Behavioral Study of Effects of Low-Level Light Therapy on Mood and Reaction Time

Depression

The goal of this project is to use low-level light therapy (LLLT) to enhance neural metabolism in the prefrontal cortex of humans, and measure the effects of LLLT on attentional bias change following a single session of attention bias modification (ABM). LLLT is non-invasive, therapeutically beneficial, and promotes a wide range of biological effects including enhancement of energy production, gene expression and prevention of cell death. Previous research has indicated that human participants show a beneficial psychological effect, including improved mood and greater sustained attention, following a single treatment of LLLT to the forehead. ABM is a computer-based cognitive task designed to decrease the mood-congruent negative attentional bias frequently observed in depressed and dysphoric individuals. Previous ABM studies have led to decrease in clinical symptoms relative to a control condition. This study will explore whether the effects of LLLT on mood and attention could improve the potency of ABM, leading to greater attention change and greater improvement of mood relative to sham LLLT.

Low-level light therapy constitutes a novel intervention shown to regulate neuronal function in cell cultures, animal models, and clinical conditions. The Gonzalez-Lima lab has previously shown that low-level light therapy can increase mitochondrial cytochrome oxidase activity, which can provide neuroprotection against toxicity and can improve the aerobic capacity of other tissue such as skeletal muscle. This suggests that the oxidative metabolism of tissue exposed to LLLT is enhanced. LLLT treatments also appear to have in vivo transcranial neurochemical effects that involve metabolic-enhancing and antioxidant systems; it is a non-invasive technique that has been used in humans to stimulate the brain as an antidepressant treatment, to alleviate muscle fatigue and enhance recovery, and to increase sustained attention during cognitive tasks. These LLLT treatments have thus been proven to be not just safe but actually beneficial in humans. Collectively, these data imply that LLLT could be used as an inexpensive, noninvasive approach to boost blood flow and energy consumption in the brain and other tissues, as well as provide neuroprotection against neurological conditions which may be related to mitochondrial dysfunction. This research could ultimately lead to the development of non-invasive, non-pharmacologic, therapeutic, cytoprotective and performance-enhancing interventions in both healthy humans and in those in need of rehabilitation efforts under conditions where neuromuscular function and movement are compromised, as well as treating neurobiological disorders in which metabolic dysfunction plays an underlying causal role, such as depression and post-traumatic stress disorder. The therapeutic use of red to near-infrared light wavelengths is based on the principle that certain molecules in living systems absorb photons and trigger signaling pathways in response to light. In biologic tissues, absorption and scattering of light (which would render it ineffective as a treatment) are maximal at wavelengths below 600 nanometers, and water absorbs light at wavelengths greater than 1150 nanometers. Thus, there is a wavelength window for biologic stimulation that covers the red to near-infrared light spectrum (between 600 and 1150 nm). Early results suggest that LLLT may have significant promise in the treatment of clinical disorders. Prior work found that a single LLLT treatment to the forehead resulted in an increased cerebral blood flow and significant beneficial effect in patients with major depression and anxiety. Previous research conducted in the Gonzalez-Lima lab showed that healthy human subjects receiving LLLT showed significantly higher positive affect at two week follow-up sessions relative to subjects in the placebo-light condition. Importantly, no adverse side effects were found in subjects for either study, either immediately after the initial treatment, or at two or four weeks post-treatment. The investigators plan to follow the LLLT treatment protocol from these two studies, immediately prior to running subjects through the ABM procedure. ABM is a technique designed to modify attentional bias, a cognitive factor that has been theorized to underlie the onset and maintenance of Major Depressive Disorder. ABM is built on the framework of the standard dot-probe task, wherein two valenced stimuli are presented side-by-side, and then followed by a target probe behind one of the stimuli. The difference in response time between probes directly behind a stimuli relative to probes on the opposite side of the stimuli can be used to operationalize attentional bias for that particular valence of stimuli. ABM uses a conditioning approach to shift this bias by staggering the frequency of probe distribution in favor of one specific valence. Eventually, participants are expected to preferentially process the favored valence of stimuli, leading to a shifting of attentional bias. This placebo-controlled study will measure whether LLLT influences the efficacy of ABM on measures of biased attention and dysphoria. Participants will be randomized to receive either active or placebo LLLT, and will then undergo an ABM procedure designed to decrease attention towards negative environmental stimuli (measured using a variant of the dot-probe task). The combination of LLLT and ABM will take place over two sessions (two days apart), and will be followed by one and two week follow-up periods to assess mood change. The investigators hypothesize that participants who receive the active LLLT will show greater change in attentional bias following ABM and greater decrease in dysphoric symptoms during follow-up compared to the placebo group.

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