About

Daniel A. Llano is a Professor in Molecular & Integrative Physiology at the Illinois College of Liberal Arts & Sciences School of Molecular & Cellular Biology. His research focuses on the mechanisms by which complex sounds, such as speech, are processed by the auditory system. He hypothesizes that the auditory system generates internal models of the sensory world and uses these models to extract meaning from complex sensory stimuli. His laboratory employs electrophysiological, optical, and anatomical approaches to study projections from the auditory cortex to subcortical structures, exploring the roles of different cortical subnetworks in complex sound processing. Llano's work investigates the functional organization of descending projections from the auditory cortex and their influence on the auditory periphery, with particular attention to the different roles played by neurons in cortical layers 5 and 6. In addition to basic science, his clinical and translational work is focused on aging and neurodegenerative diseases, especially aging-related auditory network dysfunction and changes in network properties in the auditory thalamus and cortex. He has received numerous awards for his teaching and research, including the Presidential Early Career Award for Scientists and Engineers (PECASE) in 2019, and has taught courses such as Introduction to Neurobiology and Clinical Neuroscience. Llano is affiliated with the Beckman Institute for Advanced Science and Technology and is a Physician-Surgeon at Carle Illinois College of Medicine. His research interests also encompass computational biology, neurobiology, optogenetics, sensory processing, and disease research related to aging and neurological disorders.

Research topics

• Psychology
• Medicine
• Biology
• Materials science
• Biomedical engineering
• Neuroscience
• Audiology
• Radiology
• Pathology

Selected publications

• Atypical Initial Manifestation of Sporadic Creutzfeldt-Jakob Disease as Progressive Aphasia and Palinopsia: A Case Report

  Cognitive and Behavioral Neurology · 2026-04-16

  articleSenior authorCorresponding

  Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare neurodegenerative disorder that causes rapidly progressive dementia. While it typically presents with cognitive decline, ataxia, and myoclonus, atypical presentations are increasingly recognized. Here we present the case of a 57-year-old male with the MM1 subtype of sCJD. He had an atypical presentation of progressive language difficulties and subtle visual disturbances, initially diagnosed as primary progressive aphasia. Brain MRI showed an indistinct left parietal-occipital T2 hyperintensity. Subsequent MRI scans of the brain taken over a period of several months showed left caudate diffusion restriction. EEG demonstrated left hemispheric slowing and bifrontal triphasic discharges. The patient also began exhibiting prominent visual disturbances and hallucinations, which are typically associated with the Heidenhain variant of Creutzfeldt-Jakob disease (CJD). However, his aphasia differed from the classic Heidenhain presentation. This case highlights that sCJD can be easily misdiagnosed as other neurological conditions due to its variable presentation, in this case, initially resembling primary progressive aphasia. Awareness of atypical presentations is crucial for early identification and diagnosis of sCJD.

  PublisherDOI

• Combined Nanodrops Imaging and Ultrasound Localization Microscopy for Detecting Intracerebral Hemorrhage

  Ultrasound in Medicine & Biology · 2025-01-20 · 1 citations

  articleOpen access
  PublisherOA PDFDOI

• Author response: Longitudinal Awake Imaging of Mouse Deep Brain Microvasculature with Super-resolution Ultrasound Localization Microscopy

  2025-02-27

  peer-reviewOpen access

  Ultrasound localization microscopy (ULM) is an emerging imaging modality that resolves microvasculature in deep tissues with high spatial resolution. However, existing preclinical ULM applications are largely constrained to anesthetized animals, introducing confounding vascular effects such as vasodilation and altered hemodynamics. As such, ULM quantifications (e.g., vessel diameter, density, and flow velocity) may be confounded by the use of anesthesia, undermining the usefulness of ULM in practice. Here we introduce a method to address this limitation and achieve ULM imaging in awake mouse brain. Pupillary monitoring was used to support the presence of the awake state during ULM imaging. Vasodilation induced by isoflurane was observed by ULM. Upon recovery to the awake state, reductions in vessel density and flow velocity were observed across different brain regions. In the cortex, the effects induced by isoflurane are more pronounced on venous flow than on arterial flow. In addition, serial in vivo imaging of the same animal brain at weekly intervals demonstrated the highly robust longitudinal imaging capability of the proposed technique. The consistency was further verified through quantitative analysis on individual vessels, cortical regions of arteries and veins, and subcortical regions. This study demonstrates longitudinal ULM imaging in the awake mouse brain, which is crucial for many ULM brain applications that require awake and behaving animals.

  PublisherDOI

• Cold microplasma exposure as a novel therapeutic treatment: future implications for the management of bacterial otitis media

  2025-03-19

  article
  PublisherDOI

• Longitudinal Awake Imaging of Mouse Deep Brain Microvasculature with Super-resolution Ultrasound Localization Microscopy

  eLife · 2025-10-03

  articleOpen access

  Abstract Ultrasound localization microscopy (ULM) is an emerging imaging modality that resolves microvasculature in deep tissues with high spatial resolution. However, existing preclinical ULM applications are largely constrained to anesthetized animals, introducing confounding vascular effects such as vasodilation and altered hemodynamics. As such, ULM quantifications (e.g., vessel diameter, density, and flow velocity) may be confounded by the use of anesthesia, undermining the usefulness of ULM in practice. Here we introduce a method to address this limitation and achieve ULM imaging in awake mouse brain. Pupillary monitoring was used to support the presence of the awake state during ULM imaging. Vasodilation induced by isoflurane was observed by ULM. Upon recovery to the awake state, reductions in vessel density and flow velocity were observed across different brain regions. In the cortex, the effects induced by isoflurane are more pronounced on venous flow than on arterial flow. In addition, serial in vivo imaging of the same animal brain at weekly intervals demonstrated the highly robust longitudinal imaging capability of the proposed technique. The consistency was further verified through quantitative analysis on individual vessels, cortical regions of arteries and veins, and subcortical regions. This study demonstrates longitudinal ULM imaging in the awake mouse brain, which is crucial for many ULM brain applications that require awake and behaving animals.

  PublisherDOI

• Modification and validation of a GAD-GFP mouse line without accelerated aging-related hearing loss

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-04-03 · 1 citations

  preprintOpen accessSenior authorCorresponding

  GABAergic neurons in the inferior colliculus (IC) play a crucial role in auditory processing by extracting specific features of sounds (Ono et al., 2005). The Gad67-GFP mouse model developed by Tamamaki et al. in 2003 on a Swiss background facilitates studying these neurons by using a green fluorescent protein that is expressed endogenously via the GAD67 promoter. Unfortunately, this mouse suffers from accelerated aging-related hearing loss, limiting its utility in studying the auditory system. Here, we report the results of an 8-generation backcross of this line onto CBA/CaJ mice, which produces mice with stable low-threshold hearing while retaining GFP expression in GAD+ neurons. Additionally, this study investigates mechanisms that underlie hearing loss in the Gad67-GFP mouse model by focusing specifically on cochlear hair cells (HCs) and ribbon synapses, which may contribute to both model-specific hearing loss and clinical disorders like presbycusis. Findings revealed the newly generated F1 mouse model that resulted from the Gad67-GFP x CBA/CaJ backcross maintained better hearing thresholds when compared to ABR data for Gad67 and Swiss mice and very closely resembled those of the CBA/CaJ mice, mirroring progression of presbycusis in humans. Additionally, all morphological changes observed in cochlear structure correlated to ABR thresholds. F1 mice continued maintained expression of the GAD67 promoter in the IC via immunostaining.

  PublisherDOI

• Hearing aid interventions to mitigate cognitive impairment: A critical review of the literature and meta-analysis

  medRxiv · 2025-03-26 · 1 citations

  reviewOpen accessSenior authorCorresponding

  Abstract Aging-related hearing loss (ARHL) is epidemiologically linked to the development of Alzheimer’s Disease (AD). The mechanisms underlying this relationship are not known and have important therapeutic implications. If ARHL is causally linked to the development of AD, then correction of hearing loss via hearing aids should mitigate cognitive impairments in AD and more aggressive campaigns to treat ARHL, which is widely undertreated, would be warranted. Here, we critically examine the literature involving the use of hearing aids to treat ARHL and examine the impact of hearing aids on cognition. Although many studies report beneficial effects of hearing aids on cognition, most of these studies have significant flaws in their experimental design, making it difficult to judge their outcomes. In our selection process, we prioritized randomized studies and those with blinded and placebo-controlled outcomes. We evaluated a total of 10 papers that met inclusion criteria. Within our literature review, we found two randomized placebo-controlled studies that examined the impact of hearing aids on cognition in cognitively-impaired or vulnerable older individuals with minimal risk of bias. Meta-analysis of these two studies did not yield a statistically significant benefit of hearing aid use after 6 or 12 months of use. We propose that the current literature on this topic currently lacks compelling evidence to demonstrate that hearing aid use directly benefits cognition or delays AD. We further recommend strategies for improving clinical trial design to bring greater clarity to this important issue.

  PublisherOA PDFDOI

• Cold microplasma exposure as a novel therapeutic treatment for bacterial otitis media: study results and conclusions in a small animal model

  2025-03-19

  article
  PublisherDOI

• Multiple Ischemic Strokes in a Patient Treated with Lecanemab: A Case Report

  Research Square · 2025-01-28

  preprintOpen accessSenior author
  PublisherOA PDFDOI

• A Protocol for Microprism‐Based Two‐Photon Imaging Of The Lateral Cortex In The Mouse Inferior Colliculus

  Current Protocols · 2025-12-31

  articleOpen accessSenior authorCorresponding

  The inferior colliculus (IC) is a central hub for auditory information processing that receives widespread convergent projections. The IC comprises three main subdivisions: the central nucleus of the IC (ICC), the dorsal cortex (DC), and the lateral cortex (LC). While the ICC receives primarily ascending auditory information, DC and LC receive major cortical and multisensory projections. The LC has repeated molecular motifs that govern its input-output relationships. However, because the LC is buried deep within a sulcus, it is difficult to image in behaving animals, making it challenging to answer questions about its functional organization. Here, we describe a protocol for coupling two-photon microscopy with a microprism to obtain cellular-resolution sagittal views of functional LC maps. We employed this novel approach to investigate neuronal responses to pure tones in relation to LC motifs. This method will not only provide new insights into the auditory system but will also permit imaging of hidden brain regions previously inaccessible by conventional means. © 2025 The Author(s). Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Craniotomy and implantation of the microprism. Basic Protocol 2: Data acquisition from sound-responsive neurons. Basic protocol 3: Confirming the microprism location. Basic Protocol 4: Analyzing the time traces of neuronal responses and generating a best-frequency tuning Map.

  PublisherOA PDFDOI

Recent grants

• NIH Grant K08DC008320

  NIH · $288k · 2011

• NIH Grant S10OD023569

  NIH · $771k · 2019

• NIH Grant R03DC012125

  NIH · $445k · 2015

• Fiber-Delivered Programmable Supercontinuum Laser Adaptive to EvolvingNeurophotonic Research

  NIH · $878k · 2019–2022

• Synaptic mechanisms of auditory thalamic cross-modal communication

  NIH · $1.6M · 2021–2026

Frequent coauthors

• Viswanath Devanarayan

  Eisai (United States)

  67 shared

• Baher A. Ibrahim

  University of Illinois Urbana-Champaign

  32 shared

• Nathiya Vaithiyalingam Chandra Sekaran

  Laboratoire d’immunologie intégrative du cancer

  25 shared

• Pengfei Song

  Illinois College

  25 shared

• Kevin A. Stebbings

  24 shared

• Matthew R. Lowerison

  23 shared

• Yoshitaka Shinagawa

  University of Illinois Urbana-Champaign

  21 shared

• Huan Wang

  21 shared

Labs

• Llano LabPI

  Not provided

Awards & honors

• Excellence in Teaching Recognition (2012-2019, 2021)
• Presidential Early Career Award for Scientists and Engineers…
• Helen Corley Petit Scholar (2017)
• Benjamin R. and Elinor W. Bullock and Edwin E. and Jeanne Bu…
• Advances in Medicine Award, Carle Hospital (2016)