For each predictor, a series of fourth-order polynomials were used to model a potentially nonlinear response between the predictors and the BOLD signal. Importantly, the reported findings do not depend heavily on this particular analysis approach. A more conventional nonhierarchical voxel-wise linear model produced qualitatively similar results. ( Figures S2 and S3). All

reported stereotaxic coordinates refer to the MNI template and are reported as (x, y, z). Throughout, Selleckchem GSK3 inhibitor statistical maps have been thresholded voxel-wise at p < 0.01. An additional cluster extent threshold of 38 or more contiguous voxels enforced a whole-brain correction for multiple comparisons at p < 0.05 (see Supplemental Information). Thanks to Ross Mair, Tammy Moran, Caroline West, Miguel Cutiongco, David Dornblaser, Rebecca Hersher, and Allison Hyland for assistance, Marcus Johnson for assistance with

the eye tracker, Elissa Aminoff and Wilma Koutstaal for providing stimuli, and Scott Slotnick for providing software for the Monte Carlo simulation. This work was supported by NRSA AG034699 to S.A.G. and National Institute of Health MH060941 to D.L.S. “
“It is well appreciated that central nervous system (CNS) axons do not regenerate (Bradke et al., 2012). Peripheral nervous system (PNS) axons luckily do regenerate and mount a robust response because of an selleck products intrinsic regeneration program. This cell-intrinsic regeneration program (thought to be a reactivation

of the developmental program) is turned on by a retrograde injury signal that activates a transcriptional program (Figure 1) (Cavalli et al., 2005, Hoffman, 2010 and Liu et al., 2011). The difference between CNS and PNS neuron regeneration abilities is thought to be due to two factors: an “inhibitory” CNS environment and a “weak” activation of the intrinsic regeneration program. It is not known whether the weak activation of CNS neurons is due to differences in the intrinsic regeneration program or differences in the retrograde injury signal. The observation by Neumann and Woolf (1999) that a preconditioning cut to peripheral sensory axons suddenly allowed regeneration of their CNS axons was exciting to all who had long thought and the inhibitory environment of the CNS was an insurmountable barrier. The cell-intrinsic axon regeneration capability could overcome the CNS inhibitory environment! But why was a preconditioning cut required? Did the second cut induce a novel regeneration mechanism or just increase the normal intrinsic regeneration response above a threshold level needed for regeneration in the CNS environment? Much research has gone into identifying the molecular mechanisms responsible for the improved regeneration associated with a preconditioning injury (Hoffman, 2010).