Executive Dysfunction and Prefrontal Cortex Dysregulation in Early-Onset Parkinson's Disease: An fNIRS Study.

Background: Executive function (EF) impairment is a recognized common cognitive deficit in early-onset Parkinson's disease (EOPD), profoundly impacting patient autonomy and quality of life. While EF-related cognitive decline has been extensively studied in late-onset Parkinson's disease (LOPD), research on EOPD remains limited. Addressing this gap, this study uniquely employed functional near-infrared spectroscopy (fNIRS), a technique well-adapted for assessing patients with motor challenges, to explore EF-related neural mechanisms in EOPD patients with mild cognitive impairment.

Methods: This study included 30 patients with PD, classified into distinct cognitive profiles based on comprehensive assessments of their cognitive function. To assess functional changes in the prefrontal cortex (PFC) we administered a verbal fluency test to evaluate EF during task performance. In the resting state, we recorded neural activity and analyzed the amplitude of low-frequency fluctuations (ALFF) to assess spontaneous brain activity.

Results: During executive tasks, patients with EF-dominant impairment (EOPD-EL) showed increased activation in the dorsolateral prefrontal cortex (DLPFC) and medial prefrontal cortex (mPFC), indicating disrupted balance between the executive and default mode networks. Resting-state analysis revealed reduced spontaneous activity in the ventrolateral prefrontal cortex (VLPFC), suggesting impaired regulatory efficiency in these regions. These findings support the dual syndrome hypothesis in EOPD, with EF dysfunction as a primary deficit that may lead to secondary cognitive challenges.

Conclusion: This study underscores the central role of PFC dysfunction in EOPD-related EF impairment, identifying abnormalities in the DLPFC, mPFC, and VLPFC as key contributors to cognitive decline. These results lay the groundwork for early detection of EF deficits and inform targeted interventions to mitigate cognitive decline in EOPD.