Abnormal dynamic brain activity and functional connectivity of primary motor cortex in blepharospasm
Yuhan Luo
Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China
Contribution: Formal analysis (equal), Investigation (equal), Validation (equal), Visualization (lead), Writing - original draft (lead)
Search for more papers by this authorYaomin Guo
Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China
Contribution: Formal analysis (equal), Investigation (equal), Methodology (equal), Software (lead), Validation (equal)
Search for more papers by this authorLinchang Zhong
Department of Medical Imaging, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Contribution: Investigation (equal), Writing - review & editing (equal)
Search for more papers by this authorYing Liu
Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China
Contribution: Investigation (equal), Writing - original draft (supporting)
Search for more papers by this authorChao Dang
Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China
Contribution: Investigation (supporting), Methodology (supporting)
Search for more papers by this authorYing Wang
Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China
Contribution: Project administration (supporting), Writing - review & editing (supporting)
Search for more papers by this authorJinsheng Zeng
Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China
Contribution: Funding acquisition (equal), Writing - review & editing (equal)
Search for more papers by this authorWeixi Zhang
Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China
Contribution: Project administration (equal), Writing - review & editing (supporting)
Search for more papers by this authorCorresponding Author
Kangqiang Peng
Department of Medical Imaging, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Correspondence
Gang Liu, Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, No. 58 Zhongshan Road 2, 510080 Guangzhou, China.
Email: [email protected]
Kangqiang Peng, Department of Medical Imaging, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Email: [email protected]
Contribution: Conceptualization (equal), Methodology (equal), Project administration (equal), Writing - review & editing (equal)
Search for more papers by this authorCorresponding Author
Gang Liu
Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China
Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangzhou, China
Correspondence
Gang Liu, Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, No. 58 Zhongshan Road 2, 510080 Guangzhou, China.
Email: [email protected]
Kangqiang Peng, Department of Medical Imaging, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Email: [email protected]
Contribution: Conceptualization (lead), Data curation (lead), Funding acquisition (equal), Methodology (equal), Project administration (equal), Resources (equal), Supervision (lead), Writing - review & editing (equal)
Search for more papers by this authorYuhan Luo
Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China
Contribution: Formal analysis (equal), Investigation (equal), Validation (equal), Visualization (lead), Writing - original draft (lead)
Search for more papers by this authorYaomin Guo
Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China
Contribution: Formal analysis (equal), Investigation (equal), Methodology (equal), Software (lead), Validation (equal)
Search for more papers by this authorLinchang Zhong
Department of Medical Imaging, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Contribution: Investigation (equal), Writing - review & editing (equal)
Search for more papers by this authorYing Liu
Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China
Contribution: Investigation (equal), Writing - original draft (supporting)
Search for more papers by this authorChao Dang
Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China
Contribution: Investigation (supporting), Methodology (supporting)
Search for more papers by this authorYing Wang
Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China
Contribution: Project administration (supporting), Writing - review & editing (supporting)
Search for more papers by this authorJinsheng Zeng
Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China
Contribution: Funding acquisition (equal), Writing - review & editing (equal)
Search for more papers by this authorWeixi Zhang
Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China
Contribution: Project administration (equal), Writing - review & editing (supporting)
Search for more papers by this authorCorresponding Author
Kangqiang Peng
Department of Medical Imaging, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Correspondence
Gang Liu, Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, No. 58 Zhongshan Road 2, 510080 Guangzhou, China.
Email: [email protected]
Kangqiang Peng, Department of Medical Imaging, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Email: [email protected]
Contribution: Conceptualization (equal), Methodology (equal), Project administration (equal), Writing - review & editing (equal)
Search for more papers by this authorCorresponding Author
Gang Liu
Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China
Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangzhou, China
Correspondence
Gang Liu, Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, No. 58 Zhongshan Road 2, 510080 Guangzhou, China.
Email: [email protected]
Kangqiang Peng, Department of Medical Imaging, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Email: [email protected]
Contribution: Conceptualization (lead), Data curation (lead), Funding acquisition (equal), Methodology (equal), Project administration (equal), Resources (equal), Supervision (lead), Writing - review & editing (equal)
Search for more papers by this authorYuhan Luo, Yaomin Guo, and Linchang Zhong contributed equally to this work.
Funding information
This work was funded by the Key-Area Research and Development Program of Guangdong Province (2018B030340001), the National Natural Science Foundation of China (81771137 and 81971103), the Natural Science Foundation of Guangdong Province (2016A030310132 and 2021A1515010600), the Sun Yat-Sen University Clinical Research 5010 Program (2018001), the Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases (2020B1212060017), the Southern China International Cooperation Base for Early Intervention and Functional Rehabilitation of Neurological Diseases (2015B050501003 and 2020A0505020004), Guangdong Provincial Engineering Center for Major Neurological Disease Treatment, and Guangdong Provincial Translational Medicine Innovation Platform for Diagnosis and Treatment of Major Neurological Disease
Abstract
Background and purpose
Accumulating evidence indicates that dynamic amplitude of low-frequency fluctuations (dALFF) or dynamic functional connectivity (dFC) can provide complementary information, distinct from static amplitude of low-frequency fluctuations (sALFF) or static functional connectivity (sFC), in detecting brain functional abnormalities in brain diseases. We aimed to examine whether dALFF and dFC can offer valuable information for the detection of functional brain abnormalities in patients with blepharospasm.
Methods
We collected resting-state functional magnetic resonance imaging data from 46 patients each of blepharospasm, hemifacial spasm (HFS), and healthy controls (HCs). We examined intergroup differences in sALFF and dALFF to investigate abnormal regional brain activity in patients with blepharospasm. Based on the dALFF results, we conducted seed-based sFC and dFC analyses to identify static and dynamic connectivity changes in brain networks centered on areas showing abnormal temporal variability of local brain activity in patients with blepharospasm.
Results
Compared with HCs, patients with blepharospasm displayed different brain functional change patterns characterized by increased sALFF in the left primary motor cortex (PMC) but increased dALFF variance in the right PMC. However, differences were not found between patients with HFS and HCs. Additionally, patients with blepharospasm exhibited decreased dFC strength, but no change in sFC, between right PMC and ipsilateral cerebellum compared with HCs; these findings were replicated when patients with blepharospasm were compared to those with HFS.
Conclusions
Our findings highlight that dALFF and dFC are complementary to sALFF and sFC and can provide valuable information for detecting brain functional abnormalities in blepharospasm. Blepharospasm may be a network disorder involving the cortico-ponto-cerebello-thalamo-cortical circuit.
CONFLICT OF INTEREST
The authors have stated explicitly that there are no conflicts of interest in connection with this article.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
| Filename | Description |
|---|---|
| ene15233-sup-0001-AppS1.docxWord 2007 document , 3.2 MB |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
REFERENCES
- 1Defazio G, Hallett M, Jinnah HA, Conte A, Berardelli A. Blepharospasm 40 years later. Mov Disord. 2017; 32: 498-509.
- 2Schmidt KE, Linden DE, Goebel R, Zanella FE, Lanfermann H, Zubcov AA. Striatal activation during blepharospasm revealed by fMRI. Neurology. 2003; 60: 1738-1743.
- 3Obermann M, Yaldizli O, de Greiff A, et al. Increased basal-ganglia activation performing a non-dystonia-related task in focal dystonia. Eur J Neurol. 2008; 15: 831-838.
- 4Zhou B, Wang J, Huang Y, Yang Y, Gong Q, Zhou D. A resting state functional magnetic resonance imaging study of patients with benign essential blepharospasm. J Neuroophthalmol. 2013; 33: 235-240.
- 5Yang J, Luo C, Song W, et al. Altered regional spontaneous neuronal activity in blepharospasm: a resting state fMRI study. J Neurol. 2013; 260: 2754-2760.
- 6Jochim A, Li Y, Gora-Stahlberg G, et al. Altered functional connectivity in blepharospasm/orofacial dystonia. Brain Behav. 2018; 8: e894.
- 7Ni MF, Huang XF, Miao YW, Liang ZH. Resting state fMRI observations of baseline brain functional activities and connectivities in primary blepharospasm. Neurosci Lett. 2017; 660: 22-28.
- 8Wei J, Wei S, Yang R, et al. Voxel-mirrored homotopic connectivity of resting-state functional magnetic resonance imaging in blepharospasm. Front Psychol. 2018; 9: 1620.
- 9Pan P, Wei S, Li H, et al. Voxel-wise brain-wide functional connectivity abnormalities in patients with primary blepharospasm at rest. Neural Plast. 2021; 2021: 6611703.
- 10Huang XF, Zhu MR, Shan P, et al. Multiple neural networks malfunction in primary blepharospasm: an independent components analysis. Front Hum Neurosci. 2017; 11: 235.
- 11Hutchison RM, Womelsdorf T, Allen EA, et al. Dynamic functional connectivity: promise, issues, and interpretations. NeuroImage. 2013; 80: 360-378.
- 12Allen EA, Damaraju E, Plis SM, Erhardt EB, Eichele T, Calhoun VD. Tracking whole-brain connectivity dynamics in the resting state. Cereb Cortex. 2014; 24: 663-676.
- 13Liao W, Li J, Ji GJ, et al. Endless fluctuations: temporal dynamics of the amplitude of low frequency fluctuations. IEEE Trans Med Imaging. 2019; 38: 2523-2532.
- 14Chang C, Glover GH. Time-frequency dynamics of resting-state brain connectivity measured with fMRI. NeuroImage. 2010; 50: 81-98.
- 15Lee HL, Zahneisen B, Hugger T, LeVan P, Hennig J. Tracking dynamic resting-state networks at higher frequencies using MR-encephalography. NeuroImage. 2013; 65: 216-222.
- 16Calhoun VD, Miller R, Pearlson G, Adalı T. The chronnectome: time-varying connectivity networks as the next frontier in fMRI data discovery. Neuron. 2014; 84: 262-274.
- 17Mash LE, Linke AC, Olson LA, Fishman I, Liu TT, Müller RA. Transient states of network connectivity are atypical in autism: a dynamic functional connectivity study. Hum Brain Mapp. 2019; 40: 2377-2389.
- 18Li T, Liao Z, Mao Y, et al. Temporal dynamic changes of intrinsic brain activity in Alzheimer's disease and mild cognitive impairment patients: a resting-state functional magnetic resonance imaging study. Ann Transl Med. 2021; 9: 63.
- 19Boon LI, Hepp DH, Douw L, et al. Functional connectivity between resting-state networks reflects decline in executive function in Parkinson's disease: a longitudinal fMRI study. Neuroimage Clin. 2020; 28: 102468.
- 20Yao Z, Shi J, Zhang Z, et al. Altered dynamic functional connectivity in weakly-connected state in major depressive disorder. Clin Neurophysiol. 2019; 130: 2096-2104.
- 21Kottaram A, Johnston L, Ganella E, Pantelis C, Kotagiri R, Zalesky A. Spatio-temporal dynamics of resting-state brain networks improve single-subject prediction of schizophrenia diagnosis. Hum Brain Mapp. 2018; 39: 3663-3681.
- 22Cui Q, Sheng W, Chen Y, et al. Dynamic changes of amplitude of low-frequency fluctuations in patients with generalized anxiety disorder. Hum Brain Mapp. 2020; 41: 1667-1676.
- 23Ma M, Zhang H, Liu R, et al. Static and dynamic changes of amplitude of low-frequency fluctuations in cervical discogenic pain. Front Neurosci. 2020; 14: 733.
- 24Chirumamilla VC, Dresel C, Koirala N, et al. Structural brain network fingerprints of focal dystonia. Ther Adv Neurol Disord. 2019; 12: 1278102232.
- 25Albanese A, Bhatia K, Bressman SB, et al. Phenomenology and classification of dystonia: a consensus update. Mov Disord. 2013; 28: 863-873.
- 26Hamilton M. The assessment of anxiety states by rating. Br J Med Psychol. 1959; 32: 50-55.
- 27Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960; 23: 56-62.
- 28Jankovic J, Kenney C, Grafe S, Goertelmeyer R, Comes G. Relationship between various clinical outcome assessments in patients with blepharospasm. Mov Disord. 2009; 24: 407-413.
- 29Yan CG, Wang XD, Zuo XN, Zang YF. DPABI: data processing & analysis for (resting-state) brain imaging. Neuroinformatics. 2016; 14: 339-351.
- 30Schölvinck ML, Maier A, Ye FQ, Duyn JH, Leopold DA. Neural basis of global resting-state fMRI activity. Proc Natl Acad Sci USA. 2010; 107: 10238-10243.
- 31Fox MD, Zhang D, Snyder AZ, Raichle ME. The global signal and observed anticorrelated resting state brain networks. J Neurophysiol. 2009; 101: 3270-3283.
- 32Murphy K, Birn RM, Handwerker DA, Jones TB, Bandettini PA. The impact of global signal regression on resting state correlations: are anti-correlated networks introduced? NeuroImage. 2009; 44: 893-905.
- 33Zang YF, He Y, Zhu CZ, et al. Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI. Brain Dev. 2007; 29: 83-91.
- 34Leonardi N, Van De Ville D. On spurious and real fluctuations of dynamic functional connectivity during rest. NeuroImage. 2015; 104: 430-436.
- 35Li J, Duan X, Cui Q, Chen H, Liao W. More than just statics: temporal dynamics of intrinsic brain activity predicts the suicidal ideation in depressed patients. Psychol Med. 2019; 49: 852-860.
- 36Liu J, Liao X, Xia M, He Y. Chronnectome fingerprinting: identifying individuals and predicting higher cognitive functions using dynamic brain connectivity patterns. Hum Brain Mapp. 2018; 39: 902-915.
- 37Li Z, Li K, Luo X, et al. Distinct brain functional impairment patterns between suspected non-Alzheimer disease pathophysiology and Alzheimer's disease: a study combining static and dynamic functional magnetic resonance imaging. Front Aging Neurosci. 2020; 12: 550664.
- 38Fu Z, Tu Y, Di X, et al. Characterizing dynamic amplitude of low-frequency fluctuation and its relationship with dynamic functional connectivity: an application to schizophrenia. NeuroImage. 2018; 180: 619-631.
- 39Christoff K, Irving ZC, Fox KC, Spreng RN, Andrews-Hanna JR. Mind-wandering as spontaneous thought: a dynamic framework. Nat Rev Neurosci. 2016; 17: 718-731.
- 40Federico F, Simone IL, Lucivero V, et al. Proton magnetic resonance spectroscopy in primary blepharospasm. Neurology. 1998; 51: 892-895.
- 41Delorme C, Roze E, Grabli D, et al. Explicit agency in patients with cervical dystonia: altered recognition of temporal discrepancies between motor actions and their feedback. PLoS One. 2016; 11:e162191.
- 42Delnooz CC, Pasman JW, Beckmann CF, van de Warrenburg BP. Task-free functional MRI in cervical dystonia reveals multi-network changes that partially normalize with botulinum toxin. PLoS One. 2013; 8:e62877.
- 43Ma H, Qu J, Ye L, Shu Y, Qu Q. Blepharospasm, oromandibular dystonia, and Meige syndrome: clinical and genetic update. Fron Neurol. 2021; 12: 630221.
- 44Sang L, Qin W, Liu Y, et al. Resting-state functional connectivity of the vermal and hemispheric subregions of the cerebellum with both the cerebral cortical networks and subcortical structures. NeuroImage. 2012; 61: 1213-1225.
- 45Abbruzzese G, Berardelli A. Further progress in understanding the pathophysiology of primary dystonia. Mov Disord. 2011; 26: 1185-1186.
- 46Filip P, Lungu OV, Bareš M. Dystonia and the cerebellum: a new field of interest in movement disorders? Clin Neurophysiol. 2013; 124: 1269-1276.
- 47Glickman A, Nguyen P, Shelton E, Peterson DA, Berman BD. Basal ganglia and cerebellar circuits have distinct roles in blepharospasm. Parkinsonism Relat Disord. 2020; 78: 158-164.
- 48Burciu RG, Hess CW, Coombes SA, et al. Functional activity of the sensorimotor cortex and cerebellum relates to cervical dystonia symptoms. Hum Brain Mapp. 2017; 38: 4563-4573.
- 49Agcaoglu O, Wilson TW, Wang YP, Stephen J, Calhoun VD. Resting state connectivity differences in eyes open versus eyes closed conditions. Hum Brain Mapp. 2019; 40: 2488-2498.
- 50Weng Y, Liu X, Hu H, et al. Open eyes and closed eyes elicit different temporal properties of brain functional networks. NeuroImage. 2020; 222: 117230.
