PeiJing Rong
Traditional Medicine-2015Birmingham, UK
August 03 – 05, 2015
Traditional Traditional
MedicineMedicine
20152015
Clinical Trial of Clinical Trial of Transcutaneous Vagus Nerve StimulationTranscutaneous Vagus Nerve Stimulation in Major Depressive Disorderin Major Depressive Disorder
and its Neuromechanism using fMRIand its Neuromechanism using fMRI
Peijing Rong Prof. PhD Jiliang Fang MD. PhD
China Academy of Chinese Medical Sciences
August 3th, 2015Birmingham, UK
Background
FDA approved the Vagus stimulation as a alternative treatment for drug-resistance depression in 2005.
Auricular acupuncture - Vagus nerve
• Basis of Anatomy : Concha - - Only Distribution of vagus nerve on body surface
•
Distribution of vagus N.Area of Inner organs
Transcutaneous VNS
The stimulator invented by Acupuncture Institute
it treats MDD and epilepsy effectively
Rong PJ,et al. World Science and Technology/Modernization of Traditional Chinese Medicine and Materia Medica. 2014. Vol.15 No.9: 2013-2020
Clinical trial for tVNS on Depression
tVNS on 37 MDD for 2 weeks. On days 0 and 14, showed a significantly better outcome in the
BDI. HAMD score did not change significantly in the two groups.
Review: Larger sample size and longer duration of treatment are needed.
Hein E, et al(2013).J Neural Transmission
Our Clinical Trial
Clinical controlled trial
Duration : Sept.2012 – March. 2014
Three centers : GAM Hopital CACMS FGS Hospital BUCM Acu Hospital CACMS
MDD: 160 cases mild-moderate symptom tVNS ( 91 ) stVNS ( 69 )
Methods
Parameter: 20Hz , 4-6mA , 30min per time , twice daily,
5 days in a week
12weeks for tVNS, 4 weeks for stVNS, then transfer to tVNS
Measurements Mental psychological scales :
24HAMD 17HAMA SAS SDS
Curative effect standard
Reduction of 24-HAMD score
recovery ≥75 % Significant effective 50 %~ 74 % effective 25 %~ 49 % no effective <25 %
Percentage of Efficiency
Change of clinical Measurements
Change of clinical Measurements
Clinical Trial of Transcutaneous Vagus Nerve StimulationOn Major Depression Disorder
Rong PG, Fang JL, et al. J Clinical Psychiatry under reviewing
Brain Imaging on the Neuromechanism
tVNS Modulates Default Mode Network on MDD
Fang Jiliang et al. 2015.5 Epub online Biological Psychiatry
Biological Psychiatry ( IF 10.225 )
DMN is a network of brain regions that are active when an individual is awake and at rest.
It is an interconnected and anatomically defined brain system that preferentially activates when individuals focus on internal tasks such as daydreaming, envisioning the future, retrieving memories, and gauging others' perspectives.[2
0] It is one of the most studied networks present during resting state and is one of the most easily visualized networks.[21]
Default Mode Network (DMN)
Fox. (2005) PNAS
Default Mode Network (DMN)
Using fMRI to monitor the changes of brain function Connectivity in the DMN after tVNS or sham tVNS treatment on MDD.
To find the correlation between brain response (FC) with the clinical symptom (24 HAMD).
Our fMRI study on tVNS
Jiliang Fang et al., 2014. 6 JMRI Fang Jiliang et al. 2015.5 Biological Psychiatry
Jiliang Fang et al. , 2015 Brain Stimulation Submitted
Anand A et al., Biol Psychiatry, 2005; Anand A et al., Neuropsychopharmacology, 2005; Greicius MD et al., Biol Psychiatry 2007; Bluhm R et al., Psychiatry Clin Neurosci, 2009; Zhu X et al., Biol Psychiatry, 2012; Veer IM et al., Front Syst Neurosci, 2010.
Studies on DMN of MDD
Zhu X et al., 2012
Abnormal FC in DMN of MDD
• Depression is characterized by both stimulus-induced heightened activity and a failure to normally down-regulate activity broadly within the DMN
Sheline YI, Raichle, ME. PNAS 2009
Antidepressant modulated brain Network
• antidepressant treatment may increase corticolimbic connectivity, thereby possibly increasing the regulatory influence of cortical mood-regulating regions over limbic regions.
Chen et al. (2015), Journal of Affective disorder;Anand et al. 2005, Neuropsychopharmacology
fMRI Method
• tVNS group ( 19), Control group ( 16)• 1.5T GE MRI, 6 min resting state EPI scan,
repeat once.• TR2.5s , TE30ms , Thickness 3mm , gap
0.5mm , Parallel AC-PC line 41Slices• Before and after 4 weeks treatment
fMRI data processing
• using independent component analysis (ICA) in the FMRIB, acquired the component of the default mode network.
• The FC changes after treatment (posttreatment -
pretreatment) in the tVNS group with that of the stVNS group.
• The correlation areas of FC changes and clinical measurement.
Baseline : tVNS VS. stVNS
Clinical measurement Changes
Component of Default Mode Network
tVNS VS. stVNS FC changes after treatment
stVNS VS. tVNS FC changes after treatment
tVNS VS. stVNS Important decreased FC Areas
Brain Regions of FC Changes positively associated with HAMD
Important Regions in Positive Correlation
Brain Regions of FC Changes Negatively associated with HAMD
Yellow: Important areas with FC increase
Blue: Areas with FC negatively related to HAMD
Conclusion ( 1 )
1 ) tVNS is effective for MDD
2 ) tVNS provides an easy, simple and cheap non-medication treatment for MDD.
Conclusion ( 2 )
1 ) Evidence for Hypothesis : tVNS modulating Default
Mode network(DMN).
2 ) tVNS produces Functional Connectivity changes :
Insular, dACC—Salient network, keep balance
between Executive control network and DMN
Orbital FC , Precuneus—Emotion, Cognition
The network of Vagus Nerve project to Default Mode Network
NTS :孤束核LC :蓝斑核VTA :腹侧被盖区Hyp :下丘脑Amy :杏仁核HP : 海马NAC :伏核OFC :眶回MPFC :内侧前额叶ACC :前扣带回MCC :中扣带回PCC :后扣带回
tVNS on the Neural Circuitry of Mood
Acknowledgement
• Prof. Peijing Rong, Bing Zhu, Xiaochun Yu
Institute of acupuncture, CACMS
• Assitant Prof. Jian Kong, Martinos Center, Dept. of Psychiatry,MGH, Harvard University
• Hong Yang, Yangyang Fan, Jun Liu, Honghong
Wang, Guang An Men Hospital, CACMS
Grant
•Key Program for Beijing Natural Science Foundation ( 71110070 )
•National Natural Science Foundation of China (30870668 , 81273674 , 81303056)
•Funding from Ministry of Science and Technology (2012BAF14B10)
Society of Medical ImagingChina Association of Acupuncture & Moxibustion
2014 Beijing
Welcome to join the team for acupuncture research using fMRI
Jiliang Fang [email protected]
http://zjyx.dic120.com/
Beijing, China
Traditional Medicine-2016Website: http://traditionalmedicine.conferenceseries.com/
Meet the eminent gathering once again at
Traditional Medicine-2016London, UK
October 03-05, 2016
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