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  • 1. Badoud, Simon
    et al.
    Van De Ville, Dimitri
    Nicastro, Nicolas
    Garibotto, Valentina
    Burkhard, Pierre R
    Haller, Sven
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Discriminating among degenerative parkinsonisms using advanced (123)I-ioflupane SPECT analyses2016Inngår i: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 12, s. 234-240Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    (123)I-ioflupane single photon emission computed tomography (SPECT) is a sensitive and well established imaging tool in Parkinson's disease (PD) and atypical parkinsonian syndromes (APS), yet a discrimination between PD and APS has been considered inconsistent at least based on visual inspection or simple region of interest analyses. We here reappraise this issue by applying advanced image analysis techniques to separate PD from the various APS. This study included 392 consecutive patients with degenerative parkinsonism undergoing (123)I-ioflupane SPECT at our institution over the last decade: 306 PD, 24 multiple system atrophy (MSA), 32 progressive supranuclear palsy (PSP) and 30 corticobasal degeneration (CBD) patients. Data analysis included voxel-wise univariate statistical parametric mapping and multivariate pattern recognition using linear discriminant classifiers. MSA and PSP showed less ioflupane uptake in the head of caudate nucleus relative to PD and CBD, yet there was no difference between MSA and PSP. CBD had higher uptake in both putamen relative to PD, MSA and PSP. Classification was significant for PD versus APS (AUC 0.69, p < 0.05) and between APS subtypes (MSA vs CBD AUC 0.80, p < 0.05; MSA vs PSP AUC 0.69 p < 0.05; CBD vs PSP AUC 0.69 p < 0.05). Both striatal and extra-striatal regions contain classification information, yet the combination of both regions does not significantly improve classification accuracy. PD, MSA, PSP and CBD have distinct patterns of dopaminergic depletion on (123)I-ioflupane SPECT. The high specificity of 84-90% for PD versus APS indicates that the classifier is particularly useful for confirming APS cases.

    Fulltekst (pdf)
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  • 2.
    Bas-Hoogendam, Janna Marie
    et al.
    Leiden Univ, Inst Psychol, Wassenaarseweg 52, NL-2333 AK Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Psychiat, Leiden, Netherlands.;Leiden Inst Brain & Cognit, Leiden, Netherlands..
    van Steenbergen, Henk
    Leiden Univ, Inst Psychol, Wassenaarseweg 52, NL-2333 AK Leiden, Netherlands.;Leiden Inst Brain & Cognit, Leiden, Netherlands..
    Pannekoek, J. Nienke
    Imperial Coll London, Div Brain Sci, Ctr Psychiat, Neuropsychopharmacol Unit, London, England..
    Fouche, Jean-Paul
    Univ Cape Town, Dept Psychiat & Mental Hlth, Cape Town, South Africa..
    Lochner, Christine
    UCT MRC Unit Anxiety & Stress Disorders, Cape Town, South Africa.;Univ Stellenbosch, Dept Psychiat, Tygerberg, South Africa..
    Hattingh, Coenraad J.
    Univ Cape Town, Dept Psychiat & Mental Hlth, Cape Town, South Africa..
    Cremers, Henk R.
    Univ Amsterdam, Dept Clin Psychol, Amsterdam, Netherlands..
    Furmark, Tomas
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Månsson, Kristoffer N.T.
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. Stockholm Univ, Dept Psychol, Stockholm, Sweden.;Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden..
    Frick, Andreas
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden..
    Engman, Jonas
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Boraxbekk, Carl-Johan
    Umea Univ, Umea Ctr Funct Brain Imaging UFBI, Umea, Sweden.;Copenhagen Univ Hosp Hvidovre, Ctr Funct & Diagnost Imaging & Res, DRCMR, Hvidovre, Denmark..
    Carlbring, Per
    Stockholm Univ, Dept Psychol, Stockholm, Sweden..
    Andersson, Gerhard
    Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden.;Linkoping Univ, Dept Behav Sci & Learning Psychol, Linkoping, Sweden..
    Fredrikson, Mats
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden..
    Straube, Thomas
    Univ Munster, Inst Med Psychol & Syst Neurosci, Munster, Germany..
    Peterburs, Jutta
    Univ Munster, Inst Med Psychol & Syst Neurosci, Munster, Germany..
    Klumpp, Heide
    Univ Illinois, Dept Psychiat, Chicago, IL USA.;Univ Illinois, Dept Psychol, Chicago, IL USA..
    Phanp, K. Luan
    Univ Illinois, Dept Psychiat, Chicago, IL USA.;Univ Illinois, Dept Psychol, Chicago, IL USA..
    Roelofs, Karin
    Radboud Univ Nijmegen, Behav Sci Inst, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands..
    Veltman, Dick J.
    Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Neurosci Campus Amsterdam, Amsterdam, Netherlands..
    van Tol, Marie-Jose
    Univ Groningen, Univ Med Ctr Groningen, Dept Neurosci, Groningen, Netherlands..
    Stein, Dan J.
    Univ Cape Town, Dept Psychiat & Mental Hlth, Cape Town, South Africa.;UCT MRC Unit Anxiety & Stress Disorders, Cape Town, South Africa..
    van der Wee, Nic J. A.
    Leiden Univ, Med Ctr, Dept Psychiat, Leiden, Netherlands.;Leiden Inst Brain & Cognit, Leiden, Netherlands..
    Voxel-based morphometry multi-center mega-analysis of brain structure in social anxiety disorder2017Inngår i: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 16, s. 678-688Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Social anxiety disorder (SAD) is a prevalent and disabling mental disorder, associated with significant psychiatric comorbidity. Previous research on structural brain alterations associated with SAD has yielded inconsistent results concerning the direction of the changes in graymatter (GM) in various brain regions, as well as on the relationship between brain structure and SAD-symptomatology. These heterogeneous findings are possibly due to limited sample sizes. Multisite imaging offers new opportunities to investigate SAD-related alterations in brain structure in larger samples. An international multi-center mega-analysis on the largest database of SAD structural T1-weighted 3T MRI scans to date was performed to compare GM volume of SAD-patients (n = 174) and healthy control (HC)-participants (n = 213) using voxel-based morphometry. A hypothesis-driven region of interest (ROI) approach was used, focusing on the basal ganglia, the amygdala-hippocampal complex, the prefrontal cortex, and the parietal cortex. SAD-patients had larger GM volume in the dorsal striatum when compared to HC-participants. This increase correlated positively with the severity of self-reported social anxiety symptoms. No SAD-related differences in GM volume were present in the other ROIs. Thereby, the results of this mega-analysis suggest a role for the dorsal striatum in SAD, but previously reported SAD-related changes in GM in the amygdala, hippocampus, precuneus, prefrontal cortex and parietal regions were not replicated. Our findings emphasize the importance of large sample imaging studies and the need for meta-analyses like those performed by the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium.

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  • 3.
    Brooks, S. J.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi. Groote Schuur Hosp, Dept Psychiat & Mental Hlth, Cape Town, South Africa.;Univ Cape Town, MRC Unit Anxiety & Stress Disorders, ZA-7700 Rondebosch, South Africa..
    Burch, K. H.
    Groote Schuur Hosp, Dept Psychiat & Mental Hlth, Cape Town, South Africa.;Univ Cape Town, MRC Unit Anxiety & Stress Disorders, ZA-7700 Rondebosch, South Africa.;Univ Nottingham, Dept Neurosci, Nottingham NG7 2RD, England..
    Maiorana, S. A.
    Univ Cape Town, Dept Psychol, ZA-7700 Rondebosch, South Africa..
    Cocolas, E.
    Groote Schuur Hosp, Dept Psychiat & Mental Hlth, Cape Town, South Africa.;Univ Cape Town, MRC Unit Anxiety & Stress Disorders, ZA-7700 Rondebosch, South Africa..
    Schiöth, Helgi B.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Nilsson, Emil K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Kamaloodien, K.
    Univ Western Cape, Dept Psychol, Cape Town, South Africa..
    Stein, D. J.
    Groote Schuur Hosp, Dept Psychiat & Mental Hlth, Cape Town, South Africa.;Univ Cape Town, MRC Unit Anxiety & Stress Disorders, ZA-7700 Rondebosch, South Africa..
    Psychological intervention with working memory training increases basal ganglia volume: A VBM study of inpatient treatment for methamphetamine use2016Inngår i: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 12, s. 478-491Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Protracted methamphetamine (MA) use is associated with decreased control over drug craving and altered brain volume in the frontostriatal network. However, the nature of volumetric changes following a course of psychological intervention for MA use is not yet known. Methods: 66 males (41 MA patients, 25 healthy controls, HC) between the ages of 18-50 were recruited, the MA patients from new admissions to an in-patient drug rehabilitation centre and the HC via public advertisement, both in Cape Town, South Africa. 17 MA patients received 4 weeks of treatment as usual (TAU), and 24 MA patients completed TAU plus daily 30-minute cognitive training (CT) using an N-back working memory task. Magnetic resonance imaging (MRI) at baseline and 4-week follow-up was acquired and voxel-based morphometry (VBM) was used for analysis. Results: TAU was associated with larger bilateral striatum (caudate/putamen) volume, whereas CT was associated with more widespread increases of the bilateral basal ganglia (incorporating the amygdala and hippocampus) and reduced bilateral cerebellum volume coinciding with improvements in impulsivity scores. Conclusions: While psychological intervention is associated with larger volume in mesolimbic reward regions, the utilisation of additional working memory training as an adjunct to treatment may further normalize frontostriatal structure and function.

    Fulltekst (pdf)
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  • 4. Drissi, Natasha Morales
    et al.
    Warntjes, Marcel
    Wessén, Alexander
    Szakacs, Attila
    Darin, Niklas
    Hallböök, Tove
    Landtblom, Anne-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Landtblom: Neurologi.
    Gauffin, Helena
    Engström, Maria
    Structural anomaly in the reticular formation in narcolepsy type 1, suggesting lower levels of neuromelanin2019Inngår i: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 23, artikkel-id 101875Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The aim of this study was to investigate structural changes in the brain stem of adolescents with narcolepsy, a disorder characterized by excessive daytime sleepiness, fragmented night-time sleep, and cataplexy. For this purpose, we used quantitative magnetic resonance imaging to obtain R1 and R2 relaxation rates, proton density, and myelin maps in adolescents with narcolepsy (n = 14) and healthy controls (n = 14). We also acquired resting state functional magnetic resonance imaging (fMRI) for brainstem connectivity analysis. We found a significantly lower R2 in the rostral reticular formation near the superior cerebellar peduncle in narcolepsy patients, family wise error corrected p = .010. Narcolepsy patients had a mean R2 value of 1.17 s-1 whereas healthy controls had a mean R2 of 1.31 s-1, which was a large effect size with Cohen d = 4.14. We did not observe any significant differences in R1 relaxation, proton density, or myelin content. The sensitivity of R2 to metal ions in tissue and the transition metal ion chelating property of neuromelanin indicate that the R2 deviant area is one of the neuromelanin containing nuclei of the brain stem. The close proximity and its demonstrated involvement in sleep-maintenance, specifically through orexin projections from the hypothalamus regulating sleep stability, as well as the results from the connectivity analysis, suggest that the observed deviant area could be the locus coeruleus or other neuromelanin containing nuclei in the proximity of the superior cerebellar peduncle. Hypothetically, the R2 differences described in this paper could be due to lower levels of neuromelanin in this area of narcolepsy patients.

    Fulltekst (pdf)
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  • 5.
    Emmert, Kirsten
    et al.
    Univ Hosp Geneva, Dept Radiol & Med informat, Switzerland.
    Kopel, Rotem
    Univ Hosp Geneva, Dept Radiol & Med informat, Switzerland.
    Koush, Yury
    Univ Hosp Geneva, Dept Radiol & Med informat, Switzerland.
    Maire, Raphael
    Univ Hosp Lausanne, Neurotol & Audiol Unit, Dept ENT Head & Neck Surg, Switzerland.
    Senn, Pascal
    Univ Hosp Geneva, Dept Clin Neurosci, Switzerland.
    Van De Ville, Dimitri
    Univ Hosp Geneva, Dept Radiol & Med informat, Switzerland.
    Haller, Sven
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Continuous vs. intermittent neurofeedback to regulate auditory cortex activity of tinnitus patients using real-time fMRI: A pilot study2017Inngår i: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 14, s. 97-104Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The emerging technique of real-time fMRI neurofeedback trains individuals to regulate their own brain activity via feedback from an fMRI measure of neural activity. Optimum feedback presentation has yet to be determined, particularly when working with clinical populations. To this end, we compared continuous against intermittent feedback in subjects with tinnitus.

    Fourteen participants with tinnitus completed the whole experiment consisting of nine runs (3 runs × 3 days). Prior to the neurofeedback, the target region was localized within the auditory cortex using auditory stimulation (1 kHz tone pulsating at 6 Hz) in an ON-OFF block design. During neurofeedback runs, participants received either continuous (n = 7, age 46.84 ± 12.01, Tinnitus Functional Index (TFI) 49.43 ± 15.70) or intermittent feedback (only after the regulation block) (n = 7, age 47.42 ± 12.39, TFI 49.82 ± 20.28). Participants were asked to decrease auditory cortex activity that was presented to them by a moving bar. In the first and the last session, participants also underwent arterial spin labeling (ASL) and resting-state fMRI imaging. We assessed tinnitus severity using the TFI questionnaire before all sessions, directly after all sessions and six weeks after all sessions. We then compared neuroimaging results from neurofeedback using a general linear model (GLM) and region-of-interest analysis as well as behavior measures employing a repeated-measures ANOVA. In addition, we looked at the seed-based connectivity of the auditory cortex using resting-state data and the cerebral blood flow using ASL data.

    GLM group analysis revealed that a considerable part of the target region within the auditory cortex was significantly deactivated during neurofeedback. When comparing continuous and intermittent feedback groups, the continuous group showed a stronger deactivation of parts of the target region, specifically the secondary auditory cortex. This result was confirmed in the region-of-interest analysis that showed a significant down-regulation effect for the continuous but not the intermittent group. Additionally, continuous feedback led to a slightly stronger effect over time while intermittent feedback showed best results in the first session. Behaviorally, there was no significant effect on the total TFI score, though on a descriptive level TFI scores tended to decrease after all sessions and in the six weeks follow up in the continuous group. Seed-based connectivity with a fixed-effects analysis revealed that functional connectivity increased over sessions in the posterior cingulate cortex, premotor area and part of the insula when looking at all patients while cerebral blood flow did not change significantly over time.

    Overall, these results show that continuous feedback is suitable for long-term neurofeedback experiments while intermittent feedback presentation promises good results for single session experiments when using the auditory cortex as a target region. In particular, the down-regulation effect is more pronounced in the secondary auditory cortex, which might be more susceptible to voluntary modulation in comparison to a primary sensory region.

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  • 6. Flodin, P
    et al.
    Martinsen, S
    Mannerkorpi, K
    Löfgren, M
    Bileviciute-Ljungar, I
    Kosek, E
    Fransson, P
    Normalization of aberrant resting state functional connectivity in fibromyalgia patients following a three month physical exercise therapy.2015Inngår i: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 9, s. 134-9Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Physical exercise is one of the most efficient interventions to mitigate chronic pain symptoms in fibromyalgia (FM). However, little is known about the neurophysiological mechanisms mediating these effects. In this study we investigated resting-state connectivity using functional magnetic resonance imaging (fMRI) before and after a 15 week standardized exercise program supervised by physical therapists. Our aim was to gain an understanding of how physical exercise influences previously shown aberrant patterns of intrinsic brain activity in FM. Fourteen FM patients and eleven healthy controls successfully completed the physical exercise treatment. We investigated post- versus pre-treatment changes of brain connectivity, as well as changes in clinical symptoms in the patient group. FM patients reported improvements in symptom severity. Although several brain regions showed a treatment-related change in connectivity, only the connectivity between the right anterior insula and the left primary sensorimotor area was significantly more affected by the physical exercise among the fibromyalgia patients compared to healthy controls. Our results suggest that previously observed aberrant intrinsic brain connectivity patterns in FM are partly normalized by the physical exercise therapy. However, none of the observed normalizations in intrinsic brain connectivity were significantly correlated with symptom changes. Further studies conducted in larger cohorts are warranted to investigate the precise relationship between improvements in fibromyalgia symptoms and changes in intrinsic brain activity.

  • 7. Georgiopoulos, Charalampos
    et al.
    Witt, Suzanne T
    Haller, Sven
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Dizdar, Nil
    Zachrisson, Helene
    Engström, Maria
    Larsson, Elna-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    A study of neural activity and functional connectivity within the olfactory brain network in Parkinson's disease2019Inngår i: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 23, artikkel-id 101946Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Olfactory dysfunction is an early manifestation of Parkinson's disease (PD). The present study aimed to illustrate potential differences between PD patients and healthy controls in terms of neural activity and functional connectivity within the olfactory brain network. Twenty PD patients and twenty healthy controls were examined with olfactory fMRI and resting-state fMRI. Data analysis of olfactory fMRI included data-driven tensorial independent component (ICA) and task-driven general linear model (GLM) analyses. Data analysis of resting-state fMRI included probabilistic ICA based on temporal concatenation and functional connectivity analysis within the olfactory network. ICA of olfactory fMRI identified an olfactory network consisting of the posterior piriform cortex, insula, right orbitofrontal cortex and thalamus. Recruitment of this network was less significant for PD patients. GLM analysis revealed significantly lower activity in the insula bilaterally and the right orbitofrontal cortex in PD compared to healthy controls but no significant differences in the olfactory cortex itself. Analysis of resting-state fMRI did not reveal any differences in the functional connectivity within the olfactory, default mode, salience or central executive networks between the two groups. In conclusion, olfactory dysfunction in PD is associated with less significant recruitment of the olfactory brain network. ICA could demonstrate differences in both the olfactory cortex and its main projections, compared to GLM that revealed differences only on the latter. Resting-state fMRI did not reveal any significant differences in functional connectivity within the olfactory, default mode, salience and central executive networks in this cohort.

    Fulltekst (pdf)
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  • 8.
    Hilland, Eva
    et al.
    Univ Oslo, Norwegian Ctr Mental Disorders Res NORMENT, Inst Clin Med, Oslo, Norway.;Oslo Metropolitan Univ, Fac Hlth Sci, Oslo, Norway.
    Johannessen, Cecilie
    Univ Oslo, Norwegian Ctr Mental Disorders Res NORMENT, Inst Clin Med, Oslo, Norway.
    Jonassen, Rune
    Oslo Metropolitan Univ, Fac Hlth Sci, Oslo, Norway.
    Alnaes, Dag
    Bjorknes Coll, Oslo, Norway.;Oslo Univ Hosp, Norwegian Ctr Mental Disorders Res NORMENT, Div Mental Hlth & Addict, Oslo, Norway.
    Jorgensen, Kjetil N.
    Univ Oslo, Norwegian Ctr Mental Disorders Res NORMENT, Inst Clin Med, Oslo, Norway.;Diakonhjemmet Hosp, Dept Psychiat Res, Oslo, Norway.
    Barth, Claudia
    Univ Oslo, Norwegian Ctr Mental Disorders Res NORMENT, Inst Clin Med, Oslo, Norway.;Diakonhjemmet Hosp, Dept Psychiat Res, Oslo, Norway.
    Andreou, Dimitrios
    Univ Oslo, Norwegian Ctr Mental Disorders Res NORMENT, Inst Clin Med, Oslo, Norway.;Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Stockholm Regio, Sweden.;Stockholm Hlth Care Serv, Stockholm, Stockholm Regio, Sweden.
    Nerland, Stener
    Univ Oslo, Norwegian Ctr Mental Disorders Res NORMENT, Inst Clin Med, Oslo, Norway.;Diakonhjemmet Hosp, Dept Psychiat Res, Oslo, Norway.
    Wortinger, Laura A.
    Univ Oslo, Norwegian Ctr Mental Disorders Res NORMENT, Inst Clin Med, Oslo, Norway.;Diakonhjemmet Hosp, Dept Psychiat Res, Oslo, Norway.
    Smelror, Runar E.
    Univ Oslo, Norwegian Ctr Mental Disorders Res NORMENT, Inst Clin Med, Oslo, Norway.;Diakonhjemmet Hosp, Dept Psychiat Res, Oslo, Norway.
    Wedervang-Resell, Kirsten
    Oslo Univ Hosp, Norwegian Ctr Mental Disorders Res NORMENT, Div Mental Hlth & Addict, Oslo, Norway.
    Bohman, Hannes
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Ramklint: Barn- och ungdomspsykiatri. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Stockholm Regio, Sweden.;Stockholm Hlth Care Serv, Stockholm, Stockholm Regio, Sweden.;Karolinska Inst, Dept Clin Sci & Educ, Sodersjukhuset, Stockholm, Sweden.
    Lundberg, Mathias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Ramklint: Barn- och ungdomspsykiatri. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Stockholm Regio, Sweden.;Stockholm Hlth Care Serv, Stockholm, Stockholm Regio, Sweden;Karolinska Inst, Dept Clin Sci & Educ, Sodersjukhuset, Stockholm, Sweden.
    Westlye, Lars T.
    Oslo Univ Hosp, Norwegian Ctr Mental Disorders Res NORMENT, Div Mental Hlth & Addict, Oslo, Norway.;Univ Oslo, Dept Psychol, Oslo, Norway.
    Andreassen, Ole A.
    Univ Oslo, Norwegian Ctr Mental Disorders Res NORMENT, Inst Clin Med, Oslo, Norway.;Oslo Univ Hosp, Norwegian Ctr Mental Disorders Res NORMENT, Div Mental Hlth & Addict, Oslo, Norway.
    Jonsson, Erik G.
    Univ Oslo, Norwegian Ctr Mental Disorders Res NORMENT, Inst Clin Med, Oslo, Norway.;Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Stockholm Regio, Sweden.;Stockholm Hlth Care Serv, Stockholm, Stockholm Regio, Sweden.
    Agartz, Ingrid
    Univ Oslo, Norwegian Ctr Mental Disorders Res NORMENT, Inst Clin Med, Oslo, Norway.;Diakonhjemmet Hosp, Dept Psychiat Res, Oslo, Norway.;Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Stockholm Regio, Sweden.;Stockholm Hlth Care Serv, Stockholm, Stockholm Regio, Sweden.
    Aberrant default mode connectivity in adolescents with early-onset psychosis: A resting state fMRI study2022Inngår i: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 33, artikkel-id 102881Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Abnormal default mode network (DMN) connectivity has been found in schizophrenia and other psychotic disorders. However, there are limited studies on early onset psychosis (EOP), and their results show lack of agreement. Here, we investigated within-network DMN connectivity in EOP compared to healthy controls (HC), and its relationship to clinical characteristics. A sample of 68 adolescent patients with EOP (mean age 16.53 +/- 1.12 [SD] years, females 66%) and 95 HC (mean age 16.24 +/- 1.50 [SD], females 60%) from two Scandinavian cohorts underwent resting state functional magnetic resonance imaging (rsfMRI). A group independent component analysis (ICA) was performed to identify the DMN across all participants. Dual regression was used to estimate spatial maps reflecting each participant's DMN network, which were compared between EOP and HC using voxel-wise general linear models and permutation-based analyses. Subgroup analyses were performed within the patient group, to explore associations between diagnostic subcategories and current use of psychotropic medication in relation to connectivity strength. The analysis revealed significantly reduced DMN connectivity in EOP compared to HC in the posterior cingulate cortex, precuneus, fusiform cortex, putamen, pallidum, amygdala, and insula. The subgroup analysis in the EOP group showed strongest deviations for affective psychosis, followed by other psychotic disorders and schizophrenia. There was no association between DMN connectivity strength and the current use of psychotropic medication. In conclusion, the findings demonstrate weaker DMN connectivity in adolescent patients with EOP compared to healthy peers, and differential effects across diagnostic subcategories, which may inform our understanding of underlying disease mechanisms in EOP.

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  • 9.
    Jonasson, My
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Wall, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Chiotis, Konstantinos
    Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
    Leuzy, Antoine
    Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
    Eriksson, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi.
    Antoni, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi.
    Nordberg, Agneta
    Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
    Lubberink, Mark
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Optimal timing of tau pathology imaging and automatic extraction of a reference region using dynamic [18F]THK5317 PET2019Inngår i: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 22, artikkel-id 101681Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    [F-18]THK5317 is a PET tracer for in-vivo imaging of tau associated with Alzheimer's disease (AD). This work aimed to evaluate optimal timing for standardized uptake value ratio (SUVR) measures with [F-18]THK5317 and automated generation of SUVR-1 and relative cerebral blood flow (R-1) parametric images. Nine AD patients and nine controls underwent 90 min [F-18]THK5317 scans. SUVR-1 was calculated at transient equilibrium (TE) and for seven different 20 min intervals and compared with distribution volume ratio (DVR; reference Logan). Cerebellar grey matter (MRI) was used as reference region. A supervised cluster analysis (SVCA) method was implemented to automatically generate a reference region, directly from the dynamic PET volume without the need of a structural MRI scan, for computation of SUVR-1 and R-1 images for a scan duration matching the optimal timing. TE was reached first in putamen, frontal- and parietal cortex at 22 +/- 4 min for AD patients and in putamen at 20 +/- 0 min in controls. Over all regions and subjects, SUVR20-40-1 correlated best with DVR-1, R-2 = 0.97. High correlation was found between values generated using MRI- and SVCA-based reference (R-2 = 0.93 for SUVR20-40-1; R-2 = 0.94 for R-1). SUVR20-40 allows for accurate semi-quantitative assessment of tau pathology and SVCA may be used to obtain a reference region for calculation of both SUVR-1 and R-1 with 40 min scan duration.

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  • 10.
    Latini, Francesco
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Enblad: Neurokirurgi.
    Fahlström, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Beháňová, Andrea
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för visuell information och interaktion.
    Sintorn, Ida-Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för visuell information och interaktion.
    Hodik, Monika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Staxäng, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Ryttlefors, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Enblad: Neurokirurgi.
    The link between gliomas infiltration and white matter architecture investigated with electron microscopy and diffusion tensor imaging2021Inngår i: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 31, s. 102735-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Diffuse low-grade gliomas display preferential locations in eloquent and secondary associative brain areas. The reason for this tendency is still unknown. We hypothesized that the intrinsic architecture and water diffusion properties of the white matter bundles in these regions may facilitate gliomas infiltration. Magnetic resonance imaging of one hundred and two low-grade gliomas patients were normalized to/and segmented in MNI space to create a probabilistic infiltration weighted gradient map. Diffusion tensor imaging (DTI)- based parameters were derived for five major white matter bundles, displaying high- and low grade of infiltration, (corpus callosum, cingulum, arcuate fasciculus, inferior fronto-occipital fasciculus and cortico-spinal tract), averaged over 20 healthy individuals acquired from the Human connectome project (HCP) database. Transmission electron microscopy (TEM) was used to analyze fiber density, diameter and g-ratio in 100 human white matter regions, sampled from cadaver specimens, reflecting areas with different gliomas infiltration frequency. Histological results and DTI-based parameters were compared in anatomical regions of high- and low grade of infiltration respectively. We detected differences in the infiltration frequency of five major white matter bundles. Regional differences within the same white matter bundles were detected by both TEM- and DTI analysis. Regions with high infiltration frequency (HIF) displayed a higher fiber density, smaller fiber diameter but higher myelin thickness and lower axial diffusivity compare compared with low infiltration frequency (LIF) regions. Our results  seem to indicate that the fiber diameter, myelin thickness and the  possible organization of the fibers are different in HIF compared to LIF regions and may be linked to the preferential location of diffuse low-grade gliomas.

  • 11.
    Lindström, Elin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Oddstig, Jenny
    Radiation Physics, Skåne University Hospital, SE-221 85 Lund, Sweden.
    Danfors, Torsten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Jögi, Jonas
    Clinical Physiology and Nuclear Medicine, Skåne University Hospital, SE-221 85 Lund, Sweden.
    Hansson, Oskar
    Clinical Memory Research Unit, Lund University, SE-221 00 Lund, Sweden;Memory Clinic, Skåne University Hospital, SE-205 02 Malmö, Sweden.
    Lubberink, Mark
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Image reconstruction methods affect software-aided assessment of pathologies of [18F]flutemetamol and [18F]FDG brain-PET examinations in patients with neurodegenerative diseases2020Inngår i: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 28, artikkel-id 102386Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: To assess how some of the new developments in brain positron emission tomography (PET) image reconstruction affect quantitative measures and software-aided assessment of pathology in patients with neurodegenerative diseases.

    METHODS: PET data were grouped into four cohorts: prodromal Alzheimer's disease patients and controls receiving [18F]flutemetamol, and neurodegenerative disease patients and controls receiving [18F]FDG PET scans. Reconstructed images were obtained by ordered-subsets expectation maximization (OSEM; 3 iterations (i), 16/34 subsets (s), 3/5-mm filter, ±time-of-flight (TOF), ±point-spread function (PSF)) and block-sequential regularized expectation maximization (BSREM; TOF, PSF, β-value 75-300). Standardized uptake value ratios (SUVR) and z-scores were calculated (CortexID Suite, GE Healthcare) using cerebellar gray matter, pons, whole cerebellum and whole brain as reference regions.

    RESULTS: In controls, comparable results to the normal database were obtained with OSEM 3i/16 s 5-mm reconstruction. TOF, PSF and BSREM either increased or decreased the relative uptake difference to the normal subjects' database within the software, depending on the tracer and chosen reference area, i.e. resulting in increased absolute z-scores. Normalizing to pons and whole brain for [18F]flutemetamol and [18F]FDG, respectively, increased absolute differences between reconstructions methods compared to normalizing to cerebellar gray matter and whole cerebellum when applying TOF, PSF and BSREM.

    CONCLUSIONS: Software-aided assessment of patient pathologies should be used with caution when employing other image reconstruction methods than those used for acquisition of the normal database.

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  • 12.
    Lorenzini, Luigi
    et al.
    Univ Amsterdam, Dept Radiol & Nucl Med, Amsterdam Neurosci, Med Ctr, Amsterdam, Netherlands..
    Ingala, Silvia
    Univ Amsterdam, Dept Radiol & Nucl Med, Amsterdam Neurosci, Med Ctr, Amsterdam, Netherlands..
    Wink, Alle Meije
    Univ Amsterdam, Dept Radiol & Nucl Med, Amsterdam Neurosci, Med Ctr, Amsterdam, Netherlands..
    Kuijer, Joost P. A.
    Univ Amsterdam, Dept Radiol & Nucl Med, Amsterdam Neurosci, Med Ctr, Amsterdam, Netherlands..
    Wottschel, Viktor
    Univ Amsterdam, Dept Radiol & Nucl Med, Amsterdam Neurosci, Med Ctr, Amsterdam, Netherlands..
    Dijsselhof, Mathijs
    Univ Amsterdam, Dept Radiol & Nucl Med, Amsterdam Neurosci, Med Ctr, Amsterdam, Netherlands..
    Sudre, Carole H.
    UCL, MRC Unit Lifelong Hlth & Ageing, London, England.;UCL, Dementia Res Ctr, Dept Neurodegenerat Dis, Queen Sq Inst Neurol, London, England.;UCL, Ctr Med Image Comp, London, England.;Kings Coll London, Sch Biomed Engn & Imaging Sci, London, England..
    Haller, Sven
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. CIMC Ctr Imagerie Med Cornavin, Pl Cornavin 18, CH-1201 Geneva, Switzerland..
    Gispert, Juan Domingo
    Pasqual Maragall Fdn, BBRC, Barcelona, Spain.;CIBER Fragil & Envejecimiento Saludable CIBERFES, Madrid, Spain.;Hosp del Mar Med Res Inst, IMIM, Barcelona, Spain.;Univ Pompeu Fabra, Barcelona, Spain.;CIBER Bioingn Biomat & Nanomed CIBER BBN, Madrid, Spain..
    Cash, David M.
    UCL, UK Dementia Res Inst, London, England..
    Thomas, David L.
    UCL, Neuroradiol Acad Unit, Queen Sq Inst Neurol London, London, England.;UCL, Wellcome Ctr Human Neuroimaging, Queen Sq Inst Neurol, London, England..
    Vos, Sjoerd B.
    Prados, Ferran
    UCL, Queen Sq Multiple Sclerosis Ctr, Nucl Magnet Resonance Res Unit, Queen Sq Inst Neurol, London, England.;UCL, Ctr Med Image Comp, Dept Med Phys & Biomed Engn, London, England.;Univ Oberta Catalunya, Ehlth Ctr, Barcelona, Spain..
    Petr, Jan
    Helmholtz Zentrum Dresden Rossendorf, Inst Radiopharmaceut Canc Res, Dresden, Germany..
    Wolz, Robin
    IXICO, London, England.;Imperial Coll London, London, England..
    Palombit, Alessandro
    IXICO, London, England..
    Schwarz, Adam J.
    Takeda Pharmaceut Ltd, Cambridge, MA USA..
    Chetelat, Gael
    Univ Normandie, Inst Blood and Brain Caen Normandie, Unicaen, Inserm,U1237,PhIND Physiopathol & Imaging Neurol D, F-14000 Caen, France..
    Payoux, Pierre
    Purpan Univ Hosp, Dept Nucl Med, Toulouse CHU, Toulouse, France.;Univ Toulouse, Toulouse NeuroImaging Ctr, INSERM, UPS, Toulouse, France..
    Di Perri, Carol
    Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Scotland..
    Wardlaw, Joanna M.
    Univ Edinburgh, UK Dementia Res Inst Edinburgh, Edinburgh, Scotland.;IRCCS Inst Ctr San Giovanni Dio Fatebenefratelli, Lab Alzheimers Neuroimaging & Epidemiol, Brescia, Italy..
    Frisoni, Giovanni B.
    Univ Hosp, Geneva, Switzerland.;Univ Geneva, Geneva, Switzerland.;GE Healthcare Ltd, Little Chalfont, England..
    Foley, Christopher
    Univ Edinburgh, Ctr Dementia Prevent, Edinburgh, Scotland..
    Fox, Nick C.
    Kings Coll London, Sch Biomed Engn & Imaging Sci, London, England..
    Ritchie, Craig
    Imperial Coll London, Dept Brain Sci, London, England..
    Pernet, Cyril
    Univ Edinburgh, UK Dementia Res Inst Edinburgh, Edinburgh, Scotland.;UCL, Inst Neurol & Healthcare Engn, London, England..
    Waldman, Adam
    Univ Edinburgh, UK Dementia Res Inst Edinburgh, Edinburgh, Scotland.;Univ Ghent, Ghent Inst Funct & Metab Imaging GIfMI, Ghent, Belgium..
    Barkhof, Frederik
    Univ Amsterdam, Dept Radiol & Nucl Med, Amsterdam Neurosci, Med Ctr, Amsterdam, Netherlands.;Copenhagen Univ Hosp, Neurobiol Res Unit, Rigshosp, Copenhagen, Denmark..
    Mutsaerts, Henk J. M. M.
    Univ Amsterdam, Dept Radiol & Nucl Med, Amsterdam Neurosci, Med Ctr, Amsterdam, Netherlands.;H Lundbeck & Co AS, DK-2500 Valby, Denmark..
    Consortium, E P A D
    The Open-Access European Prevention of Alzheimer?s Dementia (EPAD) MRI dataset and processing workflow2022Inngår i: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 35, artikkel-id 103106Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The European Prevention of Alzheimer Dementia (EPAD) is a multi-center study that aims to characterize the preclinical and prodromal stages of Alzheimer's Disease. The EPAD imaging dataset includes core (3D T1w, 3D FLAIR) and advanced (ASL, diffusion MRI, and resting-state fMRI) MRI sequences. Here, we give an overview of the semi-automatic multimodal and multisite pipeline that we developed to curate, preprocess, quality control (QC), and compute image-derived phenotypes (IDPs) from the EPAD MRI dataset. This pipeline harmonizes DICOM data structure across sites and performs standardized MRI pre-processing steps. A semi-automated MRI QC procedure was implemented to visualize and flag MRI images next to site-specific distributions of QC features - i.e. metrics that represent image quality. The value of each of these QC features was evaluated through comparison with visual assessment and step-wise parameter selection based on logistic regression. IDPs were computed from 5 different MRI modalities and their sanity and potential clinical relevance were ascertained by assessing their relationship with biological markers of aging and dementia. The EPAD v1500.0 data release encompassed core structural scans from 1356 participants 842 fMRI, 831 dMRI, and 858 ASL scans. From 1356 3D T1w images, we identified 17 images with poor quality and 61 with moderate quality. Five QC features - Signal to Noise Ratio (SNR), Contrast to Noise Ratio (CNR), Coefficient of Joint Variation (CJV), Foreground-Background energy Ratio (FBER), and Image Quality Rate (IQR) - were selected as the most informative on image quality by comparison with visual assessment. The multimodal IDPs showed greater impairment in associations with age and dementia biomarkers, demonstrating the potential of the dataset for future clinical analyses

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  • 13.
    Marklund, Niklas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Enblad: Neurokirurgi. Lund University, Skåne University Hospital, Department of Clinical Sciences Lund, Neurosurgery, Lund, Sweden..
    Vedung, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Enblad: Neurokirurgi.
    Lubberink, Mark
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. Medical Physics, Uppsala University Hospital, Uppsala, Sweden..
    Tegner, Yelverton
    Department of Health Sciences, Luleå University of Technology, Sweden..
    Johansson, Jakob
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Blennow, Kaj
    Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry , Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden..
    Zetterberg, Henrik
    Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry , Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.; UK Dementia Research Institute at UCL, London, United Kingdom.; Department of Neurodegenerative Disease, UCL Institute of Neurology, London, United Kingdom..
    Fahlström, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Haller, Sven
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. CIMC Ctr Imagerie Med Cornavin, Pl Cornavin 18, CH-1201 Geneva, Switzerland..
    Stenson, Staffan
    Uppsala Univ Hosp, Rehabil Med PET Ctr, Dept Neurosci, Uppsala, Sweden..
    Larsson, Elna-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Wall, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Antoni, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för Preklinisk PET-MRI. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi.
    Tau aggregation and increased neuroinflammation in athletes after sports-related concussions and in traumatic brain injury patients – A PET/MR study2021Inngår i: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 30, artikkel-id 102665Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Traumatic brain injury (TBI) and repeated sports-related concussions (rSRCs) are associated with an increased risk for neurodegeneration. Autopsy findings of selected cohorts of long-term TBI survivors and rSRC athletes reveal increased tau aggregation and a persistent neuroinflammation. To assess in vivo tau aggregation and neuroinflammation in young adult TBI and rSRC cohorts, we evaluated 9 healthy controls (mean age 26 ± 5 years; 4 males, 5 females), 12 symptomatic athletes (26 ± 7 years; 6 males, 6 females) attaining ≥3 previous SRCs, and 6 moderate-to severe TBI patients (27 ± 7 years; 4 males, 2 females) in a combined positron emission tomography (PET)/magnetic resonance (MR) scanner ≥6 months post-injury. Dual PET tracers, [18F]THK5317 for tau aggregation and [11C]PK11195 for neuroinflammation/microglial activation, were investigated on the same day. The Repeated Battery Assessment of Neurological Status (RBANS) scores, used for cognitive evaluation, were lower in both the rSRC and TBI groups (p < 0.05). Neurofilament-light (NF-L) levels were increased in plasma and cerebrospinal fluid (CSF; p < 0.05), and serum tau levels lower, in TBI although not in rSRC. In rSRC athletes, PET imaging showed increased neuroinflammation in the hippocampus and tau aggregation in the corpus callosum. In TBI patients, tau aggregation was observed in thalami, temporal white matter and midbrain; widespread neuroinflammation was found e.g. in temporal white matter, hippocampus and corpus callosum. In mixed-sex cohorts of young adult athletes with persistent post-concussion symptoms and in TBI patients, increased tau aggregation and neuroinflammation are observed at ≥6 months post-injury using PET. Studies with extended clinical follow-up, biomarker examinations and renewed PET imaging are needed to evaluate whether these findings progress to a neurodegenerative disorder or if spontaneous resolution is possible.

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  • 14. Meskaldji, Djalel-Eddine
    et al.
    Preti, Maria Giulia
    Bolton, Thomas Aw
    Montandon, Marie-Louise
    Rodriguez, Cristelle
    Morgenthaler, Stephan
    Giannakopoulos, Panteleimon
    Haller, Sven
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Van De Ville, Dimitri
    Prediction of long-term memory scores in MCI based on resting-state fMRI2016Inngår i: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 12, s. 785-795Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Resting-state functional MRI (rs-fMRI) opens a window on large-scale organization of brain function. However, establishing relationships between resting-state brain activity and cognitive or clinical scores is still a difficult task, in particular in terms of prediction as would be meaningful for clinical applications such as early diagnosis of Alzheimer's disease. In this work, we employed partial least square regression under cross-validation scheme to predict episodic memory performance from functional connectivity (FC) patterns in a set of fifty-five MCI subjects for whom rs-fMRI acquisition and neuropsychological evaluation was carried out. We show that a newly introduced FC measure capturing the moments of anti-correlation between brain areas, discordance, contains key information to predict long-term memory scores in MCI patients, and performs better than standard measures of correlation to do so. Our results highlighted that stronger discordance within default mode network (DMN) areas, as well as across DMN, attentional and limbic networks, favor episodic memory performance in MCI.

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  • 15.
    Petrican, Raluca
    et al.
    Rotman Res Inst,, Toronto, ON, Canada.
    Söderlund, Hedvig
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Kumar, Namita
    Baycrest Ctr Geriatr Care, Toronto, ON, Canada.
    Daskalakis, Zafiris J.
    Ctr Addict & Mental Hlth, Clarke Div, Toronto, ON, Canada; Univ Toronto, Toronto, ON, Canada.
    Flint, Alastair
    Univ Hlth Network, Toronto, ON, Canada; Univ Toronto, Toronto, ON, Canada.
    Levine, Brian
    Univ Toronto, Rotman Res Inst, Toronto, ON, Canada.
    Electroconvulsive therapy "corrects" the neural architecture of visuospatial memory: Implications for typical cognitive-affective functioning2019Inngår i: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 23, artikkel-id UNSP 101816Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Although electroconvulsive therapy (ECT) is a widely used and effective treatment for refractory depression, the neural underpinnings of its therapeutic effects remain poorly understood. To address this issue, here, we focused on a core cognitive deficit associated with depression, which tends to be reliably ameliorated through ECT, specifically, the ability to learn visuospatial information. Thus, we pursued three goals. First, we tested whether ECT can "normalize" the functional brain organization patterns associated with visuospatial memory and whether such corrections would predict post-ECT improvements in learning visuospatial information. Second, we investigated whether, among healthy individuals, stronger expression of the neural pattern, susceptible to adjustments through ECT, would predict reduced incidence of depression-relevant cognition and affect. Third, we sought to quantify the heritability of the ECT-correctable neural profile. Thus, in a task fMRI study with a clinical and a healthy comparison sample, we characterized two functional connectome patterns: one that typifies trait depression (i.e., differentiates patients from healthy individuals) and another that is susceptible to "normalization" through ECT. Both before and after ECT, greater expression of the trait depression neural profile was associated with more frequent repetitive thinking about past personal events (affective persistence), a hallmark of depressogenic cognition. Complementarily, post-treatment, stronger expression of the ECT-corrected neural profile was linked to improvements in visuospatial learning, a mental ability which is markedly impaired in depression. Subsequently, using data from the Human Connectome Project (HCP) (N = 333), we demonstrated that the functional brain organization of healthy participants with greater levels of subclinical depression and higher incidence of its associated cognitive deficits (affective persistence, impaired learning) shows greater similarity to the trait depression neural profile and reduced similarity to the ECT-correctable neural profile, as identified in the patient sample. These results tended to be specific to learning-relevant task contexts (working memory, perceptual relational processing). Genetic analyses based on HCP twin data (N = 128 pairs) suggested that, among healthy individuals, a functional brain organization similar to the one normalized by ECT in the patient sample is endogenous to cognitive contexts that require visuospatial processing that extends beyond the here-and-now. Broadly, the present findings supported our hypothesis that some of the therapeutic effects of ECT may be due to its correcting the expression of a naturally occurring pattern of functional brain organization that facilitates integration of internal and external cognition beyond the immediate present. Given their substantial susceptibility to both genetic and environmental effects, such mechanisms may be useful both for identifying at risk individuals and for monitoring progress of interventions targeting mood-related pathology.

    Fulltekst (pdf)
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  • 16.
    Struckmann, Wiebke
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Psykiatri.
    Bodén, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Psykiatri.
    Gingnell, Malin
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Psykiatri.
    Fällmar, David
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Persson, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Psykiatri.
    Modulation of dorsolateral prefrontal cortex functional connectivity after intermittent theta-burst stimulation in depression: combining findings from fNIRS and fMRI2022Inngår i: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 34, artikkel-id 103028Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Resting-state functional magnetic resonance imaging (fMRI) can assess modulation of functional connectivity networks following repetitive transcranial magnetic stimulation (rTMS) in the treatment of depression. Functional near-infrared spectroscopy (fNIRS) is well suited for the concurrent application during rTMS treatment sessions to capture immediate blood oxygenation (oxy-Hb) effects, however limited in spatial resolution.

    Objective: To understand the network effects behind such a prefrontal fNIRS response during rTMS, and to test whether the fNIRS signal may be predictive of treatment response, we linked data from fNIRS and fMRI within a clinical intervention study.

    Methods: 42 patients with ongoing depression were recruited and randomized to receive active or sham intermittent theta-burst stimulation (iTBS) over the dorsomedial prefrontal cortex (dmPFC) twice daily for ten days at target intensity. Oxy-Hb was recorded with fNIRS during the first, fifth, and final day of iTBS, with the probe holders located laterally to the TMS coil over regions corresponding to the left and right dorsolateral prefrontal cortex (dlPFC). Resting-state fMRI scanning was performed before and after the whole iTBS treatment course. Functional connectivity analyses were then performed using dlPFC seeds from parcels of a brain atlas showing most overlap with the fNIRS probe locations during treatment.

    Results: After active iTBS, left dlPFC-connectivity to the right insula/operculum was reduced compared to sham. The left insula showed a connectivity reduction to the left dlPFC that correlated with an improvement in symptoms. In addition, the posterior parietal cortex showed a connectivity reduction to the left dlPFC that correlated with the fNIRS signal following active iTBS. Finally, the fNIRS oxy-Hb signal from the left dlPFC-seed during the first treatment day was predictive of dlPFC-connectivity change to precentral and temporal cortex regions.

    Conclusion: By linking findings from these two different methods, this study suggests that changes within both the salience network and the central executive network affect the fNIRS response to iTBS.

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  • 17.
    Trolle, Carl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Harvard Med Sch, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Boston, MA USA.;Spaulding Neuroimaging Lab, 300 First Ave, Charlestown, MA 02129 USA..
    Goldberg, Estee
    Harvard Med Sch, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Boston, MA USA..
    Linnman, Clas
    Harvard Med Sch, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Boston, MA USA..
    Spinal cord atrophy after spinal cord injury - A systematic review and meta-analysis2023Inngår i: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 38, artikkel-id 103372Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cervical spinal cord atrophy occurs after spinal cord injury. The atrophy and how level of injury affects atrophy differs between studies. A systematic review and metaanalysis were done after systematic searches of PubMed, CINAHL, APA PsycInfo and Web of Science. English language original studies analyzing MRI cervical spinal cord cross-sectional area in adults with spinal cord injury were included. Atrophy and correlation between injury level and atrophy were estimated with random-effects models, standardized mean differences, and 95% confidence intervals. 24 studies were identified. 13/24 studies had low risk of bias. Cord atrophy meta-analysis of 18 articles corresponded to a standardized mean difference of -1.48 (95% CI -1.78 to -1.19) with moderate to large interstudy heterogeneity. Logarithmic time since injury influenced heterogeneity. Longitudinal atrophy was best described by a logarithmic model, indicating that rate of spinal atrophy decreases over time. Meta-correlation of eight studies indicated more severe atrophy in more rostral injuries (0.41, 95% CI 0.20-0.59). Larger and preferably longitudinal studies, data sharing, and standardized protocols are warranted.

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