Measuring robustness of brain networks in autism spectrum disorder with Ricci curvature.

Abstract

Ollivier-Ricci curvature is a method for measuring the robustness of connections in a network. In this work, we use curvature to measure changes in robustness of brain networks in children with autism spectrum disorder (ASD). In an open label clinical trials, participants with ASD were administered a single infusion of autologous umbilical cord blood and, as part of their clinical outcome measures, were imaged with diffusion MRI before and after the infusion. By using Ricci curvature to measure changes in robustness, we quantified both local and global changes in the brain networks and their potential relationship with the infusion. Our results find changes in the curvature of the connections between regions associated with ASD that were not detected via traditional brain network analysis.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1038/s41598-020-67474-9

Publication Info

Simhal, Anish K, Kimberly LH Carpenter, Saad Nadeem, Joanne Kurtzberg, Allen Song, Allen Tannenbaum, Guillermo Sapiro, Geraldine Dawson, et al. (2020). Measuring robustness of brain networks in autism spectrum disorder with Ricci curvature. Scientific reports, 10(1). p. 10819. 10.1038/s41598-020-67474-9 Retrieved from https://hdl.handle.net/10161/24572.

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Scholars@Duke

Carpenter

Kimberly Carpenter

Assistant Professor in Psychiatry and Behavioral Sciences

Dr. Kimberly Carpenter is a clinical neuroscientist specializing in understanding complex brain-behavior relationships in young children with autism and associated disorders. Her program of research includes four interrelated research themes: (1) Understanding the impact of comorbid disorders on clinical and behavioral outcomes of young autistic children; (2) Identification of early risk factors for the development of psychiatric and neurodevelopmental disorders; (3) Identification of brain-based biomarkers for group stratification and treatment response tracking in young children; and (4) Improving methods for screening, early identification, and treatment monitoring in autism and associated disorders. She currently leads an innovative research program exploring the shared and unique impacts that co-occurring anxiety and ADHD have on brain and behavioral biomarkers in young autistic children. She was the first to demonstrate that sensory over-responsivity, a symptom that has been described as part of a number of disorders including autism, anxiety, and ADHD, is a specific and unidirectional risk factor for the development of anxiety disorders in young children. She was also the first to demonstrate that, when accounting for comorbidity among individual anxiety disorders, specific anxiety disorders are associated with phenotypically meaningful differences in brain connectivity using MRI. Dr. Carpenter has also collaborated with experts in early childhood mental health, computer science, and engineering to develop novel technologies that utilize multi-modal methods via computer vision and machine learning to develop, refine, and test novel screening tools for early identification and treatment monitoring in young children with autism and related disorders.

Kurtzberg

Joanne Kurtzberg

Jerome S. Harris Distinguished Professor of Pediatrics

Dr. Kurtzberg is an internationally renowned expert in pediatric hematology/oncology, pediatric blood and marrow transplantation, umbilical cord blood banking and transplantation, and novel applications of cord blood and birthing tissues in the emerging fields of cellular therapies and regenerative medicine.   Dr. Kurtzberg serves as the Director of the Marcus Center for Cellular Cures (MC3), Director of the Pediatric Transplant and Cellular Therapy Program, Director of the Carolinas Cord Blood Bank, and Co-Director of the Stem Cell Transplant Laboratory at Duke University.  The Carolinas Cord Blood Bank is an FDA licensed public cord blood bank distributing unrelated cord blood units for donors for hematopoietic stem cell transplantation (HSCT) through the CW Bill Young Cell Transplantation Program.  The Robertson GMP Cell Manufacturing Laboratory supports manufacturing of RETHYMIC (BLA, Enzyvant, 2021), allogeneic cord tissue derived and bone marrow derived mesenchymal stromal cells (MSCs), and DUOC, a microglial/macrophage cell derived from cord blood.

Dr. Kurtzberg’s research in MC3 focuses on translational studies from bench to bedside, seeking to develop transformative clinical therapies using cells, tissues, molecules, genes, and biomaterials to treat diseases and injuries that currently lack effective treatments. Recent areas of investigation in MC3 include clinical trials investigating the safety and efficacy of autologous and allogeneic cord blood in children with neonatal brain injury – hypoxic ischemic encephalopathy (HIE), cerebral palsy (CP), and autism. Clinical trials testing allogeneic cord blood are also being conducted in adults with acute ischemic stroke. Clinical trials optimizing manufacturing and testing the safety and efficacy of cord tissue MSCs in children with autism, CP and HIE and adults with COVID-lung disease are underway. DUOC, given intrathecally, is under study in children with leukodystrophies and adults with primary progressive multiple sclerosis.

In the past, Dr. Kurtzberg has developed novel chemotherapeutic drugs for acute leukemias, assays enumerating ALDH bright cells to predict cord blood unit potency, methods of cord blood expansion, potency assays for targeted cell and tissue based therapies. Dr. Kurtzberg currently holds several INDs for investigational clinical trials from the FDA.  She has also trained numerous medical students, residents, clinical and post-doctoral fellows over the course of her career.

Song

Allen W Song

Professor in Radiology

The research in our lab is concerned with advancing structural and functional MRI methodologies (e.g. fast and high-resolution imaging techniques) for human brain imaging. We also aim to improve our understanding of functional brain signals, including spatiotemporal characterizations of the blood oxygenation level dependent contrast and alternative contrast mechanisms that are more directly linked to the neuronal activities. Additional effort is invested in applying and validating the developed methods to study human functional neuroanatomy.


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