Low Intensity Focused Ultrasound for Learning and Memory and Emotion Regulation

NCT ID: NCT03717922

Last Updated: 2024-03-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-28
• Study Completion Date: 2022-12-20

Brief Summary

The goal of this clinical trial is to investigate the impact of low intensity focused ultrasound pulsation (LIFUP) to two different brain regions, the amygdala and entorhinal cortex, in older adults. The main questions it aims to answer are:

1. Will LIFUP change brain activity in the targeted regions?

2. Will LIFUP to the amygdala have an impact on anxiety and emotion regulation?

3. Will LIFUP to the entorhinal cortex have an impact on memory performance?

Participants will complete two in-person visits including neuropsychological testing, MRI of the brain, and LIFUP to the brain.

Detailed Description

Medial temporal lobe (MTL)-dependent memory is impacted by a wide range of psychiatric and neurologic conditions. These cognitive limitations often result in limited functional abilities for patients. Currently available pharmacologic and behavioral treatments are somewhat controversial and have minimal evidence-based effectiveness. Recently, deep brain stimulation was used to modulate MTL activity and subsequently improve memory performance. However, such implantable devices require neurosurgery with major associated health risk. At present, there are no publications reporting non-invasive neurostimulation targeting MTL regions to improve memory. The central hypothesis of this project is that non-invasive, low intensity focused ultrasound pulsation (LIFUP) can selectively increase regional MTL activity and thus be used as a cognitive neural prosthetic capable of improving memory performance. The aims of this portion of the study focus on whether LIFUP can increase blood oxygen level dependent (BOLD) activation and perfusion (measured by arterial spin labeling) in the entorhinal cortex and functionally associated regions, and whether LIFUP to the entorhinal cortex will result in improved memory.

The 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 investigators propose the use of low intensity focused ultrasound pulsation (LIFUP) to affect amygdala activity to improve emotion regulation. The aim of this portion of the study focuses on whether LIFUP can modulate blood oxygen level dependent (BOLD) activation and perfusion (measured by arterial spin labeling) in the amygdala and functionally associated regions, and whether LIFUP to the amygdala will result in changes to anxiety levels and emotion regulation.

This study will be conducted using a crossover design in which each participant will complete two visits spaced two weeks apart. At one visit, they will receive LIFUP sonication (with parameters hypothesized to be inhibitory) to the right amygdala, and at the other, they will receive sonication (with parameters hypothesized to be excitatory) to the left entorhinal cortex. The order of conditions will be randomized and counterbalanced across participants. Participants will be blinded to condition order, and all other testing will be conducted the same at both visits. This design will allow us to test the effects of two potentially clinically-relevant targets for LIFUP, and will allow us to determine whether observed effects on brain activity, learning and memory, and emotion regulation are target-specific by comparing results between the two LIFUP paradigms.

Conditions

Brain Diseases; Memory Disorders; Learning Disabilities; Cognitive Impairment

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: DOUBLE

Study Groups

Amygdala first, then Entorhinal Cortex

Low Intensity focused ultrasound pulsation (LIFUP) will be administered to the amygdala while participants are in the MRI scanner. Then, 2 weeks later, entorhinal cortex LIFUP will be administered.

Group Type: EXPERIMENTAL

Low Intensity Focused Ultrasound Pulsation to Amygdala

Intervention Type: DEVICE

Low intensity focused ultrasound pulsation will be administered to the amygdala in 10 sonications at 650kHz, ispta 720mW/cm, pulse repetition frequency 10Hz, duty cycle 5% duration 30s, with 30s spacing between sonications. Prior to receiving LIFUP sonication, 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 T1 image will verify the position of the LIFUP transducer and allow for estimation of the spatial location of the sonication beam focus. If needed, adjustments to transducer placement will be made to ensure that the beam focus is correctly aimed; an additional T1 will be collected after adjustment. Once correct placement of the transducer has been confirmed, LIFUP will be administered.

Low Intensity Focused Ultrasound Pulsation to Entorhinal Cortex

Intervention Type: DEVICE

Low intensity focused ultrasound pulsation will be administered to the entorhinal cortex in 10 sonications at 650kHz, ispta 720mW/cm, pulse repetition frequency 100Hz, duty cycle 5% duration 30s, with 30s spacing between sonications. Prior to receiving LIFUP sonication, the LIFUP transducer will be aimed at the entorhinal cortex and gently strapped in place to their head. Participants will then return to the scanner where a T1 image will verify the position of the LIFUP transducer and allow for estimation of the spatial location of the sonication beam focus. If needed, adjustments to transducer placement will be made to ensure that the beam focus is correctly aimed; an additional T1 will be collected after adjustment. Once correct placement of the transducer has been confirmed, LIFUP will be administered.

Entorhinal Cortex first, then Amygdala

Low Intensity focused ultrasound pulsation (LIFUP) will be administered to the entorhinal cortex while participants are in the MRI scanner. Then, 2 weeks later, amygdala LIFUP will be administered.

Group Type: EXPERIMENTAL

Low Intensity Focused Ultrasound Pulsation to Amygdala

Intervention Type: DEVICE

Low intensity focused ultrasound pulsation will be administered to the amygdala in 10 sonications at 650kHz, ispta 720mW/cm, pulse repetition frequency 10Hz, duty cycle 5% duration 30s, with 30s spacing between sonications. Prior to receiving LIFUP sonication, 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 T1 image will verify the position of the LIFUP transducer and allow for estimation of the spatial location of the sonication beam focus. If needed, adjustments to transducer placement will be made to ensure that the beam focus is correctly aimed; an additional T1 will be collected after adjustment. Once correct placement of the transducer has been confirmed, LIFUP will be administered.

Low Intensity Focused Ultrasound Pulsation to Entorhinal Cortex

Intervention Type: DEVICE

Low intensity focused ultrasound pulsation will be administered to the entorhinal cortex in 10 sonications at 650kHz, ispta 720mW/cm, pulse repetition frequency 100Hz, duty cycle 5% duration 30s, with 30s spacing between sonications. Prior to receiving LIFUP sonication, the LIFUP transducer will be aimed at the entorhinal cortex and gently strapped in place to their head. Participants will then return to the scanner where a T1 image will verify the position of the LIFUP transducer and allow for estimation of the spatial location of the sonication beam focus. If needed, adjustments to transducer placement will be made to ensure that the beam focus is correctly aimed; an additional T1 will be collected after adjustment. Once correct placement of the transducer has been confirmed, LIFUP will be administered.

Interventions

Low Intensity Focused Ultrasound Pulsation to Amygdala

Low intensity focused ultrasound pulsation will be administered to the amygdala in 10 sonications at 650kHz, ispta 720mW/cm, pulse repetition frequency 10Hz, duty cycle 5% duration 30s, with 30s spacing between sonications. Prior to receiving LIFUP sonication, 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 T1 image will verify the position of the LIFUP transducer and allow for estimation of the spatial location of the sonication beam focus. If needed, adjustments to transducer placement will be made to ensure that the beam focus is correctly aimed; an additional T1 will be collected after adjustment. Once correct placement of the transducer has been confirmed, LIFUP will be administered.

Intervention Type: DEVICE

Low Intensity Focused Ultrasound Pulsation to Entorhinal Cortex

Low intensity focused ultrasound pulsation will be administered to the entorhinal cortex in 10 sonications at 650kHz, ispta 720mW/cm, pulse repetition frequency 100Hz, duty cycle 5% duration 30s, with 30s spacing between sonications. Prior to receiving LIFUP sonication, the LIFUP transducer will be aimed at the entorhinal cortex and gently strapped in place to their head. Participants will then return to the scanner where a T1 image will verify the position of the LIFUP transducer and allow for estimation of the spatial location of the sonication beam focus. If needed, adjustments to transducer placement will be made to ensure that the beam focus is correctly aimed; an additional T1 will be collected after adjustment. Once correct placement of the transducer has been confirmed, LIFUP will be administered.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• 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).

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of California, Los Angeles

OTHER

Sponsor Role: lead

Responsible Party

Taylor Kuhn

Adjunct Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Taylor P Kuhn, PhD

Role: PRINCIPAL_INVESTIGATOR

UCLA Longevity Center

Locations

University of California, Los Angeles

Los Angeles, California, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IRB#18-000104 / IRB#18-000978

Identifier Type: -

Identifier Source: org_study_id

NCT03782194

Identifier Type: -

Identifier Source: nct_alias