Traumatic Brain Injury: A Major Medical Problem That Could Be Treated Using Transcranial, Red/Near-Infrared LED Photobiomodulation

Three traumatic brain injuries (TBIs) occur every minute in the United States. TBI is a major medical problem worldwide. More than 5,000,000 Americans are living with TBI-related disabilities with an annual cost of $60–76.5 billion. Nonpenetrating, mild TBI (mTBI) is the most common type (75%). mTBI is defined by loss of consciousness (LOC) lasting £30 min (or no LOC), and with a period of altered mental status (amnesia/confusion) lasting up to 24 h. Persistent cognitive problems occur in 5–22% of cases. Sports-related concussion or mTBI, followed by cognitive dysfunction are of increasing concern both in males and females. With each successive concussion, there is a cumulative effect, including a prolonged period of recovery and progressively increased risk for re-injury. Blast TBI caused by an improvised explosive device (IED) is the signature injury of soldiers returning from Iraq and Afghanistan. It is estimated that 28% of patients with combatrelated mTBI also have clinical levels of post-traumatic stress disorder (PTSD) symptoms. Approximately 53% of individuals with TBI also report sleep disturbances. Poor sleep disrupts the clearing of metabolites from the brain, including b-amyloid and other potentially neurotoxic waste products that accumulate during periods when a person is awake. Persistent neuroinflammation may be a mechanistic link between TBI and potential for later development of neurodegenerative disease, including Alzheimer’s disease (AD). Increased microglial activity may persist for a long time post-TBI. Chronic traumatic encephalopathy (CTE), a progressive tau protein-linked neurodegenerative disease, is believed to develop (at least in part) from repeated head trauma. Symptoms include cognitive dysfunction, progressive irritability, suicidal ideation, and dementia. It may develop years after the original head trauma occurred. CTE has also been documented in United States military veterans exposed to blast injury in Iraq and Afghanistan. Structural CT or MRI brain scans show no focal brain abnormalities with nonpenetrating mTBI, although abnormalities in the white matter axons, important for connecting areas of brain cortex, can be observed on special diffusion tensor imaging MRI scans. The frontal lobes, including medial and lateral prefrontal cortex areas that are important for normal cognitive function, are especially vulnerable to damage following rapid acceleration/deceleration and twisting, for example, whiplash in a motor vehicle accident (MVA), concussive blast force, or even direct impacts to the head. Loss of brain interconnectivity from axonal damage produces the cognitive, emotional, and behavioral problems observed following TBI. In healthy controls, specific brain networks have been identified that function in a temporally coherent, correlated manner, even during the ‘‘resting state’’ (when no task is being performed). The cortical brain areas that comprise a specific brain network may be located in areas close to each other, or further away. These brain networks are studied in the MRI scanner while the participant is simply at rest, looking at a fixation point for 5–7 min. These restingstate functional connectivity MRI scans (rs fMRI) have shown abnormalities in TBI cases in specific brain networks critical for cognitive function. These networks have very low-frequency, coherent oscillations in the frequency range of 0.01–0.08 Hz. The general features appear to also be present in the brains of monkeys and small animals. There are three, highly specialized brain networks important for cognition that have been observed to be dysregulated on rs fMRI scans in TBI. The first of these is the default mode network (DMN), which consists of: (1) anterior areas in the medial frontal lobes [medial prefrontal cortex, (mPFC)]; (2) posterior areas in the medial parietal lobes [precuneus and posterior cingulate cortex (precun/ PCC)] and in posterolateral areas in the lateral parietal lobes (angular gyri); and (3) deep, medial temporal lobes/