Neuroinform (2012) 10:341–350 anatomist for volumetric analyses is cost effective and time efficient, particularly in large-scale volumetric studies. Importantly, we demonstrate that the automated technique is as sensitive in detecting pathological alterations of the thalamus relative to stereology, which promotes the use of FreeSurfer in neurological contexts. There are two additional issues that should be highlight- ed. Measurements made in the present study were of global thalamic volume. The thalamus is composed of lamellae that segregate multiple nuclei with distinct connections and functions, which are likely to be differentially affected in various neurological and neuropsychiatric disorders. For example, in disorders where the thalamus is implicated in patients also exhibiting deficits in frontal lobe functioning— such as in JME (Pulsipher, et al. 2009)—it would be expected that anterior thalamic nuclei that project to the frontal lobe would be preferentially affected (Deppe, et al. 2008). In such circumstances it will be interesting to inves- tigate structural alterations of differential thalamic subre- gions, which are measures that the techniques applied in the present study cannot provide. There are other techniques that may provide the basis for quantitative measurements of thalamic subregions based on DTI and quantitative T1 and T2 imaging (Behrens, et al. 2003; Johansen-Berg, et al. 2005; Traynor, et al. 2011). Secondly, the global estimates of thalamic volume using FreeSurfer in the present study was obtained on a Philips Intera T30 3 T MRI system, requiring no additional manual edits for (obvious) incorrect labelling of the thalamic ROI after the application of our in- house image inhomogeneity and resampling algorithm. Different MRI systems and head coils may have different image contrast characteristics that can potentially affect the performance of automated MR image analysis techniques. However, reproducibility of FreeSurfer estimated thalamic volume from serially acquired MR images on the same MR system is high (Jovicich, et al. 2009; Morey, et al. 2010), and MR system manufacturer has been shown to have little effect on volume estimates (Jovicich, et al. 2009). In summary, this study provides convincing evidence for the reliability of global thalamic measurements using FreeSurfer in healthy and damaged thalami. The use of this software is cost effective and particularly advantageous in large-scale cross-sectional studies and longitudinal investi- gations in neurological settings. Information Sharing Statement FreeSurfer software is publicly and freely available from the FreeSurferWiki resource (http://surfer.nmr.mgh.harvard.edu/ fswiki/FreeSurferWiki), which is developed and maintained at the Martinos Center for Biomedical Imaging (http:// www.nmr.mgh.harvard.edu/martinos/noFlashHome.php). All 347 software, information and support are provided online at the FreeSurferWiki webpage. Easymeasure software for volume estimation using stereology is freely available from the authors of this manuscript upon request. Dr. Mike Puddephat developed Easymeasure software at the University of Liverpool, UK. Further information can be found at (http://www.easymeasure.co.uk/). Acknowledgements This work was supported by the Transregional Collaborative Research Centre SFB/TR 3 (Project A8) of the Deutsche Forschungsgemeinschaft (DFG). EBR acknowledges support from the Neuromedical Foundation (Stiftung Neuromedizin), Münster. SM acknowledges support from the Wellcome Trust; Open access to the paper were supported by the Wellcome Trust grant number 091593/Z/10/Z. Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distri- bution, and reproduction in any medium, provided the original author (s) and the source are credited. References Acer, N., Cankaya, M. N., Isci, O., Bas, O., Camurdanoglu, M., & Turgut, M. (2010). Estimation of cerebral surface area using vertical sectioning and magnetic resonance imaging: a stereolog- ical study. Brain Research, 1310, 29–36. Adriano, F., Spoletini, I., Caltagirone, C., & Spalletta, G. (2010). Updated meta-analyses reveal thalamus volume reduction in patients with first-episode and chronic schizophrenia. Schizophrenia Research, 123(1), 1–14. Amini, L., Soltanian-Zadeh, H., Lucas, C., & Gity, M. (2004). Automatic segmentation of thalamus from brain MRI integrating fuzzy cluster- ing and dynamic contours. IEEE Transactions on Biomedical Engineering, 51(5), 800–811. Andreasen, N. C. (1997). The role of the thalamus in schizophrenia. Canadian Journal of Psychiatry, 42(1), 27–33. Bas, O., Acer, N., Mas, N., Karabekir, H. S., Kusbeci, O. Y., & Sahin, B. (2009). Stereological evaluation of the volume and volume fraction of intracranial structures in magnetic resonance images of patients with Alzheimer’s disease. Annals of Anatomy, 191(2), 186–195. Basso, M. A., Uhlrich, D., & Bickford, M. E. (2005). Cortical function: a view from the thalamus. Neuron, 45(4), 485–488. Behrens, T. E., Johansen-Berg, H., Woolrich, M. W., Smith, S. M., Wheeler-Kingshott, C. A., Boulby, P. A., Barker, G. J., Sillery, E. L., Sheehan, K., Ciccarelli, O., Thompson, A. J., Brady, J. M., & Matthews, P. M. (2003). Non-invasive mapping of connections between human thalamus and cortex using diffusion imaging. Nature Neuroscience, 6(7), 750–757. Berg, A. T., Berkovic, S. F., Brodie, M. J., Buchhalter, J., Cross, J. H., van Emde, B. W., Engel, J., French, J., Glauser, T. A., Mathern, G. W., Moshe, S. L., Nordli, D., Plouin, P., & Scheffer, I. E. (2010). Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005–2009. Epilepsia, 51(4), 676–685. Bonilha, L., Kobayashi, E., Cendes, F., & Min, Li L. (2004). Protocol for volumetric segmentation of medial temporal structures using high-resolution 3-D magnetic resonance imaging. Human Brain Mapping, 22(2), 145–154. Cherbuin, N., Anstey, K. J., Reglade-Meslin, C., & Sachdev, P. S. (2009). In vivo hippocampal measurement and memory: a