The impact of attention on the neuronal mechanisms of adaptation in humans and animals

Brain neurons adapt or change their responsiveness following the repetition of an environmental event, such as the voice or face of an individual. Neuronal adaptation/repetition effects are thought to be important because a reduced response could indicate familiarity with an individual that we have just met and help cognitive processes to recognize and remember the individual. The neuronal mechanisms of adaptation are of great interest but remain controversial.

Human functional magnetic resonance imaging (fMRI) is a non-invasive technique that is increasingly being harnessed to make inferences about neuronal responses during adaptation. Neuronal level study in animal models is required to clarify the neuronal mechanisms. However, although a number of animal neuronal studies of adaptation have shown that neurons generally reduce their firing rates to all stimuli (what is called the ‘response-fatigue’ model of adaptation), the latest human fMRI adaptation studies suggest that this perspective is incomplete. The human results indicate that certain brain regions might contain neurons that can become more selective to specific stimuli or their features after adaptation (what is called the ‘sharpened selectivity’ model). In any case, several scientific issues appear to have complicated the interpretation of the fMRI adaptation response. Namely, the impact of attention has not been studied in the same way in both species, inconsistent experimental paradigms have been used to obtain the human and animal adaptation results, and it is not clear whether the mechanisms of adaptation (which have primarily been studied in the visual system) would be comparable to those in another sensory system, such as the auditory. Therefore, despite the importance of the popular fMRI adaptation phenomenon, the neuronal mechanisms that support it remain highly controversial.

This project is designed to address this controversy by implementing a human and animal fMRI project based on the same attentionally-controlled experiment, combined with precisely targeted neuronal recordings in the animals. Specifically, we aim to: 1) evaluate whether fMRI adaptation responses are comparable in humans and animals by conducting the same attentional experiment with both species; 2) extend the latest human fMRI adaptation paradigms to the work with animals, especially the new paradigms that appear to be able to reveal regional changes in neuronal selectivity; and 3) precisely target for neuronal recordings regions showing changes in selectivity and/or those consistent with the response-fatigue model in the animals. Moreover, we aim to conduct the experiment in the visual and auditory modalities (using, respectively, faces or voices as stimuli) to address the correspondence of fMRI adaptation responses across different sensory modalities. This is an important secondary objective because electrophysiological studies have obtained auditory adaptation results in various animals that may or may not be comparable to adaptation in the visual modality of animals. Lastly, although it is not critical for the success of the project, we have the opportunity here to combine fMRI and electrophysiology in animals to be able to more directly associate the fMRI signal and neuronal responses. If successful, our UK institution would be only the second institution in the world to achieve this in conscious behaving animals.

In summary, it has become crucial to test the link between human and animal adaptation results by using the same experiment (and stimuli) based on an attentionally controlled task. Our project has the potential to greatly advance our understanding of the neuronal mechanisms of fMRI adaptation and how they might be influenced by or interact with cognitive processes such as those of attention. The results are likely to guide future efforts that employ fMRI adaptation to influence mental processes, including memory and expectancy.

Neurons change or adapt their responsiveness to the repetition of the same or similar events. However, how repetition affects neuronal responses, although of tremendous interest, still remains unclear. To date, animal electrophysiology and human imaging studies (using the popular fMRI adaptation or ‘repetition suppression’ effects) have given rise to conflicting perspectives on the neuronal mechanisms of fMRI adaptation, and whether and how attention may have affected adaptation. We propose to address this uncertainty by using the same attentionally-controlled adaptation experiment with fMRI in humans and animals, and with electrophysiological recordings in the animals. The fMRI study will allow us to test for any cross-species correspondences in regionally-specific fMRI adaptation responses. Most outcomes will be important and are needed to reconcile the controversy surrounding the interpretation of animal and human adaptation-related results. To determine whether similar mechanisms operate in auditory and visual cortices, we aim to conduct the experiment separately in the auditory and visual modalities using parametrically morphed voices or faces. The animal fMRI results will be used to target at least two brain regions for electrophysiology. The neurophysiological data (based on response measurements from single and multiple neurons, and local-field potentials) will be related to the fMRI adaptation response and quantified in relation to the theoretical models of these to clarify the neurophysiological bases that subserve regional fMRI adaptation responses. We are confident that this ambitious project is feasible given the proven experience of the co-applicants with all aspects of the project that will be needed and the research environment at the host institution.

How the brain adapts to the environment serves as an important basis for many cognitive brain functions, such as perception, attention, memory and learning. Adaptation appears to be a ubiquitous general property of many neurons across many animal species. We propose to investigate adaptation effects at multiple neurobiological levels, from single neurons to the activity of brain regions, and in humans and another species of animals. Thus, in addition to the scientific impact, our results combined with our experience with impact activities are likely to have an influence on medical research, commercial applications, and the public. Furthermore, our proposed comparative work will advance the UK priorities to reduce, refine, or replace invasive animal research, as follows.

This project will expand the UK neurobiological-research base, particularly for the staff that are presented with the unique opportunity to combine brain neuroimaging and electrophysiological techniques in behaving models. This combination is critical for detailed neuronal modelling of human brain function for medical research. Our focus on the neuronal mechanisms underlying face and voice selectivity opens up the opportunity to exploit our data for commercial applications for automated face and voice recognition. Lastly, in the short term, the research staff, technicians and students who engage in the project will develop a unique set of skills and vocational training that will help them to be competitive in medically related commercial or academic settings.

The lay public sector is another key potential beneficiary in that lay individuals will have a better understanding of how the brain supports repetition effects and their evolutionary basis. This project will also bring attention to neuronal adaptation as a prominent process in the brain, and presumably peak people’s interest on how sub-conscious processes such as this one interact with conscious processes like those that support perceptual awareness and attention.

Finally, our project will help to reduce the reliance on invasive electrophysiology in animal models and advance the use of non-invasive fMRI techniques with animals, which is an important objective of the BBSRC and the National Centre for the 3Rs (NC3Rs) with regards to refinement, reduction and replacement of animal experiments. This human and animal project highlights the ethical issues that are at the forefront of scientific research and is likely to be exemplary for other international institutions aiming to better relate human and animal research.

In sum, this multidisciplinary project will help maintain the UK’s competitive edge on the international research scene, contribute experimental brain data for systems approaches to biological research, and potentially stimulate collaboration between interdisciplinary scientists during dissemination of results at international meetings and conferences.