Combining a Breath-Synchronized Olfactometer with Brain Simulation to Study the Impact of Odors on Corticospinal Excitability and Effective Connectivity
January 19th, 2024
This paper describes using a breath-synchronized olfactometer to trigger single- and dual-coil transcranial magnetic stimulation (TMS) during odorant presentation synchronized to human nasal breathing. This combination allows us to objectively investigate how pleasant and unpleasant odors impact corticospinal excitability and brain-effective connectivity in a given individual.
Here, we aim to investigate the relationship between olfactory and motor system in the brain. We are particularly interested in exploring our pleasant and unpleasant odors will impact corticospinal accessibility and effective connectivity in both normal and pathological condition. Exploring the mechanistic basis of olfactory motor interactions requires careful consideration of two methodological aspects.
First, it is imperative to deliver different olfactory condition within the same experimental phase. Second, precise control and synchronization of olfactory and TMS stimulations with respiratory phases is required. We present a new method designed for the rigorous investigations of the modulation of corticospinal, excitability and effective connectivity that might occur during the perception of pleasant and unpleasant odors.
All the stimulations are delivered in synchrony with human nasal breathing. This method paved the way for clinical investigation, exploring aberrant interactions between olfactory and motor system. We are currently applying these methods to patients with psychiatric disorder that are associated with alterations in the adonic perception of odors and maladaptive approach or avoidance behaviors.
To begin, ask the participant to sit on a comfortable chair with both hands relaxed and pronated. Before electrode application, prepare the participant's skin by using an exfoliant scrub to lightly abrade the areas. Clean the areas with alcohol pads where electrodes will be applied.
Then apply to silver, silver chloride disposable recording electrodes using a belly tendon montage for the first dorsal interosseous muscle. Place the ground electrode on the styloid process of the ulna. Connect the electrodes to the amplifier with cables.
Integrate the system with the data acquisition system. Record the EMG signal and assess the quality of the signal displayed on the screen connected to the data acquisition system. Next, connect the TMS coil M1 to the A stimulator.
Then place a tight fitting cap over the participant's head. Use a tape measure to perform nasion-inion, tragus-tragus, and head circumference measurements based on standard cranial landmarks. Identify the scalp vertex at the intersection of the mid sagittal and inter oral lines and mark it with a pen.
Next, place the first small figure of eight coil tangentially to the scalp. Over the presumed hand area of the left M1, which is five centimeters lateral from the vertex. Then connect the TMS coil DLPFC to the B stimulator.
Use the updated scalp heuristic to locate the region of the scalp corresponding to the left DLPFC. Estimate the position of the second small figure of eight coil over the DLPFC. Download the online Excel spreadsheet calculation tool.
Enter the nasion-inion and tragus-tragus distances and the head circumference in centimeters. Report the XLA and YLA distances directly on the participant's head. Place the TMS coil DLPFC tangentially to the scalp over the presumed left DLPFC location.
With the handle pointing downward and laterally at a minus 45 degree angle to the mid sagittal line. Mark the TMS coil DLPFC placement on the cap to ensure proper coil placement throughout the experiment. Next, place the nasal canula of the olfactometer near the participant's nostrils to measure nasal breathing.
Instruct the participant to breathe normally through the nose. Turn on the portable air compressor, the olfactometer meter case, and the PC containing the software. Check all the cable connections.
Proceed to the calibration phase for 20 seconds to adjust the detection thresholds of the expiratory and inspiratory phases. Run the custom made coating script in the olfactory meter software. To deliver all combinations of spTMS and dsTMS with pleasant and unpleasant odors and no odors occurring in a random order.
A representative graph of respiratory signals showed that the expiratory and inspiratory phases are detected upon crossing the threshold. The odorant triggered immediately after the expiratory phase threshold and the TMS pulse triggered with a delay after the inspiratory phase threshold. Demonstrating that this method can precisely synchronize odorant diffusion and TMS timing according to human nasal breathing phases.
EMG and MEP recordings from the right FDI muscles showed that the peak tope amplitude of the MEPs evoked by spTMS and by dsTMS varied according to the hedonistic value of the odorant. When the results were normalized, all MEP ratios were below one. Indicating a suppressive effect of the left DLPFC on the left M1.
Overview
This study presents a novel experimental method using a breath-synchronized olfactometer combined with transcranial magnetic stimulation (TMS) to probe the interactions between olfactory perception and motor system responses. The research focuses on how pleasant and unpleasant odors modulate corticospinal excitability and effective connectivity, which could inform clinical investigations into olfactory-motor interactions.
Key Study Components
Area of Science
- Neuroscience
- Olfactory processing
- Transcranial magnetic stimulation
Background
- The interplay between olfactory stimuli and motor system responses is underexplored.
- Understanding how odors affect motor excitability has implications for clinical conditions.
- Synchronization of olfactory and TMS delivery is critical for accurate measurements.
- This approach is particularly relevant for studying psychiatric disorders that alter odor perception.
Purpose of Study
- To investigate how pleasant and unpleasant odors influence corticospinal excitability.
- To examine effective connectivity changes in normal and pathological conditions.
- To develop a rigorous method for studying olfactory-motor interactions.
Methods Used
- Utilized a breath-synchronized olfactometer alongside dual-coil TMS.
- Engaged healthy participants to assess motor responses during odor presentation.
- Synchronizing olfactory conditions with human nasal breathing was critical.
- Electromyography (EMG) was recorded to evaluate motor evoked potentials (MEPs).
- Stimuli included pleasant, unpleasant, and neutral odors presented randomly.
Main Results
- MEPs were influenced by the hedonic value of the odorants, showing varying peak amplitudes.
- Results indicated a suppressive effect of the left dorsolateral prefrontal cortex (DLPFC) on the primary motor cortex (M1).
- Key comparisons revealed the modulatory role of olfactory stimuli on motor excitability.
- Synchronizing stimuli aligned with breath phases improved experimental validity.
Conclusions
- This study enables precise investigation of olfactory-motor system interactions and the impact of odor valence.
- The novel methodology may enhance understanding of olfactory-related disorders.
- Findings have potential implications for therapeutic approaches in psychiatric contexts.
Frequently Asked Questions
Executive Industry Relevance
Integrating breath-synchronized olfactometry with TMS-based brain stimulation enables rigorous interrogation of how olfactory cues modulate motor system excitability and connectivity. This approach addresses a critical gap in understanding sensory-motor integration, supporting predictive confidence in target validation for neuropsychiatric and neurological disorder research. The method's precision and reproducibility position it as a valuable asset for early discovery and translational neuroscience pipelines.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Enables mechanistic de-risking by directly probing olfactory-motor pathway interactions.
- Supports functional target validation through quantitative assessment of corticospinal excitability changes.
- Facilitates portfolio triage by objectively discriminating odorant hedonic value and its neural impact.
Screening & Assay Development
- Prepares validated, breath-synchronized biological systems for downstream neurobehavioral assays.
- Standardizes stimulus delivery and response measurement, enhancing reproducibility across studies.
- Generates quantitative EMG and MEP outputs for reliable compound or intervention evaluation.
Translational & Preclinical Research
- Aligns with disease-relevant systems by modeling maladaptive approach-avoidance behaviors linked to odor perception.
- Enables continuity from mechanistic discovery to preclinical validation in neuropsychiatric disorder models.
- Provides predictive de-risking for interventions targeting sensory-motor integration deficits.
Pipeline & Workflow Integration
This method bridges early discovery and preclinical research by enabling hypothesis-driven testing of olfactory-motor interactions and their modulation by experimental variables.
- Discovery Biology: Supports hypothesis testing on sensory-motor pathway connectivity and modulation.
- Screening: Delivers reproducible, quantitative readouts of motor system excitability in response to controlled olfactory stimuli.
- Analytics: Provides EMG and MEP measurements for robust statistical comparison of experimental conditions.
- Translational Research: Facilitates modeling of clinically relevant behavioral phenotypes and biomarker alignment.
- Enterprise Reuse: Offers a standardized, reusable platform for cross-study and cross-indication sensory-motor research.
Operational & Enterprise Impact
- Scientific Value: Increases predictive confidence and reduces mechanistic ambiguity in sensory-motor research.
- Operational Value: Enhances standardization, reproducibility, and scalability of neurobehavioral assays.
- Strategic Value: Informs go/no-go decisions and reduces late-stage biological risk in neuropsychiatric portfolios.
- Portfolio Impact: Enables risk-adjusted prioritization of targets and interventions affecting sensory-motor integration.
Implementation Considerations
- Requires expertise in TMS, EMG, and olfactometry for accurate setup and data interpretation.
- Demands precise synchronization infrastructure for stimulus delivery and physiological recording.
- Necessitates cross-team standardization of protocols and calibration procedures.
- Adaptation may be needed for different model systems or patient populations.
- Participant variability in olfactory sensitivity and attention must be managed during testing.
