Pulsed Transcranial Red/Near-Infrared Light Therapy Using Light-Emitting Diodes Improves Cerebral Blood Flow and Cognitive Function in Veterans with Chronic Traumatic Brain Injury: A Case Series.

Objective: This study explored the outcome of applying red/near-infrared light therapy using light-emitting diodes (LEDs) pulsed with three different frequencies transcranially to treat traumatic brain injury (TBI) in Veterans. Background: Photobiomodulation therapy (PBMT) using LEDs has been shown to have positive effects on TBI in humans and animal models. Materials and methods: Twelve symptomatic military Veterans diagnosed with chronic TBI >18 months post-trauma received pulsed transcranial PBMT (tPBMT) using two neoprene therapy pads containing 220 infrared and 180 red LEDs, generating a power output of 3.3 W and an average power density of 6.4 mW/cm2 for 20 min, thrice per week over 6 weeks. Outcome measures included standardized neuropsychological test scores and qualitative and quantitative single photon emission computed tomography (SPECT) measures of regional cerebral blood flow (rCBF). Results: Pulsed tPBMT significantly improved neuropsychological scores in 6 of 15 subscales (40.0%; p < 0.05; two tailed). SPECT analysis showed increase in rCBF in 8 of 12 (66.7%) study participants. Quantitative SPECT analysis revealed a significant increase in rCBF in this subgroup of study participants and a significant difference between pre-treatment and post-treatment gamma ray counts per cubic centimeter [t = 3.77, df = 7, p = 0.007, 95% confidence interval (95,543.21-21,931.82)]. This is the first study to report quantitative SPECT analysis of rCBF in regions of interest following pulsed tPBMT with LEDs in TBI. Conclusions: Pulsed tPBMT using LEDs shows promise in improving cognitive function and rCBF several years after TBI. Larger, controlled studies are indicated.

Photobiomodulation using low-level laser therapy (LLLT) for patients with chronic traumatic brain injury: a randomized controlled trial study protocol.

BACKGROUND: Photobiomodulation using low-level laser therapy (LLLT) has been tested as a new technique to optimize recovery of patients with traumatic brain injury (TBI). The aim of this study is to evaluate inhibitory attentional control after 18 sessions of active LLLT and compare with the placebo group (sham LLLT). Our exploratory analysis will evaluate the efficacy of the active LLLT on verbal and visuospatial episodic memory, executive functions (working memory, verbal and visuospatial fluency, attentional processes), and anxiety and depressive symptoms compared to the sham group. METHODS/DESIGN: A randomized double-blinded trial will be made in 36 patients with moderate and severe TBI. The active LLLT will use an optical device composed of LEDs emitting 632 nm of radiation at the site with full potency of 830 mW. The cranial region with an area of 400 cm2 will be irradiated for 30 min, giving a total dose per session of 3.74 J/cm2. The sham LLLT group contains only an LED device with power < 1 mW, only serving to simulate the irradiation. Each patient will be irradiated three times per week for six weeks, totaling 18 sessions. Neuropsychological assessments will be held one week before the beginning of the sessions, after one week, and three months after the end of LLLT sessions. Memory domain, attention, executive functioning, and visual construction will be evaluated, in addition to symptoms of depression, anxiety, and social demographics. DISCUSSION: LLLT has been demonstrated as a safe and effective technique in significantly improving the memory, attention, and mood performance in healthy and neurologic patients. We expect that our trial can complement previous finds, as an effective low-cost therapy to improve cognitive sequel after TBI. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02393079 . Registered on 20 February 2015.

Transcranial, Red/Near-Infrared Light-Emitting Diode Therapy to Improve Cognition in Chronic Traumatic Brain Injury.

OBJECTIVE: We review the general topic of traumatic brain injury (TBI) and our research utilizing transcranial photobiomodulation (tPBM) to improve cognition in chronic TBI using red/near-infrared (NIR) light-emitting diodes (LEDs) to deliver light to the head. tPBM improves mitochondrial function increasing oxygen consumption, production of adenosine triphosphate (ATP), and improving cellular energy stores. Nitric oxide is released from the cells increasing regional blood flow in the brain. Review of published studies: In our previously published study, 11 chronic TBI patients with closed-head TBI caused by different accidents (motor vehicle accident, sports-related, improvised explosive device blast injury) and exhibiting long-lasting cognitive dysfunction received 18 outpatient treatments (Monday, Wednesday, Friday for 6 weeks) starting at 10 months to 8 years post-TBI. LED therapy is nonthermal, painless, and noninvasive. An LED-based device classified as nonsignificant risk (FDA cleared) was used. Each LED cluster head (5.35 cm diameter, 500 mW, 22.2 mW/cm2) was applied for 9 min 45 sec (13 J/cm2) using 11 locations on the scalp: midline from front-to-back hairline and bilaterally on frontal, parietal, and temporal areas. Testing was performed before and after transcranial LED (tLED; at 1 week, 1 month, and at 2 months after the 18th treatment) and showed significant improvements in executive function and verbal memory. There were also fewer post-traumatic stress disorder (PTSD) symptoms reported. Ongoing studies: Ongoing, current studies involve TBI patients who have been treated with tLED using either 26 J/cm2 per LED location on the head or treated with intranasal only (iLED) using red (633 nm) and NIR (810 nm) diodes placed into the nostrils. The NIR iLED is hypothesized to deliver photons to the hippocampus, and the red 633 nm iLED is believed to increase melatonin. Results have been similar to the previously published tLED study. Actigraphy sleep data showed increased time asleep (on average one additional hour per night) after the 18th tLED or iLED treatment. LED treatments may be performed in the home. Sham-controlled studies with veterans who have cognitive dysfunction from Gulf War Illness, blast TBI, and TBI/PTSD are currently ongoing.

Significant improvements in cognitive performance post-transcranial, red/near-infrared light-emitting diode treatments in chronic, mild traumatic brain injury: open-protocol study.

This pilot, open-protocol study examined whether scalp application of red and near-infrared (NIR) light-emitting diodes (LED) could improve cognition in patients with chronic, mild traumatic brain injury (mTBI). Application of red/NIR light improves mitochondrial function (especially in hypoxic/compromised cells) promoting increased adenosine triphosphate (ATP) important for cellular metabolism. Nitric oxide is released locally, increasing regional cerebral blood flow. LED therapy is noninvasive, painless, and non-thermal (cleared by the United States Food and Drug Administration [FDA], an insignificant risk device). Eleven chronic, mTBI participants (26-62 years of age, 6 males) with nonpenetrating brain injury and persistent cognitive dysfunction were treated for 18 outpatient sessions (Monday, Wednesday, Friday, for 6 weeks), starting at 10 months to 8 years post- mTBI (motor vehicle accident [MVA] or sports-related; and one participant, improvised explosive device [IED] blast injury). Four had a history of multiple concussions. Each LED cluster head (5.35 cm diameter, 500 mW, 22.2 mW/cm(2)) was applied for 10 min to each of 11 scalp placements (13 J/cm(2)). LEDs were placed on the midline from front-to-back hairline; and bilaterally on frontal, parietal, and temporal areas. Neuropsychological testing was performed pre-LED, and at 1 week, and 1 and 2 months after the 18th treatment. A significant linear trend was observed for the effect of LED treatment over time for the Stroop test for Executive Function, Trial 3 inhibition (p=0.004); Stroop, Trial 4 inhibition switching (p=0.003); California Verbal Learning Test (CVLT)-II, Total Trials 1-5 (p=0.003); and CVLT-II, Long Delay Free Recall (p=0.006). Participants reported improved sleep, and fewer post-traumatic stress disorder (PTSD) symptoms, if present. Participants and family reported better ability to perform social, interpersonal, and occupational functions. These open-protocol data suggest that placebo-controlled studies are warranted.

Improved cognitive function after transcranial, light-emitting diode treatments in chronic, traumatic brain injury: two case reports.

OBJECTIVE: Two chronic, traumatic brain injury (TBI) cases, where cognition improved following treatment with red and near-infrared light-emitting diodes (LEDs), applied transcranially to forehead and scalp areas, are presented. BACKGROUND: Significant benefits have been reported following application of transcranial, low-level laser therapy (LLLT) to humans with acute stroke and mice with acute TBI. These are the first case reports documenting improved cognitive function in chronic, TBI patients treated with transcranial LED. METHODS: Treatments were applied bilaterally and to midline sagittal areas using LED cluster heads [2.1″ diameter, 61 diodes (9 × 633 nm, 52 × 870 nm); 12-15 mW per diode; total power: 500 mW; 22.2 mW/cm(2); 13.3 J/cm(2) at scalp (estimated 0.4 J/cm(2) to cortex)]. RESULTS: Seven years after closed-head TBI from a motor vehicle accident, Patient 1 began transcranial LED treatments. Pre-LED, her ability for sustained attention (computer work) lasted 20 min. After eight weekly LED treatments, her sustained attention time increased to 3 h. The patient performs nightly home treatments (5 years); if she stops treating for more than 2 weeks, she regresses. Patient 2 had a history of closed-head trauma (sports/military, and recent fall), and magnetic resonance imaging showed frontoparietal atrophy. Pre-LED, she was on medical disability for 5 months. After 4 months of nightly LED treatments at home, medical disability discontinued; she returned to working full-time as an executive consultant with an international technology consulting firm. Neuropsychological testing after 9 months of transcranial LED indicated significant improvement (+1, +2SD) in executive function (inhibition, inhibition accuracy) and memory, as well as reduction in post-traumatic stress disorder. If she stops treating for more than 1 week, she regresses. At the time of this report, both patients are continuing treatment. CONCLUSIONS: Transcranial LED may improve cognition, reduce costs in TBI treatment, and be applied at home. Controlled studies are warranted.