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 fangmgh@163.com

http://zjyx.dic120.com/

Beijing, China

Traditional Medicine-2016Website: http://traditionalmedicine.conferenceseries.com/

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Traditional Medicine-2016London, UK

October 03-05, 2016