Nucleus Reuniens-Elicited Delta Oscillations Disable the Prefrontal Cortex in Schizophrenia

Schizophrenia (SZ) is a severe mental disorder associated with an array of symptoms characterized as positive, negative and cognitive dysfunctions. While SZ is a multifaceted disorder affecting several regions of the brain, altered thalamocortical systems have emerged as a leading contributor to SZ. Specifically, it has been shown that: (1) the thalamus is functionally disconnected from the prefrontal cortex (PFC) in SZ; (2) neural activity and blood flow to the PFC are greatly diminished in SZ (hypofrontality); and (3) delta oscillations are abnormally present in the PFC during the waking state in SZ. We suggest that the abnormal delta oscillations drive the other PFC signs of SZ. Specifically, decreases in energy required to maintain delta, would initiate the reduced PFC perfusion of SZ (hypofrontality), and contribute to the 'mismatched' thalamic and PFC activity of SZ. As SZ involves glutamate (NMDAR) hypofunction and dopamine hyperfunction, both NMDAR antagonists and dopamine agonists produce marked increases in delta oscillations in nucleus reuniens (RE) of the thalamus and its target structures, including the PFC. This would suggest that RE is a primary source for the elicitation of PFC delta activity, and the presence of delta during waking (together with associated signs) would indicate that the prefrontal cortex is disabled (or non-functional) in schizophrenia.