Role of prefrontal cortex in auditory-verbal hallucinations: Actor or passive bystander?

In this paper we discuss the role of the prefrontal cortex (PFC) in schizophrenia and particularly in auditory verbal hallucinations (AVH). The paper starts with a review of the concept of hypofrontality in the 1970s and a view of PFC as a passive bystander unable to regulate or control internally generated sensory impulses. We further discuss the relationship between PFC and memory processes and the hypothesis that AVH experiences occur because of intrusions of negative emotional memories, and regulation of the emotional content of the voices. Similarly, AVH experiences can be the result of failure of reality monitoring, due to aberrant discrimination between internally generated thoughts and external influences, also dependent on PFC functioning. We subsequently introduce a new view of the role of the PFC as an actor, or active agent, a kind of hyperfrontality seen in network connectivity studies. We suggest that both hypo- and hyperfrontality models may be an oversimplification of the complex relationship between brain and behavior in the generation of AVH-experiences. Rather, the impaired ability to regulate inter-network dynamics when environmental conditions change may play a central role. We therefore discuss how task-positive and task-negative cortical networks are dynamically up- and down-regulated across time at the diagnostic level, and how this affects the presence or absence of an AVH experience at the symptom level. We conclude by suggesting that it is this failure of dynamic interplay between large-scale networks that is critical for an understanding of schizophrenia in general and auditory verbal hallucinations in particular.