Low Intensity Focused Ultrasound for Learning and Memory and Emotion Regulation

NCT03717922 | Completed Results FDA Device

• 1 other identifier: IRB#18-000104 / IRB#18-000978
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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. 1.Will LIFUP change brain activity in the targeted regions?
2. 2.Will LIFUP to the amygdala have an impact on anxiety and emotion regulation?
3. 3.Will LIFUP to the entorhinal cortex have an impact on memory performance?

Conditions

Brain Diseases; Memory Disorders; Learning Disabilities; Cognitive Impairment

Keywords

Ultrasound; MRI; Learning; Memory; Cognitive Neural Prosthetic

Outcome Measures

Primary Outcomes (3)

• Rey Auditory Verbal Learning Task

  The Rey Auditory Verbal Learning Task is an assessment of verbal memory in which a list of 15 words is presented 5 times and participants are asked to repeat all the words they can remember immediately after each list presentation. This is followed by presentation and recall of an interference list. Immediately after the interference trial, the participant is asked to recall the original list. Then, 20 minutes later, they are asked to recall the original list again (delayed recall). "Learning Trials Total": Total number of words learned / successfully recalled across the five learning trials plus the post-interference immediate recall trial. This score does not include the words recalled from the interference list. "Delayed Recall": Total number of words recalled during the delayed recall trial of the Rey Auditory Verbal Learning Task

  Pre-LIFUP and Post-LIFUP at Day 1 and Day 15

• State Trait Anxiety Inventory - State (STAIS)

  The "state" section of the State Trait Anxiety Inventory. This is a 20-question self-report assessment in which participants are asked about how they feel "right now, at this very moment" in order to assess current anxiety levels. Each item is scored on a scale of 1 to 4 points. The total assessment has a range of 20 to 80 points. Higher scores represent higher levels of anxiety.

  Pre-LIFUP and Post-LIFUP at Day 1 and Day 15

• Average Perfusion in Regions Of Interest

  Average perfusion in a given region of interest, as measured by arterial spin labeling. Percent change values calculated as ((Post LIFUP Perfusion - Pre LIFUP Perfusion)/Pre LIFUP Perfusion).

  Pre-LIFUP and Post-LIFUP at Day 1 and Day 15

Secondary Outcomes (2)

• Emotional Reactivity Task

  Pre-LIFUP and Post-LIFUP at Day 1 and Day 15

• Brief Visuospatial Memory Test

  Pre-LIFUP and Post-LIFUP at Day 1 and Day 15

Study Arms (2)

Amygdala first, then Entorhinal Cortex

EXPERIMENTAL

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.

Device: Low Intensity Focused Ultrasound Pulsation to Amygdala; Device: Low Intensity Focused Ultrasound Pulsation to Entorhinal Cortex

Entorhinal Cortex first, then Amygdala

EXPERIMENTAL

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.

Device: Low Intensity Focused Ultrasound Pulsation to Amygdala; Device: Low Intensity Focused Ultrasound Pulsation to Entorhinal Cortex

Interventions

Low Intensity Focused Ultrasound Pulsation to Amygdala 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.

Amygdala first, then Entorhinal Cortex; Entorhinal Cortex first, then Amygdala

Low Intensity Focused Ultrasound Pulsation to Entorhinal Cortex 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.

Amygdala first, then Entorhinal Cortex; Entorhinal Cortex first, then Amygdala

Eligibility Criteria

• Age: 35 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must be right handed
• English must be the dominant language

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of California, Los Angeles: lead

Study Sites (1)

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Brain Diseases; Memory Disorders; Learning Disabilities; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Central Nervous System Diseases; Nervous System Diseases; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Communication Disorders; Neurodevelopmental Disorders; Mental Disorders; Cognition Disorders; Neurocognitive Disorders

Results Point of Contact

• Title: Dr. Taylor P. Kuhn, PhD
• Organization: UCLA Psychiatry & Biobehavioral Sciences

tkuhn@mednet.ucla.edu

‭(310) 829-5968‬

Study Officials

• Taylor P Kuhn, PhD

  UCLA Longevity Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participants will be blinded to exactly when the transducer is turned on, and to the region being targeted at each visit. The individual collecting the neuropsychological data will be blinded to which condition (amygdala, entorhinal cortex) the participant completed during the session. The statistical analysts for both the neuropsychological and neuroimaging data will also be blinded to condition.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Adjunct Assistant Professor

Model Details: Participants will be assigned to both study arms; the order in which they complete the arms will be randomized and counterbalanced. The two visits will be spaced apart by 2 weeks.

Study Record Dates

• First Submitted: October 22, 2018
• First Posted: October 24, 2018
• Study Start: June 28, 2019
• Primary Completion: December 20, 2022
• Study Completion: December 20, 2022
• Last Updated: March 20, 2024
• Results First Posted: March 20, 2024

Record last verified: 2024-03

Locations

US (1)