Salience network and cognitive impairment in Parkinson’s disease

Abstract

Parkinson’s disease (PD) is a neurodegenerative disease with cognitive as well as motor impairments. While much is known about the brain networks leading to motor impairments in PD, less is known about the brain networks contributing to cognitive impairments. Here, we leveraged resting-state functional magnetic resonance imaging (rs-fMRI) data from the Parkinson’s Progression Marker Initiative (PPMI) to examine network dysfunction in PD patients with cognitive impairment. We tested the hypothesis that cognitive impairments in PD involve altered connectivity of the salience network (SN), a key cortical network that detects and integrates responses to salient stimuli. We used the Montreal Cognitive Assessment (MoCA) as a continuous index of coarse cognitive function in PD. We report two major results. First, in 82 PD patients we found significant relationships between lower intra-network connectivity of the frontoparietal network (FPN; comprising the dorsolateral prefrontal and posterior parietal cortices bilaterally) with lower MoCA scores. Second, we found significant relationships between lower inter-network connectivity between the SN and the basal ganglia network (BGN) and the default mode network (DMN) with lower MoCA scores. These data support our hypothesis about the SN and provide new insights into the brain networks contributing to cognitive impairments in PD.HighlightsCognitive dysfunction is a prominent clinical symptom in Parkinson’s diseaseFunctional connectivity of the salience network is important for cognitionSalience network dynamics are altered in patients with Parkinson’s diseaseSalience network connectivity with other networks is linked to worse cognition in PD

Pathobiology of Cognitive Impairment in Parkinson Disease: Challenges and Outlooks

“…The SAN is composed of the midcingulate cortex and insula and is integrating responses to salient stimuli [ 274 ]; its control over the DMN and FPN is dysregulated in PD and aging [ 275 , 276 ]. The SAN is a key neural substrate of CI in PD [ 277 ]. The basal ganglia network (BGN) is also important, because dopamine deficiency can alter functional brain networks [ 278 , 279 , 280 ].…”

“…Recent rsfMRI studies, using the Parkinson’s Progression Markers Initiative (PPMI), a high-quality database of a large number of PD patients, reported several important findings. (1) There was reduced intra-FPN FC with alterations on posterior parietal nodes in the FPN in PD-CI [ 277 ], which was possibly due to reduced parietal metabolism [ 297 ], whereas there was no evidence of altered SAN-FPN or DMN-FPN connectivity predicting CI [ 196 , 298 ]. (2) PD-CI patients had dysfunctional SAN-BGN and SAN-DMN FC [ 277 ].…”

“…(1) There was reduced intra-FPN FC with alterations on posterior parietal nodes in the FPN in PD-CI [ 277 ], which was possibly due to reduced parietal metabolism [ 297 ], whereas there was no evidence of altered SAN-FPN or DMN-FPN connectivity predicting CI [ 196 , 298 ]. (2) PD-CI patients had dysfunctional SAN-BGN and SAN-DMN FC [ 277 ]. The SAN, according to some, included the left and right prefrontal cortex [ 277 , 299 , 300 ], whereas others did not [ 274 , 298 , 301 ].…”

“…(2) PD-CI patients had dysfunctional SAN-BGN and SAN-DMN FC [ 277 ]. The SAN, according to some, included the left and right prefrontal cortex [ 277 , 299 , 300 ], whereas others did not [ 274 , 298 , 301 ]. These findings indicate a link between SAN FC with other large-scale brain networks and CI in PD, suggesting that positive FC between these networks is necessary for the SAN to disengage the DMN during cognitive control.…”

“…Further analyses revealed differences in the α band in both regions and in θ in the dorsolateral prefrontal cortex, highlighting the involvement of the medial and lateral prefrontal cortex in motivation and cognitive control [ 310 ]. Low-frequency mid-frontal neural activity was associated with cognitive dysfunction [ 311 , 312 , 313 ], while others did not find any relationship between DMN FC and cognition in PD [ 277 ], which may be attributed to the vast heterogeneity of PD [ 281 ].…”