Low Intensity Focused Ultrasound for Emotion Regulation (LIFUPEMOT)

Low Intensity Focused Ultrasound as a Non-Invasive Neural Prosthetic for the Improvement of Emotion Regulation

Amygdala is highly involved in emotional response, emotional reactivity and anxiety. Amygdala functions are therefore involved in a wide range of psychiatric disorders including generalized and social anxiety, specific phobia, obsessive compulsive disorder and posttraumatic stress disorder. Therefore, potential clinical implications of amygdala stimulation are great. However, to date, such efforts have been limited by the inability of non-invasive neuromodulation techniques (e.g. transcranial magnetic stimulation - TMS) to reach the amygdala and the highly invasive (i.e. neurosurgical) nature of methods (e.g. deep brain stimulation - DBS) which can, but to our knowledge has rarely been used, target these areas. In order to overcome these current limitations, study invesitgators propose the use of low intensity focused ultrasound pulsation (LIFUP) to affect amygdala activity to improve emotion regulation.

Study investigators propose the use of personalized neuronavigation, based on each participant's structural brain MRI, to aim LIFUP at the amygdala in the pursuit of enhancement of emotionality in humans. A comprehensive approach will integrate behavioral and multimodal neuroimaging to assess the utility of LIFUP to increase activity in deep neural structures and in the regulation of anxiety. Further, this is the first study to use LIFUP in (A) amygdala in humans and (B) for pro-cognitive effects. Findings from this study will provide important insight into the utility of LIFUP modulation of subcortical regions and their associated networks and functions, which have wide ranging implications for clinical LIFUP as a therapeutic device for numerous patient populations. By characterizing the effect of LIFUP on the amygdala and associated networks, this study will provide the foundation on which LIFUP can be validated as an effective neural prosthetic and as a treatment tools for psychiatric patient populations. Participants will complete a brief T1-weighted structural brain scan. Then, they will be removed from the scanner and, using the T1 image in Neurocare Brainsight software, the LIFUP transducer will be aimed at the amygdala and gently strapped in place to their head. Participants will then return to the scanner where a second T1 image will verify the position of the LIFUP transducer and allow for estimation of the spatial location of the sonification beam focus (approximately .5cm long x 7mm diameter). Blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) will be collected during two conditions: short train sonification LIFUP and sham LIFUP: total time = 20min. Short train LIFUP (previously used in primary sensory cortices47 will be administered in 75 sonifications at 210 Kilohertz (KHz) frequency with pulse repetition frequency of 500 Hertz (Hz), 35mW/cm2, sonification duration 0.5s with 7s inter-stimulation interval. Sham LIFUP will involve the same procedures (e.g. participant provided the same instructions) except the sonification will not occur. Before and after completing the scan and a short break, these participants will receive short train LIFUP while they are administered a series of three computerized, amygdala-mediated emotion reactivity and regulation tasks. Given that routine clinical neuropsychological measures are designed to provide diagnostic information and are not sensitive or specific enough to precisely measure longitudinal emotional change related to an intervention, investigators will use validated experimental neurocognitive measures.

Participants will be blinded to whether or not the LIFUP transducer is on and, when on, what parameters are used. The investigator collecting the neuropsychological data will be blinded to which condition (LIFUP, sham) the participant completed during the session. The statistical analysts for both the neuropsychological and neuroimaging data will also be blinded to condition.

Low Intensity focused ultrasound pulsation will be administered to participants while they are in the fMRI scanner. Functional and perfusion MRI data will be collected before and after the sonication to allow for comparisons and investigation of pre and post sonication functional activation and connectivity.

While in the fMRI scanner, participants will have the ultrasound transducer attached to their head in the same manner as during the actual ultrasound sonication. However, during this portion of the experiment, the transducer will not be turned on. Previous, published experiments indicate that participants are unable to differentiate between when the transducer is on and off.

A low intensity, focused ultrasound pulsation causes mechanical changed without causing heating or cavitation.

Low Intensity Focused Ultrasound Pulsation Transducer is left in place on the participant's head but is not turned on during the sham procedure.

BOLD data will be collected in real-time during the ultrasound sonication, which occurs in on-off blocks. Analyses will assess the statistical relationship between BOLD signal in the brain and the time series (on vs off) of the ultrasound sonication.

Perfusion ASL fMRI data will be collected before and after sonication. Analyses will assess the statistical relationship between ASL signal throughout the brain pre and post sonication in a within subject repeated measures design.

Inclusion Criteria: Must be between 18-65 years of age Must be right handed English must be the dominant language Exclusion Criteria: contraindications for MRI (e.g. metal implants, pregnancy) history of head injury sufficient to warrant medical attention history of alcohol abuse or dependence history of substance abuse or dependence history of major psychiatric illness requiring treatment history of cancer or other neoplastic syndromes history of major neurologic illness (e.g. epilepsy).