Brain structural connectome in relation to <scp>PRRT2</scp> mutations in paroxysmal kinesigenic dyskinesia

Li, Lei; Lei, Du; Suo, Xueling; Li, Xiuli; Yang, Chen; Yang, Tianhua; Ren, Jiechuan; Chen, Guangxiang; Zhou, Dong; Kemp, Graham J.; Gong, Qiyong

doi:10.1002/hbm.25091

Cited by 11 publications

(17 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results may relate to alterations of GM structure, for which there is some evidence in PKD: direct evidence from high‐resolution T1‐weighted MRI studies have identified morphometric/volumetric GM changes in presupplementary motor area, inferior frontal gyrus (H. F. Li et al, 2019) and thalamus (Kim et al, 2015); indirect evidence from secondary PKD reported that PKD was associated with various brain abnormalities for example, in thalamus (Camac, Greene, & Khandji, 1990), putamen (Merchut & Brumlik, 1986), right frontotemporal region (Gilroy, 1982), and globus pallidus (Micheli, Fernandez Pardal, Casas Parera, & Giannaula, 1986). Our morphological network findings are consistent with a structural brain network study using DTI, which showed “weaker small‐worldness” in PKD (L. Li et al, 2020). However, there was no significant change in functional global network properties in a study of drug‐naïve PKD patients using resting‐state functional MRI (Y. Zhang et al, 2020).…”

Section: Discussionsupporting

confidence: 91%

Disruption of gray matter morphological networks in patients with paroxysmal kinesigenic dyskinesia

Lei

Niu

et al. 2020

Human Brain Mapping

Self Cite

View full text Add to dashboard Cite

This study explores the topological properties of brain gray matter (GM) networks in patients with paroxysmal kinesigenic dyskinesia (PKD) and asks whether GM network features have potential diagnostic value. We used 3D T1-weighted magnetic resonance imaging and graph theoretical approaches to investigate the topological organization of GM morphological networks in 87 PKD patients and 115 age-and sex-matched healthy controls. We applied a support vector machine to GM morphological network matrices to classify PKD patients versus healthy controls. Compared with the HC group, the GM morphological networks of PKD patients showed significant abnormalities at the global level, including an increase in characteristic path length (Lp) and decreases in local efficiency (E loc), clustering coefficient (Cp), normalized clustering coefficient (γ), and small-worldness (σ). The decrease in Cp was significantly correlated with disease duration and age of onset. The GM morphological networks of PKD patients also showed significant changes in nodal topological characteristics, mainly in the basal ganglia-thalamus circuitry, default-mode network and central executive network. Finally, we used the GM morphological network matrices to classify individuals as PKD patients versus healthy controls, achieving 87.8% accuracy. Overall, this study demonstrated disruption of GM morphological Xiuli Li and Du Lei contributed to the work equally.

show abstract

Section: Discussionsupporting

confidence: 91%

Disruption of gray matter morphological networks in patients with paroxysmal kinesigenic dyskinesia

Lei

Niu

et al. 2020

Human Brain Mapping

Self Cite

View full text Add to dashboard Cite

show abstract

“…Three studies have investigated structural abnormalities in patients with PKD using other techniques. Two of them used graph theory applied on structural covariance of GMV 35 and white matter properties 36 but did not include the cerebellum in the construction of the morphologic network used in the analyses. The remaining study investigated the basal ganglia and found a decrease in GMV and white matter abnormalities in the medial thalamus in patients with PKD.…”

Section: Discussionmentioning

confidence: 99%

Cerebellum Dysfunction in Patients With PRRT2 -Related Paroxysmal Dyskinesia

et al. 2022

View full text Add to dashboard Cite

Background and Objectives:The main culprit gene for paroxysmal kinesigenic dyskinesia, characterized by brief and recurrent attacks of involuntary movements, is PRRT2. The location of the primary dysfunction associated with paroxysmal dyskinesia remains a matter of debate and may vary depending on the etiology. While striatal dysfunction has often been implicated in these patients, evidence from preclinical models indicate that the cerebellum could also play a role. We aimed to investigate the role of the cerebellum in the pathogenesis of PRRT2-related dyskinesia in humans.Methods:We enrolled 22 consecutive right-handed patients with paroxysmal kinesigenic dyskinesia with a pathogenic variant of PRRT2, and their matched controls. Participants underwent a multi-modal neuroimaging protocol. We recorded anatomic and diffusion-weighted MRI, as well as resting-state functional MRI during which we tested the after-effects of sham and repetitive transcranial magnetic stimulation applied to the cerebellum on endogenous brain activity. We quantified: (i) the structural integrity of gray matter using voxel-based morphometry; (ii) the structural integrity of white matter using fixel-based analysis; (iii) the strength and direction of functional cerebellar connections using spectral dynamic causal modeling.Results:PRRT2 patients had: (i) decreased gray matter volume in the cerebellar lobule VI and in the medial prefrontal cortex; (ii) microstructural alterations of white matter in the cerebellum and along the tracts connecting the cerebellum to the striatum and the cortical motor areas; (iii) dysfunction of cerebellar motor pathways to the striatum and the cortical motor areas, as well as abnormal communication between the associative cerebellum (Crus I) and the medial prefrontal cortex. Cerebellar stimulation modulated communication within the motor and associative cerebellar networks, and tended to restore this communication to the level observed in healthy controls.Discussion:Patients with PRRT2-related dyskinesia have converging structural alterations of the motor cerebellum and related pathways with a dysfunction of cerebellar output towards the cerebello-thalamo-striato-cortical network. We hypothesize that abnormal cerebellar output is the primary dysfunction in patients with a PRRT2 pathogenic variant, resulting in striatal dysregulation and paroxysmal dyskinesia. More broadly, striatal dysfunction in paroxysmal dyskinesia might be secondary to aberrant cerebellar output transmitted by thalamic relays in certain disorders.Clinical trial number:NCT03481491 (https://ichgcp.net/clinical-trials-registry/NCT03481491)

show abstract

“…39 Li et al investigated the topological characteristics of white matter structural networks and found decreased nodal characteristics in the left thalamus and left inferior frontal gyrus. 40 These studies further confirmed that the thalamo-cortical connectivity abnormality plays an important role in the pathophysiological mechanisms of PKD.…”

Section: Dti and Structural Mrimentioning

confidence: 59%

“…Long et al combined fMRI and DTI studies and found that the functional connectivity and structural connectivity between the ventrolateral/anterior thalamic nucleus and the motor cortex of PKD patients were significantly enhanced 39 . Li et al investigated the topological characteristics of white matter structural networks and found decreased nodal characteristics in the left thalamus and left inferior frontal gyrus 40 . These studies further confirmed that the thalamo‐cortical connectivity abnormality plays an important role in the pathophysiological mechanisms of PKD.…”

Section: Neuroimaging Studies Of Pkdmentioning

confidence: 95%

Neural Mechanisms of Paroxysmal Kinesigenic Dyskinesia: Insights from Neuroimaging

Liu

Yan

Tian

et al. 2020

Journal of Neuroimaging

Self Cite

View full text Add to dashboard Cite

Paroxysmal kinesigenic dyskinesia (PKD) is a rare movement disorder of the nervous system, and little is known about its pathogenesis. Currently, the diagnosis of PKD is primarily based on clinical manifestations, with little objective evidence. Neuroimaging has been used to explore the pathological changes in cerebral structure and function associated with PKD. The current review highlights recent advances in neuroimaging to provide a better understanding of the neural mechanisms and early diagnosis of this disorder. Several studies utilizing single-photon emission computed tomography (CT), positron emission tomography, and structural and functional magnetic resonance imaging have found significant localized abnormalities in the caudate nucleus, putamen, pallidum, thalamus, and frontoparietal cortex in PKD patients. These studies have also revealed alterations in interhemispheric functional connectivity between the brain regions of bilateral cerebral hemispheres such as the putamen, primary motor cortex, supplementary motor area, dorsal lateral prefrontal cortex, and primary somatosensory cortex in these patients. In addition, proline-rich transmembrane protein 2 gene mutations can affect the functional organization of the brain in PKD. These results suggest that the neural mechanisms of PKD are associated with the disruption of both structural and/or functional properties in basal ganglia-thalamo-cortical circuitry and interhemispheric functional connectivity. PKD can be considered a circuitry/network disorder and is not restricted to localized structural and/or functional abnormalities. Multimodal neuroimaging combined with gene analysis can provide additional valuable information for a better understanding of the pathogenesis and early diagnosis of this disorder.

show abstract

Brain structural connectome in relation to PRRT2 mutations in paroxysmal kinesigenic dyskinesia

Cited by 11 publications

References 67 publications

Disruption of gray matter morphological networks in patients with paroxysmal kinesigenic dyskinesia

Disruption of gray matter morphological networks in patients with paroxysmal kinesigenic dyskinesia

Cerebellum Dysfunction in Patients With PRRT2 -Related Paroxysmal Dyskinesia

Neural Mechanisms of Paroxysmal Kinesigenic Dyskinesia: Insights from Neuroimaging

Contact Info

Product

Resources

About