Stephen G. Lomber - US grants

[unreadable] DESCRIPTION (provided by applicant): Following implantation of a cochlear prosthetic, auditory cortex exhibits a remarkable plasticity in its ability to establish auditory signal processing after a period of deprivation. Our long-term goal is to understand and define the capabilities of non-primary auditory cortex to establish auditory function following cochlear implant. This endeavor requires the elucidation of the essential contributions that non-primary auditory cortex makes to fundamental aurally-guided behaviors in the intact (hearing) condition, as well as an assessment of the behavioral capabilities of non-primary auditory cortex following cochlear implant in congenitally deaf subjects. The first specific aim of this application is to determine that non-primary auditory cortex contains specialized regions for the processing of pattern perception and spatial localization. In intact cats, we will examine the contributions that the anterior and posterior auditory fields (AAF and PAF, respectively) make to pattern recognition and the perception of auditory space. Each area will be reversibly deactivated with cooling and we expect to be able to doubly-dissociate pattern discrimination and spatial localization functions to AAF and PAF cortices, respectively. The second aim in the study is to determine if congenitally deaf (CD) cats with cochlear prosthetics implanted early in development (2 months of age) can establish aurally-mediated behaviors. We will test if the animals are able to attain high performance levels on the auditory discrimination, detection, and localization tasks examined in Aim 1. The results of the first two aims are brought together in Aim 3, where we will combine the CD cats with cochlear implants examined in Aim 2 with the reversible deactivation techniques used in Aim 1 to determine if the characteristic normal functional cartography of non-primary auditory cortex is established following early cochlear implantation. To accomplish this, we will reversibly deactivate AAF and PAF cortices in the CD cats with cochlear implants while performing the battery of auditory tasks described above, and compare the results with those from the intact cats in Aim 1. The results from these studies will be directly applicable to clinical situations concerning the functional outcomes of cochlear implants in young children. [unreadable] [unreadable]

[unreadable] DESCRIPTION (provided by applicant): The development of functional magnetic resonance imaging (fMRI) has greatly expanded our ability to examine neural processing while subjects perform a variety of perceptual, cognitive, or motor tasks. fMRI permits the simultaneous examination of functional activity in many different brain regions and provides a better understanding of how multiple regions work in concert to produce particular behaviors. The next necessary step in the evolution of this approach is to deactivate a specific region in the brain, while a subject is being scanned, to determine the contribution of this site to the activity of its functional network -- by examining the activity of other network components in the absence of this region. To accomplish this goal, we propose to develop a reversible deactivation approach that is fMRI-compatible. The development of this technique will be based on a well-established cryoloop technique in which a cooling device is chronically implanted in behaving animals. We propose a four-phase development program. In phase 1 (development), we will develop a non-metallic cooling device capable of deactivating specific regions of the cerebral cortex. In phase 2 (testing), we will test the device in the behaving cat by cooling regions of primary visual cortex (V1) while the animal performs a visual orienting task. Once we establish device reliability, and can produce behavioral deficits, we will anesthetize the cats and examine the function of the device in the fMRI to confirm compatibility. In phase 3 (implementation), we will chronically implant the device over a region of V1 in non-human primates that have been trained to make visually guided saccades. If V1 is successfully deactivated, saccades to targets within the scotoma should be abolished. The monkeys will be tested while performing the task in the magnet and images will be collected before, during, and after cooling deactivation. We will also examine the distant deactivation consequences on area MTN5 and the superior colliculus while the monkeys view expanding and contracting visual flow during fixation. Finally, in phase 4 (evaluation), we will administer radiolabelled 2-deoxyglucose during cooling so that we may compare the autoradiograms with the deactivation images collected in the magnet. In summary, we expect to fully develop and test a device to reversibly deactivate sites in the brain during behavioral testing in the magnet. Such a development should have wide appeal and will greatly advance our ability to dissect functional circuits with fMRI. [unreadable] [unreadable]

? DESCRIPTION (provided by applicant): The Auditory System Gordon Research Conference (Auditory GRC) consisting of ~125-150 scientists of diverse expertise will convene on July 10-15, 2016, at Bates College, to discuss and debate new findings in hearing research and related fields, under the theme of The Plastic and Dynamic Auditory System. The Auditory GRC is preceded by a smaller Gordon Research Seminar (Auditory GRS, July 9-10) and will comprise of talks and posters by 40-50 investigators-in-training, thereby serving as a gateway to the GRC. Together the Auditory GRC & GRS offer a unique combination of features, including: breadth of research, cutting-edge emphasis, mingling of investigators from all ranks and diverse sub-fields and locales, and intimate size and extended discussion time, allowing for close and sustained interactions. Some of these features arise from unique qualities of the hearing research field and others from the Gordon Conferences' established nature. Since the 1920s, the GRC organization has supported meetings famous for their unfettered debate and discussion of emerging results. The program of the 2016 Auditory GRC emphasizes plasticity in the auditory system and the diverse ways in which the auditory system adapts to genetic, environmental, and developmental changes, and the reduction and restoration of acoustic signals in the system. Investigators will present new results in areas from genetics to central nervous system physiology and behavior. Topics include genetic regulation of inner ear epithelia, hair bundles, and echolocation, hair cell transduction and synaptic transmission, noise trauma at cochlear and systems levels, and neural encoding of sound location and speech. We have learned from experience to spread different model systems and technologies throughout the sessions, so that each session has something for everyone - encouraging unusually high attendance throughout the meeting and cross-fertilization across disciplines. The clinical importance of auditory research will be highlighted with presentations that consider the mechanisms underlying human disorders (e.g. noise trauma and aging) and translational efforts to fix them (e.g., hair cell regeneration, cochlear implant). For the Auditory GRS, talks are selected from registrants' submitted abstracts and anchored by a keynote address by an invited mentor-participant who is an assistant professor. Mentoring is an active component of the GRS - in addition to the keynote speaker, the GRC organizers (also senior investigators) are available for discussion, and a mentoring session, featuring a representative from NIDCD and other grant agencies, is planned.