Effectiveness of Light for Enhancement of Cognition by Transcranial Repeated Application (ELECTRA)

Photobiomodulation (PBM), also called low-level light therapy (LLLT), uses optical power
densities less than 100 mW/cm², and usually in the red (600-700 nm) or near infrared (NIR)
780-1000 nm wavelength range. Different light sources (coherent lasers or non-coherent LEDs)
used for PBM have been shown to produce beneficial cellular effects and to be responsible for
preservation and recovery of tissue function in controlled trials in a wide range of
disorders typified by stress injury or degeneration. During PBM, absorption of red or
near-infrared photons by cytochrome c oxidase in the mitochondrial respiratory chain causes
an increase in cellular respiration that continues for much longer than the light is present
when delivered at appropriate fluence and exposure durations.

Primary cellular effects include increases in mitochondrial activity and ATP levels,
production of low levels of reactive oxygen species, induction of transcription factors
(including the pro- survival NF-kB), and inhibition of apoptosis.

Over the past decade several studies have reported that a single, transcranial PBM treatment
at 810 nm delivered to the head had significant, beneficial effect when used to treat acute
ischemic stroke in several different animal models and also in human clinical trials. A
similar approach was used to treat acute traumatic brain injury (TBI) in mice and in humans.
Pathological examination of the mouse brains demonstrated up- regulation of brain-derived
neurotrophic factor (BDNF) and stimulated neurogenesis in the hippocampus and increased
synaptogenesis in the cortex.

A clinical trial is currently in progress at MGH to treat persons with acute moderate TBI.
Several studies have shown improvement of cognitive function in persons with chronic TBI.
Studies have also been conducted in animal models and in persons with Alzheimer's disease,
Parkinson's disease, depression and anxiety.

Only a very limited number of studies have so far been carried out to test NIR
photobiomodulation in normal experimental rodents and in normal human volunteers.

In this study, an LED array light source will be used that has been cleared by the FDA for
other human uses.

Inclusion Criteria:

- Age: 18-25 or 65-85

- Women of child-bearing potential, must use a double-barrier method for birth control
(e.g. condoms with spermicide) if sexually active during the study and for 30 days
post treatment of any kind.

- Subject Informed Consent obtained in writing in compliance with local regulations
prior to enrollment into this study.

- The subject (and caregiver, if applicable) is willing to participate in this study for
at least 12 weeks.

Exclusion Criteria:

- Inability to speak or read English (necessary for cognitive testing software use).

- Pregnancy or lactation

- History of stroke or traumatic brain injury

- Substance dependence or abuse in the past 6 months

- Diagnosis with major psychiatric disease (Psychotic disorder or psychotic episode,
bipolar affective disorder)

- Diagnosed with a neurodevelopmental condition (autism or ADHD)

- A traumatic event that resulted in PTSD

- Any unstable medical illness (defined as any medical illness which has not been
well-controlled with standard-of-care medications)

- A significant skin condition (i.e., hemangioma, scleroderma, rash, open wound) or
medical implant (e.g. metal plate, implantable shunt or valve) on the head.

- Inability to understand or participate in the consent and performance of the study.

- Those with Parkinson's Disease, End Stage Renal Disease, and/or End Stage Liver
Disease