Monday, February 25, 2008

Large-scale thamamocortical model

While the Blue Brain folk want to construct an incredibly detailed model of a single cortical column, a recent paper by Izhikevich and Edelman (Large-scale model of mammalian thalamocortical systems) reports on a less detailed model of the entire human thalamocortical system.

Some of the details of their model (roughly from large-scale to lower scale) include:
1. The cortical sheet's geometry was constructed from human MRI data.
2. Projections among cortical regions were modeled using data from diffusion tensor MRI of the human brain (above image is Figure 1 of the paper showing a subset of such connections).
3. Synaptic connectivity patterns among neurons within and between cortical layers are based on detailed studies of cat visual cortex (and iterated to all of cortex).
4. Individual neurons are not modelled using the relatively computationally intensive Hodgkin-Huxely models, but a species of integrate-and-fire neuron that included a variable threshold, short-term synaptic plasticity, and long term spike-timing dependent plasticity.
5. The only subcortical structure included in the model is the thalamus, but the model does include simple simulated neuromodulatory influences (dopamine, acetylcholine).

Their model exhibited some very interesting behavior. First, larger-scale oscillatory activity that we see in real brains emerged in the model (e.g., as you would observe via EEG). Also like real brains, the model exhibited ongoing spontaneous activity in the absence of inputs (note this only occurred after an initial 'setup' period in which they simulated random synaptic release events: the learning rule seemed to take care of the rest and push the brain into a regime in which it would exhibit spontaneous activity). Quite surprisingly, they also found that when a single spike was removed from a single neuron, the state of the entire brain would diverge compared to when that spike was kept in the model. There is a lot more, so if this sounds interesting check out the paper. They also mention in the paper that they are currently examining how things change when they add sensory inputs to the model.

Of course, a great deal of work is yet to be done, a great deal of thinking through the implications (and biological relevance) of some of the model's behavior (especially its global sensitivity to single spikes, which to me sounds biologically dubious). However, I find it quite amazing that by simply stamping the basic cortical template onto a model of the entire cortical sheet, and adding the rough inter-area connections, they observed many of the qualitative features of actual cortical activity. We tend to focus so much on local synaptic connections in our models of cortex, it is easy to miss the fact that the long-range projections could have similarly drastic influences on the global behavior of the system.

This paper is just fun. First, it is a great example of how to write a modeling paper for nonmathematicians. It had enough detail to give the modeler a sense for what they did, but not so much detail that your average systems neuroscientist would instinctively throw it in the trash (as is the case with too many modelling papers). Second, it provides a beautiful example of how people interested in systems-level phenomena can build biology into their model without making the model so computationally expensive that it would take fifty years to simulate ten milliseconds of cortical activity. It will be very interesting in the future as the hyper-realist Blue Brain style models make contact with these middle-level theories. I don't see conflict, but a future of productive theory co-evolution.

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