Unique contributions of sensory discrimination and gamma synchronization deficits to cognitive, clinical, and psychosocial functional impairments in schizophrenia

Daisuke Koshiyama; Makoto Miyakoshi; Michael L Thomas; Yash B Joshi; Juan L Molina; Kumiko Tanaka-Koshiyama; Joyce Sprock; David L Braff; Neal R Swerdlow; Gregory A Light

doi:10.1016/j.schres.2020.12.042

Unique contributions of sensory discrimination and gamma synchronization deficits to cognitive, clinical, and psychosocial functional impairments in schizophrenia

Schizophr Res. 2021 Feb:228:280-287. doi: 10.1016/j.schres.2020.12.042. Epub 2021 Jan 22.

Authors

Affiliations

¹ Department of Psychiatry, University of California San Diego, La Jolla, CA, USA. Electronic address: koshiyama-sim@umin.ac.jp.
² Swartz Center for Neural Computation, University of California San Diego, La Jolla, CA, USA.
³ Department of Psychiatry, University of California San Diego, La Jolla, CA, USA; Department of Psychology, Colorado State University, Fort Collins, CO, USA.
⁴ Department of Psychiatry, University of California San Diego, La Jolla, CA, USA; VISN-22 Mental Illness, Research, Education and Clinical Center (MIRECC), VA San Diego Healthcare System, San Diego, CA, USA.
⁵ Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.

PMID: 33493776
DOI: 10.1016/j.schres.2020.12.042

Abstract

Background: Schizophrenia patients show widespread deficits in neurocognitive, clinical, and psychosocial functioning. Mismatch negativity (MMN) and gamma-band auditory steady-state response (ASSR) are robust translational biomarkers associated with schizophrenia and associated with cognitive dysfunction, negative symptom severity, and psychosocial disability. Although these biomarkers are conceptually linked as measures of early auditory information processing, it is unclear whether MMN and gamma-band ASSR account for shared vs. non-shared variance in cognitive, clinical, and psychosocial functioning.

Methods: Multiple regression analyses with MMN, gamma-band ASSR, and clinical measures were performed in large cohorts of schizophrenia outpatients (N = 428) and healthy comparison subjects (N = 283).

Results: Reduced MMN (d = 0.67), gamma-band ASSR (d = -0.40), and lower cognitive function were confirmed in schizophrenia patients. Regression analyses revealed that reduced MMN amplitude showed unique associations with lower verbal learning and negative symptoms, reduced gamma-band ASSR showed a unique association with working memory deficits, and both reduced MMN amplitude and reduced gamma-band ASSR showed an association with daily functioning impairment in schizophrenia patients.

Conclusion: MMN and ASSR measures are non-redundant and complementary measures of early auditory information processing that are associated with important domains of functioning. Studies are needed to clarify the neural substrates of MMN and gamma-band ASSR to improve our understanding of the pathophysiology of schizophrenia and accelerate their use in the development of novel therapeutic interventions.

Keywords: Cognitive function; Functional outcomes; Gamma-band auditory steady-state response (ASSR); Mismatch negativity (MMN); Negative symptoms; Schizophrenia.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Acoustic Stimulation
Auditory Perception
Cognition
Electroencephalography
Evoked Potentials, Auditory
Humans
Memory, Short-Term
Schizophrenia* / complications