The neural circuit model in psychiatry pays off

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Science Translational Medicine  01 Apr 2020:
Vol. 12, Issue 537, eabb5664
DOI: 10.1126/scitranslmed.abb5664


Noninvasive brain stimulation in depressed patients can be used to target different neural circuits, improving different symptoms.

Most psychiatrists would agree that symptoms of disorders such as depression have physical origins in the brain. However, these origins have appeared too complex or dynamic to be useful for diagnosis and treatment planning; diagnosis, therefore, depends on clinical observation and patient self-report. This has led to somewhat overlapping diagnostic criteria that some believe to have stymied the development of better treatments and interventions. In a recent study, Siddiqi et al. report a method using brain stimulation for treating different types of depression symptoms, based on neural circuit models. Their study provides a tool that could be used in clinical practice, with the subtext that it may soon be reasonable to consider treatments that directly address neural circuit dysfunction in complement with symptom improvement.

Transcranial magnetic stimulation (TMS) is a noninvasive treatment approved for treating depression. Clinicians apply an electromagnetic coil to the scalp to stimulate cells in the dorsolateral prefrontal cortex, a region implicated in cognitive control, which sends projections to many other brain regions. However, the dorsolateral prefrontal cortex is large and likely contains subdivisions that engage in different functions. Siddiqi and colleagues sought to improve treatment response by testing whether small variations in the stimulation location hit different downstream brain regions, with potentially different effects on individual symptoms, such as sleep disruption, worry, and negative mood. Stimulation of a more anterior region (closer to the left eyebrow), likely targeting connections to the insula and sensory brain regions, resulted in improvement in negative mood symptoms. Neuroscientists refer to this set of interacting regions as the “ventral attention network.” In contrast, stimulation of a more posterior region (closer to top of the head), targeting connections to the default mode network including the medial prefrontal cortex and temporal lobe, resulted in improvement in more anxiety-like symptoms and insomnia. The findings were highly generalizable, replicating in a separate group of depressed patients, as well as in a meta-analysis of published TMS trials spanning several psychiatric diagnoses.

The major tangible outcome was a new map to guide clinicians in placing stimulation coils in the optimal region to improve either negative mood or anxiety symptoms. The findings also suggest that a neural circuit–based model is ready for prime time in psychiatry. Treatments targeting dysfunction in specific neural circuits could be useful for improving specific symptoms. This was a retrospective analysis of existing data, and the clear next step is to prospectively test for differential effects of the two stimulation sites on negative mood and anxiety.

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