Table 3.
Published clinical studies on the neuroprotection effects of photobiomodulation in neuronal activities
| Study/Year | Subjects (n) | Light Source | Wavelengths | Irradiation parameters | Irradiation approach/sites | Findings |
|---|---|---|---|---|---|---|
| Wu et al. 2012 [253] | Healthy volunteers (40) | Laser, 6 diodes, Advanced Chips & Products Corp. (Hillside, NJ, USA) | 830 nm | 7 mW per diode, 20 J/cm2, 10 min, PW at 10-Hz with DC of 50% | Remote tissue irradiation; 1 site, left palm |
Increased amplitude power of alpha rhythms and theta waves mainly in posterior head regions; decreased amplitude power of beta activities in anterior head regions |
| Barrett and Gonzalez-Lima 2013 [44] | Healthy volunteers (40) | Laser, CG-5000, HD Laser Center (Dallas, TX, USA) | 1064 nm | 250 mW/cm2, 60 J/cm2, 4 min, one irradiation session, CW | Transcranially; 2 sites, unilateral (right frontal pole on 4 cm medial and lateral) |
Improved reaction time in Psychomotor Vigilance Task and performance in a delayed match-to-sample memory task; appeared sustained positive emotional states 2 weeks post-irradiation |
| Konstantinovi et al. 2013 [220] | Healthy volunteers (14) | Laser, Endolaser 476, Enraf Nonius (Rotterdam, Netherlands) | 905 nm | 50 mW/cm2, 3 J/cm2 per site, 60 sec, PW at 3000-Hz | Transcranially; 5 sites, over the primary motor cortex (M1) area, centered at the hot-spot for the FDI muscle |
Transitory reduction of the excitability in the motor cortex |
| Blanco et al. 2015 [45] | Healthy volunteers (30) | Laser, Cell Gen Therapeutics, LLC (Dallas, TX, USA) | 1064 nm | 250 mW/cm2, 60 J/cm2, 8 min, one irradiation session, CW | Transcranially; 2 sites, (lower and upper portion of right lateral forehead at EEG map sites: FP2, F4) |
Improved executive function assessed by Wisconsin Card Sorting Task |
| Chaieb et al. 2015 [255] | Healthy volunteers (55) | Laser, coupled with Weber Medical acupuncture | 810 nm | 500 mW/cm2 at scalp via 4 laser needles, 10 min, one irradiation session, CW | Transcranially; 4 sites, over the primary motor cortex (M1) area |
Decreased amplitude of motor-evoked-potentials; increased short interval cortical inhibition and decreased facilitation |
| Salgado et al. 2015 [123] | Healthy elderly women (25) | LEDs | 627 nm | 70 mW/cm2, 10 J/cm2, 30 sec for each site (total of 4 sites), 2×/week for 4 weeks | Transcranially; 4 sites, frontal and parietal regions of scalp |
Increased systolic and diastolic velocity of the left middle cerebral artery |
| Hwang et al. 2016 [46] | Healthy volunteers (60) | Laser, CG-5000, Cell Gen Therapeutics, LLC (Dallas, TX, USA) |
1064 nm | 250 mW/cm2, 60 J/cm2, 8 min, one irradiation session, CW | Transcranially; 2 sites, medial and lateral right forehead |
Improved sustained attention in the Psychomotor Vigilance Task and working memory in the delayed match-to-sample task |
| Tian et al. 2016 [18] | Healthy volunteers (12) | Laser, CG-5000, Cell Gen Therapeutics (Dallas, TX, USA) |
1064 nm | 250 mW/cm2, 13.75 J/cm2 per 1 min for 10 min, one irradiation session, CW | Transcranially; 2 sites, center of forehead (aimed at medial frontal lobes bilaterally) or right side of forehead (aimed at right lateral frontal lobe) |
Increased oxygenated hemoglobin concentration and decreased deoxygenated hemoglobin concentration in both cerebral hemispheres over time during irradiation (10 min) and post-irradiation (6 min) |
| Blanco et al. 2017 [210] | Healthy volunteers (118) | Laser, CG-5000, Cell Gen Therapeutics, LLC (Dallas, TX, USA) |
1064 nm | 250 mW/cm2, 60 J/cm2, 8 min, one irradiation session, CW | Transcranially; 2 sites, lower and upper portion of right lateral forehead at EEG map sites: FP2, F4, and F8 sites |
Improved prefrontal rule-based learning; no significant effects on information-integration learning |
| Grover et al. 2017 [221] | Healthy volunteers (31) | LEDs, LumiWave Infrared Light Therapy Device, BioCare Systems, Inc. (Parker, CO, USA) | 903 nm | 16.67 mW/cm2, 20 J/cm2 at skull, 20 min, CW | Transcranially; Multiple areas in the occipital, left temporal, and right temporal lobes above the ear line, as well as the frontal and parietal lobes |
Improved reaction time in qEEG event-related response test |
| Moghadam et al. 2017 [209] | Healthy volunteers (39) | LEDs, multi-LED array source with 20 cells, Iranbargh (Tehran, Iran) | 850 nm | 285 mW/cm2, 60 J/cm2, 2.5 min, CW | Transcranially; 1 site, right frontal pole of the cortex (at EEG map site: FP2) |
Improved attentional performance in Level-1 of parametric Go/No-task |
| Wang et al. 2017 [50] | Healthy volunteers (11) | Laser, CG-5000, Cell Gen Therapeutics, LLC (Dallas, TX, USA) |
1064 nm | 250 mW/cm2, 13.75 J/cm2 per 1 min for 8 min, one irradiation session, CW | Transcranially; 1 site, right forehead |
Increased cerebral concentrations of oxidized CCO, oxygenated and total hemoglobin during and post-irradiation |
| Naeser et al. 2011 [33] | Chronic TBI (1 with depression) (2) | LEDs, three cluster heads | 633 and 870 nm | 19.39 mW/cm2 and 22.48 mW/cm2, 13.3 J/cm2, 10 min per site, 1×/week for 6 years or 1×day for 4 months, CW | Transcranially; Bilateral left and right forehead (and multiple other areas) |
Improved executive function and memory; decreased post-traumatic stress disorder symptoms |
| Naeser et al. 2014 [30] | Chronic TBI (2 with depression) (11) | LEDs, MedX Health Model 1100 (Toronto, Canada) |
633 and 870 nm | 500 mW, 22.48 mW/cm2, 13 J/cm2, 10 min per site, 3×/week for 6 weeks, CW | Transcranially; 11 sites, midline and bilateral forehead |
Improved sleep quality; decreased post-traumatic stress disorder symptoms; improved performance in social, interpersonal, and occupational functions |
| Morries et al. 2015 [61] | Chronic TBI (6 with MDD) (10) | Laser, LiteCure LT1000, (Newark, DE, USA) Diowave 810 (Diowave, Riviera Beach, FL, USA) | 810 and 980 nm | 10 and 15 W, 14.8–28.3 J/cm2, 8–12 min per site, 2–3×/week for 8 weeks, PW at 10-Hz | Transcranially; 2 sites, bilateral (forehead) 3 bilateral (prefrontal and temporal) |
Improved symptoms of headache, sleep disturbance, cognition, mood dysregulation, anxiety, and irritability |
| Hesse et al. 2015 [198] | TBI with disorders of consciousness (5) | Laser, Power Twin 21 by MKW Laser system | 785 nm | 10 mW/cm2, 10 min, 5×/week for 6 weeks, CW | Transcranially; 5 sites, on the level of the superior crest of the fossa sphenoidale on the forehead |
Improved alertness and awareness; occurred epileptic fits as a side effect |
| Lampl et al. 2007 [199] | Acute stroke (120) | Laser, Neurothera PhotoThera Inc. (Carlsbad, CA, USA) | 808 nm | 10 mW/cm2, 1.2 J/cm2 at cortex, 2 min for each site, CW | Transcranially; 20 sites, multiple areas over the entire shaved scalp |
Positive effects of irradiation within 24 h of stroke onset evaluated by National Institutes of Health Stroke Scale, modified Rankin Scale, Barthel Index, and Glasgow Outcome Scale |
| Zivin et al. 2009 [90] | Acute stroke (660) | Laser, Neurothera PhotoThera Inc. (Carlsbad, CA, USA) | 808 nm | 10 mW/cm2, 1.2 J/cm2 at cortex, 2 min for each site, CW | Transcranially; 20 sites, multiple areas over the entire shaved scalp |
No significant positive effects of irradiation within 24 h of stroke onset |
| Hacke et al. 2014 [200] | Acute stroke (630) | Laser, Neurothera PhotoThera Inc. (Carlsbad, CA, USA) | 808 nm | 10 mW/cm2, 1.2 J/cm2 at cortex, 2 min for each site, CW | Transcranially; 20 sites, multiple areas over the entire shaved scalp |
No measurable neuroprotective effect when irradiation applied within 24 h of stroke onset |
| Boonswang et al. 2012 [201] | Chronic stroke (1) | LEDs, XR3T-1 device (THOR, London, UK) | 660 and 850 nm | 1400 mW, 2.95 J/cm2 delivered to 32 sites, 1 min for each site, spot size of 0.196 cm2, 1/week for 8 weeks | Multiple areas; 32 sites, including cerebral cortices, brainstem and cervical spine (8 sites) and core musculature and lymphatics (24 sites) |
Positive change in every area of deficits and improved physical clinical signs |
| Maksimovich 2015 [196] | Alzheimer’s disease (89) | Laser, coupled with fiber-optic light guided instrument | visible region of spectrum | 20 mw, fiber diameter of 25–100 μm, 20–40 min, CW, or PW, or combined modes | Transcatheterly; Threading a fiber optic through a catheter in femoral artery (advancing fiber optic to distal site of anterior and middle cerebral arteries) |
Improved cerebral microcirculation and cognitive recovery; decreased permanent dementia |
| Berman et al. 2017 [195] | Dementia (11) | LEDs, 15 arrays of 70 LEDs/array (total of 1100 LEDs set) |
1060–1080 nm | 6 min/day for 28 consecutive days, PW at 10-Hz with DC of 50% | Transcranially; whole brain irradiation with LED helmet |
Improved executive functioning including clock drawing, immediate recall, praxis memory, visual attention and task switching; improved EEG amplitude and connectivity measures |
| Saltmarche et al. 2017 [71] | Dementia (5) | LEDs, “810” and “Neuro” devices, Vielight, Inc. (Toronto, Canada) | 810 nm | 14.2 or 41+23 mW/cm2 per LED, 10.65 or 24.6+13.8 J/cm2, 25 or 20 min, PW at 10-Hz, for 12 weeks | Transcranially + Intranasally; Multiple areas, bilateral mesial prefrontal cortex, precuneus/posterior cingulate cortex, angular gyrus, and hippocampus |
Improved function and sleep quality; decreased angry outbursts, anxiety, and wandering |
| Vargas et al. 2017 [206] | Older adults at risk for cognitive decline (12) | Laser, CG-5000, Cell Gen Therapeutics, LLC (Dallas, TX, USA) |
1064 nm | 3.4 W, 250 mW/cm2, 120 or 137.5 J/cm2 per session, CW | Transcranially; 2 sites, forehead at 4.2-cm diameter medial site and 4.2-cm diameter lateral site (EEG map site: FP2 point) |
Improved reaction time and lapses in psychomotor vigilance task and correct responses in delayed match to sample task; increased resting-state EEG alpha, beta, and gamma power; promoted more efficient prefrontal blood-oxygen-level dependent-fMRI response |
| Maloney et al. 2010 [197] | Parkinson’s disease (8) | Laser, PL5000, Erchonia Medical Inc. (Melbourne, FL, USA) | NR | Daily for 2 weeks | Transcranially; Multiple areas (bilateral occipital, parietal, temporal, frontal lobes and along sagittal sutures) |
Improved balance, gait, freezing, cognitive function, rolling in bed, and difficulties in speech assessed by Visual Analog Scale |
| Schiffer et al. 2009 [11] | Major depressive disorder (10) | LEDs, Marubeni America Corp. (Santa Clara, CA, USA) | 810 nm | 250 mW/cm2, 60 J/cm2, 4 min, one irradiation session, CW | Transcranially; 2 sites, bilateral (right and left forehead at EEG map sites: F3, F4) |
Decreased depression and anxiety rates at 2-week post-irradiation assessed by Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale; no significant effects on cerebral blood flow |
| Cassano et al. 2015 [203] | Major depressive disorder (4) | Laser, Neurothera PhotoThera Inc. (Carlsbad, CA, USA) | 808 nm | 5 W, 700 mW/cm2, 84 J/cm2, 2 min per site, 2×/week for 3 weeks, CW | Transcranially; 4 sites, bilateral (right and left forehead center at 20 and 40 mm from sagittal line) |
Decreased depression rate at 6 to 7 weeks post-irradiation assessed by Hamilton Depression Rating Scale-17 items |
| Disner et al. 2016 [202] | Patients with elevated depression symptoms (51) | Laser, CG-5000, Cell Gen Therapeutics (Dallas, TX, USA) |
1064 nm | 250 mW/cm2, 60 J/cm2, 4 min per site, for 2 sessions, CW | Transcranially; 2 sites, medial and lateral parts of the left or right side of the forehead |
Right prefrontal irradiation improved attention bias modification intervention effects and depression symptoms |
| Petrie et al. 2016 [183] | Patients with low back pain (10) | LEDs, Thor-UK:DDII, LED-104 instrument (UK) | 660 and 850 nm | 100 mW/cm2, 3 J/cm2, 6 min per session (30 sec/site), 3× over 12 days | Remote tissue irradiation; 12 sites, symmetrical bilateral: 8 thoracic and 4 posterior-thigh sites |
Decreased depression rate assessed by one-question depression-scale; improved functional status assessed by Advise-Rehab Global Scale |
| Zalewska-Kaszubska and Obzejta 2004 [184] | Alcoholics (53) | Laser | 514 and 632.8 nm | 514 nm: 100 mW, 10 sec for each site 632.8 nm: 25 mW, 5 min |
Multiple areas on head and neck; 514 nm (auricular concha, bilaterally to 5 points) 632.8 nm (spot on the neck vessel projection) |
Decreased depression rate assessed by Beck Depression Inventory–Fast Screen; increased α-endorphin level |
| Naeser et al. 2012 [181] | Patients with aphasia (3) | LEDs, 9 red + 52 NIR diodes | NR | 22.2 mW/cm2, 13 or 13+39 J/cm2, 3×/week for 6 weeks, PW at 146-Hz | Transcranially; | Improved comprehension and interfaced assessed by picture naming tasks |
| Nawashiro et al. 2012 [19] | Patient in a persistent (1) vegetative state | LEDs, SUN-MECHATRONICS (Tokyo, Japan) | 850 nm | 11.4 mW/cm2, 20.5 J/cm2 at scalp, 30 min, 2×/day for 73 days | Transcranially; 2 sites, left and right forehead areas superior to the eyebrows |
Increased regional cerebral blood flow; improved neurological outcomes |
| Werner et al. 2016 [256] | Patients with disorders of consciousness (16) | Laser, Power Twin 21 by MKW Laser system | 785 nm | 10 mW/cm2, 10 min, 5×/week for 4 weeks, CW | Transcranially; 5 sites, along with horizontal line at the level of the upper edge of the two fossa sphenoidalis |
Improved alertness and awareness over time assessed by Revised Coma Recovery Scale |
Note: AD, Alzheimer’s disease; CCO, cytochrome c oxidase; CW, continues wave; DC, duty cycle; EEG, electroencephalography; fMRI, functional magnetic resonance imaging; LEDs, light emitting diodes; MDD, major depressive disorder; PD, Parkinson’s disease; PW, pulsed wave; qEEG, quantitative electroencephalography; TBI, traumatic brain injury