<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04431011</url>
  </required_header>
  <id_info>
    <org_study_id>200105</org_study_id>
    <secondary_id>20-N-0105</secondary_id>
    <nct_id>NCT04431011</nct_id>
  </id_info>
  <brief_title>Layer-specific Contribution to Consolidation of Skill Learning in the Primary Motor Cortex</brief_title>
  <official_title>Layer-specific Contribution to Consolidation of Skill Learning in the Primary Motor Cortex</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Neurological Disorders and Stroke (NINDS)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      Training in a new motor skill often involves periods of active practice and periods of rest.&#xD;
      During early motor skill learning, improvements in performance usually happen during the&#xD;
      short rest periods between practice sessions. Researchers want to use improved imaging&#xD;
      techniques to study the contributions of specific parts of the brain to how people learn and&#xD;
      retain movement skills.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      To learn the part played by different layers in the brain in retaining a newly learned&#xD;
      movement skill.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      Healthy, right-handed, English-speaking people age 18-50.&#xD;
&#xD;
      Design:&#xD;
&#xD;
      Participants will be screened with:&#xD;
&#xD;
        -  Medical and neurological history&#xD;
&#xD;
        -  Medicine review&#xD;
&#xD;
        -  Physical exam&#xD;
&#xD;
        -  Neurological exam.&#xD;
&#xD;
      Participants may have 2 magnetic resonance imaging (MRI) scans of the brain. During the MRI,&#xD;
      they will lie in the scanner. The scanner makes noise. They will get earplugs.&#xD;
&#xD;
      Participants will have behavior testing. A specific order of keys will be displayed on a&#xD;
      computer screen. Participants will practice typing the keys with their left hand 36 times (in&#xD;
      10-second blocks). They will repeat this test with a random order of keys.&#xD;
&#xD;
      Participants will see single numbers displayed one after the other on the computer screen.&#xD;
      They will make single tap responses using the finger that corresponds with the number on the&#xD;
      screen.&#xD;
&#xD;
      Participants will have up to 4 study sessions. Each session will take about 5 hours....&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study Description:&#xD;
&#xD;
      Training on a novel motor skill often involves periods of active practice interspersed with&#xD;
      periods of rest. During early motor skill learning, performance improvements develop&#xD;
      primarily during short offline rest periods that occur between practice blocks. These&#xD;
      performance gains during rest have been referred to as 'micro-offline consolidation'. Primary&#xD;
      motor cortex (M1) is a crucial contributor to skill consolidation, however, due to the poor&#xD;
      spatial specificity and vascular biases of available imaging methods, the specific neural&#xD;
      mechanisms of consolidation in M1 are not known. Recent innovations in functional magnetic&#xD;
      resonance imaging (fMRI) have made it possible to measure functional changes across cortical&#xD;
      layers. This study will use these techniques to investigate the contributions of specific&#xD;
      cortical layers in M1 to motor skill learning and consolidation.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      The primary aim is to determine the correlation between activity in superficial M1 cortical&#xD;
      layers and behavioral gains during microoffline rest periods. Additionally, we will evaluate&#xD;
      the role of superficial and deep cortical layers of M1 in the consolidation of motor skill&#xD;
      learning. To address this question, we will measure neural activations across cortical&#xD;
      laminae in M1 while participants consolidate a newly acquired motor skill.&#xD;
&#xD;
      Endpoints:&#xD;
&#xD;
      The primary endpoint measures will be: 1) activity in superficial M1 cortical layers during&#xD;
      micro-offline rest periods, which will be measured using vascular space occupancy (VASO) MR&#xD;
      imaging and 2) behavioral gains during micro-offline rest periods measured as correct&#xD;
      sequence typing speed (sequences per second). The secondary endpoint measure will be the&#xD;
      ratio of activity between superficial and deep M1 layers during practice and during rest&#xD;
      periods compared to pre-learning and to post-learning rest and the localizing random&#xD;
      sequence.&#xD;
&#xD;
      Exploratory endpoints will include other fMRI measures that may relate learning with layer&#xD;
      activity. For example, we will use multivoxel pattern analysis (MVPA) of activation data to:&#xD;
      (a) gain insight into the presence of layer-specific reactivation of sequence task&#xD;
      performance during rest periods; and (b) investigate whether this reactivation predicts&#xD;
      learning.&#xD;
&#xD;
      Study Population:&#xD;
&#xD;
      45 Healthy participants (18-50 years of age)&#xD;
&#xD;
      Phase:&#xD;
&#xD;
      N/A&#xD;
&#xD;
      Description of Sites/Facilities Enrolling Participants:&#xD;
&#xD;
      This protocol utilizes the NIH Clinical Center Outpatient Clinic, and NMRF core facilities.&#xD;
&#xD;
      Intervention Study Duration:&#xD;
&#xD;
      24 months&#xD;
&#xD;
      Participant Duration:&#xD;
&#xD;
      Approximately 2-5 hours per session, for up to 4 sessions over a 1-4-day time period.&#xD;
&#xD;
      Study Description:&#xD;
&#xD;
      Training on a novel motor skill often involves periods of active practice interspersed with&#xD;
      periods of rest. During early motor skill learning, performance improvements develop&#xD;
      primarily during short offline rest periods that occur between practice blocks. These&#xD;
      performance gains during rest have been referred to as &quot;micro-offline consolidation&quot;. Primary&#xD;
      motor cortex (M1) is a crucial contributor to skill consolidation; however, due to the poor&#xD;
      spatial specificity and vascular biases of available imaging methods, the specific neural&#xD;
      mechanisms of consolidation in M1 are not known. Recent innovations in functional magnetic&#xD;
      resonance imaging (fMRI) have made it possible to measure functional changes across cortical&#xD;
      layers. This study will use these techniques to investigate the contributions of specific&#xD;
      cortical layers in M1 to motor skill learning and consolidation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 21, 2021</start_date>
  <completion_date type="Anticipated">April 1, 2025</completion_date>
  <primary_completion_date type="Anticipated">January 2, 2025</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>The primary aim is to determine the role of superficial and deep cortical layers of M1 in the consolidation of motor skill learning.</measure>
    <time_frame>4 years</time_frame>
    <description>To address this question, we will measure neural activations across cortical laminae in M1 while participants consolidate a newly acquired motor skill.</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Normal Physiology</condition>
  <arm_group>
    <arm_group_label>Participants</arm_group_label>
    <description>Healthy right-handed participants aged 18-50</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Healthy right-handed adults aged 18-50&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA:&#xD;
&#xD;
          -  Age 18-50&#xD;
&#xD;
          -  English speaking&#xD;
&#xD;
          -  Right-hand dominance (&gt;74 on Edinburgh Handedness Inventory)&#xD;
&#xD;
          -  Normal neurological examination&#xD;
&#xD;
          -  Willing and able to provide informed consent&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
          -  HCPS-affiliated NIH staff (i.e. - staff from our section).&#xD;
&#xD;
          -  Current pregnancy&#xD;
&#xD;
          -  Current or past history of use of antiepileptic drugs&#xD;
&#xD;
          -  Contraindications for MRI (such as certain implants, metal fragments or devices in the&#xD;
             body) as determined by the screening clinician&#xD;
&#xD;
          -  Severe or progressive neurological, psychological or medical condition&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Leonardo G Cohen, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Institute of Neurological Disorders and Stroke (NINDS)</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Tasneem F Malik, C.R.N.P.</last_name>
    <phone>(301) 451-1335</phone>
    <email>tasneem.malik@nih.gov</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Leonardo G Cohen, M.D.</last_name>
    <phone>(301) 496-9782</phone>
    <email>cohenl1@mail.nih.gov</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>National Institutes of Health Clinical Center</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)</last_name>
      <phone>800-411-1222</phone>
      <phone_ext>TTY8664111010</phone_ext>
      <email>prpl@cc.nih.gov</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2020-N-0105.html</url>
    <description>NIH Clinical Center Detailed Web Page</description>
  </link>
  <verification_date>February 3, 2023</verification_date>
  <study_first_submitted>June 12, 2020</study_first_submitted>
  <study_first_submitted_qc>June 13, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>September 9, 2023</last_update_submitted>
  <last_update_submitted_qc>September 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Healthy</keyword>
  <keyword>Learning Consolidation</keyword>
  <keyword>Brain</keyword>
  <keyword>Natural History</keyword>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04431011
org study id: 200105
secondary id: 20-N-0105
nct id: NCT04431011
lead sponsor: 
is fda regulated drug: No
Background:

      Training in a new motor skill often involves periods of active practice and periods of rest.
      During early motor skill learning, improvements in performance usually happen during the
      short rest periods between practice sessions. Researchers want to use improved imaging
      techniques to study the contributions of specific parts of the brain to how people learn and
      retain movement skills.

      Objective:

      To learn the part played by different layers in the brain in retaining a newly learned
      movement skill.

      Eligibility:

      Healthy, right-handed, English-speaking people age 18-50.

      Design:

      Participants will be screened with:

        -  Medical and neurological history

        -  Medicine review

        -  Physical exam

        -  Neurological exam.

      Participants may have 2 magnetic resonance imaging (MRI) scans of the brain. During the MRI,
      they will lie in the scanner. The scanner makes noise. They will get earplugs.

      Participants will have behavior testing. A specific order of keys will be displayed on a
      computer screen. Participants will practice typing the keys with their left hand 36 times (in
      10-second blocks). They will repeat this test with a random order of keys.

      Participants will see single numbers displayed one after the other on the computer screen.
      They will make single tap responses using the finger that corresponds with the number on the
      screen.

      Participants will have up to 4 study sessions. Each session will take about 5 hours....
Study Description:

      Training on a novel motor skill often involves periods of active practice interspersed with
      periods of rest. During early motor skill learning, performance improvements develop
      primarily during short offline rest periods that occur between practice blocks. These
      performance gains during rest have been referred to as 'micro-offline consolidation'. Primary
      motor cortex (M1) is a crucial contributor to skill consolidation, however, due to the poor
      spatial specificity and vascular biases of available imaging methods, the specific neural
      mechanisms of consolidation in M1 are not known. Recent innovations in functional magnetic
      resonance imaging (fMRI) have made it possible to measure functional changes across cortical
      layers. This study will use these techniques to investigate the contributions of specific
      cortical layers in M1 to motor skill learning and consolidation.

      Objectives:

      The primary aim is to determine the correlation between activity in superficial M1 cortical
      layers and behavioral gains during microoffline rest periods. Additionally, we will evaluate
      the role of superficial and deep cortical layers of M1 in the consolidation of motor skill
      learning. To address this question, we will measure neural activations across cortical
      laminae in M1 while participants consolidate a newly acquired motor skill.

      Endpoints:

      The primary endpoint measures will be: 1) activity in superficial M1 cortical layers during
      micro-offline rest periods, which will be measured using vascular space occupancy (VASO) MR
      imaging and 2) behavioral gains during micro-offline rest periods measured as correct
      sequence typing speed (sequences per second). The secondary endpoint measure will be the
      ratio of activity between superficial and deep M1 layers during practice and during rest
      periods compared to pre-learning and to post-learning rest and the localizing random
      sequence.

      Exploratory endpoints will include other fMRI measures that may relate learning with layer
      activity. For example, we will use multivoxel pattern analysis (MVPA) of activation data to:
      (a) gain insight into the presence of layer-specific reactivation of sequence task
      performance during rest periods; and (b) investigate whether this reactivation predicts
      learning.

      Study Population:

      45 Healthy participants (18-50 years of age)

      Phase:

      N/A

      Description of Sites/Facilities Enrolling Participants:

      This protocol utilizes the NIH Clinical Center Outpatient Clinic, and NMRF core facilities.

      Intervention Study Duration:

      24 months

      Participant Duration:

      Approximately 2-5 hours per session, for up to 4 sessions over a 1-4-day time period.

      Study Description:

      Training on a novel motor skill often involves periods of active practice interspersed with
      periods of rest. During early motor skill learning, performance improvements develop
      primarily during short offline rest periods that occur between practice blocks. These
      performance gains during rest have been referred to as "micro-offline consolidation". Primary
      motor cortex (M1) is a crucial contributor to skill consolidation; however, due to the poor
      spatial specificity and vascular biases of available imaging methods, the specific neural
      mechanisms of consolidation in M1 are not known. Recent innovations in functional magnetic
      resonance imaging (fMRI) have made it possible to measure functional changes across cortical
      layers. This study will use these techniques to investigate the contributions of specific
      cortical layers in M1 to motor skill learning and consolidation.
observational model: Cohort
time perspective: Cross-Sectional
measure: The primary aim is to determine the role of superficial and deep cortical layers of M1 in the consolidation of motor skill learning.
time frame: 4 years
description: To address this question, we will measure neural activations across cortical laminae in M1 while participants consolidate a newly acquired motor skill.
arm group label: Participants
description: Healthy right-handed participants aged 18-50
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Leonardo G Cohen, M.D.
role: Principal Investigator
affiliation: National Institute of Neurological Disorders and Stroke (NINDS)
last name: Tasneem F Malik, C.R.N.P.
phone: (301) 451-1335
email: tasneem.malik@nih.gov
last name: Leonardo G Cohen, M.D.
phone: (301) 496-9782
email: cohenl1@mail.nih.gov
facility: 
status: Recruiting
contact: 
country: United States
url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2020-N-0105.html
description: NIH Clinical Center Detailed Web Page
responsible party type: Sponsor