Cortical plasticity in response to median nerve trauma

Median nerve injuries in adults, repaired with nerve suture, lead to incomplete functional recovery despite improved surgical technique. This results in a reduction in quality of life, poorer working ability and a considerable expense for society. Misrouting of axons at the suture site connects regenerating axons to the wrong distal end organs. When distorted signals are conveyed to the dorsal root ganglia, spinal cord, thalamus and the somatosensory cortex, somatotopic maps at all levels become reorganised in a disorderly fashion. Children often regain full sensory function after median nerve injury and repair despite impaired conduction across the injured segment. There is growing evidence that cortical plasticity is the main mechanism behind the superior recovery seen in young patients, but the exact pattern of reorganisation and its impact on functional recovery are not fully understood. The general aim of this thesis was to investigate various aspects of cortical plasticity, in particular the response to median nerve injury. To this end we used two non-invasive brain imaging techniques, functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG). In Paper I we investigated the concept of audio-tactile interaction in a healthy population. We found an increased overlap between cortical activation areas (fMRI) in patients trained with coupled tactile and auditory stimuli indicating modulation of cortical plasticity induced by cross-modal training. In Paper II we studied ageand time-dependent effects on cortical activity patterns in patients with median nerve injury by correlating age at the time of injury and time passed since injury to sensory function, and cortical activation. We found a time-dependent decline in the size of the cortical activation area during stimulation of both the median and the ulnar nerve (fMRI). Furthermore, there was greater ipsilateral activation in the patient group than in a control group from a previous study. However, the results were not conclusive on this point because the stimulation paradigms differed between the two studies (event-related in the present and block paradigm in the previous study). Paper III was performed using MEG in order to further study cortical plasticity in patients with median nerve injury. We found decreased N1 and P1 amplitudes during stimulation of the injured median nerve, and an increase in these amplitudes during ulnar nerve stimulation. Paper IV was designed to reveal any possible differences in lateralisation of cortical activation after median nerve injury and to see if this was influenced by the stimulus paradigm used. By means of a laterality index (LI) the extent of contra- and ipsilateral activation was calculated. LI is decreased (more ipsilateral activation) in patients with a median nerve injury compared to controls. This means that median nerve injury causes a shift of activity from the contralateral to the ipsilateral SI. The type of stimulus paradigm (event-related or block) did not affect LI. Our findings add to the evolving knowledge of the cortical plasticity following median nerve injury

Peripheral Sensory Deprivation Restores Critical-Period-like Plasticity to Adult Somatosensory Thalamocortical Inputs

Recent work has shown that thalamocortical (TC) inputs can be plastic after the developmental critical period has closed, but the mechanism that enables re-establishment of plasticity is unclear. Here, we find that long-term potentiation (LTP) at TC inputs is transiently restored in spared barrel cortex following either a unilateral infra-orbital nerve (ION) lesion, unilateral whisker trimming, or unilateral ablation of the rodent barrel cortex. Restoration of LTP is associated with increased potency at TC input and reactivates anatomical map plasticity induced by whisker follicle ablation. The reactivation of TC LTP is accompanied by reappearance of silent synapses. Both LTP and silent synapse formation are preceded by transient re-expression of synaptic GluN2B-containing N-methyl-D-aspartate (NMDA) receptors, which are required for the reappearance of TC plasticity. These results clearly demonstrate that peripheral sensory deprivation reactivates synaptic plasticity in the mature layer 4 barrel cortex with features similar to the developmental critical period.ope

Investigating cerebrovascular health and functional plasticity using quantitative FMRI

A healthy cerebrovasculature is necessary to maintain optimal levels of blood flow and oxygen metabolism required for overall brain health. Cerebrovascular health also promotes functional plasticity which facilitates lifelong adaptation with experience and recovery following injury. In diseases such as Multiple Sclerosis (MS), there is known vascular and metabolic dysfunction, however, patients retain variable levels of functional plasticity which aids recovery following acute bouts of inflammation. Physical exercise interventions, aimed at improving cerebral blood flow and oxygen metabolism, present a potential avenue for improving patient outcomes and slowing the progression of disability. However, there is a lack of mechanistic understanding of i) brain energetic processes underlying plasticity and ii) how aerobic fitness (AF), which is linked to increased brain plasticity, benefits brain vascular and metabolic function. The work presented in this thesis uses arterial spin labelling (ASL) functional magnetic resonance imaging (fMRI) to quantitatively characterise the vascular and metabolic processes associated with functional brain plasticity, and the effects of AF on the brain’s functional capacity in healthy adults. This thesis begins with an overview of the neurobiological processes of interest and fMRI techniques that can quantify these processes. Next, a comparison of common ASL acquisition and analysis procedures is made to establish the most appropriate methods for subsequent experimental work. Chapters 4 and 5 investigate the effects of AF on cerebrovascular function in healthy adults. Chapter 6 then gives an overview of existing functional motor plasticity work, before Chapters 7 and 8 which quantify vascular and metabolic adaptations following motor training in the healthy brain. Chapter 9, presents preliminary work in an MS cohort, applying methods from previous chapters to quantify vascular and metabolic differences between patients and controls. The general discussion in Chapter 10 summarises the main findings and contributions of this work and key areas for future research are outlined