The World Stands on the Eve of the "Physical Revolution in Brain Science" Reflections Following the Open Letter in Reply to Dr. Shilihe Zhuang

Sun Zuodong

Brain science is regarded by developed countries as humanity’s ultimate frontier of scientific research, the "jewel in the crown" of academia. The treatment of brain disorders, particularly neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), represents the absolute core priority within brain science research. For this reason, nations across the globe have successively launched dedicated brain initiatives: the European Union’s program centers on whole-brain simulation; the U.S. initiative prioritizes comprehensive brain mapping; Japan and Germany focus their strategies on robotics and digitalization. A review of these programs across Europe, the U.S., Japan and Germany reveals that therapeutic interventions for brain diseases have largely been sidelined from their agendas. This raises concerns that the brilliant "jewel in the crown" of brain science risks being reduced to an "emperor’s new clothes" in developed nations.

China’s national brain science initiative is still in the planning phase. Notably, China has achieved world-leading progress in treating neurodegenerative disorders using physical interventions via transcranial magnetic-electric stimulation technology. This achievement ought to form the foundational pillar of China’s brain science strategy and stand as our unique competitive advantage.

1 Brain Science

The complexity of the human brain matches the vastness of the universe. When confronted with the countless unknowns of cerebral function, the divide between self-proclaimed "brain scientists" and laypeople amounts to little more than the difference between someone who has run fifty paces and one who has run a hundred. Understanding the self remains humanity’s greatest intellectual challenge.

The Decade of the Brain

U.S. President George H.W. Bush signed a proclamation designating the final ten years of the 20th century (1990–1999) as the "Decade of the Brain". Its defined objectives encompassed neurogenetics, neural functional recovery, memory decline and cognitive impairment, with core priorities of brain protection and neurological disease prevention and treatment. The initiative aimed to deepen human comprehension of the brain and deliver tangible breakthroughs in preventing and managing neurological conditions including Parkinson’s disease, Alzheimer’s disease, depression and schizophrenia. While the program received minimal substantive research funding, it greatly elevated public and academic awareness of neuroscience worldwide and sparked extensive ethical and philosophical discourse surrounding brain research.

The European Human Brain Project

Launched by the European Commission in spring 2013, this ten-year initiative secured €1 billion in funding to develop a full computational model of the human brain. The program quickly drew fierce controversy, however, after officials announced its second phase would cease funding cognitive neuroscience research, prompting coordinated boycotts by specialists in the field. The dispute reached its peak in late May 2014, when the project leadership confirmed cognitive neuroscience would be excluded from all subsequent workstreams. Coincidentally, the world’s first dedicated Alzheimer’s therapeutic device was unveiled in China that same year.

The New U.S. BRAIN Initiative

Unveiled on April 7, 2013, shortly after the European program, the full title of the U.S. project is Brain Research through Advancing Innovative Neurotechnologies (BRAIN), tasked with generating a complete map of brain activity. In his White House announcement, President Barack Obama cautioned assembled scientists that the initiative would create jobs and potentially improve the lives of billions globally. He warned the U.S. against missing this pivotal window of opportunity, stressing that transformative job-creating discoveries might otherwise emerge in China, India or Germany. Obama singled out China ahead of all other nations in this warning. The U.S. Defense Advanced Research Projects Agency (DARPA), a key BRAIN Initiative participant, pledged USD 70 million over five years to fund the development of medical devices for neurological disorders and memory loss. White House officials urged scientists to pursue far more ambitious targets, citing the glacial pace of translational research spanning fruit flies, mice, dogs and humans—timelines too slow for patients already suffering from debilitating brain illnesses. As a result, the BRAIN Initiative expanded its scope to synchronize human brain investigations alongside animal model studies and explore potential interventions for cerebral pathologies. Implementation has since accelerated dramatically as the U.S. races to seize global leadership in brain science.

China’s National Brain Science Initiative

Still under formulation, media reports indicate the framework will likely adopt a "One Body, Two Wings" structure: the core pillar being fundamental brain research, paired with two complementary focus areas of brain protection and brain simulation. As highlighted earlier, China’s global lead in applying transcranial magnetic-electric stimulation to prevent and treat neurodegenerative brain diseases must anchor our national brain strategy and serve as our defining strength. The prolonged deliberation over the final plan reflects prudent, responsible governance worthy of recognition. Academician Pu Muming has emphasized that mesoscale analysis—research occupying the middle ground between micro and macro levels—holds critical importance for unraveling cerebral mechanisms. China’s program unites 23 research teams across nine institutes under the Chinese Academy of Sciences, forming a large national task force for neuroscience research. This stands in stark contrast to the U.S. BRAIN Initiative, which integrates non-governmental independent research bodies such as the Allen Institute for Brain Science into its consortium. U.S.-based Chinese scientist Jiang Jiping noted in his article When Will China’s Scientific Community Break Free from Institutional Monopolies?: "Academic institutions refer to state-run research labs and universities. In Western nations, particularly the U.S. and Europe, private enterprises constitute the primary engine of technological research, development and innovation."

Japan and Germany center their brain technology strategies on robotics and digitalization. What China terms "brain-inspired intelligence" broadly aligns with these priorities; categorizing this field as core brain science stretches the definition, as it represents an applied derivative rather than foundational neuroscience. Professor Rao Yi of Peking University has described artificial intelligence as "a grand yet pseudo-intelligent construct".

The European Human Brain Project’s goal of digitally simulating the human brain rests upon incomplete, inaccurate foundational neuroscientific theories, rendering its technical objectives analogous to building castles in the air—existing tools cannot yet trace human cognitive thought processes. President Obama underscored the economic promise of brain research: "Every dollar invested in mapping the human genome generated USD 140 in economic returns. Scientists are now mapping the human brain to unlock the mysteries of Alzheimer’s disease." He added: "This is no time to withdraw investment from scientific innovation; we must elevate research to heights unseen since the space race." Obama’s framing casts the U.S. BRAIN Initiative less as pure scientific inquiry and more as a commercial gamble, offering little tangible relief to patients enduring debilitating brain disorders today.

While the European and U.S. brain programs carry merit, their transformative potential has been vastly overhyped. Following the successful completion of the draft human genome map in 2000, scientists confidently predicted definitive cancer treatment breakthroughs within 20 to 30 years. Decades later, genome sequencing has delivered far fewer clinical solutions than promised, mirroring today’s overblown enthusiasm for Western brain initiatives. Funding alone cannot solve complex scientific challenges, no matter how large the budget. By comparison, China’s forthcoming brain initiative promises a more pragmatic, scientifically rigorous design—a sentiment shared by Academician Pu Muming, who has expressed skepticism toward European and U.S. programs. Research that fails to translate into real-world clinical solutions runs counter to China’s national priorities.

The human brain is inherently complex; artificial overcomplication of research frameworks only hinders clinical progress. A pervasive flaw among neuroscientists is overfocus on either extreme macroscale or extreme microscale research. Neurodegenerative conditions including AD and PD stand as the most urgent challenge in brain science, yet flawed methodologies and misaligned priorities plague foundational research into cerebral disorders, leaving neuroscience facing unprecedented trials.

In March 2015, epidemiologist Ioannidis and his research team at Stanford University School of Medicine published evidence exposing major methodological flaws across vast swathes of brain research. "From investigations linking genes and molecular activity to correlations between brain structure and psychiatric illness, enormous questions hang over the entire field of neuroscience," they wrote. "The vast majority of published papers cannot be trusted." Ioannidis asserted that most contemporary neuroscience publications contain erroneous conclusions, signaling a systemic crisis within the discipline. Prior to this analysis, he had repeatedly challenged pharmaceutical clinical trials, exposing false claims surrounding drug and therapeutic interventions, estimating eighty percent of relevant publications require rigorous re-evaluation and describing the field as shrouded in pervasive uncertainty. Some researchers feared his findings would spawn global radical skepticism, discrediting the entire field of neuroscience outright. Others warned government funders might slash neuroscience research budgets, eliminating promising transformative projects.

In November 2014, Elsevier, the major Dutch academic publishing house, released a report analyzing global trends in brain science research. The firm surveyed approximately 1.79 million papers published between 2009 and 2013. Metrics based on publication volume confirmed the U.S. retains global leadership, while China’s output expands at an explosive rate. China topped worldwide publication growth at 11.6%, followed by Switzerland at 6.9%; Japan’s growth rate stood at only 1.5%, below the global average of 3.9%. The report identified research into AD and other cerebral diseases alongside pharmaceutical development as the dominant research priorities globally.

In March 2015, BioMed Central, the major UK scientific publisher, retracted 43 academic papers, 41 of which had Chinese authors. Retractions stemmed from evidence of fabricated peer review processes, with the publisher hinting these cases represented merely the "tip of the iceberg" of systemic peer review fraud contaminating academic publishing. The Lancet published commentary noting: "China now ranks second only to the United States in English-language scientific paper output. However, its standards of research integrity have failed to keep pace. Research misconduct—including data fabrication, falsification, plagiarism and ghostwriting—threatens to overshadow China’s scientific achievements." The journal further argued: "This incident suggests misconduct may not be isolated to individual researchers or institutions but has permeated the broader national research culture." "While academic fraud is a global concern, China bears the brunt of this crisis." "Without profound reform to China’s research culture and regulatory oversight, massive investment in biomedical science will fail to yield reliable new discoveries or clinical evidence."

Widespread global scrutiny of Chinese biomedical research integrity creates barriers for domestic scientists seeking publication in top international journals and damages China’s global academic reputation. High-profile cases such as five former GSK China R&D employees resigning over allegations of fabricated experimental data compound this negative international perception, regardless of intent.

Curiously, the same The Lancet published an optimistic piece in 2007 stating: "China holds the potential to lead the world in both the quantity and quality of scientific research." This implies the wave of fraudulent papers largely emerged after 2007. Still, the statistic "43 retractions including 41 Chinese-authored papers" raises critical questions: how was this dataset compiled? Did the publisher apply selective sampling lacking statistical validity? If these cases are merely the tip of the iceberg, why withhold the full scope of misconduct from public view? This scandal demands deep reflection and rigorous investigation from the Chinese scientific community.

Such is the current state of global brain science. The most urgent priority worldwide is to restore integrity to neuroscience research: eliminate low-quality "junk papers" and root out unqualified, fraudulent researchers. While China’s neuroscience community cannot reshape global academia unilaterally, amid this unprecedented crisis we must uphold a core principle: we may not disclose every truth, but every statement we publish must be truthful. Pioneering Chinese neuroscientists including Zhang Xiangtong and Han Jisheng have set the benchmark for this integrity.

Self-regulation is mandatory for all brain scientists.

2 Brain Disorders

The inherent limitations of pharmaceutical chemical interventions are most starkly apparent in the treatment of AD, leaving clinicians with few effective tools. This predicament extends far beyond Alzheimer’s disease to stroke sequelae, cerebral atrophy, vascular dementia (VD), Parkinson’s disease and other severe neurological disorders. For post-stroke patients past the 8-week recovery threshold, the core therapeutic objective should center on reactivating suppressed brain cells—yet no truly effective pharmaceutical agents exist for this phase, a critical distinction from acute stroke care. During the acute phase, rapid drug administration saves lives and salvages dying neurons; in rehabilitation and chronic post-stroke stages, however, clinicians frequently overprescribe medications, with marginal improvements often stemming from spontaneous bodily recovery rather than pharmacological action—a reality unknown to most patients. Many clinical facilities already combine pharmaceutical regimens with transcranial magnetic or electrical physical therapy for stroke survivors, yet clinicians rarely clarify whether observed improvements stem from drugs or physical stimulation, leaving patients uninformed. For Parkinson’s disease, levodopa-based medications offer temporary symptomatic relief, yet most patients remain unaware of their severe adverse side effects.

Foundational research into Alzheimer’s pathogenesis remains mired in competing unproven hypotheses: the cholinergic hypothesis, amyloid-beta hypothesis, tau protein hypothesis and inflammatory hypothesis, among others. Neuroscientists and clinicians worldwide have yet to validate a single definitive mechanism, with conflicting experimental results preventing consensus.

In its 2014 year-end review of Alzheimer’s research, The Lancet cautiously reported: "No therapeutically effective drugs for AD have been identified to date. Two Phase III clinical trials of anti-amyloid-beta monoclonal antibodies failed to demonstrate significant improvements in primary cognitive or functional clinical endpoints." These results force researchers to re-evaluate amyloid-beta as a viable therapeutic target and question whether Aβ represents the root cause of AD—or merely a secondary byproduct of disease progression.

The widely accepted amyloid-beta hypothesis has faced mounting skepticism. Most notably, a landmark study from Stanford University School of Medicine upended this prevailing theory. Published April 3, 2013, in Science Translational Medicine, the research concluded: "New evidence shows fibrils formed by fragments of amyloidogenic proteins (including tau and prion proteins) rapidly alleviate neurodegenerative symptoms in mouse models under certain conditions." "We find these peptides exert beneficial effects on the brain in specific contexts." Corresponding author Professor Lawrence Steinman, a leading multiple sclerosis researcher, stated: "The longstanding consensus that amyloid proteins are inherently toxic requires revision. This paradigm shift forms the foundation of research into multiple sclerosis, AD, PD and other neurodegenerative illnesses."

On July 3, 2014, Professor Shi Yigong’s research group at Tsinghua University published a breakthrough in Nature, resolving the high-resolution three-dimensional atomic structure of human gamma-secretase for the first time worldwide, hailed as identifying the "culprit" driving Alzheimer’s disease. The work’s purported groundbreaking significance rested entirely upon the amyloid-beta hypothesis. Prior laboratories had only resolved the protease structure to 12 angstroms; Shi’s team refined resolution to 4.5 angstroms. Renowned for restrained academic language, Shi made an unprecedented public statement: "This represents the most transformative breakthrough of my professional career, surpassing the sum of all my prior research achievements combined." Mainstream media framed the discovery as the finish line of a decades-long global scientific race, declaring Chinese researchers victorious. Later reports documented further progress from Shi’s team, which used single-particle cryo-electron microscopy to capture a 4.32 angstrom high-resolution structure of human gamma-secretase, mapping the organization of all 19 transmembrane segments and defining the enzyme’s subunit assembly rules. This follow-up breakthrough appeared April 27, 2015, in the Proceedings of the National Academy of Sciences (PNAS).

If Alzheimer’s disease bears no causal link to cerebral amyloid plaque formation, the transformative weight of Shi Yigong’s landmark gamma-secretase research is fundamentally undermined. The December 15, 2014, Nature online publication by Shi’s team detailing the near-atomic resolution structure of rabbit RyR1 calcium channels was likewise prematurely labeled a "landmark achievement".

On August 18, 2015, Shi’s research group released another Nature online paper presenting a 3.4 angstrom atomic-resolution cryo-EM structure of human gamma-secretase. Tsinghua University’s official press release offered measured, objective framing of the findings: "This research provides critical foundational data to elucidate gamma-secretase function and Alzheimer’s disease pathogenesis." The release added the critical caveat: "Nonetheless, the complete pathogenesis of Alzheimer’s disease remains uncharacterized; beta-amyloid deposits are only recognized as one hallmark symptom of the disorder." This neutral framing avoids overstatement and misinterpretation. There exists an essential distinction between discovering a molecular complex and fully understanding its functional mechanisms—one that dictates the true weight of any scientific breakthrough.

Some experts advocate developing multi-target pharmaceuticals for AD treatment, an indiscriminate "shotgun" approach born of desperation rather than rigorous design. Equally unviable proposals include repurposing children’s cognitive game consoles as AD therapeutic tools or integrating pulse diagnostic devices into national brain science roadmaps—ideas analogous to the fable of the donkey with no remaining tricks. Optogenetics, which uses fiber optics to precisely modulate individual neurons, advances basic brain mapping but lacks clinical utility as a disease therapy. Electrical stimulation activates neural populations rather than single neurons, a clinical strength rather than limitation—a critical distinction frequently misrepresented in flawed critiques. Claims that electrical stimulation indiscriminately activates both excitatory and inhibitory neurons with unquantifiable therapeutic benefit betray profound ignorance of neuroscience physiology. The human brain contains hundreds of billions of neurons; implanting millions of optical fibers for universal optogenetic treatment is logistically impossible. Visual-targeted optical stimulation also fails to match the transcranial electrical stimulation’s broad phototherapeutic neural circuit modulation. Hybrid optoelectronic devices marketed for brain disease treatment amount to cynical marketing gimmicks riding the optogenetics trend, with electrical stimulation constituting the sole therapeutically active component. Ultrasound-based brain interventions carry unresolved risks: while ultrasound may theoretically dissolve vascular clots or cerebral amyloid aggregates, no methodology exists to guarantee protection of healthy neurons from collateral damage. Not all physical modalities are suitable for treating brain disorders.

Clinical practice also faces systemic challenges. A December 8 report in Australia’s Sydney Morning Herald documented nearly 200 Australian patients developing compulsive gambling or hypersexuality as severe adverse reactions to prescription Parkinson’s medications. Pharmaceutical manufacturers subsequently agreed to compensate affected patients for failing to disclose these dangerous side effects. PD is a classic neurodegenerative disorder driven by cerebral dopamine depletion; dopamine agonist drugs mimic endogenous dopamine signaling. Worldwide, four million people live with PD, two million of whom reside in China—yet many domestic clinicians still recommend these high-risk medications as the "gold standard" of care.

Identical contradictions pervade AD clinical management. My paper The Brain Cell Activation Theory was published March 11, 2015, on China Online Science and Technology Papers. Eight days later, Professor Jia Jianping, Chief of Neurology at Xuanwu Hospital, Capital Medical University, co-authored the article Defeat the Public Enemy: Alzheimer’s Disease in China Medical Tribune. Jia’s clinical research concluded: "Acetylcholinesterase inhibitors (AChEIs) constitute the most widely prescribed backbone of AD treatment worldwide. The NMDA glutamate antagonist memantine delivers robust therapeutic effects, with superior outcomes observed when memantine is combined with AChEIs." "AChEIs and NMDA antagonists represent first-line standard-of-care pharmacotherapy for AD, particularly for moderate to severe cases."

Conversely, Dr. Min Baoquan, another neurologist at Xuanwu Hospital, Capital Medical University, voiced opposing clinical perspectives in a July 3, 2014, media interview: "No definitive curative treatment for Alzheimer’s exists anywhere globally; clinicians can only deliver symptomatic management." "We prescribe memory-enhancing agents for cognitive decline and sedatives for insomnia—purely reactive symptom control." "No pharmaceutical agent directly targets the core pathological mechanism of AD." "While partial AD disease pathways have been identified, no transformative clinical breakthroughs in drug development have materialized."

Current AD medications including AChEIs and NMDA antagonists do not target degenerated cholinergic neurons themselves, offering one explanation for their inability to halt or meaningfully slow disease progression. Most pipeline AD drug candidates also target upstream or downstream molecular events secondary to cholinergic neuron loss. Repeated failures in novel AD pharmaceutical development validate this critical limitation of chemical intervention.

Overtreatment also permeates neurosurgical, interventional medical device and hospital diagnostic sectors. Ablative brain lesioning, a procedure largely abandoned in developed nations, remains widely promoted across China. Deep Brain Stimulation (DBS, or brain pacemaker implantation) has faced ethical scrutiny from the U.S. Presidential Commission for the Study of Bioethical Issues yet continues to gain popularity domestically.
In May 2014, the U.S. government released an ethics framework for the BRAIN Initiative. The Presidential Commission recommended embedding formal ethical oversight into all program activities. Commission Chair Amy Gutmann of the University of Pennsylvania explained that brain research raises unique ethical dilemmas, emphasizing rigorous validation of scientific claims amid industry and institutional hype as a core priority for ethical translational neuroscience. Gutmann referenced the fraught ethical history of psychosurgery: over 40,000 Americans underwent prefrontal lobotomy based on flimsy evidence that the procedure cured schizophrenia, depression and other psychiatric illnesses.

Portuguese physician Dr. Egas Moniz invented the lobotomy and received the 1949 Nobel Prize in Physiology or Medicine, with Portugal even issuing commemorative stamps honoring his work. This award stands widely regarded as the Nobel Committee’s most hasty, controversial and regretful decision. Lobotomy and analogous ablative brain lesions inflict irreversible severe harm on patients, leaving many survivors permanently vegetative or cognitively adrift. Gutmann warned identical ethical catastrophes could emerge from modern neuroscience research, specifically highlighting Deep Brain Stimulation (DBS). Complications arising from DBS implantation devastate patients and damage the integrity of scientific progress alike. DBS, or implanted brain pacemakers, is an interventional medical device previously approved by the U.S. FDA for Parkinson’s disease management.

The supreme ethical principle of Western medicine is primum non nocere: first, do no harm. The Hippocratic Oath demands every physician uphold this standard: "I will prescribe regimens for the good of my patients according to my ability and my judgment and never do harm to anyone. I will avoid two unethical extremes: overtreatment and ineffective treatment." "When I lack knowledge, I shall acknowledge ignorance without shame, and seek consultation from other specialists to benefit my patient." "I shall consider the patient’s family circumstances and financial burden, for only by accounting for all dimensions of their life do I truly care for their wellbeing."

3 The Brain Cell Activation Theory

The Brain Cell Activation Theory is a novel framework explaining how transcranial magnetic-electric stimulation achieves therapeutic effects for PD and AD, alternatively defined as the optimal physical activation target hypothesis for voltage-gated calcium channels. Its core tenets state: Neurodegenerative diseases including PD and AD are tightly linked to physically gated ion channel dysfunction, which can be therapeutically modulated via physical interventions. Activating neurotransmitter-releasing neurons constitutes the core therapeutic mechanism, with voltage-gated calcium channels serving as the optimal physical stimulation target. Physical modulation triggers calcium influx, inducing synaptic vesicle release of neurotransmitters at neuronal axon terminals.

In the early 1990s, I first proposed the foundational premise that "activating brain cells is the key to treating intractable cerebral disorders." The Brain Cell Activation Theory expands, refines and supplements this original claim through molecular-level mechanistic analysis. The theory delineates clear therapeutic principles, methodologies and endpoints for treating PD, AD and other neurodegenerative conditions. It further highlights the inherent limitations of pharmaceutical chemical interventions for neurodegenerative disease, suggesting physical therapy or combined physical-chemical modalities will emerge as the primary research direction for major brain disorders moving forward.

Translating the Brain Cell Activation Theory into clinical practice, non-invasive transcranial magnetic-electric stimulation devices have delivered robust therapeutic outcomes for stroke sequelae, cerebral atrophy, vascular dementia, PD, AD and depression. The framework coherently explains the cellular and molecular pathology of neurodegeneration in major brain illnesses and the mechanistic action of physical stimulation, while predicting viable therapeutic approaches for other neurotransmitter-mediated disorders. While developed primarily for cerebral conditions, the theory’s applications extend far beyond brain disease.

Any disorder characterized by selective degeneration of neurotransmitter-releasing neurons qualifies as a physically gated ion channel disease, for which physical intervention represents the preferred therapeutic modality. This spectrum includes schizophrenia, bipolar disorder, myasthenia gravis, Huntington’s chorea, epilepsy, pediatric cerebral palsy, intellectual disability, substance addiction, carbon monoxide poisoning, disorders of consciousness (vegetative state), visual and auditory impairment, coronary heart disease and diabetes. Electroacupuncture, rooted solely in traditional Chinese medical frameworks without modern molecular mechanistic grounding, risks marginalization from mainstream biomedicine—the Brain Cell Activation Theory may supply the rigorous scientific theoretical foundation it currently lacks. The Brain Cell Activation Theory represents the narrow definition of "cell activation theory"; its broader generalized iteration lays the conceptual groundwork for establishing a new academic discipline: Physical Pathology.

4 Translational Achievements in Brain Science

Forging new therapeutic pathways where pharmaceutical and surgical interventions fail is an arduous undertaking. Over twenty years separate my initial 1994 proposal of "brain cell activation" from the formal formulation of the Brain Cell Activation Theory. Guided by this framework, I sequentially developed four classes of therapeutic devices certified with Class II medical device registration licenses issued by the China Food and Drug Administration (CFDA):

1.Transcranial Electrical Encephalopathy Therapeutic Apparatus (Brain Function Rehabilitation Therapeutic Apparatus) – certified 1995; indicated for stroke sequelae, vascular dementia and cerebral atrophy

2.Depression Therapeutic Apparatus – certified 2011

3.Parkinson’s Therapeutic Apparatus – certified 2011

4.Alzheimer’s Therapeutic Apparatus – certified 2014

All devices carry verified safety profiles enabling unsupervised at-home patient use without continuous clinician oversight—a primary reason this line of technology has garnered limited attention from clinical medicine academia.

New scientific hypotheses require time to spark widespread academic discourse. Following the commercial launch of my full portfolio of brain therapeutic devices and formal publication of the Brain Cell Activation Theory, international neuroscientists have gradually shifted their perspectives and attitudes toward physical stimulation interventions.

Professor Chen Shengdi, Director of Neurology at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, noted: "Our clinical trials demonstrate that combining non-pharmacological physical therapy with early AD pharmaceutical regimens generates synergistic therapeutic effects. Adjunct physical intervention slows cognitive decline, validating its integration alongside psychological support." Professor Wang Jianzhi, Vice Dean of the Basic Medical Sciences School at Huazhong University of Science and Technology, confirmed parallel animal model research in her laboratory yielding pronounced neuroprotective outcomes. Professor Zhou Zhuan of Peking University also leads research into voltage-dependent calcium-independent cellular secretion pathways, work closely aligned with the physical gated ion channel mechanisms outlined in my theory.

Professor Jürgen Götz’s research team at the University of Queensland identified a novel ultrasound-based intervention for AD, repeatedly scanning AD-model mice to effectively clear cerebral amyloid-beta deposits. Optogenetics, developed over the past fifteen years to modulate neural activity via targeted light exposure, is widely deployed for basic neuroscience research. While neither ultrasound nor optogenetics employs magnetic-electric stimulation, both rely upon interconversion of energy forms to alter neuronal function.

This body of Chinese translational brain science research has captured global media attention. Hundreds of authoritative domestic and international outlets including CCTV’s News Network and Morning News, China National Radio, People’s Daily and Science and Technology Daily published features with headlines such as Chinese Scientists Develop the World’s First Parkinson’s Therapeutic Device, World’s First Depression Therapeutic Apparatus Developed in Harbin, and Chinese Scholars Pioneer a New Physical Therapy for Alzheimer’s Disease. Xinhua News Agency distributed English, German, French, Russian, Spanish and Arabic-language global dispatches covering the breakthrough on two separate occasions.

During a Beijing visit February 16, 2015, Ms. Rajie Long, Director of the Dementia Innovation Unit at the UK Department of Health, announced UK intentions to launch collaborative dementia research partnerships with China. Only three pharmaceutical dementia treatments exist globally, all limited to partial symptomatic relief with inevitable progressive disease decline for all patients. Western pharmaceutical firms have drastically reduced investment in novel dementia drug development. Without coordinated international collaborative research, Alzheimer’s disease will escalate into a worldwide public health crisis. Combating this pandemic demands innovative therapeutic modalities, and the global scientific community requires China’s distinct research paradigm and novel theoretical frameworks.

5 Physical Therapeutic Modalities

For decades, widespread misinterpretation of medical device regulatory frameworks alongside entrenched bias among clinical specialists has incorrectly categorized nearly all physical therapeutic equipment as "adjuvant therapy". This classification is scientifically invalid. Certain medical devices truly serve auxiliary roles—surgical instruments and diagnostic scanners, for instance, cannot function independently without hospital infrastructure and clinician operation. Other devices support pharmaceutical interventions as the primary therapeutic agent, and likewise qualify as adjunct tools. By definition, "adjuvant" care requires a primary core intervention: either clinician-delivered invasive treatment or pharmaceutical medication.

Not all medical devices mandate hospital-based administration or professional supervision, exemplified by home-use physical stimulation therapeutic equipment. While clinical physician input is necessary to draft and revise medical device laws, regulations and industry standards, granting clinicians dominant decision-making authority over device evaluation is unsound. Clinicians specialize in patient care and operate devices therapeutically but lack expertise in medical device engineering, design and mechanism development.

Pharmaceuticals and surgical interventions carry inherent narrow therapeutic limits; physical therapy delivers clinical outcomes unachievable via drugs or invasive procedures. Sidelining physical modalities extends patient hospital stays, inflates healthcare costs and drastically reduces quality of life—this reality holds especially true for brain disorder treatment. Neurodegenerative illnesses arise from physical gated ion channel dysfunction, with no pharmaceutical agent capable of resolving the underlying pathology, leaving clinicians without effective core interventions. Devices including the Aobo Alzheimer’s Therapeutic Apparatus and Aobo Parkinson’s Therapeutic Apparatus do not merely serve as supplementary care; they constitute primary first-line therapeutic interventions. Inference from the Brain Cell Activation Theory further establishes that exogenous neurotransmitter pharmaceuticals trigger severe adverse side effects and counteract physical stimulation’s therapeutic benefits—examples include levodopa for PD and AChEI/NMDA antagonist medications for AD.

Most physical therapeutic devices deliver measurable clinical improvements yet lack robust cell and molecular-level mechanistic explanations. The Brain Cell Activation Theory addresses this gap, supplying a unified molecular framework to rationalize physical stimulation’s mode of action. Drawing upon ion channel gating properties, the theory divides all human disease into three core molecular categories at the cellular level: physical disorders, chemical disorders, and mixed physical-chemical disorders. For brain disease treatment specifically, most cerebral pathologies fall under the physical disorder classification, making physical stimulation the preferred therapeutic modality.

A common concern arises: will physical therapeutic technology displace the global pharmaceutical industry? My analysis concludes physical interventions will partially replace select pharmaceutical classes while acting as synergistic adjuncts for others, with no risk of universal replacement. Antibiotics and anti-infective medications, for example, remain irreplaceable. Penicillin inventor Alexander Fleming received the Nobel Prize in Physiology or Medicine, his legacy enduring due to the revolutionary global public health impact of antibiotic pharmacotherapy.

Dr. Alexandra Z, Resident Physician of Internal Medicine at Singapore General Hospital, authored the article The Absence of Dedicated Physical Therapy Departments in China. She wrote: "Physical therapy delivering profound patient rehabilitation benefits receives little genuine institutional recognition within China, creating an urgent need to reframe national medical priorities around rehabilitative physical intervention." She recounted her complete lack of exposure to formal physiotherapy training during medical school, only encountering the concept briefly in rehabilitation curricula, subconsciously dismissing it as trivial supplementary care equivalent to massage or yoga. Three months of clinical practice in Singapore transformed this perspective entirely. Conservative clinical estimates indicate 60–70% of all hospitalized patients require formal consultation with hospital physiotherapists, with rehabilitation specialists often holding greater clinical decision-making authority than frontline ward physicians—a dynamic that challenges traditional medical hierarchies.

Nature covered President Obama’s 2015 federal research budget proposal, with U.S. National Institutes of Health (NIH) Director Francis Collins highlighting bioelectronic medicine in his budget briefing. GlaxoSmithKline identified this emerging frontier three years prior, committing USD 50 million in August 2013 to fund global bioelectronic medicine research, marking rising institutional investment in physical neuromodulation technology.

Electrical stimulation represents the most direct method of voltage-gated ion channel modulation; non-invasive transcranial magnetic-electric stimulation (TME) ultimately exerts its therapeutic effect through electrical signaling. Clinically deployed bioelectronic devices share this core principle: cochlear implants, retinal prostheses, spinal cord stimulators, cardiac pacemakers, implantable defibrillators and vagus nerve stimulators for rheumatoid arthritis and inflammatory bowel disease all operate via targeted electrical neuromodulation.

6 Conclusion and Future Outlook

Life science research, particularly neuroscience, has advanced to ultra-microscopic molecular resolution, with countless breakthrough biochemical discoveries enabled by physical laboratory tools. The Brain Cell Activation Theory itself constitutes a logical deduction built upon established biochemical research findings. Regrettably, clinical disease management consistently prioritizes pharmaceutical chemical interventions while marginalizing physical modalities, labeling them solely as auxiliary therapy and ignoring their complementary synergistic relationship with pharmacology—an error analogous to "carrying a torch while searching for a match".

Norbert Wiener, founder of cybernetics, observed: "The most abundant scientific breakthroughs emerge within the uncharted gaps dividing established research disciplines." Light, sound, electricity, magnetism, mechanical force and thermal energy all constitute physical therapeutic modalities. Transcranial electrical stimulation, transcranial magnetic-electric stimulation, optogenetics and ultrasound neuromodulation have captured intensive research focus among global brain scientists. Multiple Nobel laureates in Physiology or Medicine will likely emerge from this interdisciplinary field within the coming years. We stand at the threshold of a monumental collective scientific endeavor: the Physical Revolution in Brain Science, whether future research validates or refutes the Brain Cell Activation Theory.

I envision a future routine dialogue between patients and clinicians shaped by the maturation of Physical Pathology:

Patient: Doctor, is my condition a physical disorder or a chemical disorder? Physician: This is a physical disease. Patient: If it stems from physical ion channel dysfunction, why prescribe so many pharmaceutical medications?

This clinical reality will arrive rapidly following the formal establishment and widespread public dissemination of Physical Pathology as an academic discipline.

I hold unwavering confidence in physical therapeutic modalities and the foundational Brain Cell Activation Theory. This framework will spread like a single spark igniting a prairie fire, sparking a sweeping global Physical Revolution in Brain Science—with China poised as the movement’s birthplace and core research hub.

I remain profoundly optimistic that the world stands on the immediate eve of this cerebral physical revolution. Beyond neuroscience, this paradigm shift will eventually expand into a universal Medical Physical Revolution spanning all human organ systems. To borrow a famous metaphor:

It is a ship whose masthead glimmers on the horizon to one standing on the shore; it is a radiant sunrise ready to burst forth for one gazing eastward from a mountain peak; it is a fully formed infant stirring within its mother’s womb, poised to emerge.