A map of white matter tracts in a lesser ape, the lar gibbon.

DWI Evolution Fasciculus Hominoid Tractography

Journal

Brain structure & function
ISSN: 1863-2661
Titre abrégé: Brain Struct Funct
Pays: Germany
ID NLM: 101282001

Informations de publication

Date de publication:
31 Oct 2023
Historique:
received: 22 02 2023
accepted: 01 09 2023
medline: 31 10 2023
pubmed: 31 10 2023
entrez: 31 10 2023
Statut: aheadofprint

Résumé

The recent development of methods for constructing directly comparable white matter atlases in primate brains from diffusion MRI allows us to probe specializations unique to humans, great apes, and other primate taxa. Here, we constructed the first white matter atlas of a lesser ape using an ex vivo diffusion-weighted scan of a brain from a young adult (5.5 years) male lar gibbon. We find that white matter architecture of the gibbon temporal lobe suggests specializations that are reminiscent of those previously reported for great apes, specifically, the expansion of the arcuate fasciculus and the inferior longitudinal fasciculus in the temporal lobe. Our findings suggest these white matter expansions into the temporal lobe were present in the last common ancestor to hominoids approximately 16 million years ago and were further modified in the great ape and human lineages. White matter atlases provide a useful resource for identifying neuroanatomical differences and similarities between humans and other primate species and provide insight into the evolutionary variation and stasis of brain organization.

Identifiants

pubmed: 37904002
doi: 10.1007/s00429-023-02709-9
pii: 10.1007/s00429-023-02709-9
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/N019814/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/N019814/1
Pays : United Kingdom

Informations de copyright

© 2023. The Author(s).

Références

Amiez C, Sallet J, Hopkins WD, Meguerditchian A, Hadj-Bouziane F, Ben Hamed S, Wilson CRE, Procyk E, Petrides M (2019) Sulcal organization in the medial frontal cortex provides insights into primate brain evolution. Nat Commun 10:1–14
doi: 10.1038/s41467-019-11347-x
Apfelbach R (1972) Electrically elicited vocalizations in the Gibbon Hylobates lar (Hylobatidae), and their behavioral significance. Z Tierpsychol 30:420–430
pubmed: 5048149 doi: 10.1111/j.1439-0310.1972.tb00868.x
Avants BB, Tustison NJ, Song G, Cook PA, Klein A, Gee JC (2011) A reproducible evaluation of ANTs similarity metric performance in brain image registration. Neuroimage 54:2033–2044
pubmed: 20851191 doi: 10.1016/j.neuroimage.2010.09.025
Azadbakht H, Parkes LM, Haroon HA, Augath M, Logothetis NK, de Crespigny A, D’Arceuil HE, Parker GJM (2015) Validation of high-resolution tractography against in vivo tracing in the macaque visual cortex. Cereb Cortex 25:4299–4309
pubmed: 25787833 pmcid: 4816782 doi: 10.1093/cercor/bhu326
Behrens TEJ, Berg HJ, Jbabdi S, Rushworth MFS, Woolrich MW (2007) Probabilistic diffusion tractography with multiple fibre orientations: What can we gain? Neuroimage 34:144–155
pubmed: 17070705 doi: 10.1016/j.neuroimage.2006.09.018
Berman JI, Lanza MR, Blaskey L, Edgar JC, Roberts TPL (2013) High angular resolution diffusion imaging probabilistic tractography of the auditory radiation. Am J Neuroradiol 34:1573–1578
pubmed: 23493892 pmcid: 3987782 doi: 10.3174/ajnr.A3471
Bertelsen MF (2018) Issues surrounding surplus animals in zoos. Fowler’s zoo and wild animal medicine, current therapy. Elsevier, St Louis, MO, pp 134–137
Bruner E (2018) Human paleoneurology and the evolution of the parietal cortex. Brain Behav Evol 91:136–147
pubmed: 30099459 doi: 10.1159/000488889
Bryant KL, Li L, Eichert N, Mars RB (2020) A comprehensive atlas of white matter tracts in the chimpanzee. PLoS Biol 18:e3000971
pubmed: 33383575 pmcid: 7806129 doi: 10.1371/journal.pbio.3000971
Bryant KL, Ardesch DJ, Roumazeilles L, Scholtens LH, Khrapitchev AA, Tendler BC, Wu W, Miller KL, Sallet J, van den Heuvel MP, Mars RB (2021) Diffusion MRI data, sulcal anatomy, and tractography for eight species from the Primate Brain Bank. Brain Struct Funct 226:2497–2509
pubmed: 34264391 pmcid: 8608778 doi: 10.1007/s00429-021-02268-x
Bryant KL, Preuss TM. 2018. A Comparative Perspective on the Human Temporal Lobe. In: Bruner E,, Ogihara N,, Tanabe HC, editors. Digital Endocasts. Tokyo: Springer Japan. p. 239–258.
Carbone L, Alan Harris R, Gnerre S, Veeramah KR, Lorente-Galdos B, Huddleston J, Meyer TJ, Herrero J, Roos C, Aken B, Anaclerio F, Archidiacono N, Baker C, Barrell D, Batzer MA, Beal K, Blancher A, Bohrson CL, Brameier M, Campbell MS, Capozzi O, Casola C, Chiatante G, Cree A, Damert A, de Jong PJ, Dumas L, Fernandez-Callejo M, Flicek P, Fuchs NV, Gut I, Gut M, Hahn MW, Hernandez-Rodriguez J, Hillier LW, Hubley R, Ianc B, Izsvák Z, Jablonski NG, Johnstone LM, Karimpour-Fard A, Konkel MK, Kostka D, Lazar NH, Lee SL, Lewis LR, Liu Y, Locke DP, Mallick S, Mendez FL, Muffato M, Nazareth LV, Nevonen KA, O’Bleness M, Ochis C, Odom DT, Pollard KS, Quilez J, Reich D, Rocchi M, Schumann GG, Searle S, Sikela JM, Skollar G, Smit A, Sonmez K, ten Hallers B, Terhune E, Thomas GWC, Ullmer B, Ventura M, Walker JA, Wall JD, Walter L, Ward MC, Wheelan SJ, Whelan CW, White S, Wilhelm LJ, Woerner AE, Yandell M, Zhu B, Hammer MF, Marques-Bonet T, Eichler EE, Fulton L, Fronick C, Muzny DM, Warren WC, Worley KC, Rogers J, Wilson RK, Gibbs RA (2014) Gibbon genome and the fast karyotype evolution of small apes. Nature 513:195–201
pubmed: 25209798 pmcid: 4249732 doi: 10.1038/nature13679
Clarke E, Reichard UH, Zuberbühler K (2006) The syntax and meaning of wild gibbon songs. PLoS ONE 1:e73
pubmed: 17183705 pmcid: 1762393 doi: 10.1371/journal.pone.0000073
Connolly CJ (1950) External morphology of the primate brain. Thomas, Springfield
de Sousa AA, Sherwood CC, Mohlberg H, Amunts K, Schleicher A, MacLeod CE, Hof PR, Frahm H, Zilles K (2010) Hominoid visual brain structure volumes and the position of the lunate sulcus. J Hum Evol 58:281–292
pubmed: 20172590 doi: 10.1016/j.jhevol.2009.11.011
Dejerine J, Dejerine-Klumpke A (1895) Anatomie des centres nerveux. Rueff et Cie, Paris
Donahue CJ, Sotiropoulos SN, Jbabdi S, Hernandez-Fernandez M, Behrens TE, Dyrby TB, Coalson T, Kennedy H, Knoblauch K, Van Essen DC, Glasser MF (2016) Using diffusion tractography to predict cortical connection strength and distance: a quantitative comparison with tracers in the monkey. J Neurosci 36:6758–6770
pubmed: 27335406 pmcid: 4916250 doi: 10.1523/JNEUROSCI.0493-16.2016
Eichert N, Verhagen L, Folloni D, Jbabdi S, Khrapitchev AA, Sibson NR, Mantini D, Sallet J, Mars RB (2019) What is special about the human arcuate fasciculus? Lateralization, projections, and expansion. Cortex 118:107–115
pubmed: 29937266 pmcid: 6699597 doi: 10.1016/j.cortex.2018.05.005
Eichert N, Robinson EC, Bryant KL, Jbabdi S, Jenkinson M, Li L, Krug K, Watkins KE, Mars RB (2020) Cross-species cortical alignment identifies different types of anatomical reorganization in the primate temporal lobe. Elife 9:e53232
pubmed: 32202497 pmcid: 7180052 doi: 10.7554/eLife.53232
Falk D, Zollikofer CPE, Ponce de León M, Semendeferi K, Alatorre Warren JL, Hopkins WD (2018) Identification of in vivo sulci on the external surface of eight adult chimpanzee brains: implications for interpreting early hominin endocasts. Brain Behav Evol 91:45–58
pubmed: 29533941 doi: 10.1159/000487248
Fischl B (2012) FreeSurfer Neuroimage 62:774–781
pubmed: 22248573 doi: 10.1016/j.neuroimage.2012.01.021
Folloni D, Sallet J, Khrapitchev AA, Sibson N, Verhagen L, Mars RB (2019) Dichotomous organization of amygdala/temporal-prefrontal bundles in both humans and monkeys. Elife 8:e47175
pubmed: 31689177 pmcid: 6831033 doi: 10.7554/eLife.47175
Fouts RS (1973) Acquisition and testing of gestural signs in four young chimpanzees. Science 180:978–980
pubmed: 17735931 doi: 10.1126/science.180.4089.978
Gao Y, Parvathaneni P, Schilling KG, Wang F, Stepniewska I, Xu Z, Choe AS, Ding Z, Gore JC, Chen LM, Landman BA, Anderson AW (2016) A 3D high resolution ex vivo white matter atlas of the common squirrel monkey (Saimiri sciureus) based on diffusion tensor imaging. Proc SPIE Int Soc Opt Eng. 9784
Gardner RA, Gardner BT (1969) Teaching sign language to a chimpanzee: A standardized system of gestures provides a means of two-way communication with a chimpanzee. Science 165:664–672
pubmed: 5793972 doi: 10.1126/science.165.3894.664
Hecht EE, Gutman DA, Bradley BA, Preuss TM, Stout D (2015) Virtual dissection and comparative connectivity of the superior longitudinal fasciculus in chimpanzees and humans. Neuroimage 108:124–137
pubmed: 25534109 doi: 10.1016/j.neuroimage.2014.12.039
Heuer K, Gulban OF, Bazin PL, Osoianu A, Valabregue R, Santin M, Herbin M, Toro R (2019) Evolution of neocortical folding: a phylogenetic comparative analysis of MRI from 34 primate species. Cortex 118:275–291
pubmed: 31235272 doi: 10.1016/j.cortex.2019.04.011
Inoue Y, Sinun W, Yosida S, Okanoya K (2017) Combinatory rules and chunk structure in male Mueller’s gibbon songs. Interact Stud 18:1–25
doi: 10.1075/is.18.1.01ino
Jbabdi S, Lehman JF, Haber SN, Behrens TE (2013) Human and monkey ventral prefrontal fibers use the same organizational principles to reach their targets: tracing versus tractography. J Neurosci 33:3190–3201
pubmed: 23407972 pmcid: 3602794 doi: 10.1523/JNEUROSCI.2457-12.2013
Jenkinson M, Beckmann CF, Behrens TEJ, Woolrich MW, Smith SM (2012) FSL. Neuroimage 62:782–790
pubmed: 21979382 doi: 10.1016/j.neuroimage.2011.09.015
Latini F, Martensson J, Larsson EM, Fredrikson M, Ahs F, Hjortberg M, Aldskogius H, Ryttlefors M (2017) Segmentation of the inferior longitudinal fasciculus in the human brain: A white matter dissection and diffusion tensor tractography study. Brain Res 1675:102–115
pubmed: 28899757 doi: 10.1016/j.brainres.2017.09.005
Maier-Hein KH, Neher PF, Houde J-C, Côté M-A, Garyfallidis E, Zhong J, Chamberland M, Yeh F-C, Lin Y-C, Ji Q, Reddick WE, Glass JO, Chen DQ, Feng Y, Gao C, Wu Y, Ma J, Renjie H, Li Q, Westin C-F, Deslauriers-Gauthier S, González JOO, Paquette M, St-Jean S, Girard G, Rheault F, Sidhu J, Tax CMW, Guo F, Mesri HY, Dávid S, Froeling M, Heemskerk AM, Leemans A, Boré A, Pinsard B, Bedetti C, Desrosiers M, Brambati S, Doyon J, Sarica A, Vasta R, Cerasa A, Quattrone A, Yeatman J, Khan AR, Hodges W, Alexander S, Romascano D, Barakovic M, Auría A, Esteban O, Lemkaddem A, Thiran J-P, Cetingul HE, Odry BL, Mailhe B, Nadar MS, Pizzagalli F, Prasad G, Villalon-Reina JE, Galvis J, Thompson PM, Requejo FDS, Laguna PL, Lacerda LM, Barrett R, Dell’Acqua F, Catani M, Petit L, Caruyer E, Daducci A, Dyrby TB, Holland-Letz T, Hilgetag CC, Stieltjes B, Descoteaux M. 2017. The challenge of mapping the human connectome based on diffusion tractography. Nature Communications. 8.
Makris N, Kennedy DN, McInerney S, Sorensen AG, Wang R, Caviness VS, Pandya DN (2005) Segmentation of subcomponents within the superior longitudinal fascicle in humans: a quantitative, in vivo DT-MRI Study. Cereb Cortex 15:854–869
pubmed: 15590909 doi: 10.1093/cercor/bhh186
Malikovic A, Vucetic B, Milisavljevic M, Tosevski J, Sazdanovic P, Milojevic B, Malobabic S (2012) Occipital sulci of the human brain: variability and morphometry. Anat Sci Int 87:61–70
pubmed: 21993979 doi: 10.1007/s12565-011-0118-6
Marcus D, Harwell J, Olsen T, Hodge M, Glasser M, Prior F, Jenkinson M, Laumann T, Curtiss S, Van Essen D (2011) Informatics and data mining tools and strategies for the human connectome project. Front Neuroinform 5:4
pubmed: 21743807 pmcid: 3127103 doi: 10.3389/fninf.2011.00004
Mars RB, Neubert F-X, Verhagen L, Sallet J, Miller KL, Dunbar RIM, Barton RA (2014) Primate comparative neuroscience using magnetic resonance imaging: promises and challenges. Front Neurosci 8:298
pubmed: 25339857 pmcid: 4186285 doi: 10.3389/fnins.2014.00298
Mars RB, Verhagen L, Gladwin TE, Neubert F-X, Sallet J, Rushworth MFS (2016) Comparing brains by matching connectivity profiles. Neurosci Biobehav Rev 60:90–97
pubmed: 26627865 doi: 10.1016/j.neubiorev.2015.10.008
Mars RB, Passingham RE, Jbabdi S (2018a) Connectivity fingerprints: from areal descriptions to abstract spaces. Trends Cogn Sci 22:1026–1037
pubmed: 30241910 pmcid: 6198109 doi: 10.1016/j.tics.2018.08.009
Mars RB, Sotiropoulos SN, Passingham RE, Sallet J, Verhagen L, Khrapitchev AA, Sibson N, Jbabdi S (2018b) Whole brain comparative anatomy using connectivity blueprints. Elife 7:e35237
pubmed: 29749930 pmcid: 5984034 doi: 10.7554/eLife.35237
Mars RB, O’Muircheartaigh J, Folloni D, Li L, Glasser MF, Jbabdi S, Bryant KL (2019) Concurrent analysis of white matter bundles and grey matter networks in the chimpanzee. Brain Struct Funct 224:1021–1033
pubmed: 30569281 doi: 10.1007/s00429-018-1817-8
Miller JA, Weiner KS (2022) Unfolding the evolution of human cognition. Trends Cogn Sci 26:735–737
pubmed: 35909020 doi: 10.1016/j.tics.2022.06.008
Miller JA, Voorhies WI, Li X, Raghuram I, Palomero-Gallagher N, Zilles K, Sherwood CC, Hopkins WD, Weiner KS (2020) Sulcal morphology of ventral temporal cortex is shared between humans and other hominoids. Sci Rep 10(1):17132
pubmed: 33051475 pmcid: 7555511 doi: 10.1038/s41598-020-73213-x
Ochiai T, Grimault S, Scavarda D, Roch G, Hori T, Rivière D, Mangin JF, Régis J (2004) Sulcal pattern and morphology of the superior temporal sulcus. Neuroimage 22:706–719
pubmed: 15193599 doi: 10.1016/j.neuroimage.2004.01.023
Palomero-Gallagher N, Hoffstaedter F, Mohlberg H, Eickhoff SB, Amunts K, Zilles K (2019) Human pregenual anterior cingulate cortex: structural, functional, and connectional heterogeneity. Cereb Cortex 29:2552–2574
pubmed: 29850806 doi: 10.1093/cercor/bhy124
Petrides M (2011) The human cerebral cortex. An MRI atlas of the sulci and gyri in MNI sterotaxic space. Academic Press, Amsterdam
Reveley C, Seth AK, Pierpaoli C, Silva AC, Yu D, Saunders RC, Leopold DA, Ye FQ (2015) Superficial white matter fiber systems impede detection of long-range cortical connections in diffusion MR tractography. Proc Natl Acad Sci USA 112:E2820-2828
pubmed: 25964365 pmcid: 4450402 doi: 10.1073/pnas.1418198112
Rilling JK (2014) Comparative primate neuroimaging: insights into human brain evolution. Trends Cogn Sci 18:46–55
pubmed: 24501779 doi: 10.1016/j.tics.2013.09.013
Rilling JK, Glasser MF, Preuss TM, Ma X, Zhao T, Hu X, Behrens TEJ (2008) The evolution of the arcuate fasciculus revealed with comparative DTI. Nat Neurosci 11:426–428
pubmed: 18344993 doi: 10.1038/nn2072
Roumazeilles L, Eichert N, Bryant KL, Folloni D, Sallet J, Vijayakumar S, Foxley S, Tendler BC, Jbabdi S, Reveley C, Verhagen L, Dershowitz LB, Guthrie M, Flach E, Miller KL, Mars RB (2020) Longitudinal connections and the organization of the temporal cortex in macaques, great apes, and humans. PLoS Biol 18:e3000810
pubmed: 32735557 pmcid: 7423156 doi: 10.1371/journal.pbio.3000810
Roumazeilles L, Lange FJ, Benn RA, Andersson JLR, Bertelsen MF, Manger PR, Flach E, Khrapitchev AA, Bryant KL, Sallet J, Mars RB (2022) Cortical morphology and white matter tractography of three phylogenetically distant primates: evidence for a simian elaboration. Cereb Cortex 32:1608–1624
pubmed: 34518890 doi: 10.1093/cercor/bhab285
Savage-Rumbaugh S, McDonald K, Sevcik RA, Hopkins WD, Rubert E (1986) Spontaneous symbol acquisition and communicative use by pygmy chimpanzees (Pan paniscus). J Exp Psychol Gen 115:211–235
pubmed: 2428917 doi: 10.1037/0096-3445.115.3.211
Schilling K, Gao Y, Janve V, Stepniewska I, Landman BA, Anderson AW (2017) Confirmation of a gyral bias in diffusion MRI fiber tractography. Hum Brain Mapp 39:1449–1466
pubmed: 29266522 pmcid: 5807146 doi: 10.1002/hbm.23936
Schmahmann JD, Pandya DN (2006) Fiber pathways of the brain. Oxford University Press, Oxford
doi: 10.1093/acprof:oso/9780195104233.001.0001
Schmahmann JD, Pandya DN, Wang R, Dai G, D’Arceuil HE, de Crespigny AJ, Wedeen VJ (2007) Association fibre pathways of the brain: parallel observations from diffusion spectrum imaging and autoradiography. Brain 130:630–653
pubmed: 17293361 doi: 10.1093/brain/awl359
Schoenemann PT, Sheehan MJ, Glotzer LD (2005) Prefrontal white matter volume is disproportionately larger in humans than in other primates. Nat Neurosci 8:242–252
pubmed: 15665874 doi: 10.1038/nn1394
Swiegers J, Bhagwandin A, Sherwood CC, Bertelsen MF, Maseko BC, Hemingway J, Rockland KS, Molnár Z, Manger PR (2019) The distribution, number, and certain neurochemical identities of infracortical white matter neurons in a lar gibbon (Hylobates lar) brain. J Compar Neurol 527:1633–1653
doi: 10.1002/cne.24545
Tendler BC, Hanayik T, Ansorge O, Bangerter-Christensen S, Berns GS, Bertelsen MF, Bryant KL, Foxley S, van den Heuvel M, Prof HAF, Huszar IN, Khrapitchev AA, Leonte A, Manger PR, Menke RA, Mollink J, Mortimer D, Pallebage-Gamarallage M, Roumazeilles L, Sallet J, Scholtens LH, Scott C, Smart A, Turner MR, Wang C, Jbabdi S, Mars RB, Miller KL (2022) The Digital Brain Bank, an open access platform for post-mortem datasets. Elife 11:e73153
pubmed: 35297760 pmcid: 9042233 doi: 10.7554/eLife.73153
Thiebaut de Schotten M, Dell’Acqua F, Forkel SJ, Simmons A, Vergani F, Murphy DGM, Catani M (2011) A lateralized brain network for visuospatial attention. Nat Neurosci 14:1245–1246
pubmed: 21926985 doi: 10.1038/nn.2905
Thiebaut de Schotten M, Dell’Acqua F, Valabregue R, Catani M (2012) Monkey to human comparative anatomy of the frontal lobe association tracts. Cortex 48:82–96
pubmed: 22088488 doi: 10.1016/j.cortex.2011.10.001
van den Heuvel MP, de Reus MA, Feldman Barrett L, Scholtens LH, Coopmans FMT, Schmidt R, Preuss TM, Rilling JK, Li L (2015) Comparison of diffusion tractography and tract-tracing measures of connectivity strength in rhesus macaque connectome. Hum Brain Mapp 36:3064–3075
pubmed: 26058702 pmcid: 6869766 doi: 10.1002/hbm.22828
Wakana S, Caprihan A, Panzenboeck MM, Fallon JH, Perry M, Gollub RL, Hua K, Zhang J, Jiang H, Dubey P, Blitz A, van Zijl P, Mori S (2007) Reproducibility of quantitative tractography methods applied to cerebral white matter. Neuroimage 36:630–644
pubmed: 17481925 doi: 10.1016/j.neuroimage.2007.02.049
Warrington S, Bryant KL, Khrapitchev AA, Sallet J, Charquero-Ballester M, Douaud G, Jbabdi S, Mars RB, Sotiropoulos SN (2020) XTRACT - Standardised protocols for automated tractography in the human and macaque brain. Neuroimage 217:116923
pubmed: 32407993 doi: 10.1016/j.neuroimage.2020.116923

Auteurs

Katherine L Bryant (KL)

Wellcome Centre for Integrative Neuroimaging, Centre for Functional MRI of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, UK. katherine.bryant@univ-amu.fr.
Laboratoire de Psychologie Cognitive, Aix-Marseille Université, Marseille, France. katherine.bryant@univ-amu.fr.

Paul R Manger (PR)

School of Anatomical Sciences, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa.

Mads F Bertelsen (MF)

Centre for Zoo and Wild Animal Health, Copenhagen Zoo, Frederiksberg, Denmark.

Alexandre A Khrapitchev (AA)

Department of Oncology, University of Oxford, Oxford, UK.

Jérôme Sallet (J)

Wellcome Centre for Integrative Neuroimaging, Centre for Functional MRI of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Stem Cell and Brain Research Institute, Université Lyon 1, Inserm, Bron, France.

R Austin Benn (RA)

Wellcome Centre for Integrative Neuroimaging, Centre for Functional MRI of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Integrative Neuroscience and Cognition Center, Université de Paris, CNRS, Paris, France.

Rogier B Mars (RB)

Wellcome Centre for Integrative Neuroimaging, Centre for Functional MRI of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.

Classifications MeSH