Electrocorticography (ECOG) compared the effects of methohexital (MTH) and selective amygdalo-hippocampectomy (selAH) upon lateral temporal neocortical epileptiform activity (EA) in 31 patients with mesial temporal epilepsy. Pre-excision ECOG showed independent neocortical EA before MTH in 12/31 and after MTH in 18/31. MTH (20-50 mg) activated neocortical EA in 12 cases and induced burst-suppression (BS) over temporal neocortex in 14/31. Post-excision ECOG showed neocortical EA in 21/31 and BS in 27/31: compared with pre-excision ECOG before MTH, selAH activated neocortical EA in 15 cases. Significant correlations were found between presence of pre-excisional neocortical EA and presence of post-excisional neocortical EA (P < 0.001) and between activation of pre-excisional neocortical EA by MTH and activation of (post-excisional) neocortical EA by selAH (P < 0.006). Presence or severity of BS in the post-excision ECOG was not correlated with presence, absence or activation of post-excisional EA. Presence of neocortical EA was significantly correlated with a higher pre-operative seizure frequency (P < 0.001) but not with duration of epilepsy nor surgical outcome. Both MTH and selAH can induce neocortical BS, likely through chemical and surgical disconnection of cortex, respectively. Unrelated to induction of BS, MTH and selAH appear to decrease threshold for expression of neocortical EA in a similar fashion.