Brain connectivity abnormalities and treatment‐induced restorations in patients with cervical dystonia

Abstract

Background The relationship between brain abnormalities and phenotypic characteristics in cervical dystonia (CD) patients has not been fully established, and little is known about the neuroplastic changes induced by botulinum toxin type A (BoNT‐A) treatment. Methods Ninety‐two CD patients presenting with rotational torticollis and 45 healthy controls from our database were retrospectively screened. After clinical assessment, the 92 patients underwent baseline magnetic resonance imaging (MRI) followed by a single‐dose injection of BoNT‐A. Four weeks later, 76 out of the 92 patients were re‐evaluated with the Tsui scale for dystonia severity, and 33 out of 76 patients completed post‐treatment MRI scanning. Data‐driven global brain connectivity and regional homogeneity in tandem with seed‐based connectivity analyses were used to examine the functional abnormalities in CD and longitudinal circuit alterations that scaled with clinical response to BoNT‐A. Multiple regression models were employed for the prediction analysis of treatment efficacy. Results Cervical dystonia patients exhibited elevated baseline connectivity of the right postcentral gyrus with the left dorsomedial prefrontal cortex and right caudate nucleus, which was associated with their symptom severity. BoNT‐A reduced excessive functional connectivity between the sensorimotor cortex and right superior frontal gyrus, which was significantly correlated with changes in Tsui score. Moreover, pre‐treatment regional homogeneity of the left middle frontal gyrus was linearly related to varied response to treatment. Conclusions Our findings unravel dissociable connectivity of the sensorimotor cortex underlying the pathology of CD and central effects of BoNT‐A therapy. Furthermore, baseline regional homogeneity with the left middle frontal gyrus may represent a potential evidence‐based marker of patient stratification for BoNT‐A therapy in CD.

Is Resting State Functional MRI Effective Connectivity in Movement Disorders Helpful? A Focused Review Across Lifespan and Disease

“…While this proves challenging for DBS (a pre-post FC design is technically difficult due to the challenges of MRI after DBS including both safety and susceptibility artifact introduced from DBS lead sites), there have been some observational studies investigating FC changes after treatment with botulinum toxin in focal (cervical) dystonia and blepharospasm. 26,27,[35][36][37] Taken together, these studies demonstrate that brain network changes associated with clinical treatment in movement disorders can be respectively measured with FC.…”

Altered brain connectivity in hyperkinetic movement disorders: A review of resting-state fMRI

“…For dystonia, 46 articles were included, ( Zhang et al, 2020 , Pan et al, 2019 , Jochim et al, 2018 , Putzel et al, 2018 , Mantel et al, 2018 , Ni et al, 2017 , Huang et al, 2017 , Li et al, 2017 , Long et al, 2017 , Haslinger et al, 2017 , Kiyuna et al, 2017 , Battistella et al, 2016 , Sarasso et al, 2020 , Liu et al, 2016 , Ren et al, 2015 , Bharath et al, 2015 , Dresel et al, 2014 , Delnooz et al, 2015 , Hinkley et al, 2013 , Delnooz et al, 2013 , Delnooz et al, 2012 , Mohammadi et al, 2012 , Wei et al, 2021 , Jiang et al, 2019 , Pan et al, 2021 , Feng e al., 2021 , de Faria et al, 2020 , Norris et al, 2020 , Glickman et al, 2020 , Mantel et al, 2020 , Ma et al, 2021 , Corp et al, 2019 , Fang et al, 2021 , Giannì et al, 2022 , Qin et al, 2019 , Zito et al, 2022 , Kim et al, 2022 , Hou et al, 2022 , Ekmen et al, 2022 , Nieuwhof et al, 2022 , Filip et al, 2022 , Battistella and Simonyan, 2019 , Bianchi et al, 2019 , Kita et al, 2018 , Fuertinger and Simonyan, 2018 , Qin et al, 2018 ) concerning cervical dystonia (CD; n = 14), writer’s cramp (n = 10), laryngeal dystonia (n = 8), musician's dystonia (n = 5), paroxysmal kinesigenic dyskinesia (n = 6), blepharospasm (n = 6), oromandibular dystonia (n = 2), dyskinetic cerebral palsy (n = 2), spastic cerebral palsy (n = 1), dystonic tremor (n = 1), and generalized dystonia (n = 1). Most studies matched patients and healthy participants for age and gender.…”

“…Of the 26 studies investigating the relationship between clinical measures and resting-state brain connectivity, 10 found no significant correlation. Eight studies describe positive relationships between motor severity and brain function: 1) FC between the left and right calcarine cortex and in the SMA; ( Qin et al, 2019 ) 2) fALFF and ReHo in the caudate nucleus; ( Ni et al, 2017 ) 3) FC between both caudate nuclei; ( Ni et al, 2017 ) 4) FC between thalamus and caudate nucleus; ( Kiyuna et al, 2017 ) 5) FC between precentral gyrus and insula, dorsolateral prefrontal cortex, postcentral gyrus, and thalamus; ( Dresel et al, 2014 ) 6) ReHo in cerebellum; ( Wei et al, 2021 ) 7) FC between prefrontal cortex and postcentral gyrus, and between postcentral gyrus and caudate nucleus; ( Feng, 2021 ) 8) connectivity in the cerebellum; ( Glickman et al, 2020 ) 9) FC in supramarginal gyrus and postcentral gyrus. ( Ma et al, 2021 ) Conversely, three studies describe negative relationships between motor severity and brain function: 1) FC between both SMA; ( Jiang et al, 2019 ) 2) FC between cerebellum and visual cortex; ( Jochim et al, 2018 ) 3) FC in the superior parietal cortex.…”

Short- and Long-term Central Action of Botulinum Neurotoxin Treatment in Laryngeal Dystonia

“… 34 , 44 , 45 In other forms of dystonia, increased gray matter volume and decreased functional connectivity of middle frontal gyrus have been reported in blepharospasm, 46 , 47 its reduced structural connectivity with the basal ganglia and increased activity after positive feedback learning found in writer's cramp, 48 , 49 and pretreatment homogeneity related to varied response to BoNT injections identified in cervical dystonia. 50 By modulating middle frontal activity, BoNT treatment in these patients may have a cascading effect on the frontoparietal network activity and, hence, the control of higher-order executive function during learning and coordination of the correct sequences of complex motor behaviors, such as speech production.…”

“…Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. dystonia 50 . By modulating middle frontal activity, BoNT treatment in these patients may have cascading effects on frontoparietal network activity and, hence, the control of higher-order executive function during learning and coordination of the correct sequences of complex motor behaviors, such as speech production.…”