SLMS Academic Careers Office

Grand Challenges

12. Origins of cortico-subthalamic “hyperdirect” pathway in the motor cortex: electrophysiology and imaging

Supervisor Pair: Dr Alexander Kraskov and Professor Daniel Alexander Potential Student’s Home Department: Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology

The cortico-subthalamic “hyperdirect” pathway is a direct and fast white matter tract connecting frontal cortex and subthalamic nucleus (STN) in the basal ganglia. It has been hypothesised to play an important role in normal action inhibition behaviour and in Parkinson’s Disease (PD) pathology. Based on rodent studies, it also has been suggested that the therapeutic action of deep brain stimulation (DBS) of STN, a hugely successful treatment to ameliorate motor symptoms of PD, may be partially due to the antidromic activation of the cortical neurons projecting to the STN via the hyperdirect pathway. But in primates (including humans) we know very little about exact location of these neurons and their functional role in behaviour.

In this project, we will employ and enhance the latest diffusion magnetic resonance imaging (MRI) protocols in a non-human primate model to acquire necessary data for white matter fibre tracking using tractography. Standard tractography techniques such as diffusion tensor imaging (DTI) are insufficient to reconstruct the hyperdirect pathway, because it is right at the limits of the imaging resolution and is eclipsed by adjacent larger pathways. However, cutting edge techniques such as NODDI (neurite orientation dispersion and density imaging) combined with high-field imaging allows us to isolate smaller pathways like this. We will validate tractography findings by recording in the same animals physiologically identified cortical neurons projecting to the STN via hyperdirect pathways and in addition corticospinal neurons projecting to the spinal cord via pyramidal tract. In rodents these populations heavily overlap but this is unlikely in primates but has never been tested before.

This project will allow a Grand Challenge Student to combine state-of-the-art experimental and analysis techniques for investigation of an important physiological question which might lead to better understanding of action inhibition behaviour and, potentially, the pathology of PD