Default mode network differences between rigidity- and tremor-predominant Parkinson's disease

Abstract

Background Parkinson's disease (PD) traditionally is characterized by tremor, rigidity, and bradykinesia, although cognitive impairment also is a common symptom. The clinical presentation of PD is heterogeneous and associated with different risk factors for developing cognitive impairment. PD patients with primary akinetic/rigidity (PDAR) are more likely to develop cognitive deficits compared to those with tremor-predominant symptoms (PDT). Because cognitive impairment in PD appears to be related to changes in the default mode network (DMN), this study tested the hypothesis that DMN integrity is different between PDAR and PDT subtypes. Method Resting state fMRI (rs-fMRI) and whole brain volumetric data were obtained from 17 PDAR, 15 PDT and 24 healthy controls (HCs) using a 3T scanner. PD patients were matched closely to HCs for demographic and cognitive variables, and showed no symptoms of dementia. Voxel-based morphometry (VBM) was used to examine brain gray matter (GM) volume changes between groups. Independent component analysis (ICA) interrogated differences in the DMN among PDAR, PDT, and HC. Results There was decreased activity in the left inferior parietal cortex (IPC) and the left posterior cingulate cortex (PCC) within the DMN between PDAR and both HC and PDT subjects, even after controlling for multiple comparisons, but not between PDT and HC. GM volume differences between groups were detected at a lower threshold (p < 0.001, uncorrected). Resting state activity in IPC and PCC were correlated with some measures of cognitive performance in PD but not in HC. Conclusion This is the first study to demonstrate DMN differences between cognitively comparable PDAR and PDT subtypes. The DMN differences between PD and HC appear to be driven by the PDAR subtype. Further studies are warranted to understand the underlying neural mechanisms and their relevance to clinical and cognitive outcomes in PDAR and PDT subtypes.

Functional Connectivity Signatures of Parkinson’s Disease

“…Non-motor RSNs changes were also revealed by comparing different PD motor phenotypes. Indeed, a decreased functional connectivity within the DMN has been revealed in cognitively unimpaired akineticdominant PD patients compared to both tremor dominant patients and controls [57,58], confirming that different motor phenotypes may be related to a distinctive underlying pathophysiology, coupled with a divergent risk profile for the development of cognitive impairment [59,60]. In this framework, the presence of freezing of gait, which is considered a clinical biomarker of worse disease progression and earlier development of cognitive impairment, has been consistently associated with specific involvement of cognition and attentionrelated RSNs, encompassing frontal, parietal and temporo-occipital areas [61][62][63].…”

Changing views of the pathophysiology of Parkinsonism

“…[111][112][113][114] Although the polarity of changes is not entirely consistent between studies, imaging experiments have shown that frontal and parietal cortical activity are altered in rigid parkinsonian patients. 115,116 For example, in studies of default-mode network expression in resting-state functional MRI (fMRI) experiments, the connectivity of posterior cortical network components was found to be reduced whereas that of frontal cortical components of the network was pathologically increased. 117,118 An interpretational issue with these and similar studies is, of course, that rigidity does not develop in isolation.…”

Resting‐state Functional MRI in Parkinsonian Syndromes

“…FMRI studies showed that tremor‐dominant patients, relative to patients without tremor, had increased functional connectivity between striatal nuclei (particularly globus pallidus internal) and the cerebello‐thalamocortical circuit, which was associated with more severe tremor . On the contrary, relative to patients with tremor, cognitively unimpaired akinetic/rigid PD patients are characterized by a decreased functional connectivity of cognitive networks, such as the default mode network . An early involvement of the default mode network could be the reason why akinetic/rigid PD patients are more prone to develop cognitive deficits along the disease course .…”