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Pichiecchio, A., E. Tavazzi, G. Poloni, M. Ponzio, F. Palesi, M. Pasin, L. Piccolo, et al. "Advanced magnetic resonance imaging of neuromyelitis optica: a multiparametric approach." Multiple Sclerosis Journal 18, no. 6 (December 19, 2011): 817–24. http://dx.doi.org/10.1177/1352458511431072.
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Background: Several authors have used advanced magnetic resonance imaging (MRI) techniques to investigate whether patients with neuromyelitis optica (NMO) have occult damage in normal-appearing brain tissue, similarly to multiple sclerosis (MS). To date, the literature contains no data derived from the combined use of several advanced MRI techniques in the same NMO subjects. Objective: We set out to determine whether occult damage could be detected in the normal-appearing brain tissue of a small group of patients with NMO using a multiparametric MRI approach. Methods: Eight female patients affected by NMO (age range 44–58 years) and seven sex- and age-matched healthy controls were included. The techniques used on a 1.5 T MRI imaging scanner were magnetization transfer imaging, diffusion tensor imaging, tract-based spatial statistics, spectroscopy and voxel-based morphometry in order to analyse normal-appearing white matter and normal-appearing grey matter. Results: Structural and metabolic parameters showed no abnormalities in normal-appearing white matter of patients with NMO. Conversely, tract-based spatial statistics demonstrated a selective alteration of the optic pathways and the lateral geniculate nuclei. Diffusion tensor imaging values in the normal-appearing grey matter were found to be significantly different in the patients with NMO versus the healthy controls. Moreover, voxel-based morphometry analysis demonstrated a significant density and volume reduction of the sensorimotor cortex and the visual cortex. Conclusions: Our data disclosed occult structural damage in the brain of patients with NMO, predominantly involving regions connected with motor and visual systems. This damage seems to be the direct consequence of transsynaptic degeneration triggered by lesions of the optic nerve and spine.
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Ota, Miho, Yasuhiro Nakata, Kimiteru Ito, Kouhei Kamiya, Masafumi Ogawa, Miho Murata, Satoko Obu, Hiroshi Kunugi, and Noriko Sato. "Differential Diagnosis Tool for Parkinsonian Syndrome Using Multiple Structural Brain Measures." Computational and Mathematical Methods in Medicine 2013 (2013): 1–10. http://dx.doi.org/10.1155/2013/571289.
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Clinical differentiation of parkinsonian syndromes such as the Parkinson variant of multiple system atrophy (MSA-P) and cerebellar subtype (MSA-C) from Parkinson's disease is difficult in the early stage of the disease. To identify the correlative pattern of brain changes for differentiating parkinsonian syndromes, we applied discriminant analysis techniques by magnetic resonance imaging (MRI). T1-weighted volume data and diffusion tensor images were obtained by MRI in eighteen patients with MSA-C, 12 patients with MSA-P, 21 patients with Parkinson’s disease, and 21 healthy controls. They were evaluated using voxel-based morphometry and tract-based spatial statistics, respectively. Discriminant functions derived by step wise methods resulted in correct classification rates of 0.89. When differentiating these diseases with the use of three independent variables together, the correct classification rate was the same as that obtained with step wise methods. These findings support the view that each parkinsonian syndrome has structural deviations in multiple brain areas and that a combination of structural brain measures can help to distinguish parkinsonian syndromes.
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Hartmann, Tue, Sanne Vandborg, Raben Rosenberg, Leif Sørensen, and Poul Videbech. "Increased fractional anisotropy in cerebellum in obsessive–compulsive disorder." Acta Neuropsychiatrica 28, no. 3 (November 2, 2015): 141–48. http://dx.doi.org/10.1017/neu.2015.57.
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BackgroundPrevious morphology and diffusion-imaging studies have suggested that structural changes in white matter is an important part of the pathophysiology of obsessive–compulsive disorder (OCD). However, different methodological approaches and the heterogeneity of patient samples question the validity of the findings.Materials and methodsIn total, 30 patients were matched for age and sex with 30 healthy controls. All participants underwent T1-weighted magnetic resonance imaging, diffusion tensor imaging and T2 fluid-attenuated inversion recovery. Voxel-based morphometry and tract-based spatial statistics were used to compare white matter volumes and diffusion tensor imaging between groups. These data were analysed correcting for the effects of multiple comparisons, age, sex, severity and duration of illness as nuisance covariates. White matter hyperintensities were manually identified.ResultsIncrease in fractional anisotropy in cerebellum was the most prominent result. A decrease in fractional anisotrophy in patients comparable with previous studies was located in forceps minor. There were no differences in the white matter morphology or in the white matter hyperintensities between patients and healthy controls.ConclusionDecrease in fractional anisotrophy in forceps minor and increase in cerebellum were found, and they were not due to neither white matter hyperintensities nor morphology of the white matter. Cerebellar hyperconnectivity could be an important part of OCD pathophysiology.
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Beckmann, Yesim, Sevgin Gökçe, Nabi Zorlu, H. Sabiha Türe, and Fazıl Gelal. "Longitudinal assessment of gray matter volumes and white matter integrity in patients with medication-overuse headache." Neuroradiology Journal 31, no. 2 (January 31, 2018): 150–56. http://dx.doi.org/10.1177/1971400918756374.
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Background Medication-overuse headache is a common clinical entity, but neuroimaging studies investigating volumetric and microstructural alterations of the brain in medication-overuse headache are rare. Therefore, in the current longitidunal study we evaluated gray matter volume and white matter integrity in patients with medication-overuse headache before and after drug withdrawal. Methods A prospective study evaluated 27 patients with medication-overuse headache and 27 age-, sex-, and education-matched healthy adults. High-resolution T1-weighted magnetic resonance imaging and diffusion tensor imaging were obtained from the control group and medication-overuse headache patients before and six months after drug withdrawal. Tract-based spatial statistics of multiple diffusivity indices and voxel-based morphometry were employed to investigate white and gray matter abnormalities. Results No correlation was found between age, gender, education and smoking status in both groups. The most commonly overused medications were simple analgesics (96.3%) and combined analgesics (3.7%). The mean duration of the history of medication overuse and headaches was 56.7 ± 63.5 months. White matter diffusional and gray matter morphological alterations including volume, fractional anisotropy, radial diffusivity, and axial diffusivity analyses showed no significant relationship in the patients before and six months after withdrawal of analgesics. Also no difference was observed between the patients versus controls. Conclusion Our data demonstrated no structural alterations within the brain in medication-overuse headache.
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Zou, Liwei, Xiaoyan Wu, Shuman Tao, Yajuan Yang, Qingjun Zhang, Xuedong Hong, Yang Xie, Tingting Li, Suisheng Zheng, and Fangbiao Tao. "Anterior cingulate gyrus acts as a moderator of the relationship between problematic mobile phone use and depressive symptoms in college students." Social Cognitive and Affective Neuroscience 16, no. 5 (February 1, 2021): 484–91. http://dx.doi.org/10.1093/scan/nsab016.
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Abstract This study aimed to investigate the brain grey matter volume (GMV) related to problematic mobile phone use (PMPU), and whether these regions of GMV play a potential moderating role in the relationship between PMPU and depressive symptoms. We recruited 266 students who underwent magnetic resonance imaging (MRI) scanning. PMPU and depressive symptoms were assessed by a self-rating questionnaire for adolescent PMPU and patient health questionnaire-9, respectively. A multiple regression model was performed to detect GMV and white matter (WM) integrity associated with PMPU by voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) methods, and the moderating analysis was conducted by PROCESS using SPSS software. VBM analysis found an inverse correlation between the GMV of the anterior cingulate gyrus (ACC) and right fusiform gyrus (FFG) with PMPU (PFDR < 0.05), and TBSS analysis revealed that fractional anisotropy (FA) in the body of the corpus callosum was negatively correlated with PMPU. The correlation between PMPU and depressive symptoms was moderated by the GMV of the ACC. These results suggest that the GMV of the ACC and right FFG, as well as FA in the body of the corpus callosum, was related to PMPU, and we further found that increased GMV of the ACC could reduce the relationship between PMPU and depressive symptoms in college students.
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Sexton, Claire E., Marisa Le Masurier, Charlotte L. Allan, Mark Jenkinson, Lisa McDermott, Ukwuori G. Kalu, Lucie L. Herrmann, Kevin M. Bradley, Clare E. Mackay, and Klaus P. Ebmeier. "Magnetic resonance imaging in late-life depression: vascular and glucocorticoid cascade hypotheses." British Journal of Psychiatry 201, no. 1 (July 2012): 46–51. http://dx.doi.org/10.1192/bjp.bp.111.105361.
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BackgroundLate-life depression is a common and heterogeneous illness, associated with structural abnormalities in both grey and white matter.AimsTo examine the relationship between age at onset and magnetic resonance imaging (MRI) measures of grey and white matter to establish whether they support particular hypotheses regarding the anatomy and aetiology of network disruption in late-life depression.MethodWe studied 36 participants with late-life depression. Grey matter was examined using T1-weighted MRI and analysed using voxel-based morphometry. The hippocampus was automatically segmented and volume and shape analysis performed. White matter was examined using diffusion tensor imaging and analysed using tract-based spatial statistics.ResultsLater age at onset was significantly associated with reduced fractional anisotropy of widespread tracts, in particular the anterior thalamic radiation and superior longitudinal fasciculus. Earlier age at onset was associated with reduced hippocampal volume normalised to whole brain size bilaterally. However, no significant correlations were detected using hippocampal shape analysis or voxel-based morphometry.ConclusionsOverall, the results were compatible with the vascular hypothesis, and provided some support for the glucocorticoid cascade hypothesis.
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Goto, Masami, Osamu Abe, Junichi Hata, Issei Fukunaga, Keigo Shimoji, Akira Kunimatsu, and Tsutomu Gomi. "Adverse effects of metallic artifacts on voxel-wise analysis and tract-based spatial statistics in diffusion tensor imaging." Acta Radiologica 58, no. 2 (July 19, 2016): 211–17. http://dx.doi.org/10.1177/0284185116641348.
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Background Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique that reflects the Brownian motion of water molecules constrained within brain tissue. Fractional anisotropy (FA) is one of the most commonly measured DTI parameters, and can be applied to quantitative analysis of white matter as tract-based spatial statistics (TBSS) and voxel-wise analysis. Purpose To show an association between metallic implants and the results of statistical analysis (voxel-wise group comparison and TBSS) for fractional anisotropy (FA) mapping, in DTI of healthy adults. Material and Methods Sixteen healthy volunteers were scanned with 3-Tesla MRI. A magnetic keeper type of dental implant was used as the metallic implant. DTI was acquired three times in each participant: (i) without a magnetic keeper (FAnon1); (ii) with a magnetic keeper (FAimp); and (iii) without a magnetic keeper (FAnon2) as reproducibility of FAnon1. Group comparisons with paired t-test were performed as FAnon1 vs. FAnon2, and as FAnon1 vs. FAimp. Results Regions of significantly reduced and increased local FA values were revealed by voxel-wise group comparison analysis (a P value of less than 0.05, corrected with family-wise error), but not by TBSS. Conclusion Metallic implants existing outside the field of view produce artifacts that affect the statistical analysis (voxel-wise group comparisons) for FA mapping. When statistical analysis for FA mapping is conducted by researchers, it is important to pay attention to any dental implants present in the mouths of the participants.
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Gobbi, C., MA Rocca, E. Pagani, GC Riccitelli, E. Pravatà, M. Radaelli, F. Martinelli-Boneschi, et al. "Forceps minor damage and co-occurrence of depression and fatigue in multiple sclerosis." Multiple Sclerosis Journal 20, no. 12 (April 16, 2014): 1633–40. http://dx.doi.org/10.1177/1352458514530022.
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Objective: Using diffusion tensor magnetic resonance imaging (DT MRI), we analyzed the architectural integrity of the brain white matter (WM) from a large cohort of MS patients to identify the structural substrates of the concomitant presence of depression and fatigue. Methods: Brain dual-echo, 3D T1-weighted and DT MRI scans were acquired from 147 MS patients and 90 gender- and age-matched healthy controls (HCs). Patients were stratified by the presence of depression (92 depressed (D), 55 not depressed (nD)) and fatigue (81 fatigued (F), 66 not fatigued (nF)). Sixty-five patients had co-occurrence of depression and fatigue (DF). Whole-brain voxel-wise comparisons of WM DT MRI abnormalities were performed using tract-based-spatial-statistics (TBSS). Tract-specific analyses were run in brain WM tracts using standard-space templates. Results: Whole-brain voxel-wise analysis yielded no significant differences between patient subgroups. At tract-specific analysis, DF patients had reduced fractional anisotropy (FA) of the forceps minor. Reduced FA of the right anterior thalamic radiation and right uncinate fasciculus was found in F-MS vs not F-MS patients after correcting for depression. No significant differences were found between D vs not D-MS patients, after correcting for fatigue. Conclusions: This study provides evidence for partially overlapping damage to frontal and fronto-temporal pathways underlying depression and fatigue in MS.
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Li, Dan, Shenghong Li, and Xianjun Zeng. "Analysis of alterations in white matter integrity of adult patients with comitant exotropia." Journal of International Medical Research 46, no. 5 (March 23, 2018): 1963–72. http://dx.doi.org/10.1177/0300060518763704.
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Objective This study was performed to investigate structural abnormalities of the white matter in patients with comitant exotropia using the tract-based spatial statistics (TBSS) method. Methods Diffusion tensor imaging data from magnetic resonance images of the brain were collected from 20 patients with comitant exotropia and 20 age- and sex-matched healthy controls. The FMRIB Software Library was used to compute the diffusion measures, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). These measures were obtained using voxel-wise statistics with threshold-free cluster enhancement. Results The FA values in the right inferior fronto-occipital fasciculus (IFO) and right inferior longitudinal fasciculus were significantly higher and the RD values in the bilateral IFO, forceps minor, left anterior corona radiata, and left anterior thalamic radiation were significantly lower in the comitant exotropia group than in the healthy controls. No significant differences in the MD or AD values were found between the two groups. Conclusions Alterations in FA and RD values may indicate the underlying neuropathologic mechanism of comitant exotropia. The TBSS method can be a useful tool to investigate neuronal tract participation in patients with this disease.
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Gryglewski, Gregor, René Seiger, Pia Baldinger-Melich, Jakob Unterholzner, Benjamin Spurny, Thomas Vanicek, Andreas Hahn, Siegfried Kasper, Richard Frey, and Rupert Lanzenberger. "Changes in White Matter Microstructure After Electroconvulsive Therapy for Treatment-Resistant Depression." International Journal of Neuropsychopharmacology 23, no. 1 (November 19, 2019): 20–25. http://dx.doi.org/10.1093/ijnp/pyz059.
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Abstract Background Treatment-resistant depression is among the most debilitating conditions in psychiatry. Recent studies have associated alterations in white matter microstructure measured with magnetic resonance imaging with poor antidepressant response. Therefore, the extent to which electroconvulsive therapy, the most effective therapeutic option for treatment-resistant depression, affects white matter microstructure warrants investigation. Methods A total 13 patients suffering from severe unipolar treatment-resistant depression underwent magnetic resonance imaging with a diffusion tensor imaging sequence before and after undergoing a series of right unilateral electroconvulsive therapy. Diffusivity metrics were compared voxel-wise using tract-based spatial statistics and repeated-measures ANOVA. Results A total 12 patients responded to electroconvulsive therapy and 9 were classified as remitters. An increase in axial diffusivity was observed in the posterior limb of the internal capsule of the right hemisphere (PFWE ≤ .05). The increase in this area was higher in the right compared with the left hemisphere (P < .05). No correlation of this effect with treatment response could be found. Conclusions The strong lateralization of effects to the hemisphere of electrical stimulation suggests an effect of electroconvulsive therapy on diffusivity metrics which is dependent of electrode placement. Investigation in controlled studies is necessary to reveal to what extent the effects of electroconvulsive therapy on white matter microstructure are related to clinical outcomes and electrode placement.
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Queiroz, J., J. Oliveira, A. Maia, C. Fonseca, T. Quendera, A. Oliveira-Maia, and B. Barahona-Correa. "White matter disconnection and decreased functional connectivity between orbitofrontal cortex and the contralateral temporo-occipital cortex in adults with obsessive compulsive disorder." European Psychiatry 64, S1 (April 2021): S135—S136. http://dx.doi.org/10.1192/j.eurpsy.2021.375.
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IntroductionObsessive compulsive disorder (OCD) affects 2-3% of the general population. The neurobiology of OCD has been linked to dysfunction of cortico-striatal circuits connecting the orbitofrontal (OFC) to the striatum. Recently, this loop has become an approved target for non-invasive neuromodulatory treatment of OCD.ObjectivesTo explore structural and functional connectivity of the OFC in OCD subjects and healthy controls.Methods14 OCD patients and 12 age/sex-matched controls underwent magnetic resonance imaging (MRI) (3T-Philips scanner) for diffusion tensor imaging (DTI) and resting state functional connectivity (rsFC). DTI images were brain extracted and corrected for movement and eddy currents. A diffusion tensor model was fitted to each voxel and used to generate Fractional Anisotropy (FA) maps. Voxel-wise statistical analysis of FA was performed using Tract-Based Spatial Statistics. RsFC images were preprocessed and seed-based correlation (SBC) analysis was performed using Data Processing Assistant for Resting-State fMRI.ResultsWe found decreased values of FA in the body of the Corpus Callosum bilaterally (MNI_coordinates: x= 16, y= -16, z= 33 and x= -19, y= -16, z= 42) and left superior longitudinal fasciculus in OCD patients (fig 1, left), as well as decreased rsFC of the right superior orbitofrontal seed with the left inferior frontal gyrus and left middle occipital gyrus (fig 2, right).ConclusionsUsing an exploratory multimodal approach we found evidence of abnormal structural and functional long-range connectivity of the OFC in OCD. If confirmed in a larger sample these connectivity abnormalities could be explored as potential predictors of response to OFC-targeted non-invasive neuromodulatory interventions.DisclosureNo significant relationships.
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Nucci, Carlo, Francesco Garaci, Simone Altobelli, Francesco Di Ciò, Alessio Martucci, Francesco Aiello, Simona Lanzafame, et al. "Diffusional Kurtosis Imaging of White Matter Degeneration in Glaucoma." Journal of Clinical Medicine 9, no. 10 (September 27, 2020): 3122. http://dx.doi.org/10.3390/jcm9103122.
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Glaucoma is an optic neuropathy characterized by death of retinal ganglion cells and loss of their axons, progressively leading to blindness. Recently, glaucoma has been conceptualized as a more diffuse neurodegenerative disorder involving the optic nerve and also the entire brain. Consistently, previous studies have used a variety of magnetic resonance imaging (MRI) techniques and described widespread changes in the grey and white matter of patients. Diffusion kurtosis imaging (DKI) provides additional information as compared with diffusion tensor imaging (DTI), and consistently provides higher sensitivity to early microstructural white matter modification. In this study, we employ DKI to evaluate differences among healthy controls and a mixed population of primary open angle glaucoma patients ranging from stage I to V according to Hodapp–Parrish–Anderson visual field impairment classification. To this end, a cohort of patients affected by primary open angle glaucoma (n = 23) and a group of healthy volunteers (n = 15) were prospectively enrolled and underwent an ophthalmological evaluation followed by magnetic resonance imaging (MRI) using a 3T MR scanner. After estimating both DTI indices, whole-brain, voxel-wise statistical comparisons were performed in white matter using Tract-Based Spatial Statistics (TBSS). We found widespread differences in several white matter tracts in patients with glaucoma relative to controls in several metrics (mean kurtosis, kurtosis anisotropy, radial kurtosis, and fractional anisotropy) which involved localization well beyond the visual pathways, and involved cognitive, motor, face recognition, and orientation functions amongst others. Our findings lend further support to a causal brain involvement in glaucoma and offer alternative explanations for a number of multidomain impairments often observed in glaucoma patients.
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Messina, Roberta, Maria A. Rocca, Bruno Colombo, Elisabetta Pagani, Andrea Falini, Giancarlo Comi, and Massimo Filippi. "White matter microstructure abnormalities in pediatric migraine patients." Cephalalgia 35, no. 14 (March 20, 2015): 1278–86. http://dx.doi.org/10.1177/0333102415578428.
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Background Diffusion tensor (DT) magnetic resonance imaging (MRI) provides several quantities with the potential to disclose white matter (WM) microstructural abnormalities. We explored alterations of WM architecture in pediatric migraine patients using DT MRI and two different methods of analysis. Methods Dual-echo and DT MRI scans were acquired from 15 pediatric migraine patients and 15 age-matched controls. Whole-brain voxel-wise comparisons of WM DT MRI abnormalities were performed using tract-based-spatial-statistics (TBSS). A DT probabilistic tractography analysis was also run. Results Both TBSS and DT tractography analysis showed that, compared to controls, pediatric migraine patients had significant lower mean (MD), axial (AD) and radial (RD) diffusivity of WM tracts located in the brainstem, thalamus and fronto-temporo-occipital lobes, bilaterally. Patients also experienced increased fractional anisotropy (FA) of the optic radiations. No correlation was found between WM tract abnormalities and disease duration and attack frequency. Conclusions Pediatric migraine patients harbor diffuse brain WM microstructural abnormalities. High FA and low MD, AD and RD in these patients might be explained by repeated neuronal activation, which may lead to cell swelling and stimulate activity-dependent myelin-modulation, or by increased fiber and dendritic densities. Both these mechanisms might reflect a hyperexcitability of the brain in migraineurs.
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Bisecco, Alvino, Giuseppina Caiazzo, Alessandro d’Ambrosio, Rosaria Sacco, Simona Bonavita, Renato Docimo, Mario Cirillo, et al. "Fatigue in multiple sclerosis: The contribution of occult white matter damage." Multiple Sclerosis Journal 22, no. 13 (July 11, 2016): 1676–84. http://dx.doi.org/10.1177/1352458516628331.
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Background: A functional cortico-subcortical disconnection has been recognized in fatigued multiple sclerosis (MS) patients. Normal appearing white matter (NAWM) damage might contribute to the abovementioned disconnectivity. Objectives: To assess the relationship between fatigue and microstructural NAWM damage in relapsing-remitting (RR) MS. Methods: Sixty RRMS patients and 29 healthy controls (HC) underwent a magnetic resonance imaging (MRI) protocol including diffusion tensor imaging (DTI). Patients with a mean Fatigue Severity Scale (FSS) score ⩾ 4 were considered fatigued (fatigued MS (F-MS)). Tract-based spatial statistics were applied for voxel-wise analysis of DTI indices. A correlation analysis was performed between FSS score and DTI indices in the entire MS group. Results: Thirty MS patients were F-MS. Compared to HC, F-MS patients showed a more extensive NAWM damage than not fatigued MS (NF-MS) patients, with additional damage in the following tracts: frontal and occipital juxtacortical fibers, external capsule, uncinate fasciculus, forceps minor, superior longitudinal fasciculus, cingulum, and pons. No differences were found between F-MS and NF-MS patients. Fatigue severity correlated to DTI abnormalities of corona radiata, cingulum, corpus callosum, forceps minor, superior longitudinal fasciculus, inferior fronto-occipital fasciculus, thalamus and anterior thalamic radiation, cerebral peduncle, and midbrain. Conclusions: Fatigue is associated to a widespread microstructural NAWM damage, particularly in associative tracts connected to frontal lobes.
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Tay, S. H., M. Stephenson, N. A. Allameen, S. Narayanan, B. Lee, and A. Mak. "POS0763 A MULTIMODAL MAGNETIC RESONANCE IMAGING STUDY OF COGNITIVE FUNCTION IN SYSTEMIC LUPUS ERYTHEMATOSUS: A MACHINE LEARNING APPROACH." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 668.1–668. http://dx.doi.org/10.1136/annrheumdis-2022-eular.3452.
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BackgroundSystemic lupus erythematosus (SLE) is a multisystem autoimmune disorder that can affect the central nervous system. Cognitive dysfuncion is the most common neuropsyhiatric event in SLE patients, yet it is also one of the hardest to diagnose.ObjectivesTo investigate if multimodal imaging to assess anatomical magnetic resonance imaging (MRI) abnormalities in the brains of SLE patients can predict cognitive function.MethodsSubjects underwent voxel-based morphometry (VBM), magnetization transfer imaging (MTI), and dynamic contrast-enhanced (DCE) MRI. Automated Neuropsychological Assessment Metrics (ANAM) was used to assess cognitive function in this cross-sectional study and the primary measure was the total throughput score (TTS). TTS is the total of the throughput scores for each of the 8 ANAM subtests: (i) code substitution learning (CSL); (ii) code substitution immediate (CSI); (iii) code substitution delayed (CSD); (iv) spatial processing (SP); (v) matching to sample (MSP); (vi) running memory continuous performance test (CPT); (vii) mathematical processing (MTH) and (viii) memory search (MS). Olfactory assessment was done using the University of Pennsylvania Smell Identification Test. We used a machine learning-based model (i.e. GLMnet) to predict TTS. Subjects with active SLE disease or above 40 years old were excluded.ResultsThirty SLE patients [26 female, 32.0 (26.8-37.0) years] without clinically overt neuropsychiatric manifestations and 10 healthy controls (HCs) [9 females, 27.0 (23.0-31.5) years] were enrolled in this study. Both groups had comparable cognitive and olfactory functions. No significant differences were observed in VBM, MTR, olfactory blub and tract (OBT) volume in SLE patients compared to HCs. We observed increased blood-brain barrier (BBB) permeability parameters (Ktrans and PS) in several regions of SLE patients. DCE-MRI perfusion parameters such as perfusion (F) and vp but not permeability measures were associated with TTS. In particular, F right amygdala correlated with TTS in SLE patients (r = 0.636, FDR p < 0.05) (Table 1). Using GLMnet, we trained a multimodal MRI model comprising of VBM, MTR, DCE-MRI and OBT volume parameters to predict TTS in SLE patients (r = 0.998, p < 0.0005) (Figure 1).Figure 1.Machine learning-based models to predict cognitive function.Table 1.Correlation between ANAM tests with perfusion (F) in SLE patients, ranked in descending order of statistical significance for TTS.VariableTTSCSLCSICSDSPMSPCPTMTHMSF right amygdala0.636‡*0.520‡0.3370.437†0.559‡0.3230.633‡0.412†0.598‡F left entorhinal0.504‡0.422†0.3660.416†0.3050.1850.530‡0.1860.416†F left amygdale0.495‡0.400†0.1890.378†0.3300.2370.491‡0.376†0.449†F choroid0.469†0.384†0.2160.413†0.458†0.2020.456†0.3400.406†plexusF right rostal anterior cingulate0.453†0.3010.1180.2960.393†0.2140.547‡0.420†0.383†F right entorhinal0.448†0.368†0.2320.3120.376†0.1560.438†0.2710.407†F cerebellum white matter0.427†0.3580.2010.370†0.2730.0780.449†0.2900.297F left hippocampus0.427†0.3550.1340.390†0.3560.2030.511‡0.3360.332F brain stem0.407†0.2980.1380.2750.2940.1530.478‡0.3080.369†F right insula0.407†0.3080.0740.3000.3240.1760.437†0.3230.347F left parietal0.400†0.2630.0920.2540.2940.2240.487‡0.2740.332F ventricles0.396†0.3030.0830.3210.370†0.1920.477‡0.2860.361F right temporal0.395†0.2800.1130.2810.2880.1670.477‡0.3220.331F right hippocampus0.395†0.3070.0770.3250.3560.1900.486‡0.3570.339F right parietal0.376†0.2490.0820.2740.2830.1390.460†0.2550.311F right parahippocampal gyrus0.375†0.3530.1190.3020.3410.2410.3530.2080.273† p < 0.05, ‡ p < 0.01, *FDR p < 0.05ConclusionThese findings suggest that the BBB may be affected early in the course of cognitive dysfunction, even preceding detectable changes in other MRI sequences and machine learning algorithms can be used to predict TTS measures, even in asymptomatic SLE patients.ReferencesNil.Disclosure of InterestsSen Hee Tay: None declared, Mary Stephenson: None declared, Nur Azizah Allameen: None declared, Sriram Narayanan: None declared, Bernett Lee: None declared, Anselm Mak Speakers bureau: JnJ Apr 2019 and GSK Jan 2022, Grant/research support from: GSK - The Supported Studies Programme
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Königs, Marsh, Petra JW Pouwels, LW Ernest van Heurn, Roel Bakx, R. Jeroen Vermeulen, J. Carel Goslings, Bwee Tien Poll-The, Marleen van der Wees, Coriene E. Catsman-Berrevoets, and Jaap Oosterlaan. "Relevance of neuroimaging for neurocognitive and behavioral outcome after pediatric traumatic brain injury." Brain Imaging and Behavior 12, no. 1 (January 14, 2017): 29–43. http://dx.doi.org/10.1007/s11682-017-9673-3.
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Abstract This study aims to (1) investigate the neuropathology of mild to severe pediatric TBI and (2) elucidate the predictive value of conventional and innovative neuroimaging for functional outcome. Children aged 8–14 years with trauma control (TC) injury (n = 27) were compared to children with mild TBI and risk factors for complicated TBI (mildRF+, n = 20) or moderate/severe TBI (n = 17) at 2.8 years post-injury. Neuroimaging measures included: acute computed tomography (CT), volumetric analysis on post-acute conventional T1-weighted magnetic resonance imaging (MRI) and post-acute diffusion tensor imaging (DTI, analyzed using tract-based spatial statistics and voxel-wise regression). Functional outcome was measured using Common Data Elements for neurocognitive and behavioral functioning. The results show that intracranial pathology on acute CT-scans was more prevalent after moderate/severe TBI (65%) than after mildRF+ TBI (35%; p = .035), while both groups had decreased white matter volume on conventional MRI (ps ≤ .029, ds ≥ −0.74). The moderate/severe TBI group further showed decreased fractional anisotropy (FA) in a widespread cluster affecting all white matter tracts, in which regional associations with neurocognitive functioning were observed (FSIQ, Digit Span and RAVLT Encoding) that consistently involved the corpus callosum. FA had superior predictive value for functional outcome (i.e. intelligence, attention and working memory, encoding in verbal memory and internalizing problems) relative to acute CT-scanning (i.e. internalizing problems) and conventional MRI (no predictive value). We conclude that children with mildRF+ TBI and moderate/severe TBI are at risk of persistent white matter abnormality. Furthermore, DTI has superior predictive value for neurocognitive out-come relative to conventional neuroimaging.
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Pelizzari, Laura, Marta Cazzoli, Susanna Lipari, Maria Marcella Laganà, Monia Cabinio, Sara Isernia, Alice Pirastru, Mario Clerici, and Francesca Baglio. "Mid-term MRI evaluation reveals microstructural white matter alterations in COVID-19 fully recovered subjects with anosmia presentation." Therapeutic Advances in Neurological Disorders 15 (January 2022): 175628642211119. http://dx.doi.org/10.1177/17562864221111995.
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Background: Little is still known about the mid/long-term effects of coronavirus disease 2019 (COVID-19) on the brain, especially in subjects who have never been hospitalized due to the infection. In this neuroimaging exploratory study, we analyzed the medium-term effect of COVID-19 on the brain of people who recovered from COVID-19, experienced anosmia during the acute phase of the disease, and have never been hospitalized due to SARS-Co-V-2 infection. Methods: Forty-three individuals who had (COV+, n = 22) or had not (COV−, n = 21) been infected with SARS-Co-V-2 were included in the study; the two groups were age- and sex-matched and were investigated using 3T magnetic resonance imaging (MRI). Gray matter (GM) volume, white matter (WM) hyperintensity volume, WM microstrutural integrity (i.e. fractional anisotropy [FA], mean diffusivity [MD], axial diffusivity [AD], radial diffusivity [RD]) and cerebral blood flow (CBF) differences between the two groups were tested with either analysis of covariance or voxel-wise analyses. Results were family wise error (FWE) corrected. Results: No significant differences between COV+ and COV− groups were observed in terms of GM volume, WM hyperintensity volume, and CBF. Conversely, local WM microstructural alterations were detected in COV+ when compared with COV− with tract-based spatial statistics. Specifically, COV+ showed lower FA (pFWE-peak = 0.035) and higher RD (pFWE-peak = 0.038) than COV− in several WM regions. Conclusion: COVID-19 may produce mid/long-term microstructural effect on the brain, even in case of mild-to-moderate disease not requiring hospitalization. Further investigation and additional follow-ups are warranted to assess if the alterations reported in this study totally recover over time. As brain alterations could increase the risk of cognitive decline, greater knowledge of their trajectories is crucial to aid neurorehabilitation treatments.
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Siasios, Ioannis, Eftychia Z. Kapsalaki, Kostas N. Fountas, Aggeliki Fotiadou, Alexander Dorsch, Kunal Vakharia, John Pollina, and Vassilios Dimopoulos. "The role of diffusion tensor imaging and fractional anisotropy in the evaluation of patients with idiopathic normal pressure hydrocephalus: a literature review." Neurosurgical Focus 41, no. 3 (September 2016): E12. http://dx.doi.org/10.3171/2016.6.focus16192.
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OBJECTIVE Diffusion tensor imaging (DTI) for the assessment of fractional anisotropy (FA) and involving measurements of mean diffusivity (MD) and apparent diffusion coefficient (ADC) represents a novel, MRI-based, noninvasive technique that may delineate microstructural changes in cerebral white matter (WM). For example, DTI may be used for the diagnosis and differentiation of idiopathic normal pressure hydrocephalus (iNPH) from other neurodegenerative diseases with similar imaging findings and clinical symptoms and signs. The goal of the current study was to identify and analyze recently published series on the use of DTI as a diagnostic tool. Moreover, the authors also explored the utility of DTI in identifying patients with iNPH who could be managed by surgical intervention. METHODS The authors performed a literature search of the PubMed database by using any possible combinations of the following terms: “Alzheimer's disease,” “brain,” “cerebrospinal fluid,” “CSF,” “diffusion tensor imaging,” “DTI,” “hydrocephalus,” “idiopathic,” “magnetic resonance imaging,” “normal pressure,” “Parkinson's disease,” and “shunting.” Moreover, all reference lists from the retrieved articles were reviewed to identify any additional pertinent articles. RESULTS The literature search retrieved 19 studies in which DTI was used for the identification and differentiation of iNPH from other neurodegenerative diseases. The DTI protocols involved different approaches, such as region of interest (ROI) methods, tract-based spatial statistics, voxel-based analysis, and delta-ADC analysis. The most studied anatomical regions were the periventricular WM areas, such as the internal capsule (IC), the corticospinal tract (CST), and the corpus callosum (CC). Patients with iNPH had significantly higher MD in the periventricular WM areas of the CST and the CC than had healthy controls. In addition, FA and ADCs were significantly higher in the CST of iNPH patients than in any other patients with other neurodegenerative diseases. Gait abnormalities of iNPH patients were statistically significantly and negatively correlated with FA in the CST and the minor forceps. Fractional anisotropy had a sensitivity of 94% and a specificity of 80% for diagnosing iNPH. Furthermore, FA and MD values in the CST, the IC, the anterior thalamic region, the fornix, and the hippocampus regions could help differentiate iNPH from Alzheimer or Parkinson disease. Interestingly, CSF drainage or ventriculoperitoneal shunting significantly modified FA and ADCs in iNPH patients whose condition clinically responded to these maneuvers. CONCLUSIONS Measurements of FA and MD significantly contribute to the detection of axonal loss and gliosis in the periventricular WM areas in patients with iNPH. Diffusion tensor imaging may also represent a valuable noninvasive method for differentiating iNPH from other neurodegenerative diseases. Moreover, DTI can detect dynamic changes in the WM tracts after lumbar drainage or shunting procedures and could help identify iNPH patients who may benefit from surgical intervention.
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Seitz, Johanna, Monica Lyons, Leila Kushan, Kang Ik Kevin Cho, Tashrif Billah, Sylvain Bouix, Marek Kubicki, Carrie Bearden, and Ofer Pasternak. "M155. RECIPROCAL CHANGES IN WHITE MATTER MICROSTRUCTURE IN 22Q11.2 DELETION AND DUPLICATION SYNDROME." Schizophrenia Bulletin 46, Supplement_1 (April 2020): S194—S195. http://dx.doi.org/10.1093/schbul/sbaa030.467.
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Abstract Background The 22q11.2 deletion syndrome is a neurogenetic disorder that is associated with both physical anomalies and neurocognitive impairments. Deletion carriers have a greatly elevated risk of developing schizophrenia (SCZ); as such, it offers a compelling ‘high-penetrance’ model to explore the neuropathology of SCZ risk. Indeed, widespread structural alterations of both gray and white matter have been reported for 22q11.2 deletion carriers. Interestingly, there are also cases of duplications at the same gene locus. While less is known about the phenotype associated with 22q11.2 duplication, carriers also present physical and neurodevelopmental abnormalities, although they may have reduced risk of developing SCZ compared to the general population. The only study to date which looked at brain structure in duplication carriers found reciprocal effects of 22q11.2 deletion and duplication on cortical thickness and surface measurements. In the present study, we apply diffusion magnetic resonance imaging (MRI) to examine the white matter microstructure in both 22q11.2 deletion and duplication carriers. Methods Multi-shell diffusion-weighted images were acquired on a 3 Tesla MRI scanner from 13 healthy control individuals (HC), 25 deletion carriers, and 18 22q11.2 duplication carriers. Images were preprocessed utilizing the Human Connectome Project (HCP) Minimal Preprocessing Pipeline v4.0.0. Free Water imaging was applied, which differentiates the diffusion signal into a free-water compartment and a tissue compartment. The output parameters are the free-water fractional volume (FW) and a free-water corrected diffusion tensor from which fractional anisotropy of the tissue (FAT) is calculated. We compared FAT and FW maps between 1) HC and 22q11.2 deletion carriers and 2) HC and 22q11.2 duplication carriers using Tract-Based Spatial Statistics (TBSS) and voxel-wise, non-parametric statistics (5000 permutations, threshold-free cluster enhancement, corrected for age and sex). Lastly, white matter clusters that displayed significant differences between 22q11.2 deletion or duplication and HC were extracted. We averaged FAT and FW values over these significant clusters for each individual and correlated with the scores of the Structured Interview for Prodromal Syndromes (SIPS). Results 22q11.2 deletion carriers showed significant (p<0.05) FW reductions (72% of white matter skeleton) and FAT increase (8%) when compared to HC. In contrast, 22q11.2 duplication carriers displayed the opposite effect, with significant (p<0.05) widespread FW increase (51%) and FAT decrease (50%) when compared to HC. Both 22q11.2 deletion and duplication carriers scored higher on the SIPS than HC, with negative symptom score differences being the most pronounced (mean for HC= 1.36, mean for 22q11.2 duplication = 7.0, mean for 22q11.2 deletion =9.96, F=6.68, df=2, p<.003). FAT and FW were not associated with SIPS scores in 22q11.2 deletion syndrome. However, FAT was negatively correlated with the negative symptom score in 22q11.2 duplication carriers (Spearman rho=-.61, p<.009). Discussion We observed opposing effects of gene-dosage on FAT and FW. While we did not see an association between WM measurements and psychotic symptoms in 22q11.2 deletion, there was an association of WM structure with negative symptoms in 22q11.2 duplication carriers. These findings highlight the importance of studying the influence of reciprocal chromosomal imbalance on white matter architecture. Ongoing longitudinal studies may help advance understanding of the role of microstructural white matter abnormalities in the emergence of neuropsychiatric symptoms.
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Li, Dongyun, Lianni Mei, Huiping Li, Chunchun Hu, Bingrui Zhou, Kaifeng Zhang, Zhongwei Qiao, Xiu Xu, and Qiong Xu. "Brain structural alterations in young girls with Rett syndrome: A voxel-based morphometry and tract-based spatial statistics study." Frontiers in Neuroinformatics 16 (September 8, 2022). http://dx.doi.org/10.3389/fninf.2022.962197.
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Rett syndrome (RTT) is a neurodevelopmental disorder caused by loss-of-function variants in the MECP2 gene, currently with no cure. Neuroimaging is an important tool for obtaining non-invasive structural and functional information about the in vivo brain. Multiple approaches to magnetic resonance imaging (MRI) scans have been utilized effectively in RTT patients to understand the possible pathological basis. This study combined developmental evaluations with clinical severity, T1-weighted imaging, and diffusion tensor imaging, aiming to explore the structural alterations in cohorts of young girls with RTT, idiopathic autism spectrum disorder (ASD), or typical development. Voxel-based morphometry (VBM) was used to determine the voxel-wised volumetric characteristics of gray matter, while tract-based spatial statistics (SPSS) was used to obtain voxel-wised properties of white matter. Finally, a correlation analysis between the brain structural alterations and the clinical evaluations was performed. In the RTT group, VBM revealed decreased gray matter volume in the insula, frontal cortex, calcarine, and limbic/paralimbic regions; TBSS demonstrated decreased fractional anisotropy (FA) and increased mean diffusivity (MD) mainly in the corpus callosum and other projection and association fibers such as superior longitudinal fasciculus and corona radiata. The social impairment quotient and clinical severity were associated with these morphometric alterations. This monogenic study with an early stage of RTT may provide some valuable guidance for understanding the disease pathogenesis. At the same time, the pediatric-adjusted analytic pipelines for VBM and TBSS were introduced for significant improvement over classical approaches for MRI scans in children.
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Schröder, Yvonne, Daniela Michelle Hohmann, Tina Meller, Ulrika Evermann, Julia-Katharina Pfarr, Andreas Jansen, Inge Kamp-Becker, Sarah Grezellschak, and Igor Nenadić. "Associations of subclinical autistic-like traits with brain structural variation using diffusion tensor imaging and voxel-based morphometry." European Psychiatry 64, no. 1 (2021). http://dx.doi.org/10.1192/j.eurpsy.2021.15.
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Abstract Background Previous case–control studies of autistic spectrum disorder (ASD) have identified altered brain structure such as altered frontal and temporal cortex volumes, or decreased fractional anisotropy (FA) within the inferior fronto-occipital fasciculus in patients. It remains unclear whether subclinical autistic-like traits might also be related to variation in these brain structures. Methods In this study, we analyzed magnetic resonance imaging (MRI) data of 250 psychiatrically healthy subjects phenotyped for subclinical autistic-like traits using the Autism Spectrum Quotient (AQ). For data analysis, we used voxel-based morphometry of T1-MRIs (Computational Anatomy Toolbox) and tract-based spatial statistics for diffusion tensor imaging data. Results AQ attention switching subscale correlated negatively with FA values in the bilateral uncinate fasciculus as well as the bilateral inferior fronto-occipital fasciculus. Higher AQ attention switching subscale scores were associated with increased mean diffusivity and radial diffusivity values in the uncinate fasciculus, while axial diffusivity values within this tract show a negative correlation. AQ attention to detail subscale correlated positively with gray matter volume in the right pre- and postcentral gyrus. Conclusions We demonstrate that individuals with higher levels of autism-spectrum-like features show decreased white matter integrity in tracts associated with higher-level visual processing and increased cortical volume in areas linked to movement sequencing and working memory. Our results resemble regional brain structure alterations found in individuals with ASD. This offers opportunities to further understand the etiology and pathogenesis of the disorder and shows a subclinical continuum perspective.
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Jung, Hye-Yeon, Chongwon Pae, Iseul An, Minji Bang, Tai Kiu Choi, Sung Joon Cho, and Sang-Hyuk Lee. "A multimodal study regarding neural correlates of the subjective well-being in healthy individuals." Scientific Reports 12, no. 1 (August 11, 2022). http://dx.doi.org/10.1038/s41598-022-18013-1.
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AbstractAlthough happiness or subjective well-being (SWB) has drawn much attention from researchers, the precise neural structural correlates of SWB are generally unknown. In the present study, we aimed to investigate the associations between gray matter (GM) volumes, white matter (WM) microstructures, and SWB in healthy individuals, mainly young adults using multimodal T1 and diffusion tensor imaging studies. We enrolled 70 healthy individuals using magnetic resonance imaging. We measured their SWB using the Concise Measure of Subjective Well-Being. Voxel-wise statistical analysis of GM volumes was performed using voxel-based morphometry, while fractional anisotropy (FA) values were analyzed using tract-based spatial statistics. In healthy individuals, higher levels of SWB were significantly correlated with increased GM volumes of the anterior insula and decreased FA values in clusters of the body of the corpus callosum, precuneus WM, and fornix cres/stria terminalis. A correlational analysis revealed that GM volumes and FA values in these significant regions were significantly correlated with severity of psychological symptoms such as depression, anxiety, and quality of life. Our findings indicate that GM volumes and WM microstructures in these regions may contribute to SWB, and could be the neural basis for psychological symptom severity as well as quality of life in healthy individuals.
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Zitser, Jennifer, Melis Anatürk, Enikő Zsoldos, Abda Mahmood, Nicola Filippini, Sana Suri, Yue Leng, et al. "Sleep duration over 28 years, cognition, gray matter volume, and white matter microstructure: a prospective cohort study." Sleep 43, no. 5 (January 6, 2020). http://dx.doi.org/10.1093/sleep/zsz290.
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Abstract Study Objectives To examine the association between sleep duration trajectories over 28 years and measures of cognition, gray matter volume, and white matter microstructure. We hypothesize that consistently meeting sleep guidelines that recommend at least 7 hours of sleep per night will be associated with better cognition, greater gray matter volumes, higher fractional anisotropy, and lower radial diffusivity values. Methods We studied 613 participants (age 42.3 ± 5.03 years at baseline) who self-reported sleep duration at five time points between 1985 and 2013, and who had cognitive testing and magnetic resonance imaging administered at a single timepoint between 2012 and 2016. We applied latent class growth analysis to estimate membership into trajectory groups based on self-reported sleep duration over time. Analysis of gray matter volumes was carried out using FSL Voxel-Based-Morphometry and white matter microstructure using Tract Based Spatial Statistics. We assessed group differences in cognitive and MRI outcomes using nonparametric permutation testing. Results Latent class growth analysis identified four trajectory groups, with an average sleep duration of 5.4 ± 0.2 hours (5%, N = 29), 6.2 ± 0.3 hours (37%, N = 228), 7.0 ± 0.2 hours (45%, N = 278), and 7.9 ± 0.3 hours (13%, N = 78). No differences in cognition, gray matter, and white matter measures were detected between groups. Conclusions Our null findings suggest that current sleep guidelines that recommend at least 7 hours of sleep per night may not be supported in relation to an association between sleep patterns and cognitive function or brain structure.
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Oh, Dae Jong, Ji-Jung Jung, Seong A. Shin, Hairin Kim, Soowon Park, Bo Kyung Sohn, Bo Kyung Koo, Min Kyong Moon, Yu Kyeong Kim, and Jun-Young Lee. "Brain Structural Alterations, Diabetes Biomarkers, and Cognitive Performance in Older Adults With Dysglycemia." Frontiers in Neurology 12 (October 28, 2021). http://dx.doi.org/10.3389/fneur.2021.766216.
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Despite the high risk of dementia in older adults with type 2 diabetes, the neuroanatomical correlates of cognitive dysfunction that are particularly affected by diabetes are not well characterized. This study is aimed to examine the structural brain alterations in dysglycemic older adults. Using voxel-based morphometric and tract-based spatial statistics, we examined changes in gray matter volume, white matter volume, and microstructural integrity in older adults with prediabetes and diabetes. We also assessed the correlation of these structural changes with diabetes biomarkers and cognitive performance. A total of 74 non-demented older adults (normal, n = 14; prediabetes, n = 37; and diabetes, n = 23) participated in this study and underwent structural and diffusion magnetic resonance imaging (MRI) scans and neuropsychological tests. Subjects with diabetes showed reduced volume of cerebellar gray matter and frontal white matter and diffuse white matter dysintegrity, while those with prediabetes only showed reduced volume of insular gray matter. Atrophic changes in the cerebellum and frontal lobe and frontal white matter dysintegrity were correlated with chronic hyperglycemia and insulin resistance and worse performance in verbal memory recognition and executive function tests. Our findings suggest that chronic hyperglycemia and insulin resistance may alter brain structures forming the fronto-cerebellar network, which may cause cognitive dysfunction in older adults.
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Feis, Rogier A., Mark J. R. J. Bouts, Elise G. P. Dopper, Nicola Filippini, Verena Heise, Aaron J. Trachtenberg, John C. van Swieten, et al. "Multimodal MRI of grey matter, white matter, and functional connectivity in cognitively healthy mutation carriers at risk for frontotemporal dementia and Alzheimer's disease." BMC Neurology 19, no. 1 (December 2019). http://dx.doi.org/10.1186/s12883-019-1567-0.
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Abstract Background Frontotemporal dementia (FTD) and Alzheimer’s disease (AD) are associated with divergent differences in grey matter volume, white matter diffusion, and functional connectivity. However, it is unknown at what disease stage these differences emerge. Here, we investigate whether divergent differences in grey matter volume, white matter diffusion, and functional connectivity are already apparent between cognitively healthy carriers of pathogenic FTD mutations, and cognitively healthy carriers at increased AD risk. Methods We acquired multimodal magnetic resonance imaging (MRI) brain scans in cognitively healthy subjects with (n=39) and without (n=36) microtubule-associated protein Tau (MAPT) or progranulin (GRN) mutations, and with (n=37) and without (n=38) apolipoprotein E ε4 (APOE4) allele. We evaluated grey matter volume using voxel-based morphometry, white matter diffusion using tract-based spatial statistics (TBSS), and region-to-network functional connectivity using dual regression in the default mode network and salience network. We tested for differences between the respective carriers and controls, as well as for divergence of those differences. For the divergence contrast, we additionally performed region-of-interest TBSS analyses in known areas of white matter diffusion differences between FTD and AD (i.e., uncinate fasciculus, forceps minor, and anterior thalamic radiation). Results MAPT/GRN carriers did not differ from controls in any modality. APOE4 carriers had lower fractional anisotropy than controls in the callosal splenium and right inferior fronto-occipital fasciculus, but did not show grey matter volume or functional connectivity differences. We found no divergent differences between both carrier-control contrasts in any modality, even in region-of-interest analyses. Conclusions Concluding, we could not find differences suggestive of divergent pathways of underlying FTD and AD pathology in asymptomatic risk mutation carriers. Future studies should focus on asymptomatic mutation carriers that are closer to symptom onset to capture the first specific signs that may differentiate between FTD and AD.
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Jun Lee, Sung, Min Son Kim, and Sung Ho Jang. "White Matter Abnormalities in Spontaneous Subarachnoid Hemorrhage." Stroke 51, no. 9 (September 2020). http://dx.doi.org/10.1161/strokeaha.120.029996.
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Background and Purpose: We investigated white matter abnormalities in patients with spontaneous subarachnoid hemorrhage following aneurysmal rupture, by using tract-based spatial statistics. Methods: Sixteen patients with spontaneous subarachnoid hemorrhage due to aneurysmal rupture and 18 age- and sex-matched healthy control subjects were recruited. Voxel-wise statistical analysis of fractional anisotropy data was performed by using tract-based spatial statistics as implemented in the Functional Magnetic Resonance Imaging of the Brain Software Library. We calculated mean fractional anisotropy values across the tract skeleton and within 48 regions of interest based on the intersections between the fractional anisotropy skeleton and the probabilistic Johns Hopkins University white matter atlases. Results: Comparing the patient and control groups, the fractional anisotropy values of 44 regions of interest among the 48 regions of interest showed significant differences ( P <0.05). However, significant differences were not observed in the remaining 4 regions of interest (both retrolenticular parts of the internal capsule, the right superior longitudinal fasciculus, and the right superior corona radiata; P >0.05). Conclusions: By undertaking tract-based spatial statistics analysis, we detected wide-ranging white matter abnormalities in patients with spontaneous subarachnoid hemorrhage. Registration: URL: http://www.e-irb.com/index.jsp . Unique identifier: 2019-06-032.
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Andrews, Derek Sayre, Joshua K. Lee, Marjorie Solomon, Sally J. Rogers, David G. Amaral, and Christine Wu Nordahl. "A diffusion-weighted imaging tract-based spatial statistics study of autism spectrum disorder in preschool-aged children." Journal of Neurodevelopmental Disorders 11, no. 1 (December 2019). http://dx.doi.org/10.1186/s11689-019-9291-z.
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Abstract Background The core symptoms of autism spectrum disorder (ASD) are widely theorized to result from altered brain connectivity. Diffusion-weighted magnetic resonance imaging (DWI) has been a versatile method for investigating underlying microstructural properties of white matter (WM) in ASD. Despite phenotypic and etiological heterogeneity, DWI studies in majority male samples of older children, adolescents, and adults with ASD have largely reported findings of decreased fractional anisotropy (FA) across several commissural, projection, and association fiber tracts. However, studies in preschool-aged children (i.e., < 30–40 months) suggest individuals with ASD have increased measures of WM FA earlier in development. Methods We analyzed 127 individuals with ASD (85♂, 42♀) and 54 typically developing (TD) controls (42♂, 26♀), aged 25.1–49.6 months. Voxel-wise effects of ASD diagnosis, sex, age, and their interaction on DWI measures of FA, mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were investigated using tract-based spatial statistics (TBSS) while controlling mean absolute and relative motion. Results Compared to TD controls, males and females with ASD had significantly increased measures of FA in eight clusters (threshold-free cluster enhancement p < 0.05) that incorporated several WM tracts including regions of the genu, body, and splenium of the corpus callosum, inferior frontal-occipital fasciculi, inferior and superior longitudinal fasciculi, middle and superior cerebellar peduncles, and corticospinal tract. A diagnosis by sex interaction was observed in measures of AD across six significant clusters incorporating areas of the body, genu, and splenium of the corpus collosum. In these tracts, females with ASD showed increased AD compared to TD females, while males with ASD showed decreased AD compared to TD males. Conclusions The current findings support growing evidence that preschool-aged children with ASD have atypical measures of WM microstructure that appear to differ in directionality from alterations observed in older individuals with the condition. To our knowledge, this study represents the largest sample of preschool-aged females with ASD to be evaluated using DWI. Microstructural differences associated with ASD largely overlapped between sexes. However, differential relationships of AD measures indicate that sex likely modulates ASD neuroanatomical phenotypes. Further longitudinal study is needed to confirm and quantify the developmental relationship of WM structure in ASD.
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Vieira, Rita, Ana Coelho, Joana Reis, Carlos Portugal-Nunes, Ricardo Magalhães, Sónia Ferreira, Pedro Silva Moreira, Nuno Sousa, and João M. Bessa. "White Matter Microstructure Alterations Associated With Paroxetine Treatment Response in Major Depression." Frontiers in Behavioral Neuroscience 15 (July 22, 2021). http://dx.doi.org/10.3389/fnbeh.2021.693109.
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More than one-third of depressive patients do not achieve remission after the first antidepressant treatment. The “watch and wait” approach used to find the most effective antidepressant leads to an increased personal, social, and economic burden in society. In order to overcome this challenge, there has been a focus on studying neural biomarkers associated with antidepressant response. Diffusion tensor imaging measures have shown a promising role as predictors of antidepressant response by pointing to pretreatment differences in the white matter microstructural integrity between future responders and non-responders to different pharmacotherapies. Therefore, the aim of the present study was to explore whether response to paroxetine treatment was associated with differences in the white matter microstructure at baseline. Twenty drug-naive patients diagnosed with major depressive disorder followed a 6- to 12-week treatment with paroxetine. All patients completed magnetic resonance brain imaging and a clinical assessment at baseline and 6–12 weeks after treatment. Whole-brain tract-based spatial statistics was used to explore differences in white matter microstructural properties estimated from diffusion magnetic resonance imaging. Voxel-wise statistical analysis revealed a significant increase in fractional anisotropy and a decrease in radial diffusivity in forceps minor and superior longitudinal fasciculus in responders compared to non-responders. Thus, alterations in white matter integrity, specifically in forceps minor and the superior longitudinal fasciculus, are associated with paroxetine treatment response. These findings pave the way for personalized treatment strategies in major depression.
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Viher, Petra Verena, Katharina Stegmayer, Tobias Bracht, Andrea Federspiel, Stephan Bohlhalter, Werner Strik, Roland Wiest, and Sebastian Walther. "Neurological Soft Signs Are Associated With Altered White Matter in Patients With Schizophrenia." Schizophrenia Bulletin, August 6, 2021. http://dx.doi.org/10.1093/schbul/sbab089.
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Abstract Neurological soft signs (NSS) are related to grey matter and functional brain abnormalities in schizophrenia. Studies in healthy subjects suggest, that NSS are also linked to white matter. However, the association between NSS and white matter abnormalities in schizophrenia remains to be elucidated. The present study investigated, if NSS are related to white matter alterations in patients with schizophrenia. The total sample included 42 healthy controls and 41 patients with schizophrenia. We used the Neurological Evaluation Scale (NES), and we acquired diffusion weighted magnetic resonance imaging to assess white matter on a voxel-wise between subject statistic. In patients with schizophrenia, linear associations between NES with fractional anisotropy (FA), radial, axial, and mean diffusivity were analyzed with tract-based spatial statistics while controlling for age, medication dose, the severity of the disease, and motion. The main pattern of results in patients showed a positive association of NES with all diffusion measures except FA in important motor pathways: the corticospinal tract, internal capsule, superior longitudinal fascicle, thalamocortical radiations and corpus callosum. In addition, exploratory tractography analysis revealed an association of the right aslant with NES in patients. These results suggest that specific white matter alterations, that is, increased diffusivity might contribute to NSS in patients with schizophrenia.
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Romaniuk, Madeline, Ying Xia, Gina Fisher, Kerstin Pannek, Jurgen Fripp, Justine Evans, and Stephen Rose. "The relationship between chronic PTSD, cortical volumetry and white matter microstructure among Australian combat veterans." Military Medical Research 9, no. 1 (September 16, 2022). http://dx.doi.org/10.1186/s40779-022-00413-z.
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Abstract Background Posttraumatic stress disorder (PTSD) has been associated with volumetric and white matter microstructural changes among general and veteran populations. However, regions implicated have greatly varied and often conflict between studies, potentially due to confounding comorbidities within samples. This study compared grey matter volume and white matter microstructure among Australian combat veterans with and without a lifetime diagnosis of PTSD, in a homogenous sample assessed for known confounding comorbidities. Methods Sixty-eight male trauma-exposed veterans (16 PTSD-diagnosed; mean age 69 years) completed a battery of psychometric assessments and underwent magnetic resonance and diffusion tensor imaging. Analyses included tract-based spatial statistics, voxel-wise analyses, diffusion connectome-based group-wise analysis, and volumetric analysis. Results Significantly smaller grey matter volumes were observed in the left prefrontal cortex (P = 0.026), bilateral middle frontal gyrus (P = 0.021), and left anterior insula (P = 0.048) in the PTSD group compared to controls. Significant negative correlations were found between PTSD symptom severity and fractional anisotropy values in the left corticospinal tract (R2 = 0.34, P = 0.024) and left inferior cerebellar peduncle (R2 = 0.62, P = 0.016). No connectome-based differences in white matter properties were observed. Conclusions Findings from this study reinforce reports of white matter alterations, as indicated by reduced fractional anisotropy values, in relation to PTSD symptom severity, as well as patterns of reduced volume in the prefrontal cortex. These results contribute to the developing profile of neuroanatomical differences uniquely attributable to veterans who suffer from chronic PTSD.
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Shuster, Ethan, Amy E. Miles, Lindsay K. Heyland, Navona Calarco, Jerrold Jeyachandra, Salim Mansour, Aristotle N. Voineskos, David C. Steffens, Yuliya S. Nikolova, and Breno S. Diniz. "Neuroimaging features of depression–frailty phenotype in older adults: a pilot study." International Psychogeriatrics, February 20, 2023, 1–7. http://dx.doi.org/10.1017/s1041610223000066.
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ABSTRACT Objective: Frailty and late-life depression (LLD) often coexist and share several structural brain changes. We aimed to study the joint effect LLD and frailty have on brain structure. Design: Cross-sectional study Setting: Academic Health Center Participants: Thirty-one participants (14 LLD+Frail and 17 Never-depressed+Robust) Measurement: LLD was diagnosed by a geriatric psychiatrist according to the Diagnostic and Statistical Manual of Mental Disorders 5th edition for single episode or recurrent major depressive disorder without psychotic features. Frailty was assessed using the FRAIL scale (0–5), classifying subjects as robust (0), prefrail (1–2), and frail (3–5). Participants underwent T1-weighted magnetic resonance imaging in which covariance analysis of subcortical volumes and vertex-wise analysis of cortical thickness values were performed to access changes in grey matter. Participants also underwent diffusion tensor imaging in which tract-based spatial statistics was used with voxel-wise statistical analysis on fractional anisotropy and mean diffusion values to assess changes in white matter (WM). Results: We found a significant difference in mean diffusion values (48,225 voxels; peak voxel: pFWER=0.005, MINI coord. (X,Y,Z) = −26,−11,27) between the LLD-Frail group and comparison group. The corresponding effect size (f=0.808) was large. Conclusion: We showed the LLD+Frailty group is associated with significant microstructural changes within WM tracts compared to Never-depressed+Robust individuals. Our findings indicate the possibility of a heightened neuroinflammatory burden as a potential mechanism underlying the co-occurrence of both conditions and the possibility of a depression–frailty phenotype in older adults.
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Gan, Caiting, Lina Wang, Min Ji, Kewei Ma, Huimin Sun, Kezhong Zhang, and Yongsheng Yuan. "Abnormal interhemispheric resting state functional connectivity in Parkinson’s disease patients with impulse control disorders." npj Parkinson's Disease 7, no. 1 (July 16, 2021). http://dx.doi.org/10.1038/s41531-021-00205-7.
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AbstractImpulse control disorders (ICD) in Parkinson’s disease (PD) might be attributed to misestimate of rewards or the failure to curb inappropriate choices. The mechanisms underlying ICD were reported to involve the lateralization of monoamine network. Our objective was to probe the significant role of lateralization in the pathogenesis of ICD. Twenty-one PD patients with ICD (PD-ICD), thirty-three without ICD (PD-no ICD), and thirty-seven healthy controls (HCs) were recruited and performed T1-weighted, diffusion tensor imaging (DTI) scans and resting state functional magnetic resonance imaging (rs-fMRI). By applying the Voxel-mirrored Homotopic Connectivity (VMHC) and Freesurfer, we evaluated participants’ synchronicity of functional connectivity and structural changes between hemispheres. Also, tract-based spatial statistics (TBSS) was applied to compare fiber tracts differences. Relative to PD-no ICD group, PD-ICD group demonstrated reduced VMHC values in middle frontal gyrus (MFG). Compared to HCs, PD-ICD group mainly showed decreased VMHC values in MFG, middle and superior orbital frontal gyrus (OFG), inferior frontal gyrus (IFG) and caudate, which were related to reward processing and inhibitory control. The severity of impulsivity was negatively correlated with the mean VMHC values of MFG in PD-ICD group. Receiver operating characteristic (ROC) curves analyses uncovered that the mean VMHC values of MFG might be a potential marker identifying PD-ICD patients. However, we found no corresponding asymmetrical alteration in cortical thickness and no significant differences in fractional anisotropy (FA) and mean diffusivity (MD). Our results provided further evidence for asymmetry of functional connectivity in mesolimbic reward and response inhibition network in ICD.
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Jin, Chaoyang, Shouliang Qi, Yueyang Teng, Chen Li, Yudong Yao, Xiuhang Ruan, and Xinhua Wei. "Integrating Structural and Functional Interhemispheric Brain Connectivity of Gait Freezing in Parkinson's Disease." Frontiers in Neurology 12 (April 15, 2021). http://dx.doi.org/10.3389/fneur.2021.609866.
Full textAbstract:
Freezing of gait (FOG) has devastating consequences for patients with Parkinson's disease (PD), but the underlying pathophysiological mechanism is unclear. This was investigated in the present study by integrated structural and functional connectivity analyses of PD patients with or without FOG (PD FOG+ and PD FOG–, respectively) and healthy control (HC) subjects. We performed resting-state functional magnetic resonance imaging (fMRI) and diffusion tensor imaging of 24 PD FOG+ patients, 37 PD FOG– patients, and 24 HCs. Tract-based spatial statistics was applied to identify white matter (WM) abnormalities across the whole brain. Fractional anisotropy (FA) and mean diffusivity (MD) of abnormal WM areas were compared among groups, and correlations between these parameters and clinical severity as determined by FOG Questionnaire (FOGQ) score were analyzed. Voxel-mirrored homotopic connectivity (VMHC) was calculated to identify brain regions with abnormal interhemispheric connectivity. Structural and functional measures were integrated by calculating correlations between VMHC and FOGQ score and between FA, MD, and VMHC. The results showed that PD FOG+ and PD FOG– patients had decreased FA in the corpus callosum (CC), cingulum (hippocampus), and superior longitudinal fasciculus and increased MD in the CC, internal capsule, corona radiata, superior longitudinal fasciculus, and thalamus. PD FOG+ patients had more WM abnormalities than PD FOG– patients. FA and MD differed significantly among the splenium, body, and genu of the CC in all three groups (P < 0.05). The decreased FA in the CC was positively correlated with FOGQ score. PD FOG+ patients showed decreased VMHC in the post-central gyrus (PCG), pre-central gyrus, and parietal inferior margin. In PD FOG+ patients, VMHC in the PCG was negatively correlated with FOGQ score but positively correlated with FA in CC. Thus, FOG is associated with impaired interhemispheric brain connectivity measured by FA, MD, and VMHC, which are related to clinical FOG severity. These results demonstrate that integrating structural and functional MRI data can provide new insight into the pathophysiological mechanism of FOG in PD.