Excitatory/inhibitory ratio disruption modulates neural synchrony and flow directions in a cortical microcircuit.

Scientists used computer modeling to study brain activity patterns in autism and schizophrenia. They found that when the balance between brain cells that excite and inhibit activity is disrupted, it creates different types of unusual brain wave patterns. Different types of disruptions led to different problems with brain timing and communication, which might help explain why autism and schizophrenia symptoms vary so much between individuals.

This computational modeling study investigated how excitatory/inhibitory (E/I) balance disruption affects neural activity patterns in autism spectrum disorder and schizophrenia. Researchers developed a biologically plausible microcircuit model of visual cortex layer 2/3, incorporating excitatory pyramidal neurons and three inhibitory interneuron subtypes (parvalbumin [PV], somatostatin [SOM], and vasoactive intestinal polypeptide [VIP]). By manipulating population sizes of different interneuron subtypes, they found that decreasing PV interneurons enhanced beta and gamma oscillations with PV activity preceding pyramidal activity, while decreasing SOM interneurons impaired gamma-frequency activity with pyramidal activity preceding PV activity. The study demonstrates that different types of E/I imbalance produce distinct atypical neural behaviors, potentially explaining heterogeneous presentations in neurodevelopmental disorders.

These computational findings suggest that different subtypes of interneuron dysfunction may underlie distinct neural signatures in autism and schizophrenia. This could inform future targeted interventions and help explain symptom heterogeneity, though empirical validation in human studies is needed before clinical translation.

This is a computational modeling study without human participants or real brain data validation. The findings are theoretical and require empirical testing in actual brain tissue or human studies to confirm clinical relevance.

Autism spectrum disorder (ASD) and schizophrenia are complex and heterogeneous mental disorders involving the dysfunction of multiple neural systems. The atypical and heterogenous temporal coordinations of neuronal activity, which are widely observed in these two disorders, are hypothesized to stem from an excitatory/inhibitory (E/I) imbalance in the brain. To investigate the association between the E/I imbalance and atypical neural activities, and to assess the influence of specific subtypes of inhibitory interneurons on network activity regulation, we developed a computational microcircuit model with biologically plausible layer 2/3 of visual cortex that combined excitatory pyramidal neurons with three subtypes of inhibitory interneurons (parvalbumin [PV], somatostatin [SOM], and vasoactive intestinal polypeptide [VIP]). We numerically explored the role of distinct types of E/I imbalance by changing the population size of different subtype neurons.

We find that when the E/I balance is disrupted by decreasing the PV population size, activity of the PV population precedes that of the pyramidal population, which enhances beta and gamma oscillations. Conversely, pyramidal neuronal population activity was the precursor of PV interneuron activity when the E/I imbalance was induced by decreasing the SOM population size; this preferentially impaired gamma-frequency activity. The disruption of E/I balance altered the information flow between pyramidal and PV populations, modulating neuronal dynamics. Our results suggest that E/I imbalance due to different subtype interneurons would induce the distinct types of the atypical neural behaviors associated with neural system dysfunction.