LanguageNCT05214092
Cortical Contributions to FFR: Post-Op Outcomes
A study testing Speech sound stimulation in people with Language, run by University of Pittsburgh at 1 site in United States.
Trial summary
The purpose of this study is to better understand cortical contributions of the human temporal lobe to the frequency-following response. Frequency-following responses (FFR) are electrophysiological recordings that reflect phase-locked activity of neural ensembles in the auditory pathway and are used as an indicator of… Read more about this study
- Who is it for?
- Ages 13 to 25 years
- Conditions the study is for
- Language
- What is being tested?
- Speech sound stimulation
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Feb 2023to 1 Jan 2030
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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
- No healthy volunteers
- Child, Adult
Who may be able to join
- Individuals 13-25 years old
- Undergoing medically necessary surgical resection of Heschl's gyrus lesion
- Monolingual English speakers
- Receptive and expressive language within normal limits
- Normal or corrected-to-normal visual acuity
- Normal hearing acuity in each ear (as determined during an audiometric assessment)
- Nonverbal IQ within normal limits
- No history of autism spectrum disorder or attention-deficit hyperactivity disorder
Who cannot join
- Significant medical or neuropsychological impairment that would result in the patient being unable to participate in study activities
- History of autism or ADHD
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
UPMC Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224
About this study
Official title: Cortical Contributions to Frequency-Following Response Generation and Modulation; Post-Operative Outcomes
The purpose of this study is to better understand cortical contributions of the human temporal lobe to the frequency-following response. Frequency-following responses (FFR) are electrophysiological recordings that reflect phase-locked activity of neural ensembles in the auditory pathway and are used as an indicator of the integrity of supra-threshold speech processing. FFR was first studied in subcortical areas, but recent consensus in the literature supports the notion that it is an integrated response between subcortical and cortical neural populations. The proposed study aims to deconstruct the role of the cortex in generating and modulating the FFR. The research team will build a novel computational model of FFR mechanisms and use EEG recordings from participants who have undergone resection of lesions in Heschl's gyrus to validate model predictions.
Read the detailed description
The purpose of this study is to better understand the cortical contribution of the human temporal lobe to the generation and modulation of frequency-following responses (FFR).
The specific aims of this study is as follows:
- To build a novel computational model of cortical feedforward mechanisms involved in FFRs.
- To test model predictions of cortical removal in human participants who have undergone surgical resection of Heschl's gyrus lesions.
The hypothesis to be tested for the previously listed purposes and aims are as follows:
- When cortical areas involved in generating and modulating the FFR, in this case Heschl's gyrus, are removed or inactivated, the FFR response will be attenuated.
The frequency-following response has been used extensively in auditory processing literature as a minimally invasive method of recording the integrity of supra-threshold speech processing. It was once considered to be reflective of only subcortical activity in structures like the brainstem, however a recent consensus has been reached in research on the topic that supports the notion of cortical neural population involvement in FFR as well.
The pilot study conducted under the initial parent grant for this study (Online Modulation of Auditory Brainstem Responses to Speech) proposed that subcortical auditory processing is not a hard-wired mechanism in the human brain but is rather continuously fine-tuned to stimuli by top-down expectations. This study further demonstrated that stimulus predictability, attention, and category-relevance have a robust effect on response fidelity and can modulate the FFR. The current study proposes to study the same effects and response patterns in cortical structures. Limited studies to date have investigated the effect of auditory cortex lesions on the FFR and existing studies did not account for the variables investigated in this study that are proposed to have a significant effect on modulation of FFRs.
Even though FFR is widely accepted as a metric for measuring the integrity of speech encoding, there remains a poor understanding of the neural generators of this response. A few studies to date have already identified abnormal or dysfunctional FFR in certain clinical populations like ADHD and autism spectrum disorders. The proposed study additionally seeks to identify the potential translational utility of FFR as a biomarker for clinical conditions.
This study is innovative as data from this study will allow researchers to build a novel computational model of cortical feedforward and feedback mechanisms, which will be tested in patient participants who have undergone surgical resection of Heschl's gyrus lesions.
- Conditions
- Language
- Being tested
- 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 sound stimulationBehavioural
Participants will listen to repetitive speech sound stimuli, presented through headphones, which will induce a neural response (frequency-following response) to be measured via electroencephalography and pupillometry
| Study group | Role | What they receive |
|---|---|---|
| Neurosurgical Patients | Experimental | Patient participants with previously excised tissue within Heschl's gyrus (as dictated by clinical care) Receives: Behavioral: Speech sound stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pitch Decoding Accuracy
Pitch decoding accuracy will be measured as a stimulus-to-response correlation between stimulus pitch (in Hz) and scalp-recorded frequency-following responses (FFR). Hidden Markov models (HMMs) will be used to decode stimulus identity information from recorded FFRs.
Measured: During sEEG-EEG recording sessions, up to 3 hours total
Frequency-Following Response Magnitude
The frequency-following response magnitude will be measured by analyzing the time-domain averaged spectral peak of scalp-recorded FFRs.
Measured: During sEEG-EEG recording sessions, up to 3 hours total
Cortical Phase-Locking Limits of Frequency-Following Response
Phase-locking limits of FFRs will be measured by comparing phase coherence of stimulus waveforms and scalp-recorded FFRs. The phase-locking limit will be determined as a function of dependence on stimulus frequency.
Measured: During sEEG-EEG recording sessions, up to 3 hours total
Predictability Effects of Cortical Resection on Pitch Decoding Accuracy
The predictability effects of cortical resection on pitch decoding accuracy will be measured via comparison of decoding accuracies obtained in Outcome 1 and values predicted by a previously created computational model of frequency-following response constrained by data from neurotypical participants.
Measured: During follow-up research sessions, at least 6-months post-sEEG
Predictability Effects of Cortical Resection on Frequency-Following Response Magnitude
The predictability effects of cortical resection on frequency-following response magnitude will be measured via comparison of response magnitude measurements obtained in Outcome 3 and values predicted by a previously created computational model of frequency-following response constrained by data from neurotypical participants.
Measured: During follow-up research sessions, at least 6-months post-sEEG
Predictability Effects of Cortical Resection on Phase-Locking Limits of Frequency-Following Response
The predictability effects of cortical resection on phase-locking limits of the frequency-following response will be measured via comparison of phase-locking limits obtained in Outcome 3 and values predicted by a previously created computational model of frequency-following response constrained by data from neurotypical participants.
Measured: During follow-up research sessions, at least 6-months post-sEEG
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2022
- Study start14 Feb 2023
- Primary completion1 Jan 2027 (estimated)
- Study completion1 Jan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for LanguageStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe 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
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Deafness and Other Communication Disorders (NIDCD)
- Responsible party
- Principal investigator, Taylor Abel, University of Pittsburgh
- Investigators
- Taylor Abel, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05214092
- Sponsor's protocol ID
- STUDY21100033
- Other IDs
- R01DC013315
- Status last verified
- Jan 2026
- First submitted
- 12 Jan 2022
- Last updated
- 15 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The individual deidentified participant data intended to be shared include the individual participant data that underlie the results to be reported in published articles after deidentification. Other documents that will be available include the study protocol, statistical analysis plan, and analytic code. Data will be available as soon as possible following publication, but no later than one year upon completion. There is no end date. IPD will be made available for any purpose via open access.
Publications
Arehart KH, Kates JM, Anderson MC. Effects of noise, nonlinear processing, and linear filtering on perceived music quality. Int J Audiol. 2011 Mar;50(3):177-90. doi: 10.3109/14992027.2010.539273.
PubMed 21319935Coffey EBJ, Nicol T, White-Schwoch T, Chandrasekaran B, Krizman J, Skoe E, Zatorre RJ, Kraus N. Evolving perspectives on the sources of the frequency-following response. Nat Commun. 2019 Nov 6;10(1):5036. doi: 10.1038/s41467-019-13003-w.
PubMed 31695046White-Schwoch T, Anderson S, Krizman J, Nicol T, Kraus N. Case studies in neuroscience: subcortical origins of the frequency-following response. J Neurophysiol. 2019 Aug 1;122(2):844-848. doi: 10.1152/jn.00112.2019. Epub 2019 Jul 3.
PubMed 31268800
Study at a glance
From the registry record, last updated by the sponsor on 15 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cortical Contributions to Frequency-Following Response Generation and Modulation; Post-Operative Outcomes
- ClinicalTrials.gov ID
- NCT05214092
- Acronym / sponsor ID
- STUDY21100033
- Conditions
- Language
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Collaborators
- National Institute on Deafness and Other Communication Disorders (NIDCD)
- Study start
- 14 Feb 2023 (actual)
- Primary completion
- 1 Jan 2027 (estimated)
- Study completion
- 1 Jan 2030 (estimated)
- First posted
- 28 Jan 2022 (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 purpose of this study is to better understand cortical contributions of the human temporal lobe to the frequency-following response. Frequency-following responses (FFR) are electrophysiological recordings that reflect phase-locked activity of neural ensembles in the auditory pathway and are used as an indicator of the integrity of supra-threshold speech processing. FFR was first studied in subcortical areas, but recent consensus in the literature supports the notion that it is an integrated response between subcortical and cortical neural populations. The proposed study aims to deconstruct the role of the cortex in generating and modulating the FFR. The research team will build a novel computational model of FFR mechanisms and use EEG recordings from participants who have undergone resection of lesions in Heschl's gyrus to validate model predictions.
Detailed description
The purpose of this study is to better understand the cortical contribution of the human temporal lobe to the generation and modulation of frequency-following responses (FFR).
The specific aims of this study is as follows:
- To build a novel computational model of cortical feedforward mechanisms involved in FFRs.
- To test model predictions of cortical removal in human participants who have undergone surgical resection of Heschl's gyrus lesions.
The hypothesis to be tested for the previously listed purposes and aims are as follows:
- When cortical areas involved in generating and modulating the FFR, in this case Heschl's gyrus, are removed or inactivated, the FFR response will be attenuated.
The frequency-following response has been used extensively in auditory processing literature as a minimally invasive method of recording the integrity of supra-threshold speech processing. It was once considered to be reflective of only subcortical activity in structures like the brainstem, however a recent consensus has been reached in research on the topic that supports the notion of cortical neural population involvement in FFR as well.
The pilot study conducted under the initial parent grant for this study (Online Modulation of Auditory Brainstem Responses to Speech) proposed that subcortical auditory processing is not a hard-wired mechanism in the human brain but is rather continuously fine-tuned to stimuli by top-down expectations. This study further demonstrated that stimulus predictability, attention, and category-relevance have a robust effect on response fidelity and can modulate the FFR. The current study proposes to study the same effects and response patterns in cortical structures. Limited studies to date have investigated the effect of auditory cortex lesions on the FFR and existing studies did not account for the variables investigated in this study that are proposed to have a significant effect on modulation of FFRs.
Even though FFR is widely accepted as a metric for measuring the integrity of speech encoding, there remains a poor understanding of the neural generators of this response. A few studies to date have already identified abnormal or dysfunctional FFR in certain clinical populations like ADHD and autism spectrum disorders. The proposed study additionally seeks to identify the potential translational utility of FFR as a biomarker for clinical conditions.
This study is innovative as data from this study will allow researchers to build a novel computational model of cortical feedforward and feedback mechanisms, which will be tested in patient participants who have undergone surgical resection of Heschl's gyrus lesions.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Neurosurgical Patients | Experimental | Behavioral: Speech sound stimulationPatient participants with previously excised tissue within Heschl's gyrus (as dictated by clinical care) |
Who may qualify
- Ages
- 13 to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- Individuals 13-25 years old
- Undergoing medically necessary surgical resection of Heschl's gyrus lesion
- Monolingual English speakers
- Receptive and expressive language within normal limits
- Normal or corrected-to-normal visual acuity
Key exclusion criteria (2 listed)
- Significant medical or neuropsychological impairment that would result in the patient being unable to participate in study activities
- History of autism or ADHD
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 sound stimulationParticipants will listen to repetitive speech sound stimuli, presented through headphones, which will induce a neural response (frequency-following response) to be measured via electroencephalography and pupillometry | Behavioural | Neurosurgical Patients |
Primary outcome
Pitch Decoding Accuracy
Time frame: During sEEG-EEG recording sessions, up to 3 hours total
Pitch decoding accuracy will be measured as a stimulus-to-response correlation between stimulus pitch (in Hz) and scalp-recorded frequency-following responses (FFR). Hidden Markov models (HMMs) will be used to decode stimulus identity information from recorded FFRs.
Frequency-Following Response Magnitude
Time frame: During sEEG-EEG recording sessions, up to 3 hours total
The frequency-following response magnitude will be measured by analyzing the time-domain averaged spectral peak of scalp-recorded FFRs.
Cortical Phase-Locking Limits of Frequency-Following Response
Time frame: During sEEG-EEG recording sessions, up to 3 hours total
Phase-locking limits of FFRs will be measured by comparing phase coherence of stimulus waveforms and scalp-recorded FFRs. The phase-locking limit will be determined as a function of dependence on stimulus frequency.
Predictability Effects of Cortical Resection on Pitch Decoding Accuracy
Time frame: During follow-up research sessions, at least 6-months post-sEEG
The predictability effects of cortical resection on pitch decoding accuracy will be measured via comparison of decoding accuracies obtained in Outcome 1 and values predicted by a previously created computational model of frequency-following response constrained by data from neurotypical participants.
Predictability Effects of Cortical Resection on Frequency-Following Response Magnitude
Time frame: During follow-up research sessions, at least 6-months post-sEEG
The predictability effects of cortical resection on frequency-following response magnitude will be measured via comparison of response magnitude measurements obtained in Outcome 3 and values predicted by a previously created computational model of frequency-following response constrained by data from neurotypical participants.
Predictability Effects of Cortical Resection on Phase-Locking Limits of Frequency-Following Response
Time frame: During follow-up research sessions, at least 6-months post-sEEG
The predictability effects of cortical resection on phase-locking limits of the frequency-following response will be measured via comparison of phase-locking limits obtained in Outcome 3 and values predicted by a previously created computational model of frequency-following response constrained by data from neurotypical participants.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2026.
- Background: PubMed 21319935Arehart KH, Kates JM, Anderson MC. Effects of noise, nonlinear processing, and linear filtering on perceived music quality. Int J Audiol. 2011 Mar;50(3):177-90. doi: 10.3109/14992027.2010.539273.
- Background: PubMed 31695046Coffey EBJ, Nicol T, White-Schwoch T, Chandrasekaran B, Krizman J, Skoe E, Zatorre RJ, Kraus N. Evolving perspectives on the sources of the frequency-following response. Nat Commun. 2019 Nov 6;10(1):5036. doi: 10.1038/s41467-019-13003-w.
- Background: PubMed 31268800White-Schwoch T, Anderson S, Krizman J, Nicol T, Kraus N. Case studies in neuroscience: subcortical origins of the frequency-following response. J Neurophysiol. 2019 Aug 1;122(2):844-848. doi: 10.1152/jn.00112.2019. Epub 2019 Jul 3.
- Individual participant dataSharing planned: Yes. The individual deidentified participant data intended to be shared include the individual participant data that underlie the results to be reported in published articles after deidentification. Other documents that will be available include the study protocol, statistical analysis plan, and analytic code. Data will be available as soon as possible following publication, but no later than one year upon completion. There is no end date. IPD will be made available for any purpose via open access.
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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.
Taylor Abel, MD principal investigator
University of Pittsburgh
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 sound stimulation in people with Language, run by University of Pittsburgh 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 8 inclusion and 2 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: enrolling by invitation, as of the sponsor's last update on 15 Jan 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?
This study is still under way. Results are not available in the source record yet.
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 Decoding Accuracy (time frame: During sEEG-EEG recording sessions, up to 3 hours total). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05214092, which also lists 3 linked publications.
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 15 Jan 2026.