Friday, May 9, 2025
5/9/2025
Identification of distributed neural sources of the auditory steady-state response in psychosis Biotypes - The auditory steady-state response (aSSR) is a promising translational biomarker for psychosis. Entrainment to different frequencies of stimulation engage unique neural generators and cortical circuitry. Auditory 40-Hz gamma responses have been preferentially proposed as a schizophrenia biomarker. In a sample of over 500 total observations, with subjects across the psychosis spectrum (schizophrenia, schizoaffective disorder, bipolar disorder with psychosis) we did not find any aSSR measure that was unique to any DSM psychosis syndrome. Alternatively, neurobiologically defined psychosis subgroups (psychosis Biotypes) have unique and differentiating aSSR features. The type and extent of these differences were associated with level of cognition, independent of psychosis. In this proposal, we will use multimodal neuroimaging with electroencephalography (EEG), magnetoencephalography (MEG), and structural magnetic resonance imaging (sMRI) to investigate neural source distribution of the aSSR at multiple frequencies (20-, 40-, and 80-Hz) in psychosis cases with either deficient (psychosis Biotype-1; n=35) or exuberant (psychosis Biotype-2; n=35) neural responses to the aSSR. Both of these subgroups have poor cognition. Rather than comparing them to a mixed health group, healthy individuals will be subdivided by cognitive control (high or low, n=35 of each subgroup). The low cognitive control group will be similar to the psychosis cases on cognition but without psychosis symptoms. EEG and MEG recordings will be used to detect radial and tangential neural sources of initial auditory registration and the aSSR with high temporal resolution. EEG, with its sensitivity to both radial and tangential neural sources, will provide a link to the majority of the previous literature on this topic, while MEG, with its excellent ability to measure auditory neural signals, will yield complimentary information about the mostly tangential neural sources of the aSSR. These measures will be used to examine the distributed neural activity of the aSSR from beta to high gamma frequencies, and how they differ as a function of psychosis subtype and cognitive control abilities. Hypotheses: (1a) Biotype-2 cases will have exuberant neural activity as measured by single trial power (STP) in primary auditory cortex; (1b) Biotype-2 cases will show exuberance of their STP response in distributed cortical regions that will be more extensive in gamma frequency ranges; (1c) Biotype-1 cases will have reduced amplitude responses in primary auditory cortex and no evidence of a more distributed cortical response pattern on STP; (2a) High cognitive control healthy persons will differ from all other groups on ITC and the magnitude of its local (auditory cortical) and distributed neural sources, especially as stimulation frequency increases into the high gamma range; (2b) Low cognitive control healthy persons will not differ from the psychosis groups on ITC in auditory cortex, but will differ on magnitude of ITC sources outside of auditory cortex. This project will clarify psychosis-specific from general cognition-related features of aSSR and support a path to better etiological studies that are not currently possible using conventional diagnoses.
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