Mapping anatomical correlations across cerebral cortex (MACACC) using cortical thickness from MRI Jason P. Lerch, a Keith Worsley, a W. Philip Shaw, b Deanna K. Greenstein, b Rhoshel K. Lenroot, b Jay Giedd, b and Alan C. Evans a, * a McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, QC, Canada H3A 2B4 b National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA Received 3 June 2005; revised 22 December 2005; accepted 12 January 2006 Available online 19 April 2006 We introduce MACACC-Mapping Anatomical Correlations Across Cerebral Cortex-to study correlated changes within and across different cortical networks. The principal topic of investigation is whether the thickness of one area of the cortex changes in a statistically correlated fashion with changes in thickness of other cortical regions. We further extend these methods by introducing techniques to test whether different population groupings exhibit significantly varying MACACC patterns. The methods are described in detail and applied to a normal childhood development population (n = 292), and show that association cortices have the highest correlation strengths. Taking Brodmann Area (BA) 44 as a seed region revealed MACACC patterns strikingly similar to tractography maps obtained from diffusion tensor imaging. Furthermore, the MACACC map of BA 44 changed with age, older subjects featuring tighter correlations with BA 44 in the anterior portions of the superior temporal gyri. Lastly, IQ-dependent MAC- ACC differences were investigated, revealing steeper correlations between BA 44 and multiple frontal and parietal regions for the higher IQ group, most significantly (t = 4.0) in the anterior cingulate. D 2006 Published by Elsevier Inc. Introduction The cerebral cortex is organized into networks of functionally complementary areas. Classic examples include the dorsal and ventral visual streams, the limbic system, and the language networks. These networks are traditionally studied using functional paradigms designed to reveal the particular role of a certain area. Examples of such studies include the role of Broca’s Area in word repetition, synonym generation (Klein et al., 1997), verbal fluency (Frith et al., 1991), speech production (Buckner et al., 1995) and silent word production (Friedman et al., 1998). Functional specialization can also lead to related anatomical change. A recent study investigated the size of the hippocampus, a structure involved in spatial navigation, in London taxi drivers and found increases in size correlating with increased experience in navigating the streets of London (Maguire et al., 2000, 2003). Similarly, faster phonetic learners were found to have greater white matter density in parietal regions than slower learners (Golestani et al., 2002). Trained musicians feature enlarged primary motor and sensorimotor areas, premotor areas, anterior superior parietal areas, and inferior temporal gyri (Schlaug, 2001; Gaser and Schlaug, 2003a,b). This last example involving musicians is particularly informative as it involves multiple cortical areas, including motor, sensorimotor, and multimodal sensory areas, collaborating. Increases in anterior corpus callosum size further suggests that the intra-hemispheric connectivity of the brain is enhanced in trained musicians (Schlaug, 2001). We propose to address a related but less explored topic: as the anatomy of one cortical area changes, are there correlated morphological changes in other cortical areas? An example hypothesis from the language-processing domain might be that a population with thicker cortices in Broca’s Area will have a correspondingly larger Wernicke’s Area. The connectivity of the human cerebral cortex is not a new topic of investigation. It has traditionally been studied using fiber tracing, wherein a seed region is injected with a retrograde tracer in order to determine which areas have direct fibre connections to the seed region (Romanski et al., 1999; Petrides and Pandya, 2002). More recently the notion of functional connectivity has been promoted, i.e. areas that are functionally related will feature correlated change in a fMRI or PET functional activation study (Friston, 2002; Friston et al., 1993, 1996, 2003; Koski and Paus, 2000; Horwitz, 2003; Lee et al., 2003; Ramnani et al., 2004). We propose to study correlated anatomical changes using methods related to functional connectivity but employing morpho- metric data; we have dubbed this approach Mapping Anatomical Correlation Across Cerebral Cortex (MACACC). Of particular interest will be not just testing which areas of the cortex correlate with which other areas, but also whether the MACACC patterns vary across different categorical groupings based on demographical variables (age, gender, socio-economic status) or clinical diagnoses. 1053-8119/$ - see front matter D 2006 Published by Elsevier Inc. doi:10.1016/j.neuroimage.2006.01.042 * Corresponding author. Fax: +1 514 398 8952. E-mail address: alan@bic.mni.mcgill.ca (A.C. Evans). Available online on ScienceDirect (www.sciencedirect.com). www.elsevier.com/locate/ynimg NeuroImage 31 (2006) 993 – 1003