Browsing by Subject "WHITE-MATTER"

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  • Itokazu, Yutaka; Tajima, Nobuyoshi; Kerosuo, Laura; Somerharju, Pentti; Sariola, Hannu; Yu, Robert K.; Kakela, Reijo (2016)
    The central nervous system (CNS) harbors multiple glial fibrillary acidic protein (GFAP) expressing cell types. In addition to the most abundant cell type of the CNS, the astrocytes, various stem cells and progenitor cells also contain GFAP+ populations. Here, in order to distinguish between two types of GFAP expressing cells with or without the expression of the A2B5 antigens, we performed lipidomic analyses on A2B5+/GFAP+ and A2B5-/GFAP+ cells from rat spinal cord. First, A2B5+/GFAP- progenitors were exposed to the leukemia inhibitory factor (LIF) or bone morphogenetic protein (BMP) to induce their differentiation to A2B5+/GFAP+ cells or A2B5-/GFAP+ astrocytes, respectively. The cells were then analyzed for changes in their phospholipid, sphingolipid or acyl chain profiles by mass spectrometry and gas chromatography. Compared to A2B5+/GFAP- progenitors, A2B5-/GFAP+ astrocytes contained higher amounts of ether phospholipids (especially the species containing arachidonic acid) and sphingomyelin, which may indicate characteristics of cellular differentiation and inability for multipotency. In comparison, principal component analyses revealed that the lipid composition of A2B5+/GFAP+ cells retained many of the characteristics of A2B5+/GFAP- progenitors, but their lipid profile was different from that of A2B5-/GFAP+ astrocytes. Thus, our study demonstrated that two GFAP+ cell populations have distinct lipid profiles with the A2B5+/GFAP+ cells sharing a phospholipid profile with progenitors rather than astrocytes. The progenitor cells may require regulated low levels of lipids known to mediate signaling functions in differentiated cells, and the precursor lipid profiles may serve as one measure of the differentiation capacity of a cell population.
  • Roine, Ulrika; Roine, Timo; Salmi, Juha; Nieminen-von Wendt, Taina; Tani, Pekka; Leppämäki, Sami; Rintahaka, Pertti; Caeyenberghs, Karen; Leemans, Alexander; Sams, Mikko (2015)
    Background: Recent brain imaging findings suggest that there are widely distributed abnormalities affecting the brain connectivity in individuals with autism spectrum disorder (ASD). Using graph theoretical analysis, it is possible to investigate both global and local properties of brain's wiring diagram, i.e., the connectome. Methods: We acquired diffusion-weighted magnetic resonance imaging data from 14 adult males with high-functioning ASD and 19 age-, gender-, and IQ-matched controls. As with diffusion tensor imaging-based tractography, it is not possible to detect complex (e.g., crossing) fiber configurations, present in 60-90 % of white matter voxels; we performed constrained spherical deconvolution-based whole brain tractography. Unweighted and weighted structural brain networks were then reconstructed from these tractography data and analyzed with graph theoretical measures. Results: In subjects with ASD, global efficiency was significantly decreased both in the unweighted and the weighted networks, normalized characteristic path length was significantly increased in the unweighted networks, and strength was significantly decreased in the weighted networks. In the local analyses, betweenness centrality of the right caudate was significantly increased in the weighted networks, and the strength of the right superior temporal pole was significantly decreased in the unweighted networks in subjects with ASD. Conclusions: Our findings provide new insights into understanding ASD by showing that the integration of structural brain networks is decreased and that there are abnormalities in the connectivity of the right caudate and right superior temporal pole in subjects with ASD.
  • Panahi, Mahmod; Mesri, Naeimeh Yousefi; Samuelsson, Eva-Britt; Coupland, Kirsten G.; Forsell, Charlotte; Graff, Caroline; Tikka, Saara; Winblad, Bengt; Viitanen, Matti; Karlström, Helena; Sundström, Erik; Behbahani, Homira (2018)
    Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a familial fatal progressive degenerative disorder. One of the pathological hallmarks of CADASIL is a dramatic reduction of vascular smooth muscle cells (VSMCs) in cerebral arteries. Using VSMCs from the vasculature of the human umbilical cord, placenta and cerebrum of CADASIL patients, we found that CADASIL VSMCs had a lower proliferation rate compared to control VSMCs. Exposure of control VSMCs and endothelial cells (ECs) to media derived from CADASIL VSMCs lowered the proliferation rate of all cells examined. By quantitative RT-PCR analysis, we observed increased Transforming growth factor-beta (TGF beta) gene expression in CADASIL VSMCs. Adding TGF beta-neutralizing antibody restored the proliferation rate of CADASIL VSMCs. We assessed proliferation differences in the presence or absence of TGF beta-neutralizing antibody in ECs co-cultured with VSMCs. ECs co-cultured with CADASIL VSMCs exhibited a lower proliferation rate than those co-cultured with control VSMCs, and neutralization of TGF beta normalized the proliferation rate of ECs co-cultured with CADASIL VSMCs. We suggest that increased TGF beta expression in CADASIL VSMCs is involved in the reduced VSMC proliferation in CADASIL and may play a role in situ in altered proliferation of neighbouring cells in the vasculature.
  • Ylinen, Sari; Junttila, Katja; Laasonen, Marja; Iverson, Paul; Ahonen, Lauri Valtteri; Kujala, Teija (2019)
    Dyslexia is characterized by poor reading skills, yet often also difficulties in second-language learning. The differences between native- and second-language speech processing and the establishment of new brain representations for spoken second language in dyslexia are not, however, well understood. We used recordings of the mismatch negativity component of event-related potential to determine possible differences between the activation of long-term memory representations for spoken native- and second-language word forms in Finnish-speaking 9-11-year-old children with or without dyslexia, studying English as their second language in school. In addition, we sought to investigate whether the bottleneck of dyslexic readers' second-language learning lies at the level of word representations or smaller units and whether the amplitude of mismatch negativity is correlated with native-language literacy and related skills. We found that the activation of brain representations for familiar second-language words, but not for second-language speech sounds or native-language words, was weaker in children with dyslexia than in typical readers. Source localization revealed that dyslexia was associated with weak activation of the right temporal cortex, which has been previously linked with word-form learning. Importantly, the amplitude of the mismatch negativity for familiar second-language words correlated with native-language literacy and rapid naming scores, suggesting a close link between second-language processing and these skills.
  • Zheng, Danni; Sato, Shoichiro; Arima, Hisatomi; Heeley, Emma; Delcourt, Candice; Cao, Yongjun; Chalmers, John; Anderson, Craig S.; INTERACT2 Investigators; Scheperjans, Filip; Kaste, Markku (2016)
    Background: The kidney-brain interaction has been a topic of growing interest. Past studies of the effect of kidney function on intracerebral hemorrhage (ICH) outcomes have yielded inconsistent findings. Although the second, main phase of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2) suggests the effectiveness of early intensive blood pressure (BP) lowering in improving functional recovery after ICH, the balance of potential benefits and harms of this treatment in those with decreased kidney function remains uncertain. Study Design: Secondary analysis of INTERACT2, which randomly assigned patients with ICH with elevated systolic BP (SBP) to intensive (target SBP <140 mm Hg) or contemporaneous guideline-based (target SBP, 180 mm Hg) BP management. Setting & Participants: 2,823 patients from 144 clinical hospitals in 21 countries. Predictors: Admission estimated glomerular filtration rates (eGFRs) of patients were categorized into 3 groups based on the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine equation: normal or high, mildly decreased, and moderately to severely decreased (>90, 60-90, and Outcomes: The effect of admission eGFR on the primary outcome of death or major disability at 90 days (defined as modified Rankin Scale scores of 3-6) was analyzed using a multivariable logistic regression model. Potential effect modification of intensive BP lowering treatment by admission eGFR was assessed by interaction terms. Results: Of 2,623 included participants, 912 (35%) and 280 (11%) had mildly and moderately/severely decreased eGFRs, respectively. Patients with moderately/severely decreased eGFRs had the greatest risk for death or major disability at 90 days (adjusted OR, 1.82; 95% CI, 1.28-2.61). Effects of early intensive BP lowering were consistent across different eGFRs (P = 0.5 for homogeneity). Limitations: Generalizability issues arising from a clinical trial population. Conclusions: Decreased eGFR predicts poor outcome in acute ICH. Early intensive BP lowering provides similar treatment effects in patients with ICH with decreased eGFRs. Am J Kidney Dis. 68(1): 94-102. (C) 2016 The Authors. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is an open access article under the CC BY-NC-ND license.
  • Sairanen, Viljami; Ocampo-Pineda, Mario; Granziera, Cristina; Schiavi, Simona; Daducci, Alessandro (2022)
    A B S T R A C T The white matter structures of the human brain can be represented using diffusion-weighted MRI tractography. Unfortunately, tractography is prone to find false-positive streamlines causing a severe decline in its specificity and limiting its feasibility in accurate structural brain connectivity analyses. Filtering algorithms have been pro-posed to reduce the number of invalid streamlines but the currently available filtering algorithms are not suitable to process data that contains motion artefacts which are typical in clinical research. We augmented the Con-vex Optimization Modelling for Microstructure Informed Tractography (COMMIT) algorithm to adjust for these signals drop-out motion artefacts. We demonstrate with comprehensive Monte-Carlo whole brain simulations and in vivo infant data that our robust algorithm is capable of properly filtering tractography reconstructions despite these artefacts. We evaluated the results using parametric and non-parametric statistics and our results demonstrate that if not accounted for, motion artefacts can have severe adverse effects in human brain structural connectivity analyses as well as in microstructural property mappings. In conclusion, the usage of robust filtering methods to mitigate motion related errors in tractogram filtering is highly beneficial, especially in clinical stud-ies with uncooperative patient groups such as infants. With our presented robust augmentation and open-source implementation, robust tractogram filtering is readily available.
  • Fekonja, Lucius S.; Wang, Ziqian; Cacciola, Alberto; Roine, Timo; Aydogan, D. Baran; Mewes, Darius; Vellmer, Sebastian; Vajkoczy, Peter; Picht, Thomas (2022)
    Tumors and their location distinctly alter both local and global brain connectivity within the ipsilesional hemisphere of glioma patients. Gliomas that infiltrate networks and systems, such as the motor system, often lead to substantial functional impairment in multiple systems. Network-based statistics (NBS) allow to assess local network differences and graph theoretical analyses enable investigation of global and local network properties. Here, we used network measures to characterize glioma-related decreases in structural connectivity by comparing the ipsi- with the contralesional hemispheres of patients and correlated findings with neurological assessment. We found that lesion location resulted in differential impairment of both short and long connectivity patterns. Network analysis showed reduced global and local efficiency in the ipsilesional hemisphere compared to the contralesional hemispheric networks, which reflect the impairment of information transfer across different regions of a network.
  • Aho, Leena; Metsäranta, Marjo; Lönnberg, Piia; Wolford, Elina; Lano, Aulikki (2021)
    Objective: The aim of this study was to evaluate the ability of the neonatal neurobehavioral characteristics to act as an indicator for later neurodevelopment and neurocognitive performance. Methods: Sixty-six infants born extremely preterm ( Results: An optimal auditory orientation at term age was associated with better developmental quotients (DQ) in Personal-Social, and Hearing-Language GMDS subscale at 2 years (p < 0.05). An optimal visual alertness was associated with better Total (p < 0.01), Locomotor (p < 0.001), and Eye-Hand Coordination (p < 0.01) DQs at 2 years, and with sensorimotor function (p < 0.001) and social perception (p < 0.01) tests at 6.5 years. Conclusion: The neurobehavioral characteristics of newborns might serve as a precursor of social cognition skills and the HNNE behavior subscale offers a tool to identify infants at risk for later deficits in neurodevelopment and social cognition.
  • IMAGEN Consortium; Ernst, Monique; Benson, Brenda; Artiges, Eric; Penttilä, Jani (2019)
    This study examines the effects of puberty and sex on the intrinsic functional connectivity (iFC) of brain networks, with a focus on the default-mode network (DMN). Consistently implicated in depressive disorders, the DMN's function may interact with puberty and sex in the development of these disorders, whose onsets peak in adolescence, and which show strong sex disproportionality (females > males). The main question concerns how the DMN evolves with puberty as a function of sex. These effects are expected to involve within- and between-network iFC, particularly, the salience and the central-executive networks, consistent with the Triple-Network Model. Resting-state scans of an adolescent community sample (n = 304, male/female: 157/147; mean/std age: 14.6/0.41 years), from the IMAGEN database, were analyzed using the AFNI software suite and a data reduction strategy for the effects of puberty and sex. Three midline regions (medial prefrontal, pregenual anterior cingulate, and posterior cingulate), within the DMN and consistently implicated in mood disorders, were selected as seeds. Within- and between-network clusters of the DMN iFC changed with pubertal maturation differently in boys and girls (puberty-X-sex). Specifically, pubertal maturation predicted weaker iFC in girls and stronger iFC in boys. Finally, iFC was stronger in boys than girls independently of puberty. Brain-behavior associations indicated that lower connectivity of the anterior cingulate seed predicted higher internalizing symptoms at 2-year follow-up. In conclusion, weaker iFC of the anterior DMN may signal disconnections among circuits supporting mood regulation, conferring risk for internalizing disorders.
  • Salo, Raimo A.; Belevich, Ilya; Manninen, Eppu; Jokitalo, Eija; Gröhn, Olli; Sierra, Alejandra (2018)
    Diffusion tensor imaging (DTI) reveals microstructural features of grey and white matter non-invasively. The contrast produced by DTI, however, is not fully understood and requires further validation. We used serial block-face scanning electron microscopy (SBEM) to acquire tissue metrics, i.e., anisotropy and orientation, using three-dimensional Fourier transform-based (3D-FT) analysis, to correlate with fractional anisotropy and orientation in DTI. SBEM produces high-resolution 3D data at the mesoscopic scale with good contrast of cellular membranes. We analysed selected samples from cingulum, corpus callosum, and perilesional cortex of sham-operated and traumatic brain injury (TBI) rats. Principal orientations produced by DTI and 3D-FT in all samples were in good agreement. Anisotropy values showed similar patterns of change in corresponding DTI and 3D-FT parameters in sham-operated and TBI rats. While DTI and 3D-FT anisotropy values were similar in grey matter, 3D-FT anisotropy values were consistently lower than fractional anisotropy values from DTI in white matter. We also evaluated the effect of resolution in 3D-FT analysis. Despite small angular differences in grey matter samples, lower resolution datasets provided reliable results, allowing for analysis of larger fields of view. Overall, 3D SBEM allows for more sophisticated validation studies of diffusion imaging contrast from a tissue microstructural perspective.
  • Saarinen, Aino; Lieslehto, Johannes; Kiviniemi, Vesa; Häkli, Jani; Tuovinen, Timo; Hintsanen, Mirka; Veijola, Juha (2020)
    Background: Physiological brain pulsations have been shown to play a critical role in maintaining interstitial homeostasis in the glymphatic brain clearance mechanism. We investigated whether psychotic symptomatology is related to the physiological variation of the human brain using fMRI. Methods: The participants (N= 277) were from the Northern Finland Birth Cohort 1986. Psychotic symptoms were evaluated with the Positive Symptoms Scale of the Structured Interview for Prodromal Syndromes(SIPS). We used the coefficient of variation of BOLD signal (CVBOLD) as a proxy for physiological brain pulsatility.The CVBOLD-analyses were controlled for motion, age, sex, and educational level. The results were also compared with fMRI and voxel-based morphometry (VBM) meta-analyses of schizophrenia patients (data from theBrainmap database). Results: At the global level, participants with psychotic-like symptoms had higher CVBOLDin cerebrospinal fluid(CSF) and white matter (WM), when compared to participants with no psychotic symptoms. Voxel-wise analy-ses revealed that CVBOLDwas increased, especially in periventricular white matter, basal ganglia, cerebellum and parts of the cortical structures. Those brain regions, which included alterations of physiological fluctuation in symptomatic psychosis risk, overlappedb6% with the regions that were found to be affected in the meta-analyses of previous fMRI and VBM studies in schizophrenia patients. Motion did not vary as a function of SIPS. Conclusions: Psychotic-like symptoms were associated with elevated CVBOLDin a variety of brain regions. The CVBOLD findings may produce new information about cerebral physiological fluctuations that have been out of reach in previous fMRI and VBM studies.
  • PIPARI Study Grp; Lahti, Katri; Parkkola, Riitta; Jääsaari, Päivi; Haataja, Leena; Saunavaara, Virva (2021)
    Background Diffusion tensor imaging is a widely used imaging method of brain white matter, but it is prone to imaging artifacts. The data corrections can affect the measured values. Objective To explore the impact of susceptibility correction on diffusion metrics. Materials and methods A cohort of 27 healthy adolescents (18 boys, 9 girls, mean age 12.7 years) underwent 3-T MRI, and we collected two diffusion data sets (anterior-posterior). The data were processed both with and without susceptibility artifact correction. We derived fractional anisotropy, mean diffusivity and histogram data of fiber length distribution from both the corrected and uncorrected data, which were collected from the corpus callosum, corticospinal tract and cingulum bilaterally. Results Fractional anisotropy and mean diffusivity values significantly differed when comparing the pathways in all measured tracts. The fractional anisotropy values were lower and the mean diffusivity values higher in the susceptibility-corrected data than in the uncorrected data. We found a significant difference in total tract length in the corpus callosum and the corticospinal tract. Conclusion This study indicates that susceptibility correction has a significant effect on measured fractional anisotropy, and on mean diffusivity values and tract lengths. To receive reliable and comparable results, the correction should be used systematically.
  • Saarinen, Aino; Lieslehto, Johannes; Kiviniemi, Vesa; Tuovinen, Timo; Veijola, Juha; Hintsanen, Mirka (2020)
    Previously, schizophrenia is found to be related to the variability of the functional magnetic resonance imaging (fMRI) signal in the white matter. However, evidence about the relationship between genetic vulnerabilities and physiological fluctuation in the brain is lacking. We investigated whether familial risk for psychosis (FR) and polygenic risk score for schizophrenia (PRS) are linked with physiological fluctuation in fMRI data. We used data from the Oulu Brain and Mind study (n. = 140-149, aged 20-24 years) that is a substudy of the Northern Finland Birth Cohort 1986. The participants underwent a resting-state fMRI scan. Coefficient of variation (CV) of blood oxygen level dependent (BOLD) signal (CVBOLD) was used as a proxy of physiological fluctuation in the brain. Familial risk was defined to be present if at least one parent had been diagnosed with psychosis previously. PRS was computed based on the results of the prior GWAS by the Schizophrenia Working Group. FR or PRS were not associated with CVBOLD in cerebrospinal fluid, white matter, or grey matter. The findings did not provide evidence for the previous suggestions that genetic vulnerabilities for schizophrenia become apparent in alterations of the variation of the BOLD signal in the brain.
  • Sihvonen, Aleksi J.; Ripolles, Pablo; Särkämö, Teppo; Leo, Vera; Rodriguez-Fornells, Antoni; Saunavaara, Jani; Parkkola, Riitta; Soinila, Seppo (2017)
    Acquired amusia provides a unique opportunity to investigate the fundamental neural architectures of musical processing due to the transition from a functioning to defective music processing system. Yet, the white matter (WM) deficits in amusia remain systematically unexplored. To evaluate which WM structures form the neural basis for acquired amusia and its recovery, we studied 42 stroke patients longitudinally at acute, 3-month, and 6-month post-stroke stages using DTI [tract-based spatial statistics (TBSS) and deterministic tractography (DT)] and the Scale and Rhythm subtests of the Montreal Battery of Evaluation of Amusia (MBEA). Non-recovered amusia was associated with structural damage and subsequent degeneration in multiple WM tracts including the right inferior fronto-occipital fasciculus (IFOF), arcuate fasciculus (AF), inferior longitudinal fasciculus (ILF), uncinate fasciculus (UF), and frontal aslant tract (FAT), as well as in the corpus callosum (CC) and its posterior part (tapetum). In a linear regression analysis, the volume of the right IFOF was the main predictor of MBEA performance across time. Overall, our results provide a comprehensive picture of the large-scale deficits in intra- and interhemispheric structural connectivity underlying amusia, and conversely highlight which pathways are crucial for normal music perception.