LanguageNCT05010473
Cortical Contributions to Frequency Following Responses and Modulation
A study testing Speech and non-speech sound stimulation in people with Language, run by Northwestern University at 1 site in United States.
Trial summary
The frequency-following response (FFR), a scalp-recorded neurophonic potential, is a widely used metric of speech encoding integrity in healthy and clinical human populations. The translational potential of the FFR as a biomarker is constrained by poor understanding of its neural generators and influencing factors. Read more about this study
- Who is it for?
- Ages 13 to 25 yearsHealthy volunteers can take part
- Conditions the study is for
- Language
- What is being tested?
- Speech and non-speech sound stimulation
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 73 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Jan 2022to 4 Mar 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 13 to 25 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Age 13 years up to 25 years
- Healthy volunteers
- Native English speaking individuals with no exposure or experience to tonal languages
- Native Mandarin speakers
- Hearing sensitivity within normal limits (Puretone hearing thresholds < 25dB from 250
- Hz to 8000 Hz)
- Less than six years of formal music training or experience
Who cannot join
- Proficiency in languages other than English or Chinese
- History of or current complaint of hearing loss or tinnitus
- History of or current complaint of cognitive impairments
- Individuals with more than 5 years of formal music experience or training
- Complaints of impaired speech perception in noise
Trial locations and contacts
1 site in 1 country.
About this study
The frequency-following response (FFR), a scalp-recorded neurophonic potential, is a widely used metric of speech encoding integrity in healthy and clinical human populations. The translational potential of the FFR as a biomarker is constrained by poor understanding of its neural generators and influencing factors. This study leverages a cross-species and cross-level approach to provide mechanistic insight into the properties of the cortical source of the FFR, and elucidate the role of cortical feedback via cortico-collicular projections on modulation of the FFR as a function of stimulus context, arousal state, and category relevance. This clinical trial will focus on the influences of category relevance, predictability, and participant arousal state on the FFRs in neurotypical human participants.
Read the detailed description
Participants will listen to a variety of sounds while the frequency-following response (FFR) is recorded. The FFR is a sound-evoked response that mirrors the acoustic properties of the incoming acoustic signal with remarkable fidelity. The FFR is now recognized as an integrated response resulting from an interplay of early auditory subcortical and cortical systems. The cortical dynamics underlying the FFR are unclear. All stimuli will be normalized to the same root mean squared amplitude and stimulus duration and played at the same in-the-ear intensity. Thirty-two stimuli from human and animal natural productions with a wide-range of F0 will be used to elicit the FFR. At least 1000 artifact-free trials will be collected for every stimulus. Participants will sit in a quiet room (patients) or a sound-treated booth and listen to sounds while electroencephalography (EEG) and pupillometry signals are continuously acquired. EEG signals will be collected using Ag-AgCl scalp electrodes, with the active electrode placed at the central zero (Cz) point, the reference at the right mastoid, and the ground at the left mastoid. Contact impedence will be< 5 kΩ for all electrodes for all recording sessions, and responses will be recorded at a sampling rate of 25 kHz using Brain Vision PyCorder 1.0.7 (Brain Products, Gilching, Germany). Alternating polarities of the stimuli will be binaurally presented in sound field (identical to the animal protocols), with an inter-stimulus interval jittered between 122 to 148ms. Participants will be instructed to stay awake and refrain from making extraneous movements. EEG and pupil measures will allow continuous monitoring of participant state. The order of blocks will be counterbalanced across participants, and stimulus presentation will be controlled by E-Prime 2.0.10 software. The electrophysiological data will be preprocessed with BrainVision Analyzer 2.0 (Brain Products, Gilching, Germany), bandpass filtered (varies based on stimulus F0; 12 dB/octave, zero phase-shift). The bandpass filter will approximately reflect the lower and upper limits of phase-locking along the auditory pathway that contributes to the FFR (auditory cortex, midbrain). Responses will be segmented into epochs, baseline corrected to the mean voltage of the noise floor(-40 to 0ms). Epochs in which the amplitude exceeds ± 35μV will be considered artifacts and rejected. In each session, a preset number of artifact-free FFR trials (500 for each polarity) will be obtained. For pupillometry, participants will be seated in a chair and will place their head on a chin rest. The stabilized mount also has a small horizontal bar that they can place their forehead against. To calibrate the eye tracker, participants will be asked to follow 9 dots that appear on a monitor with their eyes. Insert earbuds will be placed in both ears, and auditory stimuli will be presented binaurally. Pupillometry data will be preprocessed to remove noise from the analysis. The pupil data will be downsampled to 50 Hz. Trials with more than 15% of the samples detected as blinks will be removed. Missing samples due to blinks will be linearly interpolated from approximately100 ms prior to and 100 ms after the blink. Pupil responses will be baseline normalized using the average pupil size in the 500-1000 ms prior to the onset of the auditory stimuli. A key variable reported will be the percent change in pupil size.
- Conditions
- Language
- Being tested
- Speech and non-speech sound stimulation
- Medical subject headings
- Language
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Speech and non-speech sound stimulationBehavioural
Listening to repetitive and extended sound presentation induces specific neural and physiological activity that we will measure via electroencephalography and pupillometry
| Study group | Role | What they receive |
|---|---|---|
| Neurotypical Human Participants | Experimental | Native speakers of Chinese and native speakers of English Receives: Behavioral: Speech and non-speech sound stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pitch tracking and decoding accuracies for dynamically varying pitch in naturally produced Mandarin tone categories
The similarity between the stimulus and the FFR will be evaluated. The pitch tracking ability will be estimated by comparing the sliding window autocorrelation pitch tracks of the stimulus and FFR. Machine learning models will be trained to decode FFR to different stimulus categories based on pitch height and pitch direction. The chance estimates of the decoding accuracies will be estimated.
Measured: During EEG session, up to 3 hours
Stimulus-specific effects in Chinese vs. English participants
The stimulus-specific effects in human participants, based on pitch tracking and decoding accuracies, will be assessed. The decoding accuracies and pitch tracking metrics for mandarin tone categories will be compared between Chinese listeners and English listeners. The focus will be to evaluate the specific benefits in Chinese listeners to track pitch height and direction patterns in Mandarin tones.
Measured: During EEG session, up to 3 hours
Arousal state and predictability effects on the FFRs
Arousal state and its dependence on encoding of predictability effects on the FFRs will be evaluated. The pitch tracking metrics and decoding accuracies will be compared across repetitive and contextual stimulus sequences while sorting the trials based on peak pupillary dilation as a proxy for arousal state. The predictability effects will be charted as a function of the arousal states and evaluated.
Measured: During simultaneous EEG and pupillometry session, up to 3 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2021
- Study start20 Jan 2022
- Primary completion4 Mar 2026
- Study completion4 Mar 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LanguageStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 73 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Deafness and Other Communication Disorders (NIDCD)
- Responsible party
- Principal investigator, Bharath Chandrasekaran, Northwestern University
- Investigators
- Bharath Chandrasekaran, PhD, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05010473
- Sponsor's protocol ID
- STU00219433
- Other IDs
- R01DC013315
- Status last verified
- Apr 2026
- First submitted
- 30 Jul 2021
- Last updated
- 24 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: We will follow the guidelines set forth by the Open Knowledge International, which is a global non-profit organization that advocates for open science and open data. Our objectives in data sharing are to provide free and open access to everyone. Consistent with ideas articulated in the Open Data Handbook (http://opendatahandbook.org/), we will apply for an open license for resources that are not deemed as intellectual properties, make data easily available in a format that is broadly accessible and ensures longevity, and advertise it on our webpages and via social media to make it discoverable.
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cortical Contributions to Frequency Following Responses and Modulation
- ClinicalTrials.gov ID
- NCT05010473
- Acronym / sponsor ID
- STU00219433
- Conditions
- Language
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 73 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Collaborators
- National Institute on Deafness and Other Communication Disorders (NIDCD)
- Study start
- 20 Jan 2022 (actual)
- Primary completion
- 4 Mar 2026 (actual)
- Study completion
- 4 Mar 2026 (actual)
- First posted
- 18 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The frequency-following response (FFR), a scalp-recorded neurophonic potential, is a widely used metric of speech encoding integrity in healthy and clinical human populations. The translational potential of the FFR as a biomarker is constrained by poor understanding of its neural generators and influencing factors. This study leverages a cross-species and cross-level approach to provide mechanistic insight into the properties of the cortical source of the FFR, and elucidate the role of cortical feedback via cortico-collicular projections on modulation of the FFR as a function of stimulus context, arousal state, and category relevance. This clinical trial will focus on the influences of category relevance, predictability, and participant arousal state on the FFRs in neurotypical human participants.
Detailed description
Participants will listen to a variety of sounds while the frequency-following response (FFR) is recorded. The FFR is a sound-evoked response that mirrors the acoustic properties of the incoming acoustic signal with remarkable fidelity. The FFR is now recognized as an integrated response resulting from an interplay of early auditory subcortical and cortical systems. The cortical dynamics underlying the FFR are unclear. All stimuli will be normalized to the same root mean squared amplitude and stimulus duration and played at the same in-the-ear intensity. Thirty-two stimuli from human and animal natural productions with a wide-range of F0 will be used to elicit the FFR. At least 1000 artifact-free trials will be collected for every stimulus. Participants will sit in a quiet room (patients) or a sound-treated booth and listen to sounds while electroencephalography (EEG) and pupillometry signals are continuously acquired. EEG signals will be collected using Ag-AgCl scalp electrodes, with the active electrode placed at the central zero (Cz) point, the reference at the right mastoid, and the ground at the left mastoid. Contact impedence will be< 5 kΩ for all electrodes for all recording sessions, and responses will be recorded at a sampling rate of 25 kHz using Brain Vision PyCorder 1.0.7 (Brain Products, Gilching, Germany). Alternating polarities of the stimuli will be binaurally presented in sound field (identical to the animal protocols), with an inter-stimulus interval jittered between 122 to 148ms. Participants will be instructed to stay awake and refrain from making extraneous movements. EEG and pupil measures will allow continuous monitoring of participant state. The order of blocks will be counterbalanced across participants, and stimulus presentation will be controlled by E-Prime 2.0.10 software. The electrophysiological data will be preprocessed with BrainVision Analyzer 2.0 (Brain Products, Gilching, Germany), bandpass filtered (varies based on stimulus F0; 12 dB/octave, zero phase-shift). The bandpass filter will approximately reflect the lower and upper limits of phase-locking along the auditory pathway that contributes to the FFR (auditory cortex, midbrain). Responses will be segmented into epochs, baseline corrected to the mean voltage of the noise floor(-40 to 0ms). Epochs in which the amplitude exceeds ± 35μV will be considered artifacts and rejected. In each session, a preset number of artifact-free FFR trials (500 for each polarity) will be obtained. For pupillometry, participants will be seated in a chair and will place their head on a chin rest. The stabilized mount also has a small horizontal bar that they can place their forehead against. To calibrate the eye tracker, participants will be asked to follow 9 dots that appear on a monitor with their eyes. Insert earbuds will be placed in both ears, and auditory stimuli will be presented binaurally. Pupillometry data will be preprocessed to remove noise from the analysis. The pupil data will be downsampled to 50 Hz. Trials with more than 15% of the samples detected as blinks will be removed. Missing samples due to blinks will be linearly interpolated from approximately100 ms prior to and 100 ms after the blink. Pupil responses will be baseline normalized using the average pupil size in the 500-1000 ms prior to the onset of the auditory stimuli. A key variable reported will be the percent change in pupil size.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Neurotypical Human Participants | Experimental | Behavioral: Speech and non-speech sound stimulationNative speakers of Chinese and native speakers of English |
Who may qualify
- Ages
- 13 to 25 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- Age 13 years up to 25 years
- Healthy volunteers
- Native English speaking individuals with no exposure or experience to tonal languages
- Native Mandarin speakers
- Hearing sensitivity within normal limits (Puretone hearing thresholds < 25dB from 250
Key exclusion criteria (5 listed)
- Proficiency in languages other than English or Chinese
- History of or current complaint of hearing loss or tinnitus
- History of or current complaint of cognitive impairments
- Individuals with more than 5 years of formal music experience or training
- Complaints of impaired speech perception in noise
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Speech and non-speech sound stimulationListening to repetitive and extended sound presentation induces specific neural and physiological activity that we will measure via electroencephalography and pupillometry | Behavioural | Neurotypical Human Participants |
Primary outcome
Pitch tracking and decoding accuracies for dynamically varying pitch in naturally produced Mandarin tone categories
Time frame: During EEG session, up to 3 hours
The similarity between the stimulus and the FFR will be evaluated. The pitch tracking ability will be estimated by comparing the sliding window autocorrelation pitch tracks of the stimulus and FFR. Machine learning models will be trained to decode FFR to different stimulus categories based on pitch height and pitch direction. The chance estimates of the decoding accuracies will be estimated.
Stimulus-specific effects in Chinese vs. English participants
Time frame: During EEG session, up to 3 hours
The stimulus-specific effects in human participants, based on pitch tracking and decoding accuracies, will be assessed. The decoding accuracies and pitch tracking metrics for mandarin tone categories will be compared between Chinese listeners and English listeners. The focus will be to evaluate the specific benefits in Chinese listeners to track pitch height and direction patterns in Mandarin tones.
Arousal state and predictability effects on the FFRs
Time frame: During simultaneous EEG and pupillometry session, up to 3 hours
Arousal state and its dependence on encoding of predictability effects on the FFRs will be evaluated. The pitch tracking metrics and decoding accuracies will be compared across repetitive and contextual stimulus sequences while sorting the trials based on peak pupillary dilation as a proxy for arousal state. The predictability effects will be charted as a function of the arousal states and evaluated.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2026.
- Individual participant dataSharing planned: Yes. We will follow the guidelines set forth by the Open Knowledge International, which is a global non-profit organization that advocates for open science and open data. Our objectives in data sharing are to provide free and open access to everyone. Consistent with ideas articulated in the Open Data Handbook (http://opendatahandbook.org/), we will apply for an open license for resources that are not deemed as intellectual properties, make data easily available in a format that is broadly accessible and ensures longevity, and advertise it on our webpages and via social media to make it discoverable.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bharath Chandrasekaran, PhD principal investigator
Northwestern University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Speech and non-speech sound stimulation in people with Language, run by Northwestern University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pitch tracking and decoding accuracies for dynamically varying pitch in naturally produced Mandarin tone categories (time frame: During EEG session, up to 3 hours). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2026.