Fidgetin is a microtubule-severing protein that pares back the labile domains of microtubules in the axon. Experimental depletion of fidgetin results in elongation of the labile domains of microtubules and faster axonal growth. To test whether fidgetin knockdown assists axonal regeneration, we plated dissociated adult rat DRGs transduced using AAV5-shRNA-fidgetin on a laminin substrate with spots of aggrecan, a growth-inhibitory chondroitin sulfate proteoglycan. This cell culture assay mimics the glial scar formed after CNS injury. Aggrecan is more concentrated at the edge of the spot, such that axons growing from within the spot toward the edge encounter a concentration gradient that causes growth cones to become dystrophic and axons to retract or curve back on themselves. Fidgetin knockdown resulted in faster-growing axons on both laminin and aggrecan and enhanced crossing of axons from laminin onto aggrecan. Strikingly, axons from within the spot grew more avidly against the inhibitory aggrecan concentration gradient to cross onto laminin, without retracting or curving back. We also tested whether depleting fidgetin improves axonal regeneration in vivo after a dorsal root crush in adult female rats. Whereas control DRG neurons failed to extend axons across the dorsal root entry zone after injury, DRG neurons in which fidgetin was knocked down displayed enhanced regeneration of axons across the dorsal root entry zone into the spinal cord. Collectively, these results establish fidgetin as a novel therapeutic target to augment nerve regeneration and provide a workflow template by which microtubule-related targets can be compared in the future.

Task‐based functional magnetic resonance imaging (tfMRI) has developed as a common alternative in epilepsy surgery to the intracarotid amobarbital procedure, also known as the Wada procedure. Prior studies have implicated tfMRI as a comparable predictor of postsurgical cognitive outcomes. However, the predictive validity of tfMRI has not been established. This preregistered systematic review and meta‐analysis (CRD42020183563) synthesizes the literature predicting postsurgical cognitive outcomes in temporal lobe epilepsy (TLE) using tfMRI. The PubMed and PsycINFO literature databases were queried for English‐language articles published between January 1, 2009 and December 31, 2020 associating tfMRI laterality indices or symmetry of task activation with outcomes in TLE. Their references were reviewed for additional relevant literature, and unpublished data from our center were incorporated. Nineteen studies were included in the meta‐analysis. tfMRI studies predicted postsurgical cognitive outcomes in left TLE (trueρ̂ = −.27, 95% confidence interval [CI] = −.32 to −.23) but not right TLE (trueρ̂ = −.02, 95% CI = −.08 to .03). Among studies of left TLE, language tfMRI studies were more robustly predictive of postsurgical cognitive outcomes (trueρ̂ = −.27, 95% CI = −.33 to −.20) than memory tfMRI studies (trueρ̂ = −.27, 95% CI = −.43 to −.11). Further moderation by cognitive outcome domain indicated language tfMRI predicted confrontation naming (trueρ̂ = −.32, 95% CI = −.41 to −.22) and verbal memory (trueρ̂ = −.26, 95% CI = −.35 to −.17) outcomes, whereas memory tfMRI forecasted only verbal memory outcomes (trueρ̂ = −.37, 95% CI = −.57 to −.18). Surgery type, birth sex, level of education, age at onset, disease duration, and hemispheric language dominance moderated study outcomes. Sensitivity analyses suggested the interval of postsurgical follow‐up, and reporting and methodological practices influenced study outcomes as well. These findings intimate tfMRI is a modest predictor of outcomes in left TLE that should be considered in the context of a larger surgical workup.