How Degrading Networks Can Increase Select Cognitive Functions.
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1
The University of Sheffield, The Department of Computer Science, United Kingdom
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2
The University of Sheffield, The Department of Psychology, United Kingdom
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3
Ecole Normale Superieure, Department d’Etudes Cognitives, France
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4
Ruhr-University Bochum, Department of Biopsychology, Germany
It has recently been shown that despite the severe cell atrophy associated with manifest Huntington's Disease (HD), increased proficiency can be demonstrated in select behavioural tasks (Beste et al., 2008). Using computational models of the striatal micro-circuit we show possible mechanisms underlying the phenomena as a result of the excitotoxicity (Fan and Raymond 2007) and the competitive and selective dynamics of signal selection in the striatum.
The increase in sensitivity to endogenous glutamate associated with HD could increase the performance of NMDA dependant tasks such as those involving auditory sensory memory (Kujala et al. 2007), in spite of the severe neural deterioration. Using Mismatch Negativity (MMN), studies by Beste et al. (2008) show that patients with symptomatic HD out perform pre-symptomatic HD (pHD) and a healthy control group, exhibiting lower reaction times and error rates for standard and deviant stimuli.
We propose that this phenomena is a feature of the network structure of striatal neurons when combined with the excitotoxicity hypothesis, occurring due to the connectivity of the striatum. Using the biologically inspired model of the striatal microcircuit taken from Humphries et al. (2010), we show competitive dynamics within the network, demonstrating an inherent competitive selective signal behaviour.
By modelling two separate cortical inputs, representing two distinct actions, to sub-populations in the striatal model, we show that the network displays preferential selectivity to a strong input signal, suppressing the activity of the weaker signal at the onset of the stronger. The network displays a further reactive selectivity: the removal of the stronger signal subsequently boosts the population response to the weaker signal, possibly encouraging behavioural switching back to the ongoing signal. Defining these two elements of selectivity allows us to investigate how this selectivity evolves as the network degrades as in manifest HD.
Mimicking the excitotoxicity. we up-regulate the NMDA conductivity versus the AMPA, progressively eliminating over-excitable neurons from the network. Using a new measure for signal selectivity, our model show that excitotoxic cell atrophy, combined with increased excitability of the surviving cells, can encourage signal selectivity. Suggesting that a pathogenic increase in a transmitter sensitivity, while encouraging cell atrophy, can mediate network level behaviour, affecting the competitive signal selection dynamics due to increased activity. Thus, our results suggest that the paradoxical cognitive enhancement of the manifest HD patients is due to their selectively enhanced signal selection in the striatum.
We suggest that the striatal model can be a useful tool to shed light onto the ramifications of hypotheses such as excitotoxicity, and by examining changes in network dynamics, may provide the basis for a select few counter-intuitively improved cognitive functions in HD patients.
References
Beste, C., Saft, C., Güntürkün, O., Falkenstein, M. (2008). Increased cognitive functioning in symptomatic Huntingtonʼs disease as revealed by behavioral and event-related potential indices of auditory sensory memory and attention. The Journal of neuroscience : the official journal of the Society for Neuroscience 28(45): 11695-702.
Fan, M., Raymond, L. (2007). N-Methyl-d-aspartate (NMDA) receptor function and excitotoxicity in Huntington's disease. Progress in neurobiology. Volume 81, Issues 5-6, April 2007, Pages 272-293
Humphries, M, Wood, R., Gurney, K. (2010). Reconstructing the Three-Dimensional GABAergic Microcircuit of the Striatum. PLoS Computational Biology 6(11)
Kujalaa, T., Tervaniemib, M., Schrögere, E. (2007). The mismatch negativity in cognitive and clinical neuroscience: Theoretical and methodological considerations. Biological Psychology, 74, 1-19.
Keywords:
brain disease network dysfunction and intervention,
excitotoxicity,
Huntington's disease,
NMDA receptors,
Selectivity,
Striatum
Conference:
BC11 : Computational Neuroscience & Neurotechnology Bernstein Conference & Neurex Annual Meeting 2011, Freiburg, Germany, 4 Oct - 6 Oct, 2011.
Presentation Type:
Poster
Topic:
brain disease, network dysfunction and intervention (please use "brain disease, network dysfunction and intervention" as keyword)
Citation:
Tomkins
A,
Humphries
M,
Vasilaki
E,
Beste
C and
Gurney
K
(2011). How Degrading Networks Can Increase Select Cognitive Functions..
Front. Comput. Neurosci.
Conference Abstract:
BC11 : Computational Neuroscience & Neurotechnology Bernstein Conference & Neurex Annual Meeting 2011.
doi: 10.3389/conf.fncom.2011.53.00221
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Received:
12 Aug 2011;
Published Online:
04 Oct 2011.
*
Correspondence:
Mr. Adam Tomkins, The University of Sheffield, The Department of Computer Science, Sheffield, South Yorkshire, S1 4DP, United Kingdom, a.tomkins@sheffield.ac.uk