Neurophysiological and anatomical studies of sound processing mechanisms in the auditory system

Lead Research Organisation: MRC Institute of Hearing Research

Abstract

While we know much about the way the ear processes sounds, the subsequent processing by the nerve cells in the auditory part of the brain, that ultimately leads to perception, is much less well understood. We are attempting to understand the complex circuits and neural pathways involved in these processes by measuring their responses to sound, assessing the effect of descending activity and mapping them anatomically. To allow microscopic examination of neuronal connections and direct manipulation of these circuits we use guinea pigs as our animal model. We have demonstrated columnar processing in the audtory cortex and specialisation in the sensitivity of different cortical areas. We have also demonstrated profound modulation of the ascending auditory information all the way down to the level of the cochlea by feedback from the auditory cortex. Anatomical and physiological studies of these brain pathways in animals provides a basis for understanding and interpreting neuroimaging data from normal humans and those with a variety of pathological conditions such as tinnitus or speech and language deficits. We are currently imaging the brains of subjects with chronic tinnitus to better undestand this distressing condition.

Technical Summary

The structure and function of the normal auditory nervous system is investigated in anaesthetised guinea pigs by a range of tract tracing, histological and neurophysiological methods. Results from this animal model direct our studies of postmortem human brain tissue, which aims to improve interpretation of human neuroimaging data from live subjects.

We study the morphology and response characteristics of single cells in the inferior colliculus using a recording and labelling technique. This type of correlative data will allow a better understanding of the neural circuitry underlying the interaction between the multiple inputs to this nucleus. Such data is surprisingly lacking for the inferior colliculus, which is an almost-obligatory relay in the ascending auditory pathway. We also apply this powerful technique to the primary auditory cortex where we investigate the processing that takes place within columnar structures perpendicular to the cortical surface.

We reversibly switch off the auditory cortex using a cryoloop to investigate the functions of the descending pathways from the cortex to the inferior colliculus, thalamus and cochlea. Combining these functional studies with tract tracing methods we seek to disentangle the contribution of descending pathways to processing of incoming auditory information.

The auditory cortex is composed of two or three core areas surrounded by six or more belt areas. We are investigating the function of these cortical areas using guinea pig vocalisations and have found that some areas appear to be specialised for analysing acoustic communication signals.

We will use histochemical methods to compare the human thalamus to that of our well characterised animal model and to relate staining in the human auditory cortex to structural magnetic resonance images from the same (post-mortem) brains. This should allow us to identify core and belt areas in the human brain in human neuroimaging studies. Identification of the core and belt areas in the human is vital for interpreting normal neuroimaging data and in identifying abnormalities associated with clinical conditions.

Finally, we are measuring the brain activity (using magnetoencephalography) associated with tinnitus in a large sample of well audiometrically characterised tinnitus sufferers. We seek to provide an objective taxonomy of different forms of tinnitus.

Publications

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Liu LF (2006) Phase-locked responses to pure tones in the inferior colliculus. in Journal of neurophysiology

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Palmer AR (2007) Some investigations into non-passive listening. in Hearing research

 
Title Cryoloop for cortical inactivation in physiological experiments 
Description We have further developed a system designed by Steven Lomber (London Ontario) called the cryoloop that allows parts of the brain to be selectively and reversably inactivated by cooling. This reversability allows the functions of the cortical areas or their connection to normal processing to be assessed. 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2007 
Provided To Others? Yes  
Impact We have demonstrated a profound impact of the descending system from the cortex on auditory process at lower levels of the system 
 
Description Application of information theory to neural data 
Organisation Hebrew University of Jerusalem
Country Israel 
Sector Academic/University 
PI Contribution We supplied the neural data which allowed Professor Nelken and his team to apply information theory methods and to compare various methods of data analysis.
Collaborator Contribution Professor Nelken and his group have introduced us to and demonstrated the utility of information theory based analysis of our neural data
Impact PMID 18093660
Start Year 2006
 
Description noise reduction in magnetic resonance scanning 
Organisation Optoacoustics Ltd
Country Israel 
Sector Private 
PI Contribution We developed a sound system that delivers antinoise to reduce noise during magnetic resonance scanning.
Collaborator Contribution The company supplied optical microphones which we have utilized in our noise reduction system.
Impact The theoretical details of this system have been fully published but only the most recent publication validating the system was since 2006 : PMID 19173422
Start Year 2006
 
Title Noise reduction system for magnetic Resonance Scanning 
Description A specially developed sound system for presentation of anti-noise to cancel and thereby reduce the noise generated during magnetic resonance scanning 
IP Reference  
Protection Copyrighted (e.g. software)
Year Protection Granted 2009
Licensed Commercial In Confidence
Impact It has so far only been used in our own research but is currently being further developed by an industrial partner.
 
Title Noise reduction for Magnetic Resonance Scanning 
Description A system for noise reduction during Magnetic Resonance Scanning involves a specially developed sound system for presenting precisely controlled anti-noise. 
Type Diagnostic Tool - Imaging
Current Stage Of Development Initial development
Year Development Stage Completed 2009
Development Status On hold
Impact At present it is only at use for our own research at Nottingham but is being developed by a commercial partner under MRCT agreements. 
 
Description Advisory Panels 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact providing expert advice on applications for grant support from these organizations

Funding of good quality research from the charity sector.
Year(s) Of Engagement Activity 2006,2007,2008,2009
 
Description Discussion Panel 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Physiological Society and Royal National Institute for the Deaf General Public discussion. Excellent feedback received

Awareness and futher information
Year(s) Of Engagement Activity 2007,2008
 
Description Invited oral presentations 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Health professionals
Results and Impact At least nine invited lectures to health professionals in the main and also to hearing aid dispensors and vetinerary surgeons

Wider dissemination of MRC funded research. Providing a deeper understanding of the basic science underpinning clicnical management of hearing loss and tinnitus for a wider professional audience
Year(s) Of Engagement Activity 2007,2008,2009
 
Description Lecturing on Tinnitus 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Health professionals
Results and Impact Providing basic scince information for health professionals in Scotland.

Informing those who manage tinnitus clinically.
Year(s) Of Engagement Activity 2007
 
Description Teaching on Tinnitus 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Health professionals
Results and Impact Pproviding a basic science underpinning for a course on the management of tinnitus

The impact is awareness and further information for health professionals.
Year(s) Of Engagement Activity 2006,2007,2008,2009
 
Description Teaching undergraduates, postgraduates and health professionals 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Approx 7 per year. Type of dissemination - Teaching, Exam tips & Questions/Hearing and Deafness/ Psychophysics and behaviour/ Auditory system/. Audience - Students/ Audiologists/Scientists. Excellent feedback received Locations: University College London, university fo Nottingham, University of Bristol, University of Salmanca

Awareness and further information attracting students to the field
Year(s) Of Engagement Activity 2006,2007,2008,2009