1. Integrity of white matter in the corpus callosum correlates with bimanual co-ordination skill Heidi Johansen-Berg 1, Valeria Della-Maggiore 3, Steve Smith 1, Tomáš Paus 2,3 1 Centre for Functional MRI of the Brain, University of Oxford, UK, 2 Brain & Body Centre, University of Nottingham, UK 3 Montreal Neurological Institute, McGill University, Canada Introduction Acknowledgements. Funded by the Wellcome Trust (HJB) and the Canadian Institutes for Health Research. We thank Jennifer Campbell for providing the pulse sequence. References 1.Larson et al, Cortex (2002) 2.Serrien et al, Eur J Neurosci (2001) 3. Tuch et al., Proc Natl Acad Scii (2005) 4. Madden et al., Neuroimage. (2004) 5.Johansen-Berg & Paus, OHBM (2005) 6. Smith et al., NeuroImage (2004) 7. Behrens et al., MRM (2003) 8. Colom et al,. Neuroimage (2006) 9. Bengtsson et al. Nat Neurosci (2005). Discussion Performance variation in bimanual co-ordination is associated with variability in white matter integrity in callosal pathways connecting motor, parietal and prefrontal regions. The spatial specificity of the correlation suggests that variation between individuals differs across functional systems. Although there are some suggestions that inter-individual variation in brain structure can be captured by a general IQ marker 8, there is evidence also for regional variations in brain structure and function reflecting specific patterns of skill 3-5,9 consistent with our findings. The current study provides us with a snapshot that makes it impossible to establish the direction of causality between structure and function. Future work should study structural markers of brain plasticity longitudinally. Bimanual co-ordination involves inter-hemispheric interactions mediated by trans-callosal motor pathways Diffusion imaging measures of fractional anistropy (FA) reflect white matter integrity Although changes in FA have been reported during development 1 and ageing 2, there is less evidence concerning the significance of variations in FA in healthy adult individuals 3-5. We aimed to test whether normal variation in bimanual coordination is related to variation in white-matter FA in the corpus callosum of healthy adult subjects. Methods 10 healthy adults (age: 21 to 45 years). Bimanual co-ordination was assessed using paced asynchronous finger- thumb opposition. Goniometers were attached along the metacarpophalangeal joint of the index fingers Movements were recorded for 12 second intervals at 10 different metronome frequencies (range = 1 to 3.3 Hz) and used to calculate the correlation between the angle time series for both hands. We calculated the ratio between the ‘threshold frequency’ (i.e., frequency at which the correlation was within a range of -.8 +/- 10 %) and the ‘best performance frequency’ (i.e., frequency at which this correlation was closest to -1) as a measure of bimanual co-ordination and used this as a regressor in subsequent image analysis. Diffusion-weighted images (60 directions, b-value 1000smm -2, 2.2mm 3 voxels, 60 slices) and T1-weighted data were acquired on a Siemens Sonata 1.5T scanner FA was calculated at each voxel using FDT (http://www.fmrib.ox.ac.uk/fsl) and then compared to bimanual co-ordination scores using Tract-based spatial statistics, TBSS 6. First, individual subject FA maps are aligned using non-linear registration. A mean FA image is calculated and used to generate a white matter tract ‘skeleton’. Individual subject FA values are warped onto this group skeleton for statistical comparisons. Probabilistic Tractography 7 was used to generate estimated tracts from callosal regions showing a correlation between FA and bimanual co- ordination skill. Results Mean FAWM skeleton subjects We found a high correlation between FA and bimanual co-ordination scores in three regions within the corpus callosum: A. Body (108 voxels, max t=4.3), B. Genu (41 voxels, max t=4.4) C. Splenium (19 voxels, max t=3.4) Search volume is restricted to corpus callosum, images are thresholded at t>2.3 (uncorrected) Pale green line indicates location of WM skeleton When the callosal regions of high correlation were used as a seed for probabilistic tractography, paths were generated to: A. Supplementary Motor Area (from body) B. Frontal pole (from genu) C. Medial occipito-parietal cortex (from splenium) Tracts are group probability maps based on tracing in 10 subjects, thresholded to include voxels present in at least 3 subjects. Correlation across individuals between performance on bimanual task (frequency ratio) and FA in voxel in the body of the corpus callosum.