[15O]H2OPositron Emission Tomography During External Trigeminal Nerve Stimulation
Christopher DeGiorgio1, Lara Schrader1, Patrick Miller2, Mary Susselman3, Cheri Geist4, Ian Cook5
1UCLA Department of Neurology, 2Neurosigma, Inc, 3Semel Insitute, UCLA, 4UCLA, 5UCLA School of Medicine and LA TMS Institute
Objective:

To advance the understanding of the mechanism of action of Trigeminal Nerve Stimulation using [15O]H2O Positron Emission Tomography.

Background:
Neuromodulation via external trigeminal nerve stimulation (eTNS) is an emerging intervention for epilepsy, attention deficit disorder and major depression. eTNS is now US FDA approved for attention deficit disorder. The effect of eTNS on cortical blood flow and metabolism is unknown. A better understanding of which brain areas are activated or deactivated by eTNS would provide a scientific basis and a roadmap to identify new disease targets and interventions.  
Design/Methods:

Five subjects with treatment resistant depression underwent eTNS. IRB approval and informed consent was obtained. [15O]H2O brain PET scans were performed using a Siemens-CTI HR+ EXACT system at the UCLA Laboratory of Neuroimaging. Three scans were performed with trigeminal stimulation ON (scans 1, 3 and 6), and three scans were performed with trigeminal stimulation OFF (scans 2, 4 and 5).  Data was analyzed comparing stimulus ON versus stimulus OFF scans. Adjustments for multiple comparisons were made using the Family Wise Error (FWER) correction.

Results:

External Trigeminal Nerve stimulation resulted in significant activations in bilateral anterior cingulate gyri, bilateral parieto-temporal cortex, left inferior frontal gyrus, and right medial and middle frontal gyri. The most significant deactivations occurred in the left para-hippocampal gyrus, right sensorimotor cortex, right superior parietal area, bilateral temporo-occipital cortex, and bilateral visual cortex.

Conclusions:

External Trigeminal Nerve stimulation (eTNS) results in significant activations during [15O]H2O PET imaging in regions associated with major depression and attention deficit disorder. Deactivations of cortical regions including the para-hippocampal gyrus, sensorimotor cortex and others provides a rationale for some of the anti-seizure effects of Trigeminal Nerve stimulation. This study advances our understanding of mechanisms of action of Trigeminal Nerve stimulation in Epilepsy and Neuropsychiatric disorders.

10.1212/WNL.0000000000217527
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