Photonic Medicine: How Shining Light Through the Skull Changes Brain Function

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The Most Radical Idea in Neurology: Light as Brain Medicine

There is a treatment for traumatic brain injury, depression, Alzheimer’s disease, and age-related cognitive decline that involves no drugs, no surgery, and no electrodes. It involves shining near-infrared light — invisible to the eyes, felt as mild warmth or nothing at all — onto the forehead and scalp. The photons penetrate the skull, enter the cerebral cortex, are absorbed by mitochondrial cytochrome c oxidase in neurons, and increase ATP production in brain tissue. Cognitive function improves. Depression lifts. The damaged brain begins to repair itself.

This is transcranial photobiomodulation (tPBM), and it represents arguably the most radical and underutilized advance in neurology of the past two decades. The mechanism is established. The clinical data are accumulating. The safety profile is excellent — no serious adverse effects have been reported in any published clinical trial. And the treatment can, in principle, be self-administered at home with commercially available devices costing a fraction of a single neurology consultation.

The reason tPBM remains outside the mainstream of neurology is not scientific. The science is strong. It is economic: light cannot be patented. A near-infrared LED that can be purchased for less than a hundred dollars competes, in efficacy for some conditions, with pharmaceutical treatments that cost thousands of dollars per year. The incentive structure of modern medicine does not reward treatments that are cheap, safe, and effective. It rewards treatments that are patentable, prescribable, and billable. Light is none of these things.

But the photons do not care about the economics. They enter the skull, find the mitochondria, and do their work.

The Physics: Can Light Actually Penetrate the Skull?

The first objection to transcranial photobiomodulation is intuitive: the skull is a solid bone. How can light pass through it?

The answer lies in the physics of near-infrared light interaction with biological tissue. The optical properties of tissue are determined by three parameters: absorption (how much light is absorbed per unit distance), scattering (how much light is redirected from its original path), and the combination of the two (effective attenuation).

In the near-infrared range (700-1100 nm), there is an “optical window” where the major chromophores in tissue — water, hemoglobin, and melanin — have relatively low absorption. Water absorbs strongly above 1000 nm. Hemoglobin absorbs strongly below 700 nm. Between these absorption peaks, near-infrared light has its minimum tissue absorption — meaning it can travel further before being absorbed.

Multiple studies have directly measured the transmission of near-infrared light through human cadaveric skulls and living subjects:

Cadaveric studies. Tedord et al. (2015) measured the penetration of 810 nm light through human cadaver skulls of varying thicknesses and found that approximately 2-3% of incident light reached the surface of the brain. This may seem low, but the power densities used clinically are high enough that this transmitted fraction delivers therapeutically relevant energy to cortical tissue.

Living subject measurements. Jagdeo et al. (2012) measured transcranial NIR light penetration in living human subjects using a photodetector placed intracranially during neurosurgery. They confirmed that near-infrared light at 830 nm penetrates the intact human skull and reaches the brain surface at detectable intensities.

Wavelength dependence. Studies consistently show that penetration increases with wavelength through the optical window: 810 nm penetrates more than 670 nm, and 1064 nm penetrates more than 810 nm. However, absorption by water increases above 1000 nm, creating a practical upper limit.

The bottom line: near-infrared light at 810-850 nm penetrates the human skull and reaches the cerebral cortex. The depth of penetration into brain tissue is estimated at 20-30 mm from the cortical surface — sufficient to reach the cortical gray matter, including the prefrontal cortex, motor cortex, and other superficial brain structures. Deeper structures (hippocampus, thalamus, brainstem) are more difficult to reach transcranially but may receive some scattered light, and intranasal and intra-aural (ear canal) delivery devices have been developed to target deeper brain structures.

Margaret Naeser: The Pioneer of Transcranial Photobiomodulation for TBI

Dr. Margaret Naeser, a research professor of neurology at Boston University School of Medicine and VA Boston Healthcare System, has been the pioneering clinical investigator of transcranial photobiomodulation for traumatic brain injury (TBI) since the early 2000s.

Naeser’s work began with a case series that would have seemed implausible had it not been published in a peer-reviewed journal. In a 2011 study published in Photomedicine and Laser Surgery, Naeser reported on two patients with chronic TBI (years after their injuries) who had failed all conventional treatments — rehabilitation therapy, cognitive behavioral therapy, and medications. Both patients received transcranial LED photobiomodulation using red (633 nm) and near-infrared (870 nm) LEDs applied to specific locations on the scalp.

The results were remarkable. Both patients showed significant improvements in:

• Executive function (planning, organization, mental flexibility)
• Verbal learning and memory
• Inhibition (the ability to suppress impulsive responses)
• Sleep quality
• Mood (reduced depression and anxiety)

These improvements occurred in patients who had been symptomatic for years and had not responded to any prior treatment. The improvements persisted for months after treatment cessation and returned when treatment was resumed — demonstrating a dose-response relationship inconsistent with placebo.

Naeser followed this with a larger open-protocol study published in 2014, treating 11 chronic TBI patients with transcranial LED therapy (26 J/cm² per treatment, 3 times per week for 6 weeks). The results showed statistically significant improvements on multiple neuropsychological tests, including the Stroop Test (executive function/inhibition), the California Verbal Learning Test (memory), and the Trail Making Test (cognitive flexibility).

In 2020, Naeser and colleagues published a sham-controlled pilot randomized controlled trial of transcranial photobiomodulation for moderate TBI, demonstrating that the active treatment group showed significantly greater improvement in PTSD symptoms and sleep quality compared to the sham group. This was among the first RCTs to demonstrate efficacy against a sham control — a critical step for establishing scientific credibility.

Naeser’s work established several key principles that have guided the field:

1. Location matters. The LED cluster placement corresponds to specific brain regions — frontal (prefrontal cortex, for executive function), temporal (temporal cortex, for language and memory), and parietal (parietal cortex, for attention and spatial processing). Treatment can be targeted to the specific cognitive deficits of each patient.

2. Wavelength combination. Naeser typically uses a combination of red (633 nm, which is absorbed by superficial cortical tissue) and near-infrared (810-870 nm, which penetrates deeper). The combination may activate different chromophores and reach different tissue depths.

3. Chronic conditions respond. Unlike many neurological treatments that work only in the acute phase, tPBM produces benefits even in chronic TBI — years or decades after the initial injury. This suggests that tPBM is not preventing acute damage but rather reactivating dormant neural repair processes by providing the energy (ATP) needed to rebuild.

Paolo Cassano: Depression and the Photon Antidepressant

Dr. Paolo Cassano, a psychiatrist at Massachusetts General Hospital and Harvard Medical School, has investigated transcranial photobiomodulation as a treatment for major depressive disorder — a condition that affects over 300 million people worldwide and for which existing treatments (antidepressant medications, psychotherapy) produce full remission in only about one-third of patients.

Cassano’s research is grounded in the neuroenergetic hypothesis of depression: the idea that depression is fundamentally a state of reduced brain energy metabolism. Neuroimaging studies consistently show that depressed patients have reduced cerebral blood flow and reduced metabolic activity in the prefrontal cortex — particularly the dorsolateral prefrontal cortex (DLPFC) and the ventromedial prefrontal cortex (vmPFC). These are the brain regions that support executive function, emotional regulation, and the capacity to envision a positive future. When these regions are metabolically depressed, the person is depressed.

If depression is, at its core, a state of insufficient prefrontal metabolic activity, then a treatment that increases prefrontal mitochondrial ATP production should be antidepressant. This is exactly what Cassano has tested.

In a 2015 pilot study published in the Journal of Clinical Psychiatry, Cassano and colleagues administered tPBM (810 nm near-infrared light, 250 mW/cm², delivered to the forehead targeting the bilateral DLPFC and vmPFC) to 10 patients with major depressive disorder. Each patient received two treatments per week for 3 weeks (6 treatments total). The primary outcome was the Hamilton Depression Rating Scale (HAM-D).

Results: the mean HAM-D score decreased from 19.8 (moderate depression) to 13.0 (mild depression) — a 34% reduction. Four of ten patients (40%) met criteria for clinical response (50% or greater reduction in HAM-D). No adverse effects were reported.

These results, while preliminary, are notable because the effect size is comparable to that of SSRI antidepressants — achieved in 3 weeks rather than the 4-8 weeks typically required for SSRI onset, without any of the side effects (sexual dysfunction, weight gain, emotional blunting, discontinuation syndrome) that SSRI treatment entails.

Cassano’s subsequent research has included sham-controlled trials and neuroimaging studies. A 2018 study used functional near-infrared spectroscopy (fNIRS) to demonstrate that tPBM at 810 nm acutely increased cerebral blood oxygenation in the prefrontal cortex — providing direct evidence that the treatment was reaching and activating the target brain tissue.

In 2019, Cassano and colleagues published a double-blind, sham-controlled randomized trial in Psychological Medicine. The trial enrolled 21 patients with moderate-to-severe depression who received either active tPBM (810 nm, delivered transcranially to prefrontal cortex) or sham treatment, twice weekly for 8 weeks. The active treatment group showed significantly greater improvement in depression scores compared to the sham group, with a large effect size (Cohen’s d = 0.87).

Trent Henderson: Transcranial Photobiomodulation for Dementia

Dr. Lew Lim and Dr. Trent Henderson have independently advanced the application of tPBM for neurodegenerative diseases, particularly Alzheimer’s disease and dementia.

Henderson, a neuropsychiatrist at the Neuro-Laser Foundation in Denver, Colorado, has published case series and pilot studies of home-based tPBM for dementia patients. His approach uses a combination of transcranial (forehead) and intranasal (through the nose) NIR delivery to target both cortical and deeper brain structures.

In a 2017 case series published in Photobiomodulation, Photomedicine, and Laser Surgery, Henderson reported on 5 patients with mild to moderate dementia who received 12 weeks of daily tPBM at 810 nm. The results included:

• Improved cognitive scores on the Mini-Mental State Examination (MMSE) and Alzheimer’s Disease Assessment Scale (ADAS-cog)
• Improved sleep quality
• Reduced anxiety and wandering behavior
• Improved ability to perform activities of daily living
• Caregiver-reported improvements in social engagement, emotional expression, and recognition of family members

The improvements occurred in patients who were on stable medications (cholinesterase inhibitors) and had been declining despite treatment — suggesting that tPBM was adding benefit beyond what pharmacotherapy could provide.

The proposed mechanism for tPBM in Alzheimer’s disease involves multiple pathways:

1. Increased mitochondrial ATP production — compensating for the mitochondrial dysfunction that is a hallmark of Alzheimer’s pathology
2. Reduced neuroinflammation — PBM modulates microglial activation and reduces pro-inflammatory cytokine production in brain tissue
3. Enhanced glymphatic clearance — improved metabolic function may support the brain’s waste clearance system, facilitating removal of beta-amyloid and tau aggregates
4. Increased BDNF production — brain-derived neurotrophic factor, the master neurotrophin that supports neuronal survival, growth, and synaptic plasticity, is upregulated by PBM
5. Increased cerebral blood flow — through NO-mediated vasodilation in cerebral vessels

A 2019 randomized controlled trial by Saltmarche et al. enrolled 60 patients with mild to moderate Alzheimer’s disease and demonstrated significant improvements in MMSE scores and ADAS-cog scores in the active tPBM group compared to sham — providing stronger evidence than the earlier case series.

The 1068 nm Wavelength: A New Frontier

Recent research has highlighted 1068 nm (near the upper end of the near-infrared optical window) as a particularly effective wavelength for transcranial photobiomodulation. A group at Durham University in the UK, led by Dr. Paul Chazot, has published preclinical studies showing that 1068 nm transcranial PBM:

• Reduces beta-amyloid plaque burden in transgenic Alzheimer’s disease mouse models
• Improves memory performance in aged mice
• Reduces neuroinflammatory markers
• Penetrates the skull more effectively than shorter wavelengths (due to reduced scattering)

Chazot’s group has proposed that the primary chromophore at 1068 nm may not be cytochrome c oxidase but water — specifically, the structured water clusters associated with mitochondrial membranes and protein hydration shells. This is a provocative hypothesis that connects tPBM research to the emerging field of water science and the biological significance of structured (exclusion zone) water.

Low-Level Laser Therapy: The Historical Roots

Transcranial photobiomodulation has its roots in low-level laser therapy (LLLT), which dates to the work of Endre Mester in Hungary in 1967. Mester was investigating whether laser radiation caused cancer in mice. He shaved their backs, irradiated them with a low-power ruby laser, and found that instead of developing cancer, the irradiated mice grew hair faster than the control group. This accidental discovery — that low-level light stimulates rather than damages biological tissue — launched the field of photobiomodulation.

Over the following decades, LLLT was applied to wound healing, musculoskeletal pain, dental conditions, and nerve repair — primarily using helium-neon lasers (632.8 nm, red) and gallium-arsenide diode lasers (780-860 nm, near-infrared). The discovery that LEDs could produce the same biological effects as lasers (because the mechanism depends on wavelength and dose, not on coherence) made the technology dramatically cheaper and more accessible.

The transition from peripheral LLLT (treating musculoskeletal conditions, wounds, and superficial tissues) to transcranial PBM (treating brain conditions) represents a paradigm shift in the field. If light can heal a wound on the skin, and if light can penetrate the skull, then light can heal a wound in the brain. The logic is straightforward. The execution is revolutionary.

The Engineering Metaphor: Light as the Brain’s Power Supply

In the engineering framework, the brain is the central processing unit of the biological computer. It consumes 20% of the body’s total energy supply — a disproportionate load for an organ that represents 2% of body mass. This energy is required for:

• Maintaining ion gradients across neuronal membranes (the basis of electrical signaling)
• Synthesizing and recycling neurotransmitters
• Building, maintaining, and pruning synapses (the basis of learning and memory)
• Running the glymphatic system (waste clearance during sleep)
• Sustaining the electromagnetic oscillations (brain waves) that correlate with conscious states
• Supporting the default mode network, attention networks, and other large-scale neural architectures

When the power supply is compromised — as in TBI, where mitochondria are damaged by mechanical shearing forces; in depression, where chronic stress and neuroinflammation impair mitochondrial function; in Alzheimer’s, where amyloid pathology and mitochondrial dysfunction create a vicious cycle of energy failure and toxic protein accumulation — the CPU cannot execute its programs. Consciousness degrades. Cognition fails. The system crashes.

Transcranial photobiomodulation is, in this framework, a direct power supply intervention. Near-infrared photons penetrate the skull, are absorbed by cytochrome c oxidase in neuronal mitochondria, dissociate the nitric oxide inhibitor, and allow the electron transport chain to resume full function. ATP production increases. The neuron has more energy. It can fire more efficiently, synthesize more neurotransmitters, maintain stronger synaptic connections, and support the complex oscillatory dynamics that underlie conscious experience.

This is not a drug that modulates a single neurotransmitter system. It is not a surgical intervention that targets a specific brain region. It is a universal energy intervention that benefits every neuron the light reaches — because every neuron needs ATP, and every neuron has mitochondria with cytochrome c oxidase.

The breadth of conditions that respond to tPBM — TBI, depression, anxiety, PTSD, Alzheimer’s, Parkinson’s, stroke recovery, age-related cognitive decline — is not a sign that the treatment is too good to be true. It is a sign that the common denominator of these conditions is mitochondrial energy failure, and that the treatment addresses the common denominator rather than the surface symptoms.

Clinical Protocols: Current Evidence-Based Approaches

Based on the published research, several tPBM protocols have demonstrated clinical efficacy:

For TBI and concussion:

• Wavelength: 810 nm near-infrared (some protocols add 633 nm red)
• Power density: 50-250 mW/cm² at the scalp surface
• Energy density: 20-60 J/cm² per treatment site
• Treatment sites: bilateral forehead (targeting DLPFC), temporal regions, parietal regions (tailored to specific deficits)
• Frequency: 3 times per week for 6-12 weeks; some protocols use daily treatment
• Devices: LED cluster heads applied to the scalp, or whole-head devices (LED helmets)

For depression:

• Wavelength: 810 nm near-infrared
• Target: bilateral prefrontal cortex (DLPFC and vmPFC)
• Power density: 250 mW/cm² at the scalp
• Treatment duration: 20-30 minutes per session
• Frequency: twice weekly for 8 weeks (Cassano protocol)
• Can be combined with antidepressant medication

For Alzheimer’s and cognitive decline:

• Wavelength: 810 nm (some protocols use 1068 nm)
• Delivery: transcranial (forehead, temporal, parietal) plus intranasal
• Frequency: daily home use for 12+ weeks
• Duration: 20-25 minutes per session
• The Vielight Neuro Gamma device (pulsed at 40 Hz — gamma frequency) has been used in clinical trials based on the hypothesis that 40 Hz entrainment may help clear amyloid (inspired by the MIT research of Li-Huei Tsai showing that 40 Hz light flicker reduces amyloid in mice)

For general cognitive enhancement (healthy individuals):

• Wavelength: 1064 nm (University of Texas at Austin studies by Francisco Gonzalez-Lima and Douglas Barrett)
• Delivery: laser applied to the right forehead
• Duration: 8-minute single session
• Effects: improved reaction time, sustained attention, working memory, and positive emotional state in healthy university students
• This is perhaps the most intriguing finding — tPBM enhances cognitive function not only in damaged brains but in healthy brains, suggesting it can optimize neural performance above baseline

Safety considerations:

• tPBM has an excellent safety profile — no serious adverse effects have been reported in published trials
• The most common adverse effect is a mild transient headache after the first few sessions
• Eye safety: do not shine high-power NIR directly into the eyes
• Epilepsy: pulsed light at certain frequencies may trigger seizures in susceptible individuals — consult a neurologist before using pulsed tPBM devices if you have epilepsy
• The treatment is non-invasive, painless, and can be self-administered with appropriate devices

The 40 Hz Connection: Light Flicker and Brain Waves

A fascinating convergence has emerged between tPBM research and the neuroscience of brain oscillations. In 2016, Li-Huei Tsai at MIT demonstrated that exposing Alzheimer’s disease model mice to a 40 Hz (gamma frequency) light flicker reduced amyloid-beta and tau pathology in the visual cortex. Subsequent studies showed that combining 40 Hz light and sound stimulation reduced pathology more broadly and improved cognitive function.

The mechanism appears to involve gamma-frequency entrainment of neural oscillations, which activates microglia (the brain’s immune cells) to clear amyloid plaques and modulates the brain’s waste clearance systems. Several tPBM devices now pulse their near-infrared output at 40 Hz, combining the mitochondrial benefits of NIR photobiomodulation with the neuroplasticity benefits of gamma-frequency stimulation.

This convergence — between light as energy (mitochondrial activation) and light as information (frequency-specific neural entrainment) — hints at a deeper truth about the relationship between light and consciousness. The brain is both an energy consumer and an information processor. Light addresses both dimensions simultaneously. It powers the hardware and patterns the software.

The Consciousness Implications

If light can change brain function — improving cognition, lifting depression, reducing anxiety, enhancing memory — then light is not just a therapeutic agent. It is a modulator of consciousness.

Consider what the tPBM research collectively demonstrates:

• Near-infrared light increases prefrontal cortical metabolic activity → enhanced executive function → greater capacity for planning, inhibition, and cognitive flexibility
• tPBM increases cerebral blood flow → better oxygen and nutrient delivery → enhanced neural efficiency → subjectively experienced as mental clarity
• tPBM increases BDNF production → enhanced neuroplasticity → greater capacity for learning, adaptation, and the formation of new neural pathways
• tPBM reduces neuroinflammation → reduced microglial activation → less “neural noise” → improved signal-to-noise ratio in neural processing → experienced as reduced brain fog and increased perceptual clarity
• tPBM at 40 Hz entrains gamma oscillations → enhanced binding of disparate neural processes into coherent conscious experience → the “unity” of perception, the sense of being a single, integrated consciousness

Each of these effects is a measurable change in brain function. Together, they constitute a measurable enhancement of the physical substrate of consciousness. The person receiving tPBM is not just healthier — they are, in a meaningful sense, more conscious. More awake. More present. More capable of the complex neural integration that underlies the richness of subjective experience.

The contemplative traditions describe practices that enhance consciousness through sustained attention (meditation), through breathwork (pranayama), through movement (yoga, tai chi), and through sound (mantra, chanting). To this list, we may need to add light. Not as a metaphor for spiritual illumination — but as a physical input that directly enhances the metabolic and oscillatory dynamics of the brain from which consciousness emerges.

The mystics say “turn toward the light.” The photobiologists say “apply 810 nm to the prefrontal cortex.” The language differs. The direction — toward light, toward energy, toward enhanced neural function and expanded awareness — is the same.

Key Researchers and References

• Margaret Naeser — Boston University / VA Boston. Pioneer of transcranial LED PBM for TBI. Published in Photomedicine and Laser Surgery (2011, 2014), Journal of Neurotrauma (2020).
• Paolo Cassano — Massachusetts General Hospital / Harvard. tPBM for major depression. Published in Journal of Clinical Psychiatry (2015), Psychological Medicine (2019).
• Trent Henderson — Neuro-Laser Foundation, Denver. tPBM for dementia. Published in Photobiomodulation, Photomedicine, and Laser Surgery (2017).
• Francisco Gonzalez-Lima — University of Texas at Austin. tPBM for cognitive enhancement in healthy subjects. Published in Lasers in Surgery and Medicine (2013).
• Li-Huei Tsai — MIT. 40 Hz gamma light/sound entrainment for Alzheimer’s disease. Published in Nature (2016), Cell (2019).
• Paul Chazot — Durham University. 1068 nm tPBM, pre-clinical Alzheimer’s research.
• Michael Hamblin — Harvard/MIT. Comprehensive reviews of tPBM mechanisms and applications.
• Key paper: Salehpour F et al. (2018) “Brain photobiomodulation therapy: a narrative review.” Molecular Neurobiology.