Modulation of cerebellar activities by acupuncture stimulation: evidence from fMRI study
Introduction
Acupuncture is used extensively in Oriental Medicine and has emerged as an important modality of complementary and alternative therapy to Western Medicine Eisenberg et al., 1993, Eisenberg et al., 1998, Kaptchuck, 2000, Richardson and Vincent, 1986. In the United States, a panel of experts concluded that acupuncture showed efficacy in treating postoperative and chemotherapy nausea and vomiting (National Institute of Health Consensus Development Panel, 1997). In spite of its long history and public acceptance, an unequivocal scientific explanation regarding the physiological mechanism of acupuncture has not been found and awaits further investigation. Various animal data and clinical observations suggest that acupuncture modulates activities in the central nervous system (CNS) and influences treatment areas via release of neurotransmitters/hormones or direct modulation of neural pathway Bing et al., 1991, Kho et al., 1993, Kiser et al., 1983, Peets and Pomeranz, 1978, Shen, 2001. Cho et al. (1998), from their pioneering functional MRI (fMRI) investigation of acupuncture, proposed CNS to be an important mediator of acupuncture effects. Subsequent fMRI investigations on several acupuncture points demonstrated that regionally specific, quantifiable activation in CNS elicited by acupuncture can be detected, providing further information for the hypothesized neuro-functional modulation Cho et al., 1998, Hui et al., 2000, Li et al., 2003, Siedentopf et al., 2002, Wu et al., 1999, Wu et al., 2002. Involvement of limbic/paralimbic systems and subcortical brain structures such as nucleus accumbens, amygdala, and hippocampus during the acupuncture stimulation was discovered from these imaging studies Hui et al., 2000, Wu et al., 1999.
Human cerebellum, with its complicated afferent and efferent connections with the cerebrum and adjacent midbrain regions, provide a crucial role in high-order cognitive functions and affective behavior in addition to its classical role in motor coordination and gating Allen et al., 1997, Desmond et al., 1997, Houk and Wise, 1995, Vaina et al., 2001. For example, pain- and attention-related loci in cerebellum Iadarola et al., 1998, Ploghaus et al., 1999 have been identified along with its role in perceptual learning (Vaina et al., 2001). A recent fMRI investigation by Wu et al. (2002) found cerebellar activity associated with electro-acupuncture of the analgesic acupoint GB34. This study provides the initial evidence of a modulatory effect of acupuncture on the cerebellum. Based on the previous findings of modulatory effects of acupuncture on the CNS, together with existing knowledge on the presence of extensive neural connections with the cerebrum Afifi and Bergman, 1998, Houk and Wise, 1995, we hypothesized that acupuncture modulates anatomically specific cerebellar neural substrates in addition to cerebral involvement.
Based on the postulation that different acupoints modulate distinct cortical networks and related symptom/disease conditions (Cho et al., 1998), we endeavored to identify symptoms associated with lesions or abnormalities in cerebellum to find a subsequent treatment acupoint. Clinical symptoms associated with lesions or strokes in the cerebellum include nausea, vomiting, dizziness, and vertigo with the presence of ataxia (Adams, 2001). Although it is not used in the treatment of stroke, Pericardium 6 (PC6, Neiguan), in the flexor aspect of the forearm between the tendons of palmaris longus and flexor carpi radialis, is a commonly used acupoint for relieving some of these symptoms Deadman and Al-Khafaji, 1998, Stux and Pomeranz, 1997. PC6 is traditionally known to be effective in treating nausea and vomiting associated with motion sickness Boehler et al., 2002, Pomeranz and Stux, 1989. It also has been used in alleviating nausea accompanying the early stage of pregnancy (morning sickness) or chemotherapy de Aloysio and Penacchioni, 1992, Shen et al., 2000, Stux and Pomeranz, 1997. Although the nausea is the result of multiple physiological processes that may not necessarily involve cerebellum, for example, mediation via vagal/sympathetic visceral nervous system, the vomiting center (VC) and a chemoreceptor trigger zone (CTZ) in medulla (Adams, 2001), we hypothesized that the cerebellum may contain important neural substrates for the clinical efficacy of PC6 with its role in vestibular control.
We performed functional MRI (fMRI) on healthy volunteers and examined the neural substrates modulated by the acupuncture stimulation of PC6. To investigate the anatomical specificity of the real acupuncture compared to classical tactile stimulation or placebo control, the acupuncture condition was contrasted to the perception of simple tactile stimulation and then to the ‘sham' stimulation of a non-acupoint proximal to PC6. Several psychophysical parameters such as pain, unpleasantness, and anxiety, as well as respiratory and heart rates were measured from subjects.
Section snippets
Participants
All procedures were conducted in accordance with the ethical guidelines set forth by the IRB. Twelve healthy volunteers (female/male = 5:7, aged 27.2 ± 6.3, all right-handed) participated in the study with informed consent. Subjects had no history of head trauma, neurological disease, substance abuse, or dependency. Subjects at the time of study were free of any transient medical problems or symptoms including chronic pain and headache. Four participants had previous experience and cultural
Psychophysical parameters
All subjects successfully underwent acupuncture stimulation. Fig. 1 shows the analysis of the three psychophysical scores and heart and respiratory rates. Across the stimulation condition, there were no significant changes in heart and respiratory rates (paired t test, P > 0.05). Neither imagery nor excessive pain was reported from any of the subjects. Level of pain was kept low throughout all conditions (paired t test across the pairs of conditions, P > 0.01). In comparison between acupuncture
Discussion
We examined the neural substrates responding to the acupuncture stimulation of PC6. Sham stimulation near the acupoint and tactile stimulation on the skin of the acupoint were given as separate conditions to examine the spatially selective efficacy of the acupoint. Primary (SI) and secondary somatosensory areas (SII) as well as bilateral insular activities were detected throughout the conditions, suggesting that the neural pathway for tactile perception was commonly engaged. Activation in
Conclusion
We demonstrated that the human cerebellum, in addition to the cerebral loci, selectively responded to the acupuncture stimulation of the PC6 acupoint. Modulation of cerebellar areas, especially relevant to vestibular neuromatrix, was found from our investigation. Further research, such as fMRI examining the brain stem, is needed to elucidate the neural circuitries involved in PC6's anti-emetic effect. The role of the cerebellum in producing therapeutic effects of acupuncture, in addition to the
Acknowledgements
This study was partially supported by the Korean Ministry of Science and Technology Grant No. M1-0107-07-0001 (To Yoo, S-S).
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