Abnormal Neural Responses During Reflexive Blinking in Blepharospasm: An Event‐Related Functional MRI Study

Abstract

BackgroundThe neurophysiological disruptions underlying blepharospasm, a disabling movement disorder characterized by increased blinking and involuntary muscle spasms of the eyelid, remain poorly understood.ObjectiveTo investigate the neural substrates underlying reflexive blinking in blepharospasm patients compared to healthy controls using simultaneous functional MRI and surface electromyography.MethodsFifteen blepharospasm patients and 15 healthy controls were recruited. Randomly timed air puffs to the left eye were used to induce reflexive eye blinks during two 8‐minute functional MRI scans. Continuous surface electromyography and video recordings were used to monitor blink responses. Imaging data were analyzed using an event‐related design.ResultsFourteen blepharospasm patients (10 female; 61.6 ± 8.0 years) and 15 controls (11 female; 60.9 ± 5.5 years) were included in the final analysis. Reflexive eye blinks in controls were associated with activation of the right hippocampus and in patients with activation of the left caudate nucleus. Reflexive blinks in blepharospasm patients showed increased activation in the right postcentral gyrus and precuneus, left precentral gyrus, and left occipital cortex compared to controls. Dystonia severity negatively correlated with activity in the left occipital cortex, and disease duration negatively correlated with reflexive‐blink activity in the cerebellum.ConclusionsReflexive blinking in blepharospasm is associated with increased activation in the caudate nucleus and sensorimotor cortices, suggesting a loss of inhibition within the sensorimotor corticobasal ganglia network. The association between decreasing neural response during reflexive blinking in the cerebellum with disease duration suggests an adaptive role. © 2020 International Parkinson and Movement Disorder Society

Thalamic structural connectivity profiles in blepharospam/Meige’s syndrome

“…To provide some perspective regarding reported hemispheric lateralization in function networks of potential relevance in the disease, right motor lateralization has been observed in studies on cerebral lesions impairing eyelid function and neuroimaging studies in volitional and spontaneous blinking ( Hanakawa et al, 2008 , van Eimeren et al, 2001 , Yoon et al, 2005 ). Left occipital lateralization is seen during left-lateralized complex task- and attention-dependent visual processing, and left lateralized functional occipital abnormality has been reported across previous fMRI studies in blepharospasm ( Jiang et al, 2019 , Kerrison et al, 2003 , Nguyen et al, 2020 ).…”

“…Regarding functional abnormality in occipital cortices, early event-related functional MRI studies hinted at abnormal involvement in primary/and or associative visual cortices within an abnormally activated visuomotor network related to simple blinking tasks (further including anterior cingulum, primary motor cortex, basal ganglia, and superior cerebellum) ( Baker et al, 2003 ). Recently, increased activity in the occipital associative cortex (in addition to increased primary somatosensory, motor cortical and cerebellar activity) has additionally been demonstrated during reflexive blinking ( Nguyen et al, 2020 ). While increases in visual input interruption in blepharospasm (mirrored by disease severity) and the resulting reduction in quantitative visual input are assumed to lead to reduced relative visual cortex glucose metabolism over time as secondary phenomenon ( Suzuki et al, 2019 ), it remains to date unclear if quantitively comparable visual input is processed differently in the disease.…”

“…Some of those studies had investigated connectivity profiles of the posterior-parietal and occipital lobe either separately ( Behrens et al, 2003a , Giraldo-Chica et al, 2018 ) or in combination ( Nair et al, 2013 , Zhang et al, 2010 ). We opted for the separate approach to discriminate potential parietal and occipital findings in light of previous functional neuroimaging observations of both abnormal connectivity profiles of occipital cortices at rest ( Jochim et al, 2018a ), and abnormal occipital activity in task activation studies related to blinking ( Baker et al, 2003 , Nguyen et al, 2020 ) or visual processing ( Suzuki et al, 2019 ). The thalamic target ROI comprised the entire thalamus including the corpus geniculatum mediale et laterale.…”

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

“…However, several recent investigations have noted abnormal precuneus function and structure in LD and other focal dystonias, such as blepharospasm, Meige syndrome, and cervical and musician's dystonias. [26][27][28][29][30][31] Evidence from these studies suggests that precuneus alterations may play a role in subtle deficits of cognitive function in patients with dystonia, including impaired visuospatial attention, 32,33 temporal discrimination, 29,34 motor imagery, or spatially guided behaviors. 35 It is plausible that restoration of precuneus activity with BoNT treatment, as shown in this study, might have an impact on improved cognitive function in these patients.…”

“…The role of precuneus in the pathophysiology of dystonia remains elusive as this region has been, by and large, out of focus of studies investigating major basal ganglia-thalamosensorimotor and cerebellar impairments in this disorder. However, several recent investigations have noted abnormal precuneus function and structure in LD and other focal dystonias, such as blepharospasm, Meige syndrome, cervical and musician's dystonias [26][27][28][29][30][31] . Evidence from these studies suggests that precuneus alterations may play a role in subtle deficits of cognitive function in dystonia patients, including impaired visuospatial attention 32,33 , temporal discrimination 29,34 , motor imagery or spatially guided behaviors 35 .…”