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.

Cingulate-basal ganglia-thalamo-cortical aspects of catatonia and implications for treatment.

The catatonic syndrome is an example of a multifactorial neurobehavioral disorder that causes much morbidity and mortality but also has the potential to unlock the mystery of how motivation and movement interact to produce behavior. In this chapter, an attempt is made to understand better the catatonic syndrome through the lens of neurobiology and neuropathophysiology updated by recent studies in molecular biology, genomics, inflammasomics, neuroimaging, neural network theory, and neuropsychopathology. This will result in a neurostructural model for the catatonic syndrome that centers on paralimbic regions including the anterior and midcingulate cortices, as they interface with striatal and thalamic nodes in the salience decision-making network. Examination of neurologic disorders like the abulic syndrome, which includes in its extreme catatonic form, akinetic mutism, will identify the cingulate cortex and paralimbic neighbors as regions of interest. This exploration has the potential to unlock mysteries of the brain cascade from motivation to movement and to clarify catatonia therapeutics. Such a synthesis may also help us discern meaning inherent in this complex neurobehavioral syndrome.

Association between catatonia and levels of hair and serum trace elements and minerals in autism spectrum disorder.

The objective of the study was to investigate the association between catatonia in autism spectrum disorder (ASD) and the levels of hair and serum trace elements and minerals in children with ASD. The levels of hair and serum trace elements and minerals of boys suffering from ASD with (n = 30) and without (n = 30) catatonia, as well as 30 age- and sex-matched neurotypical controls were assessed using ICP-MS. Hair calcium (Ca) and selenium (Se) levels were lower in ASD patients as compared to the controls. Hair mercury (Hg) levels in ASD patients were more than 3-fold and 2-fold higher as compared to the controls and children with catatonia in ASD. Hair iodine (I) and manganese (Mn) were the lowest and the highest in ASD + Catatonia, respectively. Serum aluminium (Al) and cadmium (Cd) levels in healthy controls were significantly higher in comparison to the patients of both groups. Serum chromium (Cr), copper (Cu) levels were significantly increased in patients with ASD and catatonia, whereas vanadium (V) levels were elevated in patients both with and without catatonia. Multiple regression analysis demonstrated that hair Hg and serum Al and Cd levels were negatively associated with catatonia in ASD in crude and adjusted models. Although the etiology of catatonia in ASD is unclear, the obtained data demonstrate that catatonic symptoms in ASD may be at least partially mediated by altered trace element levels. Further studies are required to elucidate the role of trace elements in the potential signaling mechanisms of catatonia.

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.

Psychomotor symptoms of schizophrenia map on the cerebral motor circuit.

Schizophrenia is a devastating disorder thought to result mainly from cerebral pathology. Neuroimaging studies have provided a wealth of findings of brain dysfunction in schizophrenia. However, we are still far from understanding how particular symptoms can result from aberrant brain function. In this context, the high prevalence of motor symptoms in schizophrenia such as catatonia, neurological soft signs, parkinsonism, and abnormal involuntary movements is of particular interest. Here, the neuroimaging correlates of these motor symptoms are reviewed. For all investigated motor symptoms, neural correlates were found within the cerebral motor system. However, only a limited set of results exists for hypokinesia and neurological soft signs, while catatonia, abnormal involuntary movements and parkinsonian signs still remain understudied with neuroimaging methods. Soft signs have been associated with altered brain structure and function in cortical premotor and motor areas as well as cerebellum and thalamus. Hypokinesia is suggested to result from insufficient interaction of thalamocortical loops within the motor system. Future studies are needed to address the neural correlates of motor abnormalities in prodromal states, changes during the course of the illness, and the specific pathophysiology of catatonia, dyskinesia and parkinsonism in schizophrenia.

[Comparative analysis of imipramine intake reactions in catatonic and wistar rats].

Chronic imipramine intake (7.5 mg/kg) leads to the stable decrease of excitable reactions to sound stimulant in Wistar rats and induced phase behavioral response in catatonic GC rats. Increased noradrenaline level in frontal cortex and striatum in Wistar animals was shown, whereas it didn't reveal noradrenaline level differences in any brain structures in GC rats. The higher blood corticosterone concentration was decreased under antidepressant reaction in GC rats. Differences between intact GC animals were found out: reduced triglyceride level, lesser body weight, and greater weight index of adrenals in comparison with Wistar rats. Various mechanisms of imipramine action in two rat strains were shown: influence on adrenergic brain system, taking part in the control of exiting behavior in Wistar rats and reaction in adrenals in GC rats.

[The structure of dependent relationship between neurons in the sensorimotor cortex of the left and right hemisphere in rabbits during immobilizing catatonia]. / Struktura zavisimykh otnoshenii mezhdu neironami sensomotornoi kory levogo i pravogo polusharii krolikov pri immobilizatsionnoi katatonii.

Relations between activities of neurons simultaneously recorded in the left and right sensorimotor brain cortices of rabbits were analyzed in a series of experiments before the induction of the immobilization state ("animal hypnosis"), in the state of immobilization, and after its termination. The total baseline percent of significant correlations between activities of neighboring (within 50 microns) neurons in the left hemisphere was significantly lower than in the right hemisphere. This characteristic of the left hemisphere changed neither in the immobilization state nor after its termination. In the right-hemisphere cortex, the total percent of correlations between neighboring neurons significantly decreased during immobilization and returned to the baseline level after the termination of this state. In contrast, percent of correlations between the activities of remote (within 500 microns) neurons in the right-hemisphere did not change during immobilization, whereas in the left cortex it changed significantly and reached its baseline level after the normalization of rabbit's state. Further analysis showed that the revealed cortical interhemispheric asymmetry is underlain by asymmetric activities of individual neurons and small neuronal populations. Thus, for example, changes in the structure of interneuronal correlations in cortical microareas of the left and macroareas of the right hemispheres could be of different directions, whereas correlated activities in microareas of the right and macroareas of the left-hemispheres could change synergetically. In other words, asymmetry was revealed at different levels of neuronal integration (neuronal pairs, micro- or macrogroups of neurons). This finding testifies to a mosaic character of neuronal activity, which finally results in the general functional asymmetry during the "animal hypnosis". Certain changes in the structure of functional relations between neurons of the sensorimotor cortex that developed in the state of "animal hypnosis" persisted and even augmented after the termination of this state.

[Malignant catatonia as paradigm of neuropsychiatric disease]. / La catatonía maligna como paradigma de enfermedad neuropsiquiátrica.

Catatonia is a large neuropsychiatric syndrome with multiple etiologies (psychiatric disorder, cerebral structural lesion, systemic disease, secondary to drugs and toxic agents) and varied clinical manifestations (cognitive and behavioral disorders, motor and speech disorders and vegetative disorders). The presence of disautonomy means a situation having vital risk, that requires immediate therapeutic intervention. A 22 year old woman was admitted due to a picture of stupor, fever, maintained postures, rigidity, seizures and tachycardia and hypertension episodes; this picture initiated four weeks earlier, with psychotic and affective symptoms and she slowly developed speech and motor activity impairment. Initially, she had been treated with neuroleptics, anticholinergics and antidepressants. The CT, MRI and CSF studies were normal. The EEG revealed diffuse slow waves and right frontotemporal paroxystic activity Laboratory determinations showed elevation of CK, coinciding with the vegetative disorder phase. The picture resolved progressively in two months, after receiving 19 sessions of electroshock therapy. In all the patients, and above all in those who receive neuroleptics, with symptoms suggesting catatonia, the presence of disautonomy should be considered as an alarm situation, which would make it necessary to discontinue the neuroleptics and to adopt special control. Electroshock therapy is the most effective therapeutic option in the situation of malignant catatonia.

[Interactions between electrical activities of the sensomotor cortex and the hippocampus during 'animal hypnosis' in rabbits]. / Vzaimootnosheniia élektricheskoi aktivnosti sensomotornoi kory i gippokampa pri "zhivotnom gipnoze" u krolikov.

The electrical activity of the left and right sensorimotor cortex and left and right dorsal hippocampus (CA3 fields) was recorded during "animal hypnosis" in rabbits. The "animal hypnosis" produced asymmetry in the spectral power of the hippocampal electrical activity due to an increase in the power of delta 1, delta 2, and theta 1 components in the left-hippocampus and decrease in the spectral power in the same ranges in the right-hippocampus. Hemispheric asymmetry in the electrical activity during the "animal hypnosis" was also expressed in the indices of coherence between the sensorimotor cortex and hippocampus. EEG coherence between the left sensorimotor cortex and left hippocampus in the delta 1, theta 1, and theta 2 ranges was higher than that between the right-side structures.

Correlation between immobility reflex and electrocortical afterdischarges in rabbits.

Correlation between immobility reflex and electrocortical after-discharges in rabbits. In each experimental session, the immobility reflex was elicited by inversion of the rabbit and afterward three electroshocks were applied at 15-min intervals. A significant negative semilogarithmic correlation between the duration of the immobility reflex and the average duration of the electrocortical afterdischarges was observed during the first two experimental sessions. In subsequent sessions such correlation disappeared. It was postulated that the inhibitory processes responsible for the immobility reflex, and those responsible for postepileptic extinction, could initially share some neural mechanisms, but with repetition, they become independent of each other.

Electroconvulsive therapy and lateralized affective systems.

The neurophysiological systems subtending generalized seizures (activated by ECT) and temporal-limbic seizures are described as well as the interactions existing between the two seizure systems. There are correlations between schizophrenia and the limbic seizure system on the one hand and the manic-depressive or bipolar syndromes and the generalized seizure system on the other which are theoretically related to the different (although overlapping) neural substrates underlying the two major syndromes of psychosis. Evidence is reviewed that indicates that in ECT-responsive depression (with both bilateral and unilateral nondominant ECT) the modus operandi hinges on right-hemispheric neural events. Neurophysiological, neurological, and acoustic threshold evidence is discussed: all of which emphasizes the importance of the nondominant hemisphere in the genesis of endogenous depressions and in their treatment with convulsive therapies. In addition, studies showing that psychotropic agents with specific antidepressant effects produce asymmetric activation of the right hemisphere (EEG) are related to the above issues.

Neuroleptic catatonia and its relationship to psychogenic catatonia.

Neuroleptics are among those pharmacological agents that can cause a nonpsychogenic catatonic state. Neuroleptic malignant syndrome (NMS) is marked by a change in state of consciousness, ranging from withdrawal through stupor to coma. In addition, it is characterized by autonomic dysfunction, hyperthermia, mutism, and rigidity. It is included in the differential diagnosis of the catatonic syndrome. Evidence is reviewed to suggest that agents responsible for improving NMS act on the dopamine (DA) gamma aminobutyric acid (GABA) connections in the mesostriatal and mesolimbic systems and also in the hypothalamus. In addition, based on symptomatology, pathophysiology, and therapeutic mechanisms, the relationship between nonpsychogenic neuroleptic-induced catatonia and psychogenic catatonia is examined.