The mood-lowering effect of tryptophan depletion: possible explanation for discrepant findings.

ventilated with positive pressure 100% oxygen. Seizure expression was monitored via scalp electroencephalography (EEG), electromyography, and visuomotor manifestations in a nonparalyzed limb. One subject (No. 1) had a chronically implanted intracerebral multicontact electrode in place, permitting recording of intracerebral EEG and TMS-induced voltage. The 2 trials with the commercial device did not produce a seizure. In contrast, each of the subsequent 8 trials withthecustomdeviceproducedageneralizedtonic-clonic seizure ranging in duration from 10 to 20 seconds, documentedbymotormanifestations, electromyography, scalp EEG, and intracerebral EEG results. Intracerebral recordings documented that peak induced voltage with the custom TMS device matched that achieved with electroconvulsive shock and occurred in the prefrontal cortex. The commercially available device achieved less than half the voltage induced by electroconvulsive shock. Magnetic seizure threshold was titrated by administering trains of increasing durationuntil a generalized seizurewas induced.Duetocoilheating,nomorethan2trains could be administered in a single session. Thus, the varioustraindurationswereadministeredacross4sessions.Seizureswere reliably obtainedwith parameter settings of 40 Hz, 90% of maximal stimulator output, administered for 4 to 5 seconds. This represents stimulation at more than 400%of the electromyographically definedmotor threshold. Stimulation at this intensity is far in excess of recommended safety guidelines for humanuse of subconvulsive rTMS. The purpose of this experiment, however, was intentionalseizureinduction,andhighintensitieswereneeded to overcome the anticonvulsant effects of anesthesia. These findingsdemonstrate the feasibilityof rTMSseizure induction under general anesthesia. The fact that the commercial devicewas incapable of eliciting seizures suggests that the broader pulsewidth and/or faster frequency of the customdevicewere needed. Futureworkwill focus onparameterizationandsafety tosupportclinicaluse inhumans as a novel convulsive treatment. The enhanced control over dosage and focality achieved with rTMSmay offer the capacity to focus seizure induction in the prefrontal cortex, thereby improving the efficacy and limiting the cognitive side effects due to medial temporal lobe stimulation.Thisanimalmodel inwhichmagneticseizurethresholdcanbeeasilyassessed,willprovide informationrelevant tosafetyguidelines for thehumanuseofnonconvulsiveand convulsive rTMS, andmay provide a newmodel for studies of epilepsy.