Lateralization Disruption and Dynamic Balance Alterations in Alzheimer's Disease: Impacts on Hemispheric Interaction and Cognitive Performance

Brain lateralization is considered evolutionarily adaptive. Impaired functional specialization is thought to cause abnormal lateralization in neurological disorders. However, the dynamic changes in brain laterality in Alzheimer's disease (AD) remain unclear. In this study, resting-state fMRI data and neuropsychological assessments from 109 participants (49 AD patients and 60 healthy controls [HC]) were used. Dynamic laterality time series were constructed by extracting the dynamic laterality index (DLI) within each sliding window. We assessed two key features: laterality reversal (LR), reflecting intra-hemispheric processing efficiency, and laterality fluctuation (LF), indicating inter-hemispheric communication. Group differences in dynamic laterality characteristics were analyzed using statistically rigorous methods, regressing out gender, age, years of education, and head movements. Spearman correlation analyses examined the relationship between laterality characteristics and cognitive performance. Our results showed that AD patients exhibited a more pronounced loss of left lateralization as well as stronger right lateralization, especially in the somatomotor network (SMN) and default mode network (DMN). Additionally, we observed decreased LR as well as increased LF with global trends in AD. These divergent changes disrupted the dynamical balance between intra- and inter-hemispheric information interaction. Notably, this imbalance depended on the degree of lateralization, and the higher order cognitive networks with high-level lateralization were more vulnerable. Importantly, the observed abnormal lateralization metrics were associated with worse cognitive impairment. Our study highlights a disruption of dynamic lateralization balance in higher order cortical networks in AD patients and reveals its potential role in the disease's pathophysiology.