Auditory mismatch impairments are characterized by core neural dysfunctions in schizophrenia.
Major theories on the neural basis of schizophrenic core symptoms highlight aberrant salience network activity (insula and anterior cingulate cortex), prefrontal hypoactivation, sensory processing deficits as well as an impaired connectivity between temporal and prefrontal cortices. The mismatch negativity is a potential biomarker of schizophrenia and its reduction might be a consequence of each of these mechanisms. In contrast to the previous electroencephalographic studies, functional magnetic resonance imaging may disentangle the involved brain networks at high spatial resolution and determine contributions from localized brain responses and functional connectivity to the schizophrenic impairments. Twenty-four patients and 24 matched control subjects underwent functional magnetic resonance imaging during an optimized auditory mismatch task. Haemodynamic responses and functional connectivity were compared between groups. These data sets further entered a diagnostic classification analysis to assess impairments on the individual patient level. In the control group, mismatch responses were detected in the auditory cortex, prefrontal cortex and the salience network (insula and anterior cingulate cortex). Furthermore, mismatch processing was associated with a deactivation of the visual system and the dorsal attention network indicating a shift of resources from the visual to the auditory domain. The patients exhibited reduced activation in all of the respective systems (right auditory cortex, prefrontal cortex, and the salience network) as well as reduced deactivation of the visual system and the dorsal attention network. Group differences were most prominent in the anterior cingulate cortex and adjacent prefrontal areas. The latter regions also exhibited a reduced functional connectivity with the auditory cortex in the patients. In the classification analysis, haemodynamic responses yielded a maximal accuracy of 83% based on four features; functional connectivity data performed similarly or worse for up to about 10 features. However, connectivity data yielded a better performance when including more than 10 features yielding up to 90% accuracy. Among others, the most discriminating features represented functional connections between the auditory cortex and the anterior cingulate cortex as well as adjacent prefrontal areas. Auditory mismatch impairments incorporate major neural dysfunctions in schizophrenia. Our data suggest synergistic effects of sensory processing deficits, aberrant salience attribution, prefrontal hypoactivation as well as a disrupted connectivity between temporal and prefrontal cortices. These deficits are associated with subsequent disturbances in modality-specific resource allocation. Capturing different schizophrenic core dysfunctions, functional magnetic resonance imaging during this optimized mismatch paradigm reveals processing impairments on the individual patient level, rendering it a potential biomarker of schizophrenia.
1 Department of Psychiatry, Psychotherapy and Psychosomatics, Medical School, RWTH Aachen University, Aachen, Germany 2 JARA-Translational Brain Medicine, Aachen, Germany.
Arnim Johannes
AJ
Gaebler
1 Department of Psychiatry, Psychotherapy and Psychosomatics, Medical School, RWTH Aachen University, Aachen, Germany 2 JARA-Translational Brain Medicine, Aachen, Germany.
Klaus
K
Mathiak
3 Neuropsychology Section, Department of Neurology, Medical School, RWTH Aachen University, Aachen, Germany 4 Neuropsychology Section, Department of Psychology, Karl Franzens University, Graz, Austria.
Jan Willem
JW
Koten
1 Department of Psychiatry, Psychotherapy and Psychosomatics, Medical School, RWTH Aachen University, Aachen, Germany 2 JARA-Translational Brain Medicine, Aachen, Germany.
Andrea Anna
AA
König
5 Department of Radiology and Medical Informatics, University of Geneva, Geneva, Switzerland 6 Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Yury
Y
Koush
7 Brain Imaging Facility, IZKF Aachen, RWTH Aachen University, Aachen, Germany.
David
D
Weyer
8 Katharina Kasper Via Nobis GmbH, Hospital for Psychiatry and Psychotherapy, Gangelt, Germany.
Conny
C
Depner
8 Katharina Kasper Via Nobis GmbH, Hospital for Psychiatry and Psychotherapy, Gangelt, Germany.
Simeon
S
Matentzoglu
9 Department of Radiology, Lurie Family Foundation MEG Imaging Centre, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
James Christopher
JC
Edgar
3 Neuropsychology Section, Department of Neurology, Medical School, RWTH Aachen University, Aachen, Germany.
Klaus
K
Willmes
1 Department of Psychiatry, Psychotherapy and Psychosomatics, Medical School, RWTH Aachen University, Aachen, Germany 2 JARA-Translational Brain Medicine, Aachen, Germany 7 Brain Imaging Facility, IZKF Aachen, RWTH Aachen University, Aachen, Germany.
Mikhail
M
Zvyagintsev
D000328:Adult; D001288:Attention / Q000502:physiology; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000503:physiopathology*; D009434:Neural Pathways / Q000503:physiopathology; D009483:Neuropsychological Tests; D012559:Schizophrenia / Q000473:pathology / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D055815:Young Adult
classification; functional magnetic resonance imaging; mismatch negativity; multivariate pattern analysis; schizophrenia