Multidisciplinary R01 Study To Explore Mechanistic Processes and Cortical Contributions to the Frequency-Following Response in Auditory Processing

A multidisciplinary research team at UPMC and the University of Pittsburgh has begun new studies that will elucidate the properties of the frequency-following response (FFR) in auditory speech processing with the ultimate goal of helping to develop translational biomarkers that can aid in the diagnosis of numerous speech-processing-related disorders and conditions.

Leading the study is principal investigator Bharath Chandrasekaran, PhD, professor and vice-chair in the Department of Communication Science and Disorders at the University of Pittsburgh. Collaborating with Dr. Chandrasekaran are co-PIs Tobias Teichert, PhD, assistant professor of psychiatry and bioengineering at the University of Pittsburgh; Srivatsun Sadagopan, PhD, assistant professor in the Department of Neurobiology at the University of Pittsburgh; and Taylor J. Abel, MD, FAANS, assistant professor in the Division of Pediatric Neurological Surgery at the University of Pittsburgh School of Medicine and surgical director of the Pediatric Epilepsy Surgery Program at UPMC Children’s Hospital of Pittsburgh. 

The new grant, titled “Cortical Contributions to Frequency-following Response Generation and Modulation,” builds upon previous NIH-funded work by Dr. Chandrasekaran and colleagues that explored how auditory brainstem responses to speech are influenced by experience-dependent plasticity.

The FFR is a well-known speech biomarker in the brain used as a metric for assessing how the brain encodes speech signals in both healthy individuals and individuals with speech processing disorders.

However, a certain amount of controversy exists in the field related to the cortical contributions of the FFR at the level of the cerebral cortex. The study team will investigate these cortical mechanisms of the FFR across different species, including humans, a non-human primate, and guinea pigs, and across scales – scalp EEG, intracranial recordings, and animal electrophysiology.

“As an epilepsy surgeon who uses stereotactic electroencephalography (SEEG) during epilepsy surgery, we have the unique ability to collect intracranial or direct brain recordings of electrical signaling and activity of cortical processing during epilepsy surgical procedures, which is essentially impossible to do in humans in any other situation because of the invasiveness of the procedure. SEEG is not something you can or would consider using in healthy subjects to obtain intracranial data,” says Dr. Abel.

The cross-disciplinary research team is uniquely positioned to perform these studies because of the varied expertise of the investigators. Dr. Chandrasekaran’s research is focused on understanding neurobiological computations that underlie human communication and learning, including studying the FFR using scalp EEG recordings; Dr. Teichert’s research involves studies of the neural mechanisms of auditory function and decision-making in nonhuman primates to better understand the nature of auditory deficits in individuals with schizophrenia;  Dr. Sadagopan’s expertise lies in the study of how the auditory system transforms the neural representation of sounds from one that is based on the sensing of individual frequencies to a representation that can support complex behaviors such as speech and perception;  and Dr. Abel specializes in studying how the brain processes auditory signals using a combination of electrophysiology, neuroimaging, and lesion mapping techniques in the human brain in epilepsy surgery patients, where both scalp EEG and SEEG can be combined to build a bridge between the two data sets.

By combining their varied scientific expertise, the study team is positioned to study FFR in humans and compare the responses to what is seen in animal models where more mechanistic-focused experiments and data can be obtained.

Study Aims Details

The first aim of the study is to perform experiments that will measure FFRs from scalp EEG recordings and intracranial recordings in all three biological systems – humans, monkeys, and guinea pigs. This data will allow the research team to  “characterize cortical phase-locking limits, laminar and frequency dependence, and hemispheric asymmetry across the models.” 

The second aim of the study will focus on obtaining intracranial and scalp EEG recordings of FFRs while subjects experience both human speech sounds and non-human vocalizations while measuring and analyzing the differences in FFR patterns within and across species. 

The third aim of the research involves the design of a computational model that “consists of a core feedforward module that is modulated by a feedback cortico-collicular module. Predictions from this model will be systematically validated in human patients with Heschl’s gyrus lesions, and using chemogenetic experiments to reversibly suppress cortico-collicular feedback in animal models.”

Toward FFRs as a Clinical Biomarker for Speech Processing Disorders

FFR now is essentially a way of measuring the integrity of speech signals in the brain. FFR can become impaired in certain speech processing disorders. Having a more fully detailed understanding of FFR and its mechanistic constituents may allow it to be used as a robust biomarker to aid in the diagnosis of various speech processing disorders. FFR also may be a way of monitoring either the progression of the disorder or perhaps even the recovery or normalization of FFR as part of a rehabilitative process or protocol for the underlying condition or clinical presentation.

Data Will Help Better Understand Speech Processing Patterns After Epilepsy Surgery

In a separate component of the grant, Dr. Abel, with this SEEG intracranial study data, will assess and better understand speech processing differences that epilepsy surgical patients have after they have had surgery and had a portion or part of their auditory cortex removed. While the data will not necessarily help inform or shape how epilepsy surgery may be performed on individual patients, the data collected will be useful in helping epilepsy surgeons better understand patient speech processing patterns  after surgery.

Reference

Cortical Contributions to Frequency-Following Response Generation and Modulation. Project Number: 2R01DC013315. Co-Principal Investigators: Bharath Chandrasekaran; Taylor Abel; Srivatsun Sadagopan; Tobias Teichert.