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Rodriguez-Sanchez, J.

Publications and source records attributed to Rodriguez-Sanchez, J..

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Measuring excitation/inhibition balance through field potentials

Several electroencephalography-based metrics have been proposed to index excitation/inhibition balance (E/I). We used single-unit and local field potential recordings from rat medial prefrontal and orbitofrontal cortex and mouse visual cortex and hippocampus to evaluate four candidate metrics against empirically-measured E/I. While 1/f slope and gamma oscillations showed region and context dependencies, broadband (6-80 Hz) and high gamma (80-150 Hz) power consistently correlated with E/I, supporting their use as proxy measures. If at least 30 minutes' data from medial prefrontal cortex were used per animal, broadband power could rank the animals by their E/I ratio, suggesting it could be used as an individual differences measure.

neuroscience↗

Fronto-Temporal Dysconnectivity and Cortical Excitability in High Schizotypy: Associations with Symptom Dimensions

BackgroundPsychosis has been conceptualised as a continuum extending from healthy individuals with psychotic-like experiences to clinical populations with schizophrenia. It is unclear which biological mechanisms found in chronic schizophrenia extend across the psychosis continuum to healthy individuals with high positive schizotypy (HS). In this study, we used computational modeling to test whether changes in effective connectivity and excitation/inhibition (E/I) balance reported in schizophrenia are also found in HS. MethodsA total of 2425 individuals from the general population were screened for HS. A subset (N=141) was invited for in-depth phenotyping. Resting-state functional magnetic resonance imaging (rsfMRI) and proton magnetic resonance spectroscopy (1H-MRS) were recorded in n=69 HS individuals and n=72 group-matched controls with low schizotypy (LS). We used dynamic causal modeling to estimate effective connectivity between bilateral primary auditory cortex (A1), superior temporal gyrus (STG), and inferior frontal gyrus (IFG). ResultsBilateral backward connectivity from IFG to STG was significantly reduced in HS compared to LS. Widespread cortical disinhibition in the auditory cortex-IFG network correlated with more severe positive schizotypy scores and impulsive nonconformity. Reduced excitability in the same network was correlated with stronger cognitive disorganisation. ConclusionsOur results favour a psychosis-continuum hypothesis, suggesting that reduced top-down drive from frontal cortex and compensatory allostatic upregulation of cortical excitability, as observed in chronic schizophrenia, also extend to groups with sub-clinical psychotic symptoms. Frontal cortex dysfunction may serve as a biologically interpretable biomarker of psychosis risk and a target for preventative interventions.

neuroscience↗

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↗