Neurological soft signs as an external marker of neuronal dysfunction in schizophrenia: Investigation with multimodal magnetic resonance imaging
Final Report Abstract
At the beginning of the 20th century, many authors proposed that a considerable number of schizophrenia patients experience genuine sensorimotor abnormalities. Recent evidence suggests that the association between psychotic symptoms and sensorimotor abnormalities in SSD reflects neuronal dysfunction in the cortico-cerebellar-thalamo-cortical circuit (CCTCC) as conceptualized in the model of “cognitive dysmetria”. If this dysfunction develops earlier than prodromal symptoms of the disorder, it might give rise to subtle sensorimotor abnormalities. In this context, subtle sensorimotor deficits such NSS have been suggested to be an external marker of underlying neuronal dysfunction that is linked with an elevated risk for developing schizophrenia. In this project we have advanced our understanding of both NSS and other more severe sensorimotor abnormalities (e.g. parkinsonism and catatonia) in SSD. The following are the four main findings of the project: (1) Our results support the notion that NSS are not significantly modulated by current antipsychotic dosage in SSD. The associations between NSS, akathisia and parkinsonism, as revealed by this project, support the genuine rather than medication-dependent origin of particular motor abnormalities in SSD. (2) Using mCCA + jICA, we found complex neural pathomechanisms underlying NSS in SSD suggesting aberrant structure and function, predominantly in cortical and cerebellar systems that critically subserve sensorimotor dynamics and psychomotor organization. (3) Our results suggest that NSS are significant predictors of poor clinical outcome in SSD at baseline and >6 months after an acute psychotic episode. These findings propose sensorimotor domain as state biomarker of SSD and support its predictive power with respect to treatment outcome. (4) NSS scores “integrative function” and right inferior parietal lobule regional homogeneity (ReHo) were significant predictors of auditory verbal hallucinations (AVH) in SSD. These data suggest significant interrelationships between sensorimotor integration abilities, brain structure and function, and AVH symptom expression. (5) Structural reorganization of white matter bundles connecting orbitofrontal/parietal, thalamic and striatal regions contribute to catatonia in SSD patients. Overall, this interdisciplinary project used multimodal neuroimaging methods and clinical as well as behavioral assessments to better understand the role of the sensorimotor domain in the development and treatment of schizophrenia spectrum disorders. This project has provided the theoretical basis for other projects examining the sensorimotor domain in psychiatric disorders.
Publications
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Patterns of co-altered brain structure and function underlying neurological soft signs in schizophrenia spectrum disorders. Hum Brain Mapp. 2019 Dec 1;40(17):5029-5041
Hirjak D, Rashidi M, Fritze S, Bertolino AL, Geiger LS, Zang Z, Kubera KM, Schmitgen MM, Sambataro F, Calhoun VD, Weisbrod M, Tost H, Wolf RC
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Moving forward: distinct sensorimotor abnormalities predict clinical outcome after 6 months in patients with schizophrenia. Eur Neuropsychopharmacol. 2020 Jul;36:72-82
Sambataro F, Fritze S, Rashidi M, Topor CE, Kubera KM, Wolf RC, Hirjak D
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Multimodal Magnetic Resonance Imaging Data Fusion Reveals Distinct Patterns of Abnormal Brain Structure and Function in Catatonia. Schizophr Bull. 2020 Jan 4;46(1):202-210
Hirjak D, Rashidi M, Kubera KM, Northoff G, Fritze S, Schmitgen MM, Sambataro F, Calhoun VD, Wolf RC
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Multiparametric mapping of white matter microstructure in catatonia. Neuropsychopharmacology. 2020 Sep;45(10):1750-1757
Wasserthal J, Maier-Hein KH, Neher PF, Northoff G, Kubera KM, Fritze S, Harneit A, Geiger LS, Tost H, Wolf RC, Hirjak D
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Neural Signature of Parkinsonism in Patients With Schizophrenia Spectrum Disorders: A Multimodal MRI Study Using Parallel ICA. Schizophr Bull. 2020 Jul 8;46(4):999-1008
Wolf RC, Rashidi M, Fritze S, Kubera KM, Northoff G, Sambataro F, Calhoun VD, Geiger LS, Tost H, Hirjak D
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Neurological soft signs in schizophrenia spectrum disorders are not confounded by current antipsychotic dosage. Eur Neuropsychopharmacol. 2020 Feb;31:47-57
Fritze S, Sambataro F, Kubera KM, Bertolino AL, Topor CE, Wolf RC, Hirjak D
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A neurodevelopmental signature of parkinsonism in schizophrenia. Schizophr Res. 2021 May;231:54-60
Wolf RC, Kubera KM, Waddington JL, Schmitgen MM, Fritze S, Rashidi M, Thieme CE, Sambataro F, Geiger LS, Tost H, Hirjak D
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Neurological Soft Signs Predict Auditory Verbal Hallucinations in Patients With Schizophrenia. Schizophr Bull. 2021 Mar 16;47(2):433-443
Wolf RC, Rashidi M, Schmitgen MM, Fritze S, Sambataro F, Kubera KM, Hirjak D
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White matter microstructure alterations in cortico-striatal networks are associated with parkinsonism in schizophrenia spectrum disorders. Eur Neuropsychopharmacol. 2021 Sep;50:64-74
Wasserthal J, Maier-Hein KH, Neher PF, Wolf RC, Northoff G, Waddington JL, Kubera KM, Fritze S, Harneit A, Geiger LS, Tost H, Hirjak D
