Grantee Research Project Results

Final Report: Magnetic Resonance Assessment of Brain Function Altered by Lead Exposure

EPA Grant Number: R829389C005
Subproject: this is subproject number 005 , established and managed by the Center Director under grant R829389
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: CECEHDPR - University of Cincinnati Center for the Study of Prevalent Neurotoxicants in Children
Center Director: Lanphear, Bruce
Title: Magnetic Resonance Assessment of Brain Function Altered by Lead Exposure
Investigators: Cecil, Kim
Institution: Children Hospital of Cincinnati
EPA Project Officer: Hahn, Intaek
Project Period: November 1, 2001 through October 31, 2006
RFA: Centers for Children's Environmental Health and Disease Prevention Research (2001) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health

Objective:

One hundred sixty one participants were recruited from the Cincinnati Lead Study (CLS), for a magnetic resonance imaging evaluation (n=159 with reportable data). These subjects have been followed from birth through early childhood with extensive documentation of lead exposure, social and medical history, intellectual attainment, neuromotor function, academic achievement, and behavior.

Research Objectives:

· To correlate childhood environmental lead exposure with changes in brain structure, neurochemistry and function assessed with volumetric magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS).

· Compare the results of the MR measures with the cognitive, behavioral and social assessments defined in the companion Project 4 to determine the significance of individual and collective measures for assessing the brain-behavior relationships.

Summary/Accomplishments (Outputs/Outcomes):

Volumetric analyses of whole brain magnetic resonance imaging data revealed significant decreases in brain volume associated with childhood blood lead concentrations. The most affected regions included frontal gray matter, specifically the anterior cingulate cortex. Areas of lead-associated gray matter volume loss were much larger and more significant in men than women.

Functional MRI:

Description and Objective of Research: Forty-five members of the CLS cohort participated in an exploratory fMRI study with four paradigms employed to broadly assess brain function associated with abilities in language, attention, working memory and inhibition, respectively. Forty-two subjects performed a verb generation task while undergoing fMRI scanning. The test interval consisted of a 30-second period of verb generation task to collect language activation data. During each test period, a series of nouns were presented orally to the subject once every five seconds. The subject was instructed to silently generate verbs associated with each noun presented. The subject was instructed to think about these verbs silently instead of saying them to avoid unnecessary motion. Five cycles of testing with a 30-second resting period between each test were performed.

Summary of Findings: Consistent with the hypotheses and with existing literature, investigators found a significant inverse association of mean childhood blood lead level with brain activation in the left frontal gyrus and left middle temporal gyrus. The diminished activation in these regions in subjects with higher childhood blood lead levels suggests that lead exposure during early childhood disrupts development of the normative neural substrates of language and leaves a long-term impact on the functional neuroanatomy of language.

The observation that these young adult subjects still use conventional brain circuitry in support of the verb general task, indicates the effect of lead exposure on the neural substrates of language is significant but not as severe as that observed with more dramatic brain injuries such as stroke or brain trauma, at least not for this cohort with low to moderately elevated childhood blood lead levels.

Conclusions: This study concluded that elevated childhood lead exposure exerts a substantial influence on the cortical organization of semantic language function in young adulthood. Imaging data from this study provide further confirmation of the adverse consequences of environmental lead exposure on cognitive abilities.

Conclusions:

Childhood lead exposure is associated with region-specific reductions in adult gray matter volume. Affected regions include the portions of the prefrontal cortex and anterior cingulate cortex responsible for executive function, mood regulation and decision-making. These neuroanatomical findings were more pronounced for males suggesting that lead-related atrophic changes have a disparate impact across genders. This analysis suggests that adverse cognitive, behavioral and motor outcomes may be related to lead’s effect on prefrontal brain development producing persistent alterations in structure.

Journal Articles:

No journal articles submitted with this report: View all 6 publications for this subproject

Supplemental Keywords:

toxicology, ADHD, behavioral assessment, behavioral deficit, genetic susceptibility, pesticides, biomarkers, environmental agents, exposure, exposure assessment, hearing loss, lead, meconium, neurotoxicity, pesticide exposure, risk assessment, toxicants, lead-based paint, lead hazard control, RFA, Scientific Discipline, Health, ENVIRONMENTAL MANAGEMENT, Toxicology, Health Risk Assessment, Chemistry, Risk Assessments, Children's Health, Biology, Risk Assessment, magentic resonance, behavioral assessment, lead, neurotoxicity, children, toxicity, behavioral deficits, biological markers, exposure assessment, biomarker

Relevant Websites:

http://www.cincinnatichildrens.org/homestudy/

Progress and Final Reports:

Original Abstract

Main Center Abstract and Reports:

R829389 CECEHDPR - University of Cincinnati Center for the Study of Prevalent Neurotoxicants in Children

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R829389C001 Neurobehavioral Effects of Prevalent Toxicants in Children
R829389C002 Validation of Meconium Markers of Fetal Neurotoxicant Exposures
R829389C003 Community-Based Research Project Identifying Residential Hazards Using Home Test Kits
R829389C004 Early Exposure to Lead and Adult Antisocial Outcome
R829389C005 Magnetic Resonance Assessment of Brain Function Altered by Lead Exposure

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The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.