<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/NCT03786185</url>
  </required_header>
  <id_info>
    <org_study_id>2089</org_study_id>
    <nct_id>NCT03786185</nct_id>
  </id_info>
  <brief_title>Neuroplasticity of Multisensory Cortical Areas Induced by Musical Training: a Translational Approach (MusicPlast)</brief_title>
  <acronym>MusicPlast</acronym>
  <official_title>Neuroplasticity of Multisensory Cortical Areas Induced by Computerized Musical Training, Across the Life Span: a Translational Approach</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Aristotle University Of Thessaloniki</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Aristotle University Of Thessaloniki</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>
      Exploiting recent methodological advancements, several neuroimaging studies suggested that&#xD;
      multisensory integration emerges from a dynamic interplay of distributed regions operating in&#xD;
      large-scale networks. Nonetheless, the cortical structures and neuronal networks underlying&#xD;
      the development of multisensory perception and plasticity, throughout the life span, have not&#xD;
      yet been studied in detail. A special case of multisensory training is musical training,&#xD;
      which utilizes stimulus' structural complexity, as well as the emotional drive that music is&#xD;
      generating to the subjects, in order to induce augmented neuroplastic effects.&#xD;
&#xD;
      Retaining the extensive neuroplastic characteristics of music training, MUSICPLAST will&#xD;
      develop, investigate and deliver a computer provided multisensory training protocol that aims&#xD;
      to induce neuroplastic changes in frontotemporal cortical areas. More specifically, the goal&#xD;
      of the proposed project is threefold: (a) The in-depth understanding and modeling of the&#xD;
      developmental trajectory of the cortical networks underlying multisensory perception, (b) the&#xD;
      modeling of the developmental trajectory of the cortical networks underlying multisensory&#xD;
      plasticity throughout the life span of healthy subjects; and (c) the translation of this&#xD;
      model in a computer provided multisensory training intervention protocol, which will cause&#xD;
      beneficial neuroplastic changes in pathological populations. Electroencephalographic,&#xD;
      behavioral and neuropsychological measurements, and advanced data analysis procedures, pre-&#xD;
      and post the training application are going to be employed in order to evaluate the resulting&#xD;
      neuroplasticity holistically. The proposed protocol will also be translated into an applied&#xD;
      intervention for 2 groups of pathological population, for which there are strong evidence&#xD;
      that a multisensory cognitive training based on music may provide beneficial neuroplastic&#xD;
      changes: elderlies suffering from mild cognitive Impairment and adolescents with dyslexia.&#xD;
&#xD;
      The project is performed in the Laboratory of Medical Physics of the Aristotle University of&#xD;
      Thessaloniki. It takes advantage of the extensive background of the laboratory in music and&#xD;
      neuroscience, in multisensory perception and in applications that translate basic&#xD;
      neuroscientific knowledge into computer based interventions for young adults and elderlies,&#xD;
      building up a solid neuroscientific ground on which multidisciplinary characteristics of the&#xD;
      project stand.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Goals and research questions&#xD;
&#xD;
      The first goal of MUSICPLAST is to explore in-depth the development of audiovisual perception&#xD;
      in the healthy human brain describing in detail the corresponding cortical networks involved.&#xD;
      High density EEG measurements (128 channels) are going to be employed for the realization of&#xD;
      this goal following a stimulation protocol which incorporates auditory, visual and&#xD;
      audiovisual correspondences in a unified multisensory oddball paradigm. Behavioral and&#xD;
      neuropsychological evaluation of the multisensory perceptual abilities of the subjects will&#xD;
      be performed in order to achieve a holistic understanding of the phenomenon. The within&#xD;
      subjects comparison of the different conditions will reveal the corresponding network, while&#xD;
      the between subjects, its developmental trajectory. The hypothesis of this experiment, is&#xD;
      that the network underlying audiovisual perception will be comprised from cortical areas&#xD;
      connecting widespread regions including dorsolateral regions of the frontal cortex. Regarding&#xD;
      its development, and based on the fact that behaviorally multisensory integration continues&#xD;
      to improve in healthy aging, it is hypothesized that the network will be reorganized showing&#xD;
      enhanced density and efficiency as the age progresses.&#xD;
&#xD;
      The second goal of MUSICPLAST is to explore in-depth the plasticity of the cortical network&#xD;
      underlying audiovisual perception in the healthy human brain, as induced via a computer&#xD;
      provided short-term musical reading training. Pre- and post- training high-density EEG,&#xD;
      behavioral and neuropsychological measurements are going to be employed for the realization&#xD;
      of this goal following the same stimulation paradigm as for the previously mentioned goal.&#xD;
      The hypothesis of this experiment, is that the network underlying audiovisual perception will&#xD;
      be reorganized showing enhanced global density and efficiency, greater connectivity between&#xD;
      temporal and frontopolar regions and a gradual decline of the amount of plasticity as a&#xD;
      result of the age increase.&#xD;
&#xD;
      The third goal of MUSICPLAST is to evaluate the effectiveness of the proposed computerized&#xD;
      music reading training protocol as a tool that will promote beneficial neuroplastic changes&#xD;
      in pathological populations and specifically, dyslectic adolescents and elderlies. Pre- and&#xD;
      post- training high-density EEG, behavioral and neuropsychological measurements are going to&#xD;
      be employed for the realization of this goal following the same stimulation paradigm as for&#xD;
      the previously mentioned goals. The hypothesis of this experiment, is that the network&#xD;
      underlying audiovisual perception will be beneficially reorganized due to the training&#xD;
      showing enhanced global density and efficiency, greater connectivity between temporal and&#xD;
      frontopolar regions and that these changes will be accompanied from improvement in the&#xD;
      corresponding behavioral and neuropsychological evaluation.&#xD;
&#xD;
      Research design and methodology Participants&#xD;
&#xD;
      A sample size analysis was conducted via G-Power based on the data from a previous relevant&#xD;
      study of the PI and indicated that the desired sample size in order to reach a power of 0.8&#xD;
      and a two sided significance level of a = 0.05 is 13 subjects in each group. In order to&#xD;
      account for possible dropouts, MUSICPLAST will include 20 subjects in each group [adolescents&#xD;
      (n = 20), young adults (n = 20), elderlies (n = 20) and controls (n=20)]. The study will be&#xD;
      conducted according to the declaration of Helsinki with regard to the participation of human&#xD;
      subjects in research.&#xD;
&#xD;
      EEG and behavioral measurements&#xD;
&#xD;
      Prior to the beginning of the training and after its completion, the participants will be&#xD;
      subjected into 2 electroencephalographic measurements. The recordings will be performed in an&#xD;
      electromagnetically shielded room located in the Medical Physics Laboratory of AUTH using a&#xD;
      Nihon Kohden EEG-1200 system with 128 active electrodes. The first measurement will be of&#xD;
      resting state activity, allowing a network analysis of resting state cortical connectivity&#xD;
      while the second will record Event Potentials via a multisensory oddball paradigm which is&#xD;
      appropriately adjusted for audiovisual perception, as it incorporates audiovisual, auditory&#xD;
      and visual mismatches within one run. This paradigm has been proposed and successfully&#xD;
      applied in a series of studies by the PI and it allows both a spatiotemporal analysis of the&#xD;
      cortical activity as well as a functional connectivity analysis.&#xD;
&#xD;
      Concurrently to the EEG measurements the subjects will respond behaviorally via button&#xD;
      presses to an audiovisual congruency task on which they have to evaluate whether the images&#xD;
      presented correspond to the tones they hear based on the rule &quot;the higher the pitch of the&#xD;
      tone - the higher the position of the circle&quot;. This measurement will allow the behavioral&#xD;
      evaluation of the discrimination accuracy of congruent and incongruent audiovisual stimuli.&#xD;
&#xD;
      Prior to the beginning of the training and after its completion, the participants will be&#xD;
      subjected into a neuropsychological evaluation, which will consist of a battery including the&#xD;
      following tests:&#xD;
&#xD;
      All subjects:&#xD;
&#xD;
      Stroop Test Trail A and B Digit Span Test Performance Subtest of Wechsler Intelligence Scale&#xD;
      Children III or Wechsler Adult Intelligence Scale according to the age.&#xD;
&#xD;
      Elderlies only:&#xD;
&#xD;
      Mini Mental State Examination (MMSE) Montreal Cognitive Assessment (MoCA) Geriatric&#xD;
      Depression Scale&#xD;
&#xD;
      Dyslectics only:&#xD;
&#xD;
      Word and nonword reading Word and nonword spelling Phonological ability&#xD;
&#xD;
      Intervention - MUSICPLAST training protocol&#xD;
&#xD;
      Each subject will receive 20 sessions of the computerized training based on a simplified&#xD;
      music reading within a period of 4 weeks. The training will be provided via a smartphone or a&#xD;
      tablet. The application will record a log file for each training session, which will last for&#xD;
      20 minutes and the log file will be directly available to the researcher, allowing him/her to&#xD;
      follow the timely participation and commitment of the subject. The stimuli used in the&#xD;
      training protocol will be constructed along the same principles of the audiovisual stimulus&#xD;
      patterns used in the EEG recordings: a visual image will show a circle on top of a background&#xD;
      of 5 horizontal lines. The duration of the patterns will be of a mean duration of 10 seconds.&#xD;
&#xD;
      The position of the circle within the five lines will either follow the rule &quot;the higher the&#xD;
      pitch of the tone, the higher the position of the circle&quot; or it will violate the above rule.&#xD;
      This rule was in principle followed also in previous studies conducted by the PI with&#xD;
      positive results regarding the induced neuroplasticity. The visual images will only represent&#xD;
      the frequency of the pitch and not the rhythmical pattern. The participant will have to&#xD;
      respond at the end of each trial via a button press whether the audiovisual input confirmed&#xD;
      or violated the above presented rule. A feedback image of a smiling face for the correct&#xD;
      responses or a not smiling face for the incorrect responses will be provided for each trial.&#xD;
      The protocol will be of adjusted difficulty, having 5 levels of difficulty which will be&#xD;
      based on 2 different factors: the presentation speed, and the difficulty of the musical&#xD;
      pattern. In contrast to the EEG measurement procedure, during which the melodic patterns will&#xD;
      be unknown to the subjects, the melodic patterns used in the training will be comprised of&#xD;
      short but identifiable parts of known musical pieces in order to engage the participants and&#xD;
      to provoke emotional response. The training will be improved in comparison to the&#xD;
      corresponding previous studies of the PI by providing feedback and by the use of known&#xD;
      musical pieces which will induce an emotional response to the trainees.&#xD;
&#xD;
      EEG data analysis and statistical procedures&#xD;
&#xD;
      The EEG data collected will be pre-processed using the Brain Electrical Source Analysis&#xD;
      software (BESA research, version 6, Megis Software, Heidelberg, Germany). The recorded data&#xD;
      will be separated in epochs of 1000 ms including a pre-stimulus interval of 200 ms. Epochs&#xD;
      will be baseline corrected using the interval from -100 to 0 ms. Current Density&#xD;
      Reconstructions (CDRs) will be calculated on the neural responses of each subject and each&#xD;
      condition using the sLORETA method55 as provided by BESA. The Matlab ® (The MathWorks, Inc.,&#xD;
      Natick, Massachusetts, United States.) toolbox HERMES56 will be used for calculating the&#xD;
      adjacency matrix from the voxel time-series. The toolbox Network Based Statistic (NBS) will&#xD;
      be used to statistically identify significant connections in the graphs, using a General&#xD;
      Linear Model approach. For the statistical analysis of the data a 2 × 2 × 2 × 2 mixed model&#xD;
      ANOVA design will be followed, with 3 within subjects factors: condition (congruent and&#xD;
      incongruent), modality (audiovisual, auditory, and visual) and time (pre- and post- training)&#xD;
      and one between subjects: (age group). The significance level will be set to p &lt; 0.05&#xD;
      corrected for multiple comparisons via Family Wise Error correction.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">August 2, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>This is a 2x2x2 mixed model design with between subjects factors condition (congruent and incongruent) and age group (adolescent, adults, elderlies) and within subjects factor time (pre, post).</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
    <masking_description>The participant is not aware of the group (intervention or control) in which s/he belongs.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in current density strength of the cortical activity as measured via EEG</measure>
    <time_frame>1 month</time_frame>
    <description>Changes in cortical activity strength caused via the training. Change is defined as statistical significance in the t-test comparison of the current density strength as reconstructed via Low Resolution Electromagnetic Tomography (LORETA) algorithm on the basis of high density EEG recordings, before compared to after the training</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in cortical connectivity as measured via EEG</measure>
    <time_frame>1 month</time_frame>
    <description>Changes in cortical connectivity caused via the training. Change is defined as statistical significance in the t-test comparison of the Transfer Entropy estimated from the cortical activity, as reconstructed via LORETA algorithm on the basis of high density EEG recordings, before compared to after the training.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in audiovisual integration functionality</measure>
    <time_frame>1 month</time_frame>
    <description>Change of accuracy in the behavioral measurement testing audiovisual integration. Change is defined as statistical significance in the t-test comparison before compared to after the training.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in cognitive functionality</measure>
    <time_frame>1 month</time_frame>
    <description>Change of scoring in neuropsychological tests related with attention, memory and performance. Change is defined as statistical significance in the t-test comparison before compared to after the training.</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">80</enrollment>
  <condition>Dyslexia</condition>
  <condition>Aging Problems</condition>
  <arm_group>
    <arm_group_label>Adolescents with dyslexia</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MusicPlast training</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Adolescents without dyslexia</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>MusicPlast training</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Young Adults</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MusicPlast training</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Young Adults Control</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>MusicPlast Control, in a similar design as MusicPlast</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Seniors</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MusicPlast training</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>MusicPlast</intervention_name>
    <description>Each subject will receive 20 sessions of the computerized training based on a simplified music reading protocol. The training will be provided via a smartphone or a tablet. Each training session will last for 20 minutes and the log file will be directly available to the researcher, allowing him/her to follow subject's timely participation. The stimuli used in the training protocol will consist of a visual image showing a circle on top of a background of 5 horizontal lines. The auditory part of the stimulus will consist of piano melodies of known songs. The position of the circle within the five lines will either follow the rule &quot;the higher the pitch of the tone, the higher the position of the circle&quot; or it will violate the above rule. The task requires audiovisual integration.</description>
    <arm_group_label>Adolescents with dyslexia</arm_group_label>
    <arm_group_label>Adolescents without dyslexia</arm_group_label>
    <arm_group_label>Seniors</arm_group_label>
    <arm_group_label>Young Adults</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>MusicPlast Control</intervention_name>
    <description>Each subject will receive 20 sessions of the computerized training within a period of 4 weeks, aiming to train visual search via spot-the-difference tasks and identification of dissonance in music. Auditory and visual stimuli are concurrently presented, but do not require audiovisual integration.</description>
    <arm_group_label>Young Adults Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Group of Adolescent dyslectics&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  13 - 18 years of age&#xD;
&#xD;
          -  normal or corrected-to-normal hearing and vision&#xD;
&#xD;
          -  Diagnosed dyslexia&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  any other than dyslexia, diagnosed neurological, mental, developmental or psychiatric&#xD;
             disorder&#xD;
&#xD;
          -  (ii) unrecovered neurological disorders (i.e., stroke, traumatic brain injury),&#xD;
&#xD;
          -  (iii) unstable medication within the last 3 months,&#xD;
&#xD;
          -  (iv) severe physical disorder, and&#xD;
&#xD;
          -  (v) concurrent participation in another relevant study.&#xD;
&#xD;
        Group of Adolescent controls&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  13 - 18 years of age&#xD;
&#xD;
          -  normal or corrected-to-normal hearing and vision&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  (I) any diagnosed neurological, mental, developmental or psychiatric disorder&#xD;
&#xD;
          -  (ii) unrecovered neurological disorders (i.e., stroke, traumatic brain injury),&#xD;
&#xD;
          -  (iii) unstable medication within the last 3 months,&#xD;
&#xD;
          -  (iv) severe physical disorder, and&#xD;
&#xD;
          -  (v) concurrent participation in another relevant study.&#xD;
&#xD;
        Group of Young Adults&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  18 - 35 years of age&#xD;
&#xD;
          -  normal or corrected-to-normal hearing and vision&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  (I) any diagnosed neurological, mental, developmental or psychiatric disorder&#xD;
&#xD;
          -  (ii) unrecovered neurological disorders (i.e., stroke, traumatic brain injury),&#xD;
&#xD;
          -  (iii) unstable medication within the last 3 months,&#xD;
&#xD;
          -  (iv) severe physical disorder, and&#xD;
&#xD;
          -  (v) concurrent participation in another relevant study.&#xD;
&#xD;
        Group of Seniors&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  65 - 100 years of age&#xD;
&#xD;
          -  normal or corrected-to-normal hearing and vision&#xD;
&#xD;
          -  normal score in a neuropsychological screening procedure which regards cognitive&#xD;
             functionality&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  (i) unrecovered neurological disorders (i.e., stroke, traumatic brain injury),&#xD;
&#xD;
          -  (ii) severe depression or psychological disorder,&#xD;
&#xD;
          -  (iii) unstable medication within the last 3 months,&#xD;
&#xD;
          -  (iv) severe physical disorder, and&#xD;
&#xD;
          -  (v) concurrent participation in another relevant study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Evangelos Paraskevopoulos, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Research Associate</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Laboratory of Medical Physics</name>
      <address>
        <city>Thessaloníki</city>
        <zip>54124</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Greece</country>
  </location_countries>
  <link>
    <url>https://users.auth.gr/parasvag/MusicPlast/</url>
    <description>project web-site</description>
  </link>
  <reference>
    <citation>Paraskevopoulos E, Kraneburg A, Herholz SC, Bamidis PD, Pantev C. Musical expertise is related to altered functional connectivity during audiovisual integration. Proc Natl Acad Sci U S A. 2015 Oct 6;112(40):12522-7. doi: 10.1073/pnas.1510662112. Epub 2015 Sep 14.</citation>
    <PMID>26371305</PMID>
  </reference>
  <reference>
    <citation>Paraskevopoulos E, Kuchenbuch A, Herholz SC, Pantev C. Multisensory integration during short-term music reading training enhances both uni- and multisensory cortical processing. J Cogn Neurosci. 2014 Oct;26(10):2224-38. doi: 10.1162/jocn_a_00620. Epub 2014 Mar 26.</citation>
    <PMID>24669793</PMID>
  </reference>
  <reference>
    <citation>Paraskevopoulos E, Kuchenbuch A, Herholz SC, Pantev C. Musical expertise induces audiovisual integration of abstract congruency rules. J Neurosci. 2012 Dec 12;32(50):18196-203. doi: 10.1523/JNEUROSCI.1947-12.2012.</citation>
    <PMID>23238733</PMID>
  </reference>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>December 20, 2018</study_first_submitted>
  <study_first_submitted_qc>December 21, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 24, 2018</study_first_posted>
  <last_update_submitted>May 4, 2023</last_update_submitted>
  <last_update_submitted_qc>May 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Aristotle University Of Thessaloniki</investigator_affiliation>
    <investigator_full_name>Panos Bamidis</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Neuroplasticity</keyword>
  <keyword>Computerized training</keyword>
  <keyword>Music reading</keyword>
  <keyword>Multisensory training</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dyslexia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Individual Participant Data (IPD) will be available upon the completion of the study via personal communication. Data shared will include EEG measurements, score on behavioral and psychometric data.</ipd_description>
  </patient_data>
  <!-- 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/NCT03786185
org study id: 2089
nct id: NCT03786185
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Exploiting recent methodological advancements, several neuroimaging studies suggested that
      multisensory integration emerges from a dynamic interplay of distributed regions operating in
      large-scale networks. Nonetheless, the cortical structures and neuronal networks underlying
      the development of multisensory perception and plasticity, throughout the life span, have not
      yet been studied in detail. A special case of multisensory training is musical training,
      which utilizes stimulus' structural complexity, as well as the emotional drive that music is
      generating to the subjects, in order to induce augmented neuroplastic effects.

      Retaining the extensive neuroplastic characteristics of music training, MUSICPLAST will
      develop, investigate and deliver a computer provided multisensory training protocol that aims
      to induce neuroplastic changes in frontotemporal cortical areas. More specifically, the goal
      of the proposed project is threefold: (a) The in-depth understanding and modeling of the
      developmental trajectory of the cortical networks underlying multisensory perception, (b) the
      modeling of the developmental trajectory of the cortical networks underlying multisensory
      plasticity throughout the life span of healthy subjects; and (c) the translation of this
      model in a computer provided multisensory training intervention protocol, which will cause
      beneficial neuroplastic changes in pathological populations. Electroencephalographic,
      behavioral and neuropsychological measurements, and advanced data analysis procedures, pre-
      and post the training application are going to be employed in order to evaluate the resulting
      neuroplasticity holistically. The proposed protocol will also be translated into an applied
      intervention for 2 groups of pathological population, for which there are strong evidence
      that a multisensory cognitive training based on music may provide beneficial neuroplastic
      changes: elderlies suffering from mild cognitive Impairment and adolescents with dyslexia.

      The project is performed in the Laboratory of Medical Physics of the Aristotle University of
      Thessaloniki. It takes advantage of the extensive background of the laboratory in music and
      neuroscience, in multisensory perception and in applications that translate basic
      neuroscientific knowledge into computer based interventions for young adults and elderlies,
      building up a solid neuroscientific ground on which multidisciplinary characteristics of the
      project stand.
Goals and research questions

      The first goal of MUSICPLAST is to explore in-depth the development of audiovisual perception
      in the healthy human brain describing in detail the corresponding cortical networks involved.
      High density EEG measurements (128 channels) are going to be employed for the realization of
      this goal following a stimulation protocol which incorporates auditory, visual and
      audiovisual correspondences in a unified multisensory oddball paradigm. Behavioral and
      neuropsychological evaluation of the multisensory perceptual abilities of the subjects will
      be performed in order to achieve a holistic understanding of the phenomenon. The within
      subjects comparison of the different conditions will reveal the corresponding network, while
      the between subjects, its developmental trajectory. The hypothesis of this experiment, is
      that the network underlying audiovisual perception will be comprised from cortical areas
      connecting widespread regions including dorsolateral regions of the frontal cortex. Regarding
      its development, and based on the fact that behaviorally multisensory integration continues
      to improve in healthy aging, it is hypothesized that the network will be reorganized showing
      enhanced density and efficiency as the age progresses.

      The second goal of MUSICPLAST is to explore in-depth the plasticity of the cortical network
      underlying audiovisual perception in the healthy human brain, as induced via a computer
      provided short-term musical reading training. Pre- and post- training high-density EEG,
      behavioral and neuropsychological measurements are going to be employed for the realization
      of this goal following the same stimulation paradigm as for the previously mentioned goal.
      The hypothesis of this experiment, is that the network underlying audiovisual perception will
      be reorganized showing enhanced global density and efficiency, greater connectivity between
      temporal and frontopolar regions and a gradual decline of the amount of plasticity as a
      result of the age increase.

      The third goal of MUSICPLAST is to evaluate the effectiveness of the proposed computerized
      music reading training protocol as a tool that will promote beneficial neuroplastic changes
      in pathological populations and specifically, dyslectic adolescents and elderlies. Pre- and
      post- training high-density EEG, behavioral and neuropsychological measurements are going to
      be employed for the realization of this goal following the same stimulation paradigm as for
      the previously mentioned goals. The hypothesis of this experiment, is that the network
      underlying audiovisual perception will be beneficially reorganized due to the training
      showing enhanced global density and efficiency, greater connectivity between temporal and
      frontopolar regions and that these changes will be accompanied from improvement in the
      corresponding behavioral and neuropsychological evaluation.

      Research design and methodology Participants

      A sample size analysis was conducted via G-Power based on the data from a previous relevant
      study of the PI and indicated that the desired sample size in order to reach a power of 0.8
      and a two sided significance level of a = 0.05 is 13 subjects in each group. In order to
      account for possible dropouts, MUSICPLAST will include 20 subjects in each group [adolescents
      (n = 20), young adults (n = 20), elderlies (n = 20) and controls (n=20)]. The study will be
      conducted according to the declaration of Helsinki with regard to the participation of human
      subjects in research.

      EEG and behavioral measurements

      Prior to the beginning of the training and after its completion, the participants will be
      subjected into 2 electroencephalographic measurements. The recordings will be performed in an
      electromagnetically shielded room located in the Medical Physics Laboratory of AUTH using a
      Nihon Kohden EEG-1200 system with 128 active electrodes. The first measurement will be of
      resting state activity, allowing a network analysis of resting state cortical connectivity
      while the second will record Event Potentials via a multisensory oddball paradigm which is
      appropriately adjusted for audiovisual perception, as it incorporates audiovisual, auditory
      and visual mismatches within one run. This paradigm has been proposed and successfully
      applied in a series of studies by the PI and it allows both a spatiotemporal analysis of the
      cortical activity as well as a functional connectivity analysis.

      Concurrently to the EEG measurements the subjects will respond behaviorally via button
      presses to an audiovisual congruency task on which they have to evaluate whether the images
      presented correspond to the tones they hear based on the rule "the higher the pitch of the
      tone - the higher the position of the circle". This measurement will allow the behavioral
      evaluation of the discrimination accuracy of congruent and incongruent audiovisual stimuli.

      Prior to the beginning of the training and after its completion, the participants will be
      subjected into a neuropsychological evaluation, which will consist of a battery including the
      following tests:

      All subjects:

      Stroop Test Trail A and B Digit Span Test Performance Subtest of Wechsler Intelligence Scale
      Children III or Wechsler Adult Intelligence Scale according to the age.

      Elderlies only:

      Mini Mental State Examination (MMSE) Montreal Cognitive Assessment (MoCA) Geriatric
      Depression Scale

      Dyslectics only:

      Word and nonword reading Word and nonword spelling Phonological ability

      Intervention - MUSICPLAST training protocol

      Each subject will receive 20 sessions of the computerized training based on a simplified
      music reading within a period of 4 weeks. The training will be provided via a smartphone or a
      tablet. The application will record a log file for each training session, which will last for
      20 minutes and the log file will be directly available to the researcher, allowing him/her to
      follow the timely participation and commitment of the subject. The stimuli used in the
      training protocol will be constructed along the same principles of the audiovisual stimulus
      patterns used in the EEG recordings: a visual image will show a circle on top of a background
      of 5 horizontal lines. The duration of the patterns will be of a mean duration of 10 seconds.

      The position of the circle within the five lines will either follow the rule "the higher the
      pitch of the tone, the higher the position of the circle" or it will violate the above rule.
      This rule was in principle followed also in previous studies conducted by the PI with
      positive results regarding the induced neuroplasticity. The visual images will only represent
      the frequency of the pitch and not the rhythmical pattern. The participant will have to
      respond at the end of each trial via a button press whether the audiovisual input confirmed
      or violated the above presented rule. A feedback image of a smiling face for the correct
      responses or a not smiling face for the incorrect responses will be provided for each trial.
      The protocol will be of adjusted difficulty, having 5 levels of difficulty which will be
      based on 2 different factors: the presentation speed, and the difficulty of the musical
      pattern. In contrast to the EEG measurement procedure, during which the melodic patterns will
      be unknown to the subjects, the melodic patterns used in the training will be comprised of
      short but identifiable parts of known musical pieces in order to engage the participants and
      to provoke emotional response. The training will be improved in comparison to the
      corresponding previous studies of the PI by providing feedback and by the use of known
      musical pieces which will induce an emotional response to the trainees.

      EEG data analysis and statistical procedures

      The EEG data collected will be pre-processed using the Brain Electrical Source Analysis
      software (BESA research, version 6, Megis Software, Heidelberg, Germany). The recorded data
      will be separated in epochs of 1000 ms including a pre-stimulus interval of 200 ms. Epochs
      will be baseline corrected using the interval from -100 to 0 ms. Current Density
      Reconstructions (CDRs) will be calculated on the neural responses of each subject and each
      condition using the sLORETA method55 as provided by BESA. The Matlab ® (The MathWorks, Inc.,
      Natick, Massachusetts, United States.) toolbox HERMES56 will be used for calculating the
      adjacency matrix from the voxel time-series. The toolbox Network Based Statistic (NBS) will
      be used to statistically identify significant connections in the graphs, using a General
      Linear Model approach. For the statistical analysis of the data a 2 × 2 × 2 × 2 mixed model
      ANOVA design will be followed, with 3 within subjects factors: condition (congruent and
      incongruent), modality (audiovisual, auditory, and visual) and time (pre- and post- training)
      and one between subjects: (age group). The significance level will be set to p < 0.05
      corrected for multiple comparisons via Family Wise Error correction.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is a 2x2x2 mixed model design with between subjects factors condition (congruent and incongruent) and age group (adolescent, adults, elderlies) and within subjects factor time (pre, post).
primary purpose: Treatment
masking: Single (Participant)
masking description: The participant is not aware of the group (intervention or control) in which s/he belongs.
measure: Change in current density strength of the cortical activity as measured via EEG
time frame: 1 month
description: Changes in cortical activity strength caused via the training. Change is defined as statistical significance in the t-test comparison of the current density strength as reconstructed via Low Resolution Electromagnetic Tomography (LORETA) algorithm on the basis of high density EEG recordings, before compared to after the training
measure: Change in cortical connectivity as measured via EEG
time frame: 1 month
description: Changes in cortical connectivity caused via the training. Change is defined as statistical significance in the t-test comparison of the Transfer Entropy estimated from the cortical activity, as reconstructed via LORETA algorithm on the basis of high density EEG recordings, before compared to after the training.
measure: Change in audiovisual integration functionality
time frame: 1 month
description: Change of accuracy in the behavioral measurement testing audiovisual integration. Change is defined as statistical significance in the t-test comparison before compared to after the training.
measure: Change in cognitive functionality
time frame: 1 month
description: Change of scoring in neuropsychological tests related with attention, memory and performance. Change is defined as statistical significance in the t-test comparison before compared to after the training.
arm group label: Adolescents with dyslexia
arm group type: Experimental
description: MusicPlast training
arm group label: Adolescents without dyslexia
arm group type: Active Comparator
description: MusicPlast training
arm group label: Young Adults
arm group type: Experimental
description: MusicPlast training
arm group label: Young Adults Control
arm group type: Active Comparator
description: MusicPlast Control, in a similar design as MusicPlast
arm group label: Seniors
arm group type: Experimental
description: MusicPlast training
intervention type: Behavioral
intervention name: MusicPlast
description: Each subject will receive 20 sessions of the computerized training based on a simplified music reading protocol. The training will be provided via a smartphone or a tablet. Each training session will last for 20 minutes and the log file will be directly available to the researcher, allowing him/her to follow subject's timely participation. The stimuli used in the training protocol will consist of a visual image showing a circle on top of a background of 5 horizontal lines. The auditory part of the stimulus will consist of piano melodies of known songs. The position of the circle within the five lines will either follow the rule "the higher the pitch of the tone, the higher the position of the circle" or it will violate the above rule. The task requires audiovisual integration.
arm group label: Adolescents with dyslexia
arm group label: Adolescents without dyslexia
arm group label: Seniors
arm group label: Young Adults
intervention type: Behavioral
intervention name: MusicPlast Control
description: Each subject will receive 20 sessions of the computerized training within a period of 4 weeks, aiming to train visual search via spot-the-difference tasks and identification of dissonance in music. Auditory and visual stimuli are concurrently presented, but do not require audiovisual integration.
arm group label: Young Adults Control
criteria: 
gender: All
minimum age: 12 Years
maximum age: 100 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Evangelos Paraskevopoulos, PhD
role: Principal Investigator
affiliation: Research Associate
facility: 
country: Greece
url: https://users.auth.gr/parasvag/MusicPlast/
description: project web-site
citation: Paraskevopoulos E, Kraneburg A, Herholz SC, Bamidis PD, Pantev C. Musical expertise is related to altered functional connectivity during audiovisual integration. Proc Natl Acad Sci U S A. 2015 Oct 6;112(40):12522-7. doi: 10.1073/pnas.1510662112. Epub 2015 Sep 14.
PMID: 26371305
citation: Paraskevopoulos E, Kuchenbuch A, Herholz SC, Pantev C. Multisensory integration during short-term music reading training enhances both uni- and multisensory cortical processing. J Cogn Neurosci. 2014 Oct;26(10):2224-38. doi: 10.1162/jocn_a_00620. Epub 2014 Mar 26.
PMID: 24669793
citation: Paraskevopoulos E, Kuchenbuch A, Herholz SC, Pantev C. Musical expertise induces audiovisual integration of abstract congruency rules. J Neurosci. 2012 Dec 12;32(50):18196-203. doi: 10.1523/JNEUROSCI.1947-12.2012.
PMID: 23238733
responsible party type: Principal Investigator
investigator affiliation: Aristotle University Of Thessaloniki
investigator full name: Panos Bamidis
investigator title: Associate Professor
mesh term: Dyslexia
sharing ipd: Undecided
ipd description: Individual Participant Data (IPD) will be available upon the completion of the study via personal communication. Data shared will include EEG measurements, score on behavioral and psychometric data.