Electrical Stimulation of the Olfactory Bulb and Tract: A Systematic Review of Preclinical and Clinical Studies

AI Summary

Human OB and OT stimulation successfully elicited olfactory percepts, demonstrating feasibility for olfactory prosthesis development.
Rodent anosmia models showed spatially selective neural responses; animals discriminated stimulation sites separated by 250 μm, supporting distinct odor encoding.
Clinical translation requires standardised protocols, large-mammal validation, and early-phase adult human studies to optimise parameters and assess therapeutic effects.

AI Summary

Electrical stimulation of the olfactory bulb (OB) and olfactory tract (OT) has emerged as a potential therapeutic approach to restore olfactory percepts and possibly improve associated conditions.

OBJECTIVE: This study aimed to systematically review preclinical and clinical electrical stimulation studies of the OB and OT, evaluate their relevance for olfactory prosthesis development, and identify key technical and translational requirements for clinical implementation.

Stimulation parameters significantly influenced outcomes: Spatially targeted, patterned stimulation produced odor-like responses and supported associative learning, whereas diffuse, high-frequency stimulation modulated mood and memory circuits.

Basic summary

Neuromodulation. 2026 Jun 11:S1094-7159(26)00151-0. doi: 10.1016/j.neurom.2026.05.009. Online ahead of print.

ABSTRACT

BACKGROUND: Olfactory dysfunction is highly prevalent worldwide and linked to major neurologic and psychiatric disorders. Electrical stimulation of the olfactory bulb (OB) and olfactory tract (OT) has emerged as a potential therapeutic approach to restore olfactory percepts and possibly improve associated conditions.

MATERIALS AND METHODS: Following Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 guidelines, PubMed, EMBASE, and Web of Science were searched until December 31, 2025. Eligible studies reported in vivo electrical stimulation of the OB or OT in mammals. A narrative synthesis of the data was undertaken.

RESULTS: Overall, 42 studies were included (38 animal, four human). Critically for prosthesis development, all four human studies successfully elicited olfactory perceptions through OB/OT stimulation. In rodent anosmia models, electrical stimulation evoked spatially selective neural responses, with animals indicating discrimination between stimulation sites spaced as close as 250 μm-establishing proof of principle for encoding distinct odor percepts. Stimulation parameters significantly influenced outcomes: Spatially targeted, patterned stimulation produced odor-like responses and supported associative learning, whereas diffuse, high-frequency stimulation modulated mood and memory circuits. The OB/OT’s extensive connectivity to limbic structures offers potential therapeutic benefits beyond smell restoration, although this requires careful parameter optimization.

CONCLUSION: OB and OT stimulation are accessible neuromodulation targets with promising but context-dependent effects. Translation requires standardized protocols, large-mammal validation, and early-phase adult human studies.

PMID:42429716 | DOI:10.1016/j.neurom.2026.05.009

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