A study conducted at the First Affiliated Hospital of Guangxi University of Chinese Medicine demonstrates that acupuncture normalizes brain functions in patients with major depressive disorder (MDD). Using functional magnetic resonance imaging (fMRI) brain scans, the Guangxi University of Chinese Medicine researchers determined that scalp acupuncture at acupoint DU20 (Baihui) restores healthy brain patters to patients experiencing major depressive disorder. Using before and after fMRIs, the researchers determined that acupuncture balances brain states in patients with severe depression and restores healthy brain functional connectivity. In addition, acupuncture successfully downregulated excessive hyperactivity of brain states found in major depressive disorder patients. The researchers determined that acupuncture allows the brain to return to a normal restful state while simultaneously reactivating brain regions suffering from abnormally low functionality.

The researchers compared the fMRI results of 29 first-episode major depressive disorder patients with fMRI results of 29 healthy subjects. The researchers identified areas of the brain with differing functional connectivity (FC) in major depressive disorder patients. After 20 minutes of electroacupuncture (EA) stimulation at acupoint DU20 (Baihui), the patients were given another fMRI scan to determine how electroacupuncture affects functional connectivity in the brain. The outcomes demonstrate that electroacupuncture has the effect of increasing functional connectivity in areas of hypoconnectivity and decreasing functional connectivity in areas of hyperconnectivity, thereby modulating the default mode network (DMN) of the brain toward healthier brain activity.  Electroacupuncture restored homeostatic resting states to the brain by balancing DMN functional connectivity.

The DMN is the area of the brain that is used for processing information when the brain is not engaged in an active task. It is involved in the conception of oneself and others, including moral and emotional judgements related to actions, as well as the rumination on past and future events. It is made up of a network of distinct areas of the brain connected both anatomically and functionally. In the absence of malformation or injury, the structural connections are relatively fixed. The degree to which these areas are functionally connected is measured by statistical analysis using technologies, including fMRI, that visually capture the change in blood flow to specific areas of the brain.

This study demonstrates how brain functional connectivity is markedly and predictably different between patients with major depressive disorder and healthy subjects. The study maps how electroacupuncture changes the patterns of functional connectivity in major depressive patients toward the patterns found in healthy subjects that do not have severe depression. Because the nature of the changes in functional connectivity are consistent among patients with major depressive disorder, the hypothesis is that these changes are a symptom or cause of major depressive disorder. The implication is that, if the effect is long-lasting, electroacupuncture can be used to normalize the functional connectivity of patients with major depressive disorder, providing relief for a devastating disease.

Major depressive disorder manifests differently in different people, but it is generally marked by feelings of hopelessness, decreased concentration, and a lack of interest in stimuli that had previously brought joy. Weight change is also common, as is a change in sleeping patterns. Patients with more severe forms of major depressive disorder may also have recurring thoughts about death or suicide. In addition to the impact it has on all aspects of a patient’s daily life, the prevalence of major depressive disorder makes it a profound public health concern. In the United States alone, up to 20% of the population suffers from mild depression, and between 2% – 5% have severe depression. Major depressive disorder dramatically decreases the quality of life of the patient and may have secondary emotional effects on their friends and family. Because lack of motivation is often associated with major depressive disorder, one’s ability to work may also be affected. The social and financial costs to families, and to society as a whole, may therefore be great. There are a variety of environmental causes, including stress and emotional trauma, though epidemiologic studies show that 40% – 50% of the risk is genetic.

Biomedical treatment protocols for major depressive disorder include various forms of antidepressant medications. First generation drugs such as tricyclic antidepressants and monoamine oxidase inhibitors (MAOIs) were developed in the 1950s and are in current use. While second generation drugs such as serotonin-selective reuptake inhibitors (SSRIs) are often better tolerated than first generation tricyclic antidepressants because they tend to have fewer adverse effects, their mechanisms of action is similar, indicating that our understanding of the mechanisms of depression and its treatment has not changed significantly since the drugs were first developed.

While 80% of patients achieve some benefit from medications, only 50% experience remission of their depression, meaning that many patients must choose between suffering from depression or the long term adverse effects of medications that are only moderately successful. The specific qualities of depression are hard to replicate in animal trials. There is a clear hereditary risk; however, the specific genes involved have not been completely identified, which makes it difficult to develop and test new drug therapies.  Finding new treatment modalities outside of the medication arena would therefore potentially help millions of people in the US, and likely billions globally, who suffer the debilitating effects of major depressive disorder.

The fMRI is useful because it is non-invasive and does not require identifying the specific genes or neurotransmitters involved in brain functioning. The fMRI maps neural activity by mapping differential blood flow. "For reasons that we still do not fully understand, neural activity triggers a much larger change in blood flow than in oxygen metabolism, and this leads to the blood being more oxygenated when neural activity increases. This somewhat paradoxical blood oxygenation level dependent (BOLD) effect is the basis for fMRI." An increase in neural activity is indicated by an increase in oxygenation of a particular area of the brain, and areas that are active at the same time are considered to be functionally connected even if they are anatomically discrete. This is the basis of functional connectivity determinations based on fMRI BOLD responses.

The Guangxi University of Chinese Medicine researchers identified specific brain regions that were reliably different in patients with major depressive disorder versus healthy subjects that did not suffer from mental illness. In the test group, they found that functional connectivity was initially diminished between the posterior cingulate cortex (PCC) and the anterior cingulate cortex (ACC), and that functional connectivity was initially higher between the PCC and the left middle prefrontal cortex (PfC), the left angular gyrus (AG) and the bilateral hippocampus (HIPP).  Each of these areas plays a distinct role in cognitive and emotional functioning that may speak to the effects felt by patients when the functional connectivity in these regions has changed.

"The posterior cingulate cortex is a highly connected and metabolically active brain region. Recent studies suggest it has an important cognitive role, although there is no consensus about what this is…. It is a key node in the default mode network and shows increased activity when individuals retrieve autobiographical memories or plan for the future, as well as during unconstrained ‘rest’ when activity in the brain is ‘free-wheeling’." This study indicates that the PCC is a central hub for communication within the DMN, as each of the areas for which the function is better known is interacting directly with the PCC.

Despite depression appearing as a disease of hypoactivity, most brain regions showed hyperactive functional connectivity with the PCC. The ACC is the exception, initially demonstrating diminished functional connectivity that was subsequently increased after electroacupuncture. "In addition to regulating autonomic and endocrine functions, it is involved in conditioned emotional learning, vocalizations associated with expressing internal states, assessments of motivational content and assigning emotional valence to internal and external stimuli, and maternal-infant interactions." Motivation and emotional responses to stimuli are two key diagnostic elements of major depressive disorder that decreased in most MDD patients. Thus, hypoactivity between the PCC and ACC is, at least in part, responsible for the decrease in these mental functions and that reversing the hypoactivity may have a positive therapeutic effect.

The fMRI of the major depressive disorder patients showed an initial hyperactivity in the PfC, AG, and HIPP as compared to the control group, and a subsequent dampening of the functional connectivity between these areas and the PCC after electroacupuncture treatment. The PfC integrates cognitive and emotional behaviors and thus aids the process of decision making. The AG has a critical role in processing language and affects thought and attention as well as spatial memory; it is also used for emotional perception and sensory interpretation. The HIPP is "implicated in cognitive-behavioral functions and emotional memory." Attention and emotional memory and behavior show clear changes in major depressive disorder patients. While it seems that these functions are impaired, it may be just the opposite; "depressed individuals over-recruit a neural network involved more generally in enhancing memory for affective stimuli, and… the degree to which they over-recruit this system is related to the severity of the symptomatology." This is consistent with the findings of the current study, which indicate that depression is related to hyperactivity of functional connectivity in the brain.

Based on the findings, additional research is warranted to confirm the experimental results of the study. Moreover, the conclusions presented by the research team corroborate the Traditional Chinese Medicine (TCM) understanding that DU20 (Baihui) modulates brain function. The research also provides a solid basis for future long-term studies about the cumulative effect of electroacupuncture for the treatment of major depressive disorder. Major depressive disorder is widespread and devastating both to the patients and their communities. The findings demonstrate that acupuncture is a potential modality that addresses the needs of patients with major depressive disorder and allows for healthier brains states.

References:
1 Deng, Demao, Hai Liao, Gaoxiong Duan, Yanfei Liu, Qianchao He, Huimei Liu, Lijun Tang, Yong Pang, and Jien Tao. "Modulation of the Default Mode Network in First-Episode, Drug-Na?ve Major Depressive Disorder via Acupuncture at Baihui (GV20) Acupoint." Frontiers in Human Neuroscience Front. Hum. Neurosci. 10 (2016): pg 3?
doi:10.3389/fnhum.2016.00230.

2 Demao Deng et al, Modulation of the Default Mode Network, pg 1

3 Demao Deng et al, Modulation of the Default Mode Network, pg 1.

4 Nestler, E. J., M. Barrot, R. J. DiLeone, A. J. Eisch, S. J. Gold, L. M. Monteggia. "Neurobiology of Depression." Neuron. 34, no. 1 (2002): 13-25. doi: 10.1016/S0896-6273(02)00653-0. dx.doi.org/10.1016/S0896-6273(02)00653-0

5 Hwang, J. W., N. Egorova, X. Q. Yang, W. Y. Zhang, J. Chen, X. Y. Yang, L. J. Hu, S. Sun, Y. Tu, and J. Kong. "Subthreshold Depression Is Associated with Impaired Resting-state Functional Connectivity of the Cognitive Control Network." Translational Psychiatry Transl Psychiatry 5, no. 11 (2015). pg 1. doi:10.1038/tp.2015.174.