Cortical Contributions to FFR: Post-Op Outcomes

Official title

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

Overview

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:

1. To build a novel computational model of cortical feedforward mechanisms involved in FFRs. 2. 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.

Interventions

• Behavioral Speech sound stimulation
  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

Primary outcome measures

• Pitch Decoding Accuracy [Time frame: During sEEG-EEG recording sessions, up to 3 hours total]
• Frequency-Following Response Magnitude [Time frame: During sEEG-EEG recording sessions, up to 3 hours total]
• Cortical Phase-Locking Limits of Frequency-Following Response [Time frame: During sEEG-EEG recording sessions, up to 3 hours total]
• Predictability Effects of Cortical Resection on Pitch Decoding Accuracy [Time frame: During follow-up research sessions, at least 6-months post-sEEG]
• Predictability Effects of Cortical Resection on Frequency-Following Response Magnitude [Time frame: During follow-up research sessions, at least 6-months post-sEEG]
• 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]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Basic science

Study locations

United States · 1 center

• UPMC Children's Hospital of Pittsburgh — Pittsburgh

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. PMID 21319935
• Coffey 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. PMID 31695046
• White-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. PMID 31268800

Identifiers

NCT: NCT05214092 · STUDY21100033 · R01DC013315

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗