The Less Things Change, the More They Remain the Same: Impaired Neural Plasticity as a Critical Target for Drug Development in Neuropsychiatry.

Abstract

Neuropsychiatric disability is related to reduced ability to change in response to clinical interventions, e.g., plasticity. Study of biomarkers and interventional strategies for plasticity, however, are sparse. In this chapter, we focus on the serial frequency discrimination task (SFDT), which is sensitive to impairments in early auditory processing (EAP) and auditory learning and has been most thoroughly studied in dyslexia and schizophrenia. In the SFDT, participants are presented with repeated paired tones ("reference" and "test") and indicate which tone is higher in pitch. Plasticity during the SFDT is critically dependent upon interactions between prefrontal "cognitive control" regions, and lower-level perceptual and motor regions that may be detected using both fMRI and time-frequency event-related potential (TF-ERP) approaches. Additionally, interactions between the cortex and striatum give insights into glutamate/dopamine interaction mechanisms. The SFDT task has been utilized in the development of N-methyl-D-aspartate receptor (NMDAR) targeted medications, which significantly modulate sensory and premotor neurophysiological activity. Deficits in pitch processing play a critical role in impaired neuro- and social cognitive function in schizophrenia and may contribute to similar impairments in dyslexia. Thus, the SFDT may be ideal for development of treatments aimed at amelioration of neuro- and social cognitive deficits across neuropsychiatric disorders.