Review
Personalized Transcranial Magnetic Stimulation in Psychiatry

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Abstract

Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation technique that allows for modulating the activity of local neural populations and related neural networks. TMS is touted as a viable intervention to normalize brain activity and alleviate some psychiatric symptoms. However, TMS interventions are known to be only moderately reliable, and the efficacy of such therapies remains to be proven for psychiatric disorders other than depression. We review new opportunities to personalize TMS interventions using neuroimaging and computational modeling, aiming to optimize treatment to suit particular individuals and clinical subgroups. Specifically, we consider the prospect of improving the efficacy of existing TMS interventions by parsing broad diagnostic categories into biologically and clinically homogeneous biotypes. Biotypes can provide distinct treatment targets for optimized TMS interventions. We further discuss the utility of computational models in refining TMS personalization and efficiently establishing optimal cortical targets for distinct biotypes. Personalizing cortical stimulation targets, treatment frequencies, and intensities can improve the therapeutic efficacy of TMS and potentially establish noninvasive brain stimulation as a viable treatment for psychiatric symptoms.

Section snippets

Transcranial Magnetic Stimulation

TMS is a validated noninvasive brain stimulation technique for modulating the activity of neurons within a region of the cortex 16, 17, 18. TMS is based on the principle of electromagnetic induction and delivers a strong, but short-lived, magnetic field that induces a perpendicular electrical field (19). The resulting electrical currents can subsequently depolarize neuronal axons (Figure 1A). The local effects of TMS are typically studied in the motor system because motor evoked potentials

TMS in Psychiatry: Challenges and Opportunities

The use of TMS as a potential tool to evaluate neural function and improve symptoms of psychiatric disorders can be traced to the 1990s 35, 36, 37, 38. TMS is now recognized for its role in managing symptoms of major depressive disorder in patients failing to respond to at least one or two courses of pharmacological treatment (39). Stimulation of the dorsolateral prefrontal cortex (DLPFC) with rTMS has consistently shown significant efficacy at the group level. Compared with placebo, 4 weeks of

TMS Effects in Regions Distant From Stimulation Site

It has long been posited that TMS can impact brain activity in regions that are distant from the stimulation site as well as modulate functional connectivity between pairs of brain regions that are not directly stimulated 59, 60, 61. More recently, neuroimaging techniques have been used to study the impact of TMS on the activity of whole-brain networks 62, 63, 64, 65 [for recent summaries see 7, 66].

For example, Eldaief et al. (62) showed that 1-Hz and 20-Hz rTMS of the left posterior inferior

Personalization of TMS Interventions

Personalizing cortical stimulation targets is motivated by the observation that patterns of abnormal brain activity vary markedly between psychiatric disorders and between individuals with the same diagnosis 7, 46, 73. To improve reliability and efficacy, TMS interventions can be tailored to each individual to account for interindividual differences in brain pathology and anatomy. The cortical stimulation target is perhaps the parameter that is most commonly considered for personalization, but

Improving Prediction and Personalization of TMS Using Computational Modeling and Network Simulation

Stimulation targets that are optimized to individual biotypes will ultimately need to be tested. Moreover, biotype analysis may indicate more than one candidate target, requiring the evaluation of different cortical sites to establish a single clinical target. Computational models to predict the local and distributed effects of TMS can help to offset the cost of empirical testing and assist with personalizing TMS protocols (13). Models for TMS fall within two broad categories: 1) biophysical

Conclusions and Future Directions

In this review, we argued that the efficacy and reliability of TMS can be enhanced with intervention personalization. We considered two complementary approaches to personalization: personalizing interventions at the biotype and single-subject levels. Biotypes delineate patient subgroups that exhibit greater homogeneity with respect to brain chemistry, connectivity, and electrophysiology as well as behavior and clinical symptoms, relative to current broad diagnostic categories. Parsing

Acknowledgments and Disclosures

This work was supported by the Australian National Health Medical Research Council (Grant Nos. APP1099082 and APP1138711 to LC, Grant No. APP1047648 to AZ).

The authors report no biomedical financial interests or potential conflicts of interest.

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