Targeted neurostimulation reverses a spatiotemporal biomarker of treatment-resistant depression

Abstract

Major depressive disorder (MDD) is widely hypothesized to result from disordered communication across brain-wide networks. Yet, prior resting-state-functional MRI (rs-fMRI) studies of MDD have studied zero-lag temporal synchrony (functional connectivity) in brain activity absent directional information. We utilize the recent discovery of stereotyped brain-wide directed signaling patterns in humans to investigate the relationship between directed rs-fMRI activity, MDD, and treatment response to FDA-approved neurostimulation paradigm termed Stanford neuromodulation therapy (SNT). We find that SNT over the left dorsolateral prefrontal cortex (DLPFC) induces directed signaling shifts in the left DLPFC and bilateral anterior cingulate cortex (ACC). Directional signaling shifts in the ACC, but not the DLPFC, predict improvement in depression symptoms, and moreover, pretreatment ACC signaling predicts both depression severity and the likelihood of SNT treatment response. Taken together, our findings suggest that ACC-based directed signaling patterns in rs-fMRI are a potential biomarker of MDD.

Brain stimulation poised to move from last resort to frontline treatment

“…The effect of stimulation on the directional flow of neural signals along circuits may also matter—both as a potential marker for treatment-resistant depression and for its response to TMS. In a 2023 study, Williams and colleagues reported that in depressed people, signals to the anterior cingulate cortex, an emotion center in the brain, flow in the wrong direction, and the SAINT protocol can correct this flow ( 2 ).…”

Effect of chronic administration of ostruthin on depression-like behavior in chronically stressed mice

“…Indeed, neuromodulation techniques, such as deep brain stimulation, have shown therapeutic effects in patients with intractable depression. These stimulations are thought to re-regulate the dysregulated neuronal activity ( Mitra et al, 2023 ). Therefore, it is expected that other neuromodulatory methods will also achieve therapeutic effects.…”