Biological Modeling in the Discovery and Validation of Cognitive Dysfunctions Biomarkers

  • François Iris


Cognitive disorders are highly heterogenous in terms of symptoms, clinical etiologies, disease progression and therapeutic responses. Furthermore, their potential biological causes remain largely unknown. Progress at these different levels is currently mired in a vicious circle.

The identification of coherent biomarkers, essential for clinical and therapeutic progress, requires an understanding of either the relevant pathogenic processes or, at the very least, of the parameters that need to be monitored. But, syndrome-dominated conceptual thinking has become a barrier to understanding the biological processes linked to diseases characterized by clinical and therapeutic heterogeneity. As a result, current biomarkers of cognitive disorders are much too numerous, too heterogenous, and too variable to serve useful purposes. This leads to an untenable situation that precludes coherent therapeutic developments since it effectively prevents defining what could constitute valid biological, clinical and therapeutic approaches. How to escape from this situation? The problem could be partly resolved by adopting the much wider views allowed by “system-wide” approaches: in effects, by constructing predictive theoretical models of what could constitute pathological cognitive processes. This, naturally, requires the integration of massive amounts of highly heterogenous and often conflicting information. This chapter aims to provide a necessarily brief overview of the concepts, the breadth of data and the variety of network dynamics that will have to be considered while proposing a functional, experimentally validated model-building approach that could be fruitfully utilized.


Pyramidal Cell GABAA Receptor Blood Oxygenation Level Dependent Basket Cell Gamma Oscillation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Attention-deficit/hyperactivity disorder


Astrocyte-conditioned medium


After-depolarization membrane potential


Ca2+-dependent, K+-mediated after-hyperpolarization


Protein kinase (for “rac-family serine/threonine-protein kinase homolog”)


Phosophorylated form of Akt


Alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid


Brain-derived neurotrphic factor


Biomarkers Definitions Working Group


Blood oxygenation level-dependent (neurophysiology)


Biochemical systems theory


Cornu ammonis, field 1/3


Protein kinase, (for “Calmodulin kinase type II”)


Calcium ion




GTP-binding protein/GTPase (for “cell division cycle protein 42”)


Transcription factor (for “F-type osteosarcoma viral oncogene homolog”)


Central nervous system


Connexins (isoforms 26, 30, 43, etc.)


Entorhinal cortex




Electric potential generated by spontaneous slow cation conductence


Electric potential generated by spontaneous patterns of activity


Ezrin-Moesin-Radixin protein family


Fascia dentata


Food & Drugs Administration (USA)


Transcription factor (for “fos-related antigen 2”)


Gamma-aminobutyric acid


Memory-associated protein (for “growth & plasticity-associated protein 43”)


GABA transporter, isoform I


Glutamate & AMPA receptors (isoforms 1 to 4)


Guanydine triphosphate catabolic enzyme


Hertz (wave frequencies measurement unit)


5-Hydroxytryptamine type 4 receptor


Intra-cranial electroencephalogram


Inhibitory post-synaptic potentials


Transcription factor (for “J-type unnamed osteosarcoma oncogene B”)


Long-term depression (neurophysiology)


Long-term potentiation (neurophysiology)


Muscarinic receptor type II


Protein kinase (for “mitogen-activated protein kinase”)


Phosphorylated form of MAPK


Protein kinase kinase (for “MAPK/Erk kinase”)


Miniature inhibitory post-synaptic conductivity


Matrix metalloproteases


Magnetic resonance imaging


Messenger ribonucleic acid


Medial septal-diagonal band nuclei


Nerve growth factor


Na+/H+ exchanger type I


Na+/H+ exchanger regulatory factor


National Institute of Health (USA)




Neuro-peptide Y


Open reading frame (coding genetic sequence)


Positron emission tomography


Phosphoinositol triphosphate kinase


Protein kinase C


Post-translational modification




Neurotrophin receptor, (for “protein of 75 kilo-dalton in molecular mass)


GTP-binding protein/GTPase (for “ras-related C3 botulinum toxin substrate 1”)


Serine/threonine-protein kinase ( for “ras-associated factor”)


GTP-binding protein/GTPase (for “rat sarcoma oncogene”)


Reticular formation


GTP-binding proteins/GTPases (for “ras homolog gene family, member A/B”)


Receptor-laden transport carriers


Adaptor protein, (for “src homology 2 domain-containing protein”)


Transforming growth factor beta receptor II, isoform 2


Neural receptor protein-tyrosine kinase, typeA/B




World Health Organization


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  1. 1.Bio-Modeling Systems26 Rue St LambertParisFrance

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