Publications

Journal Article
Viviana Siless, Juliet Y Davidow, Jared Nielsen, Qiuyun Fan, Trey Hedden, Marisa Hollinshead, Elizabeth Beam, Constanza M Vidal Bustamante, Megan C Garrad, Rosario Santillana, Emily E Smith, Aya Hamadeh, Jenna Snyder, Michelle K Drews, Koene RA Van Dijk, Margaret Sheridan, Leah H Somerville, and Anastasia Yendiki. 2020. “Registration-free analysis of diffusion MRI tractography data across subjects through the human lifespan.” Neuroimage, 214, Pp. 116703.Abstract
Diffusion MRI tractography produces massive sets of streamlines that need to be clustered into anatomically meaningful white-matter bundles. Conventional clustering techniques group streamlines based on their proximity in Euclidean space. We have developed AnatomiCuts, an unsupervised method for clustering tractography streamlines based on their neighboring anatomical structures, rather than their coordinates in Euclidean space. In this work, we show that the anatomical similarity metric used in AnatomiCuts can be extended to find corresponding clusters across subjects and across hemispheres, without inter-subject or inter-hemispheric registration. Our proposed approach enables group-wise tract cluster analysis, as well as studies of hemispheric asymmetry. We evaluate our approach on data from the pilot MGH-Harvard-USC Lifespan Human Connectome project, showing improved correspondence in tract clusters across 184 subjects aged 8-90. Our method shows up to 38% improvement in the overlap of corresponding clusters when comparing subjects with large age differences. The techniques presented here do not require registration to a template and can thus be applied to populations with large inter-subject variability, e.g., due to brain development, aging, or neurological disorders.
Suzanne N Haber, Wei Tang, Eun Young Choi, Anastasia Yendiki, Hesheng Liu, Saad Jbabdi, Amelia Versace, and Mary Phillips. 2020. “Circuits, Networks, and Neuropsychiatric Disease: Transitioning From Anatomy to Imaging.” Biol Psychiatry, 87, 4, Pp. 318-327.Abstract
Since the development of cellular and myelin stains, anatomy has formed the foundation for understanding circuitry in the human brain. However, recent functional and structural studies using magnetic resonance imaging have taken the lead in this endeavor. These innovative and noninvasive approaches have the advantage of studying connectivity patterns under different conditions directly in the human brain. They demonstrate dynamic and structural changes within and across networks linked to normal function and to a wide range of psychiatric illnesses. However, these indirect methods are unable to link networks to the hardwiring that underlies them. In contrast, anatomic invasive experimental studies can. Following a brief review of prefrontal cortical, anterior cingulate, and striatal connections and the different methodologies used, this article discusses how data from anatomic studies can help inform how hardwired connections are linked to the functional and structural networks identified in imaging studies.
Zhiqiang Sha, Kale E Edmiston, Amelia Versace, Jay C Fournier, Simona Graur, Tsafrir Greenberg, João Paulo Lima Santos, Henry W Chase, Richelle S Stiffler, Lisa Bonar, Robert Hudak, Anastasia Yendiki, Benjamin D Greenberg, Steven Rasmussen, Hesheng Liu, Gregory Quirk, Suzanne Haber, and Mary L Phillips. 2020. “Functional Disruption of Cerebello-thalamo-cortical Networks in Obsessive-Compulsive Disorder.” Biol Psychiatry Cogn Neurosci Neuroimaging, 5, 4, Pp. 438-447.Abstract
BACKGROUND: Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive, compulsive behaviors. Neuroimaging studies have implicated altered connectivity among the functional networks of the cerebral cortex in the pathophysiology of OCD. However, there has been no comprehensive investigation of the cross-talk between the cerebellum and functional networks in the cerebral cortex. METHODS: This functional neuroimaging study was completed by 44 adult participants with OCD and 43 healthy control participants. We performed large-scale data-driven brain network analysis to identify functional connectivity patterns using resting-state functional magnetic resonance imaging data. RESULTS: Participants with OCD showed lower functional connectivity within the somatomotor network and greater functional connectivity among the somatomotor network, cerebellum, and subcortical network (e.g., thalamus and pallidum; all p < .005). Network-based statistics analyses demonstrated one component comprising connectivity within the somatomotor network that showed lower connectivity and a second component comprising connectivity among the somatomotor network, and motor regions in particular, and the cerebellum that showed greater connectivity in participants with OCD relative to healthy control participants. In participants with OCD, abnormal connectivity across both network-based statistics-derived components positively correlated with OCD symptom severity (p = .006). CONCLUSIONS: To our knowledge, this study is the first comprehensive investigation of large-scale network alteration across the cerebral cortex, subcortical regions, and cerebellum in OCD. Our findings highlight a critical role of the cerebellum in the pathophysiology of OCD.
Lilla Zöllei, Camilo Jaimes, Elie Saliba, Ellen P Grant, and Anastasia Yendiki. 2019. “TRActs constrained by UnderLying INfant anatomy (TRACULInA): An automated probabilistic tractography tool with anatomical priors for use in the newborn brain.” Neuroimage, 199, Pp. 1-17.Abstract
The ongoing myelination of white-matter fiber bundles plays a significant role in brain development. However, reliable and consistent identification of these bundles from infant brain MRIs is often challenging due to inherently low diffusion anisotropy, as well as motion and other artifacts. In this paper we introduce a new tool for automated probabilistic tractography specifically designed for newborn infants. Our tool incorporates prior information about the anatomical neighborhood of white-matter pathways from a training data set. In our experiments, we evaluate this tool on data from both full-term and prematurely born infants and demonstrate that it can reconstruct known white-matter tracts in both groups robustly, even in the presence of differences between the training set and study subjects. Additionally, we evaluate it on a publicly available large data set of healthy term infants (UNC Early Brain Development Program). This paves the way for performing a host of sophisticated analyses in newborns that we have previously implemented for the adult brain, such as pointwise analysis along tracts and longitudinal analysis, in both health and disease.
Wei Tang, Saad Jbabdi, Ziyi Zhu, Michiel Cottaar, Giorgia Grisot, Julia F Lehman, Anastasia Yendiki, and Suzanne N Haber. 2019. “A connectional hub in the rostral anterior cingulate cortex links areas of emotion and cognitive control.” Elife, 8.Abstract
We investigated afferent inputs from all areas in the frontal cortex (FC) to different subregions in the rostral anterior cingulate cortex (rACC). Using retrograde tracing in macaque monkeys, we quantified projection strength by counting retrogradely labeled cells in each FC area. The projection from different FC regions varied across injection sites in strength, following different spatial patterns. Importantly, a site at the rostral end of the cingulate sulcus stood out as having strong inputs from many areas in diverse FC regions. Moreover, it was at the integrative conjunction of three projection trends across sites. This site marks a connectional hub inside the rACC that integrates FC inputs across functional modalities. Tractography with monkey diffusion magnetic resonance imaging (dMRI) located a similar hub region comparable to the tracing result. Applying the same tractography method to human dMRI data, we demonstrated that a similar hub can be located in the human rACC.
A Versace, S Graur, T Greenberg, JP Lima Santos, HW Chase, L Bonar, RS Stiffler, R Hudak, Tae Kim, A Yendiki, B Greenberg, S Rasmussen, H Liu, S Haber, and ML Phillips. 2019. “Reduced focal fiber collinearity in the cingulum bundle in adults with obsessive-compulsive disorder.” Neuropsychopharmacology, 44, 7, Pp. 1182-1188.Abstract
Obsessive-compulsive disorder (OCD) is a disabling condition, often associated with a chronic course. Given its role in attentional control, decision-making, and emotional regulation, the anterior cingulate cortex is considered to have a key role in the pathophysiology of the disorder. Notably, the cingulum bundle, being the major white matter tract connecting to this region, has been historically a target for the surgical treatment of intractable OCD. In this study, we aimed to identify the extent to which focal-more than diffuse-abnormalities in fiber collinearity of the cingulum bundle could distinguish 48 adults with OCD (mean age [SD] = 23.3 [4.5] years; F/M = 30/18) from 45 age- and sex-matched healthy control adults (CONT; mean age [SD] = 23.2 [3.8] years; F/M = 28/17) and further examine if these abnormalities correlated with symptom severity. Use of tract-profiles rather than a conventional diffusion imaging approach allowed us to characterize white matter microstructural properties along (100 segments), as opposed to averaging these measures across, the entire tract. To account for these 100 different segments of the cingulum bundle, a repeated measures analysis of variance revealed a main effect of group (OCD < CONT; F = 5.3; P = 0.024) upon fractional anisotropy (FA, a measure of fiber collinearity and/or white matter integrity), in the cingulum bundle, bilaterally. Further analyses revealed that these abnormalities were focal (middle portion) within the left and right cingulum bundle, although did not correlate with symptom severity in OCD. Findings indicate that focal abnormalities in connectivity between the anterior cingulate cortex and other prefrontal cortical regions may represent neural mechanisms of OCD.
Aina Frau-Pascual, Morgan Fogarty, Bruce Fischl, Anastasia Yendiki, and Iman Aganj. 2019. “Quantification of structural brain connectivity via a conductance model.” Neuroimage, 189, Pp. 485-496.Abstract
Connectomics has proved promising in quantifying and understanding the effects of development, aging and an array of diseases on the brain. In this work, we propose a new structural connectivity measure from diffusion MRI that allows us to incorporate direct brain connections, as well as indirect ones that would not be otherwise accounted for by standard techniques and that may be key for the better understanding of function from structure. From our experiments on the Human Connectome Project dataset, we find that our measure of structural connectivity better correlates with functional connectivity than streamline tractography does, meaning that it provides new structural information related to function. Through additional experiments on the ADNI-2 dataset, we demonstrate the ability of this new measure to better discriminate different stages of Alzheimer's disease. Our findings suggest that this measure is useful in the study of the normal brain structure, and for quantifying the effects of disease on the brain structure.
Lars M Rimol, Violeta L Botellero, Knut J Bjuland, Gro CC Løhaugen, Stian Lydersen, Kari Anne I Evensen, Ann-Mari Brubakk, Live Eikenes, Marit S Indredavik, Marit Martinussen, Anastasia Yendiki, Asta K Håberg, and Jon Skranes. 2019. “Reduced white matter fractional anisotropy mediates cortical thickening in adults born preterm with very low birthweight.” Neuroimage, 188, Pp. 217-227.Abstract
Development of the cerebral cortex may be affected by aberrant white matter development. Preterm birth with very low birth weight (VLBW) has been associated with reduced fractional anisotropy of white matter and changes in cortical thickness and surface area. We use a new methodological approach to combine white and gray matter data and test the hypothesis that white matter injury is primary, and acts as a mediating factor for concomitant gray matter aberrations, in the developing VLBW brain. T1 and dMRI data were obtained from 47 young adults born preterm with VLBW and 73 term-born peers (mean age = 26). Cortical thickness was measured across the cortical mantle and compared between the groups, using the FreeSurfer software suite. White matter pathways were reconstructed with the TRACULA software and projected to their cortical end regions, where cortical thickness was averaged. In the VLBW group, cortical thickness was increased in anteromedial frontal, orbitofrontal, and occipital regions, and fractional anisotropy (FA) was reduced in frontal lobe pathways, indicating compromised white matter integrity. Statistical mediation analyses demonstrated that increased cortical thickness in the frontal regions was mediated by reduced FA in the corpus callosum forceps minor, consistent with the notion that white matter injury can disrupt frontal lobe cortical development. Combining statistical mediation analysis with pathway projection onto the cortical surface offers a powerful novel tool to investigate how cortical regions are differentially affected by white matter injury.
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.
Rachel R Romeo, Joshua Segaran, Julia A Leonard, Sydney T Robinson, Martin R West, Allyson P Mackey, Anastasia Yendiki, Meredith L Rowe, and John DE Gabrieli. 2018. “Language Exposure Relates to Structural Neural Connectivity in Childhood.” J Neurosci, 38, 36, Pp. 7870-7877.Abstract
Neuroscience research has elucidated broad relationships between socioeconomic status (SES) and young children's brain structure, but there is little mechanistic knowledge about specific environmental factors that are associated with specific variation in brain structure. One environmental factor, early language exposure, predicts children's linguistic and cognitive skills and later academic achievement, but how language exposure relates to neuroanatomy is unknown. By measuring the real-world language exposure of young children (ages 4-6 years, 27 male/13 female), we confirmed the preregistered hypothesis that greater adult-child conversational experience, independent of SES and the sheer amount of adult speech, is related to stronger, more coherent white matter connectivity in the left arcuate and superior longitudinal fasciculi on average, and specifically near their anterior termination at Broca's area in left inferior frontal cortex. Fractional anisotropy of significant tract subregions mediated the relationship between conversational turns and children's language skills and indicated a neuroanatomical mechanism underlying the SES "language gap." whole-brain analyses revealed that language exposure was not related to any other white matter tracts, indicating the specificity of this relationship. Results suggest that the development of dorsal language tracts is environmentally influenced, specifically by early, dialogic interaction. Furthermore, these findings raise the possibility that early intervention programs aiming to ameliorate disadvantages in development due to family SES may focus on increasing children's conversational exposure to capitalize on the early neural plasticity underlying cognitive development. Over the last decade, cognitive neuroscience has highlighted the detrimental impact of disadvantaged backgrounds on young children's brain structure. However, to intervene effectively, we must know which proximal aspects of the environmental aspects are most strongly related to neural development. The present study finds that young children's real-world language exposure, and specifically the amount of adult-child conversation, correlates with the strength of connectivity in the left hemisphere white matter pathway connecting two canonical language regions, independent of socioeconomic status and the sheer volume of adult speech. These findings suggest that early intervention programs aiming to close the achievement gap may focus on increasing children's conversational exposure to capitalize on the early neural plasticity underlying cognitive development.
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.

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