<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/NCT03805854</url>
  </required_header>
  <id_info>
    <org_study_id>01/2019</org_study_id>
    <nct_id>NCT03805854</nct_id>
  </id_info>
  <brief_title>Modulating Pain Using Transcranial Alternating Stimulation (tACS) in Healthy Human Subjects</brief_title>
  <official_title>Modulating Pain Using Transcranial Alternating Stimulation (tACS) in Healthy Human Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Technical University of Munich</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>German Research Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Technical University of Munich</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>
      Pain is a highly complex and subjective phenomenon which results from the dynamic integration&#xD;
      of sensory and contextual (i.e. cognitive, emotional, and motivational) processes. Recent&#xD;
      evidence suggests that neural oscillations and their synchronization between different brain&#xD;
      areas might form the basis of these integrative functions. When investigating tonic&#xD;
      experimental pain lasting for several minutes, for example, objective stimulus intensity is&#xD;
      inversely related to alpha (8-13 Hz) and beta (13-30 Hz) oscillations in early somatosensory&#xD;
      areas, while subjective pain intensity is positively associated with gamma (30-100 Hz)&#xD;
      oscillations in prefrontal cortex. Yet, with a few exemptions, reported links between&#xD;
      oscillatory brain activity and pain have mostly been established by correlative approaches&#xD;
      which do not allow to infer causality. The current project aims at comprehensively&#xD;
      investigating the causal role of neural oscillations for tonic experimental pain in healthy&#xD;
      human subjects. To this end, transcranial alternating current stimulation (tACS) will be&#xD;
      employed to modulate oscillatory brain activity in alpha and gamma frequency bands and&#xD;
      investigate effects of this manipulation on pain perception and pain-related autonomic&#xD;
      responses. Using an established tonic pain stimulation protocol and a double-blind,&#xD;
      sham-controlled design, effects of tACS of somatosensory as well as prefrontal brain areas&#xD;
      will be investigated. Results promise to elucidate the neural mechanisms underlying tonic&#xD;
      experimental pain by testing the mechanistic role of neural oscillations in different aspects&#xD;
      of pain processing. Furthermore, they might contribute to the development of urgently needed&#xD;
      new treatment approaches for chronic pain using neuromodulatory methods.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 15, 2019</start_date>
  <completion_date type="Actual">October 23, 2019</completion_date>
  <primary_completion_date type="Actual">October 23, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Each participant will participate in 6 experimental conditions aimed at studying the effect of different tACS protocols on pain processing: (1) 10 Hz tACS of the bilateral somatosensory cortex, (2) 10 Hz tACS of the prefrontal cortex, (3) 80 Hz tACS of the bilateral somatosensory cortex, (4) 80 Hz tACS of the prefrontal cortex, (5) sham stimulation of the bilateral somatosensory cortex, and (6) sham stimulation of the prefrontal cortex. Each condition will be administered in an individual session. Sessions will be conducted in pseudo-randomized order and separated by at least 24 hours to avoid any carry-over effects of the stimulation. During each tACS administration, pain will be induced by means of an established tonic thermal stimulation paradigm lasting for several minutes (TSA-II; Medoc, Ramat Yishai, Israel) while pain ratings and autonomic responses will be recorded (Nickel et al., 2017a; Nickel et al., 2017b).</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Neither participants nor the conducting investigator will be informed about the administered tACS protocol (10 Hz tACS, 80 Hz tACS or sham stimulation) (= double-blind study). Blinding of participants will be achieved by using tACS intensities which should not evoke perceivable stimulation side effects like skin or visual sensations. Blinding of participants will be controlled using post-hoc questionnaires. An unblinded research assistant who does not interact with the participants will be responsible for initiating and monitoring the appropriate tACS protocol and, thus, enable the blinding of the conducting investigator.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in pain rating on visual analogue scale (VAS; 0: 'no pain' to 10: 'maximal tolerable pain') between sessions</measure>
    <time_frame>During 10 min thermal stimulation in each of six interventions (10 Hz tACS/80 Hz tACS/sham stimulation of the somatosensory/prefrontal cortex), which are separated by at least 24 hrs.</time_frame>
    <description>During thermal stimulation, participants will be instructed to continuously rate the currently perceived pain intensity using a finger-span device.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in skin conductance responses (µS) between sessions</measure>
    <time_frame>During 10 min thermal stimulation in each of six interventions (10 Hz tACS/80 Hz tACS/sham stimulation of the somatosensory/prefrontal cortex), which are separated by at least 24 hrs.</time_frame>
    <description>Skin conductance responses will be recorded using two electrodes attached to the index and middle finger of the left hand.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in heart rate (BPM, beats per minute) between sessions</measure>
    <time_frame>During 10 min thermal stimulation in each of six interventions (10 Hz tACS/80 Hz tACS/sham stimulation of the somatosensory/prefrontal cortex), which are separated by at least 24 hrs.</time_frame>
    <description>The electrocardiogram (ECG) will be recorded using two electrodes placed under the right clavicle and below the sternum, respectively.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in oscillatory brain activity before and after tACS application within each session</measure>
    <time_frame>Measured immediately before and after the tACS protocol in each of six interventions (10 Hz tACS/80 Hz tACS/sham stimulation of the somatosensory/prefrontal cortex), which are separated by at least 24 hrs.</time_frame>
    <description>5-minute resting state electroencephalogram (EEG) will be recorded with two electrodes placed at the same electrode positions used for the respective tACS protocol. Power of oscillatory brain activity will be quantified in the alpha (8-12 Hz) and gamma (30-100 Hz) bands.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Perception of tACS induced visual and skin sensations measured by numerical rating scale (NRS; 0: 'no sensation' to 10: 'very strong sensation')</measure>
    <time_frame>Measured immediately after the EEG measurement following each of six interventions (10 Hz tACS/80 Hz tACS/sham stimulation of the somatosensory/prefrontal cortex), which are separated by at least 24 hrs.</time_frame>
    <description>The perception of visual and skin sensations induced by the tACS protocols will be assessed using a custom questionnaire.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">39</enrollment>
  <condition>Experimental Pain in Healthy Human Subjects</condition>
  <arm_group>
    <arm_group_label>Transcranial alternating current stimulation (tACS)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>10 Hz tACS of the bilateral somatosensory cortex</intervention_name>
    <description>10 Hz tACS at 1 mA will be applied over the bilateral somatosensory cortex for 10 minutes using a Neuroconn stimulator (DC-Stimulator MR; Neuroconn, Ilmenau, Germany) and 2 5*5 cm rubber electrodes placed at electrode positions CP3 and CP4 according to the international 10-20 system.</description>
    <arm_group_label>Transcranial alternating current stimulation (tACS)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>10 Hz tACS of the prefrontal cortex</intervention_name>
    <description>10 Hz tACS at 1 mA will be applied over the prefrontal cortex for 10 minutes using a Neuroconn stimulator (DC-Stimulator MR; Neuroconn, Ilmenau, Germany) and 2 5*5 cm rubber electrodes placed at electrode positions F3 and F4 according to the international 10-20 system.</description>
    <arm_group_label>Transcranial alternating current stimulation (tACS)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>80 Hz tACS of the bilateral somatosensory cortex</intervention_name>
    <description>80 Hz tACS at 1 mA will be applied over the bilateral somatosensory cortex for 10 minutes using a Neuroconn stimulator (DC-Stimulator MR; Neuroconn, Ilmenau, Germany) and 2 5*5 cm rubber electrodes placed at electrode positions CP3 and CP4 according to the international 10-20 system.</description>
    <arm_group_label>Transcranial alternating current stimulation (tACS)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>80 Hz tACS of the prefrontal cortex</intervention_name>
    <description>80 Hz tACS at 1 mA will be applied over the prefrontal cortex for 10 minutes using a Neuroconn stimulator (DC-Stimulator MR; Neuroconn, Ilmenau, Germany) and 2 5*5 cm rubber electrodes placed at electrode positions F3 and F4 according to the international 10-20 system.</description>
    <arm_group_label>Transcranial alternating current stimulation (tACS)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sham stimulation of the bilateral somatosensory cortex</intervention_name>
    <description>10 Hz tACS at 1 mA will be applied over the bilateral somatosensory cortex for 10 seconds at the beginning of the experimental session using a Neuroconn stimulator (DC-Stimulator MR; Neuroconn, Ilmenau, Germany) and 2 5*5 cm rubber electrodes placed at electrode positions CP3 and CP4 according to the international 10-20 system.</description>
    <arm_group_label>Transcranial alternating current stimulation (tACS)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sham stimulation of the prefrontal cortex</intervention_name>
    <description>10 Hz tACS at 1 mA will be applied over the prefrontal cortex for 10 seconds at the beginning of the experimental session using a Neuroconn stimulator (DC-Stimulator MR; Neuroconn, Ilmenau, Germany) and 2 5*5 cm rubber placed at electrode positions F3 and F4 according to the international 10-20 system.</description>
    <arm_group_label>Transcranial alternating current stimulation (tACS)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  aged 18-65 years&#xD;
&#xD;
          -  Right-handedness&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Neurological or psychiatric diseases (e.g. epilepsy, stroke, depression, anxiety&#xD;
             disorders)&#xD;
&#xD;
          -  Severe general illnesses (e.g. tumors, diabetes)&#xD;
&#xD;
          -  Skin diseases (e.g. dermatitis, psoriasis or eczema)&#xD;
&#xD;
          -  Current or recurrent pain&#xD;
&#xD;
          -  Regular intake of medication&#xD;
&#xD;
          -  Surgical procedures involving the head or spinal cord&#xD;
&#xD;
          -  Head trauma followed by impairment of consciousness&#xD;
&#xD;
          -  Past fainting spells or syncopes&#xD;
&#xD;
          -  Metal (except titanium) or electronic implants&#xD;
&#xD;
          -  Side-effects following previous electrical or magnetic stimulation&#xD;
&#xD;
          -  Side-effects following previous thermal stimulation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Markus Ploner, Prof. Dr. med.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Neurology, Klinikum rechts der Isar, Technische Universität München</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Neurology, Klinikum rechts der Isar, Technische Universität München</name>
      <address>
        <city>Munich</city>
        <state>Bavaria</state>
        <zip>81675</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <reference>
    <citation>Ahn S, Prim JH, Alexander ML, McCulloch KL, Frohlich F. Identifying and Engaging Neuronal Oscillations by Transcranial Alternating Current Stimulation in Patients With Chronic Low Back Pain: A Randomized, Crossover, Double-Blind, Sham-Controlled Pilot Study. J Pain. 2019 Mar;20(3):277.e1-277.e11. doi: 10.1016/j.jpain.2018.09.004. Epub 2018 Sep 27.</citation>
    <PMID>30268803</PMID>
  </reference>
  <reference>
    <citation>Arendsen LJ, Hugh-Jones S, Lloyd DM. Transcranial Alternating Current Stimulation at Alpha Frequency Reduces Pain When the Intensity of Pain is Uncertain. J Pain. 2018 Jul;19(7):807-818. doi: 10.1016/j.jpain.2018.02.014. Epub 2018 Mar 15.</citation>
    <PMID>29551661</PMID>
  </reference>
  <reference>
    <citation>Herrmann CS, Rach S, Neuling T, Struber D. Transcranial alternating current stimulation: a review of the underlying mechanisms and modulation of cognitive processes. Front Hum Neurosci. 2013 Jun 14;7:279. doi: 10.3389/fnhum.2013.00279. eCollection 2013.</citation>
    <PMID>23785325</PMID>
  </reference>
  <reference>
    <citation>Jensen MP, Day MA, Miro J. Neuromodulatory treatments for chronic pain: efficacy and mechanisms. Nat Rev Neurol. 2014 Mar;10(3):167-78. doi: 10.1038/nrneurol.2014.12. Epub 2014 Feb 18.</citation>
    <PMID>24535464</PMID>
  </reference>
  <reference>
    <citation>Nickel MM, May ES, Tiemann L, Postorino M, Ta Dinh S, Ploner M. Autonomic responses to tonic pain are more closely related to stimulus intensity than to pain intensity. Pain. 2017 Nov;158(11):2129-2136. doi: 10.1097/j.pain.0000000000001010.</citation>
    <PMID>28700538</PMID>
  </reference>
  <reference>
    <citation>Nickel MM, May ES, Tiemann L, Schmidt P, Postorino M, Ta Dinh S, Gross J, Ploner M. Brain oscillations differentially encode noxious stimulus intensity and pain intensity. Neuroimage. 2017 Mar 1;148:141-147. doi: 10.1016/j.neuroimage.2017.01.011. Epub 2017 Jan 7.</citation>
    <PMID>28069543</PMID>
  </reference>
  <reference>
    <citation>Ploner M, Sorg C, Gross J. Brain Rhythms of Pain. Trends Cogn Sci. 2017 Feb;21(2):100-110. doi: 10.1016/j.tics.2016.12.001. Epub 2016 Dec 23.</citation>
    <PMID>28025007</PMID>
  </reference>
  <reference>
    <citation>Polania R, Nitsche MA, Ruff CC. Studying and modifying brain function with non-invasive brain stimulation. Nat Neurosci. 2018 Feb;21(2):174-187. doi: 10.1038/s41593-017-0054-4. Epub 2018 Jan 8.</citation>
    <PMID>29311747</PMID>
  </reference>
  <reference>
    <citation>Schulz E, May ES, Postorino M, Tiemann L, Nickel MM, Witkovsky V, Schmidt P, Gross J, Ploner M. Prefrontal Gamma Oscillations Encode Tonic Pain in Humans. Cereb Cortex. 2015 Nov;25(11):4407-14. doi: 10.1093/cercor/bhv043. Epub 2015 Mar 8.</citation>
    <PMID>25754338</PMID>
  </reference>
  <reference>
    <citation>Sitaram R, Ros T, Stoeckel L, Haller S, Scharnowski F, Lewis-Peacock J, Weiskopf N, Blefari ML, Rana M, Oblak E, Birbaumer N, Sulzer J. Closed-loop brain training: the science of neurofeedback. Nat Rev Neurosci. 2017 Feb;18(2):86-100. doi: 10.1038/nrn.2016.164. Epub 2016 Dec 22. Erratum In: Nat Rev Neurosci. 2019 May;20(5):314.</citation>
    <PMID>28003656</PMID>
  </reference>
  <reference>
    <citation>Vosskuhl J, Struber D, Herrmann CS. Non-invasive Brain Stimulation: A Paradigm Shift in Understanding Brain Oscillations. Front Hum Neurosci. 2018 May 25;12:211. doi: 10.3389/fnhum.2018.00211. eCollection 2018.</citation>
    <PMID>29887799</PMID>
  </reference>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>January 10, 2019</study_first_submitted>
  <study_first_submitted_qc>January 15, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 16, 2019</study_first_posted>
  <last_update_submitted>June 2, 2020</last_update_submitted>
  <last_update_submitted_qc>June 2, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 4, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Technical University of Munich</investigator_affiliation>
    <investigator_full_name>Markus Ploner</investigator_full_name>
    <investigator_title>Heisenberg Professor of Human Pain Research</investigator_title>
  </responsible_party>
  <keyword>pain</keyword>
  <keyword>tACS</keyword>
  <keyword>alpha</keyword>
  <keyword>gamma</keyword>
  <keyword>neural oscillations</keyword>
  <keyword>brain</keyword>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Pseudonymized individual participant data sets will be made available at the OSF online repository [https://osf.io/] upon publication.</ipd_description>
    <ipd_url>https://osf.io/pnd6g/</ipd_url>
  </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/NCT03805854
org study id: 01/2019
nct id: NCT03805854
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Pain is a highly complex and subjective phenomenon which results from the dynamic integration
      of sensory and contextual (i.e. cognitive, emotional, and motivational) processes. Recent
      evidence suggests that neural oscillations and their synchronization between different brain
      areas might form the basis of these integrative functions. When investigating tonic
      experimental pain lasting for several minutes, for example, objective stimulus intensity is
      inversely related to alpha (8-13 Hz) and beta (13-30 Hz) oscillations in early somatosensory
      areas, while subjective pain intensity is positively associated with gamma (30-100 Hz)
      oscillations in prefrontal cortex. Yet, with a few exemptions, reported links between
      oscillatory brain activity and pain have mostly been established by correlative approaches
      which do not allow to infer causality. The current project aims at comprehensively
      investigating the causal role of neural oscillations for tonic experimental pain in healthy
      human subjects. To this end, transcranial alternating current stimulation (tACS) will be
      employed to modulate oscillatory brain activity in alpha and gamma frequency bands and
      investigate effects of this manipulation on pain perception and pain-related autonomic
      responses. Using an established tonic pain stimulation protocol and a double-blind,
      sham-controlled design, effects of tACS of somatosensory as well as prefrontal brain areas
      will be investigated. Results promise to elucidate the neural mechanisms underlying tonic
      experimental pain by testing the mechanistic role of neural oscillations in different aspects
      of pain processing. Furthermore, they might contribute to the development of urgently needed
      new treatment approaches for chronic pain using neuromodulatory methods.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Each participant will participate in 6 experimental conditions aimed at studying the effect of different tACS protocols on pain processing: (1) 10 Hz tACS of the bilateral somatosensory cortex, (2) 10 Hz tACS of the prefrontal cortex, (3) 80 Hz tACS of the bilateral somatosensory cortex, (4) 80 Hz tACS of the prefrontal cortex, (5) sham stimulation of the bilateral somatosensory cortex, and (6) sham stimulation of the prefrontal cortex. Each condition will be administered in an individual session. Sessions will be conducted in pseudo-randomized order and separated by at least 24 hours to avoid any carry-over effects of the stimulation. During each tACS administration, pain will be induced by means of an established tonic thermal stimulation paradigm lasting for several minutes (TSA-II; Medoc, Ramat Yishai, Israel) while pain ratings and autonomic responses will be recorded (Nickel et al., 2017a; Nickel et al., 2017b).
primary purpose: Basic Science
masking: None (Open Label)
masking description: Neither participants nor the conducting investigator will be informed about the administered tACS protocol (10 Hz tACS, 80 Hz tACS or sham stimulation) (= double-blind study). Blinding of participants will be achieved by using tACS intensities which should not evoke perceivable stimulation side effects like skin or visual sensations. Blinding of participants will be controlled using post-hoc questionnaires. An unblinded research assistant who does not interact with the participants will be responsible for initiating and monitoring the appropriate tACS protocol and, thus, enable the blinding of the conducting investigator.
measure: Changes in pain rating on visual analogue scale (VAS; 0: 'no pain' to 10: 'maximal tolerable pain') between sessions
time frame: During 10 min thermal stimulation in each of six interventions (10 Hz tACS/80 Hz tACS/sham stimulation of the somatosensory/prefrontal cortex), which are separated by at least 24 hrs.
description: During thermal stimulation, participants will be instructed to continuously rate the currently perceived pain intensity using a finger-span device.
measure: Changes in skin conductance responses (µS) between sessions
time frame: During 10 min thermal stimulation in each of six interventions (10 Hz tACS/80 Hz tACS/sham stimulation of the somatosensory/prefrontal cortex), which are separated by at least 24 hrs.
description: Skin conductance responses will be recorded using two electrodes attached to the index and middle finger of the left hand.
measure: Changes in heart rate (BPM, beats per minute) between sessions
time frame: During 10 min thermal stimulation in each of six interventions (10 Hz tACS/80 Hz tACS/sham stimulation of the somatosensory/prefrontal cortex), which are separated by at least 24 hrs.
description: The electrocardiogram (ECG) will be recorded using two electrodes placed under the right clavicle and below the sternum, respectively.
measure: Changes in oscillatory brain activity before and after tACS application within each session
time frame: Measured immediately before and after the tACS protocol in each of six interventions (10 Hz tACS/80 Hz tACS/sham stimulation of the somatosensory/prefrontal cortex), which are separated by at least 24 hrs.
description: 5-minute resting state electroencephalogram (EEG) will be recorded with two electrodes placed at the same electrode positions used for the respective tACS protocol. Power of oscillatory brain activity will be quantified in the alpha (8-12 Hz) and gamma (30-100 Hz) bands.
measure: Perception of tACS induced visual and skin sensations measured by numerical rating scale (NRS; 0: 'no sensation' to 10: 'very strong sensation')
time frame: Measured immediately after the EEG measurement following each of six interventions (10 Hz tACS/80 Hz tACS/sham stimulation of the somatosensory/prefrontal cortex), which are separated by at least 24 hrs.
description: The perception of visual and skin sensations induced by the tACS protocols will be assessed using a custom questionnaire.
arm group label: Transcranial alternating current stimulation (tACS)
arm group type: Experimental
intervention type: Device
intervention name: 10 Hz tACS of the bilateral somatosensory cortex
description: 10 Hz tACS at 1 mA will be applied over the bilateral somatosensory cortex for 10 minutes using a Neuroconn stimulator (DC-Stimulator MR; Neuroconn, Ilmenau, Germany) and 2 5*5 cm rubber electrodes placed at electrode positions CP3 and CP4 according to the international 10-20 system.
arm group label: Transcranial alternating current stimulation (tACS)
intervention type: Device
intervention name: 10 Hz tACS of the prefrontal cortex
description: 10 Hz tACS at 1 mA will be applied over the prefrontal cortex for 10 minutes using a Neuroconn stimulator (DC-Stimulator MR; Neuroconn, Ilmenau, Germany) and 2 5*5 cm rubber electrodes placed at electrode positions F3 and F4 according to the international 10-20 system.
arm group label: Transcranial alternating current stimulation (tACS)
intervention type: Device
intervention name: 80 Hz tACS of the bilateral somatosensory cortex
description: 80 Hz tACS at 1 mA will be applied over the bilateral somatosensory cortex for 10 minutes using a Neuroconn stimulator (DC-Stimulator MR; Neuroconn, Ilmenau, Germany) and 2 5*5 cm rubber electrodes placed at electrode positions CP3 and CP4 according to the international 10-20 system.
arm group label: Transcranial alternating current stimulation (tACS)
intervention type: Device
intervention name: 80 Hz tACS of the prefrontal cortex
description: 80 Hz tACS at 1 mA will be applied over the prefrontal cortex for 10 minutes using a Neuroconn stimulator (DC-Stimulator MR; Neuroconn, Ilmenau, Germany) and 2 5*5 cm rubber electrodes placed at electrode positions F3 and F4 according to the international 10-20 system.
arm group label: Transcranial alternating current stimulation (tACS)
intervention type: Device
intervention name: Sham stimulation of the bilateral somatosensory cortex
description: 10 Hz tACS at 1 mA will be applied over the bilateral somatosensory cortex for 10 seconds at the beginning of the experimental session using a Neuroconn stimulator (DC-Stimulator MR; Neuroconn, Ilmenau, Germany) and 2 5*5 cm rubber electrodes placed at electrode positions CP3 and CP4 according to the international 10-20 system.
arm group label: Transcranial alternating current stimulation (tACS)
intervention type: Device
intervention name: Sham stimulation of the prefrontal cortex
description: 10 Hz tACS at 1 mA will be applied over the prefrontal cortex for 10 seconds at the beginning of the experimental session using a Neuroconn stimulator (DC-Stimulator MR; Neuroconn, Ilmenau, Germany) and 2 5*5 cm rubber placed at electrode positions F3 and F4 according to the international 10-20 system.
arm group label: Transcranial alternating current stimulation (tACS)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Markus Ploner, Prof. Dr. med.
role: Principal Investigator
affiliation: Department of Neurology, Klinikum rechts der Isar, Technische Universität München
facility: 
country: Germany
citation: Ahn S, Prim JH, Alexander ML, McCulloch KL, Frohlich F. Identifying and Engaging Neuronal Oscillations by Transcranial Alternating Current Stimulation in Patients With Chronic Low Back Pain: A Randomized, Crossover, Double-Blind, Sham-Controlled Pilot Study. J Pain. 2019 Mar;20(3):277.e1-277.e11. doi: 10.1016/j.jpain.2018.09.004. Epub 2018 Sep 27.
PMID: 30268803
citation: Arendsen LJ, Hugh-Jones S, Lloyd DM. Transcranial Alternating Current Stimulation at Alpha Frequency Reduces Pain When the Intensity of Pain is Uncertain. J Pain. 2018 Jul;19(7):807-818. doi: 10.1016/j.jpain.2018.02.014. Epub 2018 Mar 15.
PMID: 29551661
citation: Herrmann CS, Rach S, Neuling T, Struber D. Transcranial alternating current stimulation: a review of the underlying mechanisms and modulation of cognitive processes. Front Hum Neurosci. 2013 Jun 14;7:279. doi: 10.3389/fnhum.2013.00279. eCollection 2013.
PMID: 23785325
citation: Jensen MP, Day MA, Miro J. Neuromodulatory treatments for chronic pain: efficacy and mechanisms. Nat Rev Neurol. 2014 Mar;10(3):167-78. doi: 10.1038/nrneurol.2014.12. Epub 2014 Feb 18.
PMID: 24535464
citation: Nickel MM, May ES, Tiemann L, Postorino M, Ta Dinh S, Ploner M. Autonomic responses to tonic pain are more closely related to stimulus intensity than to pain intensity. Pain. 2017 Nov;158(11):2129-2136. doi: 10.1097/j.pain.0000000000001010.
PMID: 28700538
citation: Nickel MM, May ES, Tiemann L, Schmidt P, Postorino M, Ta Dinh S, Gross J, Ploner M. Brain oscillations differentially encode noxious stimulus intensity and pain intensity. Neuroimage. 2017 Mar 1;148:141-147. doi: 10.1016/j.neuroimage.2017.01.011. Epub 2017 Jan 7.
PMID: 28069543
citation: Ploner M, Sorg C, Gross J. Brain Rhythms of Pain. Trends Cogn Sci. 2017 Feb;21(2):100-110. doi: 10.1016/j.tics.2016.12.001. Epub 2016 Dec 23.
PMID: 28025007
citation: Polania R, Nitsche MA, Ruff CC. Studying and modifying brain function with non-invasive brain stimulation. Nat Neurosci. 2018 Feb;21(2):174-187. doi: 10.1038/s41593-017-0054-4. Epub 2018 Jan 8.
PMID: 29311747
citation: Schulz E, May ES, Postorino M, Tiemann L, Nickel MM, Witkovsky V, Schmidt P, Gross J, Ploner M. Prefrontal Gamma Oscillations Encode Tonic Pain in Humans. Cereb Cortex. 2015 Nov;25(11):4407-14. doi: 10.1093/cercor/bhv043. Epub 2015 Mar 8.
PMID: 25754338
citation: Sitaram R, Ros T, Stoeckel L, Haller S, Scharnowski F, Lewis-Peacock J, Weiskopf N, Blefari ML, Rana M, Oblak E, Birbaumer N, Sulzer J. Closed-loop brain training: the science of neurofeedback. Nat Rev Neurosci. 2017 Feb;18(2):86-100. doi: 10.1038/nrn.2016.164. Epub 2016 Dec 22. Erratum In: Nat Rev Neurosci. 2019 May;20(5):314.
PMID: 28003656
citation: Vosskuhl J, Struber D, Herrmann CS. Non-invasive Brain Stimulation: A Paradigm Shift in Understanding Brain Oscillations. Front Hum Neurosci. 2018 May 25;12:211. doi: 10.3389/fnhum.2018.00211. eCollection 2018.
PMID: 29887799
responsible party type: Principal Investigator
investigator affiliation: Technical University of Munich
investigator full name: Markus Ploner
investigator title: Heisenberg Professor of Human Pain Research
sharing ipd: Yes
ipd description: Pseudonymized individual participant data sets will be made available at the OSF online repository [https://osf.io/] upon publication.
ipd url: https://osf.io/pnd6g/