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  • 1. Akram, Harith
    et al.
    Dayal, Viswas
    Mahlknecht, Philipp
    Georgiev, Dejan
    Hyam, Jonathan
    Foltynie, Thomas
    Limousin, Patricia
    De Vita, Enrico
    Jahanshahi, Marjan
    Ashburner, John
    Behrens, Tim
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London, UK.
    Zrinzo, Ludvic
    Connectivity derived thalamic segmentation in deep brain stimulation for tremor2018In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 18, p. 130-142Article in journal (Refereed)
    Abstract [en]

    The ventral intermediate nucleus (VIM) of the thalamus is an established surgical target for stereotactic ablation and deep brain stimulation (DBS) in the treatment of tremor in Parkinson's disease (PD) and essential tremor (ET). It is centrally placed on a cerebello-thalamo-cortical network connecting the primary motor cortex, to the dentate nucleus of the contralateral cerebellum through the dentato-rubro-thalamic tract (DRT). The VIM is not readily visible on conventional MR imaging, so identifying the surgical target traditionally involved indirect targeting that relies on atlas-defined coordinates. Unfortunately, this approach does not fully account for individual variability and requires surgery to be performed with the patient awake to allow for intraoperative targeting confirmation. The aim of this study is to identify the VIM and the DRT using probabilistic tractography in patients that will undergo thalamic DBS for tremor. Four male patients with tremor dominant PD and five patients (three female) with ET underwent high angular resolution diffusion imaging (HARDI) (128 diffusion directions, 1.5 mm isotropic voxels and b value = 1500) preoperatively. Patients received VIM-DBS using an MR image guided and MR image verified approach with indirect targeting. Postoperatively, using parallel Graphical Processing Unit (GPU) processing, thalamic areas with the highest diffusion connectivity to the primary motor area (M1), supplementary motor area (SMA), primary sensory area (S1) and contralateral dentate nucleus were identified. Additionally, volume of tissue activation (VTA) corresponding to active DBS contacts were modelled. Response to treatment was defined as 40% reduction in the total Fahn-Tolosa-Martin Tremor Rating Score (FTMTRS) with DBS-ON, one year from surgery. Three out of nine patients had a suboptimal, long-term response to treatment. The segmented thalamic areas corresponded well to anatomically known counterparts in the ventrolateral (VL) and ventroposterior (VP) thalamus. The dentate-thalamic area, lay within the M1-thalamic area in a ventral and lateral location. Streamlines corresponding to the DRT connected M1 to the contralateral dentate nucleus via the dentate-thalamic area, clearly crossing the midline in the mesencephalon. Good response was seen when the active contact VTA was in the thalamic area with highest connectivity to the contralateral dentate nucleus. Non-responders had active contact VTAs outside the dentate-thalamic area. We conclude that probabilistic tractography techniques can be used to segment the VL and VP thalamus based on cortical and cerebellar connectivity. The thalamic area, best representing the VIM, is connected to the contralateral dentate cerebellar nucleus. Connectivity based segmentation of the VIM can be achieved in individual patients in a clinically feasible timescale, using HARDI and high performance computing with parallel GPU processing. This same technique can map out the DRT tract with clear mesencephalic crossing.

  • 2. Akram, Harith
    et al.
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Zrinzo, Ludvic
    Connectivity derived thalamic segmentation: Separating myth from reality2019In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 22, article id UNSP 101758Article in journal (Refereed)
  • 3. Badoud, Simon
    et al.
    Van De Ville, Dimitri
    Nicastro, Nicolas
    Garibotto, Valentina
    Burkhard, Pierre R
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Discriminating among degenerative parkinsonisms using advanced (123)I-ioflupane SPECT analyses2016In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 12, p. 234-240Article in journal (Refereed)
    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.

  • 4.
    Bas-Hoogendam, Janna Marie
    et al.
    Leiden University, Netherlands; Leiden Institute Brain and Cognit, Netherlands.
    van Steenbergen, Henk
    Leiden University, Netherlands; Leiden Institute Brain and Cognit, Netherlands.
    Nienke Pannekoek, J.
    Imperial Coll London, England.
    Fouche, Jean-Paul
    University of Cape Town, South Africa.
    Lochner, Christine
    UCT MRC Unit Anxiety and Stress Disorders, South Africa; University of Stellenbosch, South Africa.
    Hattingh, Coenraad J.
    University of Cape Town, South Africa.
    Cremers, Henk R.
    University of Amsterdam, Netherlands.
    Furmark, Tomas
    Uppsala University, Sweden.
    Mansson, Kristoffer N. T.
    Uppsala University, Sweden; Stockholm University, Sweden; Karolinska Institute, Sweden.
    Frick, Andreas
    Uppsala University, Sweden; Karolinska Institute, Sweden.
    Engman, Jonas
    Uppsala University, Sweden.
    Boraxbekk, Carl-Johan
    Umeå University, Sweden; Copenhagen University Hospital Hvidovre, Denmark.
    Carlbring, Per
    Stockholm University, Sweden.
    Andersson, Gerhard
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Karolinska Institute, Sweden.
    Fredrikson, Mats
    Uppsala University, Sweden; Karolinska Institute, Sweden.
    Straube, Thomas
    University of Munster, Germany.
    Peterburs, Jutta
    University of Munster, Germany.
    Klumpp, Heide
    University of Illinois, IL USA; University of Illinois, IL USA.
    Luan Phanp, K.
    University of Illinois, IL USA; University of Illinois, IL USA.
    Roelofs, Karin
    Radboud University of Nijmegen, Netherlands; Radboud University of Nijmegen, Netherlands.
    Veltman, Dick J.
    Vrije University of Amsterdam, Netherlands.
    van Tol, Marie-Jose
    University of Groningen, Netherlands.
    Stein, Dan J.
    University of Cape Town, South Africa; UCT MRC Unit Anxiety and Stress Disorders, South Africa.
    van der Wee, Nic J. A.
    Leiden University, Netherlands; Leiden Institute Brain and Cognit, Netherlands.
    Voxel-based morphometry multi-center mega-analysis of brain structure in social anxiety disorder2017In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 16, p. 678-688Article in journal (Refereed)
    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.

  • 5. Bas-Hoogendam, Janna Marie
    et al.
    van Steenbergen, Henk
    Pannekoek, J. Nienke
    Fouche, Jean-Paul
    Lochner, Christine
    Hattingh, Coenraad J.
    Cremers, Henk R.
    Furmark, Tomas
    Månsson, Kristoffer
    Frick, Andreas
    Engman, Jonas
    Boraxbekk, Carl-Johan
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Carlbring, Per
    Andersson, Gerhard
    Fredriksson, Mats
    Straube, Thomas
    Peterburs, Jutta
    Klumpp, Heide
    Phan, K. Luan
    Roelofs, Karin
    Veltman, Dick J.
    van Tol, Marie-Jose
    Stein, Dan J.
    van der Wee, Nic J. A.
    Voxel-based morphometry multi-center mega-analysis of brain structure in social anxiety disorder2017In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 16, p. 678-688Article in journal (Refereed)
    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.

  • 6. Bas-Hoogendam, Janna Marie
    et al.
    van Steenbergen, Henk
    Pannekoek, J. Nienke
    Fouche, Jean-Paul
    Lochner, Christine
    Hattingh, Coenraad J.
    Cremers, Henk R.
    Furmark, Tomas
    Månsson, Kristoffer N.T.
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Clinical psychology. Uppsala University, Sweden; Karolinska Institutet, Sweden.
    Frick, Andreas
    Engman, Jonas
    Boraxbekk, Carl-Johan
    Carlbring, Per
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Clinical psychology.
    Andersson, Gerhard
    Fredrikson, Mats
    Straube, Thomas
    Peterburs, Jutta
    Klumpp, Heide
    Phan, K. Luan
    Roelofs, Karin
    Veltman, Dick J.
    van Tol, Marie-José
    Stein, Dan J.
    van der Wee, Nic J. A.
    Voxel-based morphometry multi-center mega-analysis of brain structure in social anxiety disorder2017In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 16, p. 678-688Article in journal (Refereed)
    Abstract [en]

    Social anxiety disorder (SAD) is a prevalent and disabling mental disorder, associated with significant psychiatric co-morbidity. Previous research on structural brain alterations associated with SAD has yielded inconsistent results concerning the direction of the changes in gray matter (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. Multi-site 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.

  • 7.
    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 University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Månsson, Kristoffer N.T.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Stockholm Univ, Dept Psychol, Stockholm, Sweden.;Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden..
    Frick, Andreas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden..
    Engman, Jonas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    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 University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. 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 disorder2017In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 16, p. 678-688Article in journal (Refereed)
    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.

  • 8.
    Bergamino, Maurizio
    et al.
    Laureate Institute Brain Research, OK, USA.
    Pasternak, Ofer
    Harvard University, MA, USA.
    Farmer, Madison
    Laureate Institute Brain Research, OK, USA.
    Shenton, Martha E.
    Harvard University, MA, USA; VA Boston Healthcare Syst, MA USA.
    Hamilton, Paul
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Social and Affective Neuroscience (CSAN). Laureate Institute Brain Research, OK, USA.
    Applying a free-water correction to diffusion imaging data uncovers stress-related neural pathology in depression2016In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 10, p. 336-342Article in journal (Refereed)
    Abstract [en]

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

  • 9.
    Brooks, S. J.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology. 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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Nilsson, Emil K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    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 use2016In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 12, p. 478-491Article in journal (Refereed)
    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.

  • 10.
    Dembek, Till A.
    et al.
    Department of Neurology, University of Cologne, Cologne, Germany; Department of Stereotaxy and Functional Neurosurgery, University of Cologne, Cologne, Germany.
    Barbe, Michael T
    Department of Neurology, University of Cologne, Cologne, Germany.
    Åström, Mattias
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering. Medtronic Neuromodulation, Medtronic Eindhoven Design Center, Eindhoven, The Netherlands.
    Hoevels, Mauritius
    Department of Stereotaxy and Functional Neurosurgery, University of Cologne, Cologne, Germany.
    Visser-Vandewalle, Veerle
    Department of Stereotaxy and Functional Neurosurgery, University of Cologne, Cologne, Germany.
    Fink, Gereon R
    Department of Neurology, University of Cologne, Cologne, Germany.
    Timmermann, Lars
    Department of Neurology, University of Cologne, Cologne, Germany.
    Probabilistic mapping of deep brain stimulation effects in essential tremor2017In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 13Article in journal (Refereed)
    Abstract [en]

    Objective

    To create probabilistic stimulation maps (PSMs) of deep brain stimulation (DBS) effects on tremor suppression and stimulation-induced side-effects in patients with essential tremor (ET).

    Method

    Monopolar reviews from 16 ET-patients which consisted of over 600 stimulation settings were used to create PSMs. A spherical model of the volume of neural activation was used to estimate the spatial extent of DBS for each setting. All data was pooled and voxel-wise statistical analysis as well as nonparametric permutation testing was used to confirm the validity of the PSMs.

    Results

    PSMs showed tremor suppression to be more pronounced by stimulation in the zona incerta (ZI) than in the ventral intermediate nucleus (VIM). Paresthesias and dizziness were most commonly associated with stimulation in the ZI and surrounding thalamic nuclei.

    Discussion

    Our results support the assumption, that the ZI might be a very effective target for tremor suppression. However stimulation inside the ZI and in its close vicinity was also related to the occurrence of stimulation-induced side-effects, so it remains unclear whether the VIM or the ZI is the overall better target. The study demonstrates the use of PSMs for target selection and evaluation. While their accuracy has to be carefully discussed, they can improve the understanding of DBS effects and can be of use for other DBS targets in the therapy of neurological or psychiatric disorders as well. Furthermore they provide a priori information about expected DBS effects in a certain region and might be helpful to clinicians in programming DBS devices in the future.

    Abbreviations: DBS, Deep brain stimulation; ET, Essential tremor; PSA, Posterior subthalamic area; PSM, Probabilistic stimulation map; VIM, Ventral intermediate nucleus; VNA, Volume of neural activation; ZI, Zona incerta

  • 11. Drissi, Natasha Morales
    et al.
    Warntjes, Marcel
    Wessén, Alexander
    Szakacs, Attila
    Darin, Niklas
    Hallböök, Tove
    Landtblom, Anne-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Gauffin, Helena
    Engström, Maria
    Structural anomaly in the reticular formation in narcolepsy type 1, suggesting lower levels of neuromelanin2019In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 23, article id 101875Article in journal (Refereed)
    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.

  • 12.
    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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Continuous vs. intermittent neurofeedback to regulate auditory cortex activity of tinnitus patients using real-time fMRI: A pilot study2017In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 14, p. 97-104Article in journal (Refereed)
    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.

  • 13.
    Georgiopoulos, Charalampos
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Witt, Suzanne
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Haller, Sven
    Ctr Imagerie Rive Droite SA, Switzerland; Uppsala Univ, Sweden.
    Dizdar Segrell, Nil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology in Linköping.
    Zachrisson, Helene
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Larsson, Elna-Marie
    Uppsala Univ, Sweden.
    A study of neural activity and functional connectivity within the olfactory brain network in Parkinsons disease2019In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 23, article id UNSP 101946Article in journal (Refereed)
    Abstract [en]

    Olfactory dysfunction is an early manifestation of Parkinsons 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.

  • 14. Georgiopoulos, Charalampos
    et al.
    Witt, Suzanne T
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Dizdar, Nil
    Zachrisson, Helene
    Engström, Maria
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    A study of neural activity and functional connectivity within the olfactory brain network in Parkinson's disease2019In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 23, article id 101946Article in journal (Refereed)
    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.

  • 15.
    Haatveit, Beathe
    et al.
    Norge.
    Jensen, Jimmy
    Kristianstad University, School of Education and Environment, Avdelningen för Psykologi. Kristianstad University, Research environment Man & Biosphere Health (MABH).
    Alnæs, Dag
    Norge.
    Kaufmann, Tobias
    Norge.
    Brandt, Christine L.
    Norge.
    Thoresen, Christian
    Norge.
    Andreassen, Ole A.
    Norge.
    Melle, Ingrid
    Norge.
    Ueland, Torill
    Norge.
    Westlye, Lars T.
    Norge.
    Reduced load-dependent default mode network deactivation across executive tasks in schizophrenia spectrum disorders2016In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 12, p. 389-396Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Schizophrenia is associated with cognitive impairment and brain network dysconnectivity. Recent efforts have explored brain circuits underlying cognitive dysfunction in schizophrenia and documented altered activation of large-scale brain networks, including the task-positive network (TPN) and the task-negative default mode network (DMN) in response to cognitive demands. However, to what extent TPN and DMN dysfunction reflect overlapping mechanisms and are dependent on cognitive state remain to be determined.

    METHODS: In the current study, we investigated the recruitment of TPN and DMN using independent component analysis in patients with schizophrenia spectrum disorders (n = 29) and healthy controls (n = 21) during two different executive tasks probing planning/problem-solving and spatial working memory.

    RESULTS: We found reduced load-dependent DMN deactivation across tasks in patients compared to controls. Furthermore, we observed only moderate associations between the TPN and DMN activation across groups, implying that the two networks reflect partly independent mechanisms. Additionally, whereas TPN activation was associated with task performance in both tasks, no such associations were found for DMN.

    CONCLUSION: These results support a general load-dependent DMN dysfunction in schizophrenia spectrum disorder across two demanding executive tasks that is not merely an epiphenomenon of cognitive dysfunction.

  • 16.
    Icenhour, Adriane
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Witt, Suzanne
    Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Elsenbruch, Sigrid
    University of Duisburg Essen, Germany.
    Lowén, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Tillisch, Kirsten
    University of Calif Los Angeles, CA USA.
    Mayer, Emeran A.
    University of Calif Los Angeles, CA USA.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Brain functional connectivity is associated with visceral sensitivity in women with Irritable Bowel Syndrome2017In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 15, p. 449-457Article in journal (Refereed)
    Abstract [en]

    Increased perception of visceral stimuli is a key feature of Irritable Bowel Syndrome (IBS). While altered resting-state functional connectivity (rsFC) has been also reported in IBS, the relationship between visceral hypersensitivity and aberrant rsFC is unknown. We therefore assessed rsFC within the salience, sensorimotor and default mode networks in patients with and without visceral hypersensitivity and in healthy controls (HCs). An exploratory resting-state functional magnetic resonance imaging study was performed in 41 women with IBS and 20 HCs. Group independent component analysis was used to derive intrinsic brain networks. Rectal thresholds were determined and patients were subdivided into groups with increased (hypersensitive IBS, N = 21) or normal (normosensitive IBS, N= 20) visceral sensitivity. Between-group comparisons of rsFC were carried-out using region-of-interest analyses and peak rsFC values were extracted for correlational analyses. Relative to normosensitive IBS, hypersensitive patients showed increased positive rsFC of pregenual anterior cingulate cortex and thalamus within the salience network and of posterior insula within the sensorimotor network. When compared to both hypersensitive IBS and HCs, normosensitive IBS showed decreased positive rsFC of amygdala and decreased negative rsFC in dorsal anterior insula within the DMN. DMN and sensorimotor network rsFC were associated with rectal perception thresholds, and rsFC in posterior insula was correlated with reported symptom severity in IBS. Our exploratory findings suggest that visceral sensitivity in IBS is related to changes in FC within resting-state networks associated with interoception, salience and sensory processing. These alterations may play an important role in hypervigilance and hyperalgesia in IBS.

  • 17.
    Jonasson, My
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wall, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET-MRI Platform.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET-MRI Platform.
    Nordberg, Agneta
    Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden;Theme Aging, Karolinska University Hospital, Huddinge, Sweden.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Optimal timing of tau pathology imaging and automatic extraction of a reference region using dynamic [18F]THK5317 PET.2019In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 22, article id 101681Article in journal (Refereed)
    Abstract [en]

    [18F]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 [18F]THK5317 and automated generation of SUVR-1 and relative cerebral blood flow (R1) parametric images. Nine AD patients and nine controls underwent 90 min [18F]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 R1 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, R2 = 0.97. High correlation was found between values generated using MRI- and SVCA-based reference (R2 = 0.93 for SUVR20-40-1; R2 = 0.94 for R1). 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 R1 with 40 min scan duration.

  • 18. Meskaldji, Djalel-Eddine
    et al.
    Preti, Maria Giulia
    Bolton, Thomas Aw
    Montandon, Marie-Louise
    Rodriguez, Cristelle
    Morgenthaler, Stephan
    Giannakopoulos, Panteleimon
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Van De Ville, Dimitri
    Prediction of long-term memory scores in MCI based on resting-state fMRI2016In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 12, p. 785-795Article in journal (Refereed)
    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.

  • 19.
    Morales Drissi, Natasha
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Warntjes, Marcel Jan Bertus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Wessen, Alexander
    Linköping University.
    Szakacs, Attila
    Univ Gothenburg, Sweden.
    darin, Niklas
    Univ Gothenburg, Sweden.
    Hallbook, Tove
    Univ Gothenburg, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). Uppsala Univ, Sweden.
    Gauffin, Helena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology in Linköping.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Structural anomaly in the reticular formation in narcolepsy type 1, suggesting lower levels of neuromelanin2019In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 23, article id 101875Article in journal (Refereed)
    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.

  • 20.
    Mårtensson, Gustav
    et al.
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Clin Geriatr, Stockholm, Sweden..
    Ferreira, Daniel
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Clin Geriatr, Stockholm, Sweden..
    Cavallin, Lena
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Radiol, Stockholm, Sweden..
    Muehlboeck, J-Sebastian
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Clin Geriatr, Stockholm, Sweden..
    Wahlund, Lars-Olof
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Clin Geriatr, Stockholm, Sweden..
    Wang, Chunliang
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Medical Imaging.
    Westman, Eric
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Clin Geriatr, Stockholm, Sweden.;Kings Coll London, Ctr Neuroimaging Sci, Inst Psychiat Psychol & Neurosci, Dept Neuroimaging, London, England..
    AVRA: Automatic visual ratings of atrophy from MRI images using recurrent convolutional neural networks2019In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 23, article id UNSP 101872Article in journal (Refereed)
    Abstract [en]

    Quantifying the degree of atrophy is done clinically by neuroradiologists following established visual rating scales. For these assessments to be reliable the rater requires substantial training and experience, and even then the rating agreement between two radiologists is not perfect. We have developed a model we call AVRA (Automatic Visual Ratings of Atrophy) based on machine learning methods and trained on 2350 visual ratings made by an experienced neuroradiologist. It provides fast and automatic ratings for Scheltens' scale of medial temporal atrophy (MTA), the frontal subscale of Pasquier's Global Cortical Atrophy (GCA-F) scale, and Koedam's scale of Posterior Atrophy (PA). We demonstrate substantial inter-rater agreement between AVRA's and a neuroradiologist ratings with Cohen's weighted kappa values of kappa(w) = 0.74/0.72 (MTA left/right), kappa(w) = 0.62 (GCA-F) and kappa(w) = 0.74 (PA). We conclude that automatic visual ratings of atrophy can potentially have great scientific value, and aim to present AVRA as a freely available toolbox.

  • 21.
    Nordin, Teresa
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Zsigmond, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Pujol, Sonia
    Laboratory of Mathematics in Imaging, Brigham and Women's Hospital, Harvard Medical School, USA / Surgical Planning Laboratory, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, USA.
    Westin, Carl-Fredrik
    Laboratory of Mathematics in Imaging, Brigham and Women's Hospital, Harvard Medical School, USA.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    White matter tracing combined with electric field simulation –€“ A patient-specific approach for deep brain stimulation2019In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 24, p. 1-11, article id 102026Article in journal (Refereed)
    Abstract [en]

    Objective

    Deep brain stimulation (DBS) in zona incerta (Zi) is used for symptom alleviation in essential tremor (ET). Zi is positioned along the dentato-rubro-thalamic tract (DRT). Electric field simulations with the finite element method (FEM) can be used for estimation of a volume where the stimulation affects the tissue by applying a fixed isolevel (VDBS). This work aims to develop a workflow for combined patient-specific electric field simulation and white matter tracing of the DRT, and to investigate the influence on the VDBS from different brain tissue models, lead design and stimulation modes. The novelty of this work lies in the combination of all these components.

    Method

    Patients with ET were implanted in Zi (lead 3389, n = 3, voltage mode; directional lead 6172, n = 1, current mode). Probabilistic reconstruction from diffusion MRI (dMRI) of the DRT (n = 8) was computed with FSL Toolbox. Brain tissue models were created for each patient (two homogenous, one heterogenous isotropic, one heterogenous anisotropic) and the respective VDBS (n = 48) calculated from the Comsol Multiphysics FEM simulations. The DRT and VDBS were visualized with 3DSlicer and superimposed on the preoperative T2 MRI, and the common volumes calculated. Dice Coefficient (DC) and level of anisotropy were used to evaluate and compare the brain models.

    Result

    Combined patient-specific tractography and electric field simulation was designed and evaluated, and all patients showed benefit from DBS. All VDBS overlapped the reconstructed DRT. Current stimulation showed prominent difference between the tissue models, where the homogenous grey matter deviated most (67 < DC < 69). Result from heterogenous isotropic and anisotropic models were similar (DC > 0.95), however the anisotropic model consistently generated larger volumes related to a greater extension of the electric field along the DBS lead. Independent of tissue model, the steering effect of the directional lead was evident and consistent.

    Conclusion

    A workflow for patient-specific electric field simulations in combination with reconstruction of DRT was successfully implemented. Accurate tissue classification is essential for electric field simulations, especially when using the current control stimulation. With an accurate targeting and tractography reconstruction, directional leads have the potential to tailor the electric field into the desired region.

  • 22.
    Oltedal, Leif
    et al.
    University of Bergen, Norway; University of Calif San Diego, CA 92037 USA; University of Calif San Diego, CA 92093 USA; Haukeland Hospital, Norway.
    Bartsch, Hauke
    University of Calif San Diego, CA 92037 USA; University of Calif San Diego, CA 92093 USA.
    Evjenth Sorhaug, Ole Johan
    University of Bergen, Norway.
    Kessler, Ute
    University of Bergen, Norway; Haukeland Hospital, Norway.
    Abbott, Christopher
    University of New Mexico, NM 87131 USA.
    Dols, Annemieke
    VUmc Amsterdam, Netherlands.
    Stek, Max L.
    VUmc Amsterdam, Netherlands.
    Ersland, Lars
    Haukeland Hospital, Norway.
    Emsell, Louise
    Katholieke University of Leuven, Belgium.
    van Eijndhoven, Philip
    Donders Institute Brain Cognit and Behav, Netherlands.
    Argyelan, Miklos
    Feinstein Institute Medical Research, NY USA.
    Tendolkar, Indira
    Donders Institute Brain Cognit and Behav, Netherlands.
    Nordanskog, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Hamilton, Paul J.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Balslev Jorgensen, Martin
    Psychiat Centre Copenhagen, Denmark.
    Sommer, Iris E.
    University of Medical Centre, Netherlands.
    Heringa, Sophie M.
    University of Medical Centre, Netherlands.
    Draganski, Bogdan
    University of Lausanne, Switzerland; Max Planck Institute Human Brain and Cognit Neurosci, Germany.
    Redlich, Ronny
    Department of Psychiatry, University of Münster, Germany.
    Dannlowski, Udo
    University of Munster, Germany; University of Marburg, Germany.
    Kugel, Harald
    University of Munster, Germany.
    Bouckaert, Filip
    Katholieke University of Leuven, Belgium.
    Sienaert, Pascal
    Katholieke University of Leuven, Belgium.
    Anand, Amit
    Cleveland Clin, OH 44106 USA.
    Espinoza, Randall
    University of Calif Los Angeles, CA USA.
    Narr, Katherine L.
    University of Calif Los Angeles, CA 90024 USA.
    Holland, Dominic
    University of Calif San Diego, CA 92037 USA; University of Calif San Diego, CA 92093 USA.
    Dale, Anders M.
    University of Calif San Diego, CA 92037 USA; University of Calif San Diego, CA 92093 USA; University of Calif San Diego, CA 92093 USA.
    Oedegaard, Ketil J.
    University of Bergen, Norway; Haukeland Hospital, Norway; KG Jebsen Centre Research Neuropsychiat Disorders, Norway.
    The Global ECT-MRI Research Collaboration (GEMRIC): Establishing a multi-site investigation of the neural mechanisms underlying response to electroconvulsive therapy2017In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 14, p. 422-432Article in journal (Refereed)
    Abstract [en]

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

  • 23. Petrican, Raluca
    et al.
    Söderlund, Hedvig
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Kumar, Namita
    Daskalakis, Zafiris J.
    Flint, Alastair
    Levine, Brian
    Electroconvulsive therapy “corrects” the neural architecture of visuospatial memory: Implications for typical cognitive-affective functioning2019In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582Article in journal (Refereed)
    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 sough 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.

  • 24.
    Petrican, Raluca
    et al.
    Rotman Res Inst,, Toronto, ON, Canada.
    Söderlund, Hedvig
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    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 functioning2019In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 23, article id UNSP 101816Article in journal (Refereed)
    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.

  • 25.
    Ramezani, Mahdi
    et al.
    University of British Columbia, Canada.
    Abolmaesumi, Purang
    University of British Columbia, Canada.
    Tahmasebi, Amir
    Philips Research North Amer, NY 10510 USA.
    Bosma, Rachael
    Queens University, Canada; Queens University, Canada.
    Tong, Ryan
    Queens University, Canada.
    Hollenstein, Tom
    Queens University, Canada; Queens University, Canada.
    Harkness, Kate
    Queens University, Canada; Queens University, Canada.
    Johnsrude, Ingrid
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research. Queens University, Canada; Queens University, Canada.
    Fusion analysis of first episode depression: Where brain shape deformations meet local composition of tissue2015In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 7, p. 114-121Article in journal (Refereed)
    Abstract [en]

    Computational neuroanatomical techniques that are used to evaluate the structural correlates of disorders in the brain typically measure regional differences in gray matter or white matter, or measure regional differences in the deformation fields required to warp individual datasets to a standard space. Our aim in this study was to combine measurements of regional tissue composition and of deformations in order to characterize a particular brain disorder (here, major depressive disorder). We use structural Magnetic Resonance Imaging (MRI) data from young adults in a first episode of depression, and from an age- and sex-matched group of non-depressed individuals, and create population gray matter (GM) and white matter (WM) tissue average templates using DARTEL groupwise registration. We obtained GM and WM tissue maps in the template space, along with the deformation fields required to co-register the DARTEL template and the GM and WM maps in the population. These three features, reflecting tissue composition and shape of the brain, were used within a joint independent components analysis (jICA) to extract spatially independent joint sources and their corresponding modulation profiles. Coefficients of the modulation profiles were used to capture differences between depressed and non-depressed groups. The combination of hippocampal shape deformations and local composition of tissue (but neither shape nor local composition of tissue alone) was shown to discriminate reliably between individuals in a first episode of depression and healthy controls, suggesting that brain structural differences between depressed and non-depressed individuals do not simply reflect chronicity of the disorder but arc there from the very outset.

  • 26.
    Reckless, Greg E.
    et al.
    Norge.
    Andreassen, Ole A.
    Norge.
    Server, Andres
    Norge.
    Østefjells, Tiril
    Norge.
    Jensen, Jimmy
    Kristianstad University, School of Education and Environment, Avdelningen för Humanvetenskap.
    Negative symptoms in schizophrenia are associated with aberrant striato-cortical connectivity in a rewarded perceptual decision-making task2015In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 8, p. 290-297Article in journal (Refereed)
    Abstract [en]

    Background

    Negative symptoms in schizophrenia have been associated with structural and functional changes in the prefrontal cortex. They often persist after treatment with antipsychotic medication which targets, in particular, the ventral striatum (VS). As schizophrenia has been suggested to arise from dysfunctional connectivity between neural networks, it is possible that residual aberrant striato-cortical connectivity in medicated patients plays a role in enduring negative symptomology. The present study examined the relationship between striato-cortical connectivity and negative symptoms in medicated schizophrenia patients.

    Methods

    We manipulated motivation in a perceptual decision-making task during functional magnetic resonance imaging. Comparing healthy controls (n = 21) and medicated patients with schizophrenia (n = 18) we investigated how motivation-mediated changes in VS activation affected functional connectivity with the frontal cortex, and how changes in connectivity strength from the neutral to motivated condition related to negative symptom severity.

    Results

    A pattern of aberrant striato-cortical connectivity was observed in the presence of intact VS, but altered left inferior frontal gyrus (IFG) motivation-mediated activation in patients. The more severe the patient's negative symptoms, the less the connectivity strength between the right VS and left IFG changed from the neutral to the motivated condition. Despite aberrant striato-cortical connectivity and altered recruitment of the left IFG among patients, both patients and healthy controls adopted a more liberal response strategy in the motivated compared to the neutral condition.

    Conclusions

    The present findings suggest that there is a link between dysfunctional striato-cortical connectivity and negative symptom severity, and offer a possible explanation as to why negative symptoms persist after treatment with antipsychotics.

  • 27.
    Rieckmann, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA.
    Gomperts, S N
    Johnson, K A
    Growdon, J H
    Van Dijk, K R A
    Putamen-midbrain functional connectivity is related to striatal dopamine transporter availability in patients with Lewy body diseases2015In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 8, p. 554-559Article in journal (Refereed)
    Abstract [en]

    Prior work has shown that functional connectivity between the midbrain and putamen is altered in patients with impairments in the dopamine system. This study examines whether individual differences in midbrain-striatal connectivity are proportional to the integrity of the dopamine system in patients with nigrostriatal dopamine loss (Parkinson's disease and dementia with Lewy bodies). We assessed functional connectivity of the putamen during resting state fMRI and dopamine transporter (DAT) availability in the striatum using 11C-Altropane PET in twenty patients. In line with the hypothesis that functional connectivity between the midbrain and the putamen reflects the integrity of the dopaminergic neurotransmitter system, putamen-midbrain functional connectivity was significantly correlated with striatal DAT availability even after stringent control for effects of head motion. DAT availability did not relate to functional connectivity between the caudate and thalamus/prefrontal areas. As such, resting state functional connectivity in the midbrain-striatal pathway may provide a useful indicator of underlying pathology in patients with nigrostriatal dopamine loss.

  • 28. Tymofiyeva, Olga
    et al.
    Yuan, Justin P.
    Huang, Chiung-Yu
    Connolly, Colm G.
    Henje Blom, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry. Department of Psychiatry and the Langley Porter Psychiatric Institute, Division of Child and Adolescent Psychiatry, Weill Institute for Neurosciences, University of California, San Francisco, USA.
    Xu, Duan
    Yang, Tony T.
    Application of machine learning to structural connectome to predict symptom reduction in depressed adolescents with cognitive behavioral therapy (CBT)2019In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 23, article id 101914Article in journal (Refereed)
    Abstract [en]

    Purpose: Adolescent major depressive disorder (MDD) is a highly prevalent, incapacitating and costly illness. Many depressed teens do not improve with cognitive behavioral therapy (CBT), a first-line treatment for adolescent MDD, and face devastating consequences of increased risk of suicide and many negative health outcomes. "Who will improve with CBT?" is a crucial question that remains unanswered, and treatment planning for adolescent depression remains biologically unguided. The purpose of this study was to utilize machine learning applied to patients' brain imaging data in order to help predict depressive symptom reduction with CBT.

    Methods: We applied supervised machine learning to diffusion MRI-based structural connectome data in order to predict symptom reduction in 30 depressed adolescents after three months of CBT. A set of 21 attributes was chosen, including the baseline depression score, age, gender, two global network properties, and node strengths of brain regions previously implicated in depression. The practical and robust J48 pruned tree classifier was utilized with a 10-fold cross-validation.

    Results: The classification resulted in an 83% accuracy of predicting depressive symptom reduction. The resulting tree of size seven with only three attributes highlights the role of the right thalamus in predicting depressive symptom reduction with CBT. Additional analysis showed a significant negative correlation between the change in the depressive symptoms and the node strength of the right thalamus.

    Conclusions: Our results demonstrate that a machine learning algorithm that exclusively uses structural connectome data and the baseline depression score can predict with a high accuracy depressive symptom reduction in adolescent MDD with CBT. This knowledge can help improve treatment planning for adolescent depression.

  • 29. van Wijk, B. C. M.
    et al.
    Pogosyan, A.
    Hariz, Marwan I.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London, United Kingdom.
    Akram, H.
    Foltynie, T.
    Limousin, P.
    Horn, A.
    Ewert, S.
    Brown, P.
    Litvak, V.
    Localization of beta and high-frequency oscillations within the subthalamic nucleus region2017In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 16, p. 175-183Article in journal (Refereed)
    Abstract [en]

    Parkinsonian bradykinesia and rigidity are typically associated with excessive beta band oscillations in the subthalamic nucleus. Recently another spectral peak has been identified that might be implicated in the pathophysiology of the disease: high-frequency oscillations (HFO) within the 150-400 Hz range. Beta-HFO phase-amplitude coupling (PAC) has been found to correlate with severity of motor impairment. However, the neuronal origin of HFO and its usefulness as a potential target for deep brain stimulation remain to be established. For example, it is unclear whether HFO arise from the same neural populations as beta oscillations. We intraoperatively recorded local field potentials from the subthalamic nucleus while advancing DBS electrodes in 2 mm steps from 4 mm above the surgical target point until 2 mm below, resulting in 4 recording sites. Data from 26 nuclei from 14 patients were analysed. For each trajectory, we identified the recording site with the largest spectral peak in the beta range (13-30 Hz), and the largest peak in the HFO range separately. In addition, we identified the recording site with the largest beta-HFO PAC. Recording sites with largest beta power and largest HFO power coincided in 50% of cases. In the other 50%, HFO was more likely to be detected at a more superior recording site in the target area. PAC followed more closely the site with largest HFO (45%) than beta power (27%). HFO are likely to arise from spatially close, but slightly more superior neural populations than beta oscillations. Further work is necessary to determine whether the different activities can help fine-tune deep brain stimulation targeting.

  • 30.
    Witt, Suzanne Tyson
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Bednarska, Olga
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Keita, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Icenhour, Adriane
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Jones, Michael P.
    Department of Psychology, Macquarie University, NSW, Australia.
    Elsenbruch, Sigrid
    Institute of Medical Psychology & Behavioral Immunobiology, Essen University Hospital, Essen, Germany.
    Söderholm, Johan D
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Mayer, Emeran A.
    Department of Medicine, UCLA, Los Angeles, CA, United States of America.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Interactions between gut permeability and brain structure and function in health and irritable bowel syndrome2019In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 21, article id 101602Article in journal (Refereed)
    Abstract [en]

    Changes in brain-gut interactions have been implicated in the pathophysiology of chronic visceral pain in irritable bowel syndrome (IBS). Different mechanisms of sensitization of visceral afferent pathways may contribute to the chronic visceral pain reports and associated brain changes that characterize IBS. They include increased gut permeability and gut associated immune system activation, and an imbalance in descending pain inhibitory and facilitatory mechanisms. In order to study the involvement of these mechanisms, correlations between gut epithelial permeability and live bacterial passage, and structural and functional brain connectivity were measured in women with moderate-to-severe IBS and healthy women. The relationships between gut permeability and functional and anatomical connectivity were significantly altered in IBS compared with the healthy women. IBS participants with lower epithelial permeability reported increased IBS symptoms, which was associated with increased functional and structural connectivity in endogenous pain facilitation regions. The findings suggest that relationships between gut permeability and the brain are significantly altered in IBS and suggest the existence of IBS subtypes based on these interactions.

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