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Motilla Hoppe, J., Frick, A., Åhs, F., Linnman, C., Appel, L., Jonasson, M., . . . Furmark, T. (2018). Association between amygdala neurokinin-1 receptor availability and anxiety-related personality traits. Translational Psychiatry, 8(1), 168
Open this publication in new window or tab >>Association between amygdala neurokinin-1 receptor availability and anxiety-related personality traits
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2018 (English)In: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 8, no 1, p. 168-Article in journal (Refereed) Published
Abstract [en]

Animal studies indicate that substance P (SP) and its preferred neurokinin-1 (NK1) receptor modulate stress and anxiety-related behavior. Alterations in the SP-NK1 system have also been observed in human anxiety disorders, yet little is known about the relation between this system and individual differences in personality traits associated with anxiety propensity and approach-avoidance behavior, including trait anxiety, neuroticism, and extraversion. Exploring this relation could provide important insights into the neurobiological underpinnings of human anxiety and the etiology of anxiety disorders, as anxious traits are associated with increased susceptibility to develop psychopathological conditions. Here we examined the relationship between central NK1 receptor availability and self-rated measures of trait anxiety, neuroticism, and extraversion. The amygdala was chosen as the primary region of interest since this structure has been suggested to mediate the effect of the SP-NK1 system on anxiety. Anxious traits and NK1 receptor availability, determined with positron emission tomography and the radiotracer [11C]GR205171, were measured in 17 healthy individuals. Voxel-wise analyses showed a significant positive correlation between bilateral amygdala NK1 receptor availability and trait anxiety, and a trend in similar direction was observed for neuroticism. Conversely, extraversion was found to be negatively associated with amygdala NK1 receptor availability. Extraversion also correlated negatively with the NK1 measure in the cuneus/precuneus and fusiform gyrus according to exploratory whole-brain analyses. In conclusion, our findings indicate that amygdala NK1 receptor availability is associated with anxiety-related personality traits in healthy subjects, consistent with a modulatory role for the SP-NK1 system in human anxiety.

National Category
Pedagogy
Identifiers
urn:nbn:se:uu:diva-358759 (URN)10.1038/s41398-018-0163-1 (DOI)000443079700001 ()
Available from: 2018-08-31 Created: 2018-08-31 Last updated: 2018-12-10Bibliographically approved
Åhs, F., Rosén, J., Kastrati, G., Fredrikson, M., Ågren, T. & Lundstrom, J. N. (2018). Biological preparedness and resistance to extinction of skin conductance responses conditioned to fear relevant animal pictures: A systematic review. Neuroscience and Biobehavioral Reviews, 95, 430-437
Open this publication in new window or tab >>Biological preparedness and resistance to extinction of skin conductance responses conditioned to fear relevant animal pictures: A systematic review
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2018 (English)In: Neuroscience and Biobehavioral Reviews, ISSN 0149-7634, E-ISSN 1873-7528, Vol. 95, p. 430-437Article, review/survey (Refereed) Published
Abstract [en]

Preparedness theory is one of the most influential ideas in explaining the origin of specific phobias. The theory proposes that fear conditioning is selective to animals that have posed a threat to survival throughout human evolution, and that acquired fear memories to such threats are resistant to extinction. We reviewed fear conditioning studies testing whether autonomic responses conditioned to pictures of snakes and spiders show greater resistance to extinction than neutral cues. We identified 32 fear conditioning experiments published in 23 studies including 1887 participants. Increased resistance to extinction of conditioned responses to snake and spider pictures was found in 10 (31%) of the experiments, whereas 22 (69%) experiments did not support the hypothesis. Thus, the body of evidence suggests that preparedness theory does not explain the origin of specific phobias.

Keywords
Resistance to extinction, SCR, Phobia, Fear conditioning, Emotion, Evolution
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-373074 (URN)10.1016/j.neubiorev.2018.10.017 (DOI)000453337400027 ()30381252 (PubMedID)
Funder
Swedish Research CouncilKnut and Alice Wallenberg Foundation, KAW 2012.0141
Available from: 2019-01-11 Created: 2019-01-11 Last updated: 2019-01-11Bibliographically approved
Mårtensson, J., Lätt, J., Åhs, F., Fredriksson, M., Söderlund, H., Schiöth, H. B., . . . Nilsson, M. (2018). Diffusion tensor imaging and tractography of the white matter in normal aging: The rate-of-change differs between segments within tracts. Magnetic Resonance Imaging, 45, 113-119, Article ID S0730-725X(17)30059-0.
Open this publication in new window or tab >>Diffusion tensor imaging and tractography of the white matter in normal aging: The rate-of-change differs between segments within tracts
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2018 (English)In: Magnetic Resonance Imaging, ISSN 0730-725X, E-ISSN 1873-5894, Vol. 45, p. 113-119, article id S0730-725X(17)30059-0Article in journal (Refereed) Published
Abstract [en]

Knowledge concerning the normal aging of cerebral white matter will improve our understanding of abnormal changes in neurodegenerative diseases. The microstructural basis of white matter maturation and aging can be investigated using diffusion tensor imaging (DTI). Generally, diffusion anisotropy increases during childhood and adolescence followed by a decline in middle age. However, this process is subject to spatial variations between tracts. The aim of this study was to investigate to what extent age-related variations also occur within tracts. DTI parameters were compared between segments of two white matter tracts, the cingulate bundle (CB) and the inferior fronto-occipital fasciculus (IFO), in 257 healthy individuals between 13 and 84years of age. Segments of the CB and the IFO were extracted and parameters for each segment were averaged across the hemispheres. The data was analysed as a function of age. Results show that age-related changes differ both between and within individual tracts. Different age trajectories were observed in all segments of the analysed tracts for all DTI parameters. In conclusion, aging does not affect white matter tracts uniformly but is regionally specific; both between and within white matter tracts.

Keywords
Tractography, Inferior fronto-occipital fasciculus, Cingulum, Aging, White matter degeneration, White matter tract
National Category
Medical and Health Sciences Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-319599 (URN)10.1016/j.mri.2017.03.007 (DOI)000417772500015 ()28359912 (PubMedID)
Available from: 2017-04-06 Created: 2017-04-06 Last updated: 2019-03-15Bibliographically approved
Frans, Ö., Åhs, J., Bihre, E. & Åhs, F. (2018). Distance to Threat and Risk of Acute and Posttraumatic Stress Disorder Following Bank Robbery: A longitudinal study. Psychiatry Research, 267, 461-466
Open this publication in new window or tab >>Distance to Threat and Risk of Acute and Posttraumatic Stress Disorder Following Bank Robbery: A longitudinal study
2018 (English)In: Psychiatry Research, ISSN 0165-1781, E-ISSN 1872-7123, Vol. 267, p. 461-466Article in journal (Refereed) Published
Abstract [en]
  • Environmental factors surrounding trauma influencing PTSD risk are understudied.
  • Proximal distances to threatening individuals could increase PTSD risk directly or indirectly by increasing ASD risk.
  • Proximity to robber, ASD and PTSD was assessed in bank employees following robbery.
  • We found that proximity to robber increase PTSD risk indirectly by increasing ASD risk.
  • We speculate that proximity to threat may increase stress and arousal making trauma memories intrusive.
Abstract [en]

Identifying pathways through which environmental risk factors influence PTSD is important for understanding PTSD etiology. Here, we hypothesized that the physical proximity to threat influences PTSD risk by increasing ASD following trauma. One hundred six bank employees who had experienced a bank robbery participated in the study. A longitudinal design assessing ASD at day 2 and PTSD at day 30 was used to test the hypothesis. Participants also indicated their location in the bank at the time of the robbery. ASD was identified in 40 (38%) and PTSD in 16 (15%) of the robbery victims. Distance to the robber had a strong effect on ASD (OR 3.51, 95% CI 1.94-6.34) and a somewhat lesser effect on PTSD (OR 2.15, 95% CI 1.04-4.46), indicating that the effect of proximity to threat on PTSD 1 month following trauma could be mediated by its effect on ASD 2 days following trauma. Using structural equation modeling, we confirmed that the effect of distance on PTSD was fully mediated by ASD. These findings suggest that proximity to threat may increase PTSD risk by enhancing the acute stress response following trauma.

Place, publisher, year, edition, pages
Elsevier, 2018
National Category
Psychiatry
Identifiers
urn:nbn:se:uu:diva-355450 (URN)10.1016/j.psychres.2018.06.050 (DOI)000445983700068 ()
Funder
Swedish Research Council, 2014-1160Länsförsäkringar AB
Available from: 2018-06-29 Created: 2018-06-29 Last updated: 2018-12-07Bibliographically approved
Juvrud, J., Gredebäck, G., Åhs, F., Lerin, N., Nyström, P., Kastrati, G. & Rosén, J. (2018). The Immersive Virtual Reality Lab: Possibilities for Remote Experimental Manipulations of Autonomic Activity on a Large Scale. Frontiers in Neuroscience, 12, Article ID 305.
Open this publication in new window or tab >>The Immersive Virtual Reality Lab: Possibilities for Remote Experimental Manipulations of Autonomic Activity on a Large Scale
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2018 (English)In: Frontiers in Neuroscience, ISSN 1662-4548, E-ISSN 1662-453X, Vol. 12, article id 305Article in journal (Refereed) Published
Abstract [en]

There is a need for large-scale remote data collection in a controlled environment, and the in-home availability of virtual reality (VR) and the commercial availability of eye tracking for VR present unique and exciting opportunities for researchers. We propose and provide a proof-of-concept assessment of a robust system for large-scale in-home testing using consumer products that combines psychophysiological measures and VR, here referred to as a Virtual Lab. For the first time, this method is validated by correlating autonomic responses, skin conductance response (SCR), and pupillary dilation, in response to a spider, a beetle, and a ball using commercially available VR. Participants demonstrated greater SCR and pupillary responses to the spider, and the effect was dependent on the proximity of the stimuli to the participant, with a stronger response when the spider was close to the virtual self. We replicated these effects across two experiments and in separate physical room contexts to mimic variability in home environment. Together, these findings demonstrate the utility of pupil dilation as a marker of autonomic arousal and the feasibility to assess this in commercially available VR hardware and support a robust Virtual Lab tool for massive remote testing.

Keywords
virtual reality, eye tracking, pupil dilation, SCR, autonomic response
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-356497 (URN)10.3389/fnins.2018.00305 (DOI)000431692600001 ()29867318 (PubMedID)
Funder
Swedish Research Council, 2014-1160
Available from: 2018-07-30 Created: 2018-07-30 Last updated: 2018-07-30Bibliographically approved
Latini, F., Mårtensson, J., Larsson, E.-M., Fredriksson, M., Åhs, F., Hjortberg, M., . . . Ryttlefors, M. (2017). Segmentation of the inferior longitudinal fasciculus in the human brain: A white matter dissection and diffusion tensor tractography study.. Brain Research (1675), 102-115, Article ID S0006-8993(17)30386-4.
Open this publication in new window or tab >>Segmentation of the inferior longitudinal fasciculus in the human brain: A white matter dissection and diffusion tensor tractography study.
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2017 (English)In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, no 1675, p. 102-115, article id S0006-8993(17)30386-4Article in journal (Refereed) Published
Abstract [en]

The inferior longitudinal fascicle (ILF) is one of the major occipital-temporal association pathways. Several studies have mapped its hierarchical segmentation to specific functions. There is, however, no consensus regarding a detailed description of ILF fibre organisation. The aim of this study was to establish whether the ILF has a constant number of subcomponents. A secondary aim was to determine the quantitative diffusion proprieties of each subcomponent and assess their anatomical trajectories and connectivity patterns. A white matter dissection of 14 post-mortem normal human hemispheres was conducted to define the course of the ILF and its subcomponents. These anatomical results were then investigated in 24 right-handed, healthy volunteers using in vivo diffusion tensor imaging (DTI) and streamline tractography. Fractional anisotropy (FA), volume, fibre length and the symmetry coefficient of each fibre group were analysed. In order to show the connectivity pattern of the ILF, we also conducted an analysis of the cortical terminations of each segment. We confirmed that the main structure of the ILF is composed of three constant components reflecting the occipital terminations: the fusiform, the lingual and the dorsolateral-occipital. ILF volume was significantly lateralised to the right. The examined indices of ILF subcomponents did not show any significant difference in lateralisation. The connectivity pattern and the quantitative distribution of ILF subcomponents suggest a pivotal role for this bundle in integrating information from highly specialised modular visual areas with activity in anterior temporal territory, which has been previously shown to be important for memory and emotions.

Keywords
DTT, ILF, Occipital-temporal connectivity, Social cognition, Visual memory, White matter
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-329751 (URN)10.1016/j.brainres.2017.09.005 (DOI)000413608600011 ()28899757 (PubMedID)
Available from: 2017-09-20 Created: 2017-09-20 Last updated: 2018-02-02Bibliographically approved
Rosén, J., Kastrati, G. & Åhs, F. (2017). Social, proximal and conditioned threat. Neurobiology of Learning and Memory, 142, part B, 236-243
Open this publication in new window or tab >>Social, proximal and conditioned threat
2017 (English)In: Neurobiology of Learning and Memory, ISSN 1074-7427, E-ISSN 1095-9564, Vol. 142, part B, p. 236-243Article in journal (Refereed) Published
Abstract [en]

Responding to threats in the environment is crucial for survival. Certain types of threat produce defensive responses without necessitating previous experience and are considered innate, whereas other threats are learned by experiencing aversive consequences. Two important innate threats are whether an encountered stimulus is a member of the same species (social threat) and whether a stimulus suddenly appears proximal to the body (proximal threat). These threats are manifested early in human development and robustly elicit defensive responses. Learned threat, on the other hand, enables adaptation to threats in the environment throughout the life span. A well-studied form of learned threat is fear conditioning, during which a neutral stimulus acquires the ability to eliciting defensive responses through pairings with an aversive stimulus. If innate threats can facilitate fear conditioning, and whether different types of innate threats can enhance each other, is largely unknown. We developed an immersive virtual reality paradigm to test how innate social and proximal threats are related to each other and how they influence conditioned fear. Skin conductance responses were used to index the autonomic component of the defensive response. We found that social threat modulates proximal threat, but that neither proximal nor social threat modulates conditioned fear. Our results suggest that distinct processes regulate autonomic activity in response to proximal and social threat on the one hand, and conditioned fear on the other.

National Category
Psychology
Identifiers
urn:nbn:se:uu:diva-322732 (URN)10.1016/j.nlm.2017.05.014 (DOI)000403738900008 ()28564588 (PubMedID)
Funder
Swedish Research Council
Available from: 2017-05-29 Created: 2017-05-29 Last updated: 2019-10-24Bibliographically approved
Björkstrand, J., Ågren, T., Åhs, F., Frick, A., Larsson, E.-M., Hjorth, O., . . . Fredrikson, M. (2017). Think twice, it's all right: Long lasting effects of disrupted reconsolidation on brain and behavior in human long-term fear. Behavioural Brain Research, 324, 125-129
Open this publication in new window or tab >>Think twice, it's all right: Long lasting effects of disrupted reconsolidation on brain and behavior in human long-term fear
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2017 (English)In: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 324, p. 125-129Article in journal (Refereed) Published
Abstract [en]

Memories can be modified when recalled. Experimental fear conditioning studies support that amygdala-localized fear memories are attenuated when reconsolidation is disrupted through extinction training immediately following memory activation. Recently, using functional brain imaging in individuals with lifelong spider fears, we demonstrated that fear memory activation followed by repeated exposure to feared cues after 10 min, thereby disrupting reconsolidation, attenuated activity in the amygdala during later re-exposure, and also facilitated approach behavior to feared cues. In contrast, repeated exposure 6 h after fear memory activation, allowing for reconsolidation, did not attenuate amygdala activity and resulted in less approach behavior as compared to the group that received disrupted reconsolidation. We here evaluated if these effects are stable after 6 months and found that amygdala activity was further reduced in both groups, with a tendency towards greater reductions in the 10 min than the 6 h group. Hence, disrupted reconsolidation results in long lasting attenuation of amygdala activity. The behavioral effect, with more approach towards previously feared cues, in the 10 min than the 6 h group also persisted. Thus, the brain effect of disrupted reconsolidation is stable over 6 months and the behavioral effect also remained. We therefore conclude that disrupted reconsolidation result in a long-lasting diminished fear memory representation in the amygdala which may have clinical importance.

Keywords
Reconsolidation disruption, Extinction, Exposure therapy, Amygdala, Approach behavior, Spider fear
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-315854 (URN)10.1016/j.bbr.2017.02.016 (DOI)000397691100016 ()28214541 (PubMedID)
Funder
Swedish Research Council, 2013-2825, 2012-00804The Swedish Brain Foundation, F02014-0151
Available from: 2017-02-21 Created: 2017-02-21 Last updated: 2018-06-26Bibliographically approved
Åhs, F., Gingnell, M., Furmark, T. & Fredrikson, M. (2017). Within-session effect of repeated stress exposure on extinction circuitry function in social anxiety disorder. Psychiatry Research: Neuroimaging, 261, 85-90
Open this publication in new window or tab >>Within-session effect of repeated stress exposure on extinction circuitry function in social anxiety disorder
2017 (English)In: Psychiatry Research: Neuroimaging, ISSN 0925-4927, E-ISSN 1872-7506, Vol. 261, p. 85-90Article in journal (Refereed) Published
Abstract [en]

Anxiety reduction following repeated exposure to stressful experiences is generally held to depend on neural processes involved in extinction of conditioned fear. We predicted that repeated exposure to stressful experiences would change activity throughout the circuitry serving extinction, including ventromedial prefrontal cortex (vmPFC), the hippocampus and the amygdala. To test this prediction, 36 participants diagnosed with SAD performed two successive speeches in front of an observing audience while regional cerebral blood flow (rCBF) was recorded using positron emission tomography. To control for non-anxiolytic effects of repeated exposure, rCBF was also measured during repeated presentations of neutral and angry facial expressions. Results showed that anxiety ratings and heart rate decreased from the first to the second speech, indicating an anxiolytic effect of repeated exposure. Exposure attenuated rCBF in the amygdala whereas no change in rCBF was observed in the vmPFC or hippocampus. The rCBF-reductions in the amygdala were greater following repetition of the speech task than repetition of face exposure indicating that they were specific to anxiety attenuation and not due to a reduced novelty. Our findings suggest that amygdala-related attenuation processes are key to understanding the working mechanisms of exposure therapy.

Place, publisher, year, edition, pages
ELSEVIER IRELAND LTD, 2017
Keywords
Extinction, Social phobia, Cognitive behavior therapy, Amygdala, Hippocampus, VmPFC
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-320032 (URN)10.1016/j.pscychresns.2017.01.009 (DOI)000395958900012 ()28167379 (PubMedID)
Funder
Swedish Research CouncilThe Swedish Brain Foundation
Available from: 2017-04-13 Created: 2017-04-13 Last updated: 2017-11-29Bibliographically approved
Frick, A., Åhs, F., Michelgård Palmquist, Å., Pissiota, A., Wallenquist, U., Fernandez, M., . . . Fredrikson, M. (2016). Overlapping expression of serotonin transporters and neurokinin-1 receptors in posttraumatic stress disorder: a multi-tracer PET study. Molecular Psychiatry, 21(10), 1400-1407
Open this publication in new window or tab >>Overlapping expression of serotonin transporters and neurokinin-1 receptors in posttraumatic stress disorder: a multi-tracer PET study
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2016 (English)In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 21, no 10, p. 1400-1407Article in journal (Refereed) Published
Abstract [en]

The brain serotonergic system is colocalized and interacts with the neuropeptidergic substance P/neurokinin-1 (SP/NK1) system. Both these neurochemical systems have independently been implicated in stress and anxiety, but interactions between them might be crucial for human anxiety conditions. Here, we examined the serotonin and substance P/neurokinin-1 (SP/NK1) systems individually as well as their overlapping expression in 16 patients with posttraumatic stress disorder (PTSD) and 16 healthy controls. Participants were imaged with the highly selective radiotracers [(11)C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile (DASB) and [(11)C]GR205171 assessing serotonin transporter (SERT) and NK1 receptor availability, respectively. Voxel-wise analyses in the amygdala, our a priori-defined region of interest, revealed increased number of NK1 receptors, but not SERT in the PTSD group. Symptom severity, as indexed by the Clinician-administered PTSD Scale, was negatively related to SERT availability in the amygdala, and NK1 receptor levels moderated this relationship. Exploratory, voxel-wise whole-brain analyses revealed increased SERT availability in the precentral gyrus and posterior cingulate cortex of PTSD patients. Patients, relative to controls, displayed lower degree of overlapping expression between SERT and NK1 receptors in the putamen, thalamus, insula and lateral orbitofrontal gyrus, lower overlap being associated with higher PTSD symptom severity. Expression overlap also explained more of the symptomatology than did either system individually, underscoring the importance of taking interactions between the neurochemical systems into account. Thus, our results suggest that aberrant serotonergic-SP/NK1 couplings contribute to the pathophysiology of PTSD and, consequently, that normalization of these couplings may be therapeutically important.

National Category
Psychology
Identifiers
urn:nbn:se:uu:diva-268105 (URN)10.1038/mp.2015.180 (DOI)000384127000011 ()26619809 (PubMedID)
Funder
Swedish Research CouncilThe Swedish Brain FoundationRiksbankens JubileumsfondForte, Swedish Research Council for Health, Working Life and Welfare
Available from: 2015-12-02 Created: 2015-12-02 Last updated: 2017-12-01Bibliographically approved
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Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-6355-660x

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