Resting-State Cerebello-Cortical Dysfunction in Parkinson's Disease

Palmer, William C.; Cholerton, Brenna; Zabetian, Cyrus P.; Montine, Thomas J.; Grabowski, Thomas J.; Rane, Swati

doi:10.3389/fneur.2020.594213

Cited by 14 publications

(12 citation statements)

References 44 publications

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“…It should however be noted that functional connectivity cannot accurately assess the directionality of VTA-cerebellar connections. Overall, we corroborate previous findings that the cerebellum may be mediating cognitive function in PD through its interactions across multiple networks in the brain (Gratton et al, 2019; Palmer et al, 2021; Zhang et al, 2016). Importantly, our interpretation is limited to results in resting-state networks.…”

Section: Discussionsupporting

confidence: 91%

Distinct Alterations in Cerebellar Connectivity with Substantia Nigra and Ventral Tegmental Area in Parkinson’s Disease

Olson

et al. 2021

Preprint

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In Parkinsons disease (PD), neurodegeneration of dopaminergic neurons occurs in the midbrain, specifically targeting the substantia nigra (SN), while leaving the ventral tegmental area (VTA) relatively spared in early phases of the disease. Although the SN and VTA are known to be functionally dissociable in healthy adults, it remains unclear how this dissociation is altered in PD. To examine this issue, we performed a whole-brain analysis to compare functional coupling in PD to healthy adults using resting-state fMRI data compiled from three independent datasets. Our analysis showed that across the sample, the SN had greater coupling to the precuneus, anterior cingulate gyrus, and areas of the occipital cortex, partially replicating our previous work in healthy young adults. Notably, we also found that, in PD, VTA-right cerebellum coupling was higher than SN-right cerebellum coupling, whereas the opposite trend occurred in healthy controls. This double dissociation may reflect a compensatory role of the cerebellum in PD and could provide a potential target for future study and treatment.

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Section: Discussionsupporting

confidence: 91%

Distinct Alterations in Cerebellar Connectivity with Substantia Nigra and Ventral Tegmental Area in Parkinson’s Disease

Olson

et al. 2021

Preprint

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“…Neuroimaging studies discovered that cerebellum lobule VIII was predominantly involved in sensorimotor processes and connected with cerebral motor and sensory cortices ( Kipping et al, 2013 ). These results appeared to indicate that PD patients had abnormal sensorimotor functional circuits involving the cerebellum, as described previously ( Palmer et al, 2020 ; Wang S. et al, 2021 ). Nevertheless, the role of the sensorimotor network involving cerebellum in PD is still controversial.…”

Section: Discussionsupporting

confidence: 86%

“… Wang S. et al (2021) considered that the increased FC in the internal cerebellar networks and sensorimotor networks in PD might compensate for the motor control dysfunction to maintain the integrity of the sensorimotor network. Palmer et al (2020) proposed that persistent error detection and correction occurring in the cerebellum of PD patients induced the enhanced cerebello-cortical FC. Simioni et al (2016) advanced a new perspective that the enhanced cerebellar FC in PD patients in mild-to-moderate stages might have a compensatory role but eventually be overwhelmed by the progressive neurodegeneration.…”

Section: Discussionmentioning

confidence: 99%

Altered functional connectivity of cerebellar dentate nucleus in peak-dose dyskinesia in Parkinson’s disease

Zhang

Wang

Gan

et al. 2022

Front. Aging Neurosci.

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The cerebellum is associated with the emergence of levodopa-induced dyskinesia (LID) in Parkinson’s disease (PD), yet the neural mechanism remains obscure. Our aim was to ascertain the role of functional connectivity (FC) patterns of the cerebellar dentate nucleus (DN) in the pathogenesis of peak-dose dyskinesia in PD. Twenty-three peak-dose dyskinetic PD patients, 27 non-dyskinetic PD patients, and 36 healthy controls (HCs) were enrolled and underwent T1-weighted and resting-state functional magnetic resonance imaging (rs-fMRI) scans after dopaminergic medication intake. We selected left and right DN as the regions of interest and then employed voxel-wise FC analysis and voxel-based morphometry analysis (VBM). The correlations between the altered FC pattern and clinical scores were also examined. Finally, receiver operating characteristic (ROC) curve analysis was performed to assess the potential of DN FC measures as a feature of peak-dose dyskinesia in PD. Dyskinetic PD patients showed excessively increased FC between the left DN and right putamen compared with the non-dyskinetic. When compared with controls, dyskinetic PD patients mainly exhibited increased FC between left DN and bilateral putamen, left paracentral lobule, right postcentral gyrus, and supplementary motor area. Additionally, non-dyskinetic PD patients displayed increased FC between left DN and left precentral gyrus and right paracentral lobule compared with controls. Meanwhile, increased FC between DN (left/right) and ipsilateral cerebellum lobule VIII was observed in both PD subgroups. However, no corresponding alteration in gray matter volume (GMV) was found. Further, a positive correlation between the z-FC values of left DN-right putamen and the Unified Dyskinesia Rating Scale (UDysRS) was confirmed in dyskinetic PD patients. Notably, ROC curve analyses revealed that the z-FC values of left DN-right putamen could be a potential neuroimaging feature identifying dyskinetic PD patients. Our findings demonstrated that the excessively strengthened connectivity of DN-putamen might contribute to the pathophysiological mechanisms of peak-dose dyskinesia in PD.

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“…Our findings provide converging evidence that rTMS targeted on the cortical region could modulate the connectivity and its temporal fluctuations between cortical and deep brain regions. These findings may shed new light on the treatment of some movement disorders, which are associated with abnormalities of subcortical regions, such as Parkinson's disease, Huntington's disease and Tourette's syndrome (Garcia‐Gorro et al, 2018; Palmer et al, 2021; Ramkiran et al, 2019; Rodriguez‐Sabate et al, 2019). By applying rTMS over the cortical motor region that showed the strongest connectivity with the damaged subcortical motor regions may lead to better outcomes in patients.…”

Section: Discussionmentioning

confidence: 99%

Repetitive transcranial magnetic stimulation modulates cortical–subcortical connectivity in sensorimotor network

Chen

Fan

Wei

et al. 2021

Eur J of Neuroscience

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Repetitive transcranial magnetic stimulation (rTMS) holds the ability to modulate the connectivity within the stimulated network. However, whether and how the rTMS targeted over the primary motor cortex (M1) could affect the connectivity within the sensorimotor network (SMN) is not fully elucidated. Hence, in this study, we investigated the after‐effects of rTMS over left M1 at different frequencies on connectivity within SMN. Forty‐five healthy participants were recruited and randomly divided into three groups according to rTMS frequencies (high‐frequency [HF], 3 Hz; low‐frequency [LF], 1 Hz; and SHAM). Participants received 1‐Hz, 3‐Hz or sham stimulation and underwent two functional magnetic resonance imaging (fMRI) scanning sessions before and after rTMS intervention. Using resting‐state functional connectivity (FC) approach, we found that high‐ and low‐frequency rTMS had opposing effects on FC within the SMN, especially for connectivity with subcortical regions (i.e., putamen, thalamus and cerebellum). Specifically, the reductions in connectivity between cortical and subcortical regions within cortico‐basal ganglia thalamo‐cortical circuits and the cognitive loop of cerebellum, and increased connectivity between cortical and subdivisions within the sensorimotor loop of cerebellum were observed after high‐frequency rTMS intervention, whereas the thalamus and cognitive cerebellum subdivisions exhibited increased connectivity, and sensorimotor cerebellum subdivisions showed decreased connectivity with stimulated target after low‐frequency stimulation. Collectively, these findings demonstrated the alterations of connectivity within SMN after rTMS intervention at different frequencies and may help to understand the mechanisms of rTMS treatment for movement disorders associated with deficits in subcortical regions such as Parkinson's disease, Huntington's disease and Tourette's syndrome.

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Resting-State Cerebello-Cortical Dysfunction in Parkinson's Disease

Cited by 14 publications

References 44 publications

Distinct Alterations in Cerebellar Connectivity with Substantia Nigra and Ventral Tegmental Area in Parkinson’s Disease

Distinct Alterations in Cerebellar Connectivity with Substantia Nigra and Ventral Tegmental Area in Parkinson’s Disease

Altered functional connectivity of cerebellar dentate nucleus in peak-dose dyskinesia in Parkinson’s disease

Repetitive transcranial magnetic stimulation modulates cortical–subcortical connectivity in sensorimotor network

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