Multimodal Magnetic Resonance Imaging Data Fusion Reveals Distinct Patterns of Abnormal Brain Structure and Function in Catatonia.

Catatonia is a nosologically unspecific syndrome, which subsumes a plethora of mostly complex affective, motor, and behavioral phenomena. Although catatonia frequently occurs in schizophrenia spectrum disorders (SSD), specific patterns of abnormal brain structure and function underlying catatonia are unclear at present. Here, we used a multivariate data fusion technique for multimodal magnetic resonance imaging (MRI) data to investigate patterns of aberrant intrinsic neural activity (INA) and gray matter volume (GMV) in SSD patients with and without catatonia. Resting-state functional MRI and structural MRI data were collected from 87 right-handed SSD patients. Catatonic symptoms were examined on the Northoff Catatonia Rating Scale (NCRS). A multivariate analysis approach was used to examine co-altered patterns of INA and GMV. Following a categorical approach, we found predominantly frontothalamic and corticostriatal abnormalities in SSD patients with catatonia (NCRS total score ≥ 3; n = 24) when compared to SSD patients without catatonia (NCRS total score = 0; n = 22) matched for age, gender, education, and medication. Corticostriatal network was associated with NCRS affective scores. Following a dimensional approach, 33 SSD patients with catatonia according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision were identified. NCRS behavioral scores were associated with a joint structural and functional system that predominantly included cerebellar and prefrontal/cortical motor regions. NCRS affective scores were associated with frontoparietal INA. This study provides novel neuromechanistic insights into catatonia in SSD suggesting co-altered structure/function-interactions in neural systems subserving coordinated visuospatial functions and motor behavior.

Aberrant Hyperconnectivity in the Motor System at Rest Is Linked to Motor Abnormalities in Schizophrenia Spectrum Disorders.

Motor abnormalities are frequently observed in schizophrenia and structural alterations of the motor system have been reported. The association of aberrant motor network function, however, has not been tested. We hypothesized that abnormal functional connectivity would be related to the degree of motor abnormalities in schizophrenia. In 90 subjects (46 patients) we obtained resting stated functional magnetic resonance imaging (fMRI) for 8 minutes 40 seconds at 3T. Participants further completed a motor battery on the scanning day. Regions of interest (ROI) were cortical motor areas, basal ganglia, thalamus and motor cerebellum. We computed ROI-to-ROI functional connectivity. Principal component analyses of motor behavioral data produced 4 factors (primary motor, catatonia and dyskinesia, coordination, and spontaneous motor activity). Motor factors were correlated with connectivity values. Schizophrenia was characterized by hyperconnectivity in 3 main areas: motor cortices to thalamus, motor cortices to cerebellum, and prefrontal cortex to the subthalamic nucleus. In patients, thalamocortical hyperconnectivity was linked to catatonia and dyskinesia, whereas aberrant connectivity between rostral anterior cingulate and caudate was linked to the primary motor factor. Likewise, connectivity between motor cortex and cerebellum correlated with spontaneous motor activity. Therefore, altered functional connectivity suggests a specific intrinsic and tonic neural abnormality in the motor system in schizophrenia. Furthermore, altered neural activity at rest was linked to motor abnormalities on the behavioral level. Thus, aberrant resting state connectivity may indicate a system out of balance, which produces characteristic behavioral alterations.

Decreased density of GABA-A receptors in the left sensorimotor cortex in akinetic catatonia: investigation of in vivo benzodiazepine receptor binding.

OBJECTIVES: Catatonia is a psychomotor syndrome with concomittant akinesia and anxiety which both respond almost immediately to benzodiazepines such as lorazepam. The benzodiazepine receptor distribution was therefore investigated in akinetic catatonia with single photon emission tomography (SPECT) using iodine-123-iomazenil ((123) I Iomazenil). METHODS: Ten akinetic catatonic patients, 10 psychiatric controls (similar age, sex, medication, and underlying psychiatric diagnosis but without catatonic syndrome), and 20 healthy controls were investigated with SPECT 2 hours after injection of (123) I Iomazenil. To exclude potential effects of cerebral perfusion (r-CBF) r-CBF was additionally investigated with Tc-99mECD SPECT. RESULTS: Catatonic patients showed significantly lower iomazenil binding and altered right-left relations in the left sensorimotor cortex compared with psychiatric (p<0.001) and healthy (p<0.001) controls. In addition, there was significantly lower r-CBF in the right lower prefrontal and parietal cortex in catatonia whereas in the left sensorimotor cortex no differences in r-CBF between groups were found. Catatonic motor and affective symptoms showed significant correlations (p<0.05) with benzodiazepine binding in the left sensorimotor cortex as well as with right parietal r-CBF. CONCLUSIONS: Reduced iomazenil binding suggests decreased density of GABA-A receptors in the left sensorimotor cortex in akinetic catatonia. In addition to reduced GABA-A receptor density in the left sensorimotor cortex the parietal cortex seems to be involved in pathophysiology of catatonic symptoms. It is concluded that, considering results from correlation analyses, both emotional and motor symptoms in catatonia seem to be closely related to left sensorimotor and right parietal alterations.