that increased production of GABA is responsible for aberrantly increased synaptogenesis, as GABA functions as an excitatory neurotransmitter promoting activity-dependent synapse formation in prenatal development 139. The increase in synapse-related transcripts detected in hiPSC-derived organoids echoes a neuropathological study where a morphological increase in synaptic connections was identified in unselected patients with idiopathic autism 140. Increased density of cortical neuron minicolumns 141 and areas of aberrant cortical neuron layering 142,143 have been shown to occur in autism, but there are as yet no neuropathological studies with sufficient number of cases to demonstrate an imbalance of inhibitory over excitatory neurons in the cortex. Remarkably, the increase in FOXG1 expression in idiopathic ASD with macrocephaly has been replicated in an independent set of cases using a non-organoid neuronal differentiation protocol, along with the increase in GABAergic neuronal progenitors 144, consolidating the idea of an involvement of FOXG1-mediated GABAergic disturbance in ASD and suggesting that hiPSC modeling is robust and can yield reproducible data across hiPSC lines, patients, and laboratories. The above mentioned study 144 has also hypothesized that the Wnt signalling pathway, which when elevated causes excessive proliferation of NPCs 145,146, is paradoxically reduced in ASD with macrocephaly, and somehow this is
