1. Introduction
In recent years, acupuncture has dramatically increased in popularity and has been widely used in clinical practice in both Eastern and Western societies due to its curative effects and small side effects. Many experimental and clinical studies have been performed to test acupuncture’s efficacy and/or investigate its underlying mechanisms. However, traditional acupuncture is based on the Meridian theory, which believes that meridians are the channels in which the blood and qi flow, and acupuncture produces a therapeutic effect by modulating the flow of qi and blood. The current meridian theory (particularly the distribution of the meridians in the human body) is based on the Yellow Emperor’s Classic of Internal Medicine, a classical text believed to have been written thousands of years ago, and since then, there has been no significant change in this meridian theory.
In recent decades, innovative acupuncture modalities, such as scalp acupuncture, auricular acupuncture, abdominal acupuncture, and wrist acupuncture, have been developed based on new theories. The clinical application and efficacy of these emerging acupuncture modalities have been widely applied in acupuncture practice and have become key components of modern acupuncture. One such modality, which has been attracting more and more attention, is scalp acupuncture.
Scalp acupuncture is a modality of acupuncture, where acupuncture needles are inserted into a certain layer of the scalp and believed to be able to modulate the brain neurons of the underlying areas. The unique characteristic of scalp acupuncture is that the stimulation locations of the needles are based on modern anatomy and neurophysiology, providing a foundation for its development.
Since the emergence of scalp acupuncture in the 1970s, the scope of application of scalp acupuncture has been constantly expanding, involving various disorders. For example, scalp acupuncture has been widely used in the rehabilitation of stroke patients, as it can directly stimulate the scalp areas corresponding to the motor, sensory and language cortices, thereby improving the symptoms of stroke patients accordingly [
1,
2,
3].
In recent decades, brain imaging technologies such as magnetic resonance imaging (MRI) and positron emission tomography (PET) have been widely used to investigate the pathophysiology of brain disorders such as dementia, depression, insomnia, autism, and schizophrenia, and have significantly enhanced our understanding of the underlying mechanisms of these disorders [
4]. Nevertheless, findings from these studies have not been incorporated into scalp acupuncture protocol. Incorporating the findings from cutting-edge brain imaging tools into scalp acupuncture may present a crucial next step for the development of scalp acupuncture.
Dementia, characterized by a deterioration in cognitive function beyond what might be expected from normal ageing, is one of the most common diagnoses that impact healthspan as people age. Dementia is a challenge to patients, caregivers, and healthcare providers, and carries a heavy financial burden, with the cost of caring for dementia patients estimated to rise to 2 trillion US dollars annually by 2030 [
5]. Clinical studies have shown that acupuncture, especially scalp acupuncture, can significantly improve the clinical symptoms of patients with dementia [
6,
7,
8]. However, no research has confirmed that the stimulation targets of scalp acupuncture for treating dementia are consistent with the neuroimaging findings of dementia.
Thus, this study will initiate an attempt to develop a neuroimaging-based scalp acupuncture prescription/protocol for treatment of dementia. Specifically, we will first apply a meta-analysis on brain imaging studies of dementia and summarize surface brain regions associated with dementia that can be modulated by scalp acupuncture. Then, we will apply resting-state functional connectivity and diffusion tensor imaging (DTI) to further identify potential surface regions that are functionally/anatomically connected to deep brain structures that play an important role in dementia (i.e., hippocampus) but cannot be directly modulated by scalp acupuncture. Finally, we will develop a scalp acupuncture prescription for dementia based on the findings achieved.
4. Discussion
Scalp acupuncture is an acupuncture modality based on brain anatomy and function. Recently, the application of brain imaging tools has led to remarkable progress in the research of various neurological and psychotropic diseases, thereby building a foundation for development of scalp acupuncture protocols. In this study, we explored a new method for developing/updating the protocols for scalp acupuncture. Specifically, we integrated meta-analysis, resting-state functional connectivity, and DTI to identify potential locations for scalp acupuncture for treatment of dementia. We found brain regions such as the prefrontal cortex (mPFC/dlPFC), the MTG, the STG, the TMP, the SMA, the IOG, and the PCu to be the target areas of scalp acupuncture for treatment of dementia. Furthermore, we also used the 10-20 EEG system, the International standard scalp acupuncture system, and scalp acupoints to facilitate the location of these target areas on the scalp.
4.1. Key Regions/Locations in the Neuroimaging-Based Scalp Acupuncture Prescription
In this study, we identified multiple surface areas to be the target regions for scalp acupuncture. Our findings are consistent with the physiology/function of these brain regions.
For instance, the prefrontal cortex has been proven to play a crucial role in the pathophysiology of dementia. Burgmans and colleagues found that prefrontal atrophy was highly associated with dementia and can be considered an important predictor of the disease [
25]. More specifically, the dlPFC is highlighted in brain stimulation treatments for dementia. Previous studies have demonstrated the dlPFC as a promising target commonly used in transcranial magnetic stimulation (TMS) to improve the cognitive performance of dementia patients [
26,
27,
28]. Another study applied anodal transcranial direct current stimulation (tDCS) on the dlPFC in patients with mild vascular dementia and observed clinical benefits in patients’ short-term memory, verbal working memory, as well as executive control [
29]. Further imaging studies suggest that stimulating the dlPFC using a neuromodulation method may work through changes in dopamine concentration [
30].
Both the PCu and the mPFC are core regions of the default mode network (DMN) [
31,
32]. Recently investigators found that the DMN is particularly relevant for dementia, because the DMN regions are vulnerable to neurodegenerative pathological changes, including atrophy, deposition of the amyloid protein, and reduced glucose metabolism [
33,
34]. In addition, Wang and colleagues have reported that the hippocampus, which plays a key role in the pathology of dementia, showed decreased functional connectivity with the mPFC and the PCu in patients with Alzheimer’s disease [
35]. We also found that the PCu showed significant functional connectivity with the hippocampus. Taken together, these findings provide direct support for using the PCu and the mPFC as targets for dementia [
36,
37,
38].
Studies have indicated that individuals with dementia tend to have communication and memory difficulties. Studies have found that dementia, especially semantic dementia, is often accompanied by abnormalities of the temporal lobe [
39,
40]. The relatively clear diagnosis and pathological homogeneity of semantic dementia make the temporal regions promising targets for innovative interventions [
41]. Our results from both meta-analysis and the hippocampus functional connectivity analysis endorsed the role of the MTG, STG, and TMP. Thus, these regions are included in the scalp acupuncture prescription for treating dementia, and particularly for treatment of semantic dementia, or individuals with communication difficulties.
The SMA is another crucial region associated with memory that is typically spared in the early stage of dementia. Neuroimaging studies on both healthy and brain-damaged individuals have shown that the SMA is part of a widespread frontoparietal network underlying working memory [
42]. A recent study found that damage of the SMA is associated with working memory impairment [
43].
Based on above neuroimaging findings, we have proposed a new prescription including five treatment lines: from F3 to C3, from T3 to P3, from F3 to T3, from P3 to T5, and MS 5. In addition, the location of Shenting (GV 24), Sishencong (extra points on the head and neck (EX-HN) 1), and the bilateral Hanyan (GB 4), Qubin (GB 7) and Benshen (GB 13) also overlapped the neuroimaging results. Thus, these scalp acupoints were incorporated in our prescription.
4.2. Current Scalp Acupuncture Protocols for Dementia and Differences Compared to the Neuroimaging-Based Scalp Acupuncture Protocol
At present, there is no international standard guidance for scalp acupuncture therapy for dementia. We searched acupuncture textbooks used by Traditional Chinese Medicine Universities to summarize the scalp acupuncture treatment guidelines and commonly used scalp acupoints for dementia.
According to the scalp acupuncture treatment guidance from the textbook “Acupuncture Therapeutics” (Second edition, China Press of Traditional Chinese Medicine, 2007), the middle line of forehead (Ezhongxian, 1 cun long from Shenting (Governor Vessel (GV) 24) straight downward along the meridian, MS 1), the middle line of vertex (Dingzhongxian from Baihui (GV 20) to Qianding (GV 21) along the midline of head, MS 5), anterior temporal line (Nieqianxian, from Hanyan (Gallbladder meridian (GB) 4) to Xuanli (GB 6), MS 10), and posterior temporal line (Niehouxian, from Shuaigu (GB 8) to Qubin (GB 7). MS 11) were recommended for treatment of dementia.
Based on the textbook “Clinical Acupuncture” (First edition, China Science Publishing & Media Ltd. (CSPM), 2015), MS 1, MS 5, the anterior oblique line of vertex-temporal (Dingnieqianxiexian, from Qianding (GV 21) obliquely to Xuanli (GB 6), MS 6), and the posterior oblique line of vertex-temporal (Dingniehouxiexian, from Baihui (GV 20) obliquely to Qubin (GB 7), MS 7) were selected for scalp acupuncture guidelines in treating dementia. Please see
Figure 2C for a summary of current scalp acupuncture prescription for dementia.
Differences and similarities exist in the comparison between the neuroimaging-based prescription and the textbook-documented guidelines. Specifically, both protocols used the mPFC, SMA, IFG, PreCG, PoCG, STG, MTG, and TMP regions as stimulation targets. However, the neuroimaging-based prescription incorporates several additional areas, including the dlPFC, MFG, SFG, PCu, SPL, and IOG. We believe that these additional brain regions reflect our enhanced understanding on the brain network involved in dementia and, thus, should be incorporated into the current scalp acupuncture protocols.
4.3. Additional Application of the Neuroimaging-Based Scalp Acupuncture Prescription
It is worth noting that the locations identified in this study may not be limited to acupuncture and can also be applied to neuromodulation methods, such as transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and transcranial alternating current stimulation (tACS).
In addition, the scalp acupuncture prescription we proposed may also be integrated with traditional acupuncture theory (Traditional Chinese Medicine-based acupuncture). A crucial characteristic of traditional acupuncture treatment is that it is consistent with syndrome differentiation. Thus, the acupoints that are selected for traditional acupuncture should also consider individual diversities of patients. The protocol needs to be adjusted according to the individual’s symptoms and status at the time of use.
4.4. Limitation and Future Directions
There are several limitations to our study. First, we combined different methods to identify potential surface targets for dementia. Regions identified from Method 1 are believed to be associated with dementia pathophysiology directly, and regions identified from Method 2 and 3 are surface cortex with strong functional or anatomical connection with the key deep structure brain region associated with dementia. Understanding the derivative of these locations may help researchers choose target regions during clinical practice. Second, the aim of this study was to explore the potential brain surface targets for dementia; the application and optimization of different treatment techniques to target/modulate these brain regions is beyond the scope of this manuscript. Further, we only used the hippocampus as the region of interest in functional connectivity and DTI analyses due to its crucial role in memory and dementia. Other deep brain structures may also play an important role in dementia and may be used as the region of interest to conduct functional and anatomical connectivity analysis to extend the neuroimaging-based acupuncture protocol. Thirdly, dementia is an umbrella term used to describe clinical syndromes of progressive cognitive decline, which included subtypes such as Alzheimer’s disease, Lewy body dementia, frontotemporal dementia, vascular dementia, etc. Each of these disorders may be associated with different pathology. This study focused on dementia as a set of symptoms, including memory loss and difficulties with thinking, problem solving or language, which commonly appear in subtypes of dementia, and thus, may have common potential functional/structural mechanisms. Future studies are needed to compare the potential targets for different disorders. In addition, studies show that dementia may somehow alter the connectivity, but the extent may differ based on specific disorders and development stages (early vs. late stages). We decided to use healthy subjects, which may provide a more unbiased evaluation in Method 2 and 3. Finally and also most importantly, our findings need to be validated with clinical trials/studies on patients with dementia.