Neural mass modelling of brain stimulation to Alleviate Schizophrenia biomarkers in brain rhythms

We present a neural mass model (NMM) of the brain thalamo-cortico-thalamic (TCT) network to understand the effectiveness of non-invasive treatment with transcranial Direct Current Stimulation (tDCS) in reversing the anomalous electroencephalogram (EEG) oscillations in Schizophrenia. Our TCT NMM consists of twelve neural populations representing the thalamus and cortex modules of the visual pathway connected in a closed loop; the synaptic pathways are modelled with a 3-state kinetic framework allowing the inclusion of the slow excitatory N-methyl-D-aspartate-receptors (NMDAR). Indeed, a popular hypothesis in Schizophrenia is the hypofunction of the Glutamatergic neurotransmitter receptors, NMDAR, associated with the inhibitory Gamma-amino-butyric-acid (GABA-)ergic populations in the cortex, leading to anomalous brain oscillations. Experimental studies simulate the EEG conditions in Schizophrenia by administering sub-anesthetic dosage of Ketamine, which blocks NMDAR channels at the Magnesium binding sites. We could simulate the Ketamine-induced NMDAR channel blocking by varying the Magnesium concentration in the 3-state synaptic models of appropriate pathways. Our results show Ketamine-induced increased excitatory behaviour in the model output; the changes in the γ and σ band oscillations conform to experimental studies. A model to factor in the neuroplasticity effects of applying tDCS (after (Riedinger and Hutt, 2022)) is interfaced with the TCT NMM. Informed by experimental literature, the simulated extrinsic current induced by tDCS is set to affect the plasticity in selected pathways. With appropriate parameterisation, we could simulate the reversal of the Ketamine-induced altered EEG oscillations. Overall, our in silico study emphasises the potential of NMM in predicting protocols for tDCS towards effective personalised treatment of Schizophrenia.