1. Associations of Brain Size and Verbal Performance Depend on Handedness Christine Chiarello 1, Suzanne Welcome 1, Stephen Towler 2, Ronald Otto 3, & Christiana M. Leonard 2 University of California, Riverside 1,University of Florida, Gainesville 2, CDIC Riverside 3 Introduction Acknowledgment This research was supported by NIDCD grant 5R01DC6957. Conclusions Method We did not replicate the prior finding of Witelson, et al. (2006) that mixed-handed males fail to show a VIQ-brain volume association. Our sample size was nearly twice as large, but had a more restricted age range. We also used a more stringent criteria for consistency of handedness. However, handedness does appear to moderate the relationship between brain volume and verbal performance. For mixed-handers, greater brain volume is associated with higher scores in word recognition and comprehension, but not with asymmetry. In contrast, for consistent-handers greater brain volume is not associated with better verbal performance, but rather with increased left hemisphere specialization. Is verbal performance better in those with a larger brain? For those with a strong phenotypic expression of handedness, the answer is no. However, larger brains appear to function more asymmetrically, as suggested by some (Ringo, et al., 1994). In contrast, for those with more weakly expressed handedness, larger brains are associated with better verbal performance, but not necessarily more asymmetric performance. Consistency of handedness appears to be an important moderator of brain- behavior relationships. Brain volume varies substantially across individuals, and we recently demonstrated that individual differences in brain volume, in both men and women, account for sex differences in the relative sizes of various brain regions (Leonard, et al., in press). Brain volume is known to correlate with some measures of cognitive performance. Witelson, Beresh, & Kigar (2006) reported that verbal IQ correlated with brain size in women and in consistent right-handed men, but not in mixed-handed men. These authors suggested that functional asymmetry, indexed by handedness, moderated the relation between verbal intelligence and brain size in men, but not in women. Here we re-examine the relationship between brain volume, handedness, and verbal performance using a wider range of verbal measures (VIQ, reading subtests, RT and accuracy on 7 lexical tasks), and behavioral measures of language lateralization in a large sample of young adults. We included lateralized tasks in order to have a measure of functional asymmetry that is more directly related to language processing. References Leonard, C.M., Towler, S., Welcome, S., Halderman, L.K., Otto, R., Eckert, M.A., & Chiarello, C. (In press). Size matters: Cerebral volume influences sex differences in neuroanatomy. Cerebral Cortex. Ringo, J.L., Doty, R.W., Demeter, S., & Simard, P.Y. (1994). Time is of the essence: A conjecture that hemispheric specialization arises from interhemispheric conduction delay. Cerebral Cortex, 4, 331-343. Wechsler, D. (1999). Wechsler Abbreviated Scale of Intelligence. San Antonio, TX: The Psychological Corporation. Witelson, S.F., Beresh, H., & Kigar, D.L. (2006). Intelligence and brain size in 100 postmortem brains: sex, lateralization and age factors. Brain, 129, 386-398. Woodcock, R.W. (1998). Woodcock Reading Mastery Test-Revised Normative update (WRMT-R). Circle Pines, MN: American Guidance Service, Inc. PARTICIPANTS: 100 male, 100 female native English speakers 18-34 years of age 103 consistent-handed (exclusive preference for one hand), 97 mixed-handed PSYCHOMETRIC MEASURES: Verbal IQ estimated from Wechsler Abbreviated Scale of Intelligence (Wechsler, 1977) Reading subscales from Woodcock Reading Mastery Test - Revised (Woodcock, 1998) Word Identification (word reading) Word Attack (nonword reading) Passage Comprehension DIVIDED VISUAL FIELD TASKS: Composite Average score (averaged over LVF and RVF) and Composite Asymmetry score across the following tasks calculated separately for accuracy and reaction time: Lexical Decision Masked Word Recognition (2 AFC procedure) Word Naming Nonword Naming Semantic (manmade vs natural) Decision Verb Generation Category Generation BRAIN MEASUREMENTS FROM MRI: Gray, white and cerebrospinal fluid (csf) volumes of each cerebral hemisphere were estimated by outlining every fifth sagittal image starting at the midline. The brainstem was excluded by transection in the midcollicular plane. Inter-rater reliability of this measure is >.98 (intra class correlation). Results ConsistHandersMixedHanders NONLATERALIZED MEASURES Word Identification.181.270 Word Attack.118.112 Passage Comprehension.096.261 Composite Lexical Accuracy.077.266 Composite Lexical RT.078 -.135 LATERALIZED MEASURES Composite Lex Accuracy Asym.194-.017 Composite Lex RT Asymmetry.280 -.081 Because the handedness groups were not perfectly balanced by sex (consistent-handers: 44 male, 59 female; mixed-handers: 56 male, 41 female), we partialed out the effects of sex using multiple regression and examined the percent of variance in brain volume accounted for by performance in the two handedness groups. Most of the correlations reported above remained significant when the effects of sex were removed (italicized in the table above). In consistent-handers only, as brain volume increases, so does asymmetry of lexical processing - larger volume is associated with greater left-hemisphere processing advantages (figure, left) In mixed-handers only, as brain volume increases, nonlateralized verbal performance increases (figure, right) Most of the correlations remained significant when either gray or white matter volume was examined Correlations of total brain volume with each of the performance measures are shown below by handedness group (significant correlations in bold).  As shown below, correlations of brain volume and verbal IQ for the sex/handedness groups revealed positive correlations for all groups, contrary to Witelson, et al. (2006). Indeed, the strongest correlation was observed for mixed-handed males, the group for which Witelson, et al. failed to find an association (significant correlations in bold). ConsistHandersMixed Handers Males.271.395 Females.302.246 BRAIN VOLUME RT ASYMMETRY AVERAGE ACCURACY CONSISTENT HANDERSMIXED HANDERS