Contact Information
405 North Mathews Avenue
Urbana, IL 61801
Research Areas
Research Interests
Research Topics
Computational Biology, Imaging, Neurobiology, Optogenetics, Sensory Processing
Disease Research Interests
Aging Related Diseases, Neurological and Behavioral Disorders
Research Description
The role of top-down projections in the processing of complex sounds
Our laboratory studies the mechanisms by which complex sounds, such as speech, are processed by the auditory system. We hypothesize that the auditory system generates internal models of the sensory world, and uses these models to extract meaning from complex sensory stimuli. One potential neuronal substrate for this generative model is the massive system of descending projections from the auditory cortex to virtually every level of the subcortical auditory system. These projections are critical for shaping the response properties of neurons in the auditory periphery, but very little is known about their functional organization.
We employ electrophysiological, novel optical and advanced anatomical approaches to study the projections from the auditory cortex to subcortical structures. One specific set of issues that we address concerns the role of different cortical subnetworks in complex sound processing. For example, neurons in both cortical layer 5 and cortical layer 6 project to subcortical structures, and the neurons in these layers have very different intrinsic, integrative and synaptic properties. Our work explores the different roles that these groups of neurons play in the processing of complex sound.
Clinical/Translational
My patient care work is focused on aging and neurodegenerative disease. Consequently, our laboratory has an interest aging-related auditory network dysfunction, particularly as it relates to changes in network properties in the auditory thalamus and cortex.
Awards and Honors
Excellence in Teaching Recognition, 2012-2019, 2021
Presidential Early Career Award for Scientists and Engineers (PECASE), 2019
Helen Corley Petit Scholar, 2017
Benjamin R. and Elinor W. Bullock and Edwin E. and Jeanne Bullock
Goldberg Professorial Scholar, 2017
Advances in Medicine Award, Carle Hospital, 2016
Golden Apple Teaching Award, 2015
Courses Taught
MCB 314 - Introduction to Neurobiology
Course Director - Phase 1 Clinical Neuroscience Carle Illinois College of Medicine
Additional Campus Affiliations
Beckman Institute for Advanced Science and Technology
Physician-Surgeon at Carle Illinois College of Medicine
Speech and Hearing Science
External Links
Highlighted Publications
Basic Science:
Ibrahim BA, Shinagawa Y, Douglas A, Xiao G, Asilador AR, DA Llano (2024) Microprism-based two-photon imaging of the lateral cortex of the mouse inferior colliculus reveals novel organizational principles of the auditory midbrain. eLife, Reviewed preprint.
Wang Y, Lowerison MR, You Q, Lin B-Z, Llano DA, P Song (2024) Longitudinal Awake Imaging of Deep Mouse Brain Microvasculature with Super-resolution Ultrasound Localization Microscopy. eLife, Reviewed preprint.
Issa LK, Vaithiyalingam Chandra Sekaran N, DA Llano (2023) Highly branched and complementary distributions of layer 5 and layer 6 auditory corticofugal axons in mouse. Cerebral Cortex, Jun 29:bhad227.
Ibrahim BA, Louie JJ, Shinagawa Y, Xiao G, Asilador AR, Sable HK, Schantz S, DA Llano (2023) Developmental exposure to polychlorinated biphenyls prevents recovery from noise-induced hearing loss and disrupts the functional organization of the inferior colliculus. Journal of Neuroscience, Jun 21;43(25):4580-4597.
Ghimire M, Cai R, Ling L, Brownell KA, Hackett TA, Llano DA, DM Caspary (2023) Increased pyramidal and VIP neuronal excitability in primary auditory cortex directly correlates with tinnitus behavior Journal of Physiology, Jun;601(12):2493-2511.
Naik AG, Kenyon RV, Taheri A, Berger-Wolf T, Ibrahim B, Shinagawa and DA Llano (2023) V-Neurostack: Open-source 3D time stack software for identifying patterns in neuronal data. Journal of Neuroscience Research, Feb;101(2):217-231
Yudintsev, G, Asilador A, Sons S, Vaithiyalingam Chandra Sekaran N, Coppinger M, Nair K, Prasad M, Xiao G, Ibrahim BA, Yoshitaka Shinagawa Y, DA Llano (2021) Evidence for layer-specific connectional heterogeneity in the mouse auditory corticocollicular system. Journal of Neuroscience,Dec 1;41(48):9906-9918.
Chandrasekaran NV, Deshpande MS, Ibrahim BA, Xiao G, Shinagawa Y, Llano DA (2021) Patterns of unilateral and bilateral projections from layer 5 and 6 of the auditory cortex to the inferior colliculus in mouse. Frontiers in Systems Neuroscience, Oct 21;15:674098.
Ibrahim BA, Murphy C, Yudintsev G., Shinagawa Y, Banks MI, Llano DA (2021) Corticothalamic gating of population auditory thalamocortical transmission in mouse. eLife, May 24;10:e56645
Llano DA , Ma C, Di Fabrizio U, Taheri A, Stebbings KA, Yudintsev G, Xiao G, Kenyon RV, Berger-Wolf TY (2021) A novel dynamic network imaging analysis method reveals aging-related fragmentation of cortical networks in mouse, Network Neuroscience, Jun 21;5(2):569-590.
Lee CM, Sadowsky, RN, Schantz SL and D.A. Llano (2021) Developmental PCB exposure disrupts synaptic transmission and connectivity in the rat auditory cortex, independent of its effects on peripheral hearing threshold. eNeuro. Feb 1;8(1):ENEURO.0321-20.2021
Asilador A and D.A. Llano (2021) Top-down inference in the auditory system: Potential roles for corticofugal projections. Frontiers in Neural Circuits, Jan 22;14:615259
Lesicko A.M.H., Sons S.K. and D.A. Llano (2020) Circuit mechanisms underlying the segregation and integration of parallel processing streams in the inferior colliculus. Journal of Neuroscience, Jul 14;40(33):6328-44.
Brown JW, Taheri A, Kenyon RV, Berger-Wolf T, D.A. Llano (2020) Propagation of cortical activity via open-loop intrathalamic architectures: a computational analysis. eNeuro. Feb 25;7(1).
Liu YZ, Renteria C, Courtney CD, Ibrahim B, You S, Chaney EJ, Barkalifa R, Iyer RR, Zurauskas M, Tu H, Llano DA, Christian-Hinman CA, Boppart SA. (2020) Simultaneous two-photon activation and imaging of neural activity based on spectral-temporal modulation of supercontinuum light. Neurophotonics. Oct;7(4):045007.
Zhao Y, Maguluri G, Ferguson RD, Tu H, Paul K, Boppart SA, Llano DA , Iftimia N (2020) A portable low-cost two-photon microscope using a fiber-delivered supercontinuum generation source. Optics Letters. Feb 15;45(4):909-912.
Slater, B.J., Sons S.K., Yudintsev G., Lee C.M. and D.A. Llano (2019) Thalamocortical and intracortical inputs differentiate layer-specific mouse auditory corticocollicular neurons. Journal of Neuroscience, 39(2):256-270.
Gribkova, E.D., Ibrahim, B.A. and D.A. Llano (2018) A novel mutual information estimator to measure spike train correlations in a model thalamocortical network. Journal of Neurophysiology, Dec 1;120(6):2730-2744.
Sottile S.Y., Hackett T.A., Cai R., Llano D.A., and D.M. Caspary (2017) Presynaptic neuronal nicotinic receptors differentially shape select inputs to auditory thalamus and are negatively impacted by aging. Journal of Neuroscience, Nov 22;37(47):11377-11389.
Ibrahim B.A., Wang H., Lesicko A.M.H., Bucci B., Paul K. and D.A. Llano (2017) Effect of temperature on FAD and NADH-derived signals and neurometabolic coupling in the mouse auditory and motor cortex. JPflügers Archiv - European Journal of Physiology, Dec;469(12):1631-1649.
Patel M., Sons S., Yudintsev G., Lesicko A.M.H., Yang L., Taha G.A., Pierce S.M. and D.A. Llano (2017) Anatomical characterization of subcortical descending projections to the inferior colliculus in mouse. Journal of Comparative Neurology, Mar 1;525(4):885-900.
Lesicko A.M.H., Hristova T.S., Maigler K.C., and D.A. Llano (2016) Connectional modularity of top-down and bottom-up multimodal inputs to the lateral cortex of the inferior colliculus. Journal of Neuroscience Oct 26;36(43):11037-11050.
Paul K., Cauller L.J. and D.A. Llano (2016) Presence of a chaotic region at the sleep-wake transition in a simplified thalamocortical circuit model. Frontiers in Computational Neuroscience, Sep 1;10:91.
Stebbings, KA, Choi HW., Ravindra A., D.A. Llano (2016) The impact of aging, hearing loss and body weight on mouse hippocampal redox state, measured in brain slices using fluorescence imaging. Neurobiology of Aging, Jun;42:101-9.
Stebbings, KA, Choi HW., Ravindra A., Caspary DM, Turner JG, D.A. Llano (2016) Aging-related changes in GABAergic inhibition in the mouse auditory cortex, measured using in vitro flavoprotein autofluoresence imaging. J. Physiology. Jan 1;594(1):207-21.
Willis A.M., Slater B.J., Gribkova E., and D.A. Llano. (2015) Open-loop organization of thalamic reticular nucleus and dorsal thalamus: A computational model J. of Neurophysiology Oct;114(4):2353-67
Clinical/Translational:
Lowerison MR, Vaithiyalingam Chandra Sekaran N, Dong Z, Chen X, You Q, Llano DA, Song P. (2024) Super-Resolution Ultrasound Reveals Cerebrovascular Impairment in a Mouse Model of Alzheimer's Disease . Journal of Neuroscience. Feb 28;44(9):e1251232024.
Llano DA, Devanarayan P, Devanarayan D (2023) CSF peptides from VGF and other markers enhance prediction of MCI to AD progression using the ATN framework. Neurobiology of Aging. Jan;121:15-27.
Kwok SS, Nguyen X-MT, Wu D, Mudar RA, and DA Llano (2022) Pure tone audiometry and hearing loss in Alzheimer's disease: A metaanalysis. Frontiers in Psychology, Jan 21;12:788045.
Pérez-González D, Schreiner TG, Llano DA, Malmierca MS.(2022) Alzheimer's Disease, Hearing Loss, and Deviance Detection. . Frontiers in Neuroscience. Jun 2;16:879480.
Llano D.A., Kwok SS and V. Devanarayan (2021) Reported hearing loss in Alzheimer disease is associated with loss of brainstem and cerebellar volume. Frontiers in Human Neuroscience, Sep 24;15:739754.
Llano, D.A., and V. Devanarayan (2021). Serum phosphatidylethanolamine and lysophosphatidylethanolamine levels differentiate Alzheimer Disease from controls and predict progression from mild cognitive impairment. Journal of Alzheimer Disease,80(1):311-319.
Llano, D.A., Issa, L.K., Devanarayan, P., and V. Devanarayan (2020). Hearing loss in Alzheimer Disease is associated with altered serum lipidomic biomarker profiles. Cells, Nov 28;9(12):E2556.
Nadhimi, Y. and D.A. Llano (2020) Does hearing loss lead to dementia? A review of the literature. Hearing Research, Jul 30:108038.
Llano, D.A., Devanarayan, P. and V. Devanarayan, (2019) VGF in cerebrospinal fluid combined with conventional biomarkers enhances prediction of conversion from MCI to Alzheimer’s Disease. Alzheimer Disease and Associated Disorders, Oct-Dec;33(4):307-314.
Esmaeeli S, Murphy K, Swords GM, Ibrahim BA, Brown JW, DA Llano (2019) Visual hallucinations, thalamocortical physiology and Dementia with Lewy Bodies: A review. Neuroscience and Biobehavioral Reviews, Aug;103:337-351.
Devanarayan, P., Devanarayan, V. and D.A. Llano (2019) Identification of a simple and novel cut-point based CSF and MRI signature for predicting Alzheimer’s disease progression that reinforces the 2018 NIA-AA research framework. Journal of Alzheimer Disease, 68(2):537-550
Swords G.M., Nguyen L.T., Mudar R.A. and D.A. Llano (2018) Auditory system dysfunction in Alzheimer Disease and its prodromal states: A review. Ageing Research Reviews, Jul;44:49-59.
Llano, DA, Mudar R, Bundela S and Devanarayan D. (2017) A multivariate predictive modeling approach reveals a novel CSF peptide signature for both Alzheimer's Disease state classification and for predicting future disease progression. PLOS One,Aug 3;12(8):e0182098.
Recent Publications
Devanarayan, V., Llano, D. A., Hu, Y. H., Hampel, H., Kramer, L., Dhadda, S., & Irizarry, M. (2024). Plasma pTau181 enhances the prediction of future clinical decline in amyloid-positive mild cognitive impairment. Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring, 16(3), Article e12621. https://doi.org/10.1002/dad2.12621
Devanarayan, V., Doherty, T., Charil, A., Sachdev, P., Ye, Y., Murali, L. K., Llano, D. A., Zhou, J., Reyderman, L., Hampel, H., Kramer, L. D., Dhadda, S., & Irizarry, M. C. (2024). Plasma pTau217 predicts continuous brain amyloid levels in preclinical and early Alzheimer's disease. Alzheimer's and Dementia, 20(8), 5617-5628. https://doi.org/10.1002/alz.14073
Devanarayan, V., Ye, Y., Charil, A., Andreozzi, E., Sachdev, P., Llano, D. A., Tian, L., Zhu, L., Hampel, H., Kramer, L., Dhadda, S., & Irizarry, M. (2024). Predicting clinical progression trajectories of early Alzheimer's disease patients. Alzheimer's and Dementia, 20(3), 1725-1738. https://doi.org/10.1002/alz.13565
Lowerison, M. R., Sekaran, N. V. C., Dong, Z., Chen, X., You, Q., Llano, D. A., & Song, P. (2024). Super-Resolution Ultrasound Reveals Cerebrovascular Impairment in a Mouse Model of Alzheimer’s Disease. Journal of Endocrinology, 44(9), 1-14. Article e1251232024. https://doi.org/10.1523/JNEUROSCI.1251-23.2024
Brunelle, D. L., & Llano, D. A. (2023). Role of auditory-somatosensory corticothalamic circuit integration in analgesia. Cell Calcium, 111, Article 102717. https://doi.org/10.1016/j.ceca.2023.102717
