1. FreeSurfer Applications

2. What is it used for? Tools wielded: – Cortical thickness – Surface-based group analysis – Subcortical structure measurements – Tractography Brain states and pathologies: – Aging, Alzheimer’s, Huntington’s, autism, schizophrenia, addiction, meditation,... See ‘Citations’ on wiki home page

3. Cortical Thickness pial surface Distance between white and pial surfaces along normal vector. 1-5mm

4. Inter-Subject Averaging Subject 1 Subject 2 Native Spherical Surface-to- Surface Surface-to- Surface GLM Demographics mri_glmfit cf. Talairach

5. Volumetric Segmentation (aseg) Caudate Pallidum Putamen Amygdala Hippocampus Lateral Ventricle Thalamus White Matter Cortex Not Shown: Nucleus Accumbens Cerebellum

6. WMPARC: Volumetric Analysis/DTI ROI Analysis

7. Aging, cortical thickness Thinning of the Cerebral Cortex in Aging, D.H. Salat, R.L. Buckner, A.Z. Synder, R.S.R. Desikan, D.N. Greve, E. Busa, J.C. Morris, A.M. Dale, and B. Fischl, (2004). Cerebral Cortex, 14:721-730. Salat et al. summary: – There are substantial volumetric changes in cortical and subcortical gray matter with nondemented aging – AD may accelerate, yet also presents with distinct structural abnormalities compared to aging – Structural imaging can differentiate individuals with cognitive impairment that progress to AD from those that do not

8. Group Mean Thickness Young Old Middle Aged Salat et al., Cerebral Cortex, 2004

9. Age-associated cortical thinning Thinning in primary and association cortices Regional thinning relates to neuropsychological performance Mechanisms of thinning are unknown

10. Aging, white matter Regional white matter volume differences in nondemented aging and Alzheimer's disease, Salat D.H., D.N. Greve, J.L. Pacheco, B.T. Quinn, K.G. Helmer, R.L. Buckner, B. Fischl (2008). NeuroImage 44 (2009) 1247–1258. Salat et al. summary: – White matter volume decreases with age

11. Effects of Age and AD on Regional WM Salat et al., 2009

12. Aging, GWR signal intensity Age-associated alterations in cortical gray and white matter signal intensity and gray to white matter contrast, D.H.Salat, S.Y.Lee, A.J.van der Kouwe, D.N.Greve, B.Fischl, H.D.Rosas (2009). NeuroImage, 2009. The declining infrastructure of the aging brain., Salat DH. Brain Connect. 2011;1(4):279-93.

13. Association Between Regional GWR and Age Changes in Contrast (GWR) with Age (controlling for thickness) Salat et al., 2009

14. Association Between Regional GWR and Digit Span *All participants

15. AD biomarkers Automated MRI measures predict progression to Alzheimer’s disease, Desikan R.S., H.J. Cabral, F. Settecase, C.P. Hess, W.P. Dillon, C.M. Glastonbury, M.W. Weiner, N.J. Schmansky, D.H. Salat, B. Fischl (2010). Neurobiology of Aging, 2010, Aug;31(8):1364-74. Selective Disruption of the Cerebral Neocortex in Alzheimer’s Disease, Desikan, R.S., M.R. Sabuncu, N.J. Schmansky, M. Reuter, H.J. Cabral, C.P. Hess, M.W. Weiner, A. Biffi, C.D. Anderson, J. Rosand, D.H. Salat, T.L. Kemper, A.M. Dale, R.A. Sperling, B. Fischl, the Alzheimer’s Disease Neuroimaging Initiative (2010). PLoS ONE 5(9): e12853. The Dynamics of Cortical and Hippocampal Atrophy in Alzheimer Disease, Sabuncu, M.R., R.S. Desikan, J. Sepulcre, B.T.T. Yeo, H. Liu, N.J. Schmansky, M. Reuter, M.W. Weiner, R.L. Buckner, R.A. Sperling, B. Fischl (2011). Archives of Neurology, Vol 68 (No. 8), Aug 2011.

16. Meditation Meditation experience is associated with increased cortical thickness, Lazar, et al., (2005). NeuroReport, 16(17): 1893- 1897. Cortical regions thicker in meditators than in controls. Insula, Brodmann area (BA) 9/10, somatosensory cortex, auditory cortex.

17. Testosterone v. Hippocampal Volume Genetic influences on hippocampal volume differ as a function of testoterone level in middle-aged men, M.S. Panizzon, et al. (2011). neuroimage.2011.09.044 – The hippocampus expresses a large number of androgen receptors; therefore, in men it is potentially vulnerable to the gradual age-related decline of testosterone levels – Study demonstrates that in middle-aged men testosterone influences the degree to which hippocampal volume is determined by genetic and environmental influences. – First to show that in addition to age and aspects of the individual's environment, an endogenous factor can alter the magnitude of genetic influences on a brain structure.

18. Psychopathy v. Cortical Thinning Cortical Thinning in Psychopathy, Ly et al. (2012), Am. J. Psychiatry – Used a portable MRI scanner to access prison population – Most significant clusters were in the left insula, the left dorsal anterior cingulate cortex, the left and right precentral gyri, the left and right temporal poles, and the right inferior frontal gyrus

19. Home page walk-through http://surfer.nmr.mgh.harvard.edu/fswiki/ Many other areas of study: – schizophrenia and bipolar disorder, cortical and subcortical – MAO A gene and amygdala volume – Combat related post-traumatic stress disorder – Effect of early human (infant) diet on caudate volume and IQ – Parkinson’s disease and brain atrophy – …