Authors :
Presenting Author: Johanna M. H. Rau, Dr. med., MS – Goethe University Frankfurt
Robert Baudo, PhD – University of Chicago
Arantzazu San Agustín, PhD – University of Chicago
Daniel Biro, MD, PhD – University of Chicago
Shasha Wu, MD, PhD – University of Chicago
Naoum P. Issa, MD, PhD – University of Chicago
Joel L. Voss, PhD – University of Chicago
Rationale: Reduced functional connectivity of the hippocampus with its large-scale network has been associated with seizures and memory deficits in mesial temporal lobe epilepsy (mTLE). We hypothesize based on principles of homeostatic plasticity that normalizing this reduced connectivity could beneficially impact mTLE symptoms. Hippocampal indirectly targeted stimulation (HITS) is a transcranial magnetic stimulation (TMS) approach that increases functional connectivity and improves episodic memory performance in healthy individuals. In this pilot study, we applied HITS to subjects with mTLE. We report preliminary data on safety as well as the intervention’s impact on network function and memory.
Methods:
5 Patients with mTLE (3 bilateral, 2 post-surgical) were enrolled. All subjects completed 5 sessions of high-frequency repetitive TMS. Targets for TMS were identified in inferior parietal cortex based on individualized hippocampal functional MRI connectivity reductions relative to a normative dataset of healthy controls. Subjects completed memory tasks and functional MRI at baseline and one day following stimulation. Seizure activity was tracked with daily seizure diaries one month before through one month post-stimulation.
Results:
HITS did not evoke peri-interventional seizures in any subject. None of the subjects reported seizures on HITS days. No other major adverse events were recorded. Mean episodic memory performance as well as functional MRI connectivity of the hippocampus ipsilateral to stimulated parietal cortex to other locations of its typical network increased from baseline to post-intervention. Self-reported seizures remained at the same rate (2 subjects) or decreased (3 subjects) for the month post-intervention versus pre-intervention.
Conclusions: The safety profile of HITS appears favorable in subjects with mTLE. Our preliminary findings are not inconsistent with the potential of HITS to increase hippocampal network functional connectivity, to enhance memory performance, and to reduce seizure frequency in mTLE. Further studies with more subjects are required to rigorously test these hypotheses.
Funding: This study was partly funded by a Safadi Pilot Grant (UChicago).