title: 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.
abstract: BACKGROUND
  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.
authors.affiliation: The Cognitive Neurophysiology Laboratory, Nathan S. Kline Institute for Psychiatric Research, Program in Cognitive Neuroscience and Schizophrenia, Orangeburg, NY 10962, USA.
authors.forename: Victoria M
authors.initials: VM
authors.lastname: Leavitt
authors.forename: Sophie
authors.initials: S
authors.lastname: Molholm
authors.forename: Walter
authors.initials: W
authors.lastname: Ritter
authors.forename: Marina
authors.initials: M
authors.lastname: Shpaner
authors.forename: John J
authors.initials: JJ
authors.lastname: Foxe
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001307:Auditory Perception / Q000502:physiology*; D002540:Cerebral Cortex / Q000503:physiopathology*; D003627:Data Interpretation, Statistical; D004569:Electroencephalography; D005072:Evoked Potentials, Auditory / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000188:drug therapy / Q000523:psychology; D012559:Schizophrenia / Q000188:drug therapy; D012565:Schizophrenic Psychology