FMRI connectivity analysis of acupuncture effects on the whole brain network in mild cognitive impairment patients.

The increased risk for the elderly with mild cognitive impairment (MCI) to progress to Alzheimer's disease makes it an appropriate condition for investigation. While the use of acupuncture as a complementary therapeutic method for treating MCI is popular in certain parts of the world, the underlying mechanism is still elusive. We sought to investigate the acupuncture effects on the functional connectivity throughout the entire brain in MCI patients compared to healthy controls (HC). The functional magnetic resonance imaging experiment was performed with two different paradigms, namely, deep acupuncture (DA) and superficial acupuncture (SA), at acupoint KI3. We first identified regions showing abnormal functional connectivity in the MCI group compared to HC during the resting state and subsequently tested whether these regions could be modulated by acupuncture. Then, we made the comparison of MCI vs. HC to test whether there were any specific modulatory patterns in the poststimulus resting brain between the two groups. Finally, we made the comparisons of DA vs. SA in each group to test the effect of acupuncture with different needling depths. We found the temporal regions (hippocampus, thalamus, fusiform gyrus) showing abnormal functional connectivity during the resting state. These regions are implicated in memory encoding and retrieving. Furthermore, we found significant changes in functional connectivity related with the abnormal regions in MCI patients following acupuncture. Compared to HC, the correlations related with the temporal regions were enhanced in the poststimulus resting brain in MCI patients. Compared to SA, significantly increased correlations related with the temporal regions were found for the DA condition. The enhanced correlations in the memory-related brain regions following acupuncture may be related to the purported therapeutically beneficial effects of acupuncture for the treatment of MCI. The heterogeneous modulatory patterns between DA and SA may suggest that deep muscle insertion of acupuncture is necessary to achieve the appreciable clinical effect.

[1]  Ferenc A Jolesz,et al.  Modulation of cerebellar activities by acupuncture stimulation: evidence from fMRI study , 2004, NeuroImage.

[2]  T. Kaptchuk,et al.  Acupuncture: Theory, Efficacy, and Practice , 2002, Annals of Internal Medicine.

[3]  Yufeng Zang,et al.  Abnormal Functional Connectivity of Hippocampus During Episodic Memory Retrieval Processing Network in Amnestic Mild Cognitive Impairment , 2009, Biological Psychiatry.

[4]  H. Critchley.  Neural mechanisms of autonomic, affective, and cognitive integration , 2005, The Journal of comparative neurology.

[5]  Kuncheng Li,et al.  Altered functional connectivity in early Alzheimer's disease: A resting‐state fMRI study , 2007, Human brain mapping.

[6]  Yuan Zhou,et al.  Abnormal Cortical Networks in Mild Cognitive Impairment and Alzheimer's Disease , 2010, PLoS Comput. Biol..

[7]  Jian Kong,et al.  Acupuncture de qi, from qualitative history to quantitative measurement. , 2007, Journal of alternative and complementary medicine.

[8]  Haibin Tong,et al.  The salient characteristics of the central effects of acupuncture needling: Limbic‐paralimbic‐neocortical network modulation , 2009, Human brain mapping.

[9]  Jie Tian,et al.  Investigation of acupoint specificity by multivariate granger causality analysis from functional MRI data , 2011, Journal of magnetic resonance imaging : JMRI.

[10]  D. Mayer.  Acupuncture: an evidence-based review of the clinical literature. , 2000, Annual review of medicine.

[11]  K. Yau,et al.  Interoception: the sense of the physiological condition of the body , 2003, Current Opinion in Neurobiology.

[12]  P. Pietrini,et al.  Altered brain functional connectivity and impaired short-term memory in Alzheimer's disease. , 2001, Brain : a journal of neurology.

[13]  C. Grady,et al.  Intercorrelations of regional cerebral glucose metabolic rates in Alzheimer's disease , 1987, Brain Research.

[14]  B. Rosen,et al.  Acupuncture modulates the limbic system and subcortical gray structures of the human brain: Evidence from fMRI studies in normal subjects , 2000, Human brain mapping.

[15]  W. Qin,et al.  FMRI connectivity analysis of acupuncture effects on an amygdala-associated brain network , 2008, Molecular pain.

[16]  J. Morris,et al.  Current concepts in mild cognitive impairment. , 2001, Archives of neurology.

[17]  J V Haxby,et al.  Network analysis of PET-mapped visual pathways in Alzheimer type dementia. , 1995, Neuroreport.

[18]  Jonathan D. Cohen,et al.  Improved Assessment of Significant Activation in Functional Magnetic Resonance Imaging (fMRI): Use of a Cluster‐Size Threshold , 1995, Magnetic resonance in medicine.

[19]  E. Tangalos,et al.  Mild Cognitive Impairment Clinical Characterization and Outcome , 1999 .

[20]  Jie Tian,et al.  Time‐varied characteristics of acupuncture effects in fMRI studies , 2009, Human brain mapping.

[21]  Jie Tian,et al.  Acupuncture modulates spontaneous activities in the anticorrelated resting brain networks , 2009, Brain Research.

[22]  A. Craig.  How do you feel? Interoception: the sense of the physiological condition of the body , 2002, Nature Reviews Neuroscience.

[23]  Jie Tian,et al.  Acupuncture modulates temporal neural responses in wide brain networks: evidence from fMRI study , 2010, Molecular pain.

[24]  B. Vogt.  Pain and emotion interactions in subregions of the cingulate gyrus , 2005, Nature Reviews Neuroscience.

[25]  Jie Tian,et al.  Investigation of the large-scale functional brain networks modulated by acupuncture. , 2011, Magnetic resonance imaging.

[26]  Kyungmo Park,et al.  Acupuncture modulates resting state connectivity in default and sensorimotor brain networks , 2008, PAIN.

[27]  M. Moser,et al.  Distributed Encoding and Retrieval of Spatial Memory in the Hippocampus , 1998, The Journal of Neuroscience.

[28]  Y. Benjamini,et al.  Controlling the false discovery rate in behavior genetics research , 2001, Behavioural Brain Research.

[29]  Wei Liu,et al.  Adenosine A1 receptors mediate local anti-nociceptive effects of acupuncture , 2010, Nature Neuroscience.

[30]  Youlong Zhou,et al.  Effect of acupuncture given at the HT 7, ST 36, ST 40 and KI 3 acupoints on various parts of the brains of Alzheimer' s disease patients. , 2008, Acupuncture & electro-therapeutics research.

[31]  R. C. Oldfield.  The assessment and analysis of handedness: the Edinburgh inventory. , 1971, Neuropsychologia.

[32]  Jie Tian,et al.  Neural specificity of acupuncture stimulation at pericardium 6: Evidence from an FMRI study , 2010, Journal of magnetic resonance imaging : JMRI.

[33]  N. Tzourio-Mazoyer,et al.  Automated Anatomical Labeling of Activations in SPM Using a Macroscopic Anatomical Parcellation of the MNI MRI Single-Subject Brain , 2002, NeuroImage.

[34]  E. Bullmore,et al.  Neurophysiological architecture of functional magnetic resonance images of human brain. , 2005, Cerebral cortex.

[35]  G Lewith,et al.  Placebo controls for acupuncture studies. , 1995, Journal of the Royal Society of Medicine.

[36]  J. Morris.  The Clinical Dementia Rating (CDR) , 1993, Neurology.

[37]  Maurizio Corbetta,et al.  The human brain is intrinsically organized into dynamic, anticorrelated functional networks. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[38]  C. Jack,et al.  Mild cognitive impairment can be distinguished from Alzheimer disease and normal aging for clinical trials. , 2004, Archives of neurology.

[39]  W. Qin,et al.  Detection of dynamic brain networks modulated by acupuncture using a graph theory model , 2009 .

[40]  H. Möller,et al.  Functional connectivity of the fusiform gyrus during a face-matching task in subjects with mild cognitive impairment. , 2006, Brain : a journal of neurology.