Feasibility and clinical utility of using the tone matching test for assessment of early auditory processing in schizophrenia

Schizophrenia is associated with impairments in cognition that negatively impact recovery, making it difficult to maintain work, socialize and function independently. These cognitive deficits manifest at the level of perception as well as higher order processes such as attention, memory and reasoning. Accumulating literature on auditory perceptual processes in schizophrenia indicate that early auditory processing (EAP) deficits are found in all phases of schizophrenia and are linked to the widespread disturbances in higher order neuro- and social-cognition and to daily functioning (Donde et al., 2023; Javitt & Freedman, 2015; Thomas et al., 2017; Voss et al., 2018).

EAP deficits in schizophrenia are manifest in impaired abilities to discriminate length (Davalos et al., 2003), intensity (Holcomb et al., 1995) and pitch (Strous et al., 1995) of non-verbal sounds, as well as in segregating sequences of pitches into the different perceptual categories that form a melodic stream (McLachlan et al., 2013). Treatments that target EAP have the potential to drive downstream cognitive and functional improvements, making it critical to have a clinically feasible means to detect when EAP is impaired (Medalia et al., 2019). However, assessment of EAP has not yet been incorporated to routine clinical practice.

Because EAP assessment is rarely performed in clinical settings, EAP deficits in schizophrenia typically remain undetected unless specifically evaluated. Tests that are biased toward measurement of sensory ability are not included in standard neurocognitive assessment batteries for schizophrenia, such as the MATRICS Consensus Cognitive Battery (Nuechterlein et al., 2008), nor are they included in baseline cognitive assessments used in clinical practice of CR (Medalia et al., 2016; Medalia et al., 2017). Mismatch negativity (MMN) is an electrophysiological paradigm used to index function of early auditory regions in cortex but is impractical for clinic settings where many outpatients are treated. However, pitch discrimination, which is one of the most documented EAP impairments in schizophrenia, can be measured with the Tone Matching (TM) Test, a quick, simple, accurate and reliable way to assess pitch discrimination performance for non-verbal sounds (Donde et al., 2017; Petkova et al., 2014).

A meta-analysis of eighteen separate studies showed a statistically large TM deficit in schizophrenia (SMD=1.17, p<0.001) (Donde et al., 2023). Severely impaired TM Test performance in schizophrenia is independent from psychotic symptoms, present in about half of those diagnosed, correlates significantly with early cortical measures of auditory processing such as MMN deficits, and contributes directly to impairments in higher cognitive functions such as attention and memory (Donde et al., 2017; Donde et al., 2023; Javitt, 2009; Javitt & Sweet, 2015; Lee et al., 2018; Petkova et al., 2014). In long-term follow-up studies, TM performance has been found to be extremely stable over time, suggesting that this marker of central auditory processing reflects a trait, rather than state, psychophysiological measure (Donde et al., 2019).

As a measure of EAP dysfunction, the TM Test may serve both to identify etiologically distinct subpopulations, and as a target-engagement measure for cognitive treatments. For example, TM Test performance has been considered a potential marker of antipsychotic treatment-resistance (Donde et al., 2023), and there is evidence that people who are found impaired on the TM Test differ from those with intact TM Test performance in their need to have EAP addressed to make cognitive improvement during cognitive remediation (Medalia et al., 2019). Taken together, these qualities of the TM Test make it a good candidate for use as a clinic-based assessment of EAP.

However, the effectiveness of using the TM Test as a treatment personalization method depends upon demonstration of its feasibility and clinical utility when employed in community clinic-based programs. Feasibility refers to the convenience or ease with which tools or interventions can be used with fidelity while clinical utility examines their application in clinical practice settings. These factors were evaluated in a clinical trial of cognitive remediation for adults with schizophrenia, to inform future implementation. Specifically, this report provides information on the feasibility and clinical utility of using the TM Test to assess EAP in people with schizophrenia receiving outpatient services in a state-run large system of care. By studying the outcomes of TM test administration by community clinicians within diverse outpatient settings, this study aims to contribute information on methods to integrate scalable EAP assessment practices to personalize treatment of cognition in schizophrenia and improve recovery outcomes.

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