Effect of Non-invasive Magnetic Stimulation of the Brain on Breathlessness in Healthy Individuals. (AHrTMS)

Effect of Repetitive Transcranial Magnetic Stimulation (rTMS) of the Dorsolateral Prefrontal Cortex (DLPFC) on Hypercapnic Air Hunger Induced in Healthy Individuals.

The purpose of this study is to see if the front part of the brain called the "Dorsolateral Prefrontal Cortex" (DLPFC) has a role in our ability to feel breathlessness. The experiment will use a device that sits on the top of the head which produces a magnetic field that penetrates the scalp and excites the brain tissue directly under it. This procedure is called repetitive transcranial magnetic stimulation (rTMS), it is a painless procedure and known to be safe in healthy individuals. Previous research has shown that the pain felt when capsaicin, the active ingredient in 'chilli' powder, is applied to the hand is reduced by applying the rTMS on the scalp directly above the DLPFC part of the brain. In this experiment we want to see if breathlessness is also reduced. We will use a breathing task that will generate a moderate amount of breathlessness by adding a small amount of carbon dioxide to the inhaled air, while preventing the increase in the amount of breathing we would normally see in response to this. If we find that breathlessness produced by this breathing task is reduced after rTMS over the DLPFC, this may lead to new drugs that target this part of the brain in patients suffering from breathlessness due to heart or lung disease. The study will also improve our knowledge of how the brain enables us to feel breathlessness

Study Overview

• Status: Completed
• Conditions: Dyspnea
• Intervention / Treatment: Device: rTMS-L-DLPFC; Device: rTMS-R-DLPFC; Device: Sham rTMS-DLPFC

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 0BP
      • Oxford Brookes University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

healthy individuals, over 18 years old, with no history of heart, lung or neurological conditions

Exclusion Criteria:

• Any history of respiratory problems (including Asthma that involves regular use of inhalers)
• Any history of heart or circulatory problems (e.g. palpitations, arrhythmias, angina, BP)
• Any history of epilepsy, convulsions or seizures, migraines, or fainting
• Any history of anxiety disorders (e.g. panic attacks)
• Any history of serious head injury or brain surgery
• Any metal parts in the head (except dental wire)
• Any implants (e.g. pacemaker, insulin pump, neurostimulator)
• Pregnancy or problems with alcohol or drug abuse.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stimulation of Left DLPFC; Intervention applied to Left DLPFC located by the BeamF3 technique	Device: rTMS-L-DLPFC; 5 Hz rTMS applied using an actual coil over the left DLPFC
Active Comparator: Stimulation of Right DLPFC; Intervention applied to Right DLPFC located by the BeamF3 technique	Device: rTMS-R-DLPFC; 5Hz rTMS applied using actual coil over Right DLPFC
Sham Comparator: Sham Stimulation; Sham intervention applied to either the left or right DLPFC	Device: Sham rTMS-DLPFC; 5Hz rTMS applied using sham coil over left or right DLPFC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Air hunger	Ratings of air hunger on a 100mm Visual analog scale with the extremes defined as 'non' and 'tolerable limit'	Average of 4 steady state ratings in the last minute of air hunger tests

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bond Lader Mood questionnaire scores	Ratings provided on a 100mm visual analogue scale anchored by a negative mood descriptor at one extreme and the opposing positive mood descriptor at the other extreme. The average scores for 'sedation' descriptors, 'discontentment' descriptors, and 'relaxation' descriptors are each expressed as %maximum	Questionnaire administered immediately following pre and post intervention air hunger tests for how participants were feeling at that moment in time.
Spielberger's state-trait anxiety inventory (STAI form Y-1 and form Y2) scores	20 is the lowest score and 80 is the highest score for both state (form Y-1) and trait (Form Y-2) anxiety	Form Y-2 (trait anxiety) administered once on the initial practice day. Form Y-1 (state anxiety) administered immediately following pre and post intervention air hunger tests on test days.
Dyspnoea-12 total, physical and emotion scores	For Total score; zero indicates no dyspnoea and 36 indicates worst possible dyspnoea (expressed as %fullscale). For Physical score; zero indicates no dyspnoea in the physical domain and 21 indicates worst possible dyspnoea in physical domain (expressed as %fullscale). For Emotion score; zero indicates no dyspnoea in emotion domian and 15 indicates worst possible dyspnoea in emotion domain (expressed as %fullscale).	Administered immediately following pre and post intervention air hunger tests in relation to the "test just completed"

Collaborators and Investigators

• Sponsor: Oxford Brookes University
• Collaborators: University of Oxford
• Investigators: Principal Investigator: Shakeeb H Moosavi, PhD, Oxford Brookes University

Publications and helpful links

General Publications

• Banzett RB, Moosavi SH. Dyspnea and pain: Similarities and contrasts between two very unpleasant sensations. APS Bulletin. 2001; 11: 1-8.
• Brighina F, De Tommaso M, Giglia F, Scalia S, Cosentino G, Puma A, Panetta M, Giglia G, Fierro B. Modulation of pain perception by transcranial magnetic stimulation of left prefrontal cortex. J Headache Pain. 2011 Apr;12(2):185-91. doi: 10.1007/s10194-011-0322-8. Epub 2011 Feb 25.
• Harrison OK, Hayen A, Wager TD, Pattinson KTS. Investigating the specificity of the neurologic pain signature against breathlessness and finger opposition. Pain. 2021 Dec 1;162(12):2933-2944. doi: 10.1097/j.pain.0000000000002327.
• Herigstad M, Hayen A, Evans E, Hardinge FM, Davies RJ, Wiech K, Pattinson KTS. Dyspnea-related cues engage the prefrontal cortex: evidence from functional brain imaging in COPD. Chest. 2015 Oct;148(4):953-961. doi: 10.1378/chest.15-0416.
• Nierat MC, Hudson AL, Chaskalovic J, Similowski T, Laviolette L. Repetitive transcranial magnetic stimulation over the supplementary motor area modifies breathing pattern in response to inspiratory loading in normal humans. Front Physiol. 2015 Sep 29;6:273. doi: 10.3389/fphys.2015.00273. eCollection 2015.
• Yorke J, Moosavi SH, Shuldham C, Jones PW. Quantification of dyspnoea using descriptors: development and initial testing of the Dyspnoea-12. Thorax. 2010 Jan;65(1):21-6. doi: 10.1136/thx.2009.118521. Epub 2009 Dec 8.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2022
• Primary Completion (Actual): May 16, 2024
• Study Completion (Actual): May 16, 2024

Study Registration Dates

• First Submitted: November 12, 2022
• First Submitted That Met QC Criteria: November 12, 2022
• First Posted (Actual): November 21, 2022

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Air Hunger
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Dyspnea
• Other Study ID Numbers: HLS/2021/PH/002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The de-identified IPD used in the results publication will be made available on the Oxford Brookes University Research and digital assets repository (RADAR)
• IPD Sharing Time Frame: At the time of submission for journal publication of results
• IPD Sharing Access Criteria: RADAR shares the intellectual product of Oxford Brookes University freely and openly, either with staff and students of Oxford brookes University or with the general public and global academic community
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No