Delta oscillations in the awake state are elevated in schizophrenia (SZ) [1, 2]. In contrast to the gamma/beta oscillation abnormalities, which are a risk factor for the disease (present in unaffected relatives), the delta abnormality correlates more closely with the disease itself [3].

The thalamus is involved in delta generation, sensory gating, and sleep spindles, all of which are abnormal in SZ. Furthermore, in SZ there is a reduction in thalamic size and an increase in the volume of the adjacent third ventricle; these correlate with the delta abnormality and negative symptoms of SZ [4, 5]. Experiments in rats show that NMDAR antagonist (APV or Ketamine), when applied only to the thalamus, causes delta in the thalamus and cortex. Delta occurs because antagonist blocks NR2C channels, which contribute to resting potential because they have low Mg block and are partially activated by ambient glutamate. The resulting hyperpolarization deinactivates T-type Ca channels, which then generate delta.

The development of SZ occurs as a sudden "psychotic break". The interneuron abnormalities (and resulting gamma/beta abnormalities [3]) exist before the break and may predispose a loop of brain structures to go into positive feedback. When this occurs, delta oscillations and psychosis are generated. It was previously proposed that this loop involves the excitation of the hippocampal CA1 region (known to be selectively activated in SZ) by the thalamus (specifically the nucleus reuniens), the excitation of the VTA by the hippocampus, and the excitation of the thalamus by the VTA [6]. Further evidence for thalamic excitation of CA1 has recently been obtained [7]. The psychotic break may occur when stress (which releases dopamine) pushes the loop above the threshold for positive feedback. Consistent with a bistable system, patients normalized by antipsychotic drugs remain normal when taken off the drug, but have relapses when subsequently stressed.

In SZ, delta oscillations appear to occur in only small subregions of the thalamus, cortex and hippocampus. How might this cause "first rank" SZ symptoms, many of which involve agency, the sense of what actions are one's own? The reuniens carries "corollary discharge" about action choices from the medial PFC to the temporal lobe. The block of this information flow by delta could result in loss of "agency".

References:

1. Itoh, T., et al., LORETA analysis of three-dimensional distribution of delta band activity in schizophrenia: Relation to negative symptoms. Neuroscience research, 2011. 70(4): p. 442-8.

2. Schulman, J.J., et al., Imaging of thalamocortical dysrhythmia in neuropsychiatry. Frontiers in human neuroscience, 2011. 5: p. 69.

3. Venables, N.C., E.M. Bernat, and S.R. Sponheim, Genetic and disorder-specific aspects of resting state EEG abnormalities in schizophrenia. Schizophrenia bulletin, 2009. 35(4): p. 826-39.

4. Sponheim, S.R., et al., Clinical and biological concomitants of resting state EEG power abnormalities in schizophrenia. Biological psychiatry, 2000. 48(11): p. 1088-97.

5. Shepherd, A.M., et al., Systematic meta-review and quality assessment of the structural brain alterations in schizophrenia. Neuroscience and biobehavioral reviews, 2012. 36(4): p. 1342-56.

6. Lisman, J.E., et al., A thalamo-hippocampal-ventral tegmental area loop may produce the positive feedback that underlies the psychotic break in schizophrenia. Biological psychiatry, 2010. 68(1): p. 17-24.

7. Zhang, Y., et al., NMDAR antagonist action in thalamus imposes delta oscillations on the hippocampus. Journal of neurophysiology, 2012.