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MILITARY
MEDICINE
Non-invasive Neuromodulation for
Posttraumatic Stress Disorder:
A Trial of Image-guided, Robotic,
Transcranial Magnetic Stimulation
By: Peter T. Fox, M.D.1,2,3,4,5, Felipe Salinas, Ph.D.1,5, Mary Unzueta, M.D.6,
John Roache, Ph.D.3,5, Jack L. Lancaster, Ph.D.1,2
1. Research Imaging Institute, UT Health San Antonio, San Antonio, Texas pression (LTD), which have been firmly established in a wide
2. Department of Radiology, UT Health San Antonio, San Antonio, Texas range of species, including humans. Based on the Hebbian neu-
3. Department of Psychiatry, UT Health San Antonio, San Antonio, Texas romodulatory principal, repetitive TMS has been tested in hun-
4. Department of Neurology, UT Health San Antonio, San Antonio, Texas dreds of trials in scores of disorders, including major depressive
5. South Texas Veterans Health Care System, San Antonio, Texas disorder (MDD) and PTSD. TMS received FDA approval for
6. Laurel Ridge Treatment Center, San Antonio, Texas use in treatment resistant MDD, based on a multi-site RCT
(O'Reardon et al., 2007). TMS is not yet FDA approved for
Posttraumatic Stress Disorder or PTSD is a debilitating anx- PTSD, although preliminary trials are promising (Karsen et al.,
iety disorder experienced by ≥ 7.8 percent of the United States 2014; Clark et al., 2015).
populace over the course of their lifetime. Since 2001, over 2.5
million U.S. Service members have been deployed in combat op- Connectomic Imaging
erations, resulting in higher rates of PTSD in combat veterans re- Imaging studies have definitively demonstrated that TMS neu-
turning from Operation Iraqi Freedom (OIF; 12-20%) and
Operation Enduring Freedom (OEF: 6-12%). Although pharma- romodulatory effects are network based, simultaneously modu-
cologic and psychotherapeutic treatments have been shown to lating multiple, interconnected brain regions and extending over
help reduce PTSD symptoms, there is no definitive treatment for long distances (Fox et al., 1997, 2004, 2006; Laird et al., 2008;
PTSD. The success of PTSD treatments has been is limited by Narayana et al., 2012). Further, TMS effects at different nodes in
medication side effects and discontinuation of cognitive and be- a stimulated network can have different valences (excitatory or
havioral therapy. Consequently, alternative treatments, including inhibitory) for the same stimulus frequency (Salinas et al., 2013,
neuromoduation, need further exploration. 2016). This neurological complexity argues that TMS therapeu-
tics must be informed by realistic models of human neural net-
Transcranial Magnetic Stimulation or TMS is a noninvasive works. The richest sources of such models are a new generation
means of electrically stimulating the human brain. Magnetic fields of imaging modalities that map and quantify brain connectivity,
pass readily through biological tissues, including bone. Rapidly often termed connectomics or connectomic imaging. In addition
changing magnetic fields induce electrical currents that, in turn, to providing models of neural networks performing specific func-
depolarize neurons. In the 1950’s, Donald Hebb described the tions (e.g., somesthesis, visuomotor control or language produc-
principal of Hebbian learning, which states that repetitive firing tion), connectomic imaging can be used to detect disease-specific
of a neural system will be neuromodulatory, modifying the synap- abnormalities of information transfer. Ongoing advances in con-
tic weights of the stimulated circuits. Current formulations of nectomic imaging offer the potential for “personalized” neuro-
this principal are long-term potentiation (LTP) and long-term de- modulatory treatments, in which the treatment plan is informed
26 San Antonio Medicine • August 2017
