In addition to its role in synaptic plasticity described above, PI3K-AKT signaling pathway also has an important role in brain growth, which is altered when PI3K signaling is disturbed. For example, intracranial volume is also associated with this pathway, in particular with AKT3 intronic variants. Thyroid hormone was originally identified as the primary regulator of brain growth and cognition, and recent evidence has demonstrated that thyroid hormone produces some of its effects on the maturation and plasticity of synapses through PI3K.