A list of potential internship/bachelor/master projects

Mismatch Negativity in Schizophrenia

Lesion-repair in a model of structural plasticity:

Together with Ankur Sinha, Volker Steuber and others at University of Hertfordshire, we built a model of structural plasticity that is able to restore activity to neurons deprived of sensory input by a lesion (here). For this paper, Ankur has ran many simulations with different configurations and we have the data (weights, connections, etc…) for all these simulations. One thing we haven’t looked at, which would be a nice topic for a lab rotation, would be to see how the repaired network differs from the initial (non-lesioned) network in terms of network structure, i.e. connectivity motifs and other graph theoretic measures (here)

Identifying novel drug targets with computational models of gamma-band auditory steady-state deficits in schizophrenia

I have built a model of gamma-band auditory steady-state deficits in schizophrenia (here) and would like to use this model to search for potential targets for pharmacological manipulation (or electrical stimulation) to ameliorate these deficits (because they are believed to underlie cognitive/positive symptoms in schizophrenia). The approach would be very similar to Siekmeier and vanMaanen (here).

Ketamine effects on theta modulation of gamma oscilations

Ketamine or phencyclidine, are two NMDAR antagonists which produce psychotic symptoms in normal individuals and worsen symptoms in schizophrenic patients. Previously, it has been demonstrated that ketamine produced a decrease in theta (3–12 Hz) and increase in gamma (30–100 Hz) power when given systemically in mouse and in humans. Increased gamma power, however, appears paradoxical since NMDAR antagonism would be expected to reduce firing rates and thus reduce high-frequency activity. Therefore, it has been suggested that low concentrations of these NMDAR antagonists selectively block receptors on inhibitory circuits, whereas high concentrations produce anesthesia through antagonism of all NMDA-dependent transmission. In a model of hippocampal theta-gamma coupling in CA3, Neymotin et al. (here) investigated the mechanism of action of ketamine. While this analysis suggests a potential mechanism by which ketamine acts on the hippocampus, ist effect on cortical circuits remain elusive. Therefore, a potential follow-up on this work, would be to extend a recent model auditory cortex (see here) to show baseline theta-gamma modulations and then perform similar exploration oft he effects of ketamine.

Schizophrenia-associated genetic variants and hallucinations

Aru et al. (here) propose that modulation (by Acetyl choline and Noradrenaline) change the way Layer V pyramidal cells process input (somatic vs apical dendritic). They find a regime of ‘apical drive’, where inputs to the apical dendrites are enough to drive the cells. They also briefly mention that a pathological shift in the modulation might underlie hallucinations. Use the Hay model together with our genetic variants (here) to explore whether the changes of propagation of activity along the apical dendrite caused by the variants facilitate such a shift