Impaired Subcortical Detection of Auditory Changes in Schizophrenia but Not in Major Depression

Abstract

The mismatch negativity is a cortical response to auditory changes and its reduction is a consistent finding in schizophrenia. Recent evidence revealed that the human brain detects auditory changes already at subcortical stages of the auditory pathway. This finding, however, raises the question where in the auditory hierarchy the schizophrenic deficit first evolves and whether the well-known cortical deficit may be a consequence of dysfunction at lower hierarchical levels. Finally, it should be resolved whether mismatch profiles differ between schizophrenia and affective disorders which exhibit auditory processing deficits as well. We used functional magnetic resonance imaging to assess auditory mismatch processing in 29 patients with schizophrenia, 27 patients with major depression, and 31 healthy control subjects. Analysis included whole-brain activation, region of interest, path and connectivity analysis. In schizophrenia, mismatch deficits emerged at all stages of the auditory pathway including the inferior colliculus, thalamus, auditory, and prefrontal cortex. In depression, deficits were observed in the prefrontal cortex only. Path analysis revealed that activation deficits propagated from subcortical to cortical nodes in a feed-forward mechanism. Finally, both patient groups exhibited reduced connectivity along this processing stream. Auditory mismatch impairments in schizophrenia already manifest at the subcortical level. Moreover, subcortical deficits contribute to the well-known cortical deficits and show specificity for schizophrenia. In contrast, depression is associated with cortical dysfunction only. Hence, schizophrenia and major depression exhibit different neural profiles of sensory processing deficits. Our findings add to a converging body of evidence for brainstem and thalamic dysfunction as a hallmark of schizophrenia.

Keywords: auditory processing; depressive disorder; major; mismatch negativity; schizophrenia.

Fig 1.

Schematic illustration of the auditory mismatch paradigm. In a block design (10 min), presentation of standard stimuli (tone with complex partials, 100 ms duration, stimulus onset asynchrony = 500 ms) served as baseline (S; 30 s duration each block). During mismatch blocks (M; 30 s), 1 of 5 different deviant types was presented with a probability of 20%. Deviant types differed from the standard stimuli either in duration, location, frequency, amplitude, or an introduced gap.

Fig 2.

Whole-brain activation maps. (A) Activation clusters of the entire sample (29 patients with schizophrenia, 27 patients with major depressive disorder, and 31 healthy control subjects) for the contrast mismatch > standard (baseline) condition. (B) Group differences for the contrast mismatch > standard (baseline) condition. The lower part depicts averaged beta estimates extracted from clusters exhibiting significant group differences. Asterisks above a bar refer to significant group differences. Z-coordinates refer to the Talairach system. L = left. R = right.

Fig 3.

Region of interest activation and path analysis. Anatomical masks (left column) were applied to extract averaged beta estimates for each group (middle column). Asterisks above a bar refer to significant group differences. The proposed structural equation model is depicted in the right column. ε1–ε3 refer to error terms included in the model.