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Neural Control of Cerebral Blood Flow: Scientific Basis of Scalp Acupuncture in Treating Brain Diseases

How to Cite: Jin GY, Jin LL, Jin BX, Zheng J, He BJ, Li SJ. Neural control of cerebral blood flow: scientific basis of scalp acupuncture in treating brain diseases. Front Neurosci. 2023 Aug 15;17:1210537. doi: 10.3389/fnins.2023.1210537. PMID: 37650106; PMCID: PMC10464620.

Abstract

Scalp acupuncture (SA), as a modern acupuncture therapy in the treatment of brain diseases, especially for acute ischemic strokes, has accumulated a wealth of experience and tons of success cases, but the current hypothesized mechanisms of SA therapy still seem to lack significant scientific validity, which may not be conducive to its ultimate integration into mainstream medicine. This review explores a novel perspective about the mechanisms of SA in treating brain diseases based on its effects on cerebral blood flow (CBF). 
To date, abundant evidence has shown that CBF is significantly increased by stimulating specific SA points, areas or nerves innervating the scalp, which parallels the instant or long-term improvement of symptoms of brain diseases. Over time, the neural pathways that improve CBF by stimulating the trigeminal, the facial, and the cervical nerves have also been gradually revealed. In addition, the presence of the core SA points or areas frequently used for brain diseases can be rationally explained by the characteristics of nerve distribution, including nerve overlap or convergence in certain parts of the scalp. But such characteristics also suggest that the role of these SA points or areas is relatively specific and not due to a direct correspondence between the current hypothesized SA points, areas and the functional zones of the cerebral cortex. The above evidence chain indicates that the efficacy of SA in treating brain diseases, especially ischemic strokes, is mostly achieved by stimulating the scalp nerves, especially the trigeminal nerve to improve CBF. 
Of course, the mechanisms of SA in treating various brain diseases might be multifaceted. However, the authors believe that understanding the neural regulation of SA on CBF not only captures the main aspects of the mechanisms of SA therapy, but also facilitates the elucidation of other mechanisms, which may be of greater significance to further its clinical applications.

Illustration

Figure 1 shows the core SA points or areas frequently used for brain diseases, with the distribution of scalp nerves referenced in Khansa et al. (2016). Because acupoint is an area instead of a spot (Jin et al., 2007), in this figure, solid blue dots represent acupoints, while red bands represent the connecting areas between them or those of the international standard scalp acupuncture (ISSA) system (WHO Scientific Group, 1991); five particular SA regions are remarked by circled Arabic numbers.

Keywords: scalp acupuncture, cerebral blood flow, brain diseases, innervation of the scalp, core SA points or areas, neural stimulation, neural pathway, relative specificity

Introduction

Scalp acupuncture (SA) is a modern acupuncture therapy that first emerged in the early 1970s, and has been widely used globally due to its significant efficacy on various acute or chronic brain diseases, specifically acute ischemic strokes (Lu, 1991; Zheng et al., 2011; Wang et al., 2012; Lee et al., 2013; Zhang et al., 2013; You et al., 2018; Yi et al., 2020; Huang et al., 2021; Xue et al., 2022; Wang J. H. et al., 2022).

In extensive clinical practice, several different schools of SA have emerged, some revise (mainly by adding) the earliest proposed SA locations (point, area, or zone) corresponding to the functional zones of the cerebral cortex (Jiao, 1997; Wang, 2019); others used classic meridians or acupoints distributed on the scalp as stimulation targets (Zhu, 2007; Xue et al., 2022); some have even integrated the hypothesis of biological holography (Molnar et al., 2018) to create their own unique systems of SA. 
Therefore, although there are many schools of SA, the primary mechanism explanations generally do not go beyond the above three categories. Of these categories, the meridian theory is considered as a primitive explanation in Traditional Chinese Medicine (TCM), the biological holography theory has not yet shown any biological evidence, while the hypothesis that certain SA locations correspond to the cortical functional zones has been the most attractive and accepted. This is because during body acupuncture, visceral diseases can often manifest as reflex points or zones on the body surface of the corresponding chest, abdomen, or back, based on neural reflexes at the same or nearby spinal segment (Jin et al., 2007). This can easily lead to a common misconception that SA locations have similar correspondence to the cortical functional zones. 
However, the cranial or occipital nerves innervating the scalp have no such segmental connections with the cerebral cortex. Furthermore, the stimulation of SA is mechanical rather than transcranial electromagnetic, making it impossible to stimulate the cortical functional zones directly below the scalp. Therefore, this hypothesis has been criticized (Ye et al., 2022) or opposed by statements such as “there is currently a lack of complete evidence for the mechanism of SA” (Wang et al., 2020).

This review explores a novel perspective about the mechanisms of SA in treating brain diseases based on its effects on cerebral blood flow (CBF). As supported by the authors’ pilot study (Li et al., 1997) and subsequent research applying functional magnetic resonance imaging (fMRI) techniques, CBF has been shown to be improved by acupuncture. Many brain diseases are linked to the reduction of CBF, while SA has been widely reported to treat such brain diseases and/or to improve CBF concurrently. Numerous clinical or laboratory studies have shown stimulation of the trigeminal, the facial, and the cervical nerves innervating the scalp area (including many core SA points or areas) may improve CBF. 
Accordingly, the authors propose that the efficacy of SA for brain diseases, especially acute ischemic strokes, is likely achieved by stimulating such nerves innervated on the scalp to improve CBF. Moreover, the possible neural pathways that produce these effects and the relative specificity of scalp stimulation at different locations in improving CBF are analyzed. The latter is closely related to the optimal selection of SA points or areas. The elucidation of the scientific basis of SA in treating brain diseases will undoubtedly further its clinical applications and raise its efficacy.

Therapeutic effects of scalp acupuncture for brain diseases

Over the past 50 years, a large body of clinical evidence has been accumulated for the application of SA in the treatment of brain diseases, common cases including ischemic strokes, acute strokes, and post-stroke hemiplegia (Zheng et al., 2011; Wang et al., 2012, You et al., 2018; Huang et al., 2021; Wang Y.-F. et al., 2022). Others include autism (Yi et al., 2020), pediatric cerebral palsy (CP) (Xue et al., 2022), cognitive impairment (Zhang et al., 2013), and Parkinson’s disease (PD) (Lee et al., 2013).
Wang et al. (2012) conducted a meta-analysis of SA in the treatment of acute ischemic strokes including eight randomized controlled trials (RCTs) with 538 participants suffering from acute ischemic strokes. The results showed that SA significantly improved neurological deficit score and the clinical effective rate in the patients when compared with the control of conventional medicine (pharmaceuticals). Zheng et al. (2011) conducted a meta-analysis for evaluating the clinical outcome of SA in the treatment of acute intracerebral hemorrhage (ICH). Seven independent trials (230 patients) were included in this study. The results indicate that SA appears to be effective for improving neurological deficit scores in patients with acute hypertensive ICH and SA therapy for acute ICH is generally safe. You et al. (2018) conducted a meta-analysis to assess the clinical effectiveness of SA for stroke. Out of a total of 2,086 papers, 21 RCTs were selected. The results revealed that SA may significantly facilitate the recovery of motor and nervous functions in patients with acute to chronic stroke. A similar conclusion was reached from another meta-analysis by Huang et al. (2021), revealing that SA improves motor function in patients with post-stroke hemiparesis. Therefore, it can be said with confidence that SA has a good therapeutic effect on either acute or chronic stroke, regardless of brain infarction or ICH.
The efficacy of SA has also been well-scrutinized for many types of brain dysfunctions other than strokes. A recent meta-analysis involving 859 cases showed that SA is quite effective in dealing with autism (Yi et al., 2020). A meta-analysis consisting of 731 children of CP showed that SA was more effective than that of conventional rehabilitation in improving the symptoms of CP, and the procedure was deemed safe (Xue et al., 2022). Zhang et al. (2013) evaluated the therapeutic effect of scalp electroacupuncture (SEA) for mild cognitive impairment (MCI) in the early stage. A total of 233 MCI patients were randomly divided into three groups: the medication (nimodipine) group, the SEA group, and the syndrome differentiation group. Each patient was treated for two rounds (courses) of treatment, totaling 8 weeks. The results showed that while all three therapies improved the cognitive function of MCI patients, the efficacy rate of the SEA and syndrome differentiation groups were essentially equal, but both were far more superior to the medication group. In another RCT involving 64 infants with prenatal brain damage syndrome (BDS), Liu et al. (2016) observed that the developmental level of intelligence, motor function, linguistic, and social skills of these infants were enhanced by the intelligence seven-needle therapy that primarily stimulated Shenting (GV24), Benshen (GB13), and Sishencong (Ex.HN1) on the scalp.
Although the above studies all have significant effects of SA for various brain diseases, there are many research limitations, including smaller sample size, unclear stimulation parameters, etc.

Potential mechanisms of scalp acupuncture for strokes

Over the recent years, many animal and clinical studies have been conducted on potential mechanisms of SA in treating brain diseases, especially strokes. According to current hypothesis of SA mechanism, its effect in restoring neurological dysfunction post-stroke is the result of stimulation of specific scalp areas in a reflex somatotopic system, corresponding to the functional zones of the cerebral cortex, with bioelectric effects transmitted to the cerebral cortex through meridians and nerves, thus altering the excitability of cerebral cortical nerve cells and accelerating the establishment of cerebral collateral circulation (Sun et al., 2020).
Certain clinical studies have also observed that applying SA on the region (ISSA_MS6) of the scalp direct above the cortical motor areas could induce vasodilatation of the cerebral blood vessels and better cerebral collateral circulation, raise CBF, lower the risks for infarction, and improve motor function for ischemic stroke cases (Zhang, 2003; Hsing et al., 2012). However, these effects also occur when a number of other scalp regions are stimulated, and it is not necessary to stimulate the specific scalp region corresponding to the cortical motor area. For example, multiple paralleled SA needles inserted at Baihui (GV20) and bilateral ISSA-MS8 could effectively increase the blood flow volume of the common carotid artery, leading to a rise of the energy supply of the cerebral blood circulation (Li et al., 2009). By functional magnetic resonance imaging (fMRI), it was observed that the contralateral somatosensory association cortex, the postcentral gyrus, and the parietal lobe were triggered when SA needles were inserted at the left Sishencong (EX.HN1), Chengling (GB18), Tianchong (GB9), and Jiaosun (TH20) of healthy volunteers (Park et al., 2009). In animal experiments with acute cerebral ischemia-reperfusion injury, it was observed that SA could suppress cytokines-mediated inflammatory reaction, attenuate cerebral ischemia-reperfusion injury, and improve neurofunctional rehabilitation (Zhang et al., 2007; Zhou et al., 2009).
Mechanisms of SA in the treatment of ischemic strokes are somewhat straightforward, especially in the acute stage, as SA stimulations may help reverse brain ischemia and improve neurological function by increasing CBF as it does for the facial nerve (Borsody and Sacristan, 2016). Several studies have shown that SA can prevent persistent thrombosis and increase vasodilation of the neurovasculature in the brain, and maintain blood circulation (Wang Y.-F. et al., 2022). By using fMRI diagnostics, among acute ischemic stroke patients, SA was shown being capable to enhance functional connectivity, particularly between visual, cognitive, motor control, and planning-related brain regions (Liu et al., 2020), or strengthen the functional activities related to sensory integration, language processing, and motor coordination of the dominant cerebral hemisphere and the motor control bilateral frontal lobe (Liu et al., 2021).
Of course, the mechanisms of SA in treating hemorrhagic strokes seems to be vastly different from the treatment of ischemic strokes. The main pathophysiological manifestations after ICH include early hematoma enlargement and perihematomal edema caused by catabolic products released from the hematoma. It was proposed that mechanisms of SA, such as on Baihui (GV20) penetrating Taiyang (EX.HN5) for the brain injury induced by cerebral hemorrhage may include increasing hematoma resorption rate, reducing cerebral edema, decreasing cerebral vascular permeability, and promote repairs for blood–brain barrier damage. It also may inhibit the inflammatory response in brain tissue around hematoma and improve the patient’s immune functions. Furthermore, it may modulate vascular function, prevention of additional brain injury, and the improvement of coordination and compensation function between cortical functional zones (Jiang et al., 2001; Bao et al., 2005; Dong et al., 2006; Liu et al., 2012).
However, because hypoperfusion or ischemia of surrounding brain tissue is also common in hemorrhagic strokes or traumatic brain injuries (TBI), resulting in hematoma (Sills et al., 1996; Zazulia et al., 2001; Schubert et al., 2009), the role of SA in the treatment of hemorrhagic brain diseases, especially its sequelae, cannot be separated from the role of improving CBF.
In short, from the above studies, the effect of SA improving CBF is one of most identifiable traits, and therefore has been frequently reported. It not only serves as the basis of various chronic or long-term effects of SA described previously, but is also most closely related to the instant efficacy of SA, to be described below.

Instant effects of scalp acupuncture for stroke

Scalp acupuncture for stroke, whether hemorrhagic or ischemic, often has detectable instant effects, which means that in about 10 min after acupuncture, muscle strength in the paralyzed side could improve by 2 or more grades (Liu et al., 2012). Dong et al. (1994, 1996) found that 60.71% (34/56) ICH patients showed instant effect in the SA group, but no such luck in medication-therapy and surgery hematoma aspiration groups.
In an outpatient stroke rehabilitation unit, Molnar et al. (2018) conducted a prospective, assessor-blinded randomized control trial using Yamamoto’s New SA (YNSA), for 520 cases with post-stroke syndrome who had hemorrhagic or ischemic strokes and were admitted within 6 weeks of stroke. The results showed that in the YNSA group, all the sensory, motor, and functional scores improved significantly during the examination period until 3 years after injury. In some instances, effects were instantly observed only after a few minutes of SA, such as improved mobility of the limbs, with such effects lingering even for several weeks.
In a RCT, Wang et al. (2018) assessed the effect of SA on walking pattern of stroke patients, using three-dimensional gait analysis (3D-GA). The RCT was conducted for 30 patients in the subacute stage of ICH (1–3 months), all of whom were able to walk on their own. Participants were divided into two groups: SA (treatment group) or no intervention (control group). The treatment group received SA, a penetrating needle from Baihui (GV20) to Taiyang (EX.HN5), whose manipulation was repeated three times with an interval of 5 min. Shortly after the treatment, a significant difference was observed between the treatment and control groups in terms of spatiotemporal parameters of step length, speed and cadence and bilateral limb support. CBF has been found to be another key factor affecting gait performance (Gatouillat et al., 2015). Moreover, Inoue et al. (2002) also demonstrated that SA has a powerful and instant effect in eliminating limb paralysis caused by cerebral infarction or cerebral hemorrhage in rats.
The instant effect of SA in the treatment of strokes suggests that there must be a rapid response mechanism in the multifaceted mechanisms of SA. Because during the regulation of the physiological functions, only neural control has the characteristic of being rapid and accurate, it can be presumed that the instant effect of SA for strokes must also be achieved through rapid neural regulation. According to Liu et al. (2012), the mechanisms may be that SA improved the disorder of CBF in ischemic region, or that it changed the excitability of cerebral cortex nerve cell and led to the retroconversion of the excitability of cerebral nerve cell that was depressed by the stimulation of hemorrhage or the oppression of hematoma. SA has also shown to be capable of regulating the electrophysiological activity of brain nerve cells and changing excitability of cerebral cortex nerve cells, thus awakening brain nerve cells that were in the state of shock or dormancy after ICH (Wang et al., 2003).
The presence of the instant effect of SA not only illustrates the reliability of the curative effect of SA on acute strokes, but also suggests that its mechanism is definitely a rapid response. The improvement of CBF caused by SA is one of these rapid responses.

Brain diseases related to reduced cerebral blood flow

Reduced CBF has been commonly described in brain aging and related neurodegenerative disorders, including Huntington’s disease (HD) (Chen et al., 2012), Alzheimer’s disease (AD) (Ruitenberg et al., 2005), PD (Chen et al., 2015; Pelizzari et al., 2019; Taguchi et al., 2019; Yang et al., 2021) and post-stroke sequelae (Hillis and Tippett, 2014), etc., suggesting that it is likely an important and early commonality in their otherwise distinct pathophysiological processes (Chen et al., 2012).
Several reports have suggested reduced CBF in HD, but little is known about the extent. Chen et al. (2012) used pulsed arterial-spin labeling MRI in conjunction with high-resolution anatomical MRI to non-invasively measure regional CBF (rCBF) in 17 early stage HD subjects and 41 healthy controls, and found profound yet heterogeneous CBF reductions in the cortex, extending to the sensorimotor, paracentral, inferior temporal, and lateral occipital regions, with sparing of the neighboring postcentral gyrus, insula and medial occipital areas. CBF in subcortical regions was also profoundly reduced, and to a similar degree.
The relationship between the severity of ischemic strokes and the infarct region is obvious. In fact, even during recovery from stroke, many sequelae symptoms are associated with inadequate CBF in certain brain regions. In a previous study that clinical interventions such as thrombolysis were used to treat acute ischemic strokes, Hillis and Tippett (2014) considered that patients with large areas of hypoperfusion beyond the infarct should be candidates for intervention to restore CBF. In most cases, the salvageable ischemic tissue is mainly confined to the cortex. The degree to which an individual recovers even simple cognitive functions is influenced by changes in CBF in the early period and by their degree of education level, as well as the intensity or level of initial severity of the stroke. Reperfusion of the distinct cortical regions of the left hemisphere, in the absence of infarction in that region, would restore the associated speech function. This suggests that during the rehabilitation, restoring CBF to specific cortical regions may yield improvements in certain symptoms associated with stroke-sequelae patients.
In fact, even in hemorrhagic strokes or TBI, a reduction of CBF also can occur. Schubert et al. (2009) observed that although all 17 patients with subarachnoid hemorrhage had intracranial pressure (ICP) and cerebral perfusion pressure within normal limits, they all had significantly reduced CBF. Those patients in better clinical condition had significantly smaller reductions in CBF than those with more severe hemorrhage, and had a comparably better prognosis. Changes in hypoperfusion were more pronounced in the supratentorial region (including the cerebrum) than in the infratentorial region (including the cerebellum).
Acute ICH also has shown substantial hypoperfusion zones around the hematoma that was interpreted as regional ischemia. Although there is no evidence for ischemia in the periclot zone of hypoperfusion in acute ICH patients studied 5–22 h after hemorrhage onset (Zazulia et al., 2001), substantial regions of reduced perfusion surrounding ICH might contribute to a substandard outcome and be amenable to anti-ischemic therapy (Sills et al., 1996).
Abnormal cerebral perfusion after TBI often leads to vasospasm. Maegawa et al. (2021) studied the relationship between the two in 25 patients, and found that the cerebral hypoperfusion of subarachnoid hemorrhage in the subacute phase could develop into post-traumatic cerebral vasospasm, thus emphasized the importance of aggressive treatment to prevent the development and progression of cerebral perfusion after TBI.
Other studies have also shown CBF is significantly reduced in patients with PD (Pelizzari et al., 2019) that correlates with the severity of the disease (Yang et al., 2021). In addition, previous studies have shown that the reduction in CBF induced by Madopar (levodopa benserazide) had a negative correlation with the Unified Parkinson Disease Rating Scale (UPDRS) scores, suggesting that improvement of symptoms was associated with increased CBF in the relevant areas (Chen et al., 2015).
All in all, there is apparent growing evidence that suggests various aspects of neuro-degenerative diseases are closely associated with the changes in cerebrovascular function (Yang et al., 2021). Changes in CBF could be used as important markers for disease diagnosis, mechanism investigation, and treatment assessment (Taguchi et al., 2019). It is theorized that treatments that improve or restore CBF may attenuate or possibly prevent the onset of these disorders (Sun et al., 2019). Therefore, as long as the SA can effectively enhance CBF, these brain diseases may be indicated for SA therapy. In fact, the clinical application of SA is most effective for patients suffering these types of brain diseases with significantly lower CBF, such as acute ischemic strokes.

Effects of scalp acupuncture on cerebral blood flow

To date, numerous studies have shown that SA can increase rCBF, especially improving CBF disturbances in ischemic regions. This has been observed not only in healthy individuals (Byeon et al., 2011; Im et al., 2014) or animal experiments (Goadsby and Duckworth, 1987; Wang et al., 2017), but also confirmed during the treatment of some patients with brain diseases (Yang et al., 2021). Byeon et al. (2011) discovered that needling Baihui (GV20) increased CBF velocity in the middle cerebral artery (MCA) and anterior cerebral artery (ACA). Im et al. (2014) observed that needling Fengchi (GB20) in selected healthy male subjects increased CO2 reactivity in the basilar artery, but had no effect on the MCAs. Among other studies on the regulatory effects of acupuncture on CBF in PD, AD, and strokes, etc. (Li et al., 1999; Yong et al., 2009; Chen and Wu, 2011; Ratmansky et al., 2016; Kim et al., 2018; Ding et al., 2019; Yang et al., 2021), the stimulated locations included SA points or areas.
In a study consist of 15 PD patients with moderate symptoms, Yang et al. (2021) observed that needling Dazhui (GV14) and Fengchi (GB20) improved motor functions and subjective perception of the patients, while significantly increasing the total length of the internal carotid artery (ICA), the total length of the MCA, and the distal length of the M3 segment (that supplies blood to important components of the cortex – striatum circuit). From this, it seemed to be the mechanism by which acupuncture benefits PD patients. Besides, since the whole-brain CBF showed no significant difference before and after acupuncture, implying that acupuncture modulated the rCBF rather than increasing the whole-brain CBF.
Yong et al. (2009) observed in 30 patients of PD that SA combined with Madopar could improve the rigidity, tremor, dyskinesia and rCBF, indicating that the improvement of PD symptoms had a close relationship with the effect of SA on rCBF. Another study in the treatment of acute cerebral hemorrhage observed that the more significant the original CBF abnormality, the more significant the improvement after SA (Li et al., 1999).
Different SA points or areas from various parts of the scalp may produce different effects on rCBF, as such, the duration or intensity of acupuncture may also affect these effects. In a meta-analysis study, the effect of acupuncture was measured on the posterior circulation infarction vertigo (PCIV) that included 20 RCTs (1,541 participants) (Li et al., 2022). This study showed that acupuncture improved the vertebrobasilar blood flow velocity and achieved good efficacy for patients with PCIV. Moreover, longer duration of acupuncture interventions (more courses or sessions) and stronger stimulation (intensity) are generally more effective in improving vertebrobasilar blood flow velocity. For the acupoint selection, 33 main acupoints including SA points were used in the 20 studies, and Fengchi (GB20) was the most frequently used. Other researchers also indicated that needling Fengchi (GB20) may improve posterior cerebral circulation (Wang X.-X. et al., 2021; Wang Z.-Z. et al., 2021). Therefore, the use of Fengchi (GB20) for PCIV in clinical practice is highly recommended. Besides, Wu et al. (2017) observed the effect of long-term SA (treating for 5 months) on CBF in children with CP that SA increased the CBF, decreased the vascular resistance of ACA, MCA, and posterior cerebral artery (PCA), and improved the overall motor functions of the patients.
As mentioned above, the quantitative whole-brain CBF showed no significant difference before and after SA, implying that SA was modulating the distribution of cerebral blood supply. Therefore, in SA research or clinical practice, it may be better to observe and analyze the effect of SA on rCBF rather than the whole-brain CBF to show its impact on brain functions (Yong et al., 2009).