Functional brain activity constrained by structural connectivity reveals cohort-specific features for serum neurofilament light chain.

Biological techniques Dynamical systems

Journal

Communications medicine
ISSN: 2730-664X
Titre abrégé: Commun Med (Lond)
Pays: England
ID NLM: 9918250414506676

Informations de publication

Date de publication:
2022
Historique:
received: 16 11 2020
accepted: 07 12 2021
entrez: 23 5 2022
pubmed: 24 5 2022
medline: 24 5 2022
Statut: epublish

Résumé

Neuro-axonal brain damage releases neurofilament light chain (NfL) proteins, which enter the blood. Serum NfL has recently emerged as a promising biomarker for grading axonal damage, monitoring treatment responses, and prognosis in neurological diseases. Importantly, serum NfL levels also increase with aging, and the interpretation of serum NfL levels in neurological diseases is incomplete due to lack of a reliable model for age-related variation in serum NfL levels in healthy subjects. Graph signal processing (GSP) provides analytical tools, such as graph Fourier transform (GFT), to produce measures from functional dynamics of brain activity constrained by white matter anatomy. Here, we leveraged a set of features using GFT that quantified the coupling between blood oxygen level dependent signals and structural connectome to investigate their associations with serum NfL levels collected from healthy subjects and former athletes with history of concussions. Here we show that GSP feature from isthmus cingulate in the right hemisphere (r-iCg) is strongly linked with serum NfL in healthy controls. In contrast, GSP features from temporal lobe and lingual areas in the left hemisphere and posterior cingulate in the right hemisphere are the most associated with serum NfL in former athletes. Additional analysis reveals that the GSP feature from r-iCg is associated with behavioral and structural measures that predict aggressive behavior in healthy controls and former athletes. Our results suggest that GSP-derived brain features may be included in models of baseline variance when evaluating NfL as a biomarker of neurological diseases and studying their impact on personality traits.

Sections du résumé

Background UNASSIGNED
Neuro-axonal brain damage releases neurofilament light chain (NfL) proteins, which enter the blood. Serum NfL has recently emerged as a promising biomarker for grading axonal damage, monitoring treatment responses, and prognosis in neurological diseases. Importantly, serum NfL levels also increase with aging, and the interpretation of serum NfL levels in neurological diseases is incomplete due to lack of a reliable model for age-related variation in serum NfL levels in healthy subjects.
Methods UNASSIGNED
Graph signal processing (GSP) provides analytical tools, such as graph Fourier transform (GFT), to produce measures from functional dynamics of brain activity constrained by white matter anatomy. Here, we leveraged a set of features using GFT that quantified the coupling between blood oxygen level dependent signals and structural connectome to investigate their associations with serum NfL levels collected from healthy subjects and former athletes with history of concussions.
Results UNASSIGNED
Here we show that GSP feature from isthmus cingulate in the right hemisphere (r-iCg) is strongly linked with serum NfL in healthy controls. In contrast, GSP features from temporal lobe and lingual areas in the left hemisphere and posterior cingulate in the right hemisphere are the most associated with serum NfL in former athletes. Additional analysis reveals that the GSP feature from r-iCg is associated with behavioral and structural measures that predict aggressive behavior in healthy controls and former athletes.
Conclusions UNASSIGNED
Our results suggest that GSP-derived brain features may be included in models of baseline variance when evaluating NfL as a biomarker of neurological diseases and studying their impact on personality traits.

Identifiants

pubmed: 35603281
doi: 10.1038/s43856-021-00065-5
pii: 65
pmc: PMC9053240
doi:

Types de publication

Journal Article

Langues

eng

Pagination

8

Informations de copyright

© The Author(s) 2022.

Déclaration de conflit d'intérêts

Competing interestsThe authors declare the following competing interests: MCT has served as at advisory board for Biogen, Denali, and Roche. KB has served as a consultant, at advisory boards, or at data monitoring committees for Abcam, Axon, Biogen, JOMDD/Shimadzu, Julius Clinical, Lilly, MagQu, Novartis, Roche Diagnostics, and Siemens Healthineers, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (all outside the present paper). HZ has served at scientific advisory boards for Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics and CogRx, has given lectures in symposia sponsored by Fujirebio, Alzecure and Biogen, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). All other authors do not have any competing interests to declare.

Références

Am J Geriatr Psychiatry. 2002 Nov-Dec;10(6):687-95
pubmed: 12427577
Neuroimage. 2016 Nov 15;142:135-149
pubmed: 27480624
Int J Geriatr Psychiatry. 2016 Sep;31(9):1050-5
pubmed: 26968137
Front Psychol. 2021 Feb 09;11:547353
pubmed: 33633619
Proc Natl Acad Sci U S A. 2013 Apr 9;110(15):6169-74
pubmed: 23530246
J Affect Disord. 2021 Dec 1;295:108-115
pubmed: 34419778
Nat Hum Behav. 2018;2(2):156-164
pubmed: 30498789
J Neural Transm (Vienna). 2011 Jan;118(1):115-33
pubmed: 20936524
Proc Natl Acad Sci U S A. 2009 Feb 10;106(6):2035-40
pubmed: 19188601
Neurobiol Aging. 2000 Jul-Aug;21(4):569-76
pubmed: 10924774
Nat Med. 2019 Feb;25(2):277-283
pubmed: 30664784
J Neuropsychiatry Clin Neurosci. 2002 Fall;14(4):416-23
pubmed: 12426409
PLoS One. 2015 Aug 28;10(8):e0135886
pubmed: 26317831
Nat Commun. 2019 Oct 18;10(1):4747
pubmed: 31628329
Brain Behav. 2019 Jan;9(1):e01161
pubmed: 30488646
World J Biol Psychiatry. 2012 Jan;13(1):75-81
pubmed: 22256828
Neurobiol Aging. 2020 May;89:108-117
pubmed: 32107064
Neurology. 2017 Mar 7;88(10):930-937
pubmed: 28179466
Med Image Anal. 2021 Apr;69:101986
pubmed: 33610918
Neuroimage. 2010 Oct 1;52(4):1374-89
pubmed: 20580932
J Neurosci Res. 2001 Nov 1;66(3):510-6
pubmed: 11746370
Sci Rep. 2016 Nov 07;6:36791
pubmed: 27819296
Neurology. 2016 Sep 27;87(13):1329-36
pubmed: 27581216
Nat Methods. 2019 Jan;16(1):111-116
pubmed: 30532080
Nat Rev Dis Primers. 2016 Nov 17;2:16084
pubmed: 27853132
Artif Intell Med. 2020 Jun;106:101870
pubmed: 32593395
Clin Chem Lab Med. 2016 Oct 1;54(10):1655-61
pubmed: 27071153
Trends Neurosci. 2019 Apr;42(4):251-262
pubmed: 30808574
J Neurosci. 2009 Dec 2;29(48):15223-31
pubmed: 19955375
Commun Med (Lond). 2022 Jan 17;2:8
pubmed: 35603281
Brain. 2018 Aug 1;141(8):2382-2391
pubmed: 29860296
Annu Rev Psychol. 2013;64:499-525
pubmed: 22804773
Ageing Res Rev. 2017 Mar;34:64-76
pubmed: 27865980
Ann Clin Transl Neurol. 2016 Feb 01;3(3):216-25
pubmed: 27042681
Neuron. 2008 Sep 25;59(6):1037-50
pubmed: 18817740
Neuroimage Clin. 2013 Apr 22;2:601-11
pubmed: 24179811
Mol Psychiatry. 2008 Nov;13(11):993-1000
pubmed: 18504424
Biol Psychiatry. 2014 Jan 1;75(1):73-80
pubmed: 23647988
Am J Psychiatry. 2016 Nov 1;173(11):1119-1130
pubmed: 27523497
Neuroimage. 2006 Jul 1;31(3):968-80
pubmed: 16530430
Neurobiol Aging. 2017 Jan;49:138-144
pubmed: 27794264
Front Neurol. 2019 Aug 07;10:712
pubmed: 31447753
Brain Sci. 2019 Dec 13;9(12):
pubmed: 31847131
PLoS One. 2013 Sep 20;8(9):e75091
pubmed: 24073237
Sci Rep. 2018 Nov 26;8(1):17368
pubmed: 30478269
PLoS One. 2020 Oct 27;15(10):e0236384
pubmed: 33108404
Neurosurgery. 2019 Jul 1;85(1):11-30
pubmed: 30690521
Nat Rev Neurol. 2018 Oct;14(10):577-589
pubmed: 30171200
Brain Inj. 2013;27(3):253-61
pubmed: 23438346
Brain. 2005 Jun;128(Pt 6):1314-22
pubmed: 15716302
Front Hum Neurosci. 2014 Mar 19;8:139
pubmed: 24678292
Brain Inj. 2009 Jul;23(7):655-65
pubmed: 19557569
IEEE J Sel Top Signal Process. 2016 Oct;10(7):1189-1203
pubmed: 28439325
Neuroimage. 2021 Oct 1;239:118289
pubmed: 34171497
Eur J Neurol. 2010 Mar;17(3):377-82
pubmed: 19845747
Soc Cogn Affect Neurosci. 2021 Jul 6;16(7):716-725
pubmed: 33837772
PLoS One. 2017 Feb 27;12(2):e0172762
pubmed: 28241046
Brain Inform. 2015 Sep;2(3):167-180
pubmed: 27747507
Neuroimage. 2006 Apr 15;30(3):713-20
pubmed: 16337815
Trends Neurosci. 1998 Aug;21(8):323-31
pubmed: 9720596
Ann Neurol. 2017 Jun;81(6):857-870
pubmed: 28512753
Psychiatry Res Neuroimaging. 2019 Jan 30;283:77-82
pubmed: 30554129
Acta Neurol Scand. 2019 Sep;140(3):177-183
pubmed: 31087810
PLoS Med. 2007 Oct 16;4(10):e297
pubmed: 17941715
Eur J Neurol. 2020 Jul;27(7):1170-1177
pubmed: 32281206

Auteurs

Saurabh Sihag (S)

University of Pennsylvania, Philadelphia, PA USA.
T.J. Watson IBM Research Center, Health Care and Life Sciences, Yorktown Heights, NY USA.

Sébastien Naze (S)

T.J. Watson IBM Research Center, Health Care and Life Sciences, Yorktown Heights, NY USA.
IBM Research Australia, Melbourne, VIC Australia.

Foad Taghdiri (F)

Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON Canada.

Melisa Gumus (M)

Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON Canada.

Charles Tator (C)

Canadian Concussion Centre, University Health Network, Toronto, ON Canada.
Division of Neurosurgery, University Health Network, Toronto, ON Canada.

Robin Green (R)

Canadian Concussion Centre, University Health Network, Toronto, ON Canada.
Department of Rehabilitation Sciences, University of Toronto, Toronto, ON Canada.

Brenda Colella (B)

Department of Rehabilitation Sciences, University of Toronto, Toronto, ON Canada.

Kaj Blennow (K)

Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.

Henrik Zetterberg (H)

Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.
UK Dementia Research Institute at UCL, University College London, London, UK.

Luis Garcia Dominguez (LG)

Division of Neurology, University Health Network, Toronto, ON Canada.
Brain and Behaviour Program, The Hospital for Sick Children, Toronto, ON Canada.

Richard Wennberg (R)

Canadian Concussion Centre, University Health Network, Toronto, ON Canada.
Division of Neurology, University Health Network, Toronto, ON Canada.

David J Mikulis (DJ)

Canadian Concussion Centre, University Health Network, Toronto, ON Canada.
Division of Neuroradiology, University Health Network, Toronto, ON Canada.

Maria C Tartaglia (MC)

Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON Canada.
Canadian Concussion Centre, University Health Network, Toronto, ON Canada.
Division of Neurology, University Health Network, Toronto, ON Canada.

James R Kozloski (JR)

T.J. Watson IBM Research Center, Health Care and Life Sciences, Yorktown Heights, NY USA.

Classifications MeSH