| 1. |
- Jakabek, David, et al.
(författare)
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Regional structural hypo- and hyperconnectivity of frontal–striatal and frontal–thalamic pathways in behavioral variant frontotemporal dementia
- 2018
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Ingår i: Human Brain Mapping. - : Wiley. - 1065-9471. ; 39:10, s. 4083-4093
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Tidskriftsartikel (refereegranskat)abstract
- Behavioral variant frontotemporal dementia (bvFTD) has been predominantly considered as a frontotemporal cortical disease, with limited direct investigation of frontal–subcortical connections. We aim to characterize the grey and white matter components of frontal–thalamic and frontal–striatal circuits in bvFTD. Twenty-four patients with bvFTD and 24 healthy controls underwent morphological and diffusion imaging. Subcortical structures were manually segmented according to published protocols. Probabilistic pathways were reconstructed separately from the dorsolateral, orbitofrontal and medial prefrontal cortex to the striatum and thalamus. Patients with bvFTD had smaller cortical and subcortical volumes, lower fractional anisotropy, and higher mean diffusivity metrics, which is consistent with disruptions in frontal–striatal–thalamic pathways. Unexpectedly, regional volumes of the striatum and thalamus connected to the medial prefrontal cortex were significantly larger in bvFTD (by 135% in the striatum, p =.032, and 217% in the thalamus, p =.004), despite smaller dorsolateral prefrontal cortex connected regional volumes (by 67% in the striatum, p =.002, and 65% in the thalamus, p =.020), and inconsistent changes in orbitofrontal cortex connected regions. These unanticipated findings may represent compensatory or maladaptive remodeling in bvFTD networks. Comparisons are made to other neuropsychiatric disorders suggesting a common mechanism of changes in frontal–subcortical networks; however, longitudinal studies are necessary to test this hypothesis.
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| 2. |
- Jakabek, David, et al.
(författare)
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Structural and microstructural thalamocortical network disruption in sporadic behavioural variant frontotemporal dementia
- 2023
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Ingår i: NeuroImage: Clinical. - 2213-1582. ; 39, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Using multi-block methods we combined multimodal neuroimaging metrics of thalamic morphology, thalamic white matter tract diffusion metrics, and cortical thickness to examine changes in behavioural variant frontotemporal dementia. (bvFTD). Method: Twenty-three patients with sporadic bvFTD and 24 healthy controls underwent structural and diffusion MRI scans. Clinical severity was assessed using the Clinical Dementia Rating scale and behavioural severity using the Frontal Behaviour Inventory by patient caregivers. Thalamic volumes were manually segmented. Anterior and posterior thalamic radiation fractional anisotropy and mean diffusivity were extracted using Tract-Based Spatial Statistics. Finally, cortical thickness was assessed using Freesurfer. We used shape analyses, diffusion measures, and cortical thickness as features in sparse multi-block partial least squares (PLS) discriminatory analyses to classify participants within bvFTD or healthy control groups. Sparsity was tuned with five-fold cross-validation repeated 10 times. Final model fit was assessed using permutation testing. Additionally, sparse multi-block PLS was used to examine associations between imaging features and measures of dementia severity. Results: Bilateral anterior-dorsal thalamic atrophy, reduction in mean diffusivity of thalamic projections, and frontotemporal cortical thinning, were the main features predicting bvFTD group membership. The model had a sensitivity of 96%, specificity of 68%, and was statistically significant using permutation testing (p = 0.012). For measures of dementia severity, we found similar involvement of regional thalamic and cortical areas as in discrimination analyses, although more extensive thalamo-cortical white matter metric changes. Conclusions: Using multimodal neuroimaging, we demonstrate combined structural network dysfunction of anterior cortical regions, cortical-thalamic projections, and anterior thalamic regions in sporadic bvFTD.
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| 3. |
- Lindberg, Olof, et al.
(författare)
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Hippocampal Shape Analysis in Alzheimer's Disease and Frontotemporal Lobar Degeneration Subtypes
- 2012
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 30:2, s. 355-365
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Tidskriftsartikel (refereegranskat)abstract
- Hippocampal pathology is central to Alzheimer's disease (AD) and other forms of dementia such as frontotemporal lobar degeneration (FTLD). Autopsy studies have shown that certain hippocampal subfields are more vulnerable than others to AD and FTLD pathology, in particular the subiculum and cornu ammonis 1 (CA1). We conducted shape analysis of hippocampi segmented from structural T1 MRI images on clinically diagnosed dementia patients and controls. The subjects included 19 AD and 35 FTLD patients [13 frontotemporal dementia (FTD), 13 semantic dementia (SD), and 9 progressive nonfluent aphasia (PNFA)] and 21 controls. Compared to controls, SD displayed severe atrophy of the whole left hippocampus. PNFA and FTD also displayed atrophy on the left side, restricted to the hippocampal head in FTD. Finally, AD displayed most atrophy in left hippocampal body with relative sparing of the hippocampal head. Consistent with neuropathological studies, most atrophic deformation was found in CA1 and subiculum areas in FTLD and AD.
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| 4. |
- Looi, Jeffrey C. L., et al.
(författare)
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Morphometric analysis of subcortical structures in progressive supranuclear palsy: In vivo evidence of neostriatal and mesencephalic atrophy
- 2011
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Ingår i: Psychiatry Research: Neuroimaging. - : Elsevier BV. - 0925-4927. ; 194:2, s. 163-175
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Tidskriftsartikel (refereegranskat)abstract
- Progressive supranuclear palsy (PSP) is a neurodegenerative disease characterized by gait and postural disturbance, gaze palsy, apathy, decreased verbal fluency and dysexecutive symptoms, with some of these clinical features potentially having origins in degeneration of frontostriatal circuits and the mesencephalon. This hypothesis was investigated by manual segmentation of the caudate and putamen on MRI scans, using previously published protocols, in 15 subjects with PSP and 15 healthy age-matched controls. Midbrain atrophy was assessed by measurement of mid-sagittal area of the midbrain and pons. Shape analysis of the caudate and putamen was performed using spherical harmonics (SPHARM-PDM, University of North Carolina). The sagittal pons area/midbrain area ratio (P/M ratio) was significantly higher in the PSP group, consistent with previous findings. Significantly smaller striatal volumes were found in the PSP group - putamina were 10% smaller and caudate volumes were 17% smaller than in controls after controlling for age and intracranial volume. Shape analysis revealed significant shape deflation in PSP in the striatum, compared to controls; with regionally significant change relevant to frontostriatal and corticostriatal circuits in the caudate. Thus, in a clinically diagnosed and biomarker-confirmed cohort with early PSP, we demonstrate that neostriatal volume and shape are significantly reduced in vivo. The findings suggest a neostriatal and mesencephalic structural basis for the clinical features of PSP leading to frontostriatal and mesocortical-striatal circuit disruption. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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| 5. |
- Looi, Jeffrey C. L., et al.
(författare)
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The Australian, US, Scandinavian Imaging Exchange (AUSSIE): an innovative, virtually-integrated health research network embedded in health care
- 2014
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Ingår i: Australasian Psychiatry. - : SAGE Publications. - 1039-8562 .- 1440-1665. ; 22:3, s. 260-265
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To describe the development, design and function of an innovative international clinical research network for neuroimaging research, based in Australia, within a joint state health service/medical school. This Australian, US, Scandinavian Imaging Exchange (AUSSIE) network focuses upon identifying neuroimaging biomarkers for neuropsychiatric and neurodegenerative disease. Methods: We describe a case study of the iterative development of the network, identifying characteristic features and methods which may serve as potential models for virtual clinical research networks. This network was established to analyse clinically-derived neuroimaging data relevant to neuropsychiatric and neurodegenerative disease, specifically in relation to subcortical brain structures. Results: The AUSSIE network has harnessed synergies from the individual expertise of the component groups, primarily clinical neuroscience researchers, to analyse a variety of clinical data. Conclusion: AUSSIE is an active virtual clinical research network, analogous to a connectome, which is embedded in health care and has produced significant research, advancing our understanding of neuropsychiatric and neurodegenerative disease through the lens of neuroimaging.
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| 6. |
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| 7. |
- Macfarlane, Matthew D, et al.
(författare)
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Striatal Atrophy in the Behavioural Variant of Frontotemporal Dementia: Correlation with Diagnosis, Negative Symptoms and Disease Severity.
- 2015
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:6
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Tidskriftsartikel (refereegranskat)abstract
- Behavioural variant frontotemporal dementia (bvFTD) is associated with changes in dorsal striatal parts of the basal ganglia (caudate nucleus and putamen), related to dysfunction in the cortico-striato-thalamic circuits which help mediate executive and motor functions. We aimed to determine whether the size and shape of striatal structures correlated with diagnosis of bvFTD, and measures of clinical severity, behaviour and cognition.
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| 8. |
- Owens-Walton, Conor, et al.
(författare)
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Increased functional connectivity of thalamic subdivisions in patients with Parkinson’s disease
- 2019
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:9
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Tidskriftsartikel (refereegranskat)abstract
- Parkinson’s disease (PD) affects 2–3% of the population over the age of 65 with loss of dopaminergic neurons in the substantia nigra impacting the functioning of basal ganglia-thalamocortical circuits. The precise role played by the thalamus is unknown, despite its critical role in the functioning of the cerebral cortex, and the abnormal neuronal activity of the structure in PD. Our objective was to more clearly elucidate how functional connectivity and morphology of the thalamus are impacted in PD (n = 32) compared to Controls (n = 20). To investigate functional connectivity of the thalamus we subdivided the structure into two important regions-of-interest, the first with putative connections to the motor cortices and the second with putative connections to prefrontal cortices. We then investigated potential differences in the size and shape of the thalamus in PD, and how morphology and functional connectivity relate to clinical variables. Our data demonstrate that PD is associated with increases in functional connectivity between motor subdivisions of the thalamus and the supplementary motor area, and between prefrontal thalamic subdivisions and nuclei of the basal ganglia, anterior and dorsolateral prefrontal cortices, as well as the anterior and paracingulate gyri. These results suggest that PD is associated with increased functional connectivity of subdivisions of the thalamus which may be indicative alterations to basal ganglia-thalamocortical circuitry.
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| 9. |
- Owens-Walton, Conor, et al.
(författare)
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Midsagittal corpus callosal thickness and cognitive impairment in Parkinson's disease
- 2022
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Ingår i: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 55:7, s. 1859-1872
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Tidskriftsartikel (refereegranskat)abstract
- People diagnosed with Parkinson's disease (PD) can experience significant neuropsychiatric symptoms, including cognitive impairment and dementia, the neuroanatomical substrates of which are not fully characterised. Symptoms associated with cognitive impairment and dementia in PD may relate to direct structural changes to the corpus callosum via primary white matter pathology or as a secondary outcome due to the degeneration of cortical regions. Using magnetic resonance imaging, the corpus callosum can be investigated at the midsagittal plane, where it converges to a contiguous mass and is not intertwined with other tracts. The objective of this project was thus twofold: First, we investigated possible changes in the thickness of the midsagittal callosum and cortex in patients with PD with varying levels of cognitive impairment; and secondly, we investigated the relationship between the thickness of the midsagittal corpus callosum and the thickness of the cortex. Study participants included cognitively unimpaired PD participants (n = 35), PD participants with mild cognitive impairment (n = 22), PD participants with dementia (n = 17) and healthy controls (n = 27). We found thinning of the callosum in PD-related dementia compared with PD-related mild cognitive impairment and cognitively unimpaired PD participants. Regression analyses found thickness of the left medial orbitofrontal cortex to be positively correlated with thickness of the anterior callosum in PD-related mild cognitive impairment. This study suggests that a midsagittal thickness model can uncover changes to the corpus callosum in PD-related dementia, which occur in line with changes to the cortex in this advanced disease stage.
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| 10. |
- Owens-Walton, Conor, et al.
(författare)
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Striatal changes in Parkinson disease : An investigation of morphology, functional connectivity and their relationship to clinical symptoms
- 2018
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Ingår i: Psychiatry Research - Neuroimaging. - : Elsevier BV. - 0925-4927 .- 1872-7506. ; 275, s. 5-13
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Tidskriftsartikel (refereegranskat)abstract
- We sought to investigate morphological and resting state functional connectivity changes to the striatal nuclei in Parkinson disease (PD) and examine whether changes were associated with measures of clinical function. Striatal nuclei were manually segmented on 3T-T1 weighted MRI scans of 74 PD participants and 27 control subjects, quantitatively analysed for volume, shape and also functional connectivity using functional MRI data. Bilateral caudate nuclei and putamen volumes were significantly reduced in the PD cohort compared to controls. When looking at left and right hemispheres, the PD cohort had significantly smaller left caudate nucleus and right putamen volumes compared to controls. A significant correlation was found between greater atrophy of the caudate nucleus and poorer cognitive function, and between greater atrophy of the putamen and more severe motor symptoms. Resting-state functional MRI analysis revealed altered functional connectivity of the striatal structures in the PD group. This research demonstrates that PD involves atrophic changes to the caudate nucleus and putamen that are linked to clinical dysfunction. Our work reveals important information about a key structure-function relationship in the brain and provides support for caudate nucleus and putamen atrophy as neuroimaging biomeasures in PD.
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| 11. |
- Owens-Walton, Conor, et al.
(författare)
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Structural and functional neuroimaging changes associated with cognitive impairment and dementia in Parkinson's disease
- 2021
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Ingår i: Psychiatry Research - Neuroimaging. - : Elsevier BV. - 0925-4927. ; 312
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Tidskriftsartikel (refereegranskat)abstract
- This study seeks a better understanding of possible pathophysiological mechanisms associated with cognitive impairment and dementia in Parkinson's disease using structural and functional MRI. We investigated resting-state functional connectivity of important subdivisions of the caudate nucleus, putamen and thalamus, and also how the morphology of these structures are impacted in the disorder. We found cognitively unimpaired Parkinson's disease subjects (n = 33), compared to controls (n = 26), display increased functional connectivity of the dorsal caudate, anterior putamen and mediodorsal thalamic subdivisions with areas across the frontal lobe, as well as reduced functional connectivity of the dorsal caudate with posterior cortical and cerebellar regions. Compared to cognitively unimpaired subjects, those with mild cognitive impairment (n = 22) demonstrated reduced functional connectivity of the mediodorsal thalamus with the paracingulate cortex, while also demonstrating increased functional connectivity of the mediodorsal thalamus with the posterior cingulate cortex, compared to subjects with dementia (n = 17). Extensive volumetric and surface-based deflation was found in subjects with dementia compared to cognitively unimpaired Parkinson's disease participants and controls. Our research suggests that structures within basal ganglia-thalamocortical circuits are implicated in cognitive impairment and dementia in Parkinson's disease, with cognitive impairment and dementia associated with a breakdown in functional connectivity of the mediodorsal thalamus with para- and posterior cingulate regions of the brain respectively.
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| 12. |
- Power, Brian D., et al.
(författare)
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Morphometric analysis of thalamic volume in progressive supranuclear palsy : In vivo evidence of regionally specific bilateral thalamic atrophy
- 2017
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Ingår i: Psychiatry Research - Neuroimaging. - : Elsevier BV. - 0925-4927. ; 265, s. 65-71
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Tidskriftsartikel (refereegranskat)abstract
- We investigated whether differences were detectable in the volume and shape of the dorsal thalamus on magnetic resonance imaging in patients with progressive supranuclear palsy (PSP). Manual segmentation of the left and right thalami on magnetic resonance imaging scans occurred in 22 patients with clinically diagnosed PSP and 23 healthy controls; thalamic volumes (left, right, total) were calculated. Between group differences were explored by multivariate analysis of co-variance, using age and intracranial volume as covariates. Analysis of the shape of the thalamus was performed using the spherical harmonic point distribution method software package. Patients with PSP were found to have significant bilateral thalamic atrophy on magnetic resonance imaging; there was significant shape deflation over the anterior-lateral and anterior-ventral surfaces bilaterally, and over the right caudal thalamus. Recognizing decreased thalamic morphology in PSP patients in vivo may be an important component of an ensemble of diagnostic biomarkers in the future, particularly given the difficulty of distinguishing PSP from other Parkinsonian conditions early in the disease course.
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| 13. |
- Power, Brian D, et al.
(författare)
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Validation of a protocol for manual segmentation of the thalamus on magnetic resonance imaging scans.
- 2015
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Ingår i: Psychiatry Research. - : Elsevier BV. - 1872-7123 .- 0925-4927. ; 232:1, s. 98-105
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Tidskriftsartikel (refereegranskat)abstract
- We present a validated protocol for manual segmentation of the thalamus on T1-weighted magnetic resonance imaging (MRI) scans using brain image analysis software. The MRI scans of five normal control subjects were randomly selected from a larger cohort recruited from Lund University Hospital and Landskrona Hospital, Sweden. MRIs were performed using a 3.0T Philips MR scanner, with an eight-channel head coil, and high resolution images were acquired using a T1-weighted turbo field echo (T1 TFE) pulse sequence, with resulting voxel size 1×1×1mm(3). Manual segmentation of the left and right thalami and volume measurement was performed on 28-30 contiguous coronal slices, using ANALYZE 11.0 software. Reliability of image analysis was performed by measuring intra-class correlations between initial segmentation and random repeated segmentation of the left and right thalami (in total 10 thalami for segmentation); inter-rater reliability was measured using volumes obtained by two other experienced tracers. Intra-class correlations for two independent raters were 0.95 and 0.98; inter-class correlations between the expert rater and two independent raters were 0.92 and 0.98. We anticipate that mapping thalamic morphology in various neuropsychiatric disorders may yield clinically useful disease-specific biomarkers.
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| 14. |
- Yoo, Jae-Gon, et al.
(författare)
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MRI morphology of the hippocampus in drug-resistant temporal lobe epilepsy: shape inflation of left hippocampus and correlation of right-sided hippocampal volume and shape with visuospatial function in patients with right-sided TLE
- 2019
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Ingår i: Journal of Clinical Neuroscience. - : Elsevier BV. - 1532-2653 .- 0967-5868. ; 67, s. 68-74
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Tidskriftsartikel (refereegranskat)abstract
- We sought to quantify the morphology in vivo of hippocampi in patients with drug resistant temporal lobe epilepsy (TLE) via magnetic resonance imaging (MRI), prior to temporal lobe resection, and the correlation of surface-based shape analysis of morphology and clinical cognitive function.Thirty patients with drug-resistant TLE and twenty healthy controls underwent clinical neuropsychological testing, and brain MRI at Lund University Hospital prior to hippocampal resection. A neuroradiologist categorised radiological findings into normal hippocampus, subtle changes or definite hippocampal sclerosis. We manually segmented MRI of the hippocampus of participants using ANALYZE 11.0 software; and analysed hippocampal shape using SPHARM-PDM software.For radiologist visual-ratings of definite left hippocampal sclerosis in those with left-sided TLE, hippocampal volumes were significantly smaller compared to normal controls. In right-sided TLE we found contralateral shape inflation of the left hippocampus, partially confirming previous shape analytic studies of the hippocampus in TLE. We found significant correlation of volume and surface deflation of the right hippocampus in right-sided TLE with reduced performance on the two right-lateralised visuospatial memory tests, the Rey Complex Figure Test (Immediate and Delayed recall) and the Recognition Memory Test for faces. Decreased hippocampal volume was correlated with poorer performance on these tasks.The morphology of the hippocampus can be quantified via neuroimaging shape analysis in TLE. Contralateral shape inflation of the left hippocampus in right-sided TLE is intriguing, and may result from functional compensation and/or abnormal tissue. In right-sided TLE, hippocampal structural integrity, quantified as hippocampal shape, is correlated with lateralised visuospatial function.
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