cortex (sACC; BA 24/32), which were due to negative associations between TAS-DD and IA-related activity in NC. Contrasting NC subgroups after median-split on a whole-brain level, high TAS scores were associated with decreased neural activity during IA in the sACC and increased insula activity. Though having equally high alexithymia scores, NC-high showed increased insula activity during IA compared to MDD, whilst both groups showed decreased activity in the sACC. Conclusions: Within the context of decreased sACC activity during IA in alexithymia (NC-high and MDD), increased insula activity might mirror a compensatory mechanism in NC-high, which is disrupted in MDD.}, language = {en} } @article{WiebkingNorthoff2015, author = {Wiebking, Christine and Northoff, Georg}, title = {Neural activity during interoceptive awareness and its associations with alexithymia-An fMRI study in major depressive disorder and non-psychiatric controls}, series = {Frontiers in psychology}, volume = {6}, journal = {Frontiers in psychology}, publisher = {Frontiers Research Foundation}, address = {Lausanne}, issn = {1664-1078}, doi = {10.3389/fpsyg.2015.00589}, pages = {16}, year = {2015}, abstract = {Objective: 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. Methods: 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 TAS scores. Subsequently, IA-related neural activity was compared on a whole-brain level between the three independent samples (MDD, NC-low, NC-high). Results: Whole-brain regressions between MDD and NC revealed neural differences during IA as a function of TAS-DD (subscale difficulty describing feelings) in the supragenual anterior cingulate cortex (sACC; BA 24/32), which were due to negative associations between TAS-DD and IA-related activity in NC. Contrasting NC subgroups after median-split on a whole-brain level, high TAS scores were associated with decreased neural activity during IA in the sACC and increased insula activity. Though having equally high alexithymia scores, NC-high showed increased insula activity during IA compared to MDD, whilst both groups showed decreased activity in the sACC. Conclusions: Within the context of decreased sACC activity during IA in alexithymia (NC-high and MDD), increased insula activity might mirror a compensatory mechanism in NC-high, which is disrupted in MDD.}, language = {en} } @article{WippertWiebking2018, author = {Wippert, Pia-Maria and Wiebking, Christine}, title = {Stress and Alterations in the Pain Matrix}, series = {International Journal of Environmental Research and Public Health}, volume = {15}, journal = {International Journal of Environmental Research and Public Health}, number = {4}, publisher = {MDPI AG}, address = {Basel}, issn = {1660-4601}, doi = {10.3390/ijerph15040785}, pages = {1 -- 11}, year = {2018}, abstract = {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}, language = {en} } @article{WiebkingLinWippert2022, author = {Wiebking, Christine and Lin, Chiao-I and Wippert, Pia-Maria}, title = {Training intervention effects on cognitive performance and neuronal plasticity — A pilot study}, series = {Frontiers in Neurology, section Neurorehabilitation}, volume = {13}, journal = {Frontiers in Neurology, section Neurorehabilitation}, publisher = {Frontiers}, address = {Lausanne, Schweiz}, issn = {1664-2295}, doi = {10.3389/fneur.2022.773813}, pages = {11}, year = {2022}, abstract = {Studies suggest that people suffering from chronic pain may have altered brain plasticity, along with altered functional connectivity between pain-processing brain regions. These may be related to decreased mood and cognitive performance. There is some debate as to whether physical activity combined with behavioral therapy (e.g. cognitive distraction, body scan) may counteract these changes. However, underlying neuronal mechanisms are unclear. The aim of the current pilot study with a 3-armed randomized controlled trial design was to examine the effects of sensorimotor training for nonspecific chronic low back pain on (1) cognitive performance; (2) fMRI activity co-fluctuations (functional connectivity) between pain-related brain regions; and (3) the relationship between functional connectivity and subjective variables (pain and depression). Six hundred and sixty two volunteers with non-specific chronic low back pain were randomly allocated to a unimodal (sensorimotor training), multidisciplinary (sensorimotor training and behavioral therapy) intervention, or to a control group within a multicenter study. A subsample of patients (n = 21) from one study center participated in the pilot study presented here. Measurements were at baseline, during (3 weeks, M2) and after intervention (12 weeks, M4 and 24 weeks, M5). Cognitive performance was measured by the Trail Making Test and functional connectivity by MRI. Pain perception and depression were assessed by the Von Korff questionnaire and the Hospital and Anxiety. Group differences were calculated by univariate and repeated ANOVA measures and Bayesian statistics; correlations by Pearson's r. Change and correlation of functional connection were analyzed within a pooled intervention group (uni-, multidisciplinary group). Results revealed that participants with increased pain intensity at baseline showed higher functional connectivity between pain-related brain areas used as ROIs in this study. Though small sample sizes limit generalization, cognitive performance increased in the multimodal group. Increased functional connectivity was observed in participants with increased pain ratings. Pain ratings and connectivity in pain-related brain regions decreased after the intervention. The results provide preliminary indication that intervention effects can potentially be achieved on the cognitive and neuronal level. The intervention may be suitable for therapy and prevention of non-specific chronic low back pain.}, language = {en} }