Publications

Journal Article
Catherine S Hubbard, Lino Becerra, Nicole Heinz, Allison Ludwick, Tali Rasooly, Anastasia Yendiki, Rina Wu, Neil L Schechter, Samuel Nurko, and David Borsook. 2018. “Microstructural White Matter Abnormalities in the Dorsal Cingulum of Adolescents with IBS.” eNeuro, 5, 4.Abstract
Alterations in fractional anisotropy (FA) have been considered to reflect microstructural white matter (WM) changes in disease conditions; however, no study to date has examined WM changes using diffusion tensor imaging (DTI) in adolescents with irritable bowel syndrome (IBS). The objective of the present study was two-fold: (1) to determine whether differences in FA, and other non-FA metrics, were present in adolescents with IBS compared to healthy controls using whole-brain, region of interest (ROI)-restricted tract-based spatial statistics (TBSS) and canonical ROI DTI analyses for the cingulum bundle, and (2) to determine whether these metrics were related to clinical measures of disease duration and pain intensity in the IBS group. A total of 16 adolescents with a Rome III diagnosis of IBS (females = 12; mean age = 16.29, age range: 11.96-18.5 years) and 16 age- and gender-matched healthy controls (females = 12; mean age = 16.24; age range: 11.71-20.32 years) participated in this study. Diffusion-weighted images were acquired using a Siemens 3-T Trio Tim Syngo MRI scanner with a 32-channel head coil. The ROI-restricted TBSS and canonical ROI-based DTI analyses revealed that adolescents with IBS showed decreased FA in the right dorsal cingulum bundle compared to controls. No relationship between FA and disease severity measures was found. Microstructural WM alterations in the right dorsal cingulum bundle in adolescents with IBS may reflect a premorbid brain state or the emergence of a disease-driven process that results from complex changes in pain- and affect-related processing via spinothalamic and corticolimbic pathways.
A Versace, CD Ladouceur, S Graur, HE Acuff, LK Bonar, K Monk, A McCaffrey, A Yendiki, A Leemans, MJ Travis, VA Diwadkar, SK Holland, JL Sunshine, RA Kowatch, SM Horwitz, TW Frazier, LE Arnold, MA Fristad, EA Youngstrom, RL Findling, BI Goldstein, T Goldstein, D Axelson, B Birmaher, and ML Phillips. 2018. “Diffusion imaging markers of bipolar versus general psychopathology risk in youth at-risk.” Neuropsychopharmacology, 43, 11, Pp. 2212-2220.Abstract
Bipolar disorder (BD) is highly heritable. Thus, studies in first-degree relatives of individuals with BD could lead to the discovery of objective risk markers of BD. Abnormalities in white matter structure reported in at-risk individuals could play an important role in the pathophysiology of BD. Due to the lack of studies with other at-risk offspring, however, it remains unclear whether such abnormalities reflect BD-specific or generic risk markers for future psychopathology. Using a tract-profile approach, we examined 18 major white matter tracts in 38 offspring of BD parents, 36 offspring of comparison parents with non-BD psychopathology (depression, attention-deficit/hyperactivity disorder), and 41 offspring of healthy parents. Both at-risk groups showed significantly lower fractional anisotropy (FA) in left-sided tracts (cingulum, inferior longitudinal fasciculus, forceps minor), and significantly greater FA in right-sided tracts (uncinate fasciculus and inferior longitudinal fasciculus), relative to offspring of healthy parents (P < 0.05). These abnormalities were present in both healthy and affected youth in at-risk groups. Only offspring (particularly healthy offspring) of BD parents showed lower FA in the right superior longitudinal fasciculus relative to healthy offspring of healthy parents (P < 0.05). We show, for the first time, important similarities, and some differences, in white matter structure between offspring of BD and offspring of non-BD parents. Findings suggest that lower left-sided and higher right-sided FA in tracts important for emotional regulation may represent markers of risk for general, rather than BD-specific, psychopathology. Lower FA in the right superior longitudinal fasciculus may protect against development of BD in offspring of BD parents.
Brian L Edlow, Dirk C Keene, Daniel P Perl, Diego Iacono, Rebecca D Folkerth, William Stewart, Christine L MacDonald, Jean Augustinack, Ramon Diaz-Arrastia, Camilo Estrada, Elissa Flannery, Wayne A Gordon, Thomas J Grabowski, Kelly Hansen, Jeanne Hoffman, Christopher Kroenke, Eric B Larson, Patricia Lee, Azma Mareyam, Jennifer A McNab, Jeanne McPhee, Allison L Moreau, Anne Renz, KatieRose Richmire, Allison Stevens, Cheuk Y Tang, Lee S Tirrell, Emily H Trittschuh, Andre van der Kouwe, Ani Varjabedian, Lawrence L Wald, Ona Wu, Anastasia Yendiki, Liza Young, Lilla Zöllei, Bruce Fischl, Paul K Crane, and Kristen Dams-O'Connor. 2018. “Multimodal Characterization of the Late Effects of Traumatic Brain Injury: A Methodological Overview of the Late Effects of Traumatic Brain Injury Project.” J Neurotrauma, 35, 14, Pp. 1604-1619.Abstract
Epidemiological studies suggest that a single moderate-to-severe traumatic brain injury (TBI) is associated with an increased risk of neurodegenerative disease, including Alzheimer's disease (AD) and Parkinson's disease (PD). Histopathological studies describe complex neurodegenerative pathologies in individuals exposed to single moderate-to-severe TBI or repetitive mild TBI, including chronic traumatic encephalopathy (CTE). However, the clinicopathological links between TBI and post-traumatic neurodegenerative diseases such as AD, PD, and CTE remain poorly understood. Here, we describe the methodology of the Late Effects of TBI (LETBI) study, whose goals are to characterize chronic post-traumatic neuropathology and to identify in vivo biomarkers of post-traumatic neurodegeneration. LETBI participants undergo extensive clinical evaluation using National Institutes of Health TBI Common Data Elements, proteomic and genomic analysis, structural and functional magnetic resonance imaging (MRI), and prospective consent for brain donation. Selected brain specimens undergo ultra-high resolution ex vivo MRI and histopathological evaluation including whole-mount analysis. Co-registration of ex vivo and in vivo MRI data enables identification of ex vivo lesions that were present during life. In vivo signatures of postmortem pathology are then correlated with cognitive and behavioral data to characterize the clinical phenotype(s) associated with pathological brain lesions. We illustrate the study methods and demonstrate proof of concept for this approach by reporting results from the first LETBI participant, who despite the presence of multiple in vivo and ex vivo pathoanatomic lesions had normal cognition and was functionally independent until her mid-80s. The LETBI project represents a multidisciplinary effort to characterize post-traumatic neuropathology and identify in vivo signatures of postmortem pathology in a prospective study.
HD Rosas, P Wilkens, DH Salat, ND Mercaldo, M Vangel, AY Yendiki, and SM Hersch. 2018. “Complex spatial and temporally defined myelin and axonal degeneration in Huntington disease.” Neuroimage Clin, 20, Pp. 236-242.Abstract
Although much prior work has focused on the basal ganglia and cortical pathology that defines Huntington's disease (HD), recent studies have also begun to characterize cerebral white matter damage (Rosas et al., 2006; Dumas et al., 2012; Poudel et al., 2014). In this study, we investigated differences in the large fascicular bundles of the cerebral white matter of gene-positive HD carriers, including pre-manifest individuals and early symptomatic patients, using recently developed diffusion tractography procedures. We examined eighteen major fiber bundles in 37 patients with early HD (average age 55.2 ± 11.5, 14 male, 23 female), 31 gene-positive, motor negative pre-symptomatic HD (PHD) (average age 48.1 ± 11.5, 13 male, 18 female), and 38 healthy age-matched controls (average age 55.7 ± 8.6, 14 male, 24 female), using the TRActs Constrained by UnderLying Anatomy (TRACULA) procedure available as part of the FreeSurfer image processing software package. We calculated the mean fractional anisotropy (FA) and the mean radial (RD) and axial diffusivities (AD) for each fiber bundle. We also evaluated the relationships between diffusion measures, cognition and regional cortical thinning. We found that early changes in RD of select tracts in PHD subjects were associated with impaired performance on neuropsychological tests, suggesting that early changes in myelin might underlie early cognitive dysfunction. Finally, we found that increases in AD of select tracts were associated with regionally select cortical thinning of areas known to atrophy in HD, including the sensorimotor, supramarginal and fusiform gyrus, suggesting that AD may be reflecting pyramidal cell degeneration in HD. Together, these results suggest that white matter microstructural changes in HD reflect a complex, clinically relevant and dynamic process.
Fikret Işık Karahanoğlu, Bengi Baran, Quynh Trang Huong Nguyen, Djalel-Eddine Meskaldji, Anastasia Yendiki, Mark Vangel, Susan L Santangelo, and Dara S Manoach. 2018. “Diffusion-weighted imaging evidence of altered white matter development from late childhood to early adulthood in Autism Spectrum Disorder.” Neuroimage Clin, 19, Pp. 840-847.Abstract
Autism Spectrum Disorder (ASD) is thought to reflect disrupted development of brain connectivity characterized by white matter abnormalities and dyscoordination of activity across brain regions that give rise to core features. But there is little consensus about the nature, timing and location of white matter abnormalities as quantified with diffusion-weighted MRI. Inconsistent findings likely reflect small sample sizes, motion confounds and sample heterogeneity, particularly different age ranges across studies. We examined the microstructural integrity of major white matter tracts in relation to age in 38 high functioning ASD and 35 typically developing (TD) participants, aged 8-25, whose diffusion-weighted scans met strict data-quality criteria and survived group matching for motion. While there were no overall group differences in diffusion measures, the groups showed different relations with age. Only the TD group showed the expected positive correlations of fractional anisotropy with age. In parallel, axial diffusivity was unrelated to age in TD, but showed inverse correlations with age in ASD. Younger participants with ASD tended to have higher fractional anisotropy and axial diffusivity than their TD peers, while the opposite was true for older participants. Most of the affected tracts - cingulum bundle, inferior and superior longitudinal fasciculi - are association bundles related to cognitive, social and emotional functions that are abnormal in ASD. The manifestations of abnormal white matter development in ASD as measured by diffusion-weighted MRI depend on age and this may contribute to inconsistent findings across studies. We conclude that ASD is characterized by altered white matter development from childhood to early adulthood that may underlie abnormal brain function and contribute to core features.
Safadi Z, Grisot G, Jbabdi S, Behrens T, Heilbronner SR, McLaughlin NCR, Mandeville J, Versace A, Phillips ML, Lehman J, Yendiki A, and Haber SN. 2018. “Functional segmentation of the anterior limb of the internal capsule: linking white matter abnormalities to specific connections.” J Neurosci, 38, 8, Pp. 2106-2117.
V. Siless, K. Chang, B. Fischl, and A. Yendiki. 2018. “AnatomiCuts: Hierarchical clustering of tractography streamlines based on anatomical similarity.” NeuroImage, 166, Pp. 32-45.
K. Kenney, D. Iacono, B. L. Edlow, D. I. Katz, R. Diaz-Arrastia, K. Dams-O’Connor, D. H. Daneshvar, A. Stevens, A. L. Moreau, L. S. Tirrell, A. Varjabedian, A. Yendiki, A. van der Kouwe, A. Mareyam, J. A. McNab, W. A. Gordon, B. Fischl, A. C. McKee, and D. P. Perl. 2018. “Dementia after moderate-severe traumatic brain injury: Coexistence of multiple proteinopathies.” Journal of Neuropathology and Experimental Neurology, 77, 1, Pp. 50-63.
Randy P Auerbach, Angela Pisoni, Erin Bondy, Poornima Kumar, Jeremy G Stewart, Anastasia Yendiki, and Diego A Pizzagalli. 2017. “Neuroanatomical Prediction of Anhedonia in Adolescents.” Neuropsychopharmacology, 42, 10, Pp. 2087-2095.Abstract
Anhedonia is a transdiagnostic risk factor implicated in mental illness onset, treatment non-response, and suicidal behaviors. Prior cross-sectional research in adults has shown that anhedonia is associated with reduced dorsal striatal volume, but it is unknown whether this relationship extends to adolescents and whether reduced striatal volume prospectively predicts anhedonia. To address these gaps, the current study investigated whether striatal volume predicted anhedonia severity in adolescents. At baseline, healthy female adolescents aged 12-14 years (n=50) completed a clinical assessment, and structural MRI data were acquired on a 3 Tesla MR scanner. While in the scanner, participants also completed a peer feedback task where subjective ratings following peer 'acceptance' or 'rejection' were obtained. At the three-month follow-up, participants provided self-report assessments of anhedonia, depression, and anxiety symptoms. Three main findings emerged. First, in cross-sectional analyses, right nucleus accumbens volume was inversely related to anhedonia severity. Second, reduced bilateral putamen volume prospectively predicted anhedonia severity while controlling for baseline anhedonia, depression, and anxiety symptoms. Third, a blunted subjective response to peer acceptance (ie, neutral response to positive feedback), but not a more negative subjective response to peer rejection, contributed to anhedonia severity, but only among youth with smaller putamen volume. Collectively, these results suggest that smaller volume in striatal regions critically implicated in reward processing is associated with current and future anhedonic symptoms among healthy female youth. These anatomical features may confer vulnerability to anhedonia and thus, may inform early identification of individuals at high risk for mental illness.Neuropsychopharmacology advance online publication, 29 March 2017; doi:10.1038/npp.2017.28.
Anders M Fjell, Markus H Sneve, Håkon Grydeland, Andreas B Storsve, Inge K Amlien, Anastasia Yendiki, and Kristine B Walhovd. 2017. “Relationship between structural and functional connectivity change across the adult lifespan: A longitudinal investigation.” Hum Brain Mapp, 38, 1, Pp. 561-573.Abstract
Extensive efforts are devoted to understand the functional (FC) and structural connections (SC) of the brain. FC is usually measured by functional magnetic resonance imaging (fMRI), and conceptualized as degree of synchronicity in brain activity between different regions. SC is typically indexed by measures of white matter (WM) properties, for example, by diffusion weighted imaging (DWI). FC and SC are intrinsically related, in that coordination of activity across regions ultimately depends on fast and efficient transfer of information made possible by structural connections. Convergence between FC and SC has been shown for specific networks, especially the default mode network (DMN). However, it is not known to what degree FC is constrained by major WM tracts and whether FC and SC change together over time. Here, 120 participants (20-85 years) were tested at two time points, separated by 3.3 years. Resting-state fMRI was used to measure FC, and DWI to measure WM microstructure as an index of SC. TRACULA, part of FreeSurfer, was used for automated tractography of 18 major WM tracts. Cortical regions with tight structural couplings defined by tractography were only weakly related at the functional level. Certain regions of the DMN showed a modest relationship between change in FC and SC, but for the most part, the two measures changed independently. The main conclusions are that anatomical alignment of SC and FC seems restricted to specific networks and tracts, and that changes in SC and FC are not necessarily strongly correlated. Hum Brain Mapp 38:561-573, 2017. © 2016 Wiley Periodicals, Inc.
Joanna A Christodoulou, Jack Murtagh, Abigail Cyr, Tyler K Perrachione, Patricia Chang, Kelly Halverson, Pamela Hook, Anastasia Yendiki, Satrajit Ghosh, and John DE Gabrieli. 2016. “Relation of White-Matter Microstructure to Reading Ability and Disability in Beginning Readers.” Neuropsychology.Abstract
OBJECTIVE: We examined the white-matter microstructure of the left arcuate fasciculus, which has been associated with reading ability, in beginning readers with or without reading disability. METHOD: Groups were typically reading children (n = 26) or children with reading disability (n = 26), Ages 6-9, and equated on nonverbal cognitive abilities. Diffusion-weighted images were collected and TRACULA was used to extract fractional anisotropy measures from the left arcuate fasciculus. RESULTS: White-matter microstructure was altered in children with reading disability, who exhibited significantly reduced fractional anisotropy in the left arcuate fasciculus. Among typically reading children, lower fractional anisotropy of the left arcuate fasciculus was associated with superior pseudoword reading performance. Both the group differences and variation in reading scores among the children with reading disability were associated with radial diffusivity (but not axial diffusivity), whereas variation in reading scores among typically reading children was associated with axial diffusivity (but not radial diffusivity). CONCLUSIONS: The paradoxical findings that lower fractional anisotropy was associated both with reading disability and also with better phonological awareness in typical reading development suggest that there are different maturational trajectories of white-matter microstructure in typical readers and children with reading disability, and that this difference is unique to the beginning stages of reading acquisition. The finding that reading disability was associated with radial diffusivity, but that variation in ability among typically developing readers was associated with axial diffusivity, suggests that different neural mechanisms may be associated with reading development in children with or without reading disability. (PsycINFO Database Record
Anders M Fjell, Markus H Sneve, Andreas B Storsve, Håkon Grydeland, Anastasia Yendiki, and Kristine B Walhovd. 2016. “Brain Events Underlying Episodic Memory Changes in Aging: A Longitudinal Investigation of Structural and Functional Connectivity.” Cereb Cortex, 26, 3, Pp. 1272-86.Abstract
Episodic memories are established and maintained by close interplay between hippocampus and other cortical regions, but degradation of a fronto-striatal network has been suggested to be a driving force of memory decline in aging. We wanted to directly address how changes in hippocampal-cortical versus striatal-cortical networks over time impact episodic memory with age. We followed 119 healthy participants (20-83 years) for 3.5 years with repeated tests of episodic verbal memory and magnetic resonance imaging for quantification of functional and structural connectivity and regional brain atrophy. While hippocampal-cortical functional connectivity predicted memory change in young, changes in cortico-striatal functional connectivity were related to change in recall in older adults. Within each age group, effects of functional and structural connectivity were anatomically closely aligned. Interestingly, the relationship between functional connectivity and memory was strongest in the age ranges where the rate of reduction of the relevant brain structure was lowest, implying selective impacts of the different brain events on memory. Together, these findings suggest a partly sequential and partly simultaneous model of brain events underlying cognitive changes in aging, where different functional and structural events are more or less important in various time windows, dismissing a simple uni-factorial view on neurocognitive aging.
Anastasia Yendiki, Martin Reuter, Paul Wilkens, Diana H Rosas, and Bruce Fischl. 2016. “Joint reconstruction of white-matter pathways from longitudinal diffusion MRI data with anatomical priors.” Neuroimage, 127, Pp. 277-86.Abstract
We consider the problem of reconstructing white-matter pathways in a longitudinal study, where diffusion-weighted and T1-weighted MR images have been acquired at multiple time points for the same subject. We propose a method for joint reconstruction of a subject's pathways at all time points given the subject's entire set of longitudinal data. We apply a method for unbiased within-subject registration to generate a within-subject template from the T1-weighted images of the subject at all time points. We follow a global probabilistic tractography approach, where the unknown pathway is represented in the space of this within-subject template and propagated to the native space of the diffusion-weighted images at all time points to compute its posterior probability given the images. This ensures spatial correspondence of the reconstructed pathway among time points, which in turn allows longitudinal changes in diffusion measures to be estimated consistently along the pathway. We evaluate the reliability of the proposed method on data from healthy controls scanned twice within a month, where no changes in white-matter microstructure are expected between scans. We evaluate the sensitivity of the method on data from Huntington's disease patients scanned repeatedly over the course of several months, where changes are expected between scans. We show that reconstructing white-matter pathways jointly using the data from all time points leads to improved reliability and sensitivity, when compared to reconstructing the pathways at each time point independently.
Anne Elisabeth Sølsnes, Kam Sripada, Anastasia Yendiki, Knut Jørgen Bjuland, Heidi Furre Østgård, Synne Aanes, Kristine Hermansen Grunewaldt, Gro C Løhaugen, Live Eikenes, Asta K Håberg, Lars M Rimol, and Jon Skranes. 2016. “Limited microstructural and connectivity deficits despite subcortical volume reductions in school-aged children born preterm with very low birth weight.” Neuroimage, 130, Pp. 24-34.Abstract
Preterm birth and very low birth weight (VLBW, ≤1500 g) are worldwide problems that burden survivors with lifelong cognitive, psychological, and physical challenges. In this multimodal structural magnetic resonance imaging (MRI) and diffusion MRI (dMRI) study, we investigated differences in subcortical brain volumes and white matter tract properties in children born preterm with VLBW compared to term-born controls (mean age=8 years). Subcortical brain structure volumes and cortical thickness estimates were obtained, and fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were generated for 18 white matter tracts. We also assessed structural relationships between white matter tracts and cortical thickness of the tract endpoints. Compared to controls, the VLBW group had reduced volumes of thalamus, globus pallidus, corpus callosum, cerebral white matter, ventral diencephalon, and brain stem, while the ventricular system was larger in VLBW subjects, after controlling for age, sex, IQ, and estimated total intracranial volume. For the dMRI parameters, group differences were not significant at the whole-tract level, though pointwise analysis found shorter segments affected in forceps minor and left superior longitudinal fasciculus - temporal bundle. IQ did not correlate with subcortical volumes or dMRI measures in the VLBW group. While the deviations in subcortical volumes were substantial, there were few differences in dMRI measures between the two groups, which may reflect the influence of advances in perinatal care on white matter development.
Andreas B Storsve, Anders M Fjell, Anastasia Yendiki, and Kristine B Walhovd. 2016. “Longitudinal Changes in White Matter Tract Integrity across the Adult Lifespan and Its Relation to Cortical Thinning.” PLoS One, 11, 6, Pp. e0156770.Abstract
A causal link between decreases in white matter (WM) integrity and cortical degeneration is assumed, but there is scarce knowledge on the relationship between these changes across the adult human lifespan. We investigated changes in thickness throughout the cortical mantle and WM tract integrity derived from T1 and diffusion weighted magnetic resonance imaging (MRI) scans in 201 healthy adults aged 23-87 years over a mean interval of 3.6 years. Fractional anisotropy (FA), mean (MD), radial (RD) and axial (AD) diffusivity changes were calculated for forceps minor and major and eight major white matter tracts in each hemisphere by use of a novel automated longitudinal tractography constrained by underlying anatomy (TRACULA) approach. We hypothesized that increasing MD and decreasing FA across tracts would relate to cortical thinning, with some anatomical specificity. WM integrity decreased across tracts non-uniformly, with mean annual percentage decreases ranging from 0.20 in the Inferior Longitudinal Fasciculus to 0.65 in the Superior Longitudinal Fasciculus. For most tracts, greater MD increases and FA decreases related to more cortical thinning, in areas in part overlapping with but also outside the projected tract endings. The findings indicate a combination of global and tract-specific relationships between WM integrity and cortical thinning.
S-H Lee, J-P Coutu, P Wilkens, A Yendiki, HD Rosas, and DH Salat. 2015. “Tract-based analysis of white matter degeneration in Alzheimer's disease.” Neuroscience, 301, Pp. 79-89.Abstract
Although much prior work has focused on the known cortical pathology that defines Alzheimer's disease (AD) histologically, recent work has additionally demonstrated substantial damage to the cerebral white matter in this condition. While there is large evidence of diffuse damage to the white matter in AD, it is unclear whether specific white matter tracts exhibit a more accelerated pattern of damage and whether the damage is associated with the classical neurodegenerative changes of AD. In this study, we investigated microstructural differences in the large fascicular bundles of the cerebral white matter of individuals with AD and mild cognitive impairment (MCI), using recently developed automated diffusion tractography procedures in the Alzheimer's disease Neuroimaging Initiative (ADNI) dataset. Eighteen major fiber bundles in a total of 36 individuals with AD, 81 MCI and 60 control participants were examined with the TRActs Constrained by UnderLying Anatomy (TRACULA) procedure available as part of the FreeSurfer image processing software package. For each fiber bundle, the mean fractional anisotropy (FA), and mean, radial and axial diffusivities were calculated. Individuals with AD had increased diffusivities in both left and right cingulum-angular bundles compared to control participants (p<0.001). Individuals with MCI also had increased axial and mean diffusivities and increased FA in both cingulum-angular bundles compared to control participants (p<0.05) and decreased radial diffusivity compared to individuals with AD (p<0.05). We additionally examined how white matter deterioration relates to hippocampal volume, a traditional imaging measure of AD pathology, and found the strongest negative correlations in AD patients between hippocampal volume and the diffusivities of the cingulum-angular and cingulum-cingulate gyrus bundles and of the corticospinal tracts (p<0.05). However, statistically controlling for hippocampal volume did not remove all group differences in white matter measures, suggesting a unique contribution of white matter damage to AD unexplained by this disease biomarker. These results suggest that (1) AD-associated deterioration of white matter fibers is greatest in tracts known to be connected to areas of pathology in AD and (2) lower white matter tract integrity is more diffusely associated with lower hippocampal volume indicating that the pathology in the white matter follows to some degree the neurodegenerative staging and progression of this condition.
Stefan Ehrlich, Daniel Geisler, Anastasia Yendiki, Patricia Panneck, Veit Roessner, Vince D Calhoun, Vincent A Magnotta, Randy L Gollub, and Tonya White. 2014. “Associations of white matter integrity and cortical thickness in patients with schizophrenia and healthy controls.” Schizophr Bull, 40, 3, Pp. 665-74.Abstract
Typical brain development includes coordinated changes in both white matter (WM) integrity and cortical thickness (CT). These processes have been shown to be disrupted in schizophrenia, which is characterized by abnormalities in WM microstructure and by reduced CT. The aim of this study was to identify patterns of association between WM markers and cortex-wide CT in healthy controls (HCs) and patients with schizophrenia (SCZ). Using diffusion tensor imaging and structural magnetic resonance imaging data of the Mind Clinical Imaging Consortium study (130 HC and 111 SCZ), we tested for associations between (a) fractional anisotropy in selected manually labeled WM pathways (corpus callosum, anterior thalamic radiation, and superior longitudinal fasciculus) and CT, and (b) the number of lesion-like WM regions ("potholes") and CT. In HC, but not SCZ, we found highly significant negative associations between WM integrity and CT in several pathways, including frontal, temporal, and occipital brain regions. Conversely, in SCZ the number of WM potholes correlated with reduced CT in the left lateral temporal gyrus, left fusiform, and left lateral occipital brain area. Taken together, we found differential patterns of association between WM integrity and CT in HC and SCZ. Although the pattern in HC can be explained from a developmental perspective, the reduced gray matter CT in SCZ patients might be the result of focal but spatially heterogeneous disruptions of WM integrity.
Anastasia Yendiki, Kami Koldewyn, Sita Kakunoori, Nancy Kanwisher, and Bruce Fischl. 2014. “Spurious group differences due to head motion in a diffusion MRI study.” Neuroimage, 88, Pp. 79-90.Abstract
Diffusion-weighted MRI (DW-MRI) has become a popular imaging modality for probing the microstructural properties of white matter and comparing them between populations in vivo. However, the contrast in DW-MRI arises from the microscopic random motion of water molecules in brain tissues, which makes it particularly sensitive to macroscopic head motion. Although this has been known since the introduction of DW-MRI, most studies that use this modality for group comparisons do not report measures of head motion for each group and rely on registration-based correction methods that cannot eliminate the full effects of head motion on the DW-MRI contrast. In this work we use data from children with autism and typically developing children to investigate the effects of head motion on differences in anisotropy and diffusivity measures between groups. We show that group differences in head motion can induce group differences in DW-MRI measures, and that this is the case even when comparing groups that include control subjects only, where no anisotropy or diffusivity differences are expected. We also show that such effects can be more prominent in some white-matter pathways than others, and that they can be ameliorated by including motion as a nuisance regressor in the analyses. Our results demonstrate the importance of taking head motion into account in any population study where one group might exhibit more head motion than the other.
Hui Wang, Junfeng Zhu, Martin Reuter, Louis N Vinke, Anastasia Yendiki, David A Boas, Bruce Fischl, and Taner Akkin. 2014. “Cross-validation of serial optical coherence scanning and diffusion tensor imaging: a study on neural fiber maps in human medulla oblongata.” Neuroimage, 100, Pp. 395-404.Abstract
We established a strategy to perform cross-validation of serial optical coherence scanner imaging (SOCS) and diffusion tensor imaging (DTI) on a postmortem human medulla. Following DTI, the sample was serially scanned by SOCS, which integrates a vibratome slicer and a multi-contrast optical coherence tomography rig for large-scale three-dimensional imaging at microscopic resolution. The DTI dataset was registered to the SOCS space. An average correlation coefficient of 0.9 was found between the co-registered fiber maps constructed by fractional anisotropy and retardance contrasts. Pixelwise comparison of fiber orientations demonstrated good agreement between the DTI and SOCS measures. Details of the comparison were studied in regions exhibiting a variety of fiber organizations. DTI estimated the preferential orientation of small fiber tracts; however, it didn't capture their complex patterns as SOCS did. In terms of resolution and imaging depth, SOCS and DTI complement each other, and open new avenues for cross-modality investigations of the brain.
Kami Koldewyn, Anastasia Yendiki, Sarah Weigelt, Hyowon Gweon, Joshua Julian, Hilary Richardson, Caitlin Malloy, Rebecca Saxe, Bruce Fischl, and Nancy Kanwisher. 2014. “Differences in the right inferior longitudinal fasciculus but no general disruption of white matter tracts in children with autism spectrum disorder.” Proc Natl Acad Sci U S A, 111, 5, Pp. 1981-6.Abstract
One of the most widely cited features of the neural phenotype of autism is reduced "integrity" of long-range white matter tracts, a claim based primarily on diffusion imaging studies. However, many prior studies have small sample sizes and/or fail to address differences in data quality between those with autism spectrum disorder (ASD) and typical participants, and there is little consensus on which tracts are affected. To overcome these problems, we scanned a large sample of children with autism (n = 52) and typically developing children (n = 73). Data quality was variable, and worse in the ASD group, with some scans unusable because of head motion artifacts. When we follow standard data analysis practices (i.e., without matching head motion between groups), we replicate the finding of lower fractional anisotropy (FA) in multiple white matter tracts. However, when we carefully match data quality between groups, all these effects disappear except in one tract, the right inferior longitudinal fasciculus (ILF). Additional analyses showed the expected developmental increases in the FA of fiber tracts within ASD and typical groups individually, demonstrating that we had sufficient statistical power to detect known group differences. Our data challenge the widely claimed general disruption of white matter tracts in autism, instead implicating only one tract, the right ILF, in the ASD phenotype.

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