Background

Previous epidemiological studies have reported associations of pesticide exposure with poor cognitive function and behavioral problems. However, these findings have relied primarily on neuropsychological assessments. Questions remain about the neurobiological effects of pesticide exposure, specifically where in the brain pesticides exert their effects and whether compensatory mechanisms in the brain may have masked pesticide-related associations in studies that relied purely on neuropsychological measures.

Methods

We conducted a functional neuroimaging study in 48 farmworkers from Zarcero County, Costa Rica, in 2016. We measured concentrations of 13 insecticide, fungicide, or herbicide metabolites or parent compounds in urine samples collected during two study visits (approximately 3-5 weeks apart). We assessed cortical brain activation in the prefrontal cortex during tasks of working memory, attention, and cognitive flexibility using functional near-infrared spectroscopy (fNIRS). We estimated associations of pesticide exposure with cortical brain activation using multivariable linear regression models adjusted for age and education level.

Results

We found that higher concentrations of insecticide metabolites were associated with reduced activation in the prefrontal cortex during a working memory task. For example, 3,5,6-trichloro-2-pyridinol (TCPy; a metabolite of the organophosphate chlorpyrifos) was associated with reduced activation in the left dorsolateral prefrontal cortex (β = -2.3; 95% CI: -3.9, -0.7 per two-fold increase in TCPy). Similarly, 3-phenoxybenzoic acid (3-PBA; a metabolite of pyrethroid insecticides) was associated with bilateral reduced activation in the dorsolateral prefrontal cortices (β = -3.1; 95% CI: -5.0, -1.2 and -2.3; 95% CI: -4.5, -0.2 per two-fold increase in 3-PBA for left and right cortices, respectively). These associations were similar, though weaker, for the attention and cognitive flexibility tasks. We observed null associations of fungicide and herbicide biomarker concentrations with cortical brain activation during the three tasks that were administered.

Conclusion

Our findings suggest that organophosphate and pyrethroid insecticides may impact cortical brain activation in the prefrontal cortex - neural dynamics that could potentially underlie previously reported associations with cognitive and behavioral function. Furthermore, our study demonstrates the feasibility and utility of fNIRS in epidemiological field studies.

Main sources of manganese (Mn) in the general population are diet and drinking water. Mn is also found in ethylene bisdithiocarbamate (EBDC) fungicides used in agriculture or emitted into the air by ferromanganese plants and welding fumes, which can be additional environmental and occupational sources of exposure. High occupational Mn exposure has been linked with motor, behavioral, and cognitive impairment, but its effects on neural function remain poorly understood. We conducted a functional neuroimaging study in a sample of 48 farmworkers in Zarcero County, Costa Rica, an agricultural region where EBDC fungicides are sprayed. We measured Mn concentrations in farmworkers' toenails (n = 40 farmworkers) and hair (n = 33 farmworkers), and recorded brain activity in the dorsolateral prefrontal cortex during a letter-retrieval working memory task using functional near-infrared spectroscopy (fNIRS). We estimated exposure-outcome associations using multivariable linear regression models adjusted for age and education level. Geometric mean (geometric standard deviation) toenail and hair Mn concentrations were 0.40 μg/g (3.52) and 0.24 μg/g (3.54), respectively. We did not find strong evidence that Mn concentrations were associated with working memory-related brain activity in this sample of farmworkers; we also found null associations between working memory task accuracy and brain activity. However, our small sample size may have limited our ability to detect small effect sizes with statistical precision. Our study demonstrates that fNIRS can be a useful and feasible tool in environmental epidemiology for examining the effects of toxicants, like Mn, on neural function. This may prove to be important for elucidating neuropathological pathways that underlie previously reported associations of elevated Mn exposure with neurotoxic effects.