Coal Workers’ Pneumoconiosis (CWP) is an occupational disease caused by the long-term inhalation of mineral dust particles smaller than 5 μm in diameter. As of 2021, the number of coal dust workers is distributed in a double U shape, the incidence of CWP in China has been on the rise (Wang et al., 2023; Blackley et al., 2018), and about 20.6% of miners in the United States suffer from CWP. based on the GBZ 70–2015 national diagnostic criteria for occupational pneumoconiosis, CWP can be divided into three stages. The first stage is simple diffuse micronodules in both lungs, the second stage is aggregated micronodules, and the third stage is more complex and severe. Clinically, the irreversible pulmonary changes associated with CWP often result in chronic hypoxia, cyanosis, and progressive dyspnea. Chronic hypoxia has been linked to cognitive impairment, with studies suggesting that this relationship may stem from neurological damage. For instance, a study using a rat model of pneumoconiosis-associated cognitive impairment found that with the decrease of PaO2, chronic hypoxia led to diminished memory and learning abilities, likely due to cognitive and neurological abnormalities (Lv and Niu, 2012). On the other hand, Alcoholism is a known risk factor for alcohol-related liver disease, alcohol-induced cardiomyopathy and liver cancer (Danpanichkul et al., 2024), In addition, alcoholism has been shown to have impact on Alzheimer’s disease (AD), which is associated with structural and functional brain changes. It impairs attention, memory, and emotional and perceptual functions, contributing significantly to cognitive dysfunction (Koch et al., 2019; Dai et al., 2023). Alcoholism, therefore, plays a critical role in cognitive impairment (Selim et al., 2024; Pagni et al., 2024). Alcoholism is prevalent among CWP patients; however, studies investigating cognitive function changes in CWP patients with alcoholism remain scarce.

CWP has been shown to cause cognitive impairment through chronic hypoxia resulting from hypoxemia and chronic microvascular injury (Imaizumi et al., 2014), while alcoholism can directly affect the brain or lead to neurotrophic factor deficiencies, resulting in cognitive changes and even dementia (Sabia et al., 2014). According to the DSM-V, alcohol dependence can cause mild cognitive impairment (MCI), an intermediate stage between normal aging and dementia, characterized by cognitive decline without significant impact on daily activities, which may progress to more severe stages (Cong et al., 2023). Although the mechanisms of CWP and alcoholism differ, both can induce MCI, leading to varying degrees of cognitive and executive function impairment. Neuroimaging studies using functional Magnetic Resonance Imaging (fMRI), particularly Blood Oxygenation Level Dependent (BOLD) fMRI, have revealed changes associated with MCI (Zhe et al., 2023). For example, ALFF studies in neurodegeneration have shown reduced ALFF signals in the right medial paracentral cingulate gyrus, bilateral inferior cerebellar lobes, and bilateral precuneus cortex (Yang et al., 2018), while chronic smokers have shown different Functional Connectivity in the dorsal attention network (Zhang et al., 2017; Weidler et al., 2024). Similarly, altered ALFF signals have been reported in patients with co-morbid alcohol dependence and depression (Sun et al., 2023). These findings suggest that both pneumoconiosis-induced hypoxia and alcoholism can disrupt spontaneous neural activity in the brain, contributing to abnormal cognitive function (Marshall et al., 2015).

In this study, we hypothesize that CWP combined with alcoholism may exhibit abnormal spontaneous brain activity compared to CWP without alcohol consumption. To test this, we propose using Amplitude of Low-Frequency Fluctuation (ALFF) and seed-based functional connectivity (FC) analyses to investigate alterations in spontaneous neural activity in the brains of CWP patients with alcoholism and explore the relationship between these alterations and clinically relevant cognitive indices. Specifically, we will first compare differences in ALFF and FC indices among three groups: the CWP drinking group, the CWP non-drinking group, and the healthy control group, to identify abnormal functional brain regions. Secondly, we will analyze the correlation between imaging indices of these brain regions and clinical cognitive assessment indices. This study aims to provide insights into the abnormal neuropathological changes associated with CWP and alcoholism from an imaging perspective.

The results of this study demonstrated that pulmonary function indices (FVC, FEV1, FEV1/FVC) were higher in the CWP drinking group compared to the non-drinking group, suggesting that alcohol consumption may have a positive effect on the improvement of ventilatory function. However, the change in PaO2 was not significantly different between the two groups. The MMSE scores were comparable between the two groups, while the MoCA, SCD-Q, HAMA, HAMD, and GDS scores were higher in the drinking group than in the non-drinking group, indicating greater cognitive impairment in the non-drinking group of the CWP, which was manifested in the scale as diminished ability in executive function and delayed recall. On the other hand, alcohol may have less effect on emotional functioning in depression and anxiety. In contrast, scores on the CDT were lower in the drinking group, suggesting a correlation with visuospatial and recall reproduction abilities.

In the present study, we found increased overall ALFF signal in the right Precuneus Cortex, right Intracalcarine Cortex, Bilateral Orbitofrontal Cortex in a one-way ANOVA analysis between multiple groups of CWP. The left Orbitofrontal Cortex had increased connectivity to the right Precuneus Cortex, the left Frontal Pole had increased connectivity to the bilateral Precuneus Cortex, and the right Precuneus Cortex had increased connectivity to the right Lingual Gyrus. The Precuneus Cortex is thought to be more closely associated with the default mode network (DMN), an interconnected and highly correlated neural network (Menon, 2023) that is active at rest and has been found to be highly correlated with psychiatric disorders such as AD, Depression, and Autism (Giorgio et al., 2024; Chou et al., 2023; Yang et al., 2023). In the DMN network, the Precuneus Cortex is associated with memory perception, attention, and sensorimotor information integration (Dadario and Sughrue, 2023), and diseases can damage the Precuneus Cortex to varying degrees, resulting in dysfunction or even organic changes. It has been found that under the influence of negative emotions, Precuneus Cortex can show negative activation in fMRI (Moe et al., 2023). Run et al. also found that subjects had reduced ALFF signals in the left Precuneus Cortex under alcohol induction (Liu et al., 2018). On the other hand, cortical thickness of the Precuneus Cortex can be significantly reduced in the presence of epilepsy (Du et al., 2023). In the above studies, either in the state of negative DMN activation or under the influence of chronic alcohol, the Precuneus Cortex showed signal reduction in fMRI. However, the results of the multiple group comparison in the present study showed increased ALFF signal in the Precuneus Cortex and increased functional connectivity between the Precuneus to several brain regions, suggesting that the DMN in CWP patients with alcoholism were persistently active, reflecting the activation of memory and attention networks in patients with CWP. Previous studies have shown that the precuneus is functionally heterogeneous, exhibiting both anterior region’s self-referential thinking and posterior region’s episodic memory and visuospatial intention (He et al., 2025), The Complex function of precuneus may represent a lesser degree of damage to early CWP. On the other hand. This may be due to early cognitive impairment, leading the Precuneus Cortex to maintain general neural activity through compensatory mechanisms. This performance contributes to our enhanced understanding of abnormal brain activity in CWP patients under the influence of alcoholism.

In contrast to the non-drinking group, the left Middle Frontal Gyrus (MFG) ALFF signaling was reduced in the drinking group, whereas there was no significant alteration in functional connectivity in the left MFG. The primary functions of the MFG include the head-eye movement and writing centers (Briggs et al., 2021), while its memory-related functions are mainly associated with working memory, attention, and language-related processing. Current research on the MFG has primarily focused on psychiatric disorders such as subclinical depression, anxiety-type depression, and schizophrenia (Zhao et al., 2019; Li et al., 2023). Previous studies have reported brain abnormalities in patients with amnestic cognitive impairment (aMCI) (Wu et al., 2023), with alterations in ALFF signaling mainly observed in the right Superior Frontal Gyrus and MFG of patients with aMCI (Liu et al., 2022). These findings align with the results of the present study, which reported reduced ALFF signals in the left MFG in a chronic alcohol environment. Under the indulge of alcohol, complex decision-making and working memory functions involving the MFG are thought to be impaired, resulting in reduced spontaneous neural activity, thus contributing to cognitive decline. These findings provide evidence supporting the association between alcoholism and cognitive dysfunction in patients.

Compared to the control group, the CWP drinking group exhibited increased ALFF signals in the Orbitofrontal Cortex (OFC) bilaterally, as well as increased connectivity between the right OFC and the delta of the right Inferior Frontal Gyrus. According to the Brodmann partitioning system, the OFC is located in area 47 (BA47), situated in the middle of the Ventral Frontal Lobe bilaterally, at the junction between the Prefrontal Cortex and the Limbic system. It primarily manages the expression of the reward system and emotional responses (Ruge et al., 2025). Previous studies have identified increased functional connectivity of the OFC to the Precuneus Cortex and Posterior Cingulate Cortex in depressed patients (Karolewicz et al., 2010; Zhang et al., 2024), suggesting that early connectivity changes are associated with stress-related cognitive deficits and mood dysregulation. Alcohol use disorder has also been linked to altered functional connectivity in cortico-amygdala-striatal circuits (Nimitvilai-Roberts et al., 2025; Radoman et al., 2024), with studies reporting increased ALFF signals and functional connectivity in the OFC. This suggests that the craving for alcohol-related cues and the functioning of the OFC’s reward system may influence the onset and progression of AUD. The findings of this study support this evidence, Under the dual influence of CWP and Alcoholism, the activation of reward system is dominant, which indicating that the OFC could serve as a biomarker for analyzing neuroimaging changes in CWP patients with alcoholism.

On the other hand, compared to the control group, the CWP non-drinking group showed reduced ALFF signaling in the bilateral Temporal Poles and reduced functional connectivity of the bilateral Temporal Poles to the left Superior Frontal Gyrus and the left Frontal Pole. According to the Brodmann partitioning system, the rostral portion of the anterior temporal lobe is referred to as the Temporal Pole (BA38), which primarily manages memory storage and the expression of affective functions (Mesulam, 2023). It is specifically involved in cognitive processes such as autobiographical memory, complex visual processing, naming, and socio-emotional processing (Herlin et al., 2021). Under the influence of neurodegenerative pathologies, dysfunction in the Temporal Pole can lead to neurological disorders such as behavioral dementia, primary progressive aphasia, epilepsy, and other conditions (Gosnell et al., 2020; Herlin et al., 2020). In the present study, ALFF signaling and functional connectivity in the bilateral Temporal Poles were significantly reduced in CWP patients compared to controls. This reduction may be commonly attributed to chronic hypoxia-induced alterations in spontaneous neural activity. Previous studies have shown reduced BOLD signaling in the visual cortex under hypoxic conditions, which supports this explanation (Arngrim et al., 2019). On the other hand, Setton et al. (2022) found that functional connectivity in both the anterior and posterior hippocampus and Temporal Poles decreases with aging. However, in the present study, the age difference between the groups was not statistically significant, suggesting that the observed alterations in neural activity in the Temporal Poles are not directly attributable to age. AD is the most common neurodegenerative disease in the elderly, is characterized by region-specific nonlinear atrophy throughout the brain as it progresses from MCI to AD stages. This atrophy is most likely to occur in the superior Temporal Pole, caudate nucleus, and hippocampus (Wei et al., 2023). The findings of the present study, which reported reduced ALFF signaling and functional connectivity in the Temporal Pole bilaterally, align with this interpretation and provide further evidence of the vulnerability of the Temporal Pole to neurodegenerative processes.

The partial pressure of oxygen (PaO2) is an indicator of the tension of O2 physically dissolved in the blood at room temperature and pressure (Attaway et al., 2024). In the correlation analysis of the present study, ALFF values in the left Temporal Pole and the left Postcentral Gyrus showed a significant positive correlation with PaO2. This is hypothesized to be due to the clogging of alveoli and distal fine bronchioles by coal dust microparticles in the lungs of patients with CWP, which leads to a reduction in the oxygen content in the blood (Fan et al., 2022). Previous studies have supported the presence of altered nocturnal hypoxemia in patients with interstitial lung fibrosis (Myall et al., 2023). However, in this study, the PaO2 levels in CWP patients were above the lower limit of normal. This may be because the experimental group consisted of patients in the early stages of CWP, their imaging features are characterized by multiple diffuse micronodules in both lungs, partial blockage of alveoli, and impaired respiratory exchange thus affects brain function and metabolism. Where the body compensates to maintain normal PaO2 levels, suggesting that the effect of coal dust microparticles on alveoli and distal fine bronchioles in the early stage is relatively small.

This study has several limitations. First, the sample size of the CWP subgroup was relatively small, and future studies will expand the sample size to ensure a more accurate presentation of the results. Second, this study was cross-sectional and did not analyze brain function abnormalities over the course of CWP progression in a longitudinal manner. Lastly, the study did not account for the effects of long-term maintenance medications, other than sedative-hypnotic medications, in patients with CWP. Future follow-up studies will aim to comprehensively capture possible influencing factors and include them in the analysis of covariates, reducing the likelihood of these factors affecting scale score results and differences in brain area function.

Our study demonstrates that there are abnormalities in brain regions of spontaneous neural activity in CWP patients with alcoholism. The differences in ALFF and FC in the left Orbitofrontal Cortex, the right Intracalcarine Cortex, and the right Precuneus Cortex are closely associated with cognition-related clinical indicators. These brain regions with significant differences may serve as potential biomarkers for cognitive function assessment in CWP patients with alcoholism. The findings of this study provide valuable reference points for neurological research based on neuroimaging of cognitive impairment.