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Potential applications of temporal interference deep brain stimulation for the treatment of transdiagnostic conditions in psychiatry

Neuropsychopharmacology volume 49, pages 305–306 (2024)Cite this article

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Neuromodulation affords numerous possibilities for alleviating suffering related to psychiatric disorders, from enhancing attentional control and motivation to inhibiting exaggerated fear responses and compulsions. To date, surgically-implanted deep brain stimulation (DBS) and transcranial magnetic stimulation (TMS) are the most widely-studied approaches. Both have significant limitations. DBS is highly costly and invasive, and surgical implantation of electrodes may have adverse effects (e.g., brain hemorrhage during surgery, infection). In contrast, TMS is a non-invasive stimulation technique that involves the application of magnetic field pulses delivered by electromagnetic coils placed against the scalp. These coils deliver a current that excites cortical electrical activity. However, TMS has limited focality, in that only surface brain structures may be safely targeted (~ 0.5–1 cm). As such, TMS can only influence deeper structures via their connectivity to superficial areas, which precludes selective targeting of key subcortical structures (e.g., amygdala, striatum) implicated in transdiagnostic conditions. This places significant limitations on TMS as a tool for studying psychiatric pathophysiology as well as a treatment modality.

As such, TI offers exciting possibilities as both a tool for understanding pathophysiology and as a potential treatment. For example, TI could be used for causal manipulations of brain structures whose function in humans has largely been inferred through triangulation of preclinical experimentation and correlative neuroimaging data. It has possibilities for effectively “mapping” circuits; multiple stimulator pairs can be utilized to target multiple regions in TI, exploring connectivity through modulation of regions within a single pathway. It has numerous potential applications for intervention. Inhibitory TI of the amygdala could be used to inhibit exaggerated fear response in people with posttraumatic stress disorder in conjunction with prolonged exposure therapy. Excitatory TI of the ventral striatum may be used in anhedonic depressed individuals to enhance effortful motivation during behavioral activation therapy. Given its depth and focality, non-invasive nature, minimal adverse effects, and use of relatively inexpensive equipment, TI may open new vistas for human cognitive neuroscience and neuromodulation interventions.

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Fig. 1: Example of setup for inhibitory temporal interference with the amygdala.

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Acknowledgements

The authors wish to acknowledge the following source of funding: Imagine, Innovate, and Impact Med Tech Research Grant, Emory University School of Medicine.

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  1. Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA

    Negar Fani & Michael T. Treadway

  2. Department of Psychology, Emory University, Atlanta, GA, USA

    Michael T. Treadway

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  1. Negar Fani
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Both authors have contributed equally in the writing, editing and review of this manuscript.

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Correspondence to Negar Fani.

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NF has no financial conflicts of interest to disclose. In the past 3 years, MTT has been a paid consultant to Neumora (formerly Blackthorn Therapeutics) and Boehringer Ingelheim. None of these entities contributed to the current work and all opinions expressed herein are solely those of the authors.

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Fani, N., Treadway, M.T. Potential applications of temporal interference deep brain stimulation for the treatment of transdiagnostic conditions in psychiatry. Neuropsychopharmacol. 49, 305–306 (2024). https://doi.org/10.1038/s41386-023-01682-5

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