uu.seUppsala University Publications
Change search
Link to record
Permanent link

Direct link
BETA
Fredriksson, M
Alternative names
Publications (10 of 163) Show all publications
Frick, A., Engman, J., Wahlstedt, K., Gingnell, M., Fredrikson, M. & Furmark, T. (2018). Anterior cingulate cortex activity as a candidate biomarker for treatment selection in social anxiety disorder. BJPsych bulletin, 4(3)
Open this publication in new window or tab >>Anterior cingulate cortex activity as a candidate biomarker for treatment selection in social anxiety disorder
Show others...
2018 (English)In: BJPsych bulletin, ISSN 2056-4694, E-ISSN 2056-4708, Vol. 4, no 3Article in journal (Refereed) Published
Abstract [en]

We aimed to identify biomarkers to guide the decision to add selective serotonin reuptake inhibitors (SSRI) to psychological treatment for social anxiety disorder (SAD). Forty-eight patients with SAD underwent functional magnetic resonance imaging and collection of clinical and demographic variables before treatment with cognitive–behavioural therapy, combined on a double-blind basis with either escitalopram or placebo for 9 weeks. Pre-treatment neural reactivity to aversive faces in the dorsal anterior cingulate cortex (ACC), but not clinical/demographic variables, moderated clinical outcomes. Cross-validated individual-level predictions accurately identified 81% of responders/non-responders. Dorsal ACC reactivity is thus a potential biomarker for SAD treatment selection.

Place, publisher, year, edition, pages
Cambridges Institutes Press, 2018
Keywords
Functional magnetic resonance imaging, anxiety, prediction, selective serotonin reuptake inhibitors, cognitive–behavioural therapy, social phobia
National Category
Psychology Psychiatry
Identifiers
urn:nbn:se:uu:diva-353596 (URN)10.1192/bjo.2018.15 (DOI)000436933400012 ()29922481 (PubMedID)
Funder
Swedish Research CouncilRiksbankens JubileumsfondThe Swedish Brain FoundationForte, Swedish Research Council for Health, Working Life and WelfareSwedish Society for Medical Research (SSMF)
Available from: 2018-06-14 Created: 2018-06-14 Last updated: 2018-09-26Bibliographically approved
Brusini, I., Carneiro, M., Wang, C., Rubin, C.-J., Ring, H., Afonso, S., . . . Andersson, L. (2018). Changes in brain architecture are consistent with altered fear processing in domestic rabbits. Proceedings of the National Academy of Sciences of the United States of America, 115(28), 7380-7385
Open this publication in new window or tab >>Changes in brain architecture are consistent with altered fear processing in domestic rabbits
Show others...
2018 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 115, no 28, p. 7380-7385Article in journal (Refereed) Published
Abstract [en]

The most characteristic feature of domestic animals is their change in behavior associated with selection for tameness. Here we show, using high-resolution brain magnetic resonance imaging in wild and domestic rabbits, that domestication reduced amygdala volume and enlarged medial prefrontal cortex volume, supporting that areas driving fear have lost volume while areas modulating negative affect have gained volume during domestication. In contrast to the localized gray matter alterations, white matter anisotropy was reduced in the corona radiata, corpus callosum, and the subcortical white matter. This suggests a compromised white matter structural integrity in projection and association fibers affecting both afferent and efferent neural flow, consistent with reduced neural processing. We propose that compared with their wild ancestors, domestic rabbits are less fearful and have an attenuated flight response because of these changes in brain architecture.

National Category
Psychology Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-355452 (URN)10.1073/pnas.1801024115 (DOI)000438050900076 ()29941556 (PubMedID)
Funder
Knut and Alice Wallenberg FoundationSwedish Research CouncilThe Swedish Brain FoundationEuropean Social Fund (ESF)
Available from: 2018-06-29 Created: 2018-06-29 Last updated: 2018-09-25Bibliographically 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
Show others...
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: 2018-02-19Bibliographically approved
Engman, J., Sundström Poromaa, I., Moby, L., Wikström, J., Fredriksson, M. & Gingnell, M. (2018). Hormonal Cycle and Contraceptive Effects on Amygdala and Salience Resting-State Networks in Women with Previous Affective Side Effects on the Pill.. Neuropsychopharmacology, 43(3), 555-563
Open this publication in new window or tab >>Hormonal Cycle and Contraceptive Effects on Amygdala and Salience Resting-State Networks in Women with Previous Affective Side Effects on the Pill.
Show others...
2018 (English)In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 43, no 3, p. 555-563Article in journal (Refereed) Published
Abstract [en]

The mechanisms linking ovarian hormones to negative affect are poorly characterized, but important clues may come from the examination of the brain's intrinsic organization. Here, we studied the effects of both the menstrual cycle and oral contraceptives (OCs) on amygdala and salience network resting-state functional connectivity using a double-blind, randomized, and placebo-controlled design. Hormone levels, depressive symptoms, and resting-state functional connectivity were measured in 35 healthy women (24.9±4.2 years) who had previously experienced OC-related negative affect. All participants were examined in the follicular phase of a baseline cycle and in the third week of the subsequent cycle during treatment with either a combined OC (30 μg ethinyl estradiol/0.15 mg levonorgestrel) or placebo. The latter time point targeted the midluteal phase in placebo users and steady-state ethinyl estradiol and levonorgestrel concentrations in OC users. Amygdala and salience network connectivity generally increased with both higher endogenous and synthetic hormone levels, although amygdala-parietal cortical connectivity decreased in OC users. When in the luteal phase, the naturally cycling placebo users demonstrated higher connectivity in both networks compared with the women receiving OCs. Our results support a causal link between the exogenous administration of synthetic hormones and amygdala and salience network connectivity. Furthermore, they suggest a similar, potentially stronger, association between the natural hormonal variations across the menstrual cycle and intrinsic network connectivity.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-333689 (URN)10.1038/npp.2017.157 (DOI)000419961500011 ()28741624 (PubMedID)
Funder
Swedish Research Council, 2016-01439Forte, Swedish Research Council for Health, Working Life and Welfare, 2007-1955, 2007-2116
Available from: 2017-11-16 Created: 2017-11-16 Last updated: 2018-02-14Bibliographically approved
Ågren, T., Björkstrand, J. & Fredriksson, M. (2017). Disruption of human fear reconsolidation using imaginal and in vivo extinction. Behavioural Brain Research, 319, 9-15
Open this publication in new window or tab >>Disruption of human fear reconsolidation using imaginal and in vivo extinction
2017 (English)In: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 319, p. 9-15Article in journal (Refereed) Published
Abstract [en]

Abstract Memories are not set forever, but can be altered following reactivation, which renders memories malleable, before they are again stabilized through reconsolidation. Fear memories can be attenuated by using extinction during the malleable period. The present study adopts a novel form of extinction, using verbal instructions, in order to examine whether fear memory reconsolidation can be affected by an imaginal exposure. The extinction using verbal instructions, called imaginal extinction, consists of a recorded voice encouraging participants to imagine the scene in which fear was acquired, and to envision the stimuli before their inner eye. The voice signals stimuli appearance, and identical to standard (in vivo) extinction, participants discover that the conditioned stimulus no longer is followed by unconditioned stimulus (UCS). In this way, imaginal extinction translates clinically used imaginal exposure into the standard experimental fear conditioning paradigm. Fear was acquired by pairing pictorial stimuli with an electric shock UCS. Then, both standard and imaginal extinction were given following fear memory reactivation, either after 10 min, within the reconsolidation interval, or after 6 h, outside of the reconsolidation interval. In vivo and imaginal extinction produced comparable reductions in conditioned responses during extinction and importantly, both disrupted reconsolidation of conditioned fear and abolished stimulus discrimination between reinforced and non-reinforced cues. Thus, disrupted reconsolidation of fear conditioning can be achieved without in vivo stimulus presentation, through purely cognitive means, suggesting possible therapeutic applications.

Keywords
Memory reconsolidation, Fear conditioning, Fear extinction, Imaginal exposure, Reinstatement
National Category
Psychology
Identifiers
urn:nbn:se:uu:diva-310376 (URN)10.1016/j.bbr.2016.11.014 (DOI)000392558300002 ()27840245 (PubMedID)
Funder
Swedish Research Council
Available from: 2016-12-14 Created: 2016-12-14 Last updated: 2017-11-29Bibliographically approved
Faria, V., Gingnell, M., M. Hoppe, J., Hjorth, O., Alaie, I., Frick, A., . . . Furmark, T. (2017). Do You Believe It? Verbal Suggestions Influence the Clinical and Neural Effects of Escitalopram in Social Anxiety Disorder: A Randomized Trial. EBioMedicine (24), 179-188, Article ID S2352-3964(17)30385-7.
Open this publication in new window or tab >>Do You Believe It? Verbal Suggestions Influence the Clinical and Neural Effects of Escitalopram in Social Anxiety Disorder: A Randomized Trial
Show others...
2017 (English)In: EBioMedicine, ISSN 0360-0637, E-ISSN 2352-3964, no 24, p. 179-188, article id S2352-3964(17)30385-7Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for depression and anxiety, but their efficacy relative to placebo has been questioned. We aimed to test how manipulation of verbally induced expectancies, central for placebo, influences SSRI treatment outcome and brain activity in patients with social anxiety disorder (SAD).

METHODS: We did a randomized clinical trial, within an academic medical center (Uppsala, Sweden), of individuals fulfilling the DSM-IV criteria for SAD, recruited through media advertising. Participants were 18years or older and randomized in blocks, through a computer-generated sequence by an independent party, to nine weeks of overt or covert treatment with escitalopram (20mg daily). The overt group received correct treatment information whereas the covert group was treated deceptively with the SSRI described, by the psychiatrist, as active placebo. The treating psychiatrist was necessarily unmasked while the research staff was masked from intervention assignment. Treatment efficacy was assessed primarily with the self-rated Liebowitz Social Anxiety Scale (LSAS-SR), administered at week 0, 1, 3, 6 and 9, also yielding a dichotomous estimate of responder status (clinically significant improvement). Before and at the last week of treatment, brain activity during an emotional face-matching task was assessed with functional magnetic resonance imaging (fMRI) and during fMRI sessions, anticipatory speech anxiety was also assessed with the Spielberger State-Trait Anxiety Inventory - State version (STAI-S). Analyses included all randomized patients with outcome data at posttreatment. This study is registered at ISRCTN, number 98890605.

FINDINGS: Between March 17th 2014 and May 22nd 2015, 47 patients were recruited. One patient in the covert group dropped out after a few days of treatment and did not provide fMRI data, leaving 46 patients with complete outcome data. After nine weeks of treatment, overt (n=24) as compared to covert (n=22) SSRI administration yielded significantly better outcome on the LSAS-SR (adjusted difference 21.17, 95% CI 10.69-31.65, p<0.0001) with more than three times higher response rate (50% vs. 14%; χ(2)(1)=6.91, p=0.009) and twice the effect size (d=2.24 vs. d=1.13) from pre-to posttreatment. There was no significant between-group difference on anticipatory speech anxiety (STAI-S), both groups improving with treatment. No serious adverse reactions were recorded. On fMRI outcomes, there was suggestive evidence for a differential neural response to treatment between groups in the posterior cingulate, superior temporal and inferior frontal gyri (all z thresholds exceeding 3.68, p≤0.001). Reduced social anxiety with treatment correlated significantly with enhanced posterior cingulate (z threshold 3.24, p=0.0006) and attenuated amygdala (z threshold 2.70, p=0.003) activity.

INTERPRETATION: The clinical and neural effects of escitalopram were markedly influenced by verbal suggestions. This points to a pronounced placebo component in SSRI-treatment of SAD and favors a biopsychosocial over a biomedical explanatory model for SSRI efficacy.

FUNDING RESOURCES: The Swedish Research Council for Working Life and Social Research (grant 2011-1368), the Swedish Research Council (grant 421-2013-1366), Riksbankens Jubileumsfond - the Swedish Foundation for Humanities and Social Sciences (grant P13-1270:1).

Keywords
Expectancies, Neuroimaging, Placebo effect, SSRI, Social anxiety disorder, fMRI
National Category
Psychology General Practice
Identifiers
urn:nbn:se:uu:diva-331755 (URN)10.1016/j.ebiom.2017.09.031 (DOI)000414392900030 ()29033138 (PubMedID)
Funder
Forte, Swedish Research Council for Health, Working Life and Welfare, 2011-1368Swedish Research Council, 421-2013-1366Riksbankens Jubileumsfond, P13-1270:1
Note

Vanda Faria and Malin Gingnell contributed equally

Available from: 2017-10-18 Created: 2017-10-18 Last updated: 2018-02-12Bibliographically approved
Bas-Hoogendam, J. M., van Steenbergen, H., Pannekoek, J. N., Fouche, J.-P., Lochner, C., Hattingh, C. J., . . . van der Wee, N. J. J. (2017). Sample Size Matters: A Voxel-Based Morphometry Multi-Center Mega-Analysis of Gray Matter Volume in Social Anxiety Disorder. Paper presented at 72nd Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry (SOBP), MAY 18-20, 2017, San Diego, CA. Biological Psychiatry, 81(10), S7-S8
Open this publication in new window or tab >>Sample Size Matters: A Voxel-Based Morphometry Multi-Center Mega-Analysis of Gray Matter Volume in Social Anxiety Disorder
Show others...
2017 (English)In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 81, no 10, p. S7-S8Article in journal, Meeting abstract (Other academic) Published
Keywords
Social Anxiety Disorder, Voxel Based Morphometry
National Category
Psychology
Identifiers
urn:nbn:se:uu:diva-331803 (URN)10.1016/j.biopsych.2017.02.027 (DOI)000400348700017 ()
Conference
72nd Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry (SOBP), MAY 18-20, 2017, San Diego, CA
Funder
Swedish Research CouncilForte, Swedish Research Council for Health, Working Life and WelfareEU, FP7, Seventh Framework Programme
Available from: 2017-10-19 Created: 2017-10-19 Last updated: 2017-10-19Bibliographically 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.
Show others...
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
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
Show others...
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
Aarnio, M., Appel, L., Fredriksson, M., Gordh, T., Wolf, O., Sörensen, J., . . . Linnman, C. (2017). Visualization of painful inflammation in patients with pain after traumatic ankle sprain using [(11)C]-D-deprenyl PET/CT.. Scandinavian Journal of Pain, 17, 418-424
Open this publication in new window or tab >>Visualization of painful inflammation in patients with pain after traumatic ankle sprain using [(11)C]-D-deprenyl PET/CT.
Show others...
2017 (English)In: Scandinavian Journal of Pain, ISSN 1877-8860, E-ISSN 1877-8879, Vol. 17, p. 418-424Article in journal (Refereed) Published
Abstract [en]

BACKGROUND AND AIMS: Positron emission tomography (PET) with the radioligand [(11)C]-D-deprenyl has shown increased signal at location of pain in patients with rheumatoid arthritis and chronic whiplash injury. The binding site of [(11)C]-D-deprenyl in peripheral tissues is suggested to be mitochondrial monoamine oxidase in cells engaged in post-traumatic inflammation and tissue repair processes. The association between [(11)C]-D-deprenyl uptake and the transition from acute to chronic pain remain unknown. Further imaging studies of musculoskeletal pain at the molecular level would benefit from establishing a clinical model in a common and well-defined injury in otherwise healthy and drug-naïve subjects. The aim of this study was to investigate if [(11)C]-D-deprenyl uptake would be acutely elevated in unilateral ankle sprain and if tracer uptake would be reduced as a function of healing, and correlated with pain localizations and pain experience.

METHODS: Eight otherwise healthy patients with unilateral ankle sprain were recruited at the emergency department. All underwent [(11)C]-D-deprenyl PET/CT in the acute phase, at one month and 6-14 months after injury.

RESULTS: Acute [(11)C]-D-deprenyl uptake at the injury site was a factor of 10.7 (range 2.9-37.3) higher than the intact ankle. During healing, [(11)C]-D-deprenyl uptake decreased, but did not normalize until after 11 months. Patients experiencing persistent pain had prolonged [(11)C]-D-deprenyl uptake in painful locations.

CONCLUSIONS AND IMPLICATIONS: The data provide further support that [(11)C]-D-deprenyl PET can visualize, quantify and follow processes in peripheral tissue that may relate to soft tissue injuries, inflammation and associated nociceptive signaling. Such an objective correlate would represent a progress in pain research, as well as in clinical pain diagnostics and management.

Keywords
Ankle injuries, Carbon-11, Deprenyl, Inflammation, PET, Pain
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-333782 (URN)10.1016/j.sjpain.2017.10.008 (DOI)000419851500070 ()29126847 (PubMedID)
Available from: 2017-11-16 Created: 2017-11-16 Last updated: 2018-04-09Bibliographically approved
Organisations

Search in DiVA

Show all publications