Cortical Contributions to FFR: Post-Op Outcomes

Study Overview
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Brief Summary
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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
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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: 1. 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.

Official Title
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Cortical Contributions to Frequency-Following Response Generation and Modulation; Post-Operative Outcomes

Conditions
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Language

Intervention / Treatment
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* Behavioral: Speech sound stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: Significant medical or neuropsychological impairment that would result in the patient being unable to participate in study activities History of autism or ADHD

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 25 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neurosurgical Patients<br>Patient participants with previously excised tissue within Heschl's gyrus (as dictated by clinical care) | Behavioral: Speech sound stimulation<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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. | 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. | 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. | 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. | During follow-up research sessions, at least 6-months post-sEEG |