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  • 1.
    Augier, Eric
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten.
    Dulman, Russell S.
    NIAAA, MD USA.
    Damadzic, Ruslan
    NIAAA, MD USA.
    Pilling, Andrew
    NIAAA, MD USA.
    Hamilton, Paul
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten.
    Heilig, Markus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    The GABA(B) Positive Allosteric Modulator ADX71441 Attenuates Alcohol Self-Administration and Relapse to Alcohol Seeking in Rats2017Ingår i: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 42, nr 9, s. 1789-1799Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    GABAergic signaling is involved in modulating the reinforcing properties of alcohol, and GABA(B) receptors have been proposed as a potential target for clinical treatment of alcoholism. The orthosteric GABA(B) receptor agonist baclofen has been shown to suppress operant self-administration of alcohol in animals and alcohol use in alcohol-dependent patients, but its utility is limited by a narrow therapeutic index. We tested the effects of ADX71441, a novel GABA(B) receptor positive allosteric modulator, on alcohol-related behaviors in rats. We first assessed the effects of ADX71441 ( 1, 3, 10 and 30 mg/kg, I.P.) on both non-dependent and dependent male Wistar rats trained to self-administer 20% alcohol. We then determined the effects of ADX71441 on stress-induced as well as cue-induced relapse-like behavior. Finally, we sought to identify the brain regions through which ADX71441 may act to prevent relapse-like behavior by mapping the neuronal activation induced by stress-induced reinstatement of alcohol-seeking using c-Fos immunohistochemistry. ADX71441 dose-dependently decreased alcohol self-administration of both dependent and non-dependent animals, but its potency was higher in alcohol-dependent rats. Furthermore, both cue-and stress-induced alcohol seeking were blocked by the GABA(B) receptor positive allosteric modulator. Finally, pretreatment with 3 mg/kg of ADX71441 before stress-induced reinstatement significantly decreased c-Fos expression in a network of brain regions implicated in stress-induced relapse, comprising the nucleus accumbens shell, the dorsal raphe nucleus and the medial prefrontal cortex. Our findings support a causal role of GABAB receptors in alcohol reinforcement and relapse to alcohol seeking. These effects are observed in the absence of significant sedative side effects. Jointly, these observations indicate that GABAB receptor positive allosteric modulators merit being tested clinically for the treatment of alcoholism. Our data also point to a potential biomarker of target engagement for early clinical studies.

  • 2.
    Bergamino, Maurizio
    et al.
    Laureate Institute for Brain Research, Tulsa, OK, USA.
    Farmer, Madison
    Roosevelt University, Department of Industrial and Organizational Psychology, Chicago, IL, USA.
    Yeh, Hung-Wen
    Laureate Institute for Brain Research, Tulsa, OK, USA.
    Paul, Elisabeth
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten.
    Hamilton, Paul J.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten.
    Statistical differences in the white matter tracts in subjects with depression by using different skeletonized voxel-wise analysis approaches and DTI fitting procedures2017Ingår i: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1669, s. 131-140Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Major depressive disorder (MDD) is one of the most significant contributors to the global burden of illness. Diffusion tensor imaging (DTI) is a procedure that has been used in several studies to characterize abnormalities in white matter (WM) microstructural integrity in MDD. These studies, however, have provided divergent findings, potentially due to the large variety of methodological alternatives available in conducting DTI research. In order to determine the importance of different approaches to coregistration of DTI-derived metrics to a standard space, we compared results from two different skeletonized voxel-wise analysis approaches: the standard TBBS pipeline and the Advanced Normalization Tools (ANTs) approach incorporating a symmetric image normalization (SyN) algorithm and a group-wise template (ANTs TBSS). We also assessed effects of applying twelve different fitting procedures for the diffusion tensor. For our dataset, lower fractional anisotropy (FA) and axial diffusivity (AD) in depressed subjects compared with healthy controls were found for both methods and for all fitting procedures. No group differences were found for radial and mean diffusivity indices. Importantly, for the AD metric, the normalization methods and fitting procedures showed reliable differences, both in the volume and in the number of significant between-groups difference clusters detected. Additionally, a significant voxel-based correlation, in the left inferior fronto-occipital fasciculus, between AD and self-reported stress was found only for one of the normalization procedure (ANTs TBSS). In conclusion, the sensitivity to detect group-level effects on DTI metrics might depend on the DTI normalization and/or tensor fitting procedures used.

  • 3.
    Bergamino, Maurizio
    et al.
    Laureate Institute Brain Research, OK, USA.
    Pasternak, Ofer
    Harvard University, MA, USA.
    Farmer, Madison
    Laureate Institute Brain Research, OK, USA.
    Shenton, Martha E.
    Harvard University, MA, USA; VA Boston Healthcare Syst, MA USA.
    Hamilton, Paul
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för social och affektiv neurovetenskap (CSAN). Laureate Institute Brain Research, OK, USA.
    Applying a free-water correction to diffusion imaging data uncovers stress-related neural pathology in depression2016Ingår i: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 10, s. 336-342Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Diffusion tensor imaging (DTI) holds promise for developing our understanding of white-matter pathology in major depressive disorder (MDD). Variable findings in DTI-based investigations ofMDD, however, have thwarted development of this literature. Effects of extra-cellular free-water on the sensitivity of DTI metrics could account for some of this inconsistency. Here we investigated whether applying a free-water correction algorithm to DTI data could improve the sensitivity to detect clinical effects using DTI metrics. Only after applying this correction, we found: a) significantly decreased fractional anisotropy and axial diffusivity (AD) in the left inferior frontooccipital fasciculus (IFOF) in MDD; and b) increased self-reported stress that significantly correlated with decreased IFOF AD in depression. We estimated and confirmed the robustness of differences observed between free-water corrected and uncorrected approaches using bootstrapping. We conclude that applying a free-water correction to DTI data increases the sensitivity of DTI-based metrics to detect clinical effects in MDD. (C) 2015 The Authors. Published by Elsevier Inc.

  • 4.
    Chau, David T.
    et al.
    Laureate Institute for Brain Research, Tulsa, Oklahoma, USA.
    Fogelman, Phoebe
    University of Tennessee, Knoxville, Tennessee, USA.
    Nordanskog, Pia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Drevets, Wayne C.
    Laureate Institute for Brain Research, Tulsa, Oklahoma, USA; Janssen Research and Development, Janssen Pharmaceuticals of Johnson and Johnson, Titusville, New Jersey, USA.
    Hamilton, Paul J.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten. Laureate Institute for Brain Research, Tulsa, Oklahoma, USA.
    Distinct Neural-Functional Effects of Treatments With Selective Serotonin Reuptake Inhibitors, Electroconvulsive Therapy, and Transcranial Magnetic Stimulation and Their Relations to Regional Brain Function in Major Depression: A Meta-analysis2017Ingår i: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, ISSN 2451-9030, Vol. 2, nr 4, s. 318-326Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Functional neuroimaging studies have examined the neural substrates of treatments for major depressive disorder (MDD). Low sample size and methodological heterogeneity, however, undermine the generalizability of findings from individual studies. We conducted a meta-analysis to identify reliable neural changes resulting from different modes of treatment for MDD and compared them with each other and with reliable neural functional abnormalities observed in depressed versus control samples.

  • 5.
    Croy, Ilona
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. University of Gothenburg, Sweden; Technical University of Dresden, Germany.
    Drechsler, Edda
    Technical University of Dresden, Germany.
    Hamilton, Paul
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för social och affektiv neurovetenskap (CSAN).
    Hummel, Thomas
    Technical University of Dresden, Germany.
    Olausson, Håkan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. University of Gothenburg, Sweden.
    Olfactory modulation of affective touch processing - A neurophysiological investigation2016Ingår i: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 135, s. 135-141Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Touch can be highly emotional, and depending on the environment, it can be perceived as pleasant and comforting or disgusting and dangerous. Here, we studied the impact of context on the processing of tactile stimuli using a functional magnetic resonance imaging (fMRI) paradigm. This was achieved by embedding tactile stimulation in a variable olfactory environment. Twenty people were scanned with BOLD fMRI while receiving the following stimulus blocks: Slow stroking Touch, Civette odor (feces like), Rose odor, Touch + Civette, and Touch + Rose. Ratings of pleasantness and intensity of tactile stimuli and ratings of disgust and intensity of olfactory stimuli were collected. The impact of the olfactory context on the processing of touch was studied using covariance analyses. Coupling between olfactory processing and somatosensory processing areas was assessed with psychophysiological interaction analysis (PPI). A subjectively disgusting olfactory environment significantly reduced the perceived pleasantness of touch. The touch fMRI activation in the secondary somatosensory cortex, operculum 1 (OP1), was positively correlated with the disgust towards the odors. Decreased pleasantness of touch was related to decreased posterior insula activity. PPI analysis revealed a significant interaction between the OP1, posterior insula, and regions processing the disgust of odors (orbitofrontal cortex and amygdala). We conclude that the disgust evaluation of the olfactory environment moderates neural reactivity in somatosensory regions by upregulation of the OP1 and downregulation of the posterior insula. This adaptive regulation of affective touch processing may facilitate adaptive reaction to a potentially harmful stimulus. (C) 2016 Elsevier Inc. All rights reserved.

  • 6.
    Feldman Barrett, Lisa
    et al.
    Northeastern University, MA 02115 USA; Massachusetts Gen Hospital, MA 02129 USA; Harvard Medical Sch, MA 02129 USA; Massachusetts Gen Hospital, MA 02114 USA; Harvard Medical Sch, MA 02115 USA.
    Quigley, Karen S.
    Northeastern University, MA 02115 USA.
    Hamilton, Paul
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för social och affektiv neurovetenskap (CSAN).
    An active inference theory of allostasis and interoception in depression2016Ingår i: Philosophical Transactions of the Royal Society of London. Biological Sciences, ISSN 0962-8436, E-ISSN 1471-2970, Vol. 371, nr 1708, artikel-id 20160011Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In this paper, we integrate recent theoretical and empirical developments in predictive coding and active inference accounts of interoception (including the Embodied Predictive Interoception Coding model) with working hypotheses from the theory of constructed emotion to propose a biologically plausible unified theory of the mind that places metabolism and energy regulation (i.e. allostasis), as well as the sensory consequences of that regulation (i.e. interoception), at its core. We then consider the implications of this approach for understanding depression. We speculate that depression is a disorder of allostasis, whose myriad symptoms result from a locked in brain that is relatively insensitive to its sensory context. We conclude with a brief discussion of the ways our approach might reveal new insights for the treatment of depression. This article is part of the themed issue Interoception beyond homeostasis: affect, cognition and mental health.

  • 7.
    Frost Bellgowan, Julie
    et al.
    Laureate Institute Brain Research, OK USA.
    Molfese, Peter
    Haskins Labs Inc, CT USA.
    Marx, Michael
    Stanford University, CA 94305 USA.
    Thomason, Moriah
    Wayne State University, MI USA.
    Glen, Daniel
    NIMH, MD 20892 USA.
    Santiago, Jessica
    Laureate Institute Brain Research, OK USA.
    Gotlib, Ian H.
    Stanford University, CA 94305 USA.
    Drevets, Wayne C.
    Laureate Institute Brain Research, OK USA; Janssen Pharmaceut, Belgium.
    Hamilton, Paul J.
    Linköpings universitet, Centrum för social och affektiv neurovetenskap (CSAN). Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Laureate Institute Brain Research, OK USA.
    A Neural Substrate for Behavioral Inhibition in the Risk for Major Depressive Disorder2015Ingår i: Journal of the American Academy of Child and Adolescent Psychiatry, ISSN 0890-8567, E-ISSN 1527-5418, Vol. 54, nr 10, s. 841-848Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Behavioral inhibition (BI) is an early developing trait associated with cautiousness and development of clinical depression and anxiety. Little is known about the neural basis of BI and its predictive importance concerning risk for internalizing disorders. We looked at functional connectivity of the default-mode network (DMN) and salience network (SN), given their respective roles in self-relational and threat processing, in the risk for internalizing disorders, with an emphasis on determining the functional significance of these networks for BI. Method: We used functional magnetic resonance imaging to scan, during the resting state, children and adolescents 8 to 17 years of age who were either at high familial risk (HR; n = 16) or low familial risk (LR; n = 18) for developing clinical depression and/or anxiety. Whole-brain DMN and SN functional connectivity were estimated for each participant and compared across groups. We also compared the LR and HR groups on levels of BI and anxiety, and incorporated these data into follow-up neurobehavioral correlation analyses. Results: The HR group, relative to the LR group, showed significantly decreased DMN connectivity with the ventral striatum and bilateral sensorimotor cortices. Within the HR group, trait BI increased as DMN connectivity with the ventral striatum and sensorimotor cortex decreased. The HR and LR groups did not differ with respect to SN connectivity. Conclusion: Our findings show, in the risk for internalizing disorders, a negative functional relation between brain regions supporting self-relational processes and reward prediction. These findings represent a potential neural substrate for behavioral inhibition in the risk for clinical depression and anxiety.

  • 8.
    Hamilton, Paul J.
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för social och affektiv neurovetenskap (CSAN).
    Glover, Gary H.
    Stanford University, CA, USA.
    Bagarinao, Epifanio
    Stanford University, CA, USA.
    Chang, Catie
    National Institutes of Health, Bethesda, MD, USA.
    Mackey, Sean
    Stanford University, CA, USA.
    Sacchet, Matthew D.
    Stanford University, CA, USA.
    Gotlib, Ian H.
    Stanford University, CA, USA.
    Effects of salience-network-node neurofeedback training on affective biases in major depressive disorder2016Ingår i: Psychiatry Research: Neuroimaging, ISSN 0925-4927, E-ISSN 1872-7506, Vol. 249, s. 91-96Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Neural models of major depressive disorder (MDD) posit that over-response of components of the brains salience network (SN) to negative stimuli plays a crucial role in the pathophysiology of MDD. In the present proof-of-concept study, we tested this formulation directly by examining the affective consequences of training depressed persons to down-regulate response of SN nodes to negative material. Ten participants in the real neurofeedback group saw, and attempted to learn to down-regulate, activity from an empirically identified node of the SN. Ten other participants engaged in an equivalent procedure with the exception that they saw SN-node neurofeedback indices from participants in the real neurofeedback group. Before and after scanning, all participants completed tasks assessing emotional responses to negative scenes and to negative and positive self-descriptive adjectives. Compared to participants in the sham-neurofeedback group, from pre- to post-training, participants in the realneurofeedback group showed a greater decrease in SN-node response to negative stimuli, a greater decrease in self-reported emotional response to negative scenes, and a greater decrease in self-reported emotional response to negative self-descriptive adjectives. Our findings provide support for a neural formulation in which the SN plays a primary role in contributing to negative cognitive biases in MDD. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

  • 9.
    Hamilton, Paul
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten.
    Sacchet, Matthew D.
    Stanford Univ, CA 94305 USA.
    Hjornevik, Trine
    Oslo Univ Hosp, Norway; Norwegian Med Cyclotron Ctr, Norway; Stanford Univ, CA 94305 USA.
    Chin, Frederick T.
    Stanford Univ, CA 94305 USA.
    Shen, Bin
    Stanford Univ, CA 94305 USA.
    Kämpe, Robin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten.
    Park, Jun Hyung
    Stanford Univ, CA 94305 USA.
    Knutson, Brian D.
    Stanford Univ, CA USA.
    Williams, Leanne M.
    Stanford Univ, CA 94305 USA.
    Borg, Nicholas
    Stanford Univ, CA USA.
    Zaharchuk, Greg
    Stanford Univ, CA 94305 USA.
    Camacho, M. Catalina
    Univ Pittsburgh, PA 15260 USA.
    Mackey, Sean
    Stanford Univ, CA 94305 USA.
    Heilig, Markus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Drevets, Wayne C.
    Janssen Res and Dev LLC, NJ USA.
    Glover, Gary H.
    Stanford Univ, CA 94305 USA.
    Gambhir, Sanjiv S.
    Stanford Univ, CA 94305 USA.
    Gotlib, Ian H.
    Stanford Univ, CA USA.
    Striatal dopamine deficits predict reductions in striatal functional connectivity in major depression: a concurrent C-11-raclopride positron emission tomography and functional magnetic resonance imaging investigation2018Ingår i: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 8, artikel-id 264Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Major depressive disorder (MDD) is characterized by the altered integration of reward histories and reduced responding of the striatum. We have posited that this reduced striatal activation in MDD is due to tonically decreased stimulation of striatal dopamine synapses which results in decremented propagation of information along the corticostriatal-pallido-thalamic (CSPT) spiral. In the present investigation, we tested predictions of this formulation by conducting concurrent functional magnetic resonance imaging (fMRI) and C-11-raclopride positron emission tomography (PET) in depressed and control (CTL) participants. We scanned 16 depressed and 14 CTL participants with simultaneous fMRI and C-11-raclopride PET. We estimated raclopride binding potential (BPND), voxel-wise, and compared MDD and CTL samples with respect to BPND in the striatum. Using striatal regions that showed significant between-group BPND differences as seeds, we conducted whole-brain functional connectivity analysis using the fMRI data and identified brain regions in each group in which connectivity with striatal seed regions scaled linearly with BPND from these regions. We observed increased BPND in the ventral striatum, bilaterally, and in the right dorsal striatum in the depressed participants. Further, we found that as BPND increased in both the left ventral striatum and right dorsal striatum in MDD, connectivity with the cortical targets of these regions (default-mode network and salience network, respectively) decreased. Deficits in stimulation of striatal dopamine receptors in MDD could account in part for the failure of transfer of information up the CSPT circuit in the pathophysiology of this disorder.

  • 10.
    Oltedal, Leif
    et al.
    University of Bergen, Norway; University of Calif San Diego, CA 92037 USA; University of Calif San Diego, CA 92093 USA; Haukeland Hospital, Norway.
    Bartsch, Hauke
    University of Calif San Diego, CA 92037 USA; University of Calif San Diego, CA 92093 USA.
    Evjenth Sorhaug, Ole Johan
    University of Bergen, Norway.
    Kessler, Ute
    University of Bergen, Norway; Haukeland Hospital, Norway.
    Abbott, Christopher
    University of New Mexico, NM 87131 USA.
    Dols, Annemieke
    VUmc Amsterdam, Netherlands.
    Stek, Max L.
    VUmc Amsterdam, Netherlands.
    Ersland, Lars
    Haukeland Hospital, Norway.
    Emsell, Louise
    Katholieke University of Leuven, Belgium.
    van Eijndhoven, Philip
    Donders Institute Brain Cognit and Behav, Netherlands.
    Argyelan, Miklos
    Feinstein Institute Medical Research, NY USA.
    Tendolkar, Indira
    Donders Institute Brain Cognit and Behav, Netherlands.
    Nordanskog, Pia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Hamilton, Paul J.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten.
    Balslev Jorgensen, Martin
    Psychiat Centre Copenhagen, Denmark.
    Sommer, Iris E.
    University of Medical Centre, Netherlands.
    Heringa, Sophie M.
    University of Medical Centre, Netherlands.
    Draganski, Bogdan
    University of Lausanne, Switzerland; Max Planck Institute Human Brain and Cognit Neurosci, Germany.
    Redlich, Ronny
    Department of Psychiatry, University of Münster, Germany.
    Dannlowski, Udo
    University of Munster, Germany; University of Marburg, Germany.
    Kugel, Harald
    University of Munster, Germany.
    Bouckaert, Filip
    Katholieke University of Leuven, Belgium.
    Sienaert, Pascal
    Katholieke University of Leuven, Belgium.
    Anand, Amit
    Cleveland Clin, OH 44106 USA.
    Espinoza, Randall
    University of Calif Los Angeles, CA USA.
    Narr, Katherine L.
    University of Calif Los Angeles, CA 90024 USA.
    Holland, Dominic
    University of Calif San Diego, CA 92037 USA; University of Calif San Diego, CA 92093 USA.
    Dale, Anders M.
    University of Calif San Diego, CA 92037 USA; University of Calif San Diego, CA 92093 USA; University of Calif San Diego, CA 92093 USA.
    Oedegaard, Ketil J.
    University of Bergen, Norway; Haukeland Hospital, Norway; KG Jebsen Centre Research Neuropsychiat Disorders, Norway.
    The Global ECT-MRI Research Collaboration (GEMRIC): Establishing a multi-site investigation of the neural mechanisms underlying response to electroconvulsive therapy2017Ingår i: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 14, s. 422-432Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Major depression, currently the worlds primary cause of disability, leads to profound personal suffering and increased risk of suicide. Unfortunately, the success of antidepressant treatment varies amongst individuals and can take weeks to months in those who respond. Electroconvulsive therapy (ECT), generally prescribed for the most severely depressed and when standard treatments fail, produces a more rapid response and remains the most effective intervention for severe depression. Exploring the neurobiological effects of ECT is thus an ideal approach to better understand the mechanisms of successful therapeutic response. Though several recent neuroimaging studies show structural and functional changes associated with ECT, not all brain changes associate with clinical outcome. Larger studies that can address individual differences in clinical and treatment parameters may better target biological factors relating to or predictive of ECT-related therapeutic response. We have thus formed the Global ECT-MRI Research Collaboration (GEMRIC) that aims to combine longitudinal neuroimaging as well as clinical, behavioral and other physiological data across multiple independent sites. Here, we summarize the ECT sample characteristics from currently participating sites, and the common data-repository and standardized image analysis pipeline developed for this initiative. This includes data harmonization across sites and MRI platforms, and a method for obtaining unbiased estimates of structural change based on longitudinal measurements with serial MRI scans. The optimized analysis pipeline, together with the large and heterogeneous combined GEMRIC dataset, will provide new opportunities to elucidate the mechanisms of ECT response and the factors mediating and predictive of clinical outcomes, which may ultimately lead to more effective personalized treatment approaches. (C) 2017 The Author(s). Published by Elsevier Inc.

  • 11.
    Perini, Irene
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten.
    Gustafsson, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Barn- och ungdomspsykiatriska kliniken.
    Hamilton, Paul
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten.
    Kämpe, Robin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten.
    Zetterqvist, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Barn- och ungdomspsykiatriska kliniken.
    Heilig, Markus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    The salience of self, not social pain, is encoded by dorsal anterior cingulate and insula2018Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, artikel-id 6165Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The human neural correlates of social rejection have attracted significant research interest, but remain subject to vigorous debate. Specifically, it has been proposed that a matrix of brain regions overlapping with the classical pain matrix, and including the dorsal anterior cingulate cortex (dACC) and the anterior insular cortex (AI) is critical for processing of social rejection. The present study expands on this conceptualization, by showing that these areas are involved in processing of self-relevant social evaluation, irrespective of valence. Forty healthy adolescents (N = 20 females) were tested in a magnetic resonance imaging (MRI) scanner. We used a novel paradigm that balanced participants experience of rejection and acceptance. In addition, the paradigm also controlled for whether the social judgment was towards the participants or towards other fictitious players. By creating a "self" and "other" distinction, we show that right AI and dACC are involved in processing the salience of being judged by others, irrespective of the quality of this judgment. This finding supports the idea that these regions are not specific to social rejection or even to pain or metaphorically painful experiences, but activate to self-relevant, highly salient information.

  • 12.
    Sacchet, Matthew D.
    et al.
    Stanford University, USA; VA Boston Healthcare Syst, MA 02130 USA.
    Levy, Benjamin J.
    VA Boston Healthcare Syst, MA 02130 USA; University of San Francisco, CA 94117 USA.
    Hamilton, Paul J.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten. VA Boston Healthcare Syst, MA 02130 USA.
    Maksimovskiy, Arkadiy
    VA Boston Healthcare Syst, MA 02130 USA; Boston University, MA 02118 USA.
    Hertel, Paula T.
    VA Boston Healthcare Syst, MA 02130 USA; Trinity University, TX 78212 USA.
    Joormann, Jutta
    VA Boston Healthcare Syst, MA 02130 USA; Yale University, CT USA.
    Anderson, Michael C.
    VA Boston Healthcare Syst, MA 02130 USA; University of Cambridge, England.
    Wagner, Anthony D.
    Stanford University, CA 94305 USA; Stanford University, CA 94305 USA; VA Boston Healthcare Syst, MA 02130 USA.
    Gotlib, Ian H.
    Stanford University, CA 94305 USA; Stanford University, CA 94305 USA; VA Boston Healthcare Syst, MA 02130 USA.
    Cognitive and neural consequences of memory suppression in major depressive disorder2017Ingår i: Cognitive, Affective, & Behavioral Neuroscience, ISSN 1530-7026, E-ISSN 1531-135X, Vol. 17, nr 1, s. 77-93Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Negative biases in cognition have been documented consistently in major depressive disorder (MDD), including difficulties in the ability to control the processing of negative material. Although negative information-processing biases have been studied using both behavioral and neuroimaging paradigms, relatively little research has been conducted examining the difficulties of depressed persons with inhibiting the retrieval of negative information from long-term memory. In this study, we used the think/no-think paradigm and functional magnetic resonance imaging to assess the cognitive and neural consequences of memory suppression in individuals diagnosed with depression and in healthy controls. The participants showed typical behavioral forgetting effects, but contrary to our hypotheses, there were no differences between the depressed and nondepressed participants or between neutral and negative memories. Relative to controls, depressed individuals exhibited greater activity in right middle frontal gyrus during memory suppression, regardless of the valence of the suppressed stimuli, and differential activity in the amygdala and hippocampus during memory suppression involving negatively valenced stimuli. These findings indicate that depressed individuals are characterized by neural anomalies during the suppression of long-term memories, increasing our understanding of the brain bases of negative cognitive biases in MDD.

  • 13.
    Sailer, Uta
    et al.
    University of Gothenburg, Sweden; University of Oslo, Norway.
    Triscoli, Chantal
    University of Gothenburg, Sweden; Sahlgrens University Hospital, Sweden.
    Haggblad, Gisela
    Gothenburg University, Sweden.
    Hamilton, Paul
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för social och affektiv neurovetenskap (CSAN).
    Olausson, Håkan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Sahlgrens University Hospital, Sweden.
    Croy, Ilona
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Technical University of Dresden, Germany.
    Temporal dynamics of brain activation during 40 minutes of pleasant touch2016Ingår i: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 139, s. 360-367Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Touch is important for individuals subjective well-being, is typically rewarding, and is one of few sensory stimuli which are experienced as pleasant for a rather long time. This study tracked brain activation during slow stroking stimulation of the arm that was applied continuously for 40 min - a much longer time than what previous studies have investigated. Methods: 25 subjects were stroked for 40 min with a soft brush while they were scanned with functional Magnetic Resonance Imaging, and rated the perceived pleasantness of the brush stroking. Two resting baselines were included. Whole brain-based analyses investigated the neural response to long-lasting stroking. Results: Stroking was perceived as pleasant throughout scanning and activated areas that were previously found to be involved in the processing of pleasant touch. Activation in primary somatosensory cortex (S1) and S2, subdivision OP1, decreased over time, whereas activation in orbito-frontal gyrus (OFC) and putamen strongly increased until reaching a plateau after approximately 20 min. Similarly, functional connectivity of posterior insula with middle cingulate and striatal regions increased over time. Discussion: Long-lasting stroking was processed in similar areas as shorter-lasting stroking. The decreased activation in somatosensory cortices over time may represent stimulus habituation, whereas increased activation in OFC and putamen may relate to the stimulations subjective reward value. This involvement of reward-related brain circuits can facilitate maintenance of long-lasting social touch interactions. (C) 2016 The Authors. Published by Elsevier Inc.

  • 14.
    Strauss, Timmy
    et al.
    Tech Univ Dresden, Germany.
    Kämpe, Robin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten.
    Hamilton, Paul
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten.
    Olausson, Håkan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten.
    Rottstaedt, Fabian
    Tech Univ Dresden, Germany.
    Raue, Claudia
    Tech Univ Dresden, Germany.
    Croy, Ilona
    Tech Univ Dresden, Germany.
    Deactivation of default mode network during touch2019Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, artikel-id 1293Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Interpersonal touch possesses a strong affective component, which immediately evokes attention. The neural processing of such touch is moderated by specialized C-tactile nerve fibers in the periphery and results in central activation of somatosensory areas as well as regions involved in social processing, such as the superior temporal gyrus (STG). In the present functional neuroimaging investigation, we tested the hypothesis that the attention grasping effect of interpersonal touch as compared to impersonal touch is reflected in a more-pronounced deactivation of the default mode network (DMN). Using functional magnetic resonance imaging, we investigated the neural processing of interpersonal relative to impersonal touch conditions that were furthermore modulated by stroking velocity in order to target c-tactile nerve fibers to a different extent. A sample of 30 healthy participants (19 women, mean age 40.5 years) was investigated. In the impersonal touch, participants were stroked with a brush on the forearm. In the interpersonal touch condition, the experimenter performed the stroking with the palm of his hand. Interpersonal touch was rated as more pleasant and intense than impersonal touch and led to a stronger blood oxygen level dependent (BOLD) signal increase in the somatosensory cortex SII extending to the superior temporal cortex. Over all touch conditions, this activation was coupled in time to the deactivation of prominent nodes of the DMN. Although deactivation of the DMN was most pronounced for interpersonal touch conditions, the direct comparison did not show significant differences in DMN deactivation between interpersonal and impersonal touch or between different stroking velocities. We therefore conclude that all applied touch conditions deactivate the DMN and the strong connection to areas which code the contextual and social characteristics of affective touch may explain the attention grasping effect of touch.

  • 15.
    Strauss, Timmy
    et al.
    Tech Univ Dresden, Germany.
    Rottstaedt, Fabian
    Tech Univ Dresden, Germany.
    Sailer, Uta
    Univ Oslo, Norway.
    Schellong, Julia
    Tech Univ Dresden, Germany.
    Hamilton, Paul J.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Centrum för social och affektiv neurovetenskap. Linköpings universitet, Medicinska fakulteten.
    Raue, Claudia
    Tech Univ Dresden, Germany.
    Weidner, Kerstin
    Tech Univ Dresden, Germany.
    Croy, Ilona
    Tech Univ Dresden, Germany.
    Touch aversion in patients with interpersonal traumatization2019Ingår i: Depression and anxiety (Print), ISSN 1091-4269, E-ISSN 1520-6394, Vol. 36, nr 7, s. 635-646Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Interpersonal touch is a key aspect of human interaction and a usually very comforting experience. For patients suffering from posttraumatic stress disorders (PTSD) caused by interpersonal traumatization, such touch is affectively ambiguous. Methods In two studies, we investigated the experience and neural processing of various types of interpersonal and impersonal touch in patients as compared with healthy controls. Results Patients strongly disliked show, interpersonal skin-to-skin stroking, while controls appreciated this kind of touch. No group differences were observed for ratings of impersonal touch. Similarly, the neural activation differed between groups for interpersonal, but not for impersonal touch. The interpersonal touch aversion in patients was accompanied by enhanced blood-oxygen-level-dependent response in the superior temporal gyrus and by a pronounced reduction of response in the hippocampus. This reduction was significantly correlated to symptoms of negative alterations and arousal within the patients. Conclusion We interpret the hippocampal suppression as an attempt to control traumatic memories, evoked by interpersonal touch. This mechanism may maintain the aversion of interpersonal touch in patients with interpersonal trauma-related PTSD.

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