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Provided for non-commercial research and education use. Not for reproduction, distribution or commercial use. II samwx..I %mace I erneraa Cortex This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit: http://www.elsevier.com/copyright EFTA00301227 Authors personal copy CORTEX 49 (2033) Zoo -210 Available online at www.sciencedirect.com &Hie\ SciVerse ScienceDirect ELSEVIER Journal homepage: www.elsevier.com/locate/cortex Research report Hemispheric asymmetries of cortical volume in the human brain `s Elkhonon Goldberg a'', Donovan Roediger a, N. Erkut Kucukboyaci ail', Chad Carlson a, Orrin Devinsky °, Ruben Kuzniecky a, Eric Halgren b and Thomas Thesen a a New York University School of Medicine, New York, NY, USA b Multimodal Imaging Laboratory, University of California, San Diego, CA, USA ARTICLE INFO ABSTRACT Article history: Hemispheric asymmetry represents a cardinal feature of cerebral organization, but the Received 19 June 2011 nature of structural and functional differences between the hemispheres is far from fully Reviewed 2 September 2011 understood. Using Magnetic Resonance Imaging morphometry, we identified several Revised 27 September 2011 volumetric differences between the two hemispheres of the human brain. Heteromodal Accepted 28 October 2011 inferopanetal and lateral prefrontal cortices are more extensive in the right than left Action editor Alan Beaton hemisphere, as is visual cortex. Heteromodal mesial and orbital prefrontal and cingulate Published online 19 November 2011 cortices are more extensive in the left than right hemisphere, as are somatosensory, parts of motor, and auditory cortices. Thus, heteromodal association cortices are more exten- Keywords: sively represented on the lateral aspect of the right than in the left hemisphere, and MRI morphometry modality-specific cortices are more extensively represented on the lateral aspect of the left Cortical asymmetry than in the right hemisphere. On the mesial aspect heteromodal association cortices are Hemispheric specialization more extensively represented in the left than right hemisphere. Prefrontal cortex QD 2011 Elsevier Ltd. All rights reserved. Parietal cortex 1. Introduction between brain biology and function may be expressed on many levels other than that of gross morphology (cytoarchi- Hemispheric specialization is among the central features of tectonic, biochemical, etc.). Thus any attempt to infer regional functional cortical organization in humans. Recognition of the brain function from regional brain morphology, however functional differences between the hemispheres often trig- tempting, requires great caution and any assertion of a "bigger gers interestin their morphological differences and vice versa. is better" structure—function relationship must be tempered Indeed, gross morphological differences between the by this caveat. Such concerns notwithstanding, evidence is hemispheres are particularly interestingif they can be related growing that a reasonably direct 'bigger is better" relationship to functional differences. The degree to which such relation- often does exist between functional proficiency and gross ships can be drawn remains uncertain, since the relationship morphometric cortical characteristics of the underlying * Authors' Note: The study was approved by the Institutional Review Board of New York University. Written informed consent was obtained from all participants involved in the study. We thank Dmitri Bougakov, Barry Cohen, Michal Harciarek, Dolores Malaspina, Ralph Nixon, and Kenneth Podell for their comments. ' Corresponding author. NYU School of Medicine, 145 East 32nd Street, 5th Floor, New York, NY 10016, USA. E-mail addresses: ellchonon.goldbergenyurric.org, egneurocogeaol.com (E. Goldberg). 0010-9452/$ - see front matter 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.cortex.2011.11.002 EFTA00301228 Author's personal copy CORTEX 49 (2013) 200-210 201 substrate, such as regional volume or surface area size (Goldberg and Costa, 1981). If this were to be the case, the (Blackmon et al., 2010; Draganski et al., 2004; Fleming et al., functional implications of such cortical space allocation 2010; Maguire et al., 2000; Schneider et al., 2002). differences could be intriguing and would merit further Early efforts to identify morphological hemispheric asym- examination. However, this assertion was based on old find- metries were to a large degree motivated by the desire to ings and was limited to cortical convexity; therefore its val- identify the biological bases of the asymmetric cortical idity must be re-examined with up-to-date methods which language representation. A number of morphological asym- would target both lateral and mesial aspects of the hemi- metries have been described, notably involving planum tem- spheres. Here, we report hemispheric differences in regional perate and pars opercularis, and their relationship to left human brain volume across multiple cortical regions, both hemispheric dominance for language asserted, but some of lateral and mesial, using the more recently developed Free- the particularly influential findings were reported several Surfer Magnetic Resonance Imaging (MRI) processing meth- decades ago using what methodologies were available then odology (Fischl and Dale, 2000; Fischl et al., 2004). The (Geschwind and Levitsky, 1968; Galaburda et al., 1978; LeMay particular focus of this paper is to ascertain any systematic and Culebras, 1972). Subsequent research confirmed these differences in cortical space allocation to heteromodal versus structural asymmetries (Foundas et al., 1994, 1995; Anderson modality-specific cortices in the two hemispheres. et al., 1999; Watkins et al., 2001) but demonstrated that the relationship between structural asymmetries in the planum temperate and language lateralization is not nearly as strong or 2. Methods as direct as asserted earlier, and the very existence of such a relationship has been scrutinized (Beaton, 1997). Other 2.1. Participants structural asymmetries have also been described and subse- quently confirmed, notably "Yakovlevian torque" (Yakovlev, Structural MR1 data from adults (N = 39) aged 19-40 1972; Yakovlev and Rakic, 1966; Watkins et al., 2001; Nan (Kr , = 27.75, standard deviation — SD,r, = 6.12; 19 females et al., 2007) characterized by the right frontal and left occip- and 20 males) were analyzed. Participants were all right- ital protrusions, whose possible relationship to any functional handed as determined by the Edinburgh Handedness Inven- asymmetries remains unclear. Regional hemispheric asym- tory (Oldfield, 1971) with scores ranging from 40 to 100. They metries both in cortical thickness (Luders et al., 2006) and were all free of neurological, psychiatric, or neuro- volume (Good et al., 2001), both in gray and white matter developmental disorders based on screening interviews. They (Penhune et al., 1996; Takao et al., 2011) have been reported. were recruited as part of a community-based normative Any morphometric comparison of the two hemispheres reference sample at NYU Comprehensive Epilepsy Center. may be complicated by individual variability, which is particularly pronounced in certain structures, e.g., anterior 2.2. Imaging data acquisition cingulate and paracingulate cortex (Forint° et al., 2004; Huster et al., 2007). Furthermore, there is a growing appreciation of Two Tl-weighted volumes VT = 3.25 msec, TR = 2530 msec, sex-linked differences in regional brain morphology TI = 1.100 msec, flip angle = 7°, field of view (FOV) = 256 mm, (Witelson, 1989; Habib et al., 1991; Crespo-Facorro et al., 2001), voxel size = 1 x 1 x 1.33 mm) were obtained for each partici- including hemispheric asymmetries (Luders et al., 2009; Raz pant on a 3T Siemens Allegra scanner, acquisition parameters et al., 2004), as well as age-related hemispheric differences optimized for increased gray/white matter contrast, rigid body (Raz et al., 2004; Shaw et al., 2009). co-registered, and common space-reoriented. Images were Our understanding of the functional differences between automatically corrected for spatial distortion, registered, the two hemispheres has also been refined beyond the classic averaged to improve signal-to-noise ratio, and processed with distinction between verbal and visuo-spatial asymmetries. the FreeSurfer (4.0.2) software (httpWsurfer.nmr.mgh. Additional functional differences have been described, notably harvard.edu). Each T1-weighted image took 8:07 min. those linking the right hemisphere to cognitive novelty and exploratory behavior and the left hemisphere to cognitive 2.3. Imaging data processing familiarity androutinization. Since this functional asymmetry was first proposed (Goldberg and Costa, 1981; Goldberg et al., Averaged volumetric MRI images were used to model each 1994a), it has found support with various neuroimaging tech- subject's cortical surface with an automated procedure niques, including PET (Gold et al., 1996; Shadmehr and involving white-matter segmentation, gray/white matter Holcomb, 1997), fMR1 (Henson et al., 2000), and high- boundary tessellation, inflation of folded surface tessellation, frequency EEG (Karniya et al., 2002). It has been argued that and automatic topological defect correction (Dale et al., 1999; the "novelty-routinization" functional hemispheric asymme- Fisch' et al., 2001). try is fundamental and irreducible to the more commonly Automated analysis was performed on a 156 node invoked language-visuospatial asymmetry, since it is present computing duster and took approximately 32 h per scan. Each in a wide range of mammalian species (Vallortigara, 2000; analysis was then manually inspected which took, depending Vallortigara and Rogers, 2005; Vallortigara et al., 1999). on segmentation quality, 20-40 min. Measures of cortical To account for these functional differences, it has been thickness were obtainedby constructingestimates of the gray/ proposed that systematic differences between the two hemi- white matterboundaty by classifyingall white matter voxels in spheres exist in relative cortical space allocation to hetero- the MR1volume. The white matter surface was submillimeter modal association cortices versus modality-specific cortices accuracy-refined in delineating the gray/white matter EFTA00301229 Author's personal copy 202 CORTEX 49 (2013) 200-210 junction. Estimates of cortical thickness were made by conducted in terms of ROts volumes, each derived from measuring (1) the shortest distance from each point on the cortical thickness measures and surface area parcellation white matter surface to the pial surface, and (2) the shortest boundaries. We found multiple regional hemispheric asym- distance from each point on the pial surface to the white metries which are summarized in Fig. 1 and Table 1. In order matter surface. Cortical thickness at each vertex was to highlight the most robust and best articulated patterns of computed as the average of the two values. The accuracy of asymmetries, the results and discussion below detail only automatic parcellation methods is often undermined by indi- those asymmetries which remained significant at p <.0S level vidual variability. For this and other reasons, manual quality after a rigorous Bonferroni correction for multiple compari- inspection was performed on all reconstructions and required sons was applied (a = .00067). This correction, which lowers manual intervention in 5% of scans. All of these cases were Type I errors at the expense of Type II errors, highlighted the reinspected and all yielded good segmentation results. Maps most prominent asymmetries. These are summarized in Fig. 2 were smoothed with a Gaussian kernel (10 mm FWHM) across and described below. Here we present the result of regional the surface. Cortical surfaces from different individuals were cortical volume comparisons. We found that regional cortical morphed to a common reference brain by aligning sulcal—gyral surface comparisons were generally consistent with the patterns while minimizing shear and metric distortions (Fischl volume comparisons Thickness comparisons yielded few et at, 1999). Automatic parcellation of the cortical surface was significant asymmetries when rigorous statistical criteria performed with sulco-gyral neuroanatomic labels derived by were used. probabilistic information. Past research has validated these automatic labels against anatomical manual labels and 85% of 3.1. Whole-sample asymmetries (males and females the surface was found to be concordant (Destrieux et al., 2009, combined) 2010). Parcel regions of interest (ROI) designation as 'gyrus" or "sulcus" was based on the values of local mean curvature and Fig. lA shows uncorrected p values, while Fig. 2A shows post- average convexity, obtained from the reconstructed cortical Bonferroni significant asymmetries for the whole sample. The surfaces output from FreeSurfer, relative to a given threshold; superior frontal gyms, superior frontal sulcus, frontomarginal vertices with values below the threshold were considered sulcus, suborbital sulcus, gyms rectos, postcentral gyms, sulcal, and vertices with values equal to or above this threshold postcentral sulcus, tinplate gyms, paracentral gyms, were considered gyral. A total of 75 ROI were identified in each subcentral gyros, transverse temporal gyri, superior temporal hemisphere. In each ROI, cortical thickness estimates were gyms (lateral aspect), planum temporale, superior parietal averaged across all vertices. Regional volumes were calculated gyms, anterior occipital sulcus, ascending ramus of the lateral as the product of surface area and average cortical thickness. fissure, and circular insular sulcus (superior and inferior For the whole-sample analysis, a laterality index (U) — as aspects) were larger in the left than right (L > R) hemisphere defined by Nagata et al. (2001) — was used to control for sex- across the whole sample (all p values < .00067). Conversely, linked variability in global brain volume. Regional LI values the inferior parietal gyms, superior occipital gyms, lingual were calculated for each subject using the following equation: gyms, calcarine sulcus, lateral fissure (posterior segment), collateral transverse sulcus, middle frontal sulcus, subparietal Left — Right x 100 LI sulcus, anterior subcentral sulcus, superior temporal sulcus, Left + Right cingulate sulcus, the lateral aspect of orbital gyri, pericallosal This index spans from —100 to 100 with positive values sulcus, and Jensen sulcus were larger in the right than left indicating leftward asymmetry, negative values indicating (R> L) hemispheres (all p values < .00067). This is summarized rightward asymmetry, and zero indicating perfect symmetry. in Fig. 2A, where regions larger in the right hemisphere are For each ROI, a two-tailed single-sample t- test was used to depicted in yellow and regions larger in the left hemisphere compare the distribution of LI values against zero. To main- are depicted in blue. tain an experiment-wise error rate of .0S, Bonferroni correc- tion (a = .00067) was employed to address the problem of 3.2. Analyses of sex-linked differences multiple comparisons, where the number of comparisons was 75. In separate analyses by sex, paired-sample t-tests were When grouped by sex, leftward asymmetries (L > P) of the used to compare left and right regional volumes among each anterior occipital sulcus and lateral aspect of superior pair of contralateral ROIs. An identical Bonferroni correction temporal gyms were significant in females (both method was utilized for these pairwise tests. Areas were p values < .00067) but not males (p > .05 and p < .005, considered asymmetric if the statistical significance criterion respectively) while the cingulate gyms, planum temporale, (a = .00067) was reached. Reported visualizations map statis- and superior frontal sulcus were significantly larger on the left tical results on the 3D whole brain volume (with the parcel in males (all p values < .00067) but not females (p < .05, boundaries between the structures exhibiting the same p < .005, and p < .005, respectively). Conversely, rightward direction of laterality removed for visual clarity). asymmetry (R > L) of the lingual gyms occurred in females (p < .00067) but not males (p < .005) and the subparietal sulcus was significantly larger in the right hemisphere in 3. Results males (p < .00067) but not females (p < .005). Notably, the superior temporal and Jensen sulci and the lateral aspect of Since we were interested in the relationship between func- orbital gyri both failed to reach significance in either sex alone tionally distinctive cortical regions, the analysis has been despite displaying significant rightward asymmetry in the EFTA00301230 Author's personal copy CORTEX 49 (2013) 200-210 203 Significance (p) <.00005 .0005 .005 .05 .05 .005 .0005 <.00005 L>R R >L Pig. 1 - Regional cortical volume asymmetries in the two hemispheres uncorrected for multiple comparisons. Direction of differences and uncorrected significance levels are coded according to the color bar below: (A) whole-sample, (B) females only, (C) males only. whole-sample analysis. No parcels revealed significant later- As a result, several distinct asymmetry patterns emerged, ality in opposing directions across sexes. which are discussed below. Sex-specific results are detailed in Table 2. Fig. 111 and C shows uncorrected p values for females and males, respec- 4.1. Heteromodal association cortical asymmetries tively, while Pig. 2B and C shows post-Bonferroni significant asymmetries for each sex. Although Pigs. 1 and 2 appear to We found differences in the hemispheric representation of suggest sex differences, an ANOVA failed to reveal significant heteromodal association cortices. Heteromodal inferoparietal interactions between sex and laterality in any ROI. and ventrolateral prefrontal cortices are more extensive in the right than left hemisphere. By contrast, mesial and orbital prefrontal and cingulate cortices are more extensive in the left 4. Discussion than right hemisphere. These asymmetries closely parallel the findings by Luders et aL (2006) pertaining to cortical thickness. In this study we intentionally adopted a conservative signifi- Thus it appears that heteromodal association regions found cance criterion for data analysis, in order to identify a rela- on the lateral (convexital) aspect of the hemisphere, are more tively small number of the most robust hemispheric extensive in the right than in the left hemisphere, as predicted differences while possibly overlooking less robust differences. earlier (Goldberg and Costa, 1981). This is true both for the EFTA00301231 uthor's personal copy 204 CORTEX 4.9 (201 3) 200-210 Table 1 Regional volumetric comparisons and Lls - + x 1001 for males and females combined. For each ROI, the means a nd SDs of right and left hemisphere cortical volume (mm3) measurements, as well as the means and SDs of Lls, are listed. ROI Mean (SD) Sig. Left (mm^3) Right (inntA3) Ll Anterior occipital sulcus 1097.4 (274.3) 895.8 (298.2) 11.07 (17.52) <.05• Calcarine sulcus 3381.8 (699.1) 3903.7 (709.3) -7.21 (5.62) <.054 Central insular sulcus 289.1(81) 258.5 (72.9) 5.73 (20.7) n.s. Central sulcus 3609.6 (492) 3488.8 (633) 1.96 (5.57) n.s. Cingulate and intracingulate sulci 6797.9 (956.1) 9525.1 (1372.4) -16.63 (6.06) <.05• Cingulate gyms 9740.8 (968.5) 3979.2 (710.1) 8.44 (11.18) <.05' Cingulate sulcus (marginalis part) 1332.1 (259.9) 1312.5 (309.3) 1.11 (11.42) n.s. Circular sulcus of insula (anterior) 935.5 (153.3) 1050.3 (266.4) -5.06 (8.77) n.s. Circular sulcus of insula (inferior) 2299.2 (332.3) 1908.4 (270.8) 9.22 (5.87) <.054 Circular sulcus of insula (superior) 2778 (367.8) 2199.3 (324.6) 11.68 (5.8) <.05• Collateral transverse sulcus (anterior) 1523.3 (388.8) 1673.2 (473.8) -4.47 (15.35) n.s. Collateral transverse sulcus (posterior) 492.8 (155.3) 762.6 (212.9) -21.3 (16.74) <.05• Cuneus 3907.2 (597.6) 3399.4 (654.4) 31(7.98) n.s. Frontomarginal gyms 1032.2 (290.9) 1196.8 (314.9) -7.71(13.01) n.s. Frontomarginal sulcus 1006.4 (252.7) 764.5 (190.2) 13.19 (14.95) <.054 Cyrus rectos 2154.9 (361.5) 1669 (302.1) 12.67 (8.52) <.054 H-shaped orbital sulcus 2502 (395.1) 2428.2 (401) 1.55 (8.04) n.s. Inferior frontal gyms (opercular part) 3903.2 (653.1) 3150.7 (503) 3.59 (8.45) n.s. Inferior frontal gyms (orbital part) 871(291.7) 935.2 (233.6) -4.26 (16.47) n.s. Inferior frontal gyms (triangular part) 2698.4 (453) 2704.8 (546.5) .18 (9.12) n.s. Inferior frontal sulcus 3101.6 (798.6) 2968.4 (479.9) 1.63 (9.78) n.s. Inferior occipital gyrus and sulcus 2797 (717.6) 2832.9 (628.7) -1.05 (12.42) n.s. Inferior parietal gyms (angular part) 5535.6 (868.2) 6946.9 (1132.1) -11.69 (7.6) <.09 Inferior parietal gyms (supramarginal part) 6671.4 (1173.9) 6465.7 (1011.6) 1.39 (6.57) n.s. Inferior temporal gyms 6362.9 (1149.1) 6227 (1315) .89 (8.09) n.s. Inferior temporal sulcus 1972.1(987.2) 1793.4 (444.1) 4.63 (12.13) n.s. Insular gyms (long) 870.4 (298.7) 874.4 (172.8) -.84 (9.26) n.s. Insular gyrus (short) 1852.7 (326.6) 1776.1 (355.4) 2.38 (7.17) n.s. Intraparietal and transverse parietal sulci 3815.8 (522.2) 9022 (579.3) -2.58 (7.02) n.s. Isthmus 351.4 (101.7) 375.3 (100.4) -3.64 (12.05) n.s. Lateral fissure (horizontal ramus) 499 (191.6) 578.6 (124.1) -7.81 (13.96) n.s. Lateral fissure (posterior) 1638 (271.5) 1968.1 (250.6) -9.34 (7.33) <.0511 Lateral fissure (vertical ramus) 598.4 (166.7) 435.1 (139.5) 15.52 (21.28) <.05' Lateral occipito-temporal gyms (fusiform) 9522.9 (751) 4192.5 (804.7) 3.92 (8.47) n.s. Lateral orbital gyms 6260.5 (998.2) 6802.1 (1197.1) -4.07 (5.4) <.054 Lateral orbital sulcus 628.8 (200.3) 727.4 (299.4) -6.1(17.97) n.s. Lingual gyms 5609.9 (930.2) 6546.4 (960.8) -7.78 (7.11) <.05• Medial occipito-temporal and lingual sulci 3187.2 (574.5) 3187.3 (654.1) .11 (7.95) n.s. Medial occipito-temporal gyms 9242.8 (565.7) 4494.5 (554.2) -2.91 (7.24) n.s. (parahippocampal part) Medial orbital sulcus 913 (199.8) 858.3 (173.4) 3.34 (10.05) n.s. Medial wall 5543.9 (1079.9) 5513.1 (733.2) -2.1 (5.7) n.s. Middle frontal gyms 9632.9 (1944.6) 10211.8 (1836.7) -3.1 (7.08) n.s. Middle occipital gyms 9911.2 (579.7) 9563 (739.8) -1.49 (7.36) n.s. Middle occipital sulcus and sulcus lunatus 1550 (920.7) 1589.4 (534.9) -.32 (17.4) n.s. Middle temporal gyms 8128.8 (1368.6) 8497.4 (1359.7) -2.29 (5.48) n.s. Occipito-temporal sulcus (lateral) 1328.6 (331.5) 1413.6 (338.3) -3.3 (11.28) n.s. Paracentral gyrus 2554.8 (914.5) 2101 (337.4) 9.77 (8.13) <.05• Paracentral sulcus 318.5 (94.2) 275.2 (84.8) 7.52 (18.39) n.s. Parieto-occipital sulcus 2643.4 (591) 2828.1 (496.8) -3.62 (7.44) n.s. Pericallosal sulcus 1303.4 (211.3) 1592.1 (275.5) -9.88 (9.03) <.05• Planum polare 1873.4 (387.7) 1950.1 (400.5) -2.05 (9.81) n.s. Planum temporale 2293.3 (493.9) 1887.6 (361.7) 9.35 (11.89) <.054 Postcentral gyrus 4201.2 (677) 3556.1 (710.2) 8.57 (6.99) <.05• Postcentral sulcus 3794.8 (698.6) 3006.9 (759.1) 12.13 (8.64) <.05' Precentral gyms 6246.9 (825.9) 6211.5 (959.3) .41 (5.48) n.s. Precentral sulcus (inferior part) 2975.8 (571.5) 2615.8 (317) -3.49 (9.88) n.s. Precentral sulcus (superior part) 1933.5 (967.3) 2062.4 (398.2) —158 (11.84) n.s. Precuneus gyms 5724.6 (800.9) 5285.8 (8S7.5) —.05 (5.38) n.s. Subcallosal gyms 315.6 (194.3) 256.6 (81.8) 7.29 (30.36) n.s. EFTA00301232 205 (continued) Lit.'• ROI 1 Mean (SD) Left (mm^3) Right (mm^3) LI Subcentral gyrus 2573.9 (395) 1986.4 (386.4) 13.06 (9.43) <L0P Subcentral sulcus (anterior) 163.3 (83.8) 287.9 (109.5) -27.61 (29.22) c.09 Subcentral sulcus (posterior) 499.5 (148.3) 440 (123.2) 5.92 (16.33) n.s. Suborbital sulcus 1007.7 (249.5) 617.1 (185.8) 24.38 (13.13) <.05' Subparietal sulcus 1694.1 (342.2) 2081.9 (484.4) -9.78 (10.09) <.09 Sulcus intermedius primus (Jensen) 546.2 (259) 704.3 (275.5) -13.65 (22.15) <.05' Superior frontal gyrus 20151 (2783.3) 18661.6 (2336) 3.75 (2.92) <.05' Superior frontal sulcus 4794.6 (972.9) 4085.2 (909.9) 7.99 (8.3) <.05' Superior occipital gyms 2455.3 (452) 3098.4 (612.4) -11.34 (8.25) <.05' Superior occipital sulcus and sulcus transversalis 1699.7 (327.5) 1815.1 (327.8) -4.82 (10.95) n.s. Superior parietal gyms 5735 (977.9) 4746.1 (718.8) 9.25 (6.23) <.05' Superior temporal gyms (lateral aspect) 5907.4 (842.2) 5138.2 (788.9) 7.01 (6.41) <.05' Superior temporal sulcus 8790.3 (1275.9) 9666.6 (1151.9) -4.89 (5.61) <.05' Temporal pole 5607.1 (836.1) 5968.2 (678.1) -1.07 (6.29) n.s. Transverse temporal gyrus and intermediate sulcus 1087.6 (206.2) 840.1 (184.9) 12.94 (9.61) ‹.05' Transverse temporal sulcus 531.3 (137.2) 456.7 (100.8) 7.16 (13.78) n.s. a After Bonferroni correction for multiple comparisons. inferoparietal and for parts of the lateral prefrontal regions. By prefrontal regions, as well as for the cingulate cortex. The dual contrast, heteromodal association cortices found on the mesial dissociation in the volumetric asymmetries of lateral versus and orbital aspects of the hemisphere are more extensive in the mesial heteromodal association cortices is not commonly left than in the right hemisphere. This is true for the mesial mentioned in the literature on hemispheric differences, but it Fig. 2 — Regional cortical volume asymmetries in the two hemispheres corrected for multiple comparisons. Regions significantly larger after the correction ( p < .05) in the left hemisphere are in blue; regions significantly larger in the right hemisphere are in yellow: (A) whole-sample, (B) females only, (C) males only. EFTA00301233 .uthor's personal copy 206 CORTEX 4.9 (2013) 200-2 ID Table 2 lb gional volumetric comparisons in separate sexes. Data are presented separately for males and females. For each ROI, the means and SDs of right and left hemisphere cortical volume (mm3) measurements are listed. ROI Males Females Mean (SD) Sig. Mean (SD) Sig. Left (mmA3) Right (mmA3) Left (mmA3) Right (mmA3) Anterior occipital sulcus 1092 (272.3) 950.6 (257.8) ns. 1103.1 (283.9) 838.1 (332.8) <.05° Calcarine sulcus 3462.6 (698) 4012.5 (736.4) <.05° 3296.8 (600.3) 3789.1 (680.1) <.05° Central insular sulcus 309.8 (73.4) 274.7 (583) n.s. 267.4 (84.8) 241.4 (83.8) n.s. Central sulcus 3675.9 (596.9) 3670.5 (7124) n.s. 3539.9 (353.4) 32973 (484.6) n.s. Cingulate and intracingulate sulci 7042.7 (1030A) 10100.4 (1375.1) <.05° 6540.2 (820) 89193 (1106.8) <.05° Cingulate gyms 5140.9 (836.4) 4133.2 (729.2) <.05° 4319.6 (936.3) 3817.1 (670.3) n.s. Cingulate sulcus (marginalis part) 1390.7 (209.8) 1393.1 (331.4) ns. 1270.4 (297.3) 1227.7 (266.7) n.s. Circular sulcus of insula (anterior) 1009.2 (134.8) 1153.6 (313.7) ns. 857.9 (134.3) 941.7 (147.1) n.s. Circular sulcus of insula (inferior) 2417.7 (315.2) 2020.5 (271.6) <.05° 2174.4 (310.2) 1790.5 (120) <.05° Circular sulcus of insula (superior) 2928.6 (366.8) 2259.9 (348.5) <.05° 2619.6 (303.2) 2135.5 (293) <.05° Collateral transverse sulcus (anterior) 1548.2 (334.1) 1657.7 (557.5) ns. 1497 (447) 16895 (381.1) n.s. Collateral transverse sulcus (posterior) 522.5 (184.5) 828.4 (218.7) <.05° 461.6 (113.8) 6914 (188) <.05° Cuneus 3631.2 (480) 3575.4 (783.5) ns. 3171.5 (524.8) 3214.3 (430.9) n.s. Frontomarginal gyrus 1154.7 (279.1) 1331.5 (343.5) ns. 903.3 (249.5) 1054.9 (208.4) n.s. Frontomarginal sulcus 1077.7 (252.4) 805.2 (211.3) n.s. 931.4 (236.5) 721.6 (159.6) n.s. Cyrus rectus 2318.7 (328.2) 1800 (310.4) <.05° 1981.5 (317.3) 1531.3 (227.7) <.05° H-shaped orbital sulcus 2573.1 (435.9) 2538.3 (433.2) n.s. 2427.3 (342.8) 2312.3 (337.3) n.s. Inferior frontal gyms (opercular part) 3608.3 (766.2) 3252.9 (523.2) n.s. 3181.1 (426.6) 3043.2 (470.6) n.s. Inferior frontal gyms (orbital part) 907.8 (262.4) 989.3 (271.4) n.s. 832.3 (218.2) 878.3 (175.5) n.s. Inferior frontal gyms (triangular part) 2809.5 (520) 2880.6 (537.6) n.s. 2581.6 (345.9) 2519.7 (504.9) n.s. Inferior frontal sulcus 3274 (960.3) 3085 (582.1) n.s. 2920 (376.7) 2845.6 (312.2) n.s. Inferior occipital gyrus and sulcus 2997.7 (7444 2953 (578.9) n.s. 2585.8 (640) 2706.5 (669.2) n.s. Inferior parietal gyms (angular part) 5673.6 (872.9) 7436.8 (1005.8) <.05° 5390.3 (862.3) 6431.2 (1044.2) <.05° Inferior parietal gyms (supramarginal part) 7077.1 (1204) 6718 (1118) n.s. 6244.3 (1001.9) 6203 (834.2) n.s. Inferior temporal gyms 6877.1 (1152.9) 6610.4 (1209.7) n.s. 5821.7 (1558) 5823.5 (1330.7) n.s. Inferior temporal sulcus 2104.4 (452.3) 1949.2 (436.8) n.s. 1832.8 (495.2) 16213 (399.5) n.s. Insular gyms (lon) 880.1 (160.8) 925.2 (182.7) n.s. 860.2 (321) 821.1 (148) n.s. Insular gyrus (short) 1966.4 (312.4) 1931 (315) n.s. 1733.1 (304.5) 1613 (327.4) n.s. Intraparietal and transverse parietal mkt 3972.5 (538.7) 4225.4 (652.1) n.s. 3651 (461.9) 3807/ (406.5) n.s. Isthmus 373.6 (117.6) 412.4 (118.6) n.s. 328 (78.3) 336.2 (57.4) n.s. Lateral fissure (horizontal ramus) 528.7 (160) 607 (147.7) n.s. 467.7 (115.3) 548.6 (87.4) n.s. Lateral fissure (posterior) 1683.7 (313.7) 2071.6 (277.5) <.05° 1590 (216.9) 1859.1 (163.8) <.05° Lateral fissure (vertical ramus) 602.7 (159.3) 413.6 (139.2) n.s. 593.9 (178.5) 457.8 (139.9) n.s. Lateral occipito-temporal gyrus (fusiform) 4629/ (691) 4588.8 (773.3) n.s. 4409.4 (812.7) 3775.3 (614.3) n.s. Lateral orbital virus 6686 (964.1) 7314.6 (1339.5) n.s. 5812.7 (842.4) 6262.6 (729.5) n.s. Lateral orbital sulcus 691.4 (218) 790.7 (364.4) n.s. 562.9 (160.2) 6617 (199.8) n.s. Lingual gyms 5917.4 (9714) 6750.1 (984.9) n.s. 5286.3 (773.6) 6331.9 (911.2) <.05° Medial occipito-temporal and lingual sulci 3334.1 (492.3) 3461.4 (758.6) n.s. 3032.6 (625.8) 2898.8 (352.8) n.s. Medial occipito-temporal gyrus 4443.2 (547.1) 4657.3 (514.7) n.s. 4031.9 (517.8) 4323.1 (555.2) n.s. (parahippocampal part) Medial orbital sulcus 960.8 (152.5) 914 (203.5) n.s. 862.8 (132.8) 799.6 (112.5) n.s. Medial wall 5954.4 (9012) 5731.4 (551.7) n.s. 5110.9 (1105.3) 5283.2 (839.5) n.s. Middle frontal gyms 10194.3 (2124.6) 10775.8 (2222.3) n.s. 9041.1 (1580.6) 9618 (1087.8) n.s. Middle occipital gyms 4560.4 (585.1) 4793.6 (816.1) n.s. 4254.2 (545.2) 4320.2 (575.4) n.s. Middle occipital sulcus and sulcus lunatus 1576.1 (381.3) 1696.4 (491.6) n.s. 1522.6 (467.6) 1476.7 (568.3) n.s. Middle temporal gyms 8750.1 (1118.5) 9180 (1223.2) n.s. 7474.8 (1324.1) 7778.9 (1123) n.s. Occipito-temporal sulcus (lateral) 1410.3 (311.2) 1482.6 (373.5) n.s. 1242.7 (338.5) 1341 (289) n.s. Paracentral gyrus 2692.2 (368.1) 2187.8 (302.7) <.05° 2410.2 (420.3) 2011.7 (432.7) <.05° Paracentral sulcus 329 (103.9) 300.2 (73.2) ns. 307.5 (84.3) 248.8 (89.9) n.s. Parieto-occipital sulcus 2836 (541.8) 2962.5 (4314) ns. 2440.7 (472.7) 2686.6 (530.6) n.s. Pericallosal sulcus 1367.4 (185.9) 1637.4 (259.8) <.05° 1236 (220.1) 1544.4 (290.3) <.05° Planum polare 1930.8 (4252) 2051.8 (440.6) ns. 1812.9 (344.2) 1843.2 (332) n.s. Planum temporale 2407/ (581.6) 1889.6 (379.4) <.05° 2172.7 (356.4) 1885.5 (352.5) n.s. Postcentral gyms 4212.6 (7752) 3691.4 (715.1) <.05° 4189.2 (577.2) 3413.8 (695.2) <.05° Postcentral sulcus 4077.7 (652.3) 3292.3 (858) <.05° 3497.1 (506.3) 2706.4 (503.7) <.05° Precentral gyms 6533.2 (884.7) 6609.1 (1009.6) ns. 5945.6 (653.4) 5792.9 (711.6) n.s. Precentral sulcus (inferior part) 2544.3 (636) 2665 (370.5) ns. 2403.7 (502) 2564/ (248.8) n.s. Precentral sulcus (superior part) 2083/ (552) 2239.4 (356.1) 1775.2 (296.2) 1876.1 (359.8) n.s. Precuneus gyms 5590.3 (929.6) 5663.8 (986.3) 4942.4 (461.5) 4887/ (446.9) n.s. Subcallosal gyms 318.8 (155.1) 244.3 (85.5) 312.3 (136.3) 269.6 (77.8) n.s. EFTA00301234 Author's personal copy CORTEX 4.9 (2013) 200-210 207 in .(condnued) ROI Males Females Mean (SD) Sig. Mean (SD) Sig. Left (mmA3) Right (mmA3) Left (mmA3) Right (mmA3) Subcentral gyms 2625.2 (482.1) 2011.2 (400.1) <.05" 2519.8 (279.2) 1960.3 (380.6) <.05" Subcentral sulcus (anterior) 168.8 (95) 301.6 (107.5) as. 157.4 (72.2) 273.5 (112.6) n.s. Subcentral sulcus (posterior) 534.4 (146.5) 454.4 (107) as. 462.9 (144.9) 424.7 (139.7) n.s. Suborbital sulcus 1096 (262.8) 704.2 (184.8) <.05" 914.8 (201.9) 525.5 (139.9) <.05" Subparietal sulcus 1765.3 (416.6) 2190.8 (539) <.05" 1619.1 (228.8) 1967.2 (403.3) n.s. Sulcus intermedius primus (Jensen) 606.2 (265.4) 811.3 (326.8) as. 483.1 (231.7) 591.7 (146.5) n.s. Superior frontal gyms 21154.3 (3018.9) 19435.4 (2431.2) <.05" 19094.9 (2106.8) 17487.1 (1978.6) <.05" Superior frontal sulcus 5054.1 (971.2) 4238.2 (987.4) <.05" 4521.4 (921.4) 3924.1 (815.7) n.s. Superior occipital gyms 2620.8 (489.4) 3457.7 (536.6) <.05° 2281.2 (340.7) 2720.2 (439.6) <.05" Superior occipital sulcus and 1712 (354.6) 1807.6 (397.4) as. 1584.1 (291.3) 1822.9 (245.1) n.s. sulcus transversalis Superior parietal gyms 6141 (944.5) 5011(745.6) <.05* 5307.7 (837.6) 4467.3 (586.5) <.05" Superior temporal gyms (lateral aspect) 6205.8 (902.2) 5509 (727.7) as. 5593.4 (659.6) 4747.8 (664.2) <.05' Superior temporal sulcus 9046.6 (1251.5) 10057.2 (1069) as. 8520.5 (1278.1) 9255.6 (1116.8) n.s. Temporal pole 5982.5 (642.5) 5987.8 (612.6) as. 5211.9 (847.7) 5393.4 (619.1) n.s. Transverse temporal gyms and 1124.6 (238.6) 872.7 (213.9) <16' 1048.6 (162.8) 807.5 (147) <.05" intermediate sulcus Transverse temporal sulcus 563.2 (155.1) 457.5 (111.3) as. 497.7 (109.8) 455.9 (91.5) n.s. a After Bonfenoni correction for multiple comparisons. may be important for refining our understanding of hemi- hemisphere. By contrast, somatosensory cortex, auditory spheric specialization. Inferoparietal association cortex, near cortex, portions of premotor cortex, and motor cortices the boundary of temporal and parietal lobes, helps maintain controlling oropharyngeal structures are more extensive in attention to the outside world (Corbetta and Shulman, 2002), the left than right hemisphere. Our findings that the superior and its damage, particularly on the right side, results in atten- temporal gyms, planum temporale, and inferior portion of the tional impairment (Heilman et al., 2003). Prefrontal cortex motor areas are volumetrically larger in the left than right found on the lateral aspect of the hemisphere (dorsolateral and hemisphere parallel previously reported asymmetries in the ventrolateral) is critical for accessing and activating task- planum temperate and frontal operculum (Geschwind and relevant representations found in the posterior association Levitsky, 1968; Galaburda et al., 1978). Luders et al. (2006) re- cortices (O'Reilly and Munakata, 2000; Jonides et al., 2008; Van ported a similar pro-left hemispheric asymmetry in the Snellenberg and Wager, 2009). Close neuroanatomical connec- cortical thickness of anterior temporal-lobe structures. Our tivity and functional relationship exists between the posterior finding of pro-right hemispheric differences in the volume of heteromodal association cortices and lateral prefrontal heter- cortex implicated in visual processing parallels the cortical omodal association cortices (Goldman-Rakic, 1988; Fuster, surface differences reported by Lyttelton et al. (2009) and 2008). By contrast, mesial/orbitomesial prefrontal and anterior cortical thickness differences reported by Luders et al. (2006). cingulate cortices (ACCs) are critical for salience-driven deci- These asymmetries are broadly consistent with the sion making guided to a large extent by the organisms's internal commonly described left hemispheric dominance for states, motivations and needs (Bechara et al., 1998; Koenigs language and right hemispheric dominance for visuo-spatial et al., 2007; Botvinick et aL, 1999; Carter et al., 1999). The func- processing in humans. tional implications of the dual lateral versus mesial hetero- modal association cortical asymmetry with opposite and 4.3. Cortical space allocation on the lateral versus mesial complementary cortical space allocation are intriguing and aspects of the hemispheres they await further clarification. A possible relationship between hemispheric differences in heteromodal versus modality- Cortical space allocation on the lateral (convexital) aspect specific cortical space allocation and the differential roles of appears to follow a relatively clear pattern. Heteromodal the two hemispheres in learning was ascertained in the old association cortices are more extensively represented in the literature (Goldberg and Costa, 1981), but it clearly requires a re- right than in the left hemisphere. We found this to be true examination with modem methodology. both for the prefrontal and for the inferoparietal cortices. By contrast, modality-specific cortices are more extensively 4.2. Modality-specific cortical asymmetries represented in the left than in the right hemisphere. Our data confirmed this for somatosensory cortex, auditory cortex, We also found hemispheric differences in the modality- portions of premotor cortex, and motor cortices controlling specific cortical regional volumes. Areas implicated in visual oropharyngeal structures. This is consistent with the earlier processing are more extensive in the right than left predictions (Goldberg and Costa, 1981). EFTA00301235 Author's personal copy 208 CORTEX g (2013) 200-2 ID We found that cortical space allocation on the mesial notably schizophrenia (Chance et al., 2008; Schobel et al., 2009; aspect appears to be characterized by a more extensive Wolf et al., 2008) and fronto-temporal dementia (Boccardi et al., representation of the orbital and mesial frontal and cingulate 2003; Jeong et al., 2005; Kanda et al., 2008; Whitwell et al., 2005). cortices in the left than right hemisphere. The findings presented in this paper may help shed further light on the nature and implications of such asymmetries in 4.4. Sex•linked differences these disorders. Several patterns of hemispheric asymmetries described in Functional lateralization of the brain is present both in this paper are particularly intriguing. These include the dual females and in males and is controlled by multiple factors (Liu asymmetry of lateral versus mesial heteromodal association et al., 2009). Examination of sex-linked differences in cortical cortices, and the asymmetry of cortical space allocation morphology was not the primary focus of this study and any between heteromodal association and modality specific such differences reported here should be viewed as prelimi- association cortices on the lateral (convexital) aspects of the nary and requiring confirmation with larger samples. None- two hemispheres. In this paper we presented morphometric theless, our findings suggest volumetric asymmetry in the findings without any correlated neuropsychological data. cingulate cortex (left larger than right) in males but not in Future studies may attempt to correlate the degree of females. The functional implications of this asymmetry is expression of the asymmetries described here in healthy unclear, but it does parallel the sex-linked differences in the individuals with cognitive variables. effects of lateralized prefrontal lesions on response selection Analytic or computational models may also be illumi- in an intentionally underconstrained, ambiguous perceptual nating in understanding complex structure—function rela- preference tasks devoid of intrinsic "true-false" metric tions. The differences in cortical space allocation to (Goldberg et al., 1994a, 1994b; Goldberg and Podell, 1999). In heteromodal versus modality-specific cortices can be rela- right-handed females, both left and right frontal lesions shift tively readily represented in formal models. It may be possible responses toward extreme dependence on the perceptual to clarify the functional ramifications of the asymmetries in context, making them excessively changeable compared to cortical space allocation described in this paper computa- healthy controls. In right-handed males right frontal lesions tionally, by modeling them in multilayered neural net archi- shift responses toward extreme context dependence, but left tectures and examining the effects of parametric variations frontal lesions — toward extreme context independence within the models on learning (for a more detailed outline of characterized by excessively stable responses. this approach see Goldberg, 2009). These sex-linked differences in the lateralized prefrontal In conclusion, despite the prodigious body of work on lesion effects on response selection parallel our findings of hemispheric specialization, the riddle is far from solved, and sex-linked differences in the relative sizes of the left and right more interdisciplinary work is needed, combining neuro- ACC: they are symmetric in females and asymmetric in males. psychological, neuroimaging, computational, genetic, and ACC plays a role in resolving situations characterized by clinical approaches into a coordinated research effort. uncertainty and ambiguity (Krain et al., 2006; Pushkarskaya et al., 2010). Sex-linked differences in the degree of laterali- zation of the frontal-lobe control over response selection in REFERENCES ambiguous, underdetermined situations may be a conse- quence of sex-linked differences in the degree of structural ACC asymmetries. While ACC is not the only structure Anderson B, Southern BD, and Powers RE. Anatomic asymmetries implicated in decision making under ambiguity — so are the of the posterior superior temporal lobes: A postmortem study. orbitofrontal and mesial frontal areas — the fact that the sex- Neuropsychiatry, Neuropsychology, and Behavioral Neurology, linked differences in decision making in ambiguous environ- 12(4): 247-254, 1999. Beaton AA. The relation of planum temporale asymmetry and ments parallel the anatomical findings in ACC but not in the morphology of the corpus callosum to handedness, gender, other regions may suggest a particularly central role of ACC in and dyslexia: A review of the evidence. Brain and Language, resolving ambiguity. 60(2): 255-322, 1997. Bechara A, Damasio H, Tranel D, and Anderson SW. Dissociation 4.5. Limitations and future directions of working memory from decision making within the human prefrontal cortex. Journal of Neuroscience, 18(1): 428-437, 1998. Replication of our findings, particularly as they pertain to sex- Blackmon T, Barr WB, Kuzniecky R, DuBois J, Carlson CE, Quinn BT, et al. Phonetically irregular word pronunciation and linked differences, needs to be conducted with a larger cortical thickness in the adult brain. Neurolmage, 51(4): sample. The generalizability of our findings across lifespan is 1453-1458, 2010. unclear at this time, since changes in morphological hemi- Boccardi M, Laakso MP, Bresciani L, Galluzi 5, Geroldi C, spheric asymmetries with age have been reported (Raz et al., Beltnmello A, et aL The Mm pattern of frontal and temporal 2004; Shaw et al., 2009). Thus replications in different age brain atrophy in fronto-temporal dementia. Neurobiology of groups are important. Aging, 24(1): 95-103, 2003. Botvinick M, Nystrom LE, Fissel K, Carter CS, and Cohen JD. Further elucidation of the relationship of hemispheric Conflict monitoring versus selection-for-action in anterior asymmetries described here and neurological/neuropsychi- cingulate cortex. Nature, 402(6758): 179-181, 1999. atric disorders is another promising direction. Several neuro- Carter CS, Botvinick M, and Cohen JD. The contribution of the logical and neuropsychiatric disorders are characterized by anterior cingulate cortex to executive processes in cognition. asymmetric regional structural or physiological abnormalities, Reuiews in Neuroscience, 10(1): 49-57, 1999. EFTA00301236 Author's personal copy CORTEX 4.9 (2013) 200-210 209 Chance SA, Casanova MF, Suitela AE, and Crow TJ. Auditory Goldberg E and Podell K. Adaptive versus veridical decision cortex asymmetry, altered minicolumn spacing and absence making and the frontal lobes. Consciousness and Cognition, 8(3): of ageing effects in schizophrenia. Brain, 131(12): 3178-3192, 364-377, 1999. 2008. Goldberg E, Hamer R, Lovell M, Podell K, and Riggio S. Cognitive Corbetta M and Shulman GL. Control of goal-directed and bias, functional cortical geometry, and the frontal lobes: stimulus-driven attention in the brain. Nature Reviews Laterality, sex, and handedness. Journal of Cognitive Neuroscience, 3(3): 201-215, 2002. Neuroscience, 6(3): 276-296, 1994a. Crespo-Facorro B, Ftoiz-Santilfiez R, Perez-Iglesias R, Meta I, Goldberg E, Podell K, and Lovell M. Lateralization of frontal lobe Rodriguez-Sanchez JM, Tordesillas-Gutierrez D, et aL Sex- functions and cognitive novelty. Journal of Neuropsychiatry and specific variation of MR1-based cortical morphometry in adult Clinical Neurosciences, 6(4): 371-378, 1994b. healthy volunteers: The effect on cognitive functioning. Goldman-Rakic PS. Topography of cognition: Parallel distributed Progress in Neuro-Psychopharmaco/ogy & Biological Psychiatry, networks in primate association cortex. Annual Review of 35(2): 616-623, 2001. Neuroscience, 11: 137-156, 1988. Dale AM, Fischl B, and Sereno MI. Cortical surface-based analysis. Good CD, Johnsrude I, Ashburner J, Henson RNA, Friston ICJ, and I. Segmentation and surface reconstruction. Neurolmage, 9(2): Fnckowiak RSJ. Cerebral asymmetry and the effects of sex 179-194,1999. and handedness on brain structure: A voxel-based Destrieux C, Fischl B, Dale AM, and Halgren E. A sulcal depth- morphometric analysis of 465 normal adult human brains. based anatomical parcellation of the cerebral cortex. Neurolmage, 14(3): 685-700, 2001. Neurolmage, 47(51): 5151, 2009. Habib M, Gayraud D, Oliva A, Regis J, Salamon G, and Khalil R. Destrieux C, Fischl B, Dale A, and Halgren E. Automatic Effects of handedness and sex on the morphology of the parcellation of human cortical gyri and sulci using standard corpus callosum: A study with brain magnetic resonance anatomical nomenclature. Neurolmage, 53(1): 1-15, 2010. imaging. Brain and Cognition, 16(1): 41-61, 1991. Draganski B, Gaser C, Busch V, Schuierer G, Bogdahn U, and Heilman ICH, Watson RT, and Valenstein E. Neglect and related May A. Neuroplasticity: Changes in grey matter induced by disorders. In Heilman KH and Valenstein E (Eds), Clinical training. Nature, 427(6972): 311-312, 2004. Neuropsychology. 4th ed. NY: Oxford University Press, 2003: Fischl B and Dale AM. Measuring the thickness of the human 296-346. cerebral cortex from magnetic resonance images. Proceedings Henson R, Shallice T, and Dolan R. Neuroimaging evidence for of the National Academy of Sciences of the United States of America, dissociable forms of repetition priming. Science, 287(5456): 97(20): 11050-11055, 2000. 1269-1272, 2000. Fischl B, Sereno MI, Tootell RB, and Dale AM. High-resolution Huster Efl, Westerhausen R, Kreuder F, Schwieger E, and intersubject avenging and a coordinate system for the cortical Wittling W. Morphologic asymmetry of the human anterior surface. Human Brain Mapping, 8(4): 272-284, 1999. cingulate cortex. Neurolmage, 34(3): 888-895, 2007. Fischl B, Liu A, and Dale AM. Automated manifold surgery: Jeong Y, Cho SS, Park JM, Kang 5), Lee JS, Kang E, et al. 18F-FDG Constructing geometrically accurate and topologically correct PET findings in frontotemporal dementia: An SPM analysis models of the human cerebral cortex. IEEE Transactions on of 29 patients. Journal of Nuclear Medicine, 46(2): 233-239, Medical Imaging, 20(1): 70-80, 2001. 2005. Fischl B, van der Kouwe A, Destrieux C, Halgren E, Segonne F, Jonides J, Lewis RL, Nee DE, Lustig CA, Berman MG, and Moore KS. Salat DH, et al. Automatically parcellating the human cerebral The mind and brain of short-term memory. Annual Review of cortex. Cerebral Cortex, 14(1): 11-22, 2004. Psychology, 59: 193-224, 2008. Fleming SM, Weil RS, Nagy Z, Dolan KT, and Rees G. Relating Kamiya Y, Aihara M, Osada M, Ono C, Hatakeyama K, introspective accuracy to individual differences in brain Kanemura H, et al. Electrophysiological study of lateralization structure. Science, 329(5998): 1514-1543, 2010. in the frontal lobes (in Japanese). Japanese Journal of Cognitive Fornito A, Yucel M, Wood 5, Stuart GW, Buchanan JA, Proffitt T, Neuroscience, 3(3): 188-191, 2002. et al. Individual differences in anterior cingulate/ Kanda T, Ishii K, Uemura T, Miyamoto N, Yoshikawa T, Kono AK, paracingulate morphology are related to executive functions et al. Comparison of grey matter and metabolic reductions in in healthy males. Cerebral Cortex, 14(4): 424-431, 2004. frontotemporal dementia using FDG-PET and voxel-based Foundas AL, Leonard CM, Gilmore R, Fennel E, and Heilman KM. morphometric MR studies. European Journal of Nuclear Medicine Plenum temporal asymmetry and language dominance. and Molecular Imaging, 35(12): 2227-2234, 2008. Neuropsychologia, 32(10): 1225-1231, 1994. Koenigs M, Young L, Adolphs R, Trend D, Cushman F, Hauser M, Foundas AL, Leonard CM, and Heilman KM. Morphologic et al. Damage to the prefrontal cortex increases utilitarian cerebral asymmetries and handedness: The pars triangularis moral judgments. Nature, 446(7138): 908-911, 2007. and plenum temporale. Archives of Neurology, 52(5): 501-508, Krain AL, Wilson AM, Arbuckle R, Castellanos FX, and Milham MP. 1995. Distinct neural mechanisms of risk and ambiguity: A meta- Fuster JM. The Prefrontal Cortex. 4th ed. NY: Academic Press, 2008. analysis of decision-making. Neurolmage, 32(1): 477-484, 2006. Galaburda AM, LeMay M, Kemper TL, and Geschwind N. Right-leR LeMay M and Culebns A. Human brain - morphological asymmetries in the brain. Science, 199(4331): 852-856, 1978. differences in the hemispheres demonstrable by carotid Geschwind N and Levitsky W. Human brain: Left-right arteriography. New England Journal of Medicine, 287(4): 168-170, asymmetries in temporal speech region. Science, 161(837): 1972. 186-187,1968. Liu H, Stufflebeam SM, Sepulcre 3, Hedden T, and Buckner a. Gold JM, Berman KF, Randolph C, Goldberg TE, and Evidence from intrinsic activity that asymmetry of the human Weinberger DR. PET validation of a novel prefrontal task brain is controlled by multiple factors. Proceedings of the Delayed response alteration. Neuropsychology, 10(1): 3-10, National Academy of Sciences of the United States of America, 1996. 106(48): 20499-20503, 2009. Goldberg E. The New Executive Brain: Frontal Lobes in a Complex Luders E, Nan KL, Thompson PM, Rex DE, Jancke L, and Toga AW. World. NY: Oxford University Press, 2009. Hemispheric asymmetries in cortical thickness. Cerebral Goldberg E and Costa LD. Hemisphere differences in the Cortex, 16(8): 1232-1238, 2006. acquisition and use of descriptive systems. Brain and Language, Luders E, Gaser C, Nan KL, and Toga AW. Why sex matters: Brain 14(1): 144-173, 1981. size independent differences in gray matter distributions EFTA00301237 :,Author's personal copy 210 CORTEX 49 (2013) 200-2 IC/ between men and women. Journal of Neuroscience, 29(45): Shadmehr R and Holcomb HH. Neural correlates of motor 14265-14270,2009. memory consolidation. Science, 277(5327): 821-825, 1997. Lyttelton OC, Karama 5, Ad-Dab'bagh Y, Zatorre RJ, Shaw P, Lalonde F, Lepage C, Rabin C, Eckstrand K, Sharp W, et al. Carbonell F, Worsley K, et at Positional and surface area Development of cortical asymmetry in typically developing asymmetry of the human cerebral cortex. Neurolmage, 46(4): children and its disruption in attention-deficit/hyperactivity 895-903, 2009. disorder. Archives of General Psychiatry, 66(8): 888-896, 2009. Maguire EA, Gadian DG, Johnstrude IS, Good CD, Ashbumer J, Takao H, Abe O, Yarnasue H, Aoki 5, Sasaki H, Kasai K, et al. Gray Frakowiak RS, et al. Navigation-related structural change in and white matter asymmetries in healthy individuals aged the hippocampi of taxi drivers. Proceedings of the National 21-29 years: A voxel-based morphometry and diffusion tensor Academy of Sciences of the United States of America, 97(8): imaging study. Human Brain Mapping, 32(10): 1762-1773, 2011. 4398-4403, 2000. Vallortigara G. Comparative neuropsychology of the dual brain: A Nagata SI, Uchimura K, Hirakawa W, and Kuratsu JI. Method for stroll through animals' left and right perceptual worlds. Brain quantitatively evaluating the lateralization of linguistic and Language, 73(2): 189-219, 2000. function using functional MR imaging. American Journal of Vallortigara G and Rogers y. Survival with an asymmetrical brain: Neuroradiology, 22(5): 985-991, 2001. Advantages and disadvantages of cerebral lateralization. Nan KL, Bilder RM, Luders E, Thompson PM, Woods RP, Behavioral and Brain Sciences, 28(4): 575-633, 2005. Robinson D, et al. Asymmetries of cortical shape: Effects of Vallortigara G, Rogers p, and Bisazza A. Possible evolutionary handedness, sex and schizophrenia. Neurolmage, 34(3): origins of cognitive brain lateralization. Brain Research Reviews, 939-948, 2007. 30(2): 164-175, 1999. Oldfield RC. The assessment and analysis of handedness: The Van Snellenberg JX and Wager T. Cognitive and motivational Edinburgh inventory. Neuropsychologia, 9(1): 97-113, 1971. functions of the human prefrontal cortex. In Christensen A-L, O'Reilly RC and Munakata Y. Computational Explorations in Goldberg E, and Bougakov D (Eds), Luria's Legacy in the 22st Cognitive Neuroscience. Cambridge, MA: MIT Press, 2000. Century. NY: Oxford University Press, 2009: 30-61. Penhune VB, Zatorre RJ, MacDonald JD, and Evans AC. Watkins KE, Paus T, Lerch JP, Zijdenbos A, Collins DL, Neelin P, Interhemispheric anatomical differences in human primary et al. Structural asymmetries in the human brain: A voxel- auditory cortex: Probabilistic mapping and volume based statistical analysis of 142 MRI scans. Cerebral Cortex, measurement from magnetic resonance scans. Cerebral Cortex, 11(9): 868-877, 2001. 6(5): 661-672, 1996. Whitwell JL, Sampson EL, Watt HC, Harvey RJ, Rossor MN, and Pushkarskaya H, Liu X, Smithson M, and Joseph JE. Beyond risk Fox NC. A volumetric magnetic resonance imaging study of and ambiguity: Deciding under ignorance. Cognitive, Affective, the amygdala in frontotemporal lobar degeneration and & Behavioral Neuroscience, 10(3): 382-391, 2010. Alzheimer's disease. Dementia and Geriatric Cognitive Disorders, Raz N, Gunning-Dixon F, Head D, Rodrigue KM, Williamson A, and 20(4): 238-244, 2005. Acker JD. Aging, sexual dimorphism, and hemispheric Witelson SF. Hand and sex differences in the isthmus and genu of asymmetry of the cerebral cortex: Replicability of regional the human corpus callosum. Brain, 112(3): 799-835, 1989. differences in volume. Neurobiology of Ag mg, 25(3):377-396, 2004. Wolf RC, Hose A, Frasch K, Walter H, and Vasic N. Volumetric Schneider P, Scherg M, Dosch HG, Specht HJ, Gutschalk A, and abnormalities associated with cognitive deficits in patients Rupp A. Morphology of Heschl's gyrus reflects enhanced with schizophrenia. European Psychiatry, 23(8): 541-548, 2008. activation in the auditory cortex of musicians. Nature Yakovlev PI. A proposed definition of the limbic system. In Neuroscience, 5(7): 688-694, 2002. Hackman CH (Ed), Limbic System Mechanisms and Autonomic Schobel SA, Kelly MA, Corcoran CM, Van Heertum K, Seckinger R, Function. Springfield, IL: Charles C. Thomas, 1972: 241-283. Goetz R, et al. Anterior hippocampal and orbitofrontal cortical Yakovlev PI and Rakic P. Patterns of decussation of bulbar structural brain abnormalities in association with cognitive pyramids and distribution of pyramidal tracts on two sides of deficits in schizophrenia. Schizophrenia Research, 114(1-3): the spinal cord. Transactions of the American Neurological 110-118, 2009. Association, 91: 366-367, 1966. EFTA00301238