Award details

Cortical state and attention: How cognitive variables and neuromodulators shape neural communication and conscious perception

Reference	BB/W006758/1
Principal Investigator / Supervisor	Professor Alexander Thiele
Co-Investigators / Co-Supervisors
Institution	Newcastle University
Department	Biosciences Institute
Funding type	Research
Value (£)	997,417
Status	Current
Type	Research Grant
Start date	06/10/2022
End date	05/10/2026
Duration	48 months

Abstract

The neural basis of consciousness remains an enigma. A key theory argues that conscious perception requires attention. Attention in turn coordinates local and global brain states, allowing information, such as external stimuli, to be represented by specific neural activity patterns across cortical processing stages (so called ignition). Where ignition fails, conscious perception does not occur. However, critical assumptions of the theory, the neural activity patterns that give rise to conscious perception, and the underlying mechanisms all remain untested. To address this knowledge gap, monkeys will perform a difficult attention (change detection) task, where they report (and often fail to report) subtle stimulus changes. We thus compare neural activity related to trials of conscious report, with activity on trials of failed report (but identical stimulus conditions). Recordings from high density Neuropixels probes across cortical layers in areas V1, V4, and dorsolateral prefrontal cortex, along with EEG recordings, will reveal how attention affects the regulation and coordination of local and global cortical brain states. They will reveal whether ignition is related to conscious perception, and the underlying activity patterns. Combining local and systemic drug challenge with optogenetic stimulation during task performance will reveal how local and global brain states, and information exchange in the cortex, depends on specific acetylcholine or noradrenaline receptors. Our study tests key aspects of neural theories of consciousness. It will reveal the communication patterns within and between cortical columns that give rise to consciousness and how they are regulated by the neuromodulators acetylcholine and noradrenaline. The data provide critical cornerstones to develop quantitative models of human brain function in health and disease, which can explain how neural activity patterns are dynamically shaped by attention to result in conscious perception.

Summary

What is consciousness? How do we become aware of our surroundings and of ourselves? These questions have troubled disciplines across the humanities (e.g. philosophy, law) and the life sciences (e.g. psychology, biology, medicine) for centuries, and remain intensely debated. Biological approaches try to relate specific patterns of brain activity to reported conscious activities. This can be something as complex as explaining to a friend why a new job offer is a fantastic opportunity, or as simple as detecting (perceiving) the presence or absence of a stimulus on a screen, and reporting what is seen. This simpler example offers a way by which consciousness and its reporting can be captured and studied not only in humans, but also in other animals. The big question is: how is brain activity organised for consciousness to come about, and what differs when it fails? Many competing theories have been proposed regarding neural correlates of consciousness, but they remain largely unproven. One prominent idea is that conscious perception of a stimulus occurs if it simultaneously activates neurons across many cortical areas. Put another way, if a stimulus can "ignite" a pattern of ongoing activity across many brain areas, it is more likely to be perceived. It is believed that this only happens when certain brain areas communicate effectively with others, and when the opposite communication direction between these areas is equally effective. It is almost like an inspired discussion, where two communication partners drive one another to new heights. However, whether this is indeed the case, or how this happens, is currently unknown. Our project will explore and test this idea by recording from multiple brain areas in macaque monkeys trained to pay attention to a stimulus on a screen (without directly looking at it), and report whether (or not) it changes just ever so slightly. We will use new brain recording techniques, which allow us to simultaneously monitor the activity of hundreds of neurons across important brain areas while animals perform this task. This will allow us to test if 'ignition' is indeed the key process that underpins conscious reporting, by looking at how brain activity is affected when monkeys fail to perceive stimulus changes. We will understand where in the brain activity differences occur, and we will understand the nature of these differences. We will also investigate the specific roles of certain brain chemicals proposed to be involved by manipulating their levels in the brain. We will additionally employ novel techniques where we genetically alter neurons, so we can activate them locally by shining brief pulses of light on them. This will allow us to probe how communication within and between brain areas differs when stimuli are consciously perceived and when they are not perceived, and understand which brain chemicals are involved. The study will reveal how different parts of our brain interact to allow for conscious perception, and what goes wrong when it fails. Our data will critically test influential theories of the neural correlates of consciousness, and provide a cornerstone to refine (or refute) these. Our study has important implications for our understanding of cognition in healthy, but equally in diseased brains, and will inform current treatment strategies for attention and perceptual dysfunctions (e.g. attention deficit hyperactivity disorders, schizophrenia).

Committee	Research Committee A (Animal disease, health and welfare)
Research Topics	Neuroscience and Behaviour
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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