Behavioral Study of Effects of Low-Level Light Therapy on Mood and Reaction Time
Condition: Depression
MeSH terms: Depression
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Left Low Level Light Therapy; Attention bias modification; Right Low Level Light Therapy; Sham Low Level Light Therapy
Intervention type(s): Device; Other; Device; Device
Intervention description(s): Administration of left LLLT consists of applying light of a specific wavelength (1064 nanometers) using a laser diode, the CG-5000 high density laser (Cell Gen Therapeutics, LLC). Left LLLT will target the left forehead. The diameter parameters of stimulation are the same that showed psychologically beneficial effects in Schiffer et al. (2009). At the power level described, the energy emitted by the CG-5000 at this setting is one quarter of the skin MPE (0.250 W/cm2), exposure to it is not deemed harmful to tissue, and it causes no detectable physical damage and negligible heat.; The task will consist of a modified dot-probe paradigm. A pair of stimuli depicting a negative word and a neutral word will be presented, randomly located to the right and left side of the computer screen. The words will be presented for 1000 ms. The words will then disappear and a dot-probe will appear in the center of the screen location of one of the words (i.e., O or Q). This probe will appear on the screen until the participant presses one of two response buttons to indicate the identity of the probe. The presentation of the probe will be staggered to maximize attention for the neutral stimulus. Latency and accuracy of the button press responses are recorded by the computer.; Administration of right LLLT consists of applying light of a specific wavelength (1064 nanometers) using a laser diode, the CG-5000 high density laser (Cell Gen Therapeutics, LLC). Right LLLT will target the right forehead. The diameter parameters of stimulation are the same that showed psychologically beneficial effects in Schiffer et al. (2009). At the power level described, the energy emitted by the CG-5000 at this setting is one quarter of the skin MPE (0.250 W/cm2), exposure to it is not deemed harmful to tissue, and it causes no detectable physical damage and negligible heat.; Administration of sham LLLT is designed to resemble active LLLT from the participant's perspective, but uses a dosage markedly below the minimal necessary threshold to elicit a response.
Other intervention name(s): Transcranial laser stimulation; Cognitive bias modification; Transcranial laser stimulation; Transcranial laser stimulation
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment