RESEARCH
Development of a Behavioral Model of Hearing Loss
During my doctoral training funded by a Rhodes Scholarship at Oxford University, I developed a novel behavioral animal model of hearing loss and characterized its impact on the developing brain (Thesis: A behavioral model of bilateral cochlear implantation). The publications arising from these studies contained substantial technical contributions (e.g., signal processing in cochlear implants, development of custom intracochlear arrays, integration of visual and auditory stimuli in a behavioral paradigm and information-theoretic approaches to assess stimulus-dependent neural processing). Furthermore, I gained experience in the use of a variety of tools to probe the functional activity of the brain including single neuron electrophysiology, imaging, histology, and behavioral assessments.
Hartley DE, Vongpaisal T, Xu J, Shepherd RK, King AJ, and Isaiah A. Bilateral cochlear implantation in the ferret: A novel animal model for behavioral studies. Neurosci. Methods. 2010 Jul;190(2):214-28. PMID: 20576507; PMCID: PMC2938482
Isaiah A, Vongpaisal T, King AJ, and Hartley DEH. Multisensory training improves auditory spatial processing following bilateral cochlear implantation. J Neurosci.2014 Aug;34(33):11119-11130. PMID: 25122908; PMCID: PMC4131019
Hartley DE, Isaiah A. Envelope enhancement increases cortical sensitivity to interaural envelope delays with acoustic and electric hearing. PloS one. 2014 Aug;9(8):e104097. PMID: 25093417; PMCID: PMC4122409.
Isaiah A and Hartley DE. Can training extend current guidelines for cochlear implant candidacy? Neural Regen. Res. 2015 May;10(5):718. PMID: 26109944; PMCID: PMC4468761
Probing Brain Development Using Electrophysiology and Imaging
During my surgical residency, I undertook additional post-doctoral training during which I applied models of information processing to identify a neural substrate for the cross-modal interactions related to the early development of the auditory and visual systems. These efforts enhanced my ability to take part in and publish basic research alongside busy clinical training. More recently I have worked on the effect of socioeconomic deprivation on the developing brain using statistical and computational techniques. Lately, I have collaborated with Dr. Heather Bortfeld to set up a new model of SDB outcomes using functional near infrared spectroscopy (fNIRS) of the brain.
Petrus E,* Isaiah A,* Jones AP, et al. Crossmodal induction of thalamocortical potentiation leads to enhanced information processing in the auditory cortex. Neuron. 2014 Feb;81(3):664-673 (*equal first). PMID: 24507197; PMCID: PMC4023256
Wess JM,* Isaiah A,* Watkins PV, and Kanold PO. Subplate neurons are the first cortical neurons to respond to sensory stimuli. Proc Natl Acad Sci U S A. 2017;114(47):12602-12607. PMID: 29114043; PMCID: PMC5703299 (*equal first)
Yang F, Isaiah A, Kim WH. COVLET: Covariance-Based Wavelet-Like Transform for Statistical Analysis of Brain Characteristics in Children. In International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2020 Oct 4 (pp. 83-93). Springer, Cham.
Cho H, Park G, Isaiah A, Kim WH. Covariate Correcting Networks for Identifying Associations Between Socioeconomic Factors and Brain Outcomes in Children. In International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2021 Sep 27 (pp. 421-431). Springer, Cham.
Improvement of Standard of Care for Children With SDB
Based on a robust clinical practice in a region with high prevalence of respiratory disorders and SDB, I have participated in numerous prospective studies related to the diagnosis and management of SDB. These include the use of innovative machine learning algorithms that demonstrate the use of oximetry in predicting polysomnographic severity thresholds in resource-limited environments, a randomized controlled trial improving pain control in children with SDB undergoing adenotonsillectomy, a novel anesthetic regimen to reduce adverse events, and the use of a novel imaging paradigm to detect the site of obstruction. These studies also demonstrate ability to recruit and retain patients in clinical research studies. Cumulatively, these studies have enrolled 400+ (pre-pandemic) children supporting feasibility for similar studies.
Isaiah A, Pereira KD. Outcomes after adenotonsillectomy using a fixed anesthesia protocol in children with obstructive sleep apnea. Int J Pediatr Otorhinolaryngol. 2015 May;79(5):638-643. PMID: 25727307
Isaiah A, Kiss E, Olomu P, Koral K, Mitchell RB. Characterization of upper airway obstruction using cine MRI in children with residual obstructive sleep apnea after adenotonsillectomy. Sleep Med. 2018 Oct; 50:79-86. PMID: 30015255.
Bertoni D, Sterni LM, Pereira KD, Das G, Isaiah A*. Predicting polysomnographic severity thresholds in children using machine learning. Pediatr Res. 2020 Sep; 88(3):404-411. PMID: 32386396
Greenwell AG, Isaiah A, Pereira KD. Recovery After Adenotonsillectomy-Do Steroids Help? Outcomes from a Randomized Controlled Trial. Otolaryngol Head Neck Surg. 2021 Jul;165(1):83-88. PMID: 33228459
Investigating SDB Outcomes Using Data Science Techniques
From 2017 onwards, I have continuously collaborated with Dr Gautam Das, a database expert at University of Texas Arlington to further our understanding of pediatric SDB. Assisted by a Cooperative Travel Research Grant from the Burroughs Wellcome Fund to visit his Database Exploration Laboratory at University of Texas Arlington (UTA), I gained skills in data wrangling, manipulation, and organization, (ii) path analysis, structural equation and mediation models, and (iii) machine learning. We successfully translated this collaboration into five manuscripts.
Isaiah A, Pereira KD, and Das G. Polysomnography and Treatment-Related Outcomes of Childhood Sleep Apnea. Pediatrics. 2019;144(4):e20191097, PMID: 31533972
Isaiah A, Spanier AJ, Grattan LM, Wang Y, Pereira KD. Predictors of Behavioral Changes After Adenotonsillectomy in Pediatric Obstructive Sleep Apnea. JAMA Otolaryngology–Head & Neck Surgery. Oct 2020; 146(10):900-908, PMID: 322880655; PMCID: PMC7489416
Isaiah A, Bertoni D, Pereira KD, Diaz-Abad M, Mitchell RB, and Das G. Treatment-related changes in heart rate variability in children with sleep apnea. Otolaryngol Head Neck Surg. 2020 May;162(5):737-745. PMID: 32122243
Isaiah A, Shikara M, Pereira KD, and Das G. Refining screening questionnaires for prediction of sleep apnea severity in children. Sleep Breath. 2020 Dec; 24(4):1349-1356. PMID: 31776897
Brain Development in the ABCD Dataset
Since September 2019, I have been a co-investigator in the ABCD study. I am familiar with the recruitment and retention protocols associated with the study, the organization and analysis of the dataset. I have published two first-author high-impact papers over the course of one year and co-authored numerous others. Given my expertise that spans biostatistical and machine learning methods, I have provided guidance to graduate students and postdoctoral fellows in the analysis of the dataset, especially rigor and reproducibility of the findings. Although my own work has focused on sleep-related outcomes, I have worked on or contributed to the analysis of other exposures.