Testing a computational model of the role of cortical circuits in auditory hallucinations in people with psychosis

People who hear voices that aren't there—a symptom of psychosis called auditory hallucinations—may have overactive brain cells because a specific type of inhibitory neuron has stopped doing its job properly. This matters because auditory hallucinations are deeply distressing and affect millions of people worldwide, yet existing treatments are often ineffective. The research directly tests a long-standing theory: that reduced activity of parvalbumin-expressing interneurons (PVIs) causes a loss of inhibition in cortical circuits, allowing pyramidal neurons to fire uncontrollably and generate false perceptions. The team will give people with psychosis a drug that boosts PVI activity, then scan their brains to see if the hallucinations quieten. In parallel, they will use chemogenetic tools in mice to switch specific neuron types on and off, measuring how this alters brain rhythms linked to perception. If the model holds, it could shift treatment away from broad dopamine-blocking drugs toward targeted therapies that restore inhibitory circuit function. In the longer term, understanding how these circuits develop might allow preventive interventions before hallucinations ever begin. This is fundamental science with a direct clinical test built in—a rare combination that could refine both the theory and the treatment.