Auditory processing in schizophrenia during the middle latency period (10–50 ms): high-density electrical mapping and source analysis reveal subcortical antecedents to early cortical deficits

• Published in: Journal of psychiatry & neuroscience Vol. 32; no. 5; pp. 339 - 353
• Main Authors: Leavitt, Victoria .M., MPhil, Molholm, Sophie., PhD, Ritter, Walter., PhD, Shpaner, Marina., BA, Foxe, John .J., PhD
• Format: Journal Article
• Language: English
• Published: Ottawa, ON Canadian Medical Association 01.09.2007; CMA Impact Inc; CMA Impact, Inc
• Subjects: Adult; Adult and adolescent clinical studies; Antipsychotic Agents - therapeutic use; Auditory perception; Auditory Perception - physiology; Biological and medical sciences; Cerebral Cortex - physiopathology; Data Interpretation, Statistical; Electroencephalography; Evoked Potentials, Auditory - physiology; Female; Fundamental and applied biological sciences. Psychology; Hearing loss; Humans; Male; Medical Education; Medical research; Medical sciences; Medical tests; Middle Aged; Neurology; Physiological aspects; Psychiatric Status Rating Scales; Psychiatry; Psychoanalysis; Psychological aspects; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopathology. Psychiatry; Psychoses; Psychotic Disorders - drug therapy; Psychotic Disorders - psychology; Research Paper; Schizophrenia; Schizophrenia - drug therapy; Schizophrenic Psychology; Sensory perception; United States; Cartography; Psychology; Schizophrenia; Density; Source; Psychosis; Latent phase; Hearing; Early; Psychopathology; Subcortex; Psychiatry; Antecedent; electroencephalography; auditory-evoked potentials; event-related potentials
• ISSN: 1180-4882; 1488-2434
• DOI: 10.1016/S1180-4882(07)50060-0

Introduction Auditory sensory processing dysfunction is a core component of schizophrenia, with deficits occurring at 50 ms post-stimulus firmly established in the literature. Given that the initial afference of primary auditory cortex occurs at least 35 ms earlier, however, an essential question remains: how early in sensory processing do such deficits arise, and do they occur during initial cortical afference or earlier, which would implicate subcortical auditory dysfunction. Objective To establish the onset of the earliest deficits in auditory processing, we examined the time window demarcating the transition from subcortical to cortical processing: 10 ms to 50 ms during the so-called middle latency responses (MLRs). These remain to be adequately characterized in patients with schizophrenia. Methods We recorded auditory evoked potentials (AEPs) to simple tone-pips from 15 control subjects and 21 medicated patients with longer-term schizophrenia or schizoaffective disorder (illness duration 16 yr, standard deviation [SD] 9.4 yr), using high-density electrical scalp recordings. Between-group analyses assessed the integrity of the MLRs across groups. In addition, 2 source-localization models were conducted to address whether a distinction between subcortical and cortical generators of the MLRs can be made and whether evidence for differential dorsal and ventral pathway contributions to auditory processing deficits can be established. Results Robust auditory processing deficits were found for patients as early as 15 ms. Evidence for subcortical generators of the earliest MLR component (P20) was provided by source analysis. Topographical mapping and source localization also pointed to greater decrements in processing in the dorsal auditory pathway of patients, providing support for a theory of pervasive deficits that are organized along the lines of a dorsal–ventral distinction. Conclusions Auditory sensory dysfunction in schizophrenia begins extremely early in processing, is evident during initial cortical afference and is also seen at earlier subcortical processing stages in the thalamus. The implication is that well-established sensory processing deficits in schizophrenia may be secondary to earlier subcortical dysfunction. Our findings do not preclude the possibility of even earlier deficits in auditory sensory processing during the auditory brainstem responses.