fMRI（Functional Magnetic Resonance Imaging,fMRI ) Study of the Neural Mechanism of rTMS(Repetitive Transcranial Magnetic Stimulation,rTMS) Stimulation of the Left Dorsolateral Prefrontal Lobe in the Treatment of Nicotine Dependence
Phase: NA
Conditions: Tobacco Use Disorder, Repetitive Transcranial Magnetic Stimulation
Sponsor: Tang-Du Hospital

 
 
Study protocol 
Study life: 2024.09.07 

 
 
fMRI study of the neural mechanism of rTMS stimulation of the 
left dorsolateral prefrontal lobe in the treatment of nicotine 
dependence 
I. Research background 
Addiction, the most serious substance use disorder, is a chronic brain disease shaped by 
strong biosocial factors and has devastating consequences for both individuals and societ 
y. In China and even the world, nicotine addiction, or dependence, has long been an extre 
mely serious social and medical problem, endangering public health and one of the import 
ant causes of death around the world. About 15.2% of the global population smokes dail 
y, which represents more than 933 million people who smoke. [2] According to the "Chin 
a Smoking Harm to Health Report 2020" released in 2021, the number of smokers in Chi 
na exceeds 300 million, the smoking rate remains at a high level, and the number of deat 
hs due to smoking exceeds 1 million every year. 
At present, the main treatment methods at home and abroad, such as nicotine replaceme 
nt therapy, varenicline and bupropion drug therapy and psychological cognitive behavior th 
erapy, have a low smoking cessation rate and a high relapse rate. In recent years, a grow 
ing number of studies have found that Repetitive transcranial magnetic stimulation (rTMS) 
is a non-invasive, non-invasive treatment for reducing cravings in addicts. The basic princi 
ple is that according to the electromagnetic exchange effect, the magnetic field generated 
by the strong current in the coil penetrates the skull into the cerebral cortex, causing local 
small current in the corresponding cortex, changing the local electrical activity of the cer 
ebral cortex, so as to play a therapeutic role. 
At present, there are a few studies using rTMS to stimulate the right or/and left dorsola 
teral prefrontal lobe for the treatment of nicotine dependent patients, and the short-term im 
provement is obvious, but the sample size is small, there is no uniform conclusion and th 
e related neural mechanism is not clear. Our preliminary results show that rTMS has a si 
gnificant improvement and efficacy in heroin addiction. 
Ⅱ.Research method 
In this project, fMRI technology combined with psychobehavioral science was used to st 
udy the scientific problem of "the efficacy of left dorsolateral prefrontal rTMS in the treat 
ment of nicotine dependent patients and the relationship between the efficacy and the inter 
nal function and interaction characteristics of the large brain networks of ECN, DMN and 
SN" from an all-round perspective. After enrollment, the nicotine addicts first received rele 
vant psychobehavioral data and fMRI data collection, and then received continuous rTMS 
treatment for 2 weeks. After treatment, the above data were collected again, and then rece 
ived 1-month follow-up follow-up. Psychobehavioral data were collected once a week for 
nicotine addicts. Finally, the collected neuroimage data were analyzed to compare the diffe 
rence in efficacy between the true and false treatment groups, and to clarify the relationsh 
ip between the efficacy of nicotine dependent patients after rTMS treatment and the intern 
al functions of the large brain networks of ECN, DMN and SN as well as the interaction 
characteristics of the networks, so as to provide a scientific basis for the development of 
effective individualized treatment programs. 

 
 
Ⅲ.Test means 
1) Subject recruitment 
In order to ensure the ethical feasibility, this study intends to include 50 nicotine addict 
s receiving rTMS treatment (25 in the true rTMS treatment group and 25 in the false rT 
MS treatment group) and 25 healthy controls. The demographic matching contents of nicot 
ine addiction group and healthy control group included age, sex, education level, left and 
right handedness. 
The inclusion criteria of nicotine addiction group: 
① met the criteria of nicotine addiction in the Diagnostic and Statistical Manual of M 
ental Disorders Fifth Edition (DSM-5); 
② Right-handed; 
③ Did not receive drug treatment; Age range: 20-65 years old. 
Exclusion criteria for all subjects: 
② 
history of epilepsy; 
② Previous history of craniocerebral trauma, surgery, and serious mental or nervous sys 
tem diseases; 
③ No contraindications for MRI examination (no dentures, residual metal in the body 
due to surgery or trauma, claustrophobia); 
④ poor compliance; 
⑤ Polydrug abusers. 
2) rTMS treatment plan 
(1) Target selection: The therapeutic target of rTMS is located in the left dorsolateral pr 
efrontal lobe. For accurate positioning, we used a dedicated TMS navigator to determine t 
he specific location of the left dorsolateral prefrontal lobe (MNI coordinates: X=-50, Y=3 
0, Z=36) on the skull surface through registration with the subjects' head MRI images, an 
d marked it on the subjects' individually fitted TMS cap. (Terraneo A, Leggio L, Saladini 
M, Ermani M, Bonci A, Gallimberti L. Transcranial magnetic stimulation of dorsolateral p 
refrontal cortex reduces cocaine use: A pilot study. Eur Neuropsychopharmacol, 2016, 26 
(1): 37-44.) 
(2) rTMS parameters: TMS stimulation frequency is 10Hz, stimulation intensity is 100% 
of the motion threshold, 5s on, 10s off, for 10 minutes, a total of 2000 pulses. 
(3) rTMS treatment time: The total treatment time for each person is two weeks, five ti 
mes a week, a total of 10 times. 
3) Data collection 
(1) Psychological behavioral data collection 

 
 
It includes anxiety Rating Scale (HAMA), self-rating Depression Scale (BDI), smoking s 
urvey (FTND), basic craving assessment, craving degree assessment (cue), desired quitting 
degree assessment and NUI assessment. The psychobehavioral scale was assessed each tim 
e before fMRI data collection. Nicotine basal craving assessment and craving degree asses 
sment (cue) were assessed before and after fMRI collection and before and after each rT 
MS treatment to assess craving changes. 
(2) Imaging data collection 
Imaging data were collected using Siemens integrated PET/MRI equipment, 16-channel p 
hased array head coils and fMRI stimulator equipment. 
a) BOLD-fMRI imaging: GRE-EPI sequence was adopted, and scanning parameters were 
as follows: TR=2000 ms, TE=30 ms, layer thickness = 4mm, layer interval =0 mm, FO 
V=25.6cm×25.6cm, matrix =64×64, flip angle=90 degrees, NEX=1. 
b) 3D structural imaging of brain gray matter: MPRAGE sequence was adopted, and sc 
anning parameters were as follows: TR=1900 ms, TE= 2.43ms, TI=900ms, FOV=25.6cm×2 
5.6cm, matrix =256×256, layer thickness = 1mm, layer interval =0 mm, flip angle=20◦, N 
EX=1. 
4) Follow-up after treatment 
All nicotine addicts were followed up every Friday after rTMS treatment, and nicotine a 
ddiction Smoking survey (FTND), basal craving assessment, craving degree assessment (cu 
e) and NUI assessment were performed. Anxiety Rating Scale (HAMA) and Depression Se 
lf-Rating Scale (BDI) were added at the last follow-up. The short-term follow-up period w 
as one month to understand the treatment effect and current related status of the subjects. 
5) Imaging data processing 
(1) Main data processing software: 
Matlab2013b, SPM12 (http://www.fil.ion.ucl.ac.uk/spm) 
DPABI (http://rfmri.org/dpabi) 
FSL (http://fsl.fmrib.ox.ac.uk/fsl/fslwiki/) 
Freesurfer (http://freesurfer.net/) 
Gift (http://mialab.mrn.org/software/) 
DTI - studio (https://www.mristudio.org/wiki/Tutorial) 
PANDA (http://www.nitrc.org/projects/panda/) 
GRETNA (http://www.nitrc.org/projects/gretna/) 
MRIcro (http://www.mccauslandcenter.sc.edu/mricro/) 
The Caret (http://brainvis.wustl.edu/wiki/index.php/Caret:Download) 
BrainNet viewer (http://www.nitrc.org/projects/bnv/) 
MIMneuro (https://www.mimsoftware.com/nuclear_medicine/mim_neuro) 
Syngo. Via VB10 (https://health.siemens.com/ikm/syngo/syngo-via-apps/) 
And self-programming and so on. 
(2) fMRI data follow-up processing: 
Local consistency (Reho), low-frequency amplitude (ALFF) and power spectrum were us 
ed to detect the activation range and intensity of ECN, DMN and SN-related brain region 
s. The functional connections between ECN, DMN and SN related brain regions were anal 
yzed by seed point correlation analysis and independent component analysis. The effect lin 
kage analysis of ECN, DMN and SN was carried out using the physiological and psychol 

 
ogical interaction model. Through the above analysis, the intrinsic functional changes of E 
CN, DMN and SN large brain networks in the basal state of nicotine addicts after rTMS 
treatment and the changes of network interactions, and the relationship between them and 
relapse were discussed. 
Ⅳ.Key technologies 
1) cognitive experiment design: the cognitive fmri study of heroin addiction has been o 
ver 10 years, and the experience of cognitive experimental design has been accumulated. 
2) image data collection: this project USES Siemens second generation of integrated pet/ 
mri equipment, which has all the conditions and techniques for the completion of the fmri 
-3d high recognition volume imaging and diffusion tensor imaging, and the scanning is us 
ed to ensure the high signal-to-noise ratio and reliability of the data. 
3) data processing technology: this group has fully master the data processing method o 
f functional image, including the processing method of the static state of the task, the pro 
cessing method of the task state, and the processing method of the thickness of the brain 
gray matter, the thickness of the cortex and the integrity of the white fiber beam, and the 
use of the spm-relative dpabi-deabiding giftand fsl-and the afnig freesurferl dti-studio and 
other data analysis software.