Cerebro humano durante la adolescencia.pdf

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Development/Plasticity/Repair The Human Cerebral Cortex Flattens during Adolescence Yas ser Ale ma ´n-Go´mez, 1,2 Joost Jansse n, 1,2,3 Hugo Schnack, 4 Evan Balab an, 5 Laur a Pina-Camacho, 1,3 Fidel Alfa ro-Al magro , 1 Josefi na Castro-Forn ieles, 6 Sora ya Otero, 7 Immac ulad a Baeza, 6 Dolor es Moreno , 1,3 Nuri a Bar gall o ´, 6 Mara Parel lada, 1,2,3 Celso Arang o, 1,2,3 and Man uel Desc o 1,2,8 1 Inst itu to de I nves tig aci o ´n Sa nita ria Greg ori o Mara n ˜o ´n,  2 Centro de Inv estigac io ´n B iome ´dica en Red de Salud Mental, and  3 Servicio de Psiquiatría del Niño y Adolece nte, Hos pital Gen eral Univ ersita rio Greg orio Mar an ˜o´n, 28 007 Madri d, Spain ,  4 Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Center Utrecht, 3584 CG, Utrecht, The Netherlands,  5 The Behavioral Neurosciences Program, McGill University, Montreal, Quebec, Canada H2L1K6,  6 Departament de Psiquiatria i Psicologia Infantil i Juvenil, SGR-1119, Institut de Neurociències, Universitat de Barcelona, IDIBAPS, CIBERSAM, Hospital Clínic de Barcelona, 08036 Barcelona, Spain,  7 Unidad de Salud Mental Infanto-Juvenil, Departamento de Psiquiatría y Psicología, Hospital Universitario Marque ´s de Valdecilla, 39008 Santander, Spain, and  8 Departamento de Bioingeniería e Ingeniería Aeroespacial, Universidad Carlos III de Madrid, 28911, Legane ´s, Madrid, Spain The human cerebral cortex appears to shrink during adolescence. To delineate the dynamic morphological changes involved in this pro ces s, 52 hea lth y mal e and female ado les cents (11 –17 yea rs old ) were neuroi mag ed twice using mag net ic resonanceima gin g, approx- imate ly 2 yearsapart. Usinga novelmorphometricanalysis proced ure combin ing the FreeS urferand BrainVisaimage softw are suites,we quantifiedglobalandlobarchangeincorticalthickness,outersurfacearea,thegyrificationindex,theaverageEuclideandistancebetween opp osi ng sid es of the whi te mat ter surface (gy ralwhi te mat ter thi ckness), the convex (“e xpo sed ”) par t of theouter cor tic al sur fac e (hu ll sur fac e are a), sul cal len gth , dep th, and wid th. We fou nd tha t the cor tic al sur fac e fla ttens dur ing ado les cence. Fla tte nin g wasstron ges t in the fro nta l and occ ipi tal cor tic es, in whi ch sig nif ica nt sul cal wid eni ng and dec rea sed sul cal dep th co- occ urr ed. Glo bal ly, sul cal wid eni ng wasasso cia tedwithcorti calthinn ingand,for thefrontalcorte x,wit h los s of sur fac e are a. Forthe oth ercor tic al lob es,thinn ingwas rel ate d to gyralwhite matte r expans ion.The overal l flatt eningof the macrostruc turalthree-di mensi onalarchitect ure of the humancortex durin g adolescence thus involves changes in gray matter and effects of the maturation of white matter. Introduction Adolescence is a period of important cortical brain changes for which longitudinal MRI studies are ideally suited. Recent find- ings suggest that, during adolescence in both sexes, the cortex globally contracts because of cortical thinning (Shaw et al., 2008; Blakemore, 2012;  Brown et al., 2012;  van Soelen et al., 2012), which may be highly heritable (van Soelen et al., 2012). Annual reductions are found to be higher than 1% across most parts of the cortex (van Soelen et al., 2012; Tamnes et al., 2013) and may follow a posteroanterior pattern, with medial and dorsolateral prefrontal areas the last to show decline (Gogtay et al., 2004; Tamnes et al., 2013). During adolescence, development of gyral and sulcal surface area (SA) shows a more subtle decline com- pared with cortical thickness (CT) (Raznahan et al., 2011; Brown et al. , 20 12). Sub cor tic al whi te mat ter(WM) vol umeconti nue s to expand linearly in most but not all subcortical regions from chi ldhood to ear ly adulth ood (Len root et al. , 2007; Tamneset al., 2010;  Brouwer et al., 2012;  Brown et al., 2012). The direct rela- tionship among these processes is not well understood, nor is it known whether such a relationship is invariant over different cortical regions; better knowledge about these issues could pro- vide important insights into the dynamics of cortical develop- ment during adolescence. This study used novel surface-based morphometric methods that yielded two improvements with respect to previous surface- based studies focusing on CT and SA during brain development. First, the present analysis incorporates a new and detailed set of sul cal measurements in additi on to gyr al measur es of CT and SA. Cortical SA varies between individuals because of differences in eit her“exposed (gy ral ) or “hi dde n” (sulca l) sur fac e area or bot h. Hidden sulcal SA makes up the largest part of the human cortical sur face (VanEssen and Dru ry,1997) and varie s betwe en indiv id- uals because of changes in sulcal depth (SD), length (SL), and width (SW). Second, cortical thinning during adolescence may partly be an artifact of the maturation of WM tracts that cause voxels at the interface between WM and gray matter (GM) to change their classification (Sowell et al., 2004;  Shaw et al., 2008; Paus, 2010). The present analysis simultaneously examines the changes over time in cortical SA, CT, gyrification index (GI), hull surface Received April 5, 2013; revised Aug. 5, 2013; accepted Aug. 7, 2013. Author contributions: Y.A.-G., J.J., H.S., E.B., L.P.-C., J.C.-F., S.O., I.B., D.M., N.B., M.P., C.A., and M.D. designed research; Y.A.-G., J.J., H.S., and F.A.-A. performed research; Y.A.-G. and J.J. contributed unpublished reagents/ analytic tools; Y.A.-G., J.J., and H.S. analyzed data; Y.A.-G., J.J., H.S., E.B., and L.P.-C. wrote the paper. This study is supported by the Instituto de Salud Carlos III (CIBERSAM; PI11/02877), the Spanish Ministry of Econom y andCompeti tiven ess(Ramony CajalProgram;CENIT-ConsorciosEstrat égico s Nacio nalesenInvestiga ción Técnica- Program, AMIT -Tecnologías de Imagen Molecular Avanzadas- Project), the Autonomous Community of Madri d(S2010/BM D-2422AGES) ,the ERA-NE T NEURON(Netw orkof Europ eanFundingforNeuroscien ceResearch), Fundación Alicia Koplowitz, Fundación Mutua Madrileña, and Caja Navarra. We thank all participants and their families. The authors declare no competing financial interests. Corres pondence sh ould be addresse d to Yasser Alema´n-Go´mez , Instituto de Inv estigaci o ´n Sani taria Gre gorio Maran ˜o´n, C/Ibiza 43, 28009 Ma drid, Spain. E- mail: yalema [email protected] . DOI:10.1523/JNEUROSCI.1459-13.2013 Copyright © 201 3 the authors 0270-6474/13/3315004-07$15.00 /0 15004  The Journal of Neuroscience, September 18, 2013   33(38):15004–15010

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