www.elsevier.com/locate/brainres Available online at www.sciencedirect.com Research Report Frequency-dependent effects of contralateral repetitive transcranial magnetic stimulation on penicillin-induced seizures Ching-Yi Lin a,n,1 , Kevin Li a,1 , Linda Franic b , Jorge Gonzalez-Martinez b , Vernon W. Lin c , Imad Najm b , Yu-Shang Lee a a Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA b Epilepsy Center, Cleveland Clinic, Cleveland, OH, USA c Department of Physical Medicine and Rehabilitation, Cleveland Clinic, Cleveland, OH, USA article info Article history: Accepted 5 June 2014 Available online 14 June 2014 Keywords: Epilepsy Intracranial electroencephalograph Myoclonic seizures Generalized tonic–clonic seizures Transcranial magnetic stimulation (TMS) abstract Transcranial magnetic stimulation (TMS) has been shown to modulate multiple brain functions, warranting further exploration in clinical applications. TMS treatment for epilepsy is particularly promising because of its anti-convulsive capabilities. However, TMS has been found to both inhibit and facilitate various experimental and clinical seizures, depending on the TMS parameters used. Repetitive TMS (rTMS) pulse frequency is recognized as one of the most influential parameters and thus was investigated in this study at 1, 5 and 10 Hz for its effects on a rat model of penicillin-induced seizures. High-dose penicillin-induced seizures were char- acterized by a combination of myoclonic and tonic–clonic (GTC) seizures. rTMS effects were analyzed with intracranial electroencephalographic (iEEG) data and video-captured behaviors. Animals treated with 1 and 5 Hz consistently showed evidence of anti-convulsive properties in their iEEG-based seizure profiles when compared to sham rTMS treatment. In contrast, data from 10 Hz rTMS suggested facilitative characteristics. Our results showed that 5 Hz rTMS consistently outperformed 1 Hz rTMS in seizure suppression. This re-emphasizes the impor- tance in accurately characterizing TMS effects on seizure suppression due to the heterogeneous nature of seizures. Thus, finely tuned TMS treatment has great potential to become a powerful asset in combating epilepsy. & 2014 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.brainres.2014.06.006 0006-8993/& 2014 Elsevier B.V. All rights reserved. Abbreviations: AEDs, antiepileptic drugs; DSA, density spectral array; EEG, electroencephalographic; GTC, generalized tonic–clonic; GUI, graphical user interface; iEEG, intracranial EEG; IRR, increasing regression rates; PBS, phosphate-buffered saline; PFO, hours post- first onset; Hz, pulse per second; PS, post-rTMS stimulation; PTZ, pentylenetetrazol; rTMS, repetitive TMS; TMS, transcranial magnetic stimulation n Correspondence to: Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Ave., LRI, NE6-313, Cleveland, OH 44195, USA. Fax: þ1 216 636 4332. E-mail address: linc@ccf.org (C.-Y. Lin). 1 Both authors contributed equally to this work. brainresearch 1581 (2014)103–116