Emerging Temporal Lobe Dysfunction in People at Clinical High Risk for Psychosis

Abstract

Clinical high-risk (CHR) individuals have been increasingly utilized to investigate the prodromal phases of psychosis and progression to illness. Research has identified medial and lateral temporal lobe abnormalities in CHR individuals. Dysfunction in the medial temporal lobe, particularly the hippocampus, is linked to dysregulation of glutamate and dopamine via a hippocampal-striatal-midbrain network that may lead to aberrant signaling of salience underpinning the formation of delusions. Similarly, lateral temporal dysfunction may be linked to the disorganized speech and language impairments observed in the CHR stage. Here, we summarize the significance of these neurobiological findings in terms of emergent psychotic symptoms and conversion to psychosis in CHR populations. We propose key questions for future work with the aim to identify the neural mechanisms that underlie the development of psychosis.

Keywords: clinical high risk; dopamine; glutamate; hippocampus; schizophrenia; temporal lobe.

Figure 1

Diagram showing hippocampal midbrain striatal circuit involved in the regulation of striatal dopamine via glutamatergic, GABAergic projections (+) = excitatory pathway and (−) = inhibitory pathway. In schizophrenia and clinical high-risk (CHR) states, it is hypothesized that increased glutamatergic output from the hippocampal subiculum to the ventral striatum (blue pathway) reduces inhibition via glutamatergic and GABAergic pathways that ultimately drives ventral tegmental area (VTA) dopamine cells and dopamine release back to the striatum (red pathway).

Figure 2

Lateral temporal and frontal network encompassing the inferior frontal gyrus (IFG) (green), the superior frontal gyrus (SFG) (light blue), the Middle Frontal Gyrus (MFG) (red), the superior temporal gyrus (STG) (yellow), and the middle temporal gyrus (MTG) (blue). Networks identified via WFU_PickAtlas toolbox for SPM12 in Montreal Neurological Insitute (MNI) space.

Figure 3

Example of connectivity findings in CHR samples. (A) Increased connectivity between hippocampus and striatum, and midbrain and striatum (Modinos, et al., 2019, 96). (B) Decreased connectivity between STG and prefrontal regions (89).