A novel neurostimulation strategy for facilitating fear regulation

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Science Translational Medicine  08 Aug 2018:
Vol. 10, Issue 453, eaau7385
DOI: 10.1126/scitranslmed.aau7385


Transcranial magnetic stimulation targeting a human homolog of a rodent fear regulation circuit enhances extinction learning in healthy human subjects.

Post-traumatic stress disorder, phobias, and anxiety disorders are highly prevalent and disabling and frequently feature deficits in regulating emotional responses to anxiety-provoking stimuli. Exposure therapy is an effective treatment that relies on extinction learning, in which patients are repeatedly exposed in a safe context to anxiety-inducing stimuli and learn to overcome their fears.

Raij et al. show how transcranial magnetic stimulation (TMS) can be used to enhance extinction learning in healthy human subjects by modulating a fear-regulating brain circuit. Their subjects first underwent an aversive conditioning paradigm, in which they viewed a series of images featuring red, blue, or yellow lights and learned that the red and blue lights (conditioned stimuli) predicted something unpleasant (a mild shock). The next day, they underwent an extinction learning paradigm, in which the same cues were repeatedly presented in the absence of a shock, and they learned—akin to exposure therapy—that these cues were no longer threatening. Previous work in rats had shown that brief electrical stimulation of the infralimbic region of the medial prefrontal cortex timed to coincide with the onset of the fear-evoking stimulus was sufficient to enhance extinction memory. Motivated by these findings, Raij et al. used TMS, non-invasive neurostimulation tool, to activate the human homolog of this circuit during extinction learning at presentation of the red light only. Remarkably, they found that this brief, single-session intervention was sufficient to enhance extinction memory, as indexed by reduced autonomic skin responses to presentations of the red light only. In contrast, the subjects continued to respond to the blue light as if they expected a shock.

Importantly, they went on to show that this effect only occurred when they stimulated a specific target in the left frontal cortex that was functionally connected to the extinction learning circuit, which suggests that individualized brain circuit connectivity maps could be harnessed to enhance therapeutic effects in future studies. These exciting results highlight the potential for using TMS to facilitate psychotherapies grounded in extinction learning principles, although it will of course be critical to first replicate them in larger samples involving patients with clinical anxiety disorders. They also imply that the benefits of TMS, which is already used to treat depression, could be further enhanced by modulating the timing of the stimulation to coincide with specific psychotherapeutic interventions.

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