MTOR and microcephaly: There is also pre-clinical evidence that the final consequence of hyperactivation of the mTOR pathway depends on the stage of brain development at which it occurs: while in early stages of development in a mouse model with a gain-of-function mTOR mutant, hyperactivation causes neuronal apoptosis and microcephaly, hyperactivation of the mTOR pathway in post-mitotic neurons results in impaired neuronal migration and cellular hypertrophy, with macrocephaly and abnormal cortical architecture (40).