Low field magnetic stimulation: imaging biomarkers in geriatric bipolar depression

Introduction There is a lack of effective, evidence-based treatment for older adults with bipolar disorder (OABD) who are currently depressed. Most pharmacotherapies have not been extensively studied for use in OABD, and many patients do not respond to first-line therapies. Low Field Magnetic Stimulation (LFMS) was reviewed by the FDA in 2006 and was declared to be a “non-significant risk” device. The LFMS procedure was developed at McLean Hospital and has been studied for over 15 years as an experimental treatment for depression, but its mechanism of action is still unclear. A previous proof-of-concept study used fMRI and EEG to measure changes in brain function associated with LFMS in three healthy adult controls. Notable findings included changes in seed-based connectivity in the rostral Anterior Cingulate Cortex (rACC) and bilateral Dorso-Lateral Prefrontal Cortex (DLPFC) associated with LFMS treatment. Further observation of the biomarkers of response to LFMS in OABD will provide insight into the mechanism of action. The current protocol was developed to study the mechanism of action behind LFMS treatment using fMRI in older adults (ages 50 and older) with bipolar disorder who are actively depressed. We hypothesize that our data will reveal change in the magnitude of resting state activity in subjects treated with LFMS when compared to sham; we further hypothesize that the magnitude of change will be associated with baseline mood or change in mood, as measured by the Montgomery Asberg Depression Rating Scale (MADRS) and Positive and Negative Affect Schedule (PANAS) respectively. Methods We are conducting a randomized, sham-controlled, double blinded, cross-sectional, target engagement study of LFMS, with a target enrollment of 12 patients. Enrolled subjects complete two study visits spaced at least two weeks apart, during which time they complete mood scales and undergo fMRI before and after 20 minutes of LFMS; the two imaging sessions and treatment are completed within one hour. Subjects receive one active treatment at one visit and one sham treatment at the other visit, with the order being randomized and double-blinded. A follow-up phone call is completed at least two days after each visit. The primary hypothesis will be tested with a repeated measures ANOVA with treatment as the explanatory variable; order effects will be tested for significance, and the secondary hypothesis will be tested by adding baseline MADRS and change in PANAS as covariates. Results Recruitment is scheduled to end at the end of 2022, and data analysis is underway. We are actively recruiting OABD, ages 50 and above. Nine of 12 patients (3 female) have completed the trial thus far (mean age of 61.1 years; 3 Bipolar I Disorder, 5 Bipolar II Disorder, and 1 Unspecified Bipolar Disorder). These nine consist of three women and six men. The nine completed subjects enrolled a mean depression score of 25.66 at baseline on the MADRS. We predict that LFMS will selectively activate cortical regions associated with affective control, which in turn will lead to changes in resting state fMRI activity. We expect to observe change in the magnitude of resting state activity, post LFMS-pre LFMS, in subjects treated with active LFMS when compared to sham; we further hypothesize that the magnitude of change will be associated with baseline MADRS and change in PANAS. Conclusions Recent literature recognizes the urgent need for new treatments for OABD, as the mechanisms of depression in a geriatric population may differ from those in a younger population. Thus, we seek to understand the neurobiological processes that underlie the antidepressant effects of LFMS, as well as inform the clinical utility of this treatment in older adults. This study represents an important step toward developing novel interventions for alleviating depressive symptoms in older adults with major mood disorders. LFMS has the potential to be a promising treatment, either as a monotherapy or as an adjunct therapy, without significant risks. This research was funded by The Rogers Family Foundation