Abstract

Cognitive functions rely on specific brain circuits involving cortical and subcortical regions. However, how age-related changes in effective connectivity within the prefrontoparietal-thalamo-hippocampal circuit affect cognition remains unclear. This study included 143 healthy older adults (60 to 88 yrs) and 124 young adults (18 to 44 yrs), using regression dynamic causal modeling to analyze resting-state functional magnetic resonance imaging data. Compared to young adults, older adults showed increased reciprocal effective connectivity within the ventromedial prefrontal cortex–lateral thalamic nuclei–right caudal hippocampus circuit. Enhanced bidirectional connectivity was also observed within the frontoparietal network, between the pregenual cingulate gyrus and superior frontal gyrus, and between lateral thalamic nuclei (LTN) and frontal pole. Additionally, heightened connectivity between thalamus and hippocampus negatively correlated with cognitive performance. Our findings reveal significant age-related increases in effective connectivity within the prefrontoparietal-thalamo-hippocampal circuit, linked to cognitive performance levels. Increased connectivity may indicate compensatory mechanisms helping preserve cognitive function in healthy aging. These results advance our understanding of neural dynamics underlying cognitive aging and potential adaptive mechanisms in older adults.

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