Harvard Catalyst Profiles

Alzheimer's disease (AD) dementia refers to a particular onset and course of cognitive and functional decline associated with age together with a particular neuropathology. It is increasingly recognized that AD has a very long preclinical phase, lasting possibly >10 years. Decline in glucose metabolism and mitochondrial function are detected decades prior to clinical symptoms, making them potential therapeutic targets for AD prevention/early intervention. A substantial body of literature shows that transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light penetrates robustly into the cerebral cortex and is absorbed by the mitochondrial cytochrome c oxidase, stimulating the mitochondrial respiratory chain and leading to increased ATP production. Based on that, our study will evaluate the dose-dependent effects of t-PBM in amnestic Mild Cognitive Impairment (aMCI), an early AD stage, in a randomized clinical trial of 8 weeks of t-PBM vs. sham. The HMS student can join this research project under the supervision of Dr. Vieira and Dr. Cassano. The students will be involved in treatment visits, imaging visits and clinical visits. They will learn about the most recent techniques of neuromodulation, especially t-PBM, and their promise in the field of neuropsychiatry. They will be encouraged to participate in data analyses and scholarly work related to aMCI and AD. They will be asked to formulate scientific hypothesis and consider the methodology for testing. The student might choose to be entirely remote or hybrid or just in-person.

Down syndrome (DS) is the most common genetic cause of intellectual disability worldwide, affecting 1 in 800 births. Individuals with DS experience a unique risk profile for neuropsychiatric disease, due to chromosome dosage effects from trisomy 21. To date, effective interventions for cognition in DS are lacking. A substantial body of literature proves that transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light penetrates deeply into the cerebral cortex, modulates cortical excitability, and improves cerebral perfusion and oxygenation. t-PBM improves attention, inhibition, memory, working memory and learning. Based on that, our study hypothesis is that t-PBM can improve language (intelligibility, vocabulary, syntax and grammar), significantly more than sham, as tested after completion of 18 t-PBM sessions and at long-term follow-up. HMS students can join this research project under the supervision of Dr. Vieira and Dr. Cassano. The students will be involved in treatment visits, imaging visits and clinical visits. They will learn about the most recent techniques of neuromodulation, especially t-PBM, and their promise in the field of neuropsychiatry. They will also be encouraged to participate in data analyses and scholarly work related to language improvement for Down Syndrome. They will be asked to formulate scientific hypothesis and consider the methodology for testing. The student might choose to be entirely remote or hybrid or just in-person.

High-risk and unrestrained behaviors in bipolar disorder can lead to harmful financial outcomes. However, FDA-approved medications for manic symptoms have poor tolerability, with a 50% nonadherence. Poor adherence to medications carries a high risk of relapse and recurrence of mania, high risk of hospitalization and of suicide attempt (when mixed states). Electroconvulsive therapy (ECT) is a very effective treatment for mania and an alternative to medications; however, its use is limited by poor tolerability, stigma, access, lack of specialists, and cost. Modern noninvasive brain stimulation techniques could potentially achieve the same efficacy of ECT in controlling manic symptoms, with better tolerability, and easier access. Transcranial photobiomodulation (t-PBM), a neuromodulation technique that uses near-infrared light (NIR) to stimulate or inhibit target brain regions has shown promising early results for treating neuropsychiatric disorders. The aim of our study is to use t-PBM to modulate the right dorsolateral prefrontal cortex (r-DLPFC) in hypomania, to boost decision making, to control impulsivity as well as other manic symptoms. Also, we will evaluate changes in brain blood flow with fMRI, to demonstrate the engagement of specific brain targets for neuromodulation of impulsivity. The HMS student can join this research project under the supervision of Dr. Vieira and Dr. Cassano. The students will be involved in treatment visits, imaging visits and clinical visits. They will learn about the most recent techniques of neuromodulation, especially t-PBM, and their promise in the field of neuropsychiatry. They will be encouraged to participate in data analyses and scholarly work related to Bipolar Disorder. They will be asked to formulate scientific hypothesis and consider the methodology for testing. The student might choose to be entirely remote or hybrid or just in-person.

Major depressive disorder (MDD) is a severe disorder affecting 21 million Americans (~10%) per year and is the third leading cause of global disability. Although effective treatments exist for MDD, 43% of patients experiencing a longer than six-month MDD episode remain untreated, most of them preferring self-management over professional help. Factors limiting the adoption of interventions for MDD include delayed efficacy and burdensome side effects of medications and the time commitment for psychotherapies. In this sense, the use of device-based therapies such as transcranial photobiomodulation (t-PBM) for MDD has been well tolerated, safe, and efficacious. t-PBM with near-infrared (NIR) light penetrates robustly into the cerebral cortex and is absorbed by the mitochondrial enzyme cytochrome c oxidase (CCO), stimulating the mitochondrial respiratory chain, and leading to increased ATP production. These NIR photochemical effects have been related to antidepressant effects in animal models and in humans. The aims of our study are: 1. to evaluate the dose-dependent effects of t-PBM in MDD subjects; 2. to demonstrate target engagement by t-PBM in MDD through fMRI blood-oxygenation-level dependent (BOLD) signal change during t-PBM at three irradiance doses; 3. to determine the relationship between changes in target MDD biomarkers and clinical symptoms. The HMS student can join this research project under the supervision of Dr. Vieira and Dr. Cassano. The students will be involved in treatment visits, imaging visits and clinical visits. They will learn about the most recent techniques of neuromodulation, especially t-PBM, and their promise in the field of neuropsychiatry. They will be encouraged to participate in data analyses and scholarly work related to Depression. They will be asked to formulate scientific hypothesis and consider the methodology for testing. The student might choose to be entirely remote or hybrid or just in-person.