| 1. |
- Blain, C R V, et al.
(författare)
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Differential corticospinal tract degeneration in homozygous 'D90A' SOD-1 ALS and sporadic ALS
- 2011
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 82:8, s. 843-849
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The homogeneous genotype and stereotyped phenotype of a unique familial form of amyotrophic lateral sclerosis (ALS) (patients homozygous for aspartate-to-alanine mutations in codon 90 (homD90A) superoxide dismutase 1) provides an ideal model for studying genotype/phenotype interactions and pathological features compared with heterogeneous apparently sporadic ALS. The authors aimed to use diffusion tensor tractography to quantify and compare changes in the intracerebral corticospinal tracts of patients with both forms of ALS, building on previous work using whole-brain voxelwise group analysis. METHOD: 21 sporadic ALS patients, seven homD90A patients and 20 healthy controls underwent 1.5 T diffusion tensor MRI. Patients were assessed using 'upper motor neuron burden,' El Escorial and ALSFR-R scales. The intracranial corticospinal tract was assessed using diffusion tensor tractography measures of fractional anisotropy (FA), mean diffusivity, and radial and axial diffusivity obtained from its entire length. RESULTS: Corticospinal tract FA was reduced in sporadic ALS patients compared with both homD90A ALS patients and controls. The diffusion measures in sporadic ALS patients were consistent with anterograde (Wallerian) degeneration of the corticospinal tracts. In sporadic ALS, corticospinal tract FA was related to clinical measures. Despite a similar degree of clinical upper motor neuron dysfunction and disability in homD90A ALS patients compared with sporadic ALS, there were no abnormalities in corticospinal tract diffusion measures compared with controls. CONCLUSIONS: Diffusion tensor tractography has shown axonal degeneration within the intracerebral portion of the corticospinal tract in sporadic ALS patients, but not those with a homogeneous form of familial ALS. This suggests significant genotypic influences on the phenotype of ALS and may provide clues to slower progression of disease in homD90A patients.
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| 2. |
- Danielsen, A, et al.
(författare)
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Investigating repetition and change in musical rhythm by functional MRI
- 2014
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Ingår i: Neuroscience. - 0306-4522 .- 1873-7544. ; 275, s. 469-476
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Tidskriftsartikel (refereegranskat)abstract
- Groove-based rhythm is a basic and much appreciated feature of Western popular music. It is commonly associated with dance, movement and pleasure and is characterized by the repetition of a basic rhythmic pattern. At various points in the musical course, drum breaks occur, representing a change compared to the repeated pattern of the groove. In the present experiment, we investigated the brain response to such drum breaks in a repetitive groove. Participants were scanned with functional magnetic resonance imaging (fMRI) while listening to a previously unheard naturalistic groove with drum breaks at uneven intervals. The rhythmic pattern and the timing of its different parts as performed were the only aspects that changed from the repetitive sections to the breaks. Differences in blood oxygen level-dependent activation were analyzed. In contrast to the repetitive parts, the drum breaks activated the left cerebellum, the right inferior frontal gyrus (RIFG), and the superior temporal gyri (STG) bilaterally. A tapping test using the same stimulus showed an increase in the standard deviation of inter-tap-intervals in the breaks versus the repetitive parts, indicating extra challenges for auditory-motor integration in the drum breaks. Both the RIFG and STG have been associated with structural irregularity and increase in musical-syntactical complexity in several earlier studies, whereas the left cerebellum is known to play a part in timing. Together these areas may be recruited in the breaks due to a prediction error process whereby the internal model is being updated. This concurs with previous research suggesting a network for predictive feed-forward control that comprises the cerebellum and the cortical areas that were activated in the breaks.
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| 3. |
- Danielsen, A, et al.
(författare)
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Investigating repetition and change in musical rhythm by functional MRI
- 2014
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Ingår i: Neuroscience. - : Elsevier Ltd.. - 0306-4522 .- 1873-7544. ; 275, s. 469-476
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Tidskriftsartikel (refereegranskat)abstract
- Groove-based rhythm is a basic and much appreciated feature of Western popular music. It is commonly associated with dance, movement and pleasure and is characterized by the repetition of a basic rhythmic pattern. At various points in the musical course, drum breaks occur, representing a change compared to the repeated pattern of the groove. In the present experiment, we investigated the brain response to such drum breaks in a repetitive groove. Participants were scanned with functional magnetic resonance imaging (fMRI) while listening to a previously unheard naturalistic groove with drum breaks at uneven intervals. The rhythmic pattern and the timing of its different parts as performed were the only aspects that changed from the repetitive sections to the breaks. Differences in blood oxygen level-dependent activation were analyzed. In contrast to the repetitive parts, the drum breaks activated the left cerebellum, the right inferior frontal gyrus (RIFG), and the superior temporal gyri (STG) bilaterally. A tapping test using the same stimulus showed an increase in the standard deviation of inter-tap-intervals in the breaks versus the repetitive parts, indicating extra challenges for auditory-motor integration in the drum breaks. Both the RIFG and STG have been associated with structural irregularity and increase in musical-syntactical complexity in several earlier studies, whereas the left cerebellum is known to play a part in timing. Together these areas may be recruited in the breaks due to a prediction error process whereby the internal model is being updated. This concurs with previous research suggesting a network for predictive feed-forward control that comprises the cerebellum and the cortical areas that were activated in the breaks.
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| 4. |
- Månsson, Kristoffer N T, et al.
(författare)
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Predicting long-term outcome of Internet-delivered cognitive behavior therapy for social anxiety disorder using fMRI and support vector machine learning
- 2015
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Cognitive behavior therapy (CBT) is an effective treatment for social anxiety disorder (SAD), but many patients do not respond sufficiently and a substantial proportion relapse after treatment has ended. Predicting an individual’s long-term clinical response therefore remains an important challenge. This study aimed at assessing neural predictors of long-term treatment outcome in participants with SAD 1 year after completion of Internet-delivered CBT (iCBT). Twenty-six participants diagnosed with SAD underwent iCBT including attention bias modification for a total of 13 weeks. Support vector machines (SVMs), a supervised pattern recognition method allowing predictions at the individual level, were trained to separate long-term treatment responders from nonresponders based on blood oxygen level-dependent (BOLD) responses to self-referential criticism. The Clinical Global Impression-Improvement scale was the main instrument to determine treatment response at the 1-year follow-up. Results showed that the proportion of long-term responders was 52%(12/23). From multivariate BOLD responses in the dorsal anterior cingulate cortex (dACC) together with the amygdala, we were able to predict long-term response rate of iCBT with an accuracy of 92% (confidence interval 95% 73.2–97.6). This activation pattern was, however, not predictive of improvement in the continuous Liebowitz Social Anxiety Scale—Self-report version. Follow-up psychophysiological interaction analyses revealed that lower dACC–amygdala coupling was associated with better long-term treatment response. Thus, BOLD response patterns in the fear-expressing dACC–amygdala regions were highly predictive of long-term treatment outcome of iCBT, and the initial coupling between these regions differentiated long-term responders from nonresponders. The SVM-neuroimaging approach could be of particular clinical value as it allows for accurate prediction of treatment outcome at the level of the individual.
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| 5. |
- Månsson, Kristoffer, et al.
(författare)
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Predicting Long-Term Outcome of Cognitive Behaviour Therapy for Social Anxiety Disorder Using fMRI and Support Vector Machiness
- 2014
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Ingår i: Abstracts from the 44th Congress of the European Association for Behavioural & Cognitive Therapies.
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Konferensbidrag (refereegranskat)abstract
- Background: Cognitive behavioural therapy (CBT) has yielded robust treatment effects for social anxiety disorder (SAD) but still many patients do not respond fully to treatment, and a substantial proportion relapse after treatment has ended. Identification of robust predictors of sustained treatment responses could be of high clinical importance.Methods: We used functional magnetic resonance imaging (fMRI; 3T General Electric) to assess 26 patients (85% women, mean age 32.3 years) with SAD. Blood-oxygen-level dependent (BOLD) responses to self-referential criticism, i.e. reading sentences such as "Nobody likes you" were compared to criticism referring to other individuals. Responses in the fear network, i.e. the amygdala, hippocampus, anterior cingulate cortex (ACC), and insula, were evaluated in a Support Vector Machine (SVM) approach to predict treatment outcome one-year after Internet-delivered CBT. We applied leave-one-out cross-validation to increase the generalizability of the data.Results: At one-year follow-up, three patients had dropped out. Twelve (52%) of the assessed patients met the response criteria, i.e. very much or much improved according to the Clinical Global Impression-Improvement scale (CGI-I). SVM on initial BOLD response, accurately classified patients according to responder status, based on multi-voxel patterns in the ACC (balanced accuracy of 91.7%, p=.001), and the ACC together with the amygdala (83.0%, p=.004) as well as the hippocampus (73.9%,p=.032).Conclusions: We demonstrate that initial multi-voxel BOLD response patterns to self-referential criticism in the ACC, amygdala, and hippocampus are highly predictive of long-term improvement of CBT in patients with SAD.
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| 6. |
- Petzke, F, et al.
(författare)
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Using fMRI to evaluate the effects of milnacipran on central pain processing in patients with fibromyalgia.
- 2013
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Ingår i: Scandinavian Journal of Pain. - : Walter de Gruyter GmbH. - 1877-8860 .- 1877-8879. ; 4:2, s. 65-74
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Tidskriftsartikel (refereegranskat)abstract
- Background In recent years, the prescription of serotonin-noradrenalin reuptake inhibitors (SNRIs) for treatment of fibromyalgia (FM) has increased with reports of their efficacy. The SNRI milnacipran is approved by the U.S. Food and Drug Administration (FDA) for treatment of FM, yet, the mechanisms by which milnacipran reduces FM symptoms are unknown. A large number of neuroimaging studies have demonstrated altered brain function in patients with FM but the effect of milnacipran on central pain processing has not been investigated. The primary objective of this study was to assess the effect of milnacipran on sensitivity to pressure-evoked pain in FM. Secondary objectives were to assess the effect of milnacipran on cerebral processing of pressure-evoked pain using fMRI and the tolerability and safety of milnacipran 200 mg/day in FM. Methods 92 patients were randomized to either 13-weeks milnacipran treatment (200 mg/day) or placebo in this double-blind, placebo-controlled multicenter clinical trial. Psychophysical measures and functional MRI (fMRI) assessments were performed before and after treatment using a computer-controlled pressure-pain stimulator. Here, we present the results of several a priori defined statistical analyses. Results Milnacipran-treated patients displayed a trend toward lower pressure-pain sensitivity after treatment, compared to placebo, and the difference was greater at higher pain intensities. A single group fMRI analysis of milnacipran-treated patients indicated increased pain-evoked brain activity in the caudatus nucleus, anterior insula and amygdala after treatment, compared to before treatment; regions implicated in pain inhibitory processes. A 2 × 2 repeated measures fMRI analysis, comparing milnacipran and placebo, before and after treatment, showed that milnacipran-treated patients had greater pain-evoked activity in the precuneus/posterior cingulate cortex after treatment; a region previously implicated in intrinsic brain function and FM pathology. This finding was only significant when uncorrected for multiple comparisons. The safety analysis revealed that patients from both treatment groups had treatment-emergent adverse events where nausea was the most common complaint, reported by 43.5% of placebo patients and 71.7% of milnacipran-treated patients. Patients on milnacipran were more likely to discontinue treatment because of side effects. Conclusions Our results provide preliminary indications of increased pain inhibitory responses in milnacipran-treated FM patients, compared to placebo. The psychophysical assessments did not reach statistical significance but reveal a trend toward higher pressure-pain tolerance after treatment with milnacipran, compared to placebo, especially for higher pain intensities. Our fMRI analyses point toward increased activation of the precuneus/posterior cingulum in patients treated with milnacipran, however results were not corrected for multiple comparisons. The precuneus/posterior cingulum is a key region of the default mode network and has previously been associated with abnormal function in FM. Future studies may further explore activity within the default mode network as a potential biomarker for abnormal central pain processing. Implications The present study provides novel insights for future studies where functional neuroimaging may be used to elucidate the central mechanisms of common pharmacological treatments for chronic pain. Furthermore, our results point toward a potential mechanism for pain normalization in response to milnacipran, involving regions of the default mode network although this finding needs to be replicated in future studies.
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| 7. |
- Sweeney, M. D., et al.
(författare)
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Vascular dysfunction-The disregarded partner of Alzheimer's disease
- 2019
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 15:1, s. 158-167
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Tidskriftsartikel (refereegranskat)abstract
- Increasing evidence recognizes Alzheimer's disease (AD) as a multifactorial and heterogeneous disease with multiple contributors to its pathophysiology, including vascular dysfunction. The recently updated AD Research Framework put forth by the National Institute on Aging-Alzheimer's Association describes a biomarker-based pathologic definition of AD focused on amyloid, tau, and neuronal injury. In response to this article, here we first discussed evidence that vascular dysfunction is an important early event in AD pathophysiology. Next, we examined various imaging sequences that could be easily implemented to evaluate different types of vascular dysfunction associated with, and/or contributing to, AD pathophysiology, including changes in blood-brain barrier integrity and cerebral blood flow. Vascular imaging biomarkers of small vessel disease of the brain, which is responsible for >50% of dementia worldwide, including AD, are already established, well characterized, and easy to recognize. We suggest that these vascular biomarkers should be incorporated into the AD Research Framework to gain a better understanding of AD pathophysiology and aid in treatment efforts. (C) 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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