Friday, 18 December 2009

Research Proposal

Today I had to submit my research proposal for my thesis project. Here it is, written by myself and Dr Christian Kluge:


Rapid plastic changes in Auditory Cortex: a classical conditioning paradigm

Chris Fassnidge, Dr Christian Kluge and Professor Jon Driver

Aim

This study seeks to determine whether detection and/or discrimination of a pure auditory tone can be improved by classical conditioning, pairing a target frequency with an electric shock

Literature Review

Work by Merzenich, Weinberger, Irvine and others has shown that receptive field properties of neurons in primary auditory cortex (AI) can undergo rapid plastic changes in response to behavioral learning in animals (reviewed in Weinberger 2004, Weinberger 2007, Irvine 2007). Remarkably, these changes occur within minutes. During learning, when a target frequency acquires behavioral relevance a large number of AI pyramidal cells shift their best frequency towards this distinct frequency. This effect has been shown to depend on attention , i.e. behavioural relevance (Polley et al., 2006). Two groups of rats underwent operant conditioning with identical stimulus sets. One group responded to a target frequency and demonstrated tonotopic changes resulting in an increased representation of the target frequency, while the second group performed the task (with exactly the same stimuli) in response to a target loudness which led to changes in the topographic organisation of neurons’ preferred loudness. In non-human primates, Blake et al. (2006) demonstrated a crucial role for active cognitive control and involvement needed for tonotopic re-mapping to occur.

Later mechanistic assessment has revealed that the neurotransmitter acetylcholine (ACh) is crucially involved in these plastic processes. Pairing brief ACh infusions with the purely passive presentation of tones induced changes in the AI tonotopic maps similar to the ones observed in the experiments described above. In addition, stimulation of the nucleus basalis, the main source of corticopetal cholinergic projections, led to identical remapping. These findings are intriguing because they strongly argue against the long-held view that primary sensory cortices are merely passive input structures in which plastic changes of receptive fields occur only during early ontogeny. Instead, the studies summarised indicate that the sensitivity and perhaps even local network resonance patterns can be dynamically adapted to current behavioural requirements.

Very little work has been done in humans on this subject. Thus, we aim to behaviourally determine whether conditioning of one or another frequency can lead to improved performance in detection and/ or discrimination of pure tones, as would be predicted if human receptive fields show similar plasticity to that documented in animals.

Materials and Method

In a within-subject design (with conditioned frequencies counterbalanced over subjects), we will compare the detection (experiment A) as well as the discrimination (experiment B) of pure tones. The detection task will employ a two alternative forced choice (2AFC) scheme in which subjects have to decide which of two successively presented white noise stimuli actually contained a pure tone. In the discrimination experiment, participants will be required to decide whether the second of two successively presented pure tones was higher or lower than the first one. In both experiments tones of a range of frequencies will be used and this part of the experiment will last about 15 minutes.

After this initial detection / discrimination block, subjects will undergo classical conditioning, pairing one distinct target frequency tone with an electric shock to the forearm. After this association is established, the detection / discrimination 2AFC routines are repeated, interleaved with further conditioning blocks (“topping up”). After 40 minutes, the detection / discrimination task will cease to be interupted by further conditioning. The absence of reinforcement of the target frequency will then lead to extinction of the association between frequency and shock (extinction).

A number of potential follow-up studies are conceivable. First, the work by Blake and colleagues (2006) suggests that operant conditioning might be more effective in inducing tonotopic changes. Thus, modifications of the paradigm employing reward or punishment depending on performance are possible. Also, there are potential MEG versions of all experiments described which would, through analysis of early latency auditory components of the evoked magnetic fields, allow for a direct assessment of the underlying neurophysiological principles.

Predicted Outcomes

This series of experiments allows for three possible outcomes:
1. Conditioning may improve tone detection performance but not tone discrimination. This situation would allow for the conclusion that a greater number of neurons areresponding to the target frequency after conditioning but that this improvement does not involve a sharpening of best frequency tuning curves.
2. Conditioning may improve tone discrimination performance but not tone detection. This outcome could be interpreted as a potential increased local signal-noise ratio. This situation seems somewhat unlikely, however, since previous studies reported best frequency shifts in large numbers of cells rather than sharpening of existing tuning curves.
3. Finally, if conditioning leads to performance improvements in both detection and discrimination our interpretation would be that although there was an increase in the number of neurons responding to the target frequency, this change does not come at the expense of frequencies around it. In this situation it would be interesting to study the underlying compensatory mechanisms in a later MEG experiment.

Analysis

The data will be analyzed with ANOVA (random effects) using the SPSS statistics software package. Further analysis may be required depending on results.

Timetable

Preparatory work: January - March 2010
(generation of stimuli, programming of the actual experiment, pilot measurements)
Data collection: March - June 2010
(16 to 20 subjects each group)
Analysis and write up: June - July 2010

Budget

Participants will be reimbursed for their time and effort using existing research grants of the ICN attention group. No investment in equipment or software will be neccessary.

Ethics

Full ethical approval will be sought from the Graduate School Research Ethics Committee prior to pilot data collection. The ethics application will be submitted in early January 2010.







References

Blake, D. T., Heiser, M. A., Caywood, M., & Merzenich, M. M. (2006). Experience-dependent adult cortical plasticity requires cognitive association between sensation and reward. Neuron, 52(2), 371-381.

Irvine, D. R. F. (2007). Auditory cortical plasticity: Does it provide evidence for
cognitive processing in the auditory cortex? Hearing Research, 229(1-2), 158-170.

Polley, D. B., Steinberg, E. E., & Merzenich, M. M. (2006). Perceptual Learning Directs Auditory Cortical Map Reorganization through Top-Down Influences. The Journal of Neuroscience, 26(18), 4970–4982.

Weinberger N. M. (2004) Specific long-term memory traces in primary auditory cortex. Nature Reviews Neuroscience, 5(4), 279-290.

Weinberger N. M. (2007). Associative representational plasticity in the auditory cortex: a synthesis of two disciplines. Learning & Memory, 14(1-2) 1-16.

1 comment:

  1. Nice post, i appreciate your efforts which you have done to share information with others.

    Dissertation Proposal

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