C3NL

Network Function and Cognition

The TBI group uses functional Magnetic Resonance Imaging (fMRI), Diffusion Tensor Imaging (DTI), Positron Emission Tomography (PET), Electroencephalography (EEG) and transcranial Alternating Current Stimulation (tACS), as well as behavioural measures to investigate the effects of TBI and to better understand treatment and recovery.

One example which is currently being investigated in the lab is that of post traumatic amnesia, this being an inability to encode new memories and sustain attention. Clinically, this is an important predictor of functional outcome after TBI. For a more detailed review see: De Simoni, Sara et al. “Disconnection between the default mode network and medial temporal lobes in post-traumatic amnesia”. Brain (2016)

Blast Injury

Are cognitive impairments following blast injury the consequence of impaired brain connectivity? Blast-related TBI is the signature injury of recent conflicts in Iraq and Afghanistan. This frequently leads to cognitive and neuropsychiatric impairment, but why this happens is often unclear. In collaboration with the Defence Medical Services, we are using advanced MRI/PET imaging to investigate the pathophysiology of blast injury.

In recent publications, one elegant approach in investigating this has been to visualise the brain as a network, whereby brain regions become nodes and subsequent white-matter tracts become the connections between nodes. Hubs of information exchange within particular regions of the brain become abnormal in disease states, and therefore could be vulnerable to the effects of TBI. Therefore, it is essential to come up with a method of visualising the spread of damage along white matter or axonal tracts. See Fagerholm, Erik D., et al. “Disconnection of network hubs and cognitive impairment after traumatic brain injury” Brain (2015)

 

Pituitary Dysfunction and Brain Repair

Does growth hormone deficiency impair brain repair following TBI? Large number of patients have a degree of pituitary dysfunction following TBI. The clinical importance of this is uncertain, although growth hormone improves recovery in animal models of TBI. We are investigating whether growth hormone deficiency following TBI limits natural brain repair. Further details can be found on the Imperial Centre for Endocrinology website.

A recent publication has aimed to provide a comprehensive guide for management of pituitary dysfunction following TBI. It aimed to provide guidance on (1) who, (2) when and (3) how to screen for and manage pituitary dysfunction, including post-traumatic hypopituitarism, in adult patients with TBI. This publication has been targeted towards neurosurgeons who deal with TBI on a regular basis, but may also be relevant to clinicians from other specialties, including intensive care, surgery and medicine. For more information see Tan, Chin Lik, et al. “The screening and management of pituitary dysfunction following traumatic brain injury in adults: British Neurotrauma Group guidance.” (2017)

Axonal injury in TBI 

Previously investigated was whether inflammation persists following TBI, and increases the risk factor for developing Alzheimer’s disease (AD) (Ramlackasingh et al. Ann Neurol 2011). By using PET tracers such as amyloid (11C-PIB) for activated microglia, the results showed that inflammation can persist for many years post TBI, explaining the late development of complications post TBI.

A follow-up study aimed to (1) image β-amyloid plaque burden in TBI patients, (2) test whether traumatic axonal injury and Aβ are correlated (3) to compare this to the distribution of β-amyloid plaques in AD. We tested patients with moderate-severe TBI with (11C-PiB) PET, structural and diffusion MRI. Binding potential images of 11C-PiB which can index Aβ plaque density were computed. Our results show that increased Aβ burden was observed in TBI, with a distribution not dissimilar to AD. Our research confirms a mechanistic link between initial axonal damage in TBI and the developmental of neuropathological features in dementia or AD. Scott, Gregory, et al. “Amyloid pathology and axonal injury after brain trauma” Neurology (2016)

 

Physiological Assessment of TBI

Can TMS be used to assess the severity of diffuse axonal injury following TBI? In collaboration with Professor John Rothwell and Dr Richard Greenwood at UCL we are investigating the effects of traumatic brain injury on white matter tracts using transcutaneous magnetic stimulation (TMS). We are investigating whether structural damage to white matter tracts, as demonstrated using diffusion tensor imaging, is associated with physiological evidence of white matter damage. The aim is to develop a physiological assessment of diffuse axonal injury.

Clinical Work

Professor David Sharp (Neurology) & Dr. Tony Goldstone (Endocrinology) run a linked weekly multidisciplinary TBI follow-up clinic based at Charing Cross. Mr Mark Wilson is lead neurosurgeon at the Imperial Major Trauma Centre based at St Mary’s Hospital.

 

Video analysis of TBI in sports

Can video footage in sports be used to model and simulate impacts and strain rates within the brain? In collaboration with Dr Mazdak Ghajari and the RFU, we are investigating the effects of player velocity, impact location and resulting impact kinematics on player outcomes and brain strain. We are investigating whether different patterns of brain strain, as simulated using a mathematical model of TBI, is associated with player outcomes after impact. The aim is to be able to identify components of impacts in sports which are predictive of poor player outcomes.