Mapping Essential Tremor to a Common Brain Network Using Functional Connectivity Analysis.

Humans Essential Tremor / diagnostic imaging Brain Mapping Cerebellum / pathology Connectome Tremor Magnetic Resonance Imaging Brain Diseases / pathology Sensorimotor Cortex Neural Pathways

Journal

Neurology
ISSN: 1526-632X
Titre abrégé: Neurology
Pays: United States
ID NLM: 0401060

Informations de publication

Date de publication:
10 10 2023
Historique:
received: 12 02 2023
accepted: 09 06 2023
pmc-release: 10 10 2024
medline: 23 10 2023
pubmed: 19 8 2023
entrez: 18 8 2023
Statut: ppublish

Résumé

The cerebello-thalamo-cortical circuit plays a critical role in essential tremor (ET). However, abnormalities have been reported in multiple brain regions outside this circuit, leading to inconsistent characterization of ET pathophysiology. Here, we test whether these mixed findings in ET localize to a common functional network and whether this network has therapeutic relevance. We conducted a systematic literature search to identify studies reporting structural or metabolic brain abnormalities in ET. We then used 'coordinate network mapping,' which leverages a normative connectome (n = 1,000) of resting-state fMRI data to identify regions commonly connected to findings across all studies. To assess whether these regions may be relevant for the treatment of ET, we compared our network with a therapeutic network derived from lesions that relieved ET. Finally, we investigated whether the functional connectivity of this ET symptom network is abnormal in an independent cohort of patients with ET as compared with healthy controls. Structural and metabolic brain abnormalities in ET were located in heterogeneous regions throughout the brain. However, these coordinates were connected to a common functional brain network, including the cerebellum, thalamus, motor cortex, precuneus, inferior parietal lobe, and insula. The cerebellum was identified as the hub of this network because it was the only brain region that was both functionally connected to the findings of over 90% of studies and significantly different in connectivity compared with a control data set of other movement disorders. This network was strikingly similar to the therapeutic network derived from lesions improving ET, with key regions aligning in the thalamus and cerebellum. Furthermore, positive functional connectivity between the cerebellar network hub and the sensorimotor cortices was significantly reduced in patients with ET compared with healthy controls, and connectivity within this network was correlated with tremor severity and cognitive functioning. These findings suggest that the cerebellum is the central hub of a network commonly connected to structural and metabolic abnormalities in ET. This network may have therapeutic utility in refining and informing new targets for neuromodulation of ET.

Sections du résumé

BACKGROUND AND OBJECTIVES
The cerebello-thalamo-cortical circuit plays a critical role in essential tremor (ET). However, abnormalities have been reported in multiple brain regions outside this circuit, leading to inconsistent characterization of ET pathophysiology. Here, we test whether these mixed findings in ET localize to a common functional network and whether this network has therapeutic relevance.
METHODS
We conducted a systematic literature search to identify studies reporting structural or metabolic brain abnormalities in ET. We then used 'coordinate network mapping,' which leverages a normative connectome (n = 1,000) of resting-state fMRI data to identify regions commonly connected to findings across all studies. To assess whether these regions may be relevant for the treatment of ET, we compared our network with a therapeutic network derived from lesions that relieved ET. Finally, we investigated whether the functional connectivity of this ET symptom network is abnormal in an independent cohort of patients with ET as compared with healthy controls.
RESULTS
Structural and metabolic brain abnormalities in ET were located in heterogeneous regions throughout the brain. However, these coordinates were connected to a common functional brain network, including the cerebellum, thalamus, motor cortex, precuneus, inferior parietal lobe, and insula. The cerebellum was identified as the hub of this network because it was the only brain region that was both functionally connected to the findings of over 90% of studies and significantly different in connectivity compared with a control data set of other movement disorders. This network was strikingly similar to the therapeutic network derived from lesions improving ET, with key regions aligning in the thalamus and cerebellum. Furthermore, positive functional connectivity between the cerebellar network hub and the sensorimotor cortices was significantly reduced in patients with ET compared with healthy controls, and connectivity within this network was correlated with tremor severity and cognitive functioning.
DISCUSSION
These findings suggest that the cerebellum is the central hub of a network commonly connected to structural and metabolic abnormalities in ET. This network may have therapeutic utility in refining and informing new targets for neuromodulation of ET.

Identifiants

DOI: 10.1212/WNL.0000000000207701 PMID: 37596042 PMC: PMC10585696
pubmed: 37596042
pii: WNL.0000000000207701
doi: 10.1212/WNL.0000000000207701
pmc: PMC10585696
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e1483-e1494

Informations de copyright

© 2023 American Academy of Neurology.

Références

Mov Disord. 2020 Jul;35(7):1181-1188
pubmed: 32343870
Nat Hum Behav. 2021 Dec;5(12):1707-1716
pubmed: 34239076
Brain. 2019 Jan 1;142(1):70-79
pubmed: 30551186
Front Neurol. 2018 Jun 26;9:495
pubmed: 29997568
Brain. 2019 Jun 1;142(6):1660-1674
pubmed: 31099831
Brain. 2015 Oct;138(Pt 10):2934-47
pubmed: 26248468
Nat Rev Dis Primers. 2021 Nov 11;7(1):83
pubmed: 34764294
Brain Connect. 2014 Feb;4(1):53-69
pubmed: 24308753
Neurotherapeutics. 2020 Oct;17(4):1603-1621
pubmed: 32915385
Tremor Other Hyperkinet Mov (N Y). 2021 Jul 09;11:28
pubmed: 34277141
Hum Brain Mapp. 2021 Jun 1;42(8):2322-2331
pubmed: 33755270
J Neurol Neurosurg Psychiatry. 2019 Apr;90(4):474-482
pubmed: 30337440
Neuroimage. 2017 Apr 15;150:395-404
pubmed: 28163141
Neuroimage Clin. 2016 Oct 15;12:765-775
pubmed: 27812503
Clin Neurophysiol. 2012 Jan;123(1):61-4
pubmed: 22055842
Medicine (Baltimore). 2015 Dec;94(49):e1936
pubmed: 26656325
Ann Neurol. 2018 Jul;84(1):153-157
pubmed: 30014594
Nat Rev Neurol. 2020 Feb;16(2):69-83
pubmed: 31959938
Brain. 2018 Aug 1;141(8):2445-2456
pubmed: 29982424
Brain. 2011 Aug;134(Pt 8):2274-86
pubmed: 21747127
Hum Brain Mapp. 2021 Jul;42(10):3156-3167
pubmed: 33769638
Brain. 2020 Feb 1;143(2):541-553
pubmed: 31919494
Cerebellum. 2016 Jun;15(3):263-75
pubmed: 26626626
Mov Disord. 2009 Aug 15;24(11):1629-35
pubmed: 19514010
Brain. 2012 Jan;135(Pt 1):105-16
pubmed: 22120148
Neurosci Biobehav Rev. 2022 Aug;139:104736
pubmed: 35700753
Curr Opin Neurol. 2022 Aug 1;35(4):453-459
pubmed: 35788098
Cerebellum. 2022 Oct 10;:
pubmed: 36214998
Neuroimage. 2009 May 15;46(1):39-46
pubmed: 19457380
Neuroimage. 2012 Aug 15;62(2):782-90
pubmed: 21979382
Cerebellum. 2016 Jun;15(3):235-42
pubmed: 26129713
Mov Disord. 1998;13 Suppl 3:2-23
pubmed: 9827589
J Neurophysiol. 2007 May;97(5):3219-28
pubmed: 17344375
Elife. 2018 Aug 14;7:
pubmed: 30106371
Behav Neurol. 2010;23(1-2):65-79
pubmed: 20714062
Mov Disord. 2019 Jan;34(1):95-104
pubmed: 30345712
J Neurol. 2020 May;267(5):1358-1367
pubmed: 31974808
Cerebellum. 2020 Feb;19(1):1-5
pubmed: 31707620
Neuroradiology. 2017 Feb;59(2):157-168
pubmed: 28062908
Brain Commun. 2019;1(1):fcz006
pubmed: 31608325
Nat Commun. 2021 Jan 13;12(1):363
pubmed: 33441542
Neurol Sci. 2019 Oct;40(10):2051-2063
pubmed: 31115799
Mov Disord. 2015 Dec;30(14):1926-36
pubmed: 26407908
Ann Neurol. 2019 Dec;86(6):812-820
pubmed: 31614012
Neuroimage. 2016 Aug 15;137:70-85
pubmed: 27179606
Brain. 2018 Feb 1;141(2):472-485
pubmed: 29293948
Tremor Other Hyperkinet Mov (N Y). 2017 Mar 28;7:458
pubmed: 28373927
Lancet Neurol. 2011 Feb;10(2):148-61
pubmed: 21256454

Auteurs

Ellen Younger (E)

From the Cognitive Neuroscience Unit (E.Y., E.G.E., N.P., K.C., D.T.C.), School of Psychology, Deakin University, Geelong, Australia; Human Neuroscience (P.P., S.T.), Sapienza University of Rome; IRCCS NEUROMED (P.P.), Pozzilli, Italy; Department of Neurology (J.B.-L.) and Research Institute (i+12), University Hospital "12 de Octubre"; Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED) (J.B.-L.); Department of Medicine (J.B.-L.), Complutense University; Facultad de Ciencias Experimentales (J.P.R.), Universidad Francisco de Vitoria; Brain Damage Unit (J.P.R.), Hospital Beata María Ana, Madrid, Spain; Turku Brain and Mind Center (J.J.), Clinical Neurosciences, University of Turku; Turku PET Centre (J.J.), Neurocenter, Turku University Hospital, Finland; and Center for Brain Circuit Therapeutics (D.T.C.), Department of Neurology, Psychiatry, and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. efyounge@deakin.edu.au.

Elizabeth G Ellis (EG)

From the Cognitive Neuroscience Unit (E.Y., E.G.E., N.P., K.C., D.T.C.), School of Psychology, Deakin University, Geelong, Australia; Human Neuroscience (P.P., S.T.), Sapienza University of Rome; IRCCS NEUROMED (P.P.), Pozzilli, Italy; Department of Neurology (J.B.-L.) and Research Institute (i+12), University Hospital "12 de Octubre"; Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED) (J.B.-L.); Department of Medicine (J.B.-L.), Complutense University; Facultad de Ciencias Experimentales (J.P.R.), Universidad Francisco de Vitoria; Brain Damage Unit (J.P.R.), Hospital Beata María Ana, Madrid, Spain; Turku Brain and Mind Center (J.J.), Clinical Neurosciences, University of Turku; Turku PET Centre (J.J.), Neurocenter, Turku University Hospital, Finland; and Center for Brain Circuit Therapeutics (D.T.C.), Department of Neurology, Psychiatry, and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

Nicholas Parsons (N)

From the Cognitive Neuroscience Unit (E.Y., E.G.E., N.P., K.C., D.T.C.), School of Psychology, Deakin University, Geelong, Australia; Human Neuroscience (P.P., S.T.), Sapienza University of Rome; IRCCS NEUROMED (P.P.), Pozzilli, Italy; Department of Neurology (J.B.-L.) and Research Institute (i+12), University Hospital "12 de Octubre"; Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED) (J.B.-L.); Department of Medicine (J.B.-L.), Complutense University; Facultad de Ciencias Experimentales (J.P.R.), Universidad Francisco de Vitoria; Brain Damage Unit (J.P.R.), Hospital Beata María Ana, Madrid, Spain; Turku Brain and Mind Center (J.J.), Clinical Neurosciences, University of Turku; Turku PET Centre (J.J.), Neurocenter, Turku University Hospital, Finland; and Center for Brain Circuit Therapeutics (D.T.C.), Department of Neurology, Psychiatry, and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

Patrizia Pantano (P)

From the Cognitive Neuroscience Unit (E.Y., E.G.E., N.P., K.C., D.T.C.), School of Psychology, Deakin University, Geelong, Australia; Human Neuroscience (P.P., S.T.), Sapienza University of Rome; IRCCS NEUROMED (P.P.), Pozzilli, Italy; Department of Neurology (J.B.-L.) and Research Institute (i+12), University Hospital "12 de Octubre"; Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED) (J.B.-L.); Department of Medicine (J.B.-L.), Complutense University; Facultad de Ciencias Experimentales (J.P.R.), Universidad Francisco de Vitoria; Brain Damage Unit (J.P.R.), Hospital Beata María Ana, Madrid, Spain; Turku Brain and Mind Center (J.J.), Clinical Neurosciences, University of Turku; Turku PET Centre (J.J.), Neurocenter, Turku University Hospital, Finland; and Center for Brain Circuit Therapeutics (D.T.C.), Department of Neurology, Psychiatry, and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
ORCID: 0000-0001-9659-8294

Silvia Tommasin (S)

From the Cognitive Neuroscience Unit (E.Y., E.G.E., N.P., K.C., D.T.C.), School of Psychology, Deakin University, Geelong, Australia; Human Neuroscience (P.P., S.T.), Sapienza University of Rome; IRCCS NEUROMED (P.P.), Pozzilli, Italy; Department of Neurology (J.B.-L.) and Research Institute (i+12), University Hospital "12 de Octubre"; Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED) (J.B.-L.); Department of Medicine (J.B.-L.), Complutense University; Facultad de Ciencias Experimentales (J.P.R.), Universidad Francisco de Vitoria; Brain Damage Unit (J.P.R.), Hospital Beata María Ana, Madrid, Spain; Turku Brain and Mind Center (J.J.), Clinical Neurosciences, University of Turku; Turku PET Centre (J.J.), Neurocenter, Turku University Hospital, Finland; and Center for Brain Circuit Therapeutics (D.T.C.), Department of Neurology, Psychiatry, and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

Karen Caeyenberghs (K)

From the Cognitive Neuroscience Unit (E.Y., E.G.E., N.P., K.C., D.T.C.), School of Psychology, Deakin University, Geelong, Australia; Human Neuroscience (P.P., S.T.), Sapienza University of Rome; IRCCS NEUROMED (P.P.), Pozzilli, Italy; Department of Neurology (J.B.-L.) and Research Institute (i+12), University Hospital "12 de Octubre"; Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED) (J.B.-L.); Department of Medicine (J.B.-L.), Complutense University; Facultad de Ciencias Experimentales (J.P.R.), Universidad Francisco de Vitoria; Brain Damage Unit (J.P.R.), Hospital Beata María Ana, Madrid, Spain; Turku Brain and Mind Center (J.J.), Clinical Neurosciences, University of Turku; Turku PET Centre (J.J.), Neurocenter, Turku University Hospital, Finland; and Center for Brain Circuit Therapeutics (D.T.C.), Department of Neurology, Psychiatry, and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

Julián Benito-León (J)

From the Cognitive Neuroscience Unit (E.Y., E.G.E., N.P., K.C., D.T.C.), School of Psychology, Deakin University, Geelong, Australia; Human Neuroscience (P.P., S.T.), Sapienza University of Rome; IRCCS NEUROMED (P.P.), Pozzilli, Italy; Department of Neurology (J.B.-L.) and Research Institute (i+12), University Hospital "12 de Octubre"; Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED) (J.B.-L.); Department of Medicine (J.B.-L.), Complutense University; Facultad de Ciencias Experimentales (J.P.R.), Universidad Francisco de Vitoria; Brain Damage Unit (J.P.R.), Hospital Beata María Ana, Madrid, Spain; Turku Brain and Mind Center (J.J.), Clinical Neurosciences, University of Turku; Turku PET Centre (J.J.), Neurocenter, Turku University Hospital, Finland; and Center for Brain Circuit Therapeutics (D.T.C.), Department of Neurology, Psychiatry, and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

Juan Pablo Romero (JP)

From the Cognitive Neuroscience Unit (E.Y., E.G.E., N.P., K.C., D.T.C.), School of Psychology, Deakin University, Geelong, Australia; Human Neuroscience (P.P., S.T.), Sapienza University of Rome; IRCCS NEUROMED (P.P.), Pozzilli, Italy; Department of Neurology (J.B.-L.) and Research Institute (i+12), University Hospital "12 de Octubre"; Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED) (J.B.-L.); Department of Medicine (J.B.-L.), Complutense University; Facultad de Ciencias Experimentales (J.P.R.), Universidad Francisco de Vitoria; Brain Damage Unit (J.P.R.), Hospital Beata María Ana, Madrid, Spain; Turku Brain and Mind Center (J.J.), Clinical Neurosciences, University of Turku; Turku PET Centre (J.J.), Neurocenter, Turku University Hospital, Finland; and Center for Brain Circuit Therapeutics (D.T.C.), Department of Neurology, Psychiatry, and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

Juho Joutsa (J)

From the Cognitive Neuroscience Unit (E.Y., E.G.E., N.P., K.C., D.T.C.), School of Psychology, Deakin University, Geelong, Australia; Human Neuroscience (P.P., S.T.), Sapienza University of Rome; IRCCS NEUROMED (P.P.), Pozzilli, Italy; Department of Neurology (J.B.-L.) and Research Institute (i+12), University Hospital "12 de Octubre"; Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED) (J.B.-L.); Department of Medicine (J.B.-L.), Complutense University; Facultad de Ciencias Experimentales (J.P.R.), Universidad Francisco de Vitoria; Brain Damage Unit (J.P.R.), Hospital Beata María Ana, Madrid, Spain; Turku Brain and Mind Center (J.J.), Clinical Neurosciences, University of Turku; Turku PET Centre (J.J.), Neurocenter, Turku University Hospital, Finland; and Center for Brain Circuit Therapeutics (D.T.C.), Department of Neurology, Psychiatry, and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

Daniel T Corp (DT)

From the Cognitive Neuroscience Unit (E.Y., E.G.E., N.P., K.C., D.T.C.), School of Psychology, Deakin University, Geelong, Australia; Human Neuroscience (P.P., S.T.), Sapienza University of Rome; IRCCS NEUROMED (P.P.), Pozzilli, Italy; Department of Neurology (J.B.-L.) and Research Institute (i+12), University Hospital "12 de Octubre"; Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED) (J.B.-L.); Department of Medicine (J.B.-L.), Complutense University; Facultad de Ciencias Experimentales (J.P.R.), Universidad Francisco de Vitoria; Brain Damage Unit (J.P.R.), Hospital Beata María Ana, Madrid, Spain; Turku Brain and Mind Center (J.J.), Clinical Neurosciences, University of Turku; Turku PET Centre (J.J.), Neurocenter, Turku University Hospital, Finland; and Center for Brain Circuit Therapeutics (D.T.C.), Department of Neurology, Psychiatry, and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Mapping Essential Tremor to a Common Brain...
questionsmedicales.fr › Maladies du système nerveux › Maladies du système nerveux central › Troubles de la motricité › Tremblement essentiel › Mapping Essential Tremor to a Common Brain...
questionsmedicales.fr › Techniques d'investigation › Neuroimagerie › Neuroimagerie fonctionnelle › Cartographie cérébrale › Mapping Essential Tremor to a Common Brain...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Tronc cérébral › Rhombencéphale › Métencéphale › Cervelet › Mapping Essential Tremor to a Common Brain...
questionsmedicales.fr › Techniques d'investigation › Neuroimagerie › Neuroimagerie fonctionnelle › Cartographie cérébrale › Connectome › Mapping Essential Tremor to a Common Brain...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Manifestations neurologiques › Dyskinésies › Tremblement › Mapping Essential Tremor to a Common Brain...
questionsmedicales.fr › Diagnostic › Techniques et procédures diagnostiques › Imagerie diagnostique › Tomographie › Imagerie par résonance magnétique › Mapping Essential Tremor to a Common Brain...
questionsmedicales.fr › Maladies du système nerveux › Maladies du système nerveux central › Encéphalopathies › Mapping Essential Tremor to a Common Brain...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Prosencéphale › Télencéphale › Cerveau › Cortex cérébral › Cortex sensorimoteur › Mapping Essential Tremor to a Common Brain...
questionsmedicales.fr › Système nerveux › Voies nerveuses › Mapping Essential Tremor to a Common Brain...