Background Cognitive functions are found to generally decline in manifest HD. However, data published by our group (Beste et al, J Neurosci 2008;28:11695–702) challenged this view by showing that some cognitive domains related to attentional processes showed an elevated level of performance. While we could only speculate about the possible mechanisms in this study, we now provide neurocomputational insights in the possible neurobiological mechanisms that may mediate the counterintutive pattern of results.
Methods/techniques We simulated basal ganglia (striatal) networks in computational models and systematically varied the degree on medium spiny neuron degeneration as well as the strength of NMDA receptor currents. The results of these simulations well support the empirically observed increase in pre-attentive processing. The simulations suggest that under some special constellations concerning the degree of NMDA/AMPA receptor ratio as well as the degree of medium spiny neuron degeneration, paradoxical elevated levels of cognitive processes are evident.
Conclusions In HD there are cognitive subdomains, which do not undergo a decline but an improvement in functioning. We provide a neurobiological basis for further research efforts in understanding these processes.
- Computational modelling
- NMDA receptors