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

Summary

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.

Abstract

It is widely accepted that olfactory stimulation elicits motor behaviors, such as approaching pleasant odorants and avoiding unpleasant ones, in animals and humans. Recently, studies using electroencephalography and transcranial magnetic stimulation (TMS) have demonstrated a strong link between processing in the olfactory system and activity in the motor cortex in humans. To better understand the interactions between the olfactory and the motor systems and to overcome some of the previous methodological limitations, we developed a new method combining an olfactometer that synchronizes the random order presentation of odorants with different hedonic values and the TMS (single- and dual-coil) triggering with nasal breathing phases. This method allows probing the modulations of corticospinal excitability and effective ipsilateral connectivity between the dorsolateral prefrontal cortex and the primary motor cortex that could occur during pleasant and unpleasant odor perception. The application of this method will allow for objectively discriminating the pleasantness value of an odorant in a given participant, indicating the biological impact of the odorant on brain effective connectivity and excitability. In addition, this could pave the way for clinical investigations in patients with neurological or neuropsychiatric disorders who may exhibit odor hedonic alterations and maladaptive approach-avoidance behaviors.

Introduction

It is widely accepted that olfactory stimulation elicits automatic reactions and motor behaviors. For example, in humans, the existence of an avoidance motor response (leaning away from the odor source) occurring 500 ms after negative odor onset has been recently demonstrated¹. By recording freely moving human participants exploring odors emanating from flasks, Chalençon et al. (2022) showed that motor behaviors (i.e., speed of approach to the nose and withdrawal of the flask containing the odorant) are closely linked to odor hedonics². Moreover, a close link between processing in the olfactory system and activity i....

Protocol

All experimental procedures described in the following sections have been approved by an Ethics Committee (CPP Ile de France VII, Paris, France, protocol number 2022-A01967-36) in accordance with the Declaration of Helsinki. All participants provided written informed consent before study enrollment.

1. Participant recruitment

1. Inclusion/exclusion criteria.
   1. Include adult (> 18 years) participants. Screen all participants for any contraindications to T.......

Discussion

The protocol above describes a novel method combining the use of a breath-synchronized olfactometer with single- and dual-coil TMS to investigate changes in corticospinal excitability and effective connectivity depending on the hedonic value of the odorants. This setup will allow for objectively discriminating the pleasantness value of an odorant in a given participant, indicating the biological impact of the odorant on brain effective connectivity and reactivity. The critical steps in this protocol involve both TMS.......

Materials

Name	Company	Catalog Number	Comments
Acquisition board (8 channels)	National Instrument	NI USB-6009
Air compressor	Jun-Air	Model6-15
Alcohol prep pads	Any
Butyric acid	Sigma-Aldrich	B103500	Negative odorant
Desktop computer	Dell	Latitude 3520
EMG system	Biopac System	MP150
Isoamyl acetate	Sigma-Aldrich	W205508	Positive odorant
Nasal cannula	SEBAC France	O1320
Programmable pulse generator	A.M.P.I	Master-8
Surface electrodes	Kendall Medi-trace	FS327
TMS coil (X2)	MagStim	D40 Alpha B.I. coil
TMS machine	MagStim	Bistim2
Tube 6 mm x 20 m	Radiospare	686-2671	Pneumatic connection
USB-RS232	Radiospare	687-7806
U-shaped tubes	VS technologies	VS110115