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Berndt, L. C. S.

Publications and source records attributed to Berndt, L. C. S..

2 recordsLinked to original sources

A Canonical Microcircuit for Estimating Excitation/Inhibition (E/I) Balance

Excitation/inhibition (E/I) balance is crucial for maintaining healthy brain function and can be disrupted in various neurological and psychiatric disorders. Despite its importance, there are few tools to study E/I balance non-invasively in humans. Here, we propose a canonical microcircuit model to estimate E/I balance from non-invasive magneto- and electroencephalography (M/EEG) recordings by parameterising global pyramidal and inhibitory cell excitability. We first establish that E/I parameters are identifiable and recoverable. We then explore the effects of these new parameters and their interaction with other parameters in a series of simulations. To highlight the clinical relevance of this new model, we simulate changes in E/I balance and their impact on event-related potentials (ERPs) derived from paired-click, passive and active oddball paradigms, which are among the most robust clinical biomarkers of schizophrenia. Our simulations show that a loss of pyramidal cell excitability can explain reduced ERP amplitudes across all three paradigms, mirroring empirical findings in schizophrenia. This method may serve as a computational assay for estimating synaptopathy and E/I balance from non-invasive M/EEG recordings across various clinical conditions thereby advancing efforts to develop personalised interventions to restore E/I balance.

neuroscience↗

Restoring Synaptic Balance in Schizophrenia: Insights from a thalamo-cortical conductance-based model.

The dysconnectivity hypothesis of schizophrenia suggests that atypical, aberrant neural communication underlies the disorders diverse symptoms. Building on this framework, our study introduces a novel approach to understanding schizophrenia and exploring potential ways to adjust neural activity through synaptic restoration. Using a combination of magnetoencephalography data and dynamic causal modeling, we identified specific synaptic disturbances in schizophrenia patients, including increased NMDA receptor-mediated excitation in superficial pyramidal neurons and reduced GABA-B receptor-mediated inhibition between interneurons and pyramidal cells. These findings reveal a critical imbalance in excitation and inhibition within thalamo-cortical circuits, manifesting as altered gamma and alpha oscillations. The cornerstone of our research is an in silico synaptic restoration analysis, which demonstrates that targeted modifications to AMPA, NMDA, GABA-A, and GABA-B receptor-mediated connections can recalibrate altered neural activity in schizophrenia, aligning it with healthy control patterns. This restoration approach not only highlights the complex nature of synaptic dysfunction in the disorder but also identifies specific pathways as potential therapeutic targets, offering new avenues for investigating schizophrenias diverse symptomatology.

neuroscience↗