The functions and dysfunctions of the basal ganglia

We have previously developed a unifying theory of their implementation of action-selection algorithms, how action selection is controlled by the neuromodulator dopamine, and how disruption of this action selection underlies symptoms of the disparate basal ganglia-related disorders. Building on this are three collaborative projects:

  1. Paradoxical cognitive enhancement in Huntington’s disease and its implications for basal ganglia function. With Christian Beste, cognitive neuroscientist at Ruhr-Universitat, Bochum, supplying behavioural and EEG data from controls and Huntington’s disease patients.
  2. Dopaminergic control of action-outcome learning. With the labs of Peter Redgrave (experimental) and Kevin Gurney (computational) at Sheffield University.
  3. Probabilistic population coding of action selection. With Mehdi Khamassi at ISIR, Universite Pierre et Marie Curie, Paris.
The classic anatomy of the dorsal basal ganglia (grey-shaded structures are outside the basal ganglia).

The classic anatomy of the dorsal basal ganglia (grey-shaded structures are outside the basal ganglia).

Many sensory, association, and prefrontal cortical areas project to the striatum, and many also project to the subthalamic nucleus (STN). Both in turn project to the other nuclei of the basal ganglia: the dopaminergic neurons of the substantia nigra pars compacta (SNc), the globus pallidus (GP), and the “output” nucleus – the substantia nigra pars reticulata.

Rectangular box sizes are proportional to the number of neurons in each structure, emphasising the dominance of the striatum —dorsal striatum contains around 2.8 million MSNs in one hemisphere of the rat.

Modelling deep-brain stimulation therapies for Parkinson’s disease.

Modelling deep-brain stimulation therapies for Parkinson’s disease.

High-frequency stimulation of the subthalamic nucleus (STN) is the main target for deep brain stimulation, but how this stimulation produces improvements in motor symptoms is unknown. We simulate high-frequency stimulation of the STN in our spiking-neuron model of the basal ganglia (left) to investigate how the stimulation affects the basal ganglia network.

An example simulation output is shown top right, where the onset of stimulation synchronises many neuron outputs to the stimulation frequency (bottom right: fidelity is the proportion of spikes time-locked to a stimulation pulse); but also shows that stimulation paradoxically drives many neurons to near silence in all three structures.