Resting-state functional connectivity is modulated by cognitive reserve in early Parkinson's disease

Sonia Di Tella; Matteo De Marco; Francesca Baglio; Maria Caterina Silveri; Annalena Venneri

doi:10.3389/fpsyg.2023.1207988

Resting-state functional connectivity is modulated by cognitive reserve in early Parkinson's disease

Front Psychol. 2023 Aug 25:14:1207988. doi: 10.3389/fpsyg.2023.1207988. eCollection 2023.

Authors

Sonia Di Tella^{1

2}, Matteo De Marco³, Francesca Baglio², Maria Caterina Silveri¹, Annalena Venneri^{3

4}

Affiliations

¹ Department of Psychology, Università Cattolica del Sacro Cuore, Milan, Italy.
² IRCCS, Fondazione Don Carlo Gnocchi Onlus, Milan, Italy.
³ Department of Life Sciences, Brunel University London, Uxbridge, United Kingdom.
⁴ Department of Medicine and Surgery, University of Parma, Parma, Italy.

Abstract

Background: Fronto-striatal disconnection is thought to be at the basis of dysexecutive symptoms in patients with Parkinson's disease (PD). Multiple reserve-related processes may offer resilience against functional decline. Among these, cognitive reserve (CR) refers to the adaptability of cognitive processes.

Objective: To test the hypothesis that functional connectivity of pathways associated with executive dysfunction in PD is modulated by CR.

Methods: Twenty-six PD patients and 24 controls underwent resting-state functional magnetic resonance imaging. Functional connectivity was explored with independent component analysis and seed-based approaches. The following networks were selected from the outcome of the independent component analysis: default-mode (DMN), left and right fronto-parietal (l/rFPN), salience (SalN), sensorimotor (SMN), and occipital visual (OVN). Seed regions were selected in the substantia nigra and in the dorsolateral and ventromedial prefrontal cortex for the assessment of seed-based functional connectivity maps. Educational and occupational attainments were used as CR proxies.

Results: Compared with their counterparts with high CR, PD individuals with low CR had reduced posterior DMN functional connectivity in the anterior cingulate and basal ganglia, and bilaterally reduced connectivity in fronto-parietal regions within the networks defined by the dorsolateral and ventrolateral prefrontal seeds. Hyper-connectivity was detected within medial prefrontal regions when comparing low-CR PD with low-CR controls.

Conclusion: CR may exert a modulatory effect on functional connectivity in basal ganglia and executive-attentional fronto-parietal networks. In PD patients with low CR, attentional control networks seem to be downregulated, whereas higher recruitment of medial frontal regions suggests compensation via an upregulation mechanism. This upregulation might contribute to maintaining efficient cognitive functioning when posterior cortical function is progressively reduced.

Keywords: Parkinson’s disease; brain reserve; cognitive reserve; functional MRI; imaging; resting-state networks.