Low-Intensity Focused Ultrasound of the Amygdala for Bipolar Disorder

Bipolar disorder (BD) is a mood disorder characterized by episodes of mania and/or depression. BD is the sixth leading cause of disability in the world and has been associated with significant financial costs of $151 billion. First-line treatments include medications like lithium and lamotrigine, and cognitive behavioral therapy. Unfortunately, close to half of individuals with BD do not adhere to treatment often due to side effects such as weight gain, sedation, and cognitive impairment. Therefore, identifying new tolerable treatments for BD patients would be worthwhile.

Individuals with BD show emotion dysregulation, which is associated with deficits in the corticolimbic network. Specifically, cortical brain regions, such as the prefrontal cortex, fail to regulate limbic regions, such as the amygdala, in BD. Pharmacological treatments for BD can decrease amygdala and increase anterior cingulate cortex activation during emotional stimuli, and increase amygdala-ventromedial prefrontal cortex resting-state functional connectivity, which is correlated with clinical improvement. Literature has also consistently shown that amygdala volumes are reduced in BD with a significant negative correlation between amygdala volume and activation during emotional stimuli.

Neuromodulation has showed great promise in psychiatry. Transcranial magnetic stimulation (TMS) has been FDA approved for depression and obsessive-compulsive disorder. Deep brain stimulation (DBS) has also been FDA approved for treatment-resistant OCD. These neuromodulation methods have advantages and disadvantages; TMS is noninvasive but is limited to modulating cortical brain regions (i.e., it cannot reach subcortical brain regions). DBS can stimulate deeper brain regions but requires invasive neurosurgery and long-term maintenance of the device. A newer neuromodulation modality is transcranial focused ultrasound (tFUS), which noninvasively allows access to deep brain regions. We have completed a randomized controlled study of n=30 healthy individuals showing that tFUS targeting the amygdala can decrease amygdala and fear network activation during a threat-inducing task and resting-state functional connectivity. The reduction in amygdala activation was correlated with decreased self-reported anxiety.

Due to the amygdala's role in BD, we propose an initial feasibility study using tFUS to target the amygdala to change corticolimbic network activation during emotion regulation and amygdala-corticolimbic network resting-state functional connectivity in individuals with BD.

Specific Aims: