Altered functional network topology correlates with clinical measures in very early-stage, drug-naïve Parkinson's disease

Sreenivasan, Karthik; Mishra, Virendra; Bird, Christopher; Zhuang, Xiaowei; Yang, Zhiguo; Cordes, Dietmar; Walsh, Ryan R.

doi:10.1016/j.parkreldis.2019.02.001

Cited by 24 publications

(34 citation statements)

References 32 publications

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Section: Sample Size and Statistical Analysesmentioning

confidence: 99%

“…In several recent publications on suitable sample sizes for functional neuroimaging studies using graph theory analysis, it has been found that a group size of approximately 20 is sufficient (Gargouri et al, 2016;Sreenivasan et al, 2019). Finally, the partial correlation coefficient was used to analyze the correlations between the ROIs that showed intergroup differences and both the cognitive domains (neuropsychological assessment composites) and the clinical variables (duration and severity of disease) in ET patients, controlling the effect of age and sex.…”

Section: Sample Size and Statistical Analysesmentioning

confidence: 99%

“…Graph theory analysis also provides regional metrics to define the connectivity properties of particular brain regions, such as their connections with the rest of the brain, the length of these connections or the relationship with their nearest regions (Wang, Li, Metzak, He, & Woodward, 2010). Unlike previous techniques, graph theory approach permits one to not only visualize the overall connectivity pattern among all the brain regions, but also to quantitatively characterize the global organization (Medaglia, 2017; providing a novel insight into the biological mechanisms of many neurological diseases, such as mild cognitive impairment and Alzheimer's disease (Khazaee, Ebrahimzadeh, & Babajani-Feremi, 2016), epilepsy (Chiang, Stern, Engel Jr., Levin, & Haneef, 2014), Huntington's disease (Gargouri et al, 2016), and Parkinson's disease (Gottlich et al, 2013;Sreenivasan et al, 2019;Zhang, Liu, Chen, Liu, & Wang, 2015), among others. Only one previous study applied graph theory analysis to longitudinal rs-fMRI data in eight ET patients before and after a focal lesion in the ventralis intermedius nucleus of the thalamus, using MRI-guided high-intensity focused ultrasound.…”

Section: Introductionmentioning

confidence: 99%

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Graph theory analysis of resting‐state functional magnetic resonance imaging in essential tremor

Benito‐León

Sanz‐Morales

Melero

et al. 2019

Human Brain Mapping

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Essential tremor (ET) is a neurological disease with both motor and nonmotor manifestations; however, little is known about its underlying brain basis. Furthermore, the overall organization of the brain network in ET remains largely unexplored. We investigated the topological properties of brain functional network, derived from resting‐state functional magnetic resonance imaging (MRI) data, in 23 ET patients versus 23 healthy controls. Graph theory analysis was used to assess the functional network organization. At the global level, the functional network of ET patients was characterized by lower small‐worldness values than healthy controls—less clustered functionality of the brain. At the regional level, compared with the healthy controls, ET patients showed significantly higher values of global efficiency, cost and degree, and a shorter average path length in the left inferior frontal gyrus (pars opercularis), right inferior temporal gyrus (posterior division and temporo‐occipital part), right inferior lateral occipital cortex, left paracingulate, bilateral precuneus bilaterally, left lingual gyrus, right hippocampus, left amygdala, nucleus accumbens bilaterally, and left middle temporal gyrus (posterior part). In addition, ET patients showed significant higher local efficiency and clustering coefficient values in frontal medial cortex bilaterally, subcallosal cortex, posterior cingulate cortex, parahippocampal gyri bilaterally (posterior division), right lingual gyrus, right cerebellar flocculus, right postcentral gyrus, right inferior semilunar lobule of cerebellum and culmen of vermis. Finally, the right intracalcarine cortex and the left orbitofrontal cortex showed a shorter average path length in ET patients, while the left frontal operculum and the right planum polare showed a higher betweenness centrality in ET patients. In conclusion, the efficiency of the overall brain functional network in ET is disrupted. Further, our results support the concept that ET is a disorder that disrupts widespread brain regions, including those outside of the brain regions responsible for tremor.

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Section: Sample Size and Statistical Analysesmentioning

confidence: 99%

Section: Sample Size and Statistical Analysesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Graph theory analysis of resting‐state functional magnetic resonance imaging in essential tremor

Benito‐León

Sanz‐Morales

Melero

et al. 2019

Human Brain Mapping

View full text Add to dashboard Cite

show abstract

“…These analyses have shown significant changes in the global efficiency, local efficiency and clustering coefficient in the whole brain [2,26] or within specific networks in PD patients [36,39,64]. Changes in the nodal network topology of prefrontal and supplementary motor areas as well as the striatum and thalamus [16,38,55,67] have also been reported in PD patients, sometimes in association with clinical measures [37,56].…”

Section: Introductionmentioning

confidence: 87%

Directed brain connectivity identifies widespread functional network changes in Parkinson’s disease

Mijalkov

Volpe

Pereira

2021

Preprint

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Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by topological changes in large-scale functional brain networks. These networks are commonly analysed using undirected correlations between the activation signals of brain regions. However, this approach suffers from an important drawback: it assumes that brain regions get activated at the same time, despite previous evidence showing that brain activation features causality, with signals being typically generated in one region and then propagated to other ones. Thus, in order to address this limitation, in this study we developed a new method to assess whole-brain directed functional connectivity in patients with PD and healthy controls using anti-symmetric delayed correlations, which capture better this underlying causality. To test the potential of this new method, we compared it to standard connectivity analyses based on undirected correlations. Our results show that whole-brain directed connectivity identifies widespread changes in the functional networks of PD patients compared to controls, in contrast to undirected methods. These changes are characterized by increased global efficiency, clustering and transitivity as well as lower modularity. In addition, changes in the directed connectivity patterns in the precuneus, thalamus and superior frontal gyrus were associated with motor, executive and memory deficits in PD patients. Altogether, these findings suggest that directional brain connectivity is more sensitive to functional network changes occurring in PD compared to standard methods. This opens new opportunities for the analysis of brain connectivity and the development of new brain connectivity markers to track PD progression.

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“…fMRI revealed altered functional connectivity in cortical and subcortical regions, particularly in striatum, of PD patients (Hacker et al, 2012). These alterations occurred very early and were not associated with tremor manifestation, but varied depending on disease stage, PD subtype, and pharmacological treatment (Sreenivasan et al, 2019). The main problem of this application in rodents is represented by the small size of the mouse and rat brains.…”

Section: Pet Imaging Of Other Neuronal Targetsmentioning

confidence: 99%

Translation Imaging in Parkinson’s Disease: Focus on Neuroinflammation

Belloli

Morari

Murtaj

et al. 2020

Front. Aging Neurosci.

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Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the appearance of α-synuclein insoluble aggregates known as Lewy bodies. Neurodegeneration is accompanied by neuroinflammation mediated by cytokines and chemokines produced by the activated microglia. Several studies demonstrated that such an inflammatory process is an early event, and contributes to oxidative stress and mitochondrial dysfunctions. α-synuclein fibrillization and aggregation activate microglia and contribute to disease onset and progression. Mutations in different genes exacerbate the inflammatory phenotype in the monogenic compared to sporadic forms of PD. Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) with selected radiopharmaceuticals allow in vivo imaging of molecular modifications in the brain of living subjects. Several publications showed a reduction of dopaminergic terminals and dopamine (DA) content in the basal ganglia, starting from the early stages of the disease. Moreover, non-dopaminergic neuronal pathways are also affected, as shown by in vivo studies with serotonergic and glutamatergic radiotracers. The role played by the immune system during illness progression could be investigated with PET ligands that target the microglia/macrophage Translocator protein (TSPO) receptor. These agents have been used in PD patients and rodent models, although often without attempting correlations with other molecular or functional parameters. For example, neurodegeneration and brain plasticity can be monitored using the metabolic marker 2-Deoxy-2-[ 18 F]fluoroglucose ([ 18 F]-FDG), while oxidative stress can be probed using the copper-labeled diacetyl-bis(N-methyl-thiosemicarbazone) ([Cu]-ATSM) radioligand, whose striatal-specific binding ratio in PD patients seems to correlate with a disease rating scale and motor scores. Also, structural and functional modifications during disease progression may be evaluated by Magnetic Resonance Imaging (MRI), using different parameters as iron content or cerebral volume. In this review article, we propose

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Altered functional network topology correlates with clinical measures in very early-stage, drug-naïve Parkinson's disease

Cited by 24 publications

References 32 publications

Graph theory analysis of resting‐state functional magnetic resonance imaging in essential tremor

Graph theory analysis of resting‐state functional magnetic resonance imaging in essential tremor

Directed brain connectivity identifies widespread functional network changes in Parkinson’s disease

Translation Imaging in Parkinson’s Disease: Focus on Neuroinflammation

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