Topological network properties of resting-state functional connectivity patterns are associated with metal mixture exposure in adolescents

Azzurra Invernizzi; Elza Rechtman; Kristie Oluyemi; Stefano Renzetti; Paul Curtin; Elena Colicino; Claudia Ambrosi; Lorella Mascaro; Alessandra Patrono; Daniele Corbo; Giuseppa Cagna; Roberto Gasparotti; Abraham Reichenberg; Cheuk Y Tang; Donald R Smith; Donatella Placidi; Roberto G Lucchini; Robert O Wright; Megan K Horton

doi:10.3389/fnins.2023.1098441

Topological network properties of resting-state functional connectivity patterns are associated with metal mixture exposure in adolescents

Front Neurosci. 2023 Feb 6:17:1098441. doi: 10.3389/fnins.2023.1098441. eCollection 2023.

Authors

Azzurra Invernizzi¹, Elza Rechtman¹, Kristie Oluyemi^{1

2

3

4}, Stefano Renzetti⁵, Paul Curtin¹, Elena Colicino¹, Claudia Ambrosi⁶, Lorella Mascaro⁷, Alessandra Patrono⁵, Daniele Corbo⁵, Giuseppa Cagna⁵, Roberto Gasparotti⁵, Abraham Reichenberg⁸, Cheuk Y Tang⁹, Donald R Smith¹⁰, Donatella Placidi⁵, Roberto G Lucchini^{5

11}, Robert O Wright¹, Megan K Horton¹

Affiliations

¹ Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
² Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
³ The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
⁴ Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
⁵ Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy.
⁶ ASST Cremona Hospital, Cremona, Italy.
⁷ ASST Spedali Civili Hospital, Brescia, Italy.
⁸ Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
⁹ Department of Medical Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy.
¹⁰ Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, CA, United States.
¹¹ Department of Environmental Health Sciences, Robert Stempel School of Public Health, Florida International University, Miami, FL, United States.

Abstract

Introduction: Adolescent exposure to neurotoxic metals adversely impacts cognitive, motor, and behavioral development. Few studies have addressed the underlying brain mechanisms of these metal-associated developmental outcomes. Furthermore, metal exposure occurs as a mixture, yet previous studies most often consider impacts of each metal individually. In this cross-sectional study, we investigated the relationship between exposure to neurotoxic metals and topological brain metrics in adolescents.

Methods: In 193 participants (53% females, ages: 15-25 years) enrolled in the Public Health Impact of Metals Exposure (PHIME) study, we measured concentrations of four metals (manganese, lead, copper, and chromium) in multiple biological media (blood, urine, hair, and saliva) and acquired resting-state functional magnetic resonance imaging scans. Using graph theory metrics, we computed global and local efficiency (global:GE; local:LE) in 111 brain areas (Harvard Oxford Atlas). We used weighted quantile sum (WQS) regression models to examine association between metal mixtures and each graph metric (GE or LE), adjusted for sex and age.

Results: We observed significant negative associations between the metal mixture and GE and LE [βGE = -0.076, 95% CI (-0.122, -0.031); βLE= -0.051, 95% CI (-0.095, -0.006)]. Lead and chromium measured in blood contributed most to this association for GE, while chromium measured in hair contributed the most for LE.

Discussion: Our results suggest that exposure to this metal mixture during adolescence reduces the efficiency of integrating information in brain networks at both local and global levels, informing potential neural mechanisms underlying the developmental toxicity of metals. Results further suggest these associations are due to combined joint effects to different metals, rather than to a single metal.

Keywords: exposure; global and local efficiency; graph theory; neurotoxic metals; resting state–fMRI; topological network properties.

Abstract

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