News and Updates

Stay updated with the latest news, research, and public talks from the Psychiatry Neuroimaging Laboratory.

Recent Publications

Below is a list of the most recent publications from the PNL. For a complete list of any author’s publications, please use the PubMed or Google Scholar link on the Lab Members profile, which you can access by clicking on the lab members photo on the Team page.

Single- versus two-test criteria for cognitive impairment: associations with CSF and imaging markers in former American football players

2025 Jan 20:1-25.
doi: 10.1080/13854046.2025.2451828. Online ahead of print.

Monica T Ly 1 2Caroline Altaras 1 2Yorghos Tripodis 1 2 3Charles H Adler 4Laura J Balcer 5Charles Bernick 6 7Henrik Zetterberg 8 9 10 11 12 13Kaj Blennow 12 13Elaine R Peskind 14 15Sarah J Banks 16 17William B Barr 18Jennifer V Wethe 19Steve Lenio 1 2Mark W Bondi 16 20Lisa M Delano-Wood 16 20Robert C Cantu 1 2Michael J Coleman 21David W Dodick 4 22Jesse Mez 1 2 23Daniel H Daneshvar 24 25 26Joseph N Palmisano 27Brett Martin 27Alexander P Lin 21 28Inga K Koerte 21 29Sylvain Bouix 21 30Jeffrey L Cummings 31Eric M Reiman 32 33 34 35 36Martha E Shenton 21 37Robert A Stern 1 2 38 39Michael L Alosco 1 2

 

Affiliations

  • 1Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
  • 2Boston University Alzheimer’s Disease Research Center and Chronic Traumatic Encephalopathy Center, Boston, MA, USA.
  • 3Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
  • 4Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale, AZ, USA.
  • 5Departments of Neurology, Population Health and Ophthalmology, NYU Grossman School of Medicine, New York, NY, USA.
  • 6Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA.
  • 7Department of Neurology, University of Washington, Seattle, WA, USA.
  • 8Department of Neurodegenerative Disease, UCL Institute of Neurology, London, United Kingdom.
  • 9UK Dementia Research Institute at UCL, UCL Institute of Neurology, University College London, London, United Kingdom.
  • 10Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China.
  • 11Wisconsin Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
  • 12Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
  • 13Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
  • 14VA Northwest Mental Illness Research, Education, and Clinical Center, Seattle, WA, USA.
  • 15Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, USA.
  • 16Department of Psychiatry, University of California San Diego Health, La Jolla, CA, USA.
  • 17Department of Neurosciences, University of California, San Diego, CA, USA.
  • 18Department of Neurology, NYU Grossman School of Medicine, New York, NY, USA.
  • 19Department of Psychiatry and Psychology, Mayo Clinic School of Medicine, Mayo Clinic Arizona, Scottsdale, AZ, USA.
  • 20VA San Diego Healthcare System, San Diego, CA, USA.
  • 21Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s Hospital, Boston, MA, USA.
  • 22Atria Academy of Science and Medicine, New York, NY, USA.
  • 23Framingham Heart Study, Framingham, MA, USA.
  • 24Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA, USA.
  • 25Department of Physical Medicine and Rehabilitation, Massachusetts General Hospital, Boston, MA, USA.
  • 26Department of Physical Medicine and Rehabilitation, Mass General Brigham-Spaulding Rehabilitation, Charlestown, MA, USA.
  • 27Biostatistics and Epidemiology Data Analytics Center (BEDAC), Boston University School of Public Health, Boston, MA, USA.
  • 28Center for Clinical Spectroscopy, Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA.
  • 29cBRAIN, Department of Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy, Ludwigs-Maximilians-Universität, Munich, Germany.
  • 30Department of Software Engineering and Information Technology, École de technologie supérieure, Université du Québec, Montréal, QC, Canada.
  • 31Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas, Las Vegas, NV, USA.
  • 32Banner Alzheimer’s Institute, Phoenix, AZ, USA.
  • 33Evelyn F. McKnight Brain Institute, University of Arizona, Phoenix, AZ, USA.
  • 34School of Life Sciences, Arizona State University, Phoenix, AZ, USA.
  • 35Translational Genomics Research Institute, Phoenix, AZ, USA.
  • 36Arizona Alzheimer’s Consortium, Phoenix, AZ, USA.
  • 37Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA.
  • 38Department of Neurosurgery, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
  • 39Department of Anatomy & Neurobiology and Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.

Abstract

Objective: Cognitive impairment is a core feature of traumatic encephalopathy syndrome (TES), the putative clinical syndrome of chronic traumatic encephalopathy-a neuropathological disease associated with repetitive head impacts (RHI). Careful operationalization of cognitive impairment is essential to improving the diagnostic specificity and accuracy of TES criteria. We compared single- versus two-test criteria for cognitive impairment in their associations with CSF and imaging biomarkers in male former American football players. Method: 169 participants from the DIAGNOSE CTE Research Project completed neuropsychological tests of memory and executive functioning. Cognitive impairment was identified by single-test criteria (z≤-1.5 on one test) and two-test criteria (z<-1 on two tests within a domain). ANCOVAs adjusting for age, race, education, body mass index, word-reading score, and APOE ε4 status assessed whether single- or two-test criteria predicted CSF markers (Aβ1-42, p-tau181, p-tau181/Aβ1-42, total tau, neurofilament light [NfL], glial fibrillary acidic protein [GFAP]) and MRI markers (hippocampal volume, cortical thickness, white matter hyperintensities). Results: Ninety-nine participants met single-test criteria for cognitive impairment. Sixty-six met two-test criteria. Participants who met two-test criteria had greater exposure to RHI than those who did not (p=.04). Two-test criteria were -associated with higher CSF p-tau181/Aβ1-42 (q=.02) and CSF NfL (q=.02). The association between two-test criteria and CSF NfL remained after excluding amyloid-positive participants (q=.04). Single-test criteria were not associated with any biomarkers (q‘s>.05). Conclusions: Two-test but not single-test criteria for cognitive impairment were associated with markers of neurodegeneration. Future clinical research in TES may benefit from applying two-test criteria to operationalize cognitive impairment.

Keywords: axonal injury; cognitive impairment; neurodegeneration; repeated head trauma; repetitive head impact; traumatic encephalopathy syndrome.

Exploring the link between inflammation and brain function after metabolic-bariatric surgery: A year-long fMRI study

2025 Jan 16.
 doi: 10.1111/dom.16181. Online ahead of print.

Magdalena Szwed 1Adrian Falkowski 2 3Johanna Seitz-Holland 4 5Alina Borkowska 1Maciej Michalik 3Marek Kubicki 4 6 7Krzysztof Szwed 1 3 8

Affiliations

  • 1Department of Clinical Neuropsychology, Faculty of Health Sciences, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Toruń, Poland.
  • 2Faculty of Mathematics and Computer Science, Nicolaus Copernicus University, Toruń, Poland.
  • 3Clinic of General and Minimally Invasive Surgery, Jan Biziel University Hospital No. 2 in Bydgoszcz, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland.
  • 4Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • 5Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
  • 6Department of Psychiatry, Center for Morphometric Analysis, A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • 7Laboratory of Mathematics in Imaging, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • 8Faculty of Medicine, Bydgoszcz University of Science and Technology, Bydgoszcz, Poland.

Abstract

Background: Metabolic-bariatric surgery (MBS) transcends weight loss and offers wide-ranging health benefits, including positive effects on brain function. However, the mechanisms behind these effects remain unclear, particularly in the context of significant postoperative changes in the inflammatory profile characteristic of MBS. Understanding how inflammation influences postoperative brain function can enhance our decision-making on patient eligibility for MBS and create new opportunities to improve the outcomes of this popular treatment.

Objective: To identify brain regions where spontaneous neural activity and functional connectivity are linked with the evolving inflammatory profile following MBS.

Methods: We investigated the relationship between the perioperative ratio of interleukin (IL)-6 to IL-10 and both the amplitude of low-frequency fluctuation (ALFF) and functional connectivity across 375 brain regions. We examined 36 patients at three time points: 1 week before, and 3 and 12 months after laparoscopic sleeve gastrectomy.

Results: Initially, the IL-6/IL-10 ratio increased during the early postoperative period but then decreased to levels lower than the preoperative values 1 year after surgery. We observed that ALFF in four subcortical structures decreased with a rising IL-6/IL-10 ratio and increased with a declining ratio. Conversely, 16 cortical regions displayed the opposite trend. Additionally, functional connectivity between the left insula and bilateral medial prefrontal cortex increased with a rising IL-6/IL-10 ratio and decreased with a declining ratio.

Conclusions: Our study is the first to identify brain regions significantly linked to inflammation after MBS. Importantly, many of the discovered areas were previously shown to be involved in the pathogenesis of obesity or are targets of contemporary medical treatments. Consequently, our findings offer valuable insights for future obesity research, especially in the context of potential therapeutic opportunities.

Keywords: bariatric surgery; clinical physiology; obesity therapy; observational study

DDEvENet: Evidence-based ensemble learning for uncertainty-aware brain parcellation using diffusion MRIre

2025 Jan 4:120:102489.
doi: 10.1016/j.compmedimag.2024.102489. Online ahead of print

Chenjun Li 1Dian Yang 1Shun Yao 2Shuyue Wang 3Ye Wu 4Le Zhang 1Qiannuo Li 5Kang Ik Kevin Cho 6Johanna Seitz-Holland 6Lipeng Ning 6Jon Haitz Legarreta 6Yogesh Rathi 6Carl-Fredrik Westin 6Lauren J O’Donnell 6Nir A Sochen 7Ofer Pasternak 6Fan Zhang 8

PMID: 39787735

DOI: 10.1016/j.compmedimag.2024.102489

Affiliations

  • 1University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
  • 2The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
  • 3The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • 4Nanjing University of Science and Technology, Nanjing, Jiangsu, China.
  • 5East China University of Science and Technology, Shanghai, China.
  • 6Harvard Medical School, Boston, MA, USA.
  • 7School of Mathematical Sciences, University of Tel Aviv, Tel Aviv, Israel.
  • 8University of Electronic Science and Technology of China, Chengdu, Sichuan, China. Electronic address: fan.zhang@uestc.edu.cn.

Abstract

In this study, we developed an Evidential Ensemble Neural Network based on Deep learning and Diffusion MRI, namely DDEvENet, for anatomical brain parcellation. The key innovation of DDEvENet is the design of an evidential deep learning framework to quantify predictive uncertainty at each voxel during a single inference. To do so, we design an evidence-based ensemble learning framework for uncertainty-aware parcellation to leverage the multiple dMRI parameters derived from diffusion MRI. Using DDEvENet, we obtained accurate parcellation and uncertainty estimates across different datasets from healthy and clinical populations and with different imaging acquisitions. The overall network includes five parallel subnetworks, where each is dedicated to learning the FreeSurfer parcellation for a certain diffusion MRI parameter. An evidence-based ensemble methodology is then proposed to fuse the individual outputs. We perform experimental evaluations on large-scale datasets from multiple imaging sources, including high-quality diffusion MRI data from healthy adults and clinically diffusion MRI data from participants with various brain diseases (schizophrenia, bipolar disorder, attention-deficit/hyperactivity disorder, Parkinson’s disease, cerebral small vessel disease, and neurosurgical patients with brain tumors). Compared to several state-of-the-art methods, our experimental results demonstrate highly improved parcellation accuracy across the multiple testing datasets despite the differences in dMRI acquisition protocols and health conditions. Furthermore, thanks to the uncertainty estimation, our DDEvENet approach demonstrates a good ability to detect abnormal brain regions in patients with lesions that are consistent with expert-drawn results, enhancing the interpretability and reliability of the segmentation results.

Keywords: Brain parcellation; Deep learning; Diffusion MRI; Uncertainty estimation.

Diffusion tensor imaging with free-water correction reveals distinctions between severe and attenuated subtypes in Mucopolysaccharidosis type I

2025 Jan;48(1):e12830.
doi: 10.1002/jimd.12830.

 

Alena Svatkova 1 2 3Ofer Pasternak 4Julie B Eisengart 1Kyle D Rudser 5Petr Bednařík 2 3Bryon A Mueller 6Kathleen A Delaney 1Elsa G Shapiro 1Chester B Whitley 1Igor Nestrašil 1

Affiliations

  • 1Department of Pediatrics, Medical School, University of Minnesota, Minneapolis, Minnesota, USA.
  • 2Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Amager and Hvidovre, Copenhagen, Denmark.
  • 3Department of Radiology, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Amager and Hvidovre, Copenhagen, Denmark.
  • 4Departments of Psychiatry and Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • 5Division of Biostatistics and Health Data Science, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA.
  • 6Department of Psychiatry & Behavioral Sciences, University of Minnesota, Minneapolis, Minnesota, USA.

Abstract

Mucopolysaccharidosis type I (MPS I) is an inherited lysosomal storage disorder leading to deleterious brain effects. While animal models suggested that MPS I severely affects white matter (WM), whole-brain diffusion tensor imaging (DTI) analysis was not performed due to MPS-related morphological abnormalities. 3T DTI data from 28 severe (MPS IH, treated with hematopoietic stem cell transplantation-HSCT), 16 attenuated MPS I patients (MPS IA) enrolled under the study protocol NCT01870375, and 27 healthy controls (HC) were analyzed using the free-water correction (FWC) method to resolve macrostructural partial volume effects and unravel differences in DTI metrics accounting for microstructural abnormalities. FWC analysis in MPS IH compared to HC revealed higher free-water fraction (FWF) in all WM regions with increased radial (RD) and mean diffusivity (MD). Higher RD, MD, and FWF in cingulate and FWF in temporal WM were observed in MPS IA relative to HC. FWF and RD in the corpus callosum (CC) were higher in MPS IH than in MPS IA. Reaction time was correlated with fractional anisotropy (FA) in frontal and parietal WM in MPS IH. FA in temporal and central WM correlated with d-prime in MPS IA. The HSCT age was related to FA in parietal WM and FWF in frontal WM in MPS IH. FWC delineated subtype-specific WM microstructural abnormalities linked to myelination that were more extensive in MPS IH than IA, with CC findings being a key differentiator between subtypes. Earlier age at HSCT was related to preserved WM microstructure in the brain of MPS IH patients. Free water-corrected DTI distinguishes severe and attenuated MPS I patients and reveals a relationship between attention, age at HSCT, and white matter microstructure.

Keywords: Hurler syndrome; Mucopolysaccharidosis type I; attenuated MPS; diffusion tensor imaging (DTI); free‐water; perivascular Virchow Robin spaces.

Cellular and extracellular white matter alterations after childhood trauma experience in individuals with schizophrenia

2025 Jan 6:1-10. 
doi: 10.1017/S0033291724003064. Online ahead of print.

Maria R Dauvermann 1 2Laura Costello 1Giulia Tronchin 1Emma Corley 1Laurena Holleran 1David Mothersill 1 3 4Karolina I Rokita 1Ruán Kane 1Brian Hallahan 1Colm McDonald 1Ofer Pasternak 5 6 7Gary Donohoe 1Dara M Cannon 1

 

Affiliations

  • 1Center for Neuroimaging, Cognition and Genomics (NICOG), Clinical Neuroimaging Laboratory, Galway Neuroscience Centre, University of Galway, Galway, Ireland.
  • 2Institute for Mental Health, School of Psychology, University of Birmingham, Birmingham, UK.
  • 3Department of Psychology, School of Business, National College of Ireland, Dublin, Ireland.
  • 4Department of Psychiatry, Trinity College Dublin, St. James’s Hospital, Dublin, Ireland.
  • 5Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA.
  • 6Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA.
  • 7Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Abstract

Background: Childhood trauma (CT) is related to altered fractional anisotropy (FA) in individuals with schizophrenia (SZ). However, it remains unclear whether CT may influence specific cellular or extracellular compartments of FA in SZ with CT experience. We extended our previous study on FA in SZ (Costello et al., 2023) and examined the impact of CT on hypothesized lower free water-corrected FA (FAT) and higher extracellular free water (FW).

Method: Thirty-seven SZ and 129 healthy controls (HC) were grouped into the ‘none/low’ or ‘high’ CT group. All participants underwent diffusion-weighted magnetic resonance imaging. We performed tract-based spatial statistics to study the main effects of diagnostic group and CT, and the interaction between CT and diagnostic group across FAT and FW.

Results: SZ displayed lower FAT within the corpus callosum and corona radiata compared to HC (p < 0.05, Threshold-Free Cluster Enhancement (TFCE)). Independent of diagnosis, we observed lower FAT (p < 0.05, TFCE) and higher FW (p < 0.05, TFCE) in both SZ and HC with high CT levels compared to SZ and HC with none or low CT levels. Furthermore, we did not identify an interaction between CT and diagnostic group (p > 0.05, TFCE).

Conclusions: These novel findings suggest that the impact of CT on lower FAT may reflect cellular rather than extracellular alterations in established schizophrenia. This highlights the impact of CT on white matter microstructure, regardless of diagnostic status.

Keywords: childhood Trauma; diffusion-weighted magnetic resonance imaging; fractional anisotropy; free water; schizophrenia; tract-based spatial statistic.

Learning to Match 2D Keypoints Across Preoperative MR and Intraoperative Ultrasound

2025:15186:78-87. 
doi: 10.1007/978-3-031-73647-6_8. Epub 2024 Oct 5.

Hassan Rasheed 1 2 3Reuben Dorent 1Maximilian Fehrentz 1 2Daniil Morozov 1 2Tina Kapur 1William M Wells 3rd 1 4Alexandra Golby 1Sarah Frisken 1Julia A Schnabel 2 3Nazim Haouchine 1

    • PMID: 39736888

Affiliations

  • 1Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, USA.
  • 2Technical University of Munich, Munich, Germany.
  • 3Helmholtz Center Munich, Munich, Germany.
  • 4Massachusetts Institute of Technology, Cambridge, MA, USA.

Abstract

We propose in this paper a texture-invariant 2D keypoints descriptor specifically designed for matching preoperative Magnetic Resonance (MR) images with intraoperative Ultrasound (US) images. We introduce a matching-by-synthesis strategy, where intraoperative US images are synthesized from MR images accounting for multiple MR modalities and intraoperative US variability. We build our training set by enforcing keypoints localization over all images then train a patient-specific descriptor network that learns texture-invariant discriminant features in a supervised contrastive manner, leading to robust keypoints descriptors. Our experiments on real cases with ground truth show the effectiveness of the proposed approach, outperforming the state-of-the-art methods and achieving 80.35% matching precision on average.

Combined T1-weighted MRI and diffusion MRI tractography of paraventricular, locus coeruleus, and dorsal vagal complex connectivity in brainstem-hypothalamic nuclei

2024 Nov 22;11(4):e99010036. doi: 10.14440/jbm.2024.0043. eCollection 2024.

Nikos Makris 1 2 3 4 5 6 7Poliana Hartung Toppa 6Richard J Rushmore 1 5 6Kayley Haggerty 6George Papadimitriou 6Stuart Tobet 7 8Yogesh Rathi 1 6Marek Kubicki 1 6 7 9Edward Yeterian 6 10Agustin Castañeyra-Perdomo 3Jill M Goldstein 2 7 11

PMID: 39839090
PMCID: PMC11744066
DOI: 10.14440/jbm.2024.0043

Affiliations

  • 1Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States.
  • 2Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, United States.
  • 3Anatomy and Physiology Area, Department of Basic Medical Sciences, Faculty of Health Sciences, University of La Laguna, San Cristobal de La Laguna 38000, Tenerife, Spain.
  • 4Department of Cognitive, Social and Organizational Psychology, Faculty of Health Sciences, University of La Laguna, University Institute of Neuroscience, San Cristobal de La Laguna 38000, Tenerife, Spain.
  • 5Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, Massachusetts 02118, United States.
  • 6Center for Morphometric Analysis, Department of Psychiatry and Neurology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129 United States.
  • 7Innovation Center on Sex Differences in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, United States.
  • 8Department of Biomedical Sciences, School of Biomedical Engineering, Colorado State University, Fort Collins, Colorado 80523, United States.
  • 9Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States.
  • 10Department of Psychology, Colby College, Waterville, Maine 04901 United States.
  • 11Department of Medicine, Harvard Medical School, Boston, Massachusetts 02114, United States.

Abstract

Background: Current multimodal neuroimaging plays a critical role in studying clinical conditions such as cardiovascular disease, major depression, and other disorders related to chronic stress. These conditions involve the brainstem-hypothalamic network, specifically the locus coeruleus (LC), dorsal vagal complex (DVC), and paraventricular nucleus (PVN) of the hypothalamus, collectively referred to as the “DVC-LC-PVN circuitry.” This circuitry is strongly associated with the norepinephrine (NE) and epinephrine (E) neurotransmitter systems, which are implicated in the regulation of key autonomic functions, such as cardiovascular and respiratory control, stress response, and cognitive and emotional behaviors.

Keywords: Diffusion magnetic resonance imaging; Dorsal vagal complex; Locus coeruleus; Major depressive disorder; Paraventricular nucleus of the hypothalamus.

A generative model of the connectome with dynamic axon growth

2024 Dec 10;8(4):1192-1211.doi: 10.1162/netn_a_00397. eCollection 2024.

Yuanzhe Liu 1 2Caio Seguin 2 3Richard F Betzel 3Daniel Han 4Danyal Akarca 5 6Maria A Di Biase 2 7Andrew Zalesky 1 2

      • PMID: 39735503

     

    Affiliations

    • 1Department of Biomedical Engineering, Faculty of Engineering and Information Technology, The University of Melbourne, Melbourne, VIC, Australia.
    • 2Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Melbourne, VIC, Australia.
    • 3Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA.
    • 4School of Mathematics and Statistics, University of New South Wales, Sydney, NSW, Australia.
    • 5MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, UK.
    • 6Department of Electrical and Electronic Engineering, Imperial College London, London, UK.
    • 7Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA.

    Abstract

    Connectome generative models, otherwise known as generative network models, provide insight into the wiring principles underpinning brain network organization. While these models can approximate numerous statistical properties of empirical networks, they typically fail to explicitly characterize an important contributor to brain organization-axonal growth. Emulating the chemoaffinity-guided axonal growth, we provide a novel generative model in which axons dynamically steer the direction of propagation based on distance-dependent chemoattractive forces acting on their growth cones. This simple dynamic growth mechanism, despite being solely geometry-dependent, is shown to generate axonal fiber bundles with brain-like geometry and features of complex network architecture consistent with the human brain, including lognormally distributed connectivity weights, scale-free nodal degrees, small-worldness, and modularity. We demonstrate that our model parameters can be fitted to individual connectomes, enabling connectome dimensionality reduction and comparison of parameters between groups. Our work offers an opportunity to bridge studies of axon guidance and connectome development, providing new avenues for understanding neural development from a computational perspective.

    Keywords: Axon simulation; Connectome; Generative model; Network neuroscience.

    Plain language summary

    Generative models of the human connectome provide insight into principles driving brain network development. However, current models do not capture axonal outgrowth, which is crucial to the formation of neural circuits. We develop a novel generative connectome model featuring dynamic axonal outgrowth, revealing the contribution of microscopic axonal guidance to the network topology and axonal geometry of macroscopic connectomes. Simple axonal outgrowth rules representing continuous chemoaffinity gradients are shown to generate complex, brain-like topologies and realistic axonal fascicle architectures. Our model is sufficiently sensitive to capture subtle interindividual differences in axonal outgrowth between healthy adults. Our results are significant because they reveal core principles that may give rise to both complex brain networks and brain-like axonal bundles, unifying neurogenesis across scales.

    Olfactory function is reduced in a subset of former elite American football players with traumatic encephalopathy syndrome

    2024 Jan 1:49:bjae043.
    doi: 10.1093/chemse/bjae043.

    Ben J Braunecker 1Jenna R Groh 2Charles H Adler 1Michael L Alosco 2David W Dodick 1Yorghos Tripodis 3Laura J Balcer 4Charles Bernick 5Sarah J Banks 6William B Barr 7Jennifer V Wethe 8Joseph N Palmisano 9Brett Martin 9Kaitlin Hartlage 9Robert C Cantu 2Yonas E Geda 10Douglas I Katz 2Jesse Mez 2 11Jeffery L Cummings 12Martha E Shenton 13 14Eric M Reiman 15Robert A Stern 2 16

      • PMID: 39657828

     

    Affiliations

    • 1Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale, AZ, United States.
    • 2Boston University Alzheimer’s Disease Research Center, Boston University CTE Center, Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, United States.
    • 3Department of Biostatistics, Boston University School of Public Health, Boston, MA, United States.
    • 4Department of Neurology, Population Health and Ophthalmology, NYU Grossman School of Medicine, New York, NY, United States.
    • 5Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, United States.
    • 6Departments of Neuroscience and Psychiatry, University of California, San Diego, CA, United States.
    • 7Department of Neurology, NYU Grossman School of Medicine, New York, NY, United States.
    • 8Department of Psychiatry and Psychology, Mayo Clinic School of Medicine, Mayo Clinic Arizona, Scottsdale, AZ, United States.
    • 9Biostatistics and Epidemiology Data Analytics Center (BEDAC), Boston University School of Public Health, Boston, MA, United States.
    • 10Department of Neurology and the Franke Neuroscience Education Center, Barrow Neurological Institute, Phoenix, AZ, United States.
    • 11Framingham Heart Study, Framingham, MA, United States.
    • 12Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas, Las Vegas, NV, United States.
    • 13Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Department of Radiology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, United States.
    • 14Department of Psychiatry, Massachusetts General Hospital, Boston, MA, United States.
    • 15Banner Alzheimer’s Institute, University of Arizona, Arizona State University, Translational Genomics Research Institute, and Arizona Alzheimer’s Consortium, Phoenix, AZ, United States.
    • 16Department of Anatomy & Neurobiology, Boston University Chobanian & Avedisian, Boston, MA, United States.

    Abstract

    Former American football players are at risk for developing traumatic encephalopathy syndrome (TES), the clinical disorder associated with neuropathologically diagnosed chronic traumatic encephalopathy (CTE). The objective of this study was to determine whether hyposmia is present in traumatic encephalopathy syndrome. The study included 119 former professional American football players, 60 former college football players, and 58 same-age asymptomatic unexposed men from the DIAGNOSE CTE Research Project. All subjects included in the analysis had completed the Brief Smell Identification Test (B-SIT). Traumatic encephalopathy syndrome and the level of CTE certainty were diagnosed using the 2021 NINDS consensus diagnostic criteria. TES is categorized antemortem by provisional levels of increasing CTE certainty: Suggestive, Possible, and Probable. Former players who had traumatic encephalopathy syndrome and Probable CTE had lower B-SIT scores than those with TES and Suggestive CTE. Hyposmia was more likely in the former players with TES who were either CTE Possible or Probable than in those who did not have TES or had TES but were less likely to have CTE, or CTE Suggestive. There was no difference in B-SIT scores between all former players versus unexposed men nor overall between the football players with and without TES. We conclude that lower B-SIT scores may be a clinical biomarker for underlying CTE in former American football players.

    Keywords: chronic traumatic encephalopathy; hyposmia; traumatic encephalopathy syndrome.

    A short scale to measure health-related quality of life after traumatic brain injury in children and adolescents (QOLIBRI-OS-KID/ADO): psychometric properties and German reference values

    2024 Nov;33(11):3039-3056.
    doi: 10.1007/s11136-024-03764-3. Epub 2024 Aug 31.

    Marina Zeldovich 1 2Leonie Krol 3Inga K Koerte 4 5Katrin Cunitz 6 7Matthias Kieslich 8Marlene Henrich 8Knut Brockmann 9Anna Buchheim 6Michael Lendt 10Christian Auer 11 12Axel Neu 13Joenna Driemeyer 14Ulrike Wartemann 15Claudius Thomé 16Daniel Pinggera 16Steffen Berweck 17Michaela V Bonfert 18Joachim Suss 19Holger Muehlan 20Nicole von Steinbuechel 6

      • PMID: 39215856

    Affiliations

    • 1Institute of Psychology, Faculty of Psychology and Sport Science, University of Innsbruck, Innsbruck, Austria. marina.zeldovich@uibk.ac.at.
    • 2Faculty of Psychotherapy Science, Sigmund Freud University, Vienna, Austria. marina.zeldovich@uibk.ac.at.
    • 3Department of Psychology, Clinical Psychology and Psychotherapy, Philipps University of Marburg, Marburg, Germany.
    • 4cBRAIN / Department of Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy, LMU University Hospital, Ludwig-Maximilian University, Munich, Germany.
    • 5Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Mass General Brigham, Boston, USA.
    • 6Institute of Psychology, Faculty of Psychology and Sport Science, University of Innsbruck, Innsbruck, Austria.
    • 7Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, Goettingen, Germany.
    • 8Department of Paediatric Neurology, Hospital of Goethe University, Frankfurt, Germany.
    • 9Interdisciplinary Pediatric Center for Children with Developmental Disabilities and Severe Chronic Disorders, Department of Pediatrics and Adolescent Medicine, University Medical Center, Goettingen, Germany.
    • 10Neuropediatrics, St. Mauritius Therapeutic Clinic, Meerbusch, Germany.
    • 11Department of Neurosurgery, Kepler University Hospital GmbH, Johannes Kepler University Linz, Linz, Austria.
    • 12Clinical Research Institute für Neurosciences, Faculty of Medicine, Johannes Kepler University Linz, Linz, Austria.
    • 13Department of Neurology and Neuropediatry, VAMED Klinik Geesthacht GmbH, Geesthacht, Germany.
    • 14Department of Pediatrics, University of Hamburg-Eppendorf, Hamburg, Germany.
    • 15Department of Neuropediatrics, VAMED Klinik Hohenstücken GmbH, Brandenburg an der Havel, Germany.
    • 16Department of Neurosurgery, Medical University lnnsbruck, Innsbruck, Austria.
    • 17Specialist Center for Paediatric Neurology, Neurorehabilitation and Epileptology, Schoen Klinik, Vogtareuth, Germany.
    • 18Department of Pediatric Neurology and Developmental Medicine and LMU Center for Development and Children with Medical Complexity, Dr. Von Hauner Children’s Hospital, LMU University Hospital, Munich, Germany.
    • 19Department of Pediatric Surgery, Wilhelmstift Catholic Children’s Hospital, Hamburg, Germany.
    • 20Department of Health and Prevention, University of Greifswald, Greifswald, Germany.

    Abstract

    Purpose: The impact of pediatric traumatic brain injury (pTBI) on health-related quality of life (HRQoL) in children and adolescents remains understudied. Short scales have some advantages in terms of economy and administration over longer scales, especially in younger children. The aim of the present study is to psychometrically evaluate the six-item German version of the QOLIBRI-OS-KID/ADO scale for children and adolescents. In addition, reference values from a general German pediatric population are obtained to assist clinicians and researchers in the interpretation of HRQoL after pTBI.

    Methods: A total of 297 individuals after TBI and 1997 from a general population sample completed the questionnaire. Reliability, validity, and comparability of the assessed construct were examined.

    Results: The questionnaire showed satisfactory reliability (α = 0.75 and ω = 0.81 and α = 0.85 and ω = 0.86 for the TBI and general population samples, respectively). The QOLIBRI-OS-KID/ADO was highly correlated with its long version (R2 = 67%) and showed an overlap with disease-specific HRQoL (R2 = 55%) in the TBI sample. The one-dimensional factorial structure could be replicated and tested for measurement invariance between samples, indicating a comparable HRQoL construct assessment. Therefore, reference values and cut-offs indicating clinically relevant impairment could be provided using percentiles stratified by factors significantly associated with the total score in the regression analyses (i.e., age group and gender).

    Conclusion: In combination with the cut-offs, the QOLIBRI-OS-KID/ADO provides a cost-effective screening tool, complemented by interpretation guidelines, which may help to draw clinical conclusions and indications such as further administration of a longer version of the instrument to gain more detailed insight into impaired HRQoL domains or omission of further steps in the absence of an indication.

    Keywords: Health-related quality of life (HRQoL); Patient-reported outcome measure (PROM); Pediatric traumatic brain injury (pTBI); Reference values.

    Tractography-Based Automated Identification of Retinogeniculate Visual Pathway With Novel Microstructure-Informed Supervised Contrastive Learning

    2024 Dec 1;45(17):e70071.
    doi: 10.1002/hbm.70071.

    Sipei Li 1 2Wei Zhang 1Shun Yao 3 4Jianzhong He 5Jingjing Gao 1Tengfei Xue 6Guoqiang Xie 7Yuqian Chen 4Erickson F Torio 4Yuanjing Feng 4Dhiego C A Bastos 4Yogesh Rathi 4Nikos Makris 4Ron Kikinis 4Wenya Linda Bi 4Alexandra J Golby 4Lauren J O’Donnell 4Fan Zhang 1 4

    Affiliations

    • 1School of Information and Communication Engineering, University of Electronic Science and Technology of China, Chengdu, China.
    • 2Department of Bioengineering, University of Pennsylvania, Pennsylvania, USA.
    • 3The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
    • 4Brigham and Women’s Hospital, Harvard Medical School, Massachusetts, USA.
    • 5College of Information Engineering, Zhejiang University of Technology, Hangzhou, China.
    • 6School of Computer Science, University of Sydney, New South Wales, Australia.
    • 7Department of Neurosurgery, Nuclear Industry 215 Hospital of Shaanxi Province, Shaanxi, China.

    Abstract

    The retinogeniculate visual pathway (RGVP) is responsible for carrying visual information from the retina to the lateral geniculate nucleus. Identification and visualization of the RGVP are important in studying the anatomy of the visual system and can inform the treatment of related brain diseases. Diffusion MRI (dMRI) tractography is an advanced imaging method that uniquely enables in vivo mapping of the 3D trajectory of the RGVP. Currently, identification of the RGVP from tractography data relies on expert (manual) selection of tractography streamlines, which is time-consuming, has high clinical and expert labor costs, and is affected by inter-observer variability. In this paper, we present a novel deep learning framework, DeepRGVP, to enable fast and accurate identification of the RGVP from dMRI tractography data. We design a novel microstructure-informed supervised contrastive learning method that leverages both streamline label and tissue microstructure information to determine positive and negative pairs. We propose a new streamline-level data augmentation method to address highly imbalanced training data, where the number of RGVP streamlines is much lower than that of non-RGVP streamlines. In the experiments, we perform comparisons with several state-of-the-art deep learning methods that were designed for tractography parcellation. Furthermore, to assess the generalizability of the proposed RGVP method, we apply our method to dMRI tractography data from neurosurgical patients with pituitary tumors. In comparison with the state-of-the-art methods, we show superior RGVP identification results using DeepRGVP with significantly higher accuracy and F1 scores. In the patient data experiment, we show DeepRGVP can successfully identify RGVPs despite the effect of lesions affecting the RGVPs. Overall, our study shows the high potential of using deep learning to automatically identify the RGVP.

    Keywords: cranial nerves; diffusion MRI; retinogeniculate visual pathway; tractography.