Project Outline

While the majority of human neuroscience focusses on the cerebral cortex, the macroscopic organisation of mammalian brains is extremely consistent, suggesting the existence of preserved organisational principles which confer an advantage to overall brain function and behaviour. In particular, the thalamus occupies a unique position in the hierarchy of sensory information processing of all mammals: it is the first port of call within the brain for the vast majority of incoming sensory information (the exception being olfaction, for which there are orbitofrontal as well as thalamic inputs). It is crucial for cognitive, motor and perceptual functions, and many neuropsychiatric and neurological disorders have thalamic abnormalities, including schizophrenia, focal and generalised epilepsy, Parkinson’s disease, multiple sclerosis and other neurodegenerative disorders. The thalamus and thalamocortical interactions are also crucial for the control of attention, sleep, vigilance and consciousness, areas where we have a particular interest. For example, the reduction in responsiveness to environmental stimuli that is characteristic of sleep onset is accomplished by inhibition of thalamocortical neurons by thalamic reticular nucleus (TRN) neurons. It has recently been suggested that this mechanism is shared on a much shorter timescale with shifts in attention. Similarly, functional and metabolic changes caused by cell loss and deafferentation in the thalamus and other forebrain structures appears to be at the root of disturbances of consciousness after severe brain injuries. Finally, control of the alpha rhythm, the dominant brain oscillation measured using electro- and magnet-encephalography (EEG/MEG) and a key marker of attentional allocation, is the result of interactions between the thalamus, the TRN and the cortex.

While these fundamental control principles governing how the brain reacts to sensory stimuli and how it generates the oscillatory activity which coordinates different regions have been shown in animal models, they have yet to be demonstrated in humans. This project will use advanced, non-invasive neuroimaging to develop a detailed understanding of the role of the human thalamus. In particular, we are keen to develop understanding of how thalamocortical and intra-thalamic connections are modified in relation to sleep deprivation and vigilance, and in relation to changes in the alpha rhythm and attention.

The primary methods that will be used are structural and functional MRI, EEG to measure changes in vigilance and the alpha oscillation. In pilot data we have demonstrated that the TRN can be identified using specific MRI sequences at 3T and at 7T, and will build on and optimise this work to allow detailed investigation of the TRN, which has not been done in humans previously. Additionally, and depending on the candidate interests, they may be able to test some of their methods in patients with consciousness impairments after brain injury.

Relevant papers

Kerry MC, Brown VJ. The Thalamic Reticular Nucleus: more than a sensory nucleus? Neuroscientist 8(4):302–305 (2002)

Guillery RW, Feig SL, Lozsadi DA. Paying attention to the thalamic reticular nucleus. Trends Neurosci 21, 28-32 (1998)

Sherman SM. The thalamus is more than just a relay. Curr. Opin. Neurobiol. 17, 417–422 (2007).

Sherman SM. Thalamus plays a central role in ongoing cortical functioning. Nat. Neurosci. 19, 533–541 (2016).

Techniques

• Designing, planning, and running novel paradigms to study thalamic activity and thalamocortical interactions
• Structural and functional MRI focussed on the thalamus
• EEG and EEG-fMRI
• Actigraphy to monitor sleep patterns
• Advanced signal processing and statistical analyses