Stage-specific functional networks associated with cognitive impairment in Parkinson's disease: a pilot fNIRS study

Abstract

Objective: This study aimed to investigate cortical activation and functional connectivity during Stroop task performance in Parkinson's disease (PD) using functional near-infrared spectroscopy (fNIRS).

Methods: Forty-five individuals with PD and fourteen healthy controls completed neuropsychological assessments and underwent fNIRS scanning while performing the Stroop task. PD participants were categorized into normal cognition (PD-NC, n = 6), mild cognitive impairment (PD-MCI, n = 22), and dementia (PDD, n = 17) groups. Z scores were calculated across cognitive domains, including attention, working memory, executive function, language, memory, and visuospatial function.

Results: During the Stroop task, significant hypoactivation in the dorsolateral prefrontal cortex (DLPFC), primary motor cortex (M1), and premotor cortex (PMC) were observed in the PD-MCI group, while PDD patients showed increased activation in the medial prefrontal cortex (mPFC), orbitofrontal cortex (OFC), and dorsolateral prefrontal cortex (DLPFC). Increased activation in DLPFC was significantly correlated with poorer executive function outcomes. Functional connectivity analysis revealed that both PD-NC and PD-MCI groups had significantly enhanced interhemispheric connectivity compared to healthy controls, with pronounced interhemispheric connectivity in PD-MCI. In contrast, the PDD group exhibited reduced connectivity among the premotor cortex (PMC), ventrolateral prefrontal cortex (VLPFC), and orbitofrontal cortex (OFC), compared to the PD-MCI group.

Conclusion: While PD-MCI patients showed reduced cortical activation relative to PDD, they exhibited extensive connectivity across cortical regions, suggesting an expanded cortical network as compensation. In PDD, the mPFC, left OFC, and left DLPFC displayed the highest cortical activation and alongside reduced functional connectivity, which may reflect widespread atrophy across multiple brain regions. These findings highlight fNIRS as a potential tool for characterizing cognitive impairment stages in PD.

Keywords: Parkinson's disease; cognitive impairment; cortical activation; functional connectivity; functional near-infrared spectroscopy.

Figure 1

Configuration of fNIRS channels.

Figure 2

Behavior results for task performance: (A) rate of correct answer; (B) response times.

Figure 3

Activation patterns during the Stroop task in the HC group: (A) right view; (B) superior view; (C) left view. Colors represent mean β-values over time, with red indicating higher activation compared to blue regions.

Figure 4

Activation patterns during the Stroop task in the PD-NC group: (A) right view; (B) superior view; (C) left view. Colors represent mean β-values over time, with red indicating higher activation compared to blue regions.

Figure 5

Activation patterns during the Stroop task in the PD-MCI group: (A) right view; (B) superior view; (C) left view. Colors represent mean β-values over time, with red indicating higher activation compared to blue regions.

Figure 6

Activation patterns during the Stroop task in the PDD group: (A) right view; (B) superior view; (C) left view. Colors represent mean β-values over time, with red indicating higher activation compared to blue regions.

Figure 7

(A–C) illustrate the right, superior, and left hemispheres, respectively, depicting the fNIRS channels with significant differences after the FDR correction.

Figure 8

Correlation analysis between the averaged ΔHbO2 and demographic and clinical characteristics. The Averaged ΔHbO2 of the left DLPFC was negatively correlated with the MMSE (A) and The Averaged ΔHbO2 of the left PMC was negatively correlated with the accuracy (B) The Averaged ΔHbO2 of the left DLPFC was negatively correlated with the accuracy (C).

Figure 9

The task state functional connectivity in deoxyhemoglobin. (A) Group-averaged task-state functional connectivity matrix diagram. (B) ROI-based connections with significant inter-group differences (p < 0.05, FDR corrected). (C) The results of post-hoc comparisons (p < 0.05, Bonferroni corrected). The color bar indicates the statistical significance threshold.