In-vehicle toluene exposure affects functional connectivity of working memory retrieval networks

• First evidence linking low-level toluene to WM retrieval network changes. • EEG with DTF revealed FC changes despite stable behavior. • Prefrontal-temporal connectivity increased despite stable behavior. • This study provides the basis for in-vehicle air quality standards. With the aim to investigate the impact of in-vehicle toluene exposure on working memory (WM) retrieval networks, twenty-three healthy adults underwent 4-hour exposures to toluene at concentrations of 0, 17.5, 35, or 70 ppb within a simulated vehicle. After exposure, all participants completed a WM task while cortical electroencephalography signals were recorded. The functional connectivity (FC) strengths of WM retrieval networks were compared across the four groups using direct transfer function (DTF) analysis. Results indicated that exposure to 70 ppb toluene significantly increased the FC strengths of the WM retrieval network, particularly in the frontal cortex ( P < 0.05). Specifically, DTF values for FZ-T5, FZ-F3, F3-T5, F4-T6, and F7-T5 were higher at 70 ppb than those at 0 ppb ( P < 0.05, P < 0.01, P < 0.001, P < 0.05, P < 0.05, respectively). The DTF values for FZ-F3 and F3-T5 at 35 ppb were higher than those at 0 ppb ( P < 0.01). The DTF FZ-F3 value at 17.5 ppb was higher than that at 0 ppb ( P < 0.01). The results suggest that even ppb-level, in-vehicle toluene exposure can significantly impact WM retrieval networks. The observed increase in FC strengths involved the medial prefrontal-to-left dorsolateral prefrontal cortex network, and several prefrontal-to-inferior temporal gyrus pathways. This dose-dependent enhancement of FC within critical cognitive networks presents a plausible neurophysiological mechanism for how in-vehicle toluene exposure may disrupt normal WM retrieval processes.