**1. Introduction**

Acupuncture has been gaining popularity for treatment of various disorders as an alternative therapy and has been used for years as treatment for a wide range of ailments from lower back pain to stroke to osteoarthritis to Parkinson's disease (PD) [1–5]. Classical acupuncture is based on 14 mapped main channels on the body with about 365 acupoints distributed on the channels (meridian system); the flow of Qi (the vital life force or "energy") maintains the balance and harmony of Yin and Yang. Any blockage of these channels or abnormal movement of Qi will result in illness, and acupuncture, by stimulating these acupoints along the meridian channels with needles, helps to restore movement of the Qi and Qi homeostasis (De Qi), thus modulating the autonomic nervous system and relieving the symptoms of various illnesses [6, 7]. The underlying mechanism of acupuncture has been under intense investigation and many theories have been discussed in the scientific community. For example, connective tissues or perivascular space with decreased electrical impedance and increased electrical conductivity have been suggested to constitute the meridian channels with acupoints along the pathway [7, 8]. Nevertheless, the efficacy of acupuncture remains largely unclear because of a skeptical attitude of how acupuncture works (especially within the framework of Western Medicine),

**8**

*Acupuncture - Resolving Old Controversies and Pointing New Pathways*

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[2] Reston J. Now, About My Operation in Peking. New York Times. July 26:1. 1971. Retrieved from: http://select. nytimes.com/gst/abstract.html?res=FB0 D11FA395C1A7493C4AB178CD85F4587

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[6] Birch S, Lee MS, Alraek T, Kim T-H. Overview of treatment guidelines and clinical practical guidelines that recommend the use of acupuncture: A bibliometric analysis. The Journal of Alternative and Complementary Medicine. 2018;**24**(8):752-769. DOI:

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methodological flaws, and an absence of rigorous studies using objective outcome measures [1]. To date, the clinical outcomes of acupuncture are assessed by empirical observations rather than by objective, quality analysis [1, 3, 5].

Recent, rapid advances in technology, especially the use of functional magnetic resonance imaging (fMRI) to map global and/or target-specific bran regions, have shown great promise and could be extremely helpful for acupuncture studies in human subjects when combined with subjective measurements [8]. Pharmacological MRI (phMRI), a new application of fMRI, is using fMRI methods to map drug-induced activations inside the brain [9]. In this chapter, we discuss how phMRI can be used to map dopaminergic drug-induced changes in the brain before and after acupuncture treatment in parkinsonian monkeys. Similarly, fMRI methods have been used in the PD clinic. As an example, with acute acupuncture stimulations at GB34, analysis of fMRI signals showed activations in the putamen and the primary motor cortex, and these activations induced by acupuncture were correlated with patient self-reported improvements of finger-tapping [10]. Furthermore, phMRI has been used to monitor other treatments associated with PD in a preclinical, translational study [11]. The utility of fMRI/phMRI has even been extended to differentiate dysfunction in the basal ganglia between parkinsonian and aged monkeys [12]. Based on those clinical and preclinical studies, these imaging modalities have the possibility to help untangle the underlying neural mechanisms of acupuncture.

To date, few studies have been conducted *in vivo* to directly investigate the relationship between acute acupuncture stimulation and its effects on modulating neurotransmitters especially in large animals such as the rhesus macaque. In this chapter, to our knowledge, we would be the first to begin exploring whether acupuncture stimulation could suppress, or activate, cortical glutamate in normal and PD monkeys. In addition, we will also review fMRI and phMRI studies to provide some direct evidence demonstrating the relationship between acupuncture and neuronal activity and changes in neurotransmitter signaling in the CNS.
