Transcutaneous vagus nerve stimulation enhances reward-effort efficiency in major depressive disorder

Major depressive disorder (MDD) is a highly prevalent psychiatric disorder with changes in motivation to work for rewards being a core symptom. Global cases of MDD have risen rapidly in the past decades, yet around one third of MDD patients do not respond to first-line treatment. Impaired motivation in MDD is an important treatment target, as anhedonia is a key negative predictor of recovery. Transcutaneous vagus nerve stimulation (tVNS) has emerged as a promising non-invasive therapy for MDD. The vagus nerve drives parasympathetic activity and has connections to multiple brain circuits implicated in MDD. However, the effects of tVNS on the core features of MDD, such as changes in motivation and reward-effort decision-making, remain relatively unexplored. The aim of this study was to investigate how tVNS impacted reward-effort efficiency – how optimally individuals decided to allocate physical effort to gain rewards – and to determine whether a diagnosis of MDD and depressive symptom severity modulated potential tVNS effects. Based on previous studies showing the benefits of tVNS in MDD, we hypothesised that tVNS would improve reward-effort efficiency.

In this randomised, single-blind, crossover, controlled trial (MODULATE Depression: DRKS00024823), we used a Grip Strength Effort Task (GSET) to investigate how tVNS affects choices to exert different levels of physical effort for varying monetary rewards in MDD patients (n=53) and a non-depressed control group (n=45). Stimulation was applied at the cymba conchae of the right ear using biphasic electrical pulses (250 µs pulse width, 25 Hz, 32 s on / 28–30 s off) and sham stimulation was applied at the earlobe. Depressive symptom severity was assessed using the Beck Depression Inventory-II (BDI-II) and participants were grouped using established clinical cut offs: no-to-minimal symptoms (BDI-II ≤13; n=51), mild-to-moderate symptoms (BDI-II 14–28; n=28), and severe symptoms (BDI-II ≥29; n=19). The key outcome, reward-effort efficiency, was analysed using mixed effects logistic regression.

Compared to sham stimulation, tVNS enhanced reward-effort efficiency in participants with severe depressive symptoms (BDI-II ≥29; β=0.931, SE=0.370, p=0.012; estimated probabilities: sham=0.894, tVNS=0.946; p=0.022). These effects were not observed in participants with no-to-minimal or mild-to-moderate depressive symptoms. The effect of tVNS on reward-effort efficiency was driven by reductions in unnecessary effort in the severe BDI-II group (sham=0.100, tVNS=0.018; p=0.045), that is, a reduction in choices to exert additional effort when this was not required to gain a larger reward. When BDI-II scores were treated as a continuous variable, all key findings were replicated. These findings suggest that tVNS leads to a more efficient allocation of effort when gaining rewards in MDD, and highlight a potential motivational mechanism by which tVNS exerts its therapeutic effects. Future work should establish whether these effects reflect a general enhancement of executive functions, such as cognitive flexibility, and investigate the neurocomputational mechanisms involved by combining tVNS with neuroimaging and psychopharmacological interventions.

References

No references