Event Abstract Back to Event A large-scale model of thalamocortical dysrhythmia Henning Proske1*, Daniel Jeanmonod2, Daniel Kiper3 and Paul Verschure4 1 Uni/ETH, Switzerland 2 Universitaetsspital, Switzerland 3 Institute of Neuroinformatics, Switzerland 4 Universitat Pompeu Fabra, Spain Several neuropathologies such as Parkinson's Disease, neuropathic pain and major depression have shown to correlate with the existence of 2-5 Hz bursting discharges in thalamic neurons [1] and characteristic shifts in the power-spectrum of EEG/MEG measures [2,3,4]. These shifts are coherent with the disease associated bursting activity in the thalamus. It has been suggested that clinical symptoms arise from the abnormal interaction that the repetitive and synchronized bursting in thalamic cells has on the dynamical stability of neocortical circuits (thalamocortical dysrhythmia - TCD). Indeed, these symptoms can be significantly ameliorated by focal lesions to specific locations in the thalamus. The original description of TCD as proposed by Llinas and others provides an abstract model to explain the above pattern of physiological data that is observed in patients. Two open question pertain to how exactly hyperpolarisation in the thalamic relays leads to low-frequency bursting and, secondly, how the low-frequency activity in turn spreads from specific locations to entrain large parts of the thalamocortical system. In order to answer these questions we have built a large-scale computational model of the thalamocortical system that shows the generation, persistence, and spread of low-frequency activity through the thalamocortical system. Our model also shows how low-frequency dysrhythmia originates in single neurons, slowly invades individual thalamocortical modules and subsequently spreads to large-scale cell ensembles. In our model persistent TCD can result from an interaction between recurrent feedback within the thalamus and cell-intrinsic mechanisms. Furthermore, divergent thalamocortical and corticothalamic excitatory connections provide a substrate for the synchronization and spread of low-frequency activation through the whole thalamocortical system. Starting with replicating the known physiology of TCD our model generates a number of testable predictions: 1. Excitatory noise leads to a decrease of the probability of bursting in thalamic cells by interfering with the intrinsic hyperpolarisation-activated current (Ih). 2. Recurrent bursting in the thalamus depends largely on the time-scale of the thalamic reticular inhibition on the thalamic relay neurons. 3. Higher-order thalamic nuclei will be particularly affected by the bursting activity due to their divergent projections. Hence, our model of TCD shows that the specific symptomatology of neuropathologies result from the impact of local perturbations on the system level organization of the brain.