Department Role: Epileptologist; Director, Neuromodulation Program
Research Focus Areas: Noninvasive Brain Stimulation, Epilepsy, Traumatic Brain Injury
Our laboratory's major focus is on the development of novel methods to treat brain injury, particularly the type of brain injury that leads to epilepsy. We work to identify biological targets which can stop or prevent seizures if manipulated by either brain stimulation or by novel drugs that we are testing in our lab.
We have adapted methods for transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) to rodents, to in vitro brain slice preparations, and more recently to zebrafish (an emerging experimental tool in epilepsy). TMS and tDCS have in common the capacity to safely induce durable changes in neuronal activity. Limited experience with human patients, including those treated at Boston Children's Hospital, shows that TMS and tDCS have realistic prospects in suppressing seizures. Yet whether these techniques can prevent the onset of epilepsy after various forms of brain injury has not been tested. To characterize the cellular mechanisms by which TMS and tDCS exert their effect, and ultimately to optimize their clinical efficacy, we are testing these techniques in rodent epilepsy models, including models of traumatic brain injury (TBI).
To determine how best to match the cellular changes induced by noninvasive brain stimulation those of brain injury and epilepsy, we are also studying the molecular changes associated with TBI in rats. A second major focus has grown out of this work: testing novel pharmaceutical approaches to prevent brain injury and seizures after TBI.
In parallel to our laboratory experiments, we have ongoing clinical projects aimed to further develop techniques for noninvasive brain stimulation, particularly TMS and tDCS, as diagnostic and therapeutic tools in child neurology.
About Alexander Rotenberg
Alex Rotenberg was born in Chernovtsy, Ukraine. He is a graduate of Johns Hopkins University (BA) and the State University of New York, Downstate Medical Center (MD, PhD). He is an active member of the American Epilepsy Society.. His current appointment is as Associate Professor of Neurology, Harvard Medical School.
(Selected publications from ongoing experiments)
- Muller, P. A., Dhamne, S. C., Vahabzadeh-Hagh, A. M., Pascual-Leone, A., Jensen, F. E., & Rotenberg, A. (2014). Suppression of motor cortical excitability in anesthetized rats by low frequency repetitive transcranial magnetic stimulation. PloS one, 9(3), e91065.
- Goodrich, G. S., Kabakov, A. Y., Hameed, M. Q., Dhamne, S. C., Rosenberg, P. A., & Rotenberg, A. (2013). Ceftriaxone treatment after traumatic brain injury restores expression of the glutamate transporter, GLT-1, reduces regional gliosis, and reduces post-traumatic seizures in the rat. Journal of neurotrauma,30(16), 1434-1441.
- Kabakov, A. Y., Muller, P. A., Pascual-Leone, A., Jensen, F. E., & Rotenberg, A. (2012). Contribution of axonal orientation to pathway-dependent modulation of excitatory transmission by direct current stimulation in isolated rat hippocampus. Journal of neurophysiology, 107(7), 1881-1889.
- Hsieh, T. H., Dhamne, S. C., Chen, J. J. J., Pascual-Leone, A., Jensen, F. E., & Rotenberg, A. (2012). A new measure of cortical inhibition by mechanomyography and paired-pulse transcranial magnetic stimulation in unanesthetized rats. Journal of neurophysiology, 107(3), 966-972.
- Bae, E. H., Theodore, W. H., Fregni, F., Cantello, R., Pascual-Leone, A., & Rotenberg, A. (2011). An estimate of placebo effect of repetitive transcranial magnetic stimulation in epilepsy. Epilepsy & Behavior, 20(2), 355-359.
- Vahabzadeh-Hagh, A. M., Muller, P. A., Pascual-Leone, A., Jensen, F. E., & Rotenberg, A. (2011). Measures of cortical inhibition by paired-pulse transcranial magnetic stimulation in anesthetized rats. Journal of neurophysiology, 105(2), 615-624.
- Rotenberg, A. (2010). Prospects for clinical applications of transcranial magnetic stimulation and real-time EEG in epilepsy. Brain topography, 22(4), 257-266.
- Rotenberg, A., Muller, P. A., Vahabzadeh-Hagh, A. M., Navarro, X., López-Vales, R., Pascual-Leone, A., & Jensen, F. (2010). Lateralization of forelimb motor evoked potentials by transcranial magnetic stimulation in rats. Clinical Neurophysiology, 121(1), 104-108.
- Rotenberg, A., Bae, E. H., Takeoka, M., Tormos, J. M., Schachter, S. C., & Pascual-Leone, A. (2009). Repetitive transcranial magnetic stimulation in the treatment of epilepsia partialis continua. Epilepsy & Behavior, 14(1), 253-257.
- Rotenberg, A., Muller, P., Birnbaum, D., Harrington, M., Riviello, J. J., Pascual-Leone, A., & Jensen, F. E. (2008). Seizure suppression by EEG-guided repetitive transcranial magnetic stimulation in the rat. Clinical Neurophysiology,119(12), 2697-2702.
(Selected publications from Ph.D. Thesis)
- Rotenberg, A., Abel, T., Hawkins, R. D., Kandel, E. R., & Muller, R. U. (2000). Parallel instabilities of long-term potentiation, place cells, and learning caused by decreased protein kinase A activity. The Journal of Neuroscience, 20(21), 8096-8102.
- Rotenberg, A., Mayford, M., Hawkins, R. D., Kandel, E. R., & Muller, R. U. (1996). Mice expressing activated CaMKII lack low frequency LTP and do not form stable place cells in the CA1 region of the hippocampus. Cell, 87(7), 1351-1361.
Dhamne, S.C., Ekstein, D., Zhuo, Z., Gersner, R., Zurakowski, D., Loddenkemper, T., Pascual-Leone, A., Jensen, F.E., & Rotenberg, A. (2015). Acute seizure suppression by transcranial direct current stimulation in rats. Ann Clin Transl Neurol (in press)