Browsing by Subject "HUMAN BRAIN"

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  • Kauppi, Jukka-Pekka; Pajula, Juha; Tohka, Jussi (2014)
    In the inter-subject correlation (ISC) based analysis of the functional magnetic resonance imaging (fMRI) data, the extent of shared processing across subjects during the experiment is determined by calculating correlation coefficients between the fMRI time series of the subjects in the corresponding brain locations. This implies that ISC can be used to analyze fMRI data without explicitly modeling the stimulus and thus ISC is a potential method to analyze fMRI data acquired under complex naturalistic stimuli. Despite of the suitability of ISC based approach to analyze complex fMRI data, no generic software tools have been made available for this purpose, limiting a widespread use of ISC based analysis techniques among neuroimaging community. In this paper, we present a graphical user interface (GUI) based software package, ISC Toolbox, implemented in Matlab for computing various ISC based analyses. Many advanced computations such as comparison of ISCs between different stimuli, time window ISC, and inter-subject phase synchronization are supported by the toolbox. The analyses are coupled with resampling based statistical inference. The ISC based analyses are data and computation intensive and the ISC toolbox is equipped with mechanisms to execute the parallel computations in a cluster environment automatically and with an automatic detection of the cluster environment in use. Currently, SGE-based (Oracle Grid Engine, Son of a Grid Engine, or Open Grid Scheduler) and Slurm environments are supported. In this paper, we present a detailed account on the methods behind the ISC Toolbox, the implementation of the toolbox and demonstrate the possible use of the toolbox by summarizing selected example applications. We also report the computation time experiments both using a single desktop computer and two grid environments demonstrating that parallelization effectively reduces the computing time.
  • Burunat, Iballa; Brattico, Elvira; Puoliväli, Tuomas; Ristaniemi, Tapani; Sams, Mikko; Toiviainen, Petri (2015)
    Musical training leads to sensory and motor neuroplastic changes in the human brain. Motivated by findings on enlarged corpus callosum in musicians and asymmetric somatomotor representation in string players, we investigated the relationship between musical training, callosal anatomy, and interhemispheric functional symmetry during music listening. Functional symmetry was increased in musicians compared to nonmusicians, and in keyboardists compared to string players. This increased functional symmetry was prominent in visual and motor brain networks. Callosal size did not significantly differ between groups except for the posterior callosum in musicians compared to nonmusicians. We conclude that the distinctive postural and kinematic symmetry in instrument playing cross-modally shapes information processing in sensory-motor cortical areas during music listening. This cross-modal plasticity suggests that motor training affects music perception.
  • Altavilla, Riccardo; Caso, Valeria; Bandini, Fabio; Agnelli, Giancarlo; Tsivgoulis, Georgios; Yaghi, Shadi; Furie, Karen L.; Tadi, Prasanna; Becattini, Cecilia; Zedde, Marialuisa; Abdul-Rahim, Azmil H.; Lees, Kennedy R.; Alberti, Andrea; Venti, Michele; Acciarresi, Monica; D'Amore, Cataldo; Mosconi, Maria Giulia; Cimini, Ludovica Anna; Fusaro, Jessica; Bovi, Paolo; Carletti, Monica; Rigatelli, Alberto; Cappellari, Manuel; Putaala, Jukka; Tomppo, Liisa; Tatlisumak, Turgut; Marcheselli, Simona; Pezzini, Alessandro; Poli, Loris; Padovani, Alessandro; Masotti, Luca; Vannucchi, Vieri; Sohn, Sung-Il; Lorenzini, Gianni; Tassi, Rossana; Guideri, Francesca; Acampa, Maurizio; Martini, Giuseppe; Ntaios, George; Athanasakis, George; Makaritsis, Konstantinos; Karagkiozi, Efstathia; Vadikolias, Konstantinos; Liantinioti, Chrysoula; Chondrogianni, Maria; Mumoli, Nicola; Consoli, Domenico; Galati, Franco; Sacco, Simona; Carolei, Antonio; Tiseo, Cindy; Corea, Francesco; Ageno, Walter; Bellesini, Marta; Silvestrelli, Giorgio; Ciccone, Alfonso; Lanari, Alessia; Scoditti, Umberto; Denti, Licia; Mancuso, Michelangelo; Maccarrone, Miriam; Ulivi, Leonardo; Orlandi, Giovanni; Giannini, Nicola; Gialdini, Gino; Tassinari, Tiziana; De Lodovici, Maria Luisa; Bono, Giorgio; Rueckert, Christina; Baldi, Antonio; D'Anna, Sebastiano; Toni, Danilo; Letteri, Federica; Giuntini, Martina; Lotti, Enrico Maria; Flomin, Yuriy; Pieroni, Alessio; Kargiotis, Odysseas; Karapanayiotides, Theodore; Monaco, Serena; Baronello, Mario Maimone; Csiba, Laszlo; Szabo, Lilla; Chiti, Alberto; Giorli, Elisa; Del Sette, Massimo; Imberti, Davide; Zabzuni, Dorjan; Doronin, Boris; Volodina, Vera; Michel, Patrik; Vanacker, Peter; Barlinn, Kristian; Pallesen, Lars-Peder; Barlinn, Jessica; Deleu, Dirk; Melikyan, Gayane; Ibrahim, Faisal; Akhtar, Naveed; Gourbali, Vanessa; Paciaroni, Maurizio (2019)
    Background and Purpose- Bridging therapy with low-molecular-weight heparin reportedly leads to a worse outcome for acute cardioembolic stroke patients because of a higher incidence of intracerebral bleeding. However, this practice is common in clinical settings. This observational study aimed to compare (1) the clinical profiles of patients receiving and not receiving bridging therapy, (2) overall group outcomes, and (3) outcomes according to the type of anticoagulant prescribed. Methods- We analyzed data of patients from the prospective RAF and RAF-NOACs studies. The primary outcome was defined as the composite of ischemic stroke, transient ischemic attack, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding observed at 90 days after the acute stroke. Results- Of 1810 patients who initiated oral anticoagulant therapy, 371 (20%) underwent bridging therapy with full-dose low-molecular-weight heparin. Older age and the presence of leukoaraiosis were inversely correlated with the use of bridging therapy. Forty-two bridged patients (11.3%) reached the combined outcome versus 72 (5.0%) of the nonbridged patients (P=0.0001). At multivariable analysis, bridging therapy was associated with the composite end point (odds ratio, 2.3; 95% CI, 1.4-3.7; P Conclusions- Our findings suggest that patients receiving low-molecular-weight heparin have a higher risk of early ischemic recurrence and hemorrhagic transformation compared with nonbridged patients.
  • Grimaldi, Mirko; Sisinni, Bianca; Fivela, Barbara Gili; Invitto, Sara; Resta, Donatella; Alku, Paava; Brattico, Elvira (2014)
  • Girchenko, Polina; Lahti, Jari; Czamara, Darina; Knight, Anna K.; Jones, Meaghan J.; Suarez Figueiredo, Anna; Hämäläinen, Esa; Kajantie, Eero; Laivuori, Hannele; Villa, Pia M.; Reynolds, Rebecca M.; Kobor, Michael S.; Smith, Alicia K.; Binder, Elisabeth B.; Räikkönen, Katri (2017)
    Background: A recent study has shown that it is possible to accurately estimate gestational age (GA) at birth from the DNA methylation (DNAm) of fetal umbilical cord blood/newborn blood spots. This DNAm GA predictor may provide additional information relevant to developmental stage. In 814 mother-neonate pairs, we evaluated the associations between DNAm GA and a number of maternal and offspring characteristics. These characteristics reflect prenatal environmental adversity and are expected to influence newborn developmental stage. Results: DNAm GA acceleration (GAA; i.e., older DNAm GA than chronological GA) of the offspring at birth was associated with maternal age of over 40 years at delivery, pre-eclampsia and fetal demise in a previous pregnancy, maternal pre-eclampsia and treatment with antenatal betamethasone in the index pregnancy, lower neonatal birth size, lower 1-min Apgar score, and female sex. DNAm GA deceleration (GAD; i.e., younger DNAm GA than chronological GA) of the offspring at birth was associated with insulin-treated gestational diabetes mellitus (GDM) in a previous pregnancy and Sjogren's syndrome. These findings were more accentuated when the DNAm GA calculation was based on the raw difference between DNAm GA and GA than on the residual from the linear regression of DNAm GA on GA. Conclusions: Our findings show that variations in the DNAm GA of the offspring at birth are associated with a number of maternal and offspring characteristics known to reflect exposure to prenatal environmental adversity. Future studies should be aimed at determining if this biological variation is predictive of developmental adversity.
  • Hämäläinen, Sini; Joutsa, Juho; Sihvonen, Aleksi J.; Leminen, Alina; Lehtonen, Minna (2018)
    Bilingualism is a sustained experience associated with structural changes in cortical grey matter (GM) morphology. Apart from a few studies, a dominant method used to assess bilingualism-induced GM changes has been the voxel-based morphometry (VBM) analysis. While VBM is sensitive to GM volume/density differences in general, it cannot be used to identify whether the observed difference is due to relative changes in, e.g., cortical thickness, area or folding, as it uses a single combined measure of them all. Here, we used surface-based analysis (SBA) approach to investigate whether early acquisition of a second language (L2) affects the cortical GM morphology relative to late L2 acquisition. More specifically, our aim was to test a hypothesis that early acquisition of two languages induces GM changes that are predominantly surface area-driven, while late acquisition is supposedly characterised with primarily thickness-driven changes. To this end, several surface-based measures were concurrently compared between the groups. In line with the hypothesis, the results revealed that early bilingual experience is associated with significantly extended cortical surface area over the left pars opercularis and the right superior temporal gyrus. Contrary to our expectations, however, we found no evidence supporting the postulated association between late L2 acquisition and increased cortical thickness. Nevertheless, our study highlights the importance of including cortical surface measures when investigating bilingualism related GM modulations.
  • Sulkava, Sonja; Ollila, Hanna M.; Alasaari, Jukka; Puttonen, Sampsa; Harma, Mikko; Viitasalo, Katriina; Lahtinen, Alexandra; Lindstrom, Jaana; Toivola, Auli; Sulkava, Raimo; Kivimaki, Mika; Vahtera, Jussi; Partonen, Timo; Silander, Kaisa; Porkka-Heiskanen, Tarja; Paunio, Tiina (2017)
    Study Objectives: Tolerance to shift work varies; only some shift workers suffer from disturbed sleep, fatigue, and job-related exhaustion. Our aim was to explore molecular genetic risk factors for intolerance to shift work. Methods: We assessed intolerance to shift work with job-related exhaustion symptoms in shift workers using the emotional exhaustion subscale of the Maslach Burnout Inventory-General Survey, and carried out a genome-wide association study (GWAS) using Illumina's Human610-Quad BeadChip (n = 176). The most significant findings were further studied in three groups of Finnish shift workers (n = 577). We assessed methylation in blood cells with the Illumina HumanMethylation450K BeadChip, and examined gene expression levels in the publicly available eGWAS Mayo data. Results: The second strongest signal identified in the GWAS (p = 2.3 x 10E-6) was replicated in two of the replication studies with p Conclusions: These findings suggest that a variant near MTNR1A may be associated with job-related exhaustion in shift workers. The risk variant may exert its effect via epigenetic mechanisms, potentially leading to reduced melatonin signaling in the brain. These results could indicate a link between melatonin signaling, a key circadian regulatory mechanism, and tolerance to shift work.
  • Ruuth, Riikka; Kuusela, Linda; Mäkelä, Teemu; Melkas, Susanna; Korvenoja, Antti (2019)
    Aim and scope: A Gradient Echo Plural Contrast Imaging technique (GEPCI) is a post-processing method, which can be used to obtain quantitative T2* values and generate multiple synthetic contrasts from a single acquisition. However, scan duration and image reconstruction from k-space data present challenges in a clinical workflow. This study aimed at optimizing image reconstruction and acquisition duration to facilitate a post-processing method for synthetic image contrast creation in clinical settings. Materials and methods: This study consists of tests using the American College of Radiology (ACR) image quality phantom, two healthy volunteers, four mild traumatic brain injury patients and four small vessel disease patients. The measurements were carried out on a 3.0 T scanner with multiple echo times. Reconstruction from k-space data and DICOM data with two different coil-channel combination modes were investigated. Partial Fourier techniques were tested to optimize the scanning time. Conclusions: Sum of squares coil-channel combination produced artifacts in phase images, but images created with adaptive combination were artifact-free. The voxel-wise median signed difference of T2* between the vendor's adaptive channel combination and k-space reconstruction modes was 2.9 +/- 0.7 ms for white matter and 4.5 +/- 0.6 ms for gray matter. Relative white matter/gray matter contrast of all synthetic images and contrast-to-noise ratio of synthetic T1-weighted images were almost equal between reconstruction modes. Our results indicate that synthetic contrasts can be generated from the vendor's DICOM data with the adaptive combination mode without affecting the quantitative T2* values or white matter/gray matter contrast.
  • Hotta, Jaakko; Zhou, Guangyu; Harno, Hanna; Forss, Nina; Hari, Riitta (2017)
    Introduction: Many central pathophysiological aspects of complex regional pain syndrome (CRPS) are still unknown. Although brain-imaging studies are increasingly supporting the contribution of the central nervous system to the generation and maintenance of the CRPS pain, the brain's white-matter alterations are seldom investigated. Methods: In this study, we used diffusion tensor imaging to explore white-matter changes in twelve CRPS-type-1 female patients suffering from chronic right upper-limb pain compared with twelve healthy control subjects. Results: Tract-based spatial-statistics analysis revealed significantly higher mean diffusivity, axial diffusivity, and radial diffusivity in the CRPS patients, suggesting that the structural connectivity is altered in CRPS. All these measures were altered in the genu, body, and splenium of corpus callosum, as well as in the left anterior and posterior and the right superior parts of the corona radiata. Axial diffusivity was significantly correlated with clinical motor symptoms at whole-brain level, supporting the physiological significance of the observed white-matter abnormalities. Conclusions: Altogether, our findings further corroborate the involvement of the central nervous system in CRPS.
  • Roine, Ulrika; Salmi, Juha; Roine, Timo; Nieminen-von Wendt, Taina; Leppämäki, Sami; Rintahaka, Pertti; Tani, Pekka; Leemans, Alexander; Sams, Mikko (2015)
  • Heinonen, Jarmo; Numminen, Jussi; Hlushchuk, Yevhen; Antell, Henrik; Taatila, Vesa; Suomala, Jyrki (2016)
    Scientific findings have suggested a two-fold structure of the cognitive process. By using the heuristic thinking mode, people automatically process information that tends to be invariant across days, whereas by using the explicit thinking mode people explicitly process information that tends to be variant compared to typical previously learned information patterns. Previous studies on creativity found an association between creativity and the brain regions in the prefrontal cortex, the anterior cingulate cortex, the default mode network and the executive network. However, which neural networks contribute to the explicit mode of thinking during idea generation remains an open question. We employed an fMRI paradigm to examine which brain regions were activated when participants (n = 16) mentally generated alternative uses for everyday objects. Most previous creativity studies required participants to verbalize responses during idea generation, whereas in this study participants produced mental alternatives without verbalizing. This study found activation in the left anterior insula when contrasting idea generation and object identification. This finding suggests that the insula (part of the brain's salience network) plays a role in facilitating both the central executive and default mode networks to activate idea generation. We also investigated closely the effect of the serial order of idea being generated on brain responses: The amplitude of fMRI responses correlated positively with the serial order of idea being generated in the anterior cingulate cortex, which is part of the central executive network. Positive correlation with the serial order was also observed in the regions typically assigned to the default mode network: the precuneus/ cuneus, inferior parietal lobule and posterior cingulate cortex. These networks support the explicit mode of thinking and help the individual to convert conventional mental models to new ones. The serial order correlated negatively with the BOLD responses in the posterior presupplementarymotor area, left premotor cortex, right cerebellum and left inferior frontal gyrus. This finding might imply that idea generation without a verbal processing demand reflecting lack of need for new object identification in idea generation events. The results of the study are consistent with recent creativity studies, which emphasize that the creativity process involves working memory capacity to spontaneously shift between different kinds of thinking modes according to the context.
  • Semenova, Svetlana; Rozov, Stanislav; Panula, Pertti (2017)
    Catechol-O-methyltransferase (COMT; EC 2.1.1.6) is an enzyme with multiple functions in vertebrates. COMT methylates and thus inactivates catecholamine neurotransmitters and metabolizes xenobiotic catechols. Gene polymorphism rs4680 that influences the enzymatic activity of COMT affects cognition and behavior in humans. The zebrafish is widely used as an experimental animal in many areas of biomedical research, but most aspects of COMT function in this species have remained uncharacterized. We hypothesized that both comt genes play essential roles in zebrafish. Both comt-a and comt-b were widely expressed in zebrafish tissues, but their relative abundance varied considerably. Homogenates of zebra fish organs, including the brain, showed enzymatic COMT activity that was the highest in the liver and kidney. Treatment of larval zebrafish with the COMT inhibitor Ro41-0960 shifted the balance of catecholamine metabolic pathways towards increased oxidative metabolism. Whole-body concentrations of dioxyphenylacetic acid (DOPAC), a product of dopamine oxidation, were increased in the inhibitor treated larvae, although the dopamine levels were unchanged. Thus, COMT is likely to participate in the processing of catecholamine neurotransmitters in the zebrafish, but the inhibition of COMT in larval fish is compensated efficiently and does not have pronounced effects on dopamine levels. (C) 2017 Elsevier Inc. All rights reserved.
  • Liljeström, Mia; Kujala, Jan; Stevenson, Claire; Salmelin, Riitta (2015)
  • Paciaroni, Maurizio; Agnelli, Giancarlo; Falocci, Nicola; Tsivgoulis, Georgios; Vadikolias, Kostantinos; Liantinioti, Chrysoula; Chondrogianni, Maria; Bovi, Paolo; Carletti, Monica; Cappellari, Manuel; Zedde, Marialuisa; Ntaios, George; Karagkiozi, Efstathia; Athanasakis, George; Makaritsis, Kostantinos; Silvestrelli, Giorgio; Lanari, Alessia; Ciccone, Alfonso; Putaala, Jukka; Tomppo, Liisa; Tatlisumak, Turgut; Abdul-Rahim, Azmil H.; Lees, Kennedy R.; Alberti, Andrea; Venti, Michele; Acciarresi, Monica; D'Amore, Cataldo; Becattini, Cecilia; Mosconi, Maria Giulia; Cimini, Ludovica Anna; Soloperto, Rossana; Masotti, Luca; Vannucchi, Vieri; Lorenzini, Gianni; Tassi, Rossana; Guideri, Francesca; Acampa, Maurizio; Martini, Giuseppe; Sohn, Sung-Il; Marcheselli, Simona; Mumoli, Nicola; De Lodovici, Maria Luisa; Bono, Giorgio; Furie, Karen L.; Tadi, Prasanna; Yaghi, Shadi; Toni, Danilo; Letteri, Federica; Tassinari, Tiziana; Kargiotis, Odysseas; Lotti, Enrico Maria; Flomin, Yuriy; Mancuso, Michelangelo; Maccarrone, Miriam; Giannini, Nicola; Bandini, Fabio; Pezzini, Alessandro; Poli, Loris; Padovani, Alessandro; Scoditti, Umberto; Denti, Licia; Consoli, Domenico; Galati, Franco; Sacco, Simona; Carolei, Antonio; Tiseo, Cindy; Gourbali, Vanessa; Orlandi, Giovanni; Giuntini, Martina; Chiti, Alberto; Giorli, Elisa; Gialdini, Gino; Corea, Francesco; Ageno, Walter; Bellesini, Marta; Colombo, Giovanna; Monaco, Serena; Baronello, Mario Maimone; Karapanayiotides, Theodore; Caso, Valeria (2017)
    Background-The optimal timing to administer non-vitamin K oral anticoagulants (NOACs) in patients with acute ischemic stroke and atrial fibrillation is unclear. This prospective observational multicenter study evaluated the rates of early recurrence and major bleeding (within 90 days) and theirtiming in patients with acute ischemic stroke and atrial fibrillation who received NOACs for secondary prevention. Methods and Results-Recurrence was defined as the composite of ischemic stroke, transient ischemic attack, and symptomatic systemic embolism, and major bleeding was defined as symptomatic cerebral and major extracranial bleeding. For the analysis, 1127 patients were eligible: 381 (33.8%) were treated with dabigatran, 366 (32.5%) with rivaroxaban, and 380 (33.7%) with apixaban. Patients who received dabigatran were younger and had lower admission National Institutes of Health Stroke Scale score and less commonly had a CHA(2)DS(2)-VASc score >4 and less reduced renal function. Thirty-two patients (2.8%) had early recurrence, and 27 (2.4%) had major bleeding. The rates of early recurrence and major bleeding were, respectively, 1.8% and 0.5% in patients receiving dabigatran, 1.6% and 2.5% in those receiving rivaroxaban, and 4.0% and 2.9% in those receiving apixaban. Patients who initiated NOACs within 2 days after acute stroke had a composite rate of recurrence and major bleeding of 12.4%; composite rates were 2.1% for those who initiated NOACs between 3 and 14 days and 9.1% for those who initiated > 14 days after acute stroke. Conclusions-In patients with acute ischemic stroke and atrial fibrillation, treatment with NOACs was associated with a combined 5% rate of ischemic embolic recurrence and severe bleeding within 90 days.
  • Maria, Ambika; Shekhar, Shashank; Nissilä, Ilkka; Kotilahti, Kalle; Huotilainen, Minna; Karlsson, Linnea; Karlsson, Hasse; Tuulari, Jetro J. (2018)
    Emotional stimuli processing during childhood helps us to detect salient cues in our environment and prepares us for our social life. In early childhood, the emotional valences of auditory and visual input are salient and relevant cues of social aspects of the environment, and it is of special interest to understand how exactly the processing ofemotional stimuli develops. Near-infrared spectroscopy (NIRS) is a noninvasive neuroimaging tool that has proven valuable in studying emotional processing in children. After conducting a systematic search of PubMed, Web of Science, and Embase databases, we examined 50 NIRS studies performed to study emotional stimuli processing in children in the first 2 years of age. We found that the majority of these studies are done in infants and the most commonly used stimuli are visual and auditory. Many of the reviewed studies suggest the involvement of bilateral temporal areas in emotional processing of visual and auditory stimuli. It is unclear which neural activation patterns reflect maturation and at what age the emotional encoding reaches those typically seen in adults. Our review provides an overview of the database on emotional processing in children up to 2 years of age. Furthermore, it demonstrates the need to include the less-studied age range of 1 to 2 years, and suggests the use of combined audio-visual stimuli and longitudinal studies for future research on emotional processing in children. Thus, NIRS might be a vital tool to study the associations between the early pattern of neural responses and socioemotional development later in life.
  • Zhou, Guangyu; Hotta, Jaakko; Lehtinen, Maria K.; Forss, Nina; Hari, Riitta (2015)
    The choroid plexus, located in brain ventricles, has received surprisingly little attention in clinical neuroscience. In morphometric brain analysis, we serendipitously found a 21% increase in choroid plexus volume in 12 patients suffering from complex regional pain syndrome (CRPS) compared with age- and gender-matched healthy subjects. No enlargement was observed in a group of 8 patients suffering from chronic pain of other etiologies. Our findings suggest involvement of the choroid plexus in the pathogenesis of CRPS. Since the choroid plexus can mediate interaction between peripheral and brain inflammation, our findings pinpoint the choroid plexus as an important target for future research of central pain mechanisms.
  • Sihvonen, Aleksi J.; Särkämö, Teppo; Ripolles, Pablo; Leo, Vera; Saunavaara, Jani; Parkkola, Riitta; Rodriguez-Fornells, Antoni; Soinila, Seppo (2017)
    Brain damage causing acquired amusia disrupts the functional music processing system, creating a unique opportunity to investigate the critical neural architectures of musical processing in the brain. In this longitudinal fMRI study of stroke patients (N = 41) with a 6-month follow-up, we used natural vocal music (sung with lyrics) and instrumental music stimuli to uncover brain activation and functional network connectivity changes associated with acquired amusia and its recovery. In the acute stage, amusic patients exhibited decreased activation in right superior temporal areas compared to non-amusic patients during instrumental music listening. During the follow-up, the activation deficits expanded to comprise a wide-spread bilateral frontal, temporal, and parietal network. The amusics showed less activation deficits to vocal music, suggesting preserved processing of singing in the amusic brain. Compared to non-recovered amusics, recovered amusics showed increased activation to instrumental music in bilateral frontoparietal areas at 3 months and in right middle and inferior frontal areas at 6 months. Amusia recovery was also associated with increased functional connectivity in right and left frontoparietal attention networks to instrumental music. Overall, our findings reveal the dynamic nature of deficient activation and connectivity patterns in acquired amusia and highlight the role of dorsal networks in amusia recovery.
  • Hatton, Sean N.; Panizzon, Matthew S.; Vuoksimaa, Eero; Hagler, Donald J.; Fennema-Notestine, Christine; Rinker, Daniel; Eyler, Lisa T.; Franz, Carol E.; Lyons, Michael J.; Neale, Michael C.; Tsuang, Ming T.; Dale, Anders M.; Kremen, William S. (2018)
    Two basic neuroimaging-based characterizations of white matter tracts are the magnitude of water diffusion along the principal tract orientation (axial diffusivity, AD) and water diffusion perpendicular to the principal orientation (radial diffusivity, RD). It is generally accepted that decreases in AD reflect disorganization, damage, or loss of axons, whereas increases in RD are indicative of disruptions to the myelin sheath. Previous reports have detailed the heritability of individual AD and RD measures, but have not examined the extent to which the same or different genetic or environmental factors influence these two phenotypes (except for corpus callosum). We implemented bivariate twin analyses to examine the shared and independent genetic influences on AD and RD. In the Vietnam Era Twin Study of Aging, 393 men (mean age = 61.8 years, SD = 2.6) underwent diffusion-weighted magnetic resonance imaging. We derived fractional anisotropy (FA), mean diffusivity (MD), AD, and RD estimates for 11 major bilateral white matter tracts and the mid-hemispheric corpus callosum, forceps major, and forceps minor. Separately, AD and RD were each highly heritable. In about three-quarters of the tracts, genetic correlations between AD and RD were >.50 (median = .67) and showed both unique and common variance. Genetic variance of FA and MD were predominately explained by RD over AD. These findings are important for informing genetic association studies of axonal coherence/damage and myelination/demyelination. Thus, genetic studies would benefit from examining the shared and unique contributions of AD and RD.
  • Psychiat Genomics Consortium; 23andMe Res Team; Psychosis Endopheno-types Int Cons; Wellcome Trust Case Control Consor; Lee, Phil H.; Anttila, Verneri; Won, Hyejung; Kaprio, Jaakko; Keski-Rahkonen, Anna; Churchhouse, Claire; Rehnström, Karola; Raevuori, Anu; Palotie, Aarno; Daly, Mark J.; Neale, Benjamin M. (2019)
    Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.
  • Pajula, Juha; Kauppi, Jukka-Pekka; Tohka, Jussi (2012)