Understanding psychotic pathophysiology with transient, sustained, and oscillatory auditory neural response abnormalities
Hamm, Jordan Paul
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Auditory processing abnormalities are a core feature of psychosis and may underlie perceptual distortions and cognitive deficits characteristic of major psychotic disorders such as schizophrenia (SZ) and psychotic bipolar disorder (BDP). Attempts at linking experimentally quantified auditory processing abnormalities to underlying biological disease mechanisms and genetic causes have thus far been inconclusive. Such investigations might benefit from i) characterizing abnormalities with respect to underlying psychopathological domains (psychotic, affective) as they cut across DSM-IV diagnostic categories, and ii) appreciating the complexity of the auditory neural response through the use of powerful electrophysiological and analytic tools. Indeed auditory stimulus evoked cortical potentials (measured with scalp electroencephalography) involve spatiotemporally distinct transients (n100 and p200 peaks), sustained slow-potentials, and brief oscillatory events in low (theta), mid (alpha/beta), and high (gamma) frequency bandwidths. Each of these oscillations index unique aspects of local and distributed auditory cortical circuitry. The present set of investigations sought to examine each of these components in the context of interacting psychopathological domains (psychotic versus affective). Measurements were also taken from unaffected family members of persons with SZ or BDP and analysed in the context of both protective and risk factors. The manifold of results indicate that low frequency (delta-theta band) and widely distributed (P300) cortical events show little specificity toward psychotic and affect domains of psychopathology, display general heritability, and are present regardless of context. Early occurring mid-frequency (alpha) and transient events (n100, p200) display psychotic and affective domain specificity, complex heritability patterns (enhanced in non-psychotic first-degree relatives), and are partially ameliorated when auditory stimuli are attended. Finally, high-frequency response abnormalities show the least heritability and are substantially influenced by physical stimulation properties (but not attention). Altogether, this pattern of low versus high frequency and early versus late cortical potentials provides a series of specific hypotheses for future genetic research with regard to neurochemical (gaba/glutamate versus cholinergic/adrenergic) and neuroanatomical (large versus small scale connectivity) pathological processes underlying psychosis and their heterogeneous co-presentations.