Single and repeated sessions of transcranial infrared laser stimulation to the anterior prefrontal cortex in older adults with bipolar disorder

Older adults with bipolar disorder (BD) exhibit greater cognitive decline than is expected for age-matched controls and clinical interventions intended for mood stabilization are not targeted to prevent or ameliorate cognitive decline in this population. Euthymic adults with BD still present with cognitive impairment, even though they are not currently experiencing symptoms of depression or mania. There is evidence of mitochondrial deficits and prefrontal (PFC) hypometabolism in BD, which leads to mitochondrial-induced oxidative stress and damage. Transcranial infrared laser stimulation (TILS) is a non-invasive form of photobiomodulation, in which photons delivered to the PFC can oxidize the mitochondrial enzyme, cytochrome c oxidase (CCO). TILS upregulates the enzymatic activity of CCO and increases differential levels of oxygenated vs. deoxygenated hemoglobin (HbD), an index of cerebral oxygenation and blood flow. The first objective of this dissertation was to use a novel method of broadband near-infrared spectroscopy to assess if TILS to bilateral anterior PFC (Brodmann area 10) produces beneficial effects on mitochondrial energy metabolism (CCO) and cerebral oxygenation (HbD) in older (>45 years of age), euthymic adults with BD. This study found for the first time that TILS of the PFC in adults with BD served to increase oxidized CCO and HbD concentrations after a single session of TILS, with the increase of oxidized CCO starting within the first minute of stimulation. By increasing oxidized CCO and HbD concentrations, TILS has the potential ability to stabilize dysfunctional mitochondrial energy production and prevent additional oxidative damage in the PFC of adults with BD. The second objective of this dissertation was to examine if TILS to the same bilateral PFC regions produces beneficial effects on cognition in older, euthymic adults with BD. Cognitive functions, such as cognitive flexibility, verbal fluency, working memory, sustained attention and impulsivity, were used in this dissertation because they have been shown to differentiate between healthy older adults and older adults with BD. This pilot study found TILS-induced improvements in cognitive performance on tasks that measure cognitive flexibility, sustained attention and impulsivity, after five sessions of TILS. There were no adverse effects of TILS reported in any of the studies. In conclusion, we found that TILS was both safe and effective in adults with BD. TILS is a novel, non-invasive, easily administered intervention that enhances brain mitochondrial metabolism and oxygenation and alleviates cognitive impairment. Enhancing these PFC functions with TILS might alleviate the accelerated cognitive decline and dysfunctional mitochondrial output present in older, euthymic adults with BD