xml: <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/NCT05966532</url>
    </required_header>
    <id_info>
      <org_study_id>STU-2021-1131</org_study_id>
      <nct_id>NCT05966532</nct_id>
    </id_info>
    <brief_title>Emotional Cognition: Establishing Constructs and Neural-Behavioral Mechanisms in Older Adults With Depression</brief_title>
    <acronym>ENSURE</acronym>
    <official_title>Emotional Cognition: Establishing Constructs and Neural-Behavioral Mechanisms in Older Adults With Depression (ENSURE; R21 MH130870)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Texas Southwestern Medical Center</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>The University of Texas at Arlington</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>National Institute of Mental Health (NIMH)</agency>
        <agency_class>NIH</agency_class>
      </collaborator>
    </sponsors>
    <source>University of Texas Southwestern Medical Center</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This is a cross-sectional pilot study designed to establish hot and cold cognitive functions&#xD;
        and underlying neurocircuitry in older adults with MDD. The investigators will study 60&#xD;
        participants aged 21-80 years old with MDD. All participants will undergo clinical and&#xD;
        neurocognitive assessment, and Magnetoencephalography (MEG)/Magnetic resonance imaging (MRI)&#xD;
        procedures at one time point. The investigators will also enroll 60 demographically matched&#xD;
        comparable, never-depressed healthy participants (controls) to establish cognitive&#xD;
        benchmarks. Healthy controls will complete clinical and neurocognitive measures at one time&#xD;
        point. To attain a balanced sample of adults across the lifespan, the investigators will&#xD;
        enroll participants such that each age epoch (e.g., 21-30, 31-40, etc.) has a total of ten&#xD;
        subjects (n=10) in both the healthy control cohort and depressed cohort.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Major depressive disorder (MDD) is a common, chronic, and disabling disorder that affects&#xD;
        individuals across the lifespan. Research has consistently found that a core domain of MDD is&#xD;
        cognitive dysfunction, with the majority of clinical research focusing on cold cognitive&#xD;
        functions such as attention, memory, and executive function. However, emotional &quot;hot&quot;&#xD;
        cognitive impairments are also frequently observed in domains such as emotion processing,&#xD;
        impulsivity, reward processing, and social cognition, and as with cold cognitive processes,&#xD;
        have been implicated in both disease course and treatment outcomes.&#xD;
  &#xD;
        The nomenclature of &quot;cold&quot; and &quot;hot&quot; cognitive function has been used to differentiate&#xD;
        between those functions that are less influenced by emotional stimuli and/or processes (i.e.,&#xD;
        &quot;cold&quot; cognitive function) and those that have an emotional component and/or influence (i.e.,&#xD;
        &quot;hot&quot; cognitive function). The delineation of cold and hot cognitive function has critical&#xD;
        implications for new mechanistic explanations and targeted antidepressant treatment&#xD;
        development. Other researchers have proposed a testable cognitive neuropsychological model of&#xD;
        MDD that describes the interaction of both cold and hot cognitive functions, underlying&#xD;
        neurocircuitry, and proposed associated treatments.&#xD;
  &#xD;
        Despite ample evidence of impairments associated with hot cognitive processes, behaviors, and&#xD;
        associated neural circuity, there is significantly limited information regarding hot&#xD;
        cognitive function in adults across the lifespan with MDD. Prior research has been limited by&#xD;
        1) measurement of only one or two hot cognitive functions, 2) no integration of cold and hot&#xD;
        cognitive function assessment, and 3) sparse information on hot cognition and associated&#xD;
        neurocircuitry in adults over the age of 60. Given the importance of cognitive dysfunction&#xD;
        and aging on disease course and overall functioning in MDD, it is critical to identify&#xD;
        mechanisms of action and targeted treatment approaches that will improve cognition to achieve&#xD;
        the ultimate goal of improving overall disease course, functioning, and quality of life.&#xD;
        Identification of brain network alterations associated with particular hot cognitive&#xD;
        functions and treatments that modify these regions will move us closer toward personalized&#xD;
        medicine and improved patient outcomes. A first critical step in this endeavor is to better&#xD;
        characterize hot cognitive dysfunctions in MDD, their relationship to cold cognitive&#xD;
        dysfunctions, potential effects of age on these dysfunctions, and information on the&#xD;
        associated underlying neurocircuitry in older adults.&#xD;
  &#xD;
        In the proposed preliminary study, 60 adults across the lifespan with MDD will complete&#xD;
        clinical and cognitive measures, and MEG at one time-point. The investigators will also&#xD;
        enroll 60 demographically matched comparable never-depressed healthy controls to establish&#xD;
        cognitive benchmarks. The investigators will use existing healthy control data to establish&#xD;
        resting-state MEG benchmarks. The study aims are:&#xD;
  &#xD;
        Aim 1. Establish and integrate hot and cold cognitive dysfunction in adults across the&#xD;
        lifespan.&#xD;
  &#xD;
        H1.1. Adults with MDD compared to healthy controls will have significantly greater hot and&#xD;
        cold cognitive dysfunction as measured by a Neuropsychological Test Battery to Evaluate&#xD;
        Emotion, Motivation, Impulsivity, and Social Cognition (EMOTICOM) and the California Verbal&#xD;
        Learning Test - Third Edition (CVLT-3)/Delis-Kaplan Executive Function System (D-KEFS),&#xD;
        respectively.&#xD;
  &#xD;
        H1.2. Age will be associated with greater hot and cold cognitive dysfunction.&#xD;
  &#xD;
        Aim 2. Establish and compare specific brain networks underlying hot and cold cognitive tasks.&#xD;
  &#xD;
        H2.1. EMOTICOM Emotion Recognition and Categorization task scores will be associated with&#xD;
        resting-state MEG connectivity metrics in the salience network,&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">December 2025</completion_date>
    <primary_completion_date type="Anticipated">August 2025</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Case-Control</observational_model>
      <time_perspective>Cross-Sectional</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Emotion Processing Domain: Emotional Intensity Morphing Task</measure>
      <time_frame>baseline visit, total time= 5 minutes</time_frame>
      <description>Assesses the point of intensity for fascial emotion recognition. Faces are presented with slowly morphing emotional expressions (e.g., happy, sad, angry) that increases (point of detection) or decrease (emotion no longer perceived).&#xD;
  Intensity threshold for each emotion and each condition (i.e., increases and decrease).</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Emotion Processing Domain: Emotional Recognition Task-Eyes</measure>
      <time_frame>baseline visit, total time= 12 minutes</time_frame>
      <description>Assesses accuracy and affective bias of emotional recognition. Participants identify emotion(e.g., happy, sad) based on 250ms presentation of eyes only.&#xD;
  Hit rate (i.e., correct identification of each emotion).</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Emotion Processing Domain: Face Affective Go No-Go</measure>
      <time_frame>baseline visit, total time= 6 minutes</time_frame>
      <description>Assesses affective bias associated with emotional faces. Participant must identify the target facial emotion (e.g., happy, sad), while ignoring other emotions.&#xD;
  Discrimination accuracy (d-prime score for each emotion).</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Reward Processing and Learning: Adapted Cambridge Gambling Task</measure>
      <time_frame>baseline visit, total time= 10 minutes</time_frame>
      <description>Assesses value-based choice. Participants bet on expected outcomes when presented with a colored (orange, purple) roulette wheel with the proportions of each color indicating 1 of 5 levels of certain/uncertain outcomes in the context of win or loss conditions.&#xD;
  Risk Adjustment scores based on level of probability of win or loss.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Reward Processing and Learning: Reinforcement Learning Task</measure>
      <time_frame>baseline visit, total time= 10 minutes</time_frame>
      <description>Assesses reward and punishment learning. Participants are shown colored circles and choose the one they believe is more likely to win money. There are two conditions (no lose and no win).&#xD;
  Learning rate (alpha) based on how fast participant learns new information (both win and loss).&#xD;
  Risk Adjustment scores based on level of probability of win or loss.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Impulsivity: Discounting Task</measure>
      <time_frame>baseline visit, total time= 7 minutes</time_frame>
      <description>Assesses rate of discounting across 5 levels of delay and 5 of probability. Participants decide between a standard fixed amount vs an immediately available alternative.&#xD;
  Indifference points for each length of delay/degree of uncertainly, noted by area under the curve.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Social Cognition: Moral Emotions Task</measure>
      <time_frame>baseline visit, total time= 13 minutes</time_frame>
      <description>Assesses moral judgment/emotional reactions to social situations. Cartoons depict characters intentionally or unintentionally harming one another. Participants rate feelings (e.g., guilt, shame) as either the victim or antagonizer in the scenario.&#xD;
  Average ratings of guilt and shame in each scenario (victim or antagonizer).</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Montreal Cognitive Assessment (MoCA): Cold Cognitive Function Testing.</measure>
      <time_frame>Day 1/baseline</time_frame>
      <description>Description: Cold cognitive function will be measured by Montreal Cognitive Assessment (MoCA). MoCA assesses multiple cognitive domains: attention, concentration, executive functions, memory, language, visuospatial skills, abstraction, calculation and orientation. Possible scores range from 0-30, where score ≥ 26 is considered to be normal.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Everyday Cognition (ECog): Cold Cognitive Function Testing</measure>
      <time_frame>Day 1</time_frame>
      <description>Cold cognitive function will be measured by Everyday Cognition (ECog), ECog scale is a validated informant-rated questionnaire that includes one global factor and six domain-specific factors: 6 domains: everyday memory, language, visuospatial and perceptual abilities, planning, organization, and divided attention. Each item is scored based on a four-point scale: 1 = better or no change compared to 10 years earlier; 2 =questionable/occasionally worse; 3 = consistently a little worse; 4 = consistently much worse. The total score will be calculated as the sum of all 39 items. Higher scores indicates worse daily function</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Test of Premorbid Function (TOPF): Cold Cognitive Function Testing</measure>
      <time_frame>Day 1</time_frame>
      <description>Cold cognitive function will be measured by Test of Premorbid Function (TOPF), TOPF estimates an individual's pre-morbid cognitive and memory functioning. Possible scores range from 80 - 130, where higher scores indicate better pre-morbid cognitive functioning.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>California Verbal Learning Test-3 (CVLT-3): Cold Cognitive Function Testing</measure>
      <time_frame>Day 1</time_frame>
      <description>Cold cognitive function will be measured by California Verbal Learning Test-3 (CVLT-3), CVLT-3 measures verbal learning and memory. Possible scores range from 0 - 16, where higher scores indicate better performance.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Delis-Kaplan Executive Function System (DKEF)-Color-Word Interference: Cold Cognitive Function Testing</measure>
      <time_frame>Day 1</time_frame>
      <description>Cold cognitive function will be measured by Delis-Kaplan Executive Function System (D-KEF) Color-Word Interference, it is made up of color naming, word reading, and inhibition, is measured in seconds, a smaller number represents a better outcome.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Delis-Kaplan Executive Function System (DKEF)-Tower Test: Cold Cognitive Function Testing</measure>
      <time_frame>Day 1</time_frame>
      <description>Cold cognitive function will be measured by D-KEF Tower test, it is a measure of executive function. Total achievement scores indicate the highest score participants scored on the test. Possible score range from 0 - 30, higher scores indicate better performance.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Delis-Kaplan Executive Function System (D-KEF)-Verbal Fluency Performance: Cold Cognitive Function Testing</measure>
      <time_frame>Day 1</time_frame>
      <description>Cold cognitive function will be measured by D-KEFs Verbal Fluency Test, made up of letter fluency and category fluency, is measured by number of responses, a larger number represents a better outcome.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>MEG: Magnetoencephalography</measure>
      <time_frame>Baseline Day1</time_frame>
      <description>Six minutes, eyes-open resting-state scan will be completed. Before the scan, five coils will be secured to the participant's head and 3D digitizer will be used to map the location of the coils, fiducials, and scalp surface, MEG data will be co-registered to their high-resolution structural T1-weighted MRI. This will provide a four-dimensional (4D) image of brain activity, similar to Functional magnetic resonance imaging (fMRI).</description>
    </secondary_outcome>
    <number_of_groups>2</number_of_groups>
    <enrollment type="Anticipated">138</enrollment>
    <condition>Major Depressive Disorder (MDD)</condition>
    <condition>Healthy Adult Volunteer</condition>
    <arm_group>
      <arm_group_label>Major Depressive Disorder (MDD) Participants:</arm_group_label>
      <description>Male and female subjects&#xD;
  Age between 21-80 years old&#xD;
  Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) diagnosis of major depressive disorder (MDD) based on Mini Neuropsychiatric Interview&#xD;
  Inventory of Depressive Symptomatology; Clinician Rated version (IDS-C) total score &gt; 14&#xD;
  Able to read, write, and comprehend English&#xD;
  Provide informed consent; willing to comply with study protocol.&#xD;
  Note: For individuals with MDD diagnosis: As part of the screening procedures, the Mini International Neuropsychiatric Interview (MINI-7.0 for DSM-5) will be conducted to determine eligibility. This is related to Inclusion Criteria #3.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Healthy Volunteer Participants:</arm_group_label>
      <description>Male and female subjects&#xD;
  Age between 21-80 years old&#xD;
  Able to read, write, and comprehend English&#xD;
  Provide informed consent; willing to comply with study protocol</description>
    </arm_group>
    <intervention>
      <intervention_type>Behavioral</intervention_type>
      <intervention_name>Hot Cognitive Task</intervention_name>
      <description>Emotion processing:&#xD;
  Participants will be shown a series of faces that appear quickly and be asked to identify what emotion is shown.&#xD;
  Participants will be shown a face of an emotion and indicate if participant can see the emotion changing.&#xD;
  Participant will be shown a series of emotions and asked to respond to only a specific emotion.&#xD;
  Motivation reward and processing:&#xD;
  Participant will play with a simulated roulette and make a bet to evaluate their decision-making behavior.&#xD;
  Participant will be shown colored circles and choose the one more likely to win money.&#xD;
  Impulsivity:&#xD;
  • Participant will be shown a series of stimuli where they will be asked to respond to the correct stimulus.&#xD;
  Social cognition:&#xD;
  Participant will be shown a series of moral situations in which a character is accidentally or intentionally harmed and be asked to rate the degree of guilt from the perspective of the victim or perpetrator.</description>
      <arm_group_label>Healthy Volunteer Participants:</arm_group_label>
      <arm_group_label>Major Depressive Disorder (MDD) Participants:</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Behavioral</intervention_type>
      <intervention_name>Cold cognitive tasks</intervention_name>
      <description>Montreal Cognitive Assessment (MoCA) - This will ask participants questions related to their cognition such as visuospatial skills, naming, memory, attention, language, and recall.&#xD;
  Measurement of Everyday Cognition (ECog) - This scale will ask participants about their everyday memory, language, visuospatial ability, organization, and divided attention.&#xD;
  Test of Premorbid Function (TOPF) - This test will evaluate memory performance and abilities of stud participants before onset pre-morbid status.&#xD;
  California Verbal Learning Test -3rd Edition (CVLT-3) -This test will measure verbal learning and memory of study participants.&#xD;
  Three tests from the Delis-Kaplan Executive Function System (D-KEFS; Verbal Fluency, Color-Word Interference, and Tower Tests). -These measures assess word finding and problem-solving ability.</description>
      <arm_group_label>Healthy Volunteer Participants:</arm_group_label>
      <arm_group_label>Major Depressive Disorder (MDD) Participants:</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Structural magnetic resonance imaging (sMRI)</intervention_name>
      <description>This is a non-invasive procedure to assess the structure and function of participant's brain. Structural neuroanatomical data will be acquired using structural magnetic resonance. Imaging (sMRI) with the University of Texas Southwestern (UTSW) 3T (three Tesla field) Siemens Prisma MRI scanner. Prior to participation, the investigator's team will screen participant's to ensure eligibility to participate in the sMRI scan.</description>
      <arm_group_label>Major Depressive Disorder (MDD) Participants:</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Magnetoencephalography imaging (MEG)</intervention_name>
      <description>This is a non-invasive procedure to measure participant's brain activity. Participants will be sitting inside the machine in a chamber, with more space than a traditional MRI machine. A hat will be placed on top of participant's head which records their brain activity. Resting-state MEG recordings will occur in a three-layer magnetically shielded room (MSR) following our UTSW Advanced Neuroscience Imaging Research (ANSIR) established procedures. Before the scan, five coils will be secured to participant's head and a three-dimensional (3D) digitizer will be used to map the location of the coils, fiducials, and scalp surface. During recording, an electric current with a unique frequency label (i.e., 320 Hz) will be fed to each coil, which will permit real time head location tracking and subsequent offline head motion correction.</description>
      <arm_group_label>Major Depressive Disorder (MDD) Participants:</arm_group_label>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          Investigators will study 60 participants aged 21-80 years old with major depressive&#xD;
          disorder (MDD). Only participants with MDD will undergo clinical and neurocognitive&#xD;
          assessment, and MEG/MRI procedures at one time point. Investigators team will also enroll&#xD;
          60 demographically matched comparable, never-depressed healthy participants (controls) to&#xD;
          establish cognitive benchmarks. Healthy controls will complete clinical and neurocognitive&#xD;
          measures at one time point. To attain a balanced sample of adults across the lifespan,&#xD;
          research teams will enroll participants such that each age epoch (e.g., 21-30, 31-40, etc.)&#xD;
          has a total of ten subjects (n=10) in both the healthy control cohort and depressed cohort.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Male and female participants&#xD;
  &#xD;
            2. Age between 21-80 years old&#xD;
  &#xD;
            3. DSM-5 diagnosis of major depressive disorder (MDD) based on Mini Neuropsychiatric&#xD;
               Interview&#xD;
  &#xD;
            4. Inventory of Depressive Symptomatology-Clinician Rated version (IDS-C) total score &gt;&#xD;
               14&#xD;
  &#xD;
            5. Able to read, write, and comprehend English&#xD;
  &#xD;
            6. Provide informed consent; willing to comply with study protocol&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. History of bipolar disorder, schizophrenia, or schizoaffective disorder&#xD;
  &#xD;
            2. Presence of psychotic features&#xD;
  &#xD;
            3. Lifetime central nervous system (CNS) disease (including head injury with loss of&#xD;
               consciousness &gt; 5 minutes)&#xD;
  &#xD;
            4. History of neurodevelopmental disorder (e.g., Autism spectrum disorder)&#xD;
  &#xD;
            5. History of medical conditions that can affect neurocognitive function as well as be&#xD;
               confounded with age (e.g., thyroid disease, endocrine illnesses)&#xD;
  &#xD;
            6. History and current use of hormonal replacement therapy&#xD;
  &#xD;
            7. Women who are pregnant&#xD;
  &#xD;
            8. Current use of medications with known impacts on neurocognitive function (e.g.,&#xD;
               acetylcholinesterase inhibitors, amphetamine, methylphenidate, vortioxetine,&#xD;
               sedatives)&#xD;
  &#xD;
            9. Alcohol/substance use disorder within past 3 months&#xD;
  &#xD;
           10. DSM-5 diagnosis of major cognitive impairment and Measurement of Everyday Cognition&#xD;
               (ECog) total score &gt; 4&#xD;
  &#xD;
           11. Current sensory or physical impairment that interferes with testing.&#xD;
  &#xD;
           12. Contraindication to MRI and MEG (only for depressed participants) (e.g., any&#xD;
               electronic / metallic implants near or within the head or body, claustrophobia)&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>21 Years</minimum_age>
      <maximum_age>80 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Shawn McClintock, PhD</last_name>
      <phone>214-648-2806</phone>
      <email>shawn.mcclintock@utsouthwestern.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Aatika Parwaiz, MPH</last_name>
      <phone>214-648-2806</phone>
      <email>aatika.parwaiz@utsouthwestern.edu</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>University of Texas Arlington</name>
        <address>
          <city>Arlington</city>
          <state>Texas</state>
          <zip>76010</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Tracy Greer, PhD</last_name>
        <phone>817-272-1063</phone>
        <email>tracy.greer@uta.edu</email>
      </contact>
      <contact_backup>
        <last_name>Kaitlin Killian</last_name>
        <phone>817-272-1063</phone>
        <email>kaitlin.killian@mavs.uta.edu</email>
      </contact_backup>
      <investigator>
        <last_name>Tracy Greer, PhD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>University of Texas Southwestern Medical Center</name>
        <address>
          <city>Dallas</city>
          <state>Texas</state>
          <zip>75390-9127</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Shawn McClintock, PhD</last_name>
        <phone>214-648-2806</phone>
        <email>shawn.mcclintock@utsouthwestern.edu</email>
      </contact>
      <contact_backup>
        <last_name>Aatika Parwaiz, MPH</last_name>
        <phone>214-648-2806</phone>
        <email>aatika.parwaiz@utsouthwestern.edu</email>
      </contact_backup>
      <investigator>
        <last_name>Shawn McClintock, PhD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <link>
      <url>https://www.frontiersin.org/articles/10.3389/fnbeh.2016.00025/full</url>
      <description>EMOTICOM: A Neuropsychological Test Battery to Evaluate Emotion, Motivation, Impulsivity, and Social Cognition</description>
    </link>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>July 21, 2023</study_first_submitted>
    <study_first_submitted_qc>July 21, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">July 28, 2023</study_first_posted>
    <last_update_submitted>September 14, 2023</last_update_submitted>
    <last_update_submitted_qc>September 14, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 18, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>University of Texas Southwestern Medical Center</investigator_affiliation>
      <investigator_full_name>Shawn McClintock</investigator_full_name>
      <investigator_title>Professor</investigator_title>
    </responsible_party>
    <keyword>Emotional Cognition</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Depressive Disorder</mesh_term>
      <mesh_term>Depressive Disorder, Major</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05966532
  org study id: STU-2021-1131
  nct id: NCT05966532
  lead sponsor: 
  collaborator: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This is a cross-sectional pilot study designed to establish hot and cold cognitive functions
        and underlying neurocircuitry in older adults with MDD. The investigators will study 60
        participants aged 21-80 years old with MDD. All participants will undergo clinical and
        neurocognitive assessment, and Magnetoencephalography (MEG)/Magnetic resonance imaging (MRI)
        procedures at one time point. The investigators will also enroll 60 demographically matched
        comparable, never-depressed healthy participants (controls) to establish cognitive
        benchmarks. Healthy controls will complete clinical and neurocognitive measures at one time
        point. To attain a balanced sample of adults across the lifespan, the investigators will
        enroll participants such that each age epoch (e.g., 21-30, 31-40, etc.) has a total of ten
        subjects (n=10) in both the healthy control cohort and depressed cohort.
  Major depressive disorder (MDD) is a common, chronic, and disabling disorder that affects
        individuals across the lifespan. Research has consistently found that a core domain of MDD is
        cognitive dysfunction, with the majority of clinical research focusing on cold cognitive
        functions such as attention, memory, and executive function. However, emotional "hot"
        cognitive impairments are also frequently observed in domains such as emotion processing,
        impulsivity, reward processing, and social cognition, and as with cold cognitive processes,
        have been implicated in both disease course and treatment outcomes.
  
        The nomenclature of "cold" and "hot" cognitive function has been used to differentiate
        between those functions that are less influenced by emotional stimuli and/or processes (i.e.,
        "cold" cognitive function) and those that have an emotional component and/or influence (i.e.,
        "hot" cognitive function). The delineation of cold and hot cognitive function has critical
        implications for new mechanistic explanations and targeted antidepressant treatment
        development. Other researchers have proposed a testable cognitive neuropsychological model of
        MDD that describes the interaction of both cold and hot cognitive functions, underlying
        neurocircuitry, and proposed associated treatments.
  
        Despite ample evidence of impairments associated with hot cognitive processes, behaviors, and
        associated neural circuity, there is significantly limited information regarding hot
        cognitive function in adults across the lifespan with MDD. Prior research has been limited by
        1) measurement of only one or two hot cognitive functions, 2) no integration of cold and hot
        cognitive function assessment, and 3) sparse information on hot cognition and associated
        neurocircuitry in adults over the age of 60. Given the importance of cognitive dysfunction
        and aging on disease course and overall functioning in MDD, it is critical to identify
        mechanisms of action and targeted treatment approaches that will improve cognition to achieve
        the ultimate goal of improving overall disease course, functioning, and quality of life.
        Identification of brain network alterations associated with particular hot cognitive
        functions and treatments that modify these regions will move us closer toward personalized
        medicine and improved patient outcomes. A first critical step in this endeavor is to better
        characterize hot cognitive dysfunctions in MDD, their relationship to cold cognitive
        dysfunctions, potential effects of age on these dysfunctions, and information on the
        associated underlying neurocircuitry in older adults.
  
        In the proposed preliminary study, 60 adults across the lifespan with MDD will complete
        clinical and cognitive measures, and MEG at one time-point. The investigators will also
        enroll 60 demographically matched comparable never-depressed healthy controls to establish
        cognitive benchmarks. The investigators will use existing healthy control data to establish
        resting-state MEG benchmarks. The study aims are:
  
        Aim 1. Establish and integrate hot and cold cognitive dysfunction in adults across the
        lifespan.
  
        H1.1. Adults with MDD compared to healthy controls will have significantly greater hot and
        cold cognitive dysfunction as measured by a Neuropsychological Test Battery to Evaluate
        Emotion, Motivation, Impulsivity, and Social Cognition (EMOTICOM) and the California Verbal
        Learning Test - Third Edition (CVLT-3)/Delis-Kaplan Executive Function System (D-KEFS),
        respectively.
  
        H1.2. Age will be associated with greater hot and cold cognitive dysfunction.
  
        Aim 2. Establish and compare specific brain networks underlying hot and cold cognitive tasks.
  
        H2.1. EMOTICOM Emotion Recognition and Categorization task scores will be associated with
        resting-state MEG connectivity metrics in the salience network,
  observational model: Case-Control
  time perspective: Cross-Sectional
  measure: Emotion Processing Domain: Emotional Intensity Morphing Task
  time frame: baseline visit, total time= 5 minutes
  description: Assesses the point of intensity for fascial emotion recognition. Faces are presented with slowly morphing emotional expressions (e.g., happy, sad, angry) that increases (point of detection) or decrease (emotion no longer perceived).
  Intensity threshold for each emotion and each condition (i.e., increases and decrease).
  measure: Emotion Processing Domain: Emotional Recognition Task-Eyes
  time frame: baseline visit, total time= 12 minutes
  description: Assesses accuracy and affective bias of emotional recognition. Participants identify emotion(e.g., happy, sad) based on 250ms presentation of eyes only.
  Hit rate (i.e., correct identification of each emotion).
  measure: Emotion Processing Domain: Face Affective Go No-Go
  time frame: baseline visit, total time= 6 minutes
  description: Assesses affective bias associated with emotional faces. Participant must identify the target facial emotion (e.g., happy, sad), while ignoring other emotions.
  Discrimination accuracy (d-prime score for each emotion).
  measure: Reward Processing and Learning: Adapted Cambridge Gambling Task
  time frame: baseline visit, total time= 10 minutes
  description: Assesses value-based choice. Participants bet on expected outcomes when presented with a colored (orange, purple) roulette wheel with the proportions of each color indicating 1 of 5 levels of certain/uncertain outcomes in the context of win or loss conditions.
  Risk Adjustment scores based on level of probability of win or loss.
  measure: Reward Processing and Learning: Reinforcement Learning Task
  time frame: baseline visit, total time= 10 minutes
  description: Assesses reward and punishment learning. Participants are shown colored circles and choose the one they believe is more likely to win money. There are two conditions (no lose and no win).
  Learning rate (alpha) based on how fast participant learns new information (both win and loss).
  Risk Adjustment scores based on level of probability of win or loss.
  measure: Impulsivity: Discounting Task
  time frame: baseline visit, total time= 7 minutes
  description: Assesses rate of discounting across 5 levels of delay and 5 of probability. Participants decide between a standard fixed amount vs an immediately available alternative.
  Indifference points for each length of delay/degree of uncertainly, noted by area under the curve.
  measure: Social Cognition: Moral Emotions Task
  time frame: baseline visit, total time= 13 minutes
  description: Assesses moral judgment/emotional reactions to social situations. Cartoons depict characters intentionally or unintentionally harming one another. Participants rate feelings (e.g., guilt, shame) as either the victim or antagonizer in the scenario.
  Average ratings of guilt and shame in each scenario (victim or antagonizer).
  measure: Montreal Cognitive Assessment (MoCA): Cold Cognitive Function Testing.
  time frame: Day 1/baseline
  description: Description: Cold cognitive function will be measured by Montreal Cognitive Assessment (MoCA). MoCA assesses multiple cognitive domains: attention, concentration, executive functions, memory, language, visuospatial skills, abstraction, calculation and orientation. Possible scores range from 0-30, where score ≥ 26 is considered to be normal.
  measure: Everyday Cognition (ECog): Cold Cognitive Function Testing
  time frame: Day 1
  description: Cold cognitive function will be measured by Everyday Cognition (ECog), ECog scale is a validated informant-rated questionnaire that includes one global factor and six domain-specific factors: 6 domains: everyday memory, language, visuospatial and perceptual abilities, planning, organization, and divided attention. Each item is scored based on a four-point scale: 1 = better or no change compared to 10 years earlier; 2 =questionable/occasionally worse; 3 = consistently a little worse; 4 = consistently much worse. The total score will be calculated as the sum of all 39 items. Higher scores indicates worse daily function
  measure: Test of Premorbid Function (TOPF): Cold Cognitive Function Testing
  time frame: Day 1
  description: Cold cognitive function will be measured by Test of Premorbid Function (TOPF), TOPF estimates an individual's pre-morbid cognitive and memory functioning. Possible scores range from 80 - 130, where higher scores indicate better pre-morbid cognitive functioning.
  measure: California Verbal Learning Test-3 (CVLT-3): Cold Cognitive Function Testing
  time frame: Day 1
  description: Cold cognitive function will be measured by California Verbal Learning Test-3 (CVLT-3), CVLT-3 measures verbal learning and memory. Possible scores range from 0 - 16, where higher scores indicate better performance.
  measure: Delis-Kaplan Executive Function System (DKEF)-Color-Word Interference: Cold Cognitive Function Testing
  time frame: Day 1
  description: Cold cognitive function will be measured by Delis-Kaplan Executive Function System (D-KEF) Color-Word Interference, it is made up of color naming, word reading, and inhibition, is measured in seconds, a smaller number represents a better outcome.
  measure: Delis-Kaplan Executive Function System (DKEF)-Tower Test: Cold Cognitive Function Testing
  time frame: Day 1
  description: Cold cognitive function will be measured by D-KEF Tower test, it is a measure of executive function. Total achievement scores indicate the highest score participants scored on the test. Possible score range from 0 - 30, higher scores indicate better performance.
  measure: Delis-Kaplan Executive Function System (D-KEF)-Verbal Fluency Performance: Cold Cognitive Function Testing
  time frame: Day 1
  description: Cold cognitive function will be measured by D-KEFs Verbal Fluency Test, made up of letter fluency and category fluency, is measured by number of responses, a larger number represents a better outcome.
  measure: MEG: Magnetoencephalography
  time frame: Baseline Day1
  description: Six minutes, eyes-open resting-state scan will be completed. Before the scan, five coils will be secured to the participant's head and 3D digitizer will be used to map the location of the coils, fiducials, and scalp surface, MEG data will be co-registered to their high-resolution structural T1-weighted MRI. This will provide a four-dimensional (4D) image of brain activity, similar to Functional magnetic resonance imaging (fMRI).
  arm group label: Major Depressive Disorder (MDD) Participants:
  description: Male and female subjects
  Age between 21-80 years old
  Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) diagnosis of major depressive disorder (MDD) based on Mini Neuropsychiatric Interview
  Inventory of Depressive Symptomatology; Clinician Rated version (IDS-C) total score > 14
  Able to read, write, and comprehend English
  Provide informed consent; willing to comply with study protocol.
  Note: For individuals with MDD diagnosis: As part of the screening procedures, the Mini International Neuropsychiatric Interview (MINI-7.0 for DSM-5) will be conducted to determine eligibility. This is related to Inclusion Criteria #3.
  arm group label: Healthy Volunteer Participants:
  description: Male and female subjects
  Age between 21-80 years old
  Able to read, write, and comprehend English
  Provide informed consent; willing to comply with study protocol
  intervention type: Behavioral
  intervention name: Hot Cognitive Task
  description: Emotion processing:
  Participants will be shown a series of faces that appear quickly and be asked to identify what emotion is shown.
  Participants will be shown a face of an emotion and indicate if participant can see the emotion changing.
  Participant will be shown a series of emotions and asked to respond to only a specific emotion.
  Motivation reward and processing:
  Participant will play with a simulated roulette and make a bet to evaluate their decision-making behavior.
  Participant will be shown colored circles and choose the one more likely to win money.
  Impulsivity:
  • Participant will be shown a series of stimuli where they will be asked to respond to the correct stimulus.
  Social cognition:
  Participant will be shown a series of moral situations in which a character is accidentally or intentionally harmed and be asked to rate the degree of guilt from the perspective of the victim or perpetrator.
  arm group label: Healthy Volunteer Participants:
  arm group label: Major Depressive Disorder (MDD) Participants:
  intervention type: Behavioral
  intervention name: Cold cognitive tasks
  description: Montreal Cognitive Assessment (MoCA) - This will ask participants questions related to their cognition such as visuospatial skills, naming, memory, attention, language, and recall.
  Measurement of Everyday Cognition (ECog) - This scale will ask participants about their everyday memory, language, visuospatial ability, organization, and divided attention.
  Test of Premorbid Function (TOPF) - This test will evaluate memory performance and abilities of stud participants before onset pre-morbid status.
  California Verbal Learning Test -3rd Edition (CVLT-3) -This test will measure verbal learning and memory of study participants.
  Three tests from the Delis-Kaplan Executive Function System (D-KEFS; Verbal Fluency, Color-Word Interference, and Tower Tests). -These measures assess word finding and problem-solving ability.
  arm group label: Healthy Volunteer Participants:
  arm group label: Major Depressive Disorder (MDD) Participants:
  intervention type: Other
  intervention name: Structural magnetic resonance imaging (sMRI)
  description: This is a non-invasive procedure to assess the structure and function of participant's brain. Structural neuroanatomical data will be acquired using structural magnetic resonance. Imaging (sMRI) with the University of Texas Southwestern (UTSW) 3T (three Tesla field) Siemens Prisma MRI scanner. Prior to participation, the investigator's team will screen participant's to ensure eligibility to participate in the sMRI scan.
  arm group label: Major Depressive Disorder (MDD) Participants:
  intervention type: Other
  intervention name: Magnetoencephalography imaging (MEG)
  description: This is a non-invasive procedure to measure participant's brain activity. Participants will be sitting inside the machine in a chamber, with more space than a traditional MRI machine. A hat will be placed on top of participant's head which records their brain activity. Resting-state MEG recordings will occur in a three-layer magnetically shielded room (MSR) following our UTSW Advanced Neuroscience Imaging Research (ANSIR) established procedures. Before the scan, five coils will be secured to participant's head and a three-dimensional (3D) digitizer will be used to map the location of the coils, fiducials, and scalp surface. During recording, an electric current with a unique frequency label (i.e., 320 Hz) will be fed to each coil, which will permit real time head location tracking and subsequent offline head motion correction.
  arm group label: Major Depressive Disorder (MDD) Participants:
  study pop: 
  sampling method: Probability Sample
  criteria: 
  gender: All
  minimum age: 21 Years
  maximum age: 80 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Shawn McClintock, PhD
  phone: 214-648-2806
  email: shawn.mcclintock@utsouthwestern.edu
  last name: Aatika Parwaiz, MPH
  phone: 214-648-2806
  email: aatika.parwaiz@utsouthwestern.edu
  facility: 
  status: Not yet recruiting
  contact: 
  contact backup: 
  investigator: 
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  investigator: 
  country: United States
  url: https://www.frontiersin.org/articles/10.3389/fnbeh.2016.00025/full
  description: EMOTICOM: A Neuropsychological Test Battery to Evaluate Emotion, Motivation, Impulsivity, and Social Cognition
  responsible party type: Principal Investigator
  investigator affiliation: University of Texas Southwestern Medical Center
  investigator full name: Shawn McClintock
  investigator title: Professor
  mesh term: Depressive Disorder
  mesh term: Depressive Disorder, Major
  sharing ipd: Undecided