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Low Intensity Focused Ultrasound for Learning and Memory (LIFUPMEM)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03717922
Recruitment Status : Not yet recruiting
First Posted : October 24, 2018
Last Update Posted : April 18, 2019
Sponsor:
Information provided by (Responsible Party):
Taylor Kuhn, University of California, Los Angeles

Brief Summary:
Hippocampus and 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 study focus on whether LIFUP can increased blood oxygen level dependent (BOLD) activation in the entorhinal cortex and functionally associated regions, whether this increased activation is greater using short train or long train LIFUP parameters, and whether this LIFUP-induced activation, when applied during learning, results in improved memory.

Condition or disease Intervention/treatment Phase
Brain Diseases Memory Disorders Learning Disabilities Cognitive Impairment Device: Low Intensity Focused Ultrasound Pulsation Device: SHAM Ultrasound Not Applicable

Detailed Description:
This proposal proposes the use of personalized neuronavigation, based on each participant's structural brain MRI, to aim LIFUP at the white matter underlying the entorhinal cortex in the pursuit of enhancement of learning and memory 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 enhancement of memory. Further, this is the first study to use LIFUP in (A) ventral cortical and hippocampal regions 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. 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 software60, the LIFUP transducer will be aimed at the white matter underlying the entorhinal cortex 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). BOLD fMRI will be collected during three conditions, randomized and counterbalanced across participants (with sham always separating the two LIFUP conditions: short train sonification LIFUP, sham LIFUP long train LIFUP: total time = 30min. Short train LIFUP (previously used in primary sensory cortices47 will be administered in 75 sonifications at 210 KHz frequency with pulse repetition frequency of 500Hz, 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 LIFUP47 while they are administered a series of three computerized, hippocampally-dependent episodic memory tasks. Given that routine clinical neuropsychological measures are designed to provide diagnostic information and are not sensitive or specific enough to precisely measure longitudinal cognitive change related to an intervention, we will use validated experimental neurocognitive measures.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description: 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.
Primary Purpose: Other
Official Title: Low Intensity Focused Ultrasound of Medial Temporal Lobe Regions for the Improvement of Learning and Memory
Estimated Study Start Date : May 15, 2019
Estimated Primary Completion Date : October 31, 2022
Estimated Study Completion Date : October 31, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Memory Ultrasound

Arm Intervention/treatment
Experimental: MRI ultrasound sonication
Low Intensity focused ultrasound pulsation will be administered to participants while they are in the fMRI scanner. Functional and perfusion MR data will be collected before and after the sonication to allow for comparisons and investigation of pre and post sonication functional activation and connectivity.
Device: Low Intensity Focused Ultrasound Pulsation
BOLD fMRI will be collected during two conditions (given that the timecourse of LIFUP related changes is unknown, sham will always precede the LIFUP condition). LIFUP (previously used in primary sensory cortices will be administered in 75 sonifications at 210 KHz frequency with pulse repetition frequency of 500Hz, 35mW/cm2, sonification duration 0.5s with 7s inter-stimulation intervals. Sham LIFUP will involve the same procedures (e.g. participant provided the same instructions) except the sonification will not occur.

Sham Comparator: Sham Ultrasound
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.
Device: SHAM Ultrasound
BOLD fMRI will be collected while the ultrasound trandsducer is not turned on. Participants are unable to tell whether the transducer is on or off.




Primary Outcome Measures :
  1. Rey Auditory Verbal Learning Task [ Time Frame: Day 1 ]
    Number of words learned across each learning trial and number of words recalled during the delayed recall trial will be compared before and after sonication for each participant in a within subject design.


Secondary Outcome Measures :
  1. BOLD fMRI Signal in Entorhinal Cortex [ Time Frame: Day 1 ]
    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.

  2. Perfusion ASL fMRI Signal throughout Brain [ Time Frame: Day 1 ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Must be between 35-65 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03717922


Contacts
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Contact: Taylor Kuhn, PhD 310-825-2283 tkuhn@mednet.ucla.edu
Contact: Malina Beatrice mbeatrice@mednet.ucla.edu

Sponsors and Collaborators
University of California, Los Angeles

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Responsible Party: Taylor Kuhn, Adjunct Assistant Professor, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT03717922    
Other Study ID Numbers: IRB#18-000104
First Posted: October 24, 2018    Key Record Dates
Last Update Posted: April 18, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Keywords provided by Taylor Kuhn, University of California, Los Angeles:
Ultrasound
MRI
Learning
Memory
Cognitive Neural Prosthetic
Additional relevant MeSH terms:
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Brain Diseases
Memory Disorders
Learning Disorders
Cognitive Dysfunction
Cognition Disorders
Neurocognitive Disorders
Mental Disorders
Central Nervous System Diseases
Nervous System Diseases
Neurobehavioral Manifestations
Neurologic Manifestations
Signs and Symptoms
Communication Disorders
Neurodevelopmental Disorders