Auditory Brain Atlas

Hackett Laboratory

  • Established in January 2000: Dept. of Hearing & Speech Sciences, Vanderbilt University School of Medicine.
  • Research focuses on neuroanatomical features of the central auditory pathways, with emphasis on the auditory cortex and thalamus.
  • The content included in this prototype of the Auditory Brain Atlas is representative of tissue assays from in-house and collaborative experiments.

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Dr. Troy A. Hackett (Vanderbilt University)
  • Central auditory systems organization
  • Multisensory systems integration
  • Developmental plasticity and reorganization
  • Genomic, proteomic, connectomic profiling

Model systems
  • Human, monkey, cat, mouse
  • Normal and hearing impaired
  • Adult and developing
  • Connectivity (tract tracing)
  • Neural archictecture (cytoarchitecture, myeloarchitecture, chemoarchitecture)
  • Genomic/proteomic profiling (RNAseq, in situ hybridization, immunohistochemistry)
  • Neurophysiology (single and multiunit extracellular recordings; profiling of basic auditory response properties)

Description of Research Program

I. Background
Dr. Hackett has devoted his entire career to research and clinical practice in communication disorders. He is currently an associate professor at Vanderbilt University, with appointments in the departments of Hearing and Speech Sciences and Psychology. He was initially trained as an audiologist, and engaged in full-time clinical practice for 5 years before pursuing doctoral studies. Research training during undergraduate and graduate studies in audiology at Indiana University included mentored projects in vowel perception (Dr. Diane Kewley-Port), psychoacoustics (Dr. Charles Watson), and prescriptive hearing aid fittings (Dr. Larry Humes). During subsequent pre- and postdoctoral training at Vanderbilt University, mentored by Dr. Jon Kaas, the PI moved into auditory neuroscience, and began to focus on the anatomical and physiological organization of auditory cortex and subcortical pathways. Postdoctoral training was funded by an NRSA from NIDCD. In January 2000, the PI became an assistant professor in the Dept. of Hearing and Speech Sciences in the Vanderbilt Univ. School of Medicine, with a secondary appointment in Psychology. The PI teaches doctoral students in audiology and auditory neuroscience, and has been continuously engaged in studies of the central auditory and multisensory pathways as a faculty member and NIH-funded investigator since January 2000. From 2012 to present, the PI has devoted 50% effort to train and establish a new line of auditory research under an NIDCD K18 grant. The short-term goal was to equip the PI and his laboratory with the techniques of molecular biology. The long-term goal was to combine conventional and modern techniques to more fully profile and characterize structure (genomic, proteomic, connectomic). This broadened neuroanatomical approach is being applied to ongoing and new lines of research focused on the structure and function of central auditory structures in normal and clinical populations.

II. Research Interests and Accomplishments
As an established independent investigator, the research program of the PI has focused on combined anatomical and physiological studies of auditory and multisensory pathways in major animal models, including mice, cats, nonhuman primates, and humans.

(1) Auditory pathways of human and nonhuman primates: anatomy and physiology
The PI is an internationally recognized expert on the anatomical and physiological organization of auditory cortex and thalamus, and is best known for studies of nonhuman primates and humans. Between 2000 and 2012 , models of auditory thalamic and cortical organization were established for two primate species (macaque and marmoset monkey). These models have been widely adopted by the auditory research community as a reference for electrophysiological and functional imaging studies of monkeys and humans (for review, see Hackett, 2011). Techniques used in these studies include conventional architectonic analyses, tract tracing, immunohistochemistry, and in situ hybridization. Electrophysiological techniques include single and multielectrode unit recordings. This work was funded by F32 DC00249 from 1997-1999 and NIH/NIDCD grant R01 DC04318 from 2001 to 2012. In 2012, this R01 grant was deliberately terminated by the PI to train and conduct research in molecular biology under K18 DC012527 from 2012 through 2014.

(2) Multisensory pathways
The PI is also widely recognized for studies of multisensory processing involving the auditory, somatosensory, and visual pathways. Through collaborations with Dr. Charles Schroeder (Columbia Univ.)(2003 - present) and Dr. Mark Wallace (Vanderbilt Univ.)(2009 - present), the PI has conducted neuroanatomical studies in primates and cats to identify and characterize the circuits that contribute to multisensory integration in auditory and multisensory brain areas. These discoveries have had the added benefit of expanding the scope of the auditory cortex model to include links with multiple sensory and associative areas distributed throughout the thalamus and cortex. NIH grants to Drs. Schroeder (R01MH061989; NIDCD R01 DC011490) and Wallace (NIMH R01MH063861) have provided salary and material support to the PI as a consultant, co-investigator or co-PI for conducting the anatomical studies pertaining to those projects.

(3) Central auditory connectivity in adult and developing mice
Recently, the PI has become involved in collaborative studies of thalamocortical and corticothalamic organization of adult and developing mice with Dr. Daniel Polley (Harvard Univ., Eaton Peabody Lab). Two completed studies combined multiple techniques to (1) establish functional topography in the mouse thalamocortical pathway (Hackett et al 2011), and (2) determine the influence of ephrin/EphA guidance on the fate of corticothalamic projections from auditory cortex to the medial geniculate body (Torii et al 2011). These studies led to the development of the K18 proposal to profile gene and protein expression in the auditory pathways of developing mice.

(4) Gene and protein expression profiling of auditory pathways in developing mice
In 2012, the PI received a K18 grant from NIDCD, which provides support for established scientists to add a new dimension to their research program. The training is provided in the context of a small-scale research study, mentored by an individual with expertise. The study (ongoing) has two primary aims: 1) to use next generation RNA sequencing to track changes in gene expression in cortical and subcortical auditory areas before and after the onset of hearing in mice (postnatal days P7 to adult); 2) to validate and contextualize the sequencing data using targeted qPCR, in situ hybridization, and immunohistochemical assays of selected genes/proteins. Collaborators on this project are Drs. Dan Polley (Eaton-Peabody / Harvard; developing mice) and Karoly Mirnics (Vanderbilt; mentor).

III. Future and ongoing pilot projects
(1) Plasticity in auditory pathways of adult and developing mice with hearing loss
Two additional projects (new) are focused on plasticity in auditory cortex and subcortical pathways associated with peripheral hearing loss in adult and developing mice. These projects are pilot projects in collaboration with Dan Polley. Briefly, the Polley laboratory is characterizing plastic changes associated with the onset of unilateral/bilateral hearing loss at different postnatal ages, including adults. The Hackett laboratory is using the tools developed from the K18 grant to profile changes in gene and protein expression associated with the hearing loss.

(2) Plasticity in auditory pathways of adult monkeys with noise-induced hearing loss
This project aims to characterize the neurophysiological and neuroanatomical correlates of acquired hearing loss in a primate model. Dr. Ramnarayan Ramachandran (Vanderbilt) received pilot funding from the university to conduct these studies. The Ramachandran lab is characterizing neurophysiological changes in the auditory brainstem. The Hackett lab will profile changes in gene and protein expression at all levels of the central auditory pathway.

(3) Auditory Brain Atlas
Only a fraction of the structural data collected in the experiments summarized above are contained within published manuscripts. Thousands of unpublished images and profiling data should be made publicly available for reference and hypothesis generation. Toward that end, the PI has begun to develop this web-based resource to serve as a repository for structural data past, present and future. These data would include genomic, proteomic, connectomic and conventional assays of central auditory structures. As time and resources permit, content available in this Atlas will be expanded. Content will include data from in-house and collaborative efforts with other laboratories.

Relevant Publications (chronological by publication type and subject)

Research Papers: Auditory (and other sensory) pathways: human and nonhuman primate

Hackett TA, Stepniewska, I., Kaas, J.H. (1998) Subdivisions of auditory cortex and ipsilateral cortical connections of the parabelt auditory cortex in macaque monkeys. Journal of Comparative Neurology, 394:475-495. PMID: 9590556

Hackett TA, Stepniewska, I., Kaas, J.H. (1998) Thalamocortical connections of parabelt auditory cortex in macaque monkeys. Journal of Comparative Neurology, 400:271-286. PMID: 9766404

Hackett TA, Stepniewska, I., Kaas, J.H.(1999) Callosal connections of the parabelt auditory cortex in macaque monkeys. European Journal of Neuroscience, 11:856-866. PMID: 10103079

Hackett TA, Stepniewska, I., Kaas, J.H.(1999) Prefrontal connections of the auditory parabelt cortex in macaque monkeys. Brain Research., 817:45-58. PMID: 9889315
Florence S.L., Hackett TA., Strata, F. (2000) Thalamic and cortical contributions to neural plasticity after limb amputation. Journal of Neurophysiology, 83:3154-3159. PMID: 10805710

Florence, S.L., Boydston L.A., Hackett TA, Taub-Lachoff, H., Strata, F., Niblock M.M. (2001) Sensory enrichment promotes cortical, not thalamic, refinement of disorder produced by peripheral nerve injury. European Journal of Neuroscience, 13:1755-1766. PMID: ?

Hackett TA., Preuss, T.M., Kaas, J.H. (2001) Architectonic identification of the core region in auditory cortex of macaques, chimpanzees, and humans. Journal of Comparative Neurology, 441:197-222. PMID: 11745645

Kajikawa Y, de la Mothe L, Blumell S, Hackett TA (2005). A comparison of neuron response properties in areas A1 and CM of the marmoset monkey auditory cortex: tones and broad band noise. J Neurophysiol, 93(1):22-34. PMID: 15342713

de la Mothe L, Blumell S, Kajikawa Y, Hackett TA (2006a) Cortical connections of auditory cortex in marmoset monkeys: core and medial belt regions. J Comp Neurol., 496:27-71. PMID: 16528722

de la Mothe L, Blumell S, Kajikawa Y, Hackett TA (2006b) Thalamic connections of auditory cortex in marmoset monkeys: core and medial belt regions. J Comp Neurol., 496:72-96. PMID: 16528728

Kajikawa Y, de la Mothe L, Blumell S, Sterbing-D'Angelo SJ, D'Angelo W, Camalier CR, Hackett TA (2008). Coding of FM sweep train repetition rate in area CM of marmoset auditory cortex. Hearing Res, 239(1-2):107-125. PMID: 18342463. PMCID: PMC2581800

Hackett TA, de la Mothe LA (2009) Regional and laminar distribution of the vesicular glutamate transporter, VGluT2, in the macaque monkey auditory cortex. J Chem Neuroanat., 38:106-116. PMID: 19446630. PMCID: PMC2774764

Kajikawa Y, Camalier CR, de la Mothe LA, D’Angelo WR, Sterbing-D’Angelo, SJ, Hackett TA (2011) Auditory cortical tuning to band-pass noise in primate A1 and CM: A comparison to pure tones. Neurosci. Res., 70:401-407. PMID: 21540062. PMCID: PMC3130097

Balaram P, Hackett TA, Kaas JH (2011) VGLUT1 mRNA and protein expression in the visual system of prosimian galagos (Otolemur garnetti). Eye and Brain, 3:81-98. PMID: 22912561. PMCID: PMC3422692

Hackett TA, Takahata T, Balaram P. (2011) VGLUT1 and VGLUT2 mRNA expression in the primate auditory pathway, Hear Res., 274(1-2):129-41. PMID: 21111036. PMCID: PMC3073021

de la Mothe LA, Blumell S, Kajikawa Y, Hackett TA (2012) Cortical connections of auditory cortex in marmoset monkeys: lateral belt and parabelt regions. Anat Rec, 295(5):800-821. PMID: 22461313. PMCID: PMC3379817

de la Mothe LA, Blumell S, Kajikawa Y, Hackett TA (2012) Thalamic connections of auditory cortex in marmoset monkeys: lateral belt and parabelt regions. Anat Rec, 295(5):822-836. PMID: 22467603. PMC Journal – In Process

Bryant KL, Suwyn C, Reding K, Smiley J, Hackett TA, Preuss TM (2012) Evidence for ape and human specializations in geniculostriate projections from VGLUT2 immunohistochemistry. Brain Behav Evol., Ms No.: 201202003. PMID: 22889767. PMCID: PMC3503454

Camalier CR, D’Angelo WR, Sterbing-D’Angelo SJ, de la Mothe LA, Hackett TA (2012) Neural latencies across auditory cortex of macaque support a dorsal stream supramodal timing advantage in primates. Proc. Natl. Acad. Sci. USA, Oct 16. PMID: 23074251. PMCID: PMC3497796

Miller DJ, Lackey EP, Hackett TA, Kaas JH (2013) Development of myelination and cholinergic innervation in the central auditory system of a prosimian primate (Otolemur garnetti). J Comp. Neurol, 521:3804-3816.

Balaram P, Hackett TA, Kaas JH (2013) 2 Differential expression of vesicular glutamate transporters 1 and 2 may identify distinct modes of glutamatergic transmission in the macaque visual system. J. Chem. Neuroanat., 50-51:21-38. PMID 23524295.

Smiley JF, Hackett TA, Preuss TM, Bleiwas C, Figarsky K, Mann JJ, Rosoklija G, Javitt DC, Dwork AJ (2013) Hemispheric asymmetry of primary auditory cortex and Heschl's gyrus in schizophrenia and nonpsychiatric brains. Psychiatry Res. 2013 Oct 19. PMID: 24148910.

Hackett TA, de la Mothe LA, Camalier CR, Falchier A, Lakatos P, Kajikawa Y, Schroeder CE. (2014) Feedforward and feedback projections of caudal belt and parabelt areas of auditory cortex: refining the hierarchical model. Front. Neurosci., Apr 22 online, 8(72):1-21.

Kajikawa Y, Frey S, Ross D, Falchier A,
Hackett TA, Schroeder CE (2015) Auditory properties in the parabelt regions of the superior temporal gyrus in the awake macaque monkey: an initial survey. J Neurosci., 35:4140-4150.

Research Papers: Adult and developing mouse auditory pathways: genomic, proteomic, connectivity

Hackett TA, Rinaldi Barkat T, O'Brien BM, Hensch TK, Polley DB (2011) Linking topography to tonotopy in the mouse auditory thalamocortical circuit. J Neurosci., 31(8):2983-2995. PMID: 21414920. PMCID: PMC3073837

Torii M, Hackett TA, Rakic P, Levitt P, Polley DB (2012) EphA Signaling Impacts Development of Topographic Connectivity in Auditory Corticofugal Systems. Cereb Cortex, 23(4): 775-785. PMID: 22490549. PMCID: PMC3593572

Hackett TA, Clause AR, Takahata T, Hackett NJ, Polley DB (2015) Differential maturation of vesicular glutamate and GABA transporter expression in the mouse auditory forebrain during the first weeks of hearing. Brain Structure Function, July 10, epub ahead of print.

Hackett TA, Guo Y, Clause AR, Hackett NJ, Garbett K, Zhang P, Polley DB (2015) Transcriptional maturation of the mouse auditory forebrain. BMC Genomics, Aug 14;16(1):606. doi: 10.1186/s12864-015-1709-8. PMID: 26271746

Research Papers and Reviews: Multisensory interactions, anatomical mechanisms

Schroeder, C.E., Smiley, J., Fu K-M.G., McGinnis, T., O’Connell, M.N., Hackett TA (2003) Anatomical mechanisms and functional implications of multisensory convergence in early cortical processing. Int J Psychophysiol, 50:5-17. PMID: 14511832

Fu, K-M.G., Johnston, T.A., Shah, A.S., Arnold, L.A., Smiley, J., Hackett TA, Garraghty, P.E., Schroeder, C.E. (2003) Auditory cortical neurons respond to somatosensory stimulation. J Neurosci, 23(20):7510 –7515. PMID: 12930789

Smiley JF, Hackett TA, Ulbert I, Karmos G, Lakatos P, Javitt DC, Schroeder CE (2007) Multisensory convergence in auditory cortex, I. Cortical connections of the caudal superior temporal plane. J Comp Neurol, 502:894-923. PMID: 17447261

Hackett TA, Smiley, J.F., Ulbert, I., Karmos, G., Lakatos, P., de la Mothe, L.A., Schroeder, C.E. (2007) Sources of somatosensory input to the caudal belt areas of auditory cortex. Perception, 36: 1419-1430. PMID: 18265825.

Hackett TA, de la Mothe LA, Ulbert I, Karmos G, Smiley JF, Schroeder CE (2007) Multisensory convergence in auditory cortex, II. Thalamocortical connections of the caudal superior temporal plane. J Comp Neurol, 502:924-952. PMID: 17444488

Falchier A, Schroeder CE, Hackett TA, Lakatos P, Nascimento-Silva S, Ulbert I, Karmos G, Smiley JF (2009) Projection from visual areas V2 and Prostriata to caudal auditory cortex in the monkey. Cereb Cortex, 20:1529-1538. PMID: 19875677. PMCID: PMC2882821

Hackett TA, Schroeder CE (2009) Multisensory integration in auditory and auditory-related areas of cortex, Hearing Res, 258:1 – 3. PMID: 19932881. PMCID: Editorial

Hackett, TA, Schroeder, CE (2009) Special issue of Hearing Research, devoted to multisensory integration in auditory cortex. Hear Res., vol. 258.

Schroeder CE, Lakatos P, Smiley J, and Hackett TA (2007) How and why do multisensory inputs target auditory cortex? In Auditory Evoked Potentials, R. Burkhard, M. Don and J. Eggermont (Eds.), 651-671.

Hackett, TA (2012) Multisensory Convergence in the Thalamus. In B. Stein et al (eds.) New Handbook of Multisensory Processing, 2nd Ed, MIT Press, 49-66.

Morrilon B,
Hackett TA, Kajikawa Y, Schroeder CE (2015) Predictive motor control of sensory dynamics in auditory active sensing. Curr Opin Neurobiol, 31:230-238.

Research Papers: Methodological

Kajikawa Y, Hackett TA (2005) Entropy analysis of neuronal spike train synchrony. J Neurosci Methods, 149:90-93. PMID: 16026849

Hackett TA, Karmos G, Schroeder CE, Ulbert I, Sterbing-D’Angelo SJ, D’AngeloWR, Kajikawa Y, Blumell S, de la Mothe L. (2005) Neurosurgical access to cortical areas in the lateral fissure of primates. J Neurosci Methods, 141:103-113. PMID: 15585294

O’Malley MR, Wittkopf JE, Cutler JL, Labadie RF, Hackett TA, Haynes DS (2006) Fluorescent retrograde axonal tracing of the facial nerve. Laryngoscope, 116:1792-1797. PMID: 17003730

Luczak A, Hackett TA, Kajikawa Y, Laubach.M (2004). Multivariate receptive field mapping in marmoset auditory cortex. J Neurosci Methods, 136:77-85. PMID: 15126048

Review Articles: Auditory pathways organization

Kaas, J.H., Hackett TA (1998) Subdivisions and levels of processing in primate auditory cortex. Audiology and Neuro-otology, 3:73-85. PMID: 9575378

Kaas, J.H., Hackett TA (1999) ‘What’ and ‘where’ processing in auditory cortex. Nature Neuroscience, 2:1045-1047. PMID: 10570476

Kaas, J.H., Hackett TA, Tramo, M.J. (1999) Auditory processing in primate cerebral cortex. Current Opinion in Neurobiology, 9(2), 164-170. PMID: 10322185

Kaas, J.H., Hackett TA (2000) Subdivisions of auditory cortex and processing streams in primates. Proc. Natl. Acad. Sci. USA, 97(22):11793-11799. PMID: 11050211. PMCID: PMC34351

Kaas, J.H., Hackett TA (2000) How the visual projection map instructs the auditory computational map. Journal of Comparative Neurology, 421:143-145. PMID: 10813777

Hackett TA (2008) Anatomical organization of the auditory cortex. J Am Acad Audiol., 19:774-779. PMID: 19358457. PMC Journal – In Process

Hackett TA (2011) Information flow in the auditory cortical network. Hearing Res, 271:133-146. PMID: 20116421. PMCID: PMC3022347

Hackett TA (2015) Anatomic organization of the auditory cortex. Handbook Clin Neurol., 129:27-53.

Book Chapters: Auditory pathways organization

Kaas, J.H., Hackett, T.A. (1999) The Auditory System. In M.Wong-Riley (ed)., Neurology Secrets, Hanley and Belfus, Inc., pp. 99-114.

Hackett, T.A., Kaas, J.H. (2002) Auditory Processing in the Primate Brain. In M. Gallagher and R.J. Nelson (Eds.), Handbook of Psychology, Vol. 3: Biological Psychology, Wiley & Sons: New York.

Hackett, T.A. (2002) The Comparative Anatomy of the Primate Auditory Cortex. In Primate Audition: Behavior and Neurobiology, A. Ghazanfar (Ed.), CRC Press, Boca Raton, FL, pp. 199-226.

Hackett, T.A., Kaas, J.H. (2004) Auditory cortex in primates: functional subdivisions and processing streams. In M.S. Gazzaniga (Ed.)., The Cognitive Neurosciences III, 3rd Edition, Boston: MIT Press.

Kaas, J.H., Hackett, T.A. (2005) Subdivisions and connections of the auditory cortex in primates: a working model. In R Konig, P. Heil, E. Budinger, H. Scheich (Eds)., The Auditory Cortex: Towards a Synthesis of Human and Animal Research, Mahwah N.J.:Lawrence Erlbaum., pp. 7 – 26.

Kaas, J.H., Hackett, T.A. (2005) The functional neuroanatomy of the auditory cortex. In P Dallos and D Oertel (Eds)., Handbook of the Senses: Audition.

Hackett, TA (2007) Organization of the Thalamocortical Auditory Pathways in Primates. In Auditory Evoked Potentials. R Burkard, M. Don, J. Eggermont (Eds.), New York:Lippincott, Williams, and Wilkins, 428-440.

Hackett TA (2007) Organization and correspondence of the auditory cortex of humans and nonhuman primates. In Evolution of the Nervous System, JH Kaas (Ed.)., Oxford: Elsevier; pp. 109-119.

Hackett TA (2009) Organization of the central auditory pathways in nonhuman primates and humans. In Current Controversies in Central Auditory Processing Disorders (CAPD), AT Cacace and DJ McFarland (Eds.), San Diego: Plural Publishing, 15-46.

Hackett TA, Kaas JH (2009) Audition. In Handbook of Neuroscience for the Behavioral Sciences. GG Berntson and JT Cacioppo (Eds.), John Wiley and Sons, 251-266.

Malmierca MM, Hackett TA (2010) Structural and functional organization of the auditory brain. In OUP Handbook of Auditory Science, Volume 2, The Auditory Brain, AR Palmer and A Rees (Eds.), Oxford: Elsevier, 9 – 42.

Hackett TA, Phillips DP (2011) The Commisural Auditory System. In The Auditory Cortex, JA Winer and CE Schreiner (Eds.), New York: Springer-Verlag, 117-132.

Hackett, T.A., Kaas, J.H. (2011) Auditory Processing in Primate Brains. In M. Gallagher and R.J. Nelson (Eds.), Handbook of Psychology, Second Edition.

Hackett, TA (2015) Anatomical organization of the auditory cortex. In Celesia and Hickok (eds). The auditory system (Handbook of Clinical Neurology). 129:27-53. doi: 10.1016/B978-0-444-62630-1.00002-0. PMID: 25726261.