Lead exposure is associated with functional and microstructural changes in the healthy human brain

Hikaru Takeuchi,Takayuki Nozawa,Tsuyoshi Araki,Yasuyuki Taki,Carlos Makoto Miyauchi,Susum Yokota,Kunio Iizuka,Atsushi Sekiguchi,Seishu Nakagawa,Rui Nouchi,Shigeyuki Ikeda,Ryuta Kawashima,Yuka Kotozaki,Ryoichi Yokoyama,Magistro Daniele,Sugiko Hanawa,Yuko Sassa,Kohei Sakaki

doi:10.1038/s42003-021-02435-0

Abstract

Lead is a toxin known to harm many organs in the body, particularly the central nervous system, across an individual’s lifespan. To date, no study has yet investigated the associations between body lead level and the microstructural properties of gray matter areas, and brain activity during attention-demanding tasks. Here, utilizing data of diffusion tensor imaging, functional magnetic resonance imaging and cognitive measures among 920 typically developing young adults, we show greater hair lead levels are weakly but significantly associated with (a) increased working memory-related activity in the right premotor and pre-supplemental motor areas, (b) lower fractional anisotropy (FA) in white matter areas near the internal capsule, (c) lower mean diffusivity (MD) in the dopaminergic system in the left hemisphere and other widespread contingent areas, and (d) greater MD in the white matter area adjacent to the right fusiform gyrus. Higher lead levels were also weakly but significantly associated with lower performance in tests of high-order cognitive functions, such as the psychometric intelligence test, greater impulsivity measures, and higher novelty seeking and extraversion. These findings reflect the weak effect of daily lead level on the excitability and microstructural properties of the brain, particularly in the dopaminergic system.

Highlights

Lead is a toxin known to harm many organs in the body, the central nervous system, across an individual’s lifespan
Data from the Cincinnati Lead Study revealed that young adults with higher blood lead levels in early childhood show lower regional gray-matter volume in various areas (N = 157)[15], reduced fractional anisotropy (FA) throughout the white matter, increased or decreased mean diffusivity (MD) of the white matter depending on the region (N = 91)[16], decreased
No study has yet revealed the accurate association between body lead level and brain activity during attention-demanding tasks. Considering this knowledge gap, the purpose of the present study is to investigate the associations between body lead level and MD in the dopaminergic system (MDDS) and brain activity during attention-demanding tasks using a large sample size and robust statistics

Summary

Introduction

Lead is a toxin known to harm many organs in the body, the central nervous system, across an individual’s lifespan. No study has yet investigated the associations between body lead level and the microstructural properties of gray matter areas, and brain activity during attention-demanding tasks. Higher lead levels were weakly but significantly associated with lower performance in tests of high-order cognitive functions, such as the psychometric intelligence test, greater impulsivity measures, and higher novelty seeking and extraversion. These findings reflect the weak effect of daily lead level on the excitability and microstructural properties of the brain, in the dopaminergic system. Marshall et al.[18] revealed that children of lower-income families living in areas with high risk of lead exposure show lower cognitive test scores and cortical volumes in a cross-sectional study of 9712 children

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