Combining a Breath-Synchronized Olfactometer with Brain Simulation to Study the Impact of Odors on Corticospinal Excitability and Effective Connectivity

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.