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Editor—Summer Leaf
Blepharospasm (BSP) is one of the most common types of dystonia, characterized by frequent, symmetrical, involuntary spasms of the eyelids, which can cause difficulty opening eyes, facial deformation, and functional blindness
。 However, its etiology and pathophysiology have not been fully elucidated, and the clinical treatment methods are relatively limited
.
Conventional wisdom holds that BSP is primarily associated with structural and functional disturbances in the basal ganglia [1,2].
In recent years, with the development of neuroimaging and neuropsychology, existing studies generally believe that BSP is a disorder of brain network connections [3], involving changes in brain structure other than basal ganglia such as sensorimotor cortex, thalamus, cerebellum, and brainstem [4-6].
Two brain circuits that may be associated include the sensorimotor cortex-basal ganglia-thalamus-sensorimotor cortex circuit and the sensorimotor cortex-cerebellum -Thalamus-sensorimotor cortical circuit[7].
However, most previous studies have been small, inconsistent, and neglected to explore patterns
of brain circuit changes associated with the course or severity of BSP disease.
In addition, BSP-related brain changes are complex, and in addition to the mechanism of the disease itself, excessive movement of the face can also cause secondary changes
in the brain.
Therefore, whether the changes in brain structure or circuitry found in previous studies are caused by the disease itself or by excessive facial movement still need to be further clarified
.
In September 2022, Liu Gang's team from the First Affiliated Hospital of Sun Yat-sen University and Hu Qingmao's team at the Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, delivered a presentation on Brain The research paper "Supplementary motor area driving changes of structural brain network in blepharospasm" reveals the supplementary motor area SMA) may be an area of pathological damage in the early stages of BSP, which acts as the "driving core" of gray matter volume changes that make BSP The increase in gray matter volume gradually expanded to the cortex-basal ganglia-brainstem motor pathway and the cortical region of the visual-sensorimotor integration pathway with the prolongation of the disease course, challenging the traditional view
that BSP is mainly due to basal ganglia damage.
At the same time, the results also provide new and effective evidence
for BSP as a brain network connection disorder disease.
The results of this study are expected to achieve clinical translation, providing new and potential therapeutic targets for non-invasive neuromodulation in the treatment of dystonia
.
Associate Prof.
Jinping Xu, M.
S.
Yuhan Luo and Prof.
Kangqiang Peng are the co-first authors of the paper, and Prof.
Gang Liu and Prof.
Qingmao Hu are the corresponding authors
.
such as disease course and disease severity scale evaluation were completed.
First, the study used voxel-based morphometry (VBM) to explore BSP The gray matter volume changes mode
.
In order to reduce the influence of confounders, the researchers used age and sex as covariates, and found that when compared with HFS patients and HCs, BSP patients had left and right SMA The volume of gray matter increased significantly, while no significant difference was seen between patients with HFS and HCs (Figure 1).
In further structural covariance network analysis (SCN), it was found that when compared with HCs, The increase in the volume of gray matter in the right side of SMA in BSP patients was significantly synergistic with
the increase in gray matter volume in the right brain stem, left superior frontal gyrus, left SMA and left paracentral gyrus.
Previous neuroimaging studies have also observed a significant increase in gray matter volume, spontaneous neural activity, and functional connections in patients with BSP [8-10], and these results have consistently confirmed SMA It is of great significance
in the pathophysiology of BSP.
However, unlike Suzuki et al.
's inference based on studies that did not include HFS patients as controls, the increase in gray matter volume is a secondary alteration of facial hyperkinesis in BSP patients [11].
The study suggests that the increase in gray matter volume in SMA is likely due
to the mechanism of the disease itself.
Fig.
1 Comparison of gray matter volume between three groups
(Source: Xu, JP.
et al.
, Brain, 2022）
for elucidating the pathophysiological mechanism related to dystonia.
In addition, the researchers used modular analysis to discover two brain circuits that originate from right-sided SMA, including right-sided SMA-right-putamen/left-mid-occipital gyrus- Right brainstem-right tarar gyrus (SMA.
R-PUT.
R/MOG.
L-BS.
R-CAL.
R) Pathway (Figure 2A) and right SMA-right lingual gyrus-left lingual gyrus/left parietal gyrus - Right SMA/Right superior frontal gyrus-Right SMA/Right anterior central gyrus (SMA.
R-LING.
R-LING.
L/SPG.
L-SMA.
R/SFG.
R-SMA.
R/PreCG.
R) pathway (Figure 2B), indicating that with the prolongation of the course of the disease, the gray matter volume increase of BSP gradually expanded to the cortical and subcortical regions involved in the above two circuits under the drive of SMA on the right side, respectively.
Again, strong evidence
is provided for the conclusion that SMA is an early pathological damage area of BSP.
The above results suggest that SMA can be used as a new potential therapeutic target for non-invasive neuromodulation in BSP patients, and its effectiveness
can be further verified by prospective studies of large samples, randomized and sham stimulus controls in the future.
Fig.
2 Granger causal structure covariate network analysis combined with modular analysis and functional coding analysis results (Source: Xu, JP.
et al.
, Brain, 2022).
Based on the above findings, the researchers further clarified the functions of the above pathways with the help of
functional coding analysis.
The results showed that SMA.
R-PUT.
R/MOG.
L-BS.
R-CAL.
R is mainly related to motor execution and visual movement (Figure 2C).
This pathway has been reported to belong to the cortico-basal ganglia pathway [12,13], and involves multiple brain regions such as SMA, putamen, brainstem, and talar gyrus that are closely related to activities such as eye movements, blinking reflexes, and orbicularis oculi muscle contraction [14-16].
。 Therefore, the investigators concluded that the excessive, involuntary spasms of the eyelids in BSP patients may be due to
dysfunction of the cortical-basal ganglia pathway.
And SMA.
R-LING.
R-LING.
L/SPG.
L-SMA.
R/SFG.
R-SMA.
The R/PreCG.
R pathway is mainly related to motor learning and visual motor information integration (Figure 2D).
Among them, the lingual gyrus plays a role in visual attention, and the intensity of blepharospasm in BSP patients is significantly positively correlated with its activity[3]; The superior parietal gyrus also plays an important role in the integration of somatosensory and visual-motor information [17].
At the same time, patients with BSP have been clinically observed to have sensory trickery and paresthesia, such as dry eyes and photophobia
.
Based on the above views and findings, the researchers deduced that the abnormality of this pathway may be secondary changes caused by the loss of functional vision caused by the continuous closure of the eyelids in BSP patients, mainly related to
the paresthesias of BSP.
Notably, the pattern of structural changes in the brain over time found in the study is based on "pseudo-time series" findings of the course of the disease, rather than true time series
from longitudinal studies.
Previous studies have pointed out heterogeneity in the clinical presentation of patients with BSP, with different subtypes of BSP having different spasticity patterns, spasticity severity, and tendency to spread [18].
However, in a five-year follow-up study, clinical heterogeneity in BSP does not imply different pathophysiology, and that different patterns of progression are driven by common pathophysiology [19].
At the same time, caSCN analysis using "pseudo-time series" based on the course of disease has been successfully used to explore temporal lobe epilepsy, schizophrenia, depression, and generalized anxiety disorder [20-23].
and other neuropsychiatric diseases have led to new prospective research results
.
The above evidence shows that caSCN analysis based on disease course can be used to construct a temporal causal model of brain structure changes in BSP, and the results of real time series based on longitudinal studies will further verify its reliability
in the future.
In summary, studies have shown that the auxiliary motor zone (SMA) may be an area of pathological damage in the early stages of blepharospasm (BSP), and as the course of the disease prolongs, the increase in gray matter volume gradually expands to the cortex-, driven by the right SMA The basal ganglia-brainstem motor pathway region and the cortical region of the visual-sensorimotor integration pathway suggest that BSP has a pattern
of abnormal changes in brain structure based on the progression of the disease.
The results of the study add new objective evidence for BSP as a disorder of brain network connection, and are also expected to provide a potential therapeutic target for non-invasive neuromodulation in the treatment of dystonia and achieve clinical translation
.
The study also has some limitations
.
Firstly, the covariate network analysis of Granger causal structure is based on the analysis of group time series data, which can only indirectly reveal the possible temporal causal relationship of gray matter volume change, but cannot directly reflect the disease progression process in real chronological order, and cannot explore its correlation
with clinical variables 。 Secondly, some patients receive oral drug treatment, such as anticholinergic drugs, benzodiazepines, muscle relaxants, anti-dopaminergic drugs, antiepileptic drugs, anti-anxiety drugs, etc.
, or receive botulinum toxin injection treatment, although the researchers have taken measures to avoid interference as much as possible, it is still difficult to completely rule out the potential impact of the above interventions on the research results, and further exploration
is needed in future work.
Original link:https://pubmed.
ncbi.
nlm.
nih.
gov/36130317/
About the corresponding author:
Liu Gang, Deputy Chief Physician and Master Supervisorof the First Affiliated Hospital of Sun Yat-sen University.
Mainly engaged in neuroimaging research on motor and cognitive impairment after stroke, neuroimaging research
on dystonia.
In recent years, he has presided over one youth and one general project of the National Natural Science Foundation of China
.
As a research backbone, he participated in one national key research and development plan and participated in a number of national and provincial scientific research projects
.
As the first or corresponding author in Brain, Movement Disorders, Stroke, European Journal of Neurology, 9 articles were published in high-level journals such as Neurorehabilitation and Neural Repair, and 5 high-level articles were
published in other journals.
A selection of past articles
[1] Science-Du Yang team and others collaborated to develop non-opioid-free analgesics that target adrenergic receptors
[2] NPJ Parkinsons Dis—Wang Xikim's team found that high PSQI is an independent risk factor for dyskinesia in Parkinson's disease
[3] Ann Neurol-Chen Wanjin/Fan Dongsheng's research group revealed that heterozygous mutations in the SerRS gene lead to fibular muscular atrophy
[4] SCI ADV—astrocyte subset plasticity regulates heroin relapse, providing a basis for the treatment of drug addiction relapse
[5] J Neurosci-Hu Bo's research group revealed the role of dorsal hippocampal vigilin positive interneurons in joint motor learning and their network activity mechanism
[6] CNSNT—Gu Xiaoping's team revealed that enhancing astrocyte networks can improve brain network abnormalities and cognitive dysfunction caused by long-term isoflurane anesthesia
[7] Nat Aging—Glial cells in mouse with Alzheimer's disease participate in synaptic clearance through the complement pathway
[8] J Neuroinflammation—Chen Gang's research group revealed that Schwann cell Pannexin 1 regulates neuropathic pain by mediating inflammatory responses
[9] NPP—Luo Xiongjian's research group uses Mendelian randomization to screen potential drug targets for the treatment of mental illness
[10] Adv SCI—Chai Renjie's team has made important progress in the regeneration of functional hair cells in cochlear organoids
Recommended high-quality scientific research training courses[1] Symposium on Single Cell Sequencing and Spatial Transcriptomics Data Analysis (October 29-30, Tencent Online Conference)[2] Symposium on Patch-clamping and Optogenetics and Calcium Imaging Technology (October 15-16, 2022 Tencent Conference) Conference/Forum Preview & Review[1] Preview | Neuromodulation and Brain-Computer Interface Conference (October 13-14, Beijing time) (U.
S.
Pacific Time: October 12-13)
[2] Conference report - The human brain and the machine are gradually getting closer, and the brain-computer interface "black technology" is shining into reality
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End of this article
