Individuals with anxiety exhibit high clinical usage of benzodiazepines, particularly among those with long-term use, yet the impact of these medications on cognitive function remains inconclusive. Previous research has predominantly focused on epidemiological data and metabolic measurements, often overlooking both cortical activation and the synchrony between different brain regions. This study investigates how brain neuronal activities are modulated in both long-term benzodiazepine users and nonusers during cognitive tasks, offering insights into the neural mechanisms underlying cognitive function. Fifty older adults with anxiety disorders participated in this study, including 31 long-term benzodiazepine users (BZD group) and 19 nonusers (control group). Functional near-infrared spectroscopy was used to assess cortical activation and functional connectivity during a verbal fluency task. Our study is the first to find a greater interhemispheric functional connectivity in chronic benzodiazepine users. However, no notable differences were detected between the two groups regarding behavioral performance, cortical activation, or changes in oxygenated hemoglobin concentration. Moreover, cumulative dosage of benzodiazepines use had no significant effect on dorsolateral prefrontal cortex activation. Long-term benzodiazepines use does not affect brain activation but impacts functional connectivity. The increased interhemispheric connectivity may serve to maintain the stability of brain networks, and this enhanced connectivity could be associated with the long-term adaptive disinhibition of GABAergic neurotransmission.
Supplementary Information: The online version contains supplementary material available at 10.1038/s41598-026-39359-w.
Keywords: Anxiety disorders; Benzodiazepines; Cognitive effects; Functional near-infrared spectroscopy; GABAergic system; Long term adverse effects; Sedatives addiction.