Dusan Hirjak

Motor dysfunction within the schizophrenia-spectrum: A dimensional step towards an underappreciated domain

At the beginning of the 20th century, genuine motor abnormalities (GMA) were considered to be intricately linked to schizophrenia. Subsequently, however, GMA have been increasingly regarded as unspecific transdiagnostic phenomena or related to side effects of antipsychotic treatment. Despite possible medication confounds, within the schizophrenia spectrum GMA have been categorized into three broad categories, i.e. neurological soft signs, abnormal involuntary movements and catatonia. Schizophrenia patients show a substantial overlap across a broad range of distinct motor signs and symptoms suggesting a prominent involvement of the motor system in disease pathophysiology. There have been several attempts to increase reliability and validity in diagnosing schizophrenia based on behavior and neurobiology, yet relatively little attention has been paid to the motor domain in the past. Nevertheless, accumulating neuroscientific evidence suggests the possibility of a motor endophenotype in schizophrenia, and that GMA could represent a specific dimension within the schizophrenia-spectrum. Here, we review current neuroimaging research on GMA in schizophrenia with an emphasis on distinct and common mechanisms of brain dysfunction. Based on a dimensional approach we show that multimodal neuroimaging combined with fine-grained clinical examination can result in a comprehensive characterization of structural and functional brain changes that are presumed to underlie core GMA in schizophrenia. We discuss the possibility of a distinct motor domain, together with its implications for future research. Investigating GMA by means of multimodal neuroimaging can essentially contribute at identifying novel and biologically reliable phenotypes in psychiatry.

Neurological Soft Signs and Brainstem Morphology in First-Episode Schizophrenia

Background: Minor motor and sensory deficits or neurological soft signs (NSS) have frequently been reported in patients with schizophrenia at any stage of their illness. NSS have been demonstrated to correlate with neuroanatomical abnormalities in various brain regions. Despite its important role in the integration and coordination of automatic motor actions, the brainstem has so far rather been ignored in previous neuroimaging studies on NSS in schizophrenia. Method: We investigated 21 right-handed first-episode schizophrenia patients using high-resolution magnetic resonance imaging at 3 T. The severity of NSS was measured with the Heidelberg Scale. Associations between NSS and both brainstem volume and shape changes were examined. Results: Higher NSS scores were significantly associated with structural alterations in the brainstem. According to volume measurements higher NSS scores correlated with global changes of the brainstem. Using shape analyses these associations referred to regionally specific morphometric alterations predominantly in the midbrain and pons. Conclusion: The findings suggest that brainstem morphometric alterations are associated with the severity of NSS in patients with first-episode schizophrenia. They further indicate the involvement of the brainstem in the pathogenesis of schizophrenia.

Local brain gyrification as a marker of neurological soft signs in schizophrenia

Patients with psychiatric disorders of significant neurodevelopmental origin, such as schizophrenia and autism frequently experience genuine motor abnormalities, such as neurological soft signs (NSS). Previous MRI studies in patients with schizophrenia have shown that NSS are associated with abnormal cortical, thalamic and cerebellar structure and function. So far, however, no neuroimaging study focused on the role of the local gyrification index (LGI) in the pathophysiology of NSS. This study sought to explore the relationship between NSS and folding patterns of the cerebral cortex that are thought to be established during early brain development. In this study, whole brain high-resolution magnetic resonance imaging (MRI) at 3 Tesla was used to investigate the LGI in 33 patients with recent-onset schizophrenia. Cortical reconstruction was performed with the Freesurfer image analysis suite. NSS were examined on the Heidelberg Scale and related to LGI. Age, gender, years of education and medication were considered as potential confounding variables. In summary, higher NSS scores were positively associated with morphological changes of LGI predominantly in parietal and occipital areas. Our results confirm the hypothesis of a significant relationship between LGI changes and the NSS expression in schizophrenia. Investigation of LGI may help to explain subtle motor symptoms such as NSS in schizophrenia.

Multiparametric mapping of neurological soft signs in healthy adults

Minor motor and sensory deficits or neurological soft signs (NSS) are frequently found in patients with schizophrenia at any stage of their illness. Although previous studies have reported that NSS are associated with altered structure and function within fronto-parietal areas, it remains unclear whether the neuroanatomical basis of NSS may be confounded by underlying pathological processes, and by antipsychotic treatment. Morphological brain correlates of NSS in healthy subjects have seldom been investigated. This study evaluated the relationship between NSS levels and abnormalities of subcortical and cortical structures in healthy individuals. High-resolution MRI data at 3 Tesla were obtained from 68 healthy individuals. Automated segmentation of caudate nucleus, putamen, globus pallidus, thalamus, and brainstem was performed using both FSL-FIRST and Freesurfer. The surface-based analysis via Freesurfer enabled calculation of cortical thickness, area and folding (local gyrification index). NSS were examined on the Heidelberg Scale and related to both subcortical and cortical measurements. Using two fully automated brain segmentations methods, we found no significant association between NSS levels and morphological changes in subcortical structures. Higher NSS scores were associated with morphological changes of cortical thickness, area and folding in multiple areas comprising superior frontal, middle temporal, insular and postcentral regions. Our findings demonstrate the benefit of surface-based approaches when investigating brain correlates of NSS. The data lend further support to the hypothesis that NSS in healthy individuals involve multiple cortical rather than subcortical brain regions.

Delusions of Technical Alien Control: A Phenomenological Description of Three Cases

Background: A considerable number of schizophrenic patients develop delusions of technical alien control. In such cases, patients experience their thoughts, movements and feelings to be controlled by mysterious machines and contemporary technologies such as computers, the internet, X-rays and lasers. Methods: In this paper, we describe 3 cases of patients with disorders of self-experience and schizophrenic delusions involving a controlling technical device. We also analyse case reports from historical and modern psychiatric literature which describe ‘influencing machines’ and similar phenomena. Results: Of the 3 patients analysed, all complained of being controlled and impaired by some form of contemporary technology. Moreover, the presented cases illustrate psychopathological phenomena such as self-centrality, loss of ego boundaries, subjectification of perception, ‘paradoxes of delusions’, morbid objectification and loss of the sense of agency. Conclusion: Delusions of technical alien control and influencing machines constitute a characteristic form of delusional ideation in schizophrenic patients. They may be preceded by prodromal schizophrenic alterations such as disembodiment, alienation and reification of self-experience, depersonalization, derealization and bodily hallucinations. We propose that these prior experiences, especially if technically reifying in nature, may give rise to the phenomenon of technical delusions, thus expressing a particular affinity of basic self-experience in schizophrenia to modern technology. This is also consistent with the pathoplasticity hypothesis.

Reduced Gray to White Matter Tissue Intensity Contrast in Schizophrenia

Background While numerous structural magnetic resonance imaging (MRI) studies revealed changes of brain volume or density, cortical thickness and fibre integrity in schizophrenia, the effect of tissue alterations on the contrast properties of neural structures has so far remained mostly unexplored. Methods Whole brain high-resolution MRI at 3 Tesla was used to investigate tissue contrast and cortical thickness in patients with schizophrenia and healthy controls. Results Patients showed significantly decreased gray to white matter contrast in large portions throughout the cortical mantle with preponderance in inferior, middle, superior and medial temporal areas as well as in lateral and medial frontal regions. The extent of these intensity contrast changes exceeded the extent of cortical thinning. Further, contrast changes remained significant after controlling for cortical thickness measurements. Conclusions Our findings clearly emphasize the presence of schizophrenia related brain tissue changes that alter the imaging properties of brain structures. Intensity contrast measurements might not only serve as a highly sensitive metric but also as a potential indicator of a distinct pathological process that might be independent from volume or thickness alterations.

Hippocampal Morphology and Autobiographic Memory in Mild Cognitive Impairment and Alzheimer’s Disease

Autobiographical memory (AM) comprises memories of ones own past that are characterized by a sense of subjective time and autonoetic awareness. AM deficits are among the major complaints of patients with Alzheimers disease (AD) even in early or preclinical stages. However, little is known on the association between cerebral alterations and AM in mild cognitive impairment (MCI) and AD. In the current study, patients with AD or MCI and healthy controls underwent high-resolution magnetic resonance imaging (MRI) and neuropsychological testing including semi-structured assessment of semantic and episodic AM of distinct lifetime periods. In MRI analysis, FSL-FIRST was used to automatically ascertain volume and shape of the hippocampal formation. Episodic, but not semantic AM loss was associated with morphological changes of the hippocampus, primarily involving the left hemisphere. According to shape analyses, these associations referred to regionally specific rather than global atrophy of the hippocampus. Our study demonstrates that loss of episodic AM early in the course of AD is associated with regionally confined hippocampal atrophy, thus supporting the multiple trace theory for the role of the hippocampus in episodic AM. Our findings are not only relevant for the understanding of memory function, but may also contribute to facilitating the early diagnosis of AD.

Overcoming Disembodiment: The Effect of Movement Therapy on Negative Symptoms in Schizophrenia- A Multicenter Randomized Controlled Trial

Objective: Negative symptoms of patients with Schizophrenia are resistant to medical treatment or conventional group therapy. Understanding schizophrenia as a form of disembodiment of the self, a number of scientists have argued that the approach of embodiment and associated embodied therapies, such as Dance and Movement Therapy (DMT) or Body Psychotherapy (BPT), may be more suitable to explain the psychopathology underlying the mental illness and to address its symptoms. Hence the present randomized controlled trial (DRKS00009828, http://apps.who.int/trialsearch/) aimed to examine the effectiveness of manualized movement therapy (BPT/DMT) on the negative symptoms of patients with schizophrenia. Method:A total of 68 out-patients with a diagnosis of a schizophrenia spectrum disorder were randomly allocated to either the treatment (n = 44, 20 sessions of BPT/DMT) or the control condition [n = 24, treatment as usual (TAU)]. Changes in negative symptom scores on the Scale for the Assessment of Negative Symptoms (SANS) were analyzed using Analysis of Covariance (ANCOVA) with Simpson-Angus Scale (SAS) scores as covariates in order to control for side effects of antipsychotic medication. Results:After 20 sessions of treatment (BPT/DMT or TAU), patients receiving movement therapy had significantly lower negative symptom scores (SANS total score, blunted affect, attention). Effect sizes were moderate and mean symptom reduction in the treatment group was 20.65%. Conclusion:The study demonstrates that embodied therapies, such as BPT/DMT, are highly effective in the treatment of patients with schizophrenia. Results strongly suggest that BPT/DMT should be embedded in the daily clinical routine.

Neurological Abnormalities in Recent-Onset Schizophrenia and Asperger-Syndrome

Background: Neurological abnormalities including a variety of subtle deficits such as discrete impairments in sensory integration, motor coordination (MOCO), and sequencing of complex motor acts are frequently found in patients with schizophrenia (SZ) and commonly referred to as neurological soft signs (NSS). Asperger-syndrome (AS) is characterized by sensory-motor difficulties as well. However, the question whether the two disorders share a common or a disease-specific pattern of NSS remains unresolved. Method: A total of 78 age- and education-matched participants [26 patients with recent-onset SZ, 26 individuals with AS, and 26 healthy controls (HC)] were recruited for the study. Analyses of covariance (ANCOVAs), with age, years of education, and medication included as covariates, were used to examine group differences on total NSS and the five subscale scores. Discriminant analyses were employed to identify the NSS subscales that maximally discriminate between the three groups. Results: Significant differences among the three groups were found in NSS total score and on the five NSS subscales. The clinical groups differed significantly in the NSS subscale MOCO. The correct discriminant rate between patients with SZ and individuals with AS was 61.5%. The correct discriminant rate was 92.3% between individuals with AS and HC, and 80.8% between SZ patients and HC, respectively. Conclusion: Our findings provide new evidence for the presence of NSS in AS and lend further support to previously reported difficulties in movement control in this disorder. According to the present results, SZ and AS seem to be characterized by both quantitative and qualitative NSS expression.

Cortical features of distinct developmental trajectories in patients with delusional infestation

Background: Although there is strong neuroimaging evidence that cortical alterations are a core feature of schizophrenia spectrum disorders, it still remains unclear to what extent such abnormalities occur in monothematic delusional disorders. In individuals with delusional infestation (DI), the delusional belief to be infested with pathogens, previous structural MRI studies have shown prefrontal, temporal, parietal, insular, thalamic and striatal gray matter volume changes. Differential contributions of cortical features of evolutionary and genetic origin (such as cortical thickness, area and folding) which may distinctly contribute to DI pathophysiology are unclear at present. Methods: In this study, 18 patients with DI and 20 healthy controls (HC) underwent MRI scanning at 1.0 T. Using surface‐based analyses we calculated cortical thickness, surface area and local gyrification index (LGI). Whole‐brain differences between patients and controls were investigated. Results: Surface analyses revealed frontoparietal patterns exhibiting altered cortical thickness, surface area and LGI in DI patients compared to controls. Higher cortical thickness was found in the right medial orbitofrontal cortex (p < 0.05, cluster‐wise probability [CWP] corrected). Smaller surface area in patients was found in the left inferior temporal gyrus, the precuneus, the pars orbitalis of the right frontal gyrus, and the lingual gyrus (p < 0.05, CWP corr.). Lower LGI was found in the left postcentral, bilateral precentral, right middle temporal, inferior parietal, and superior parietal gyri (p < 0.01, CWP corr.). Conclusion: This study lends further support to the hypothesis that cortical features of distinct evolutionary and genetic origin differently contribute to the pathogenesis of delusional disorders. Regions in which atrophy was observed are part of neural circuits associated with perception, visuospatial control and self‐awareness. The data are in line with the notion of a content‐specific neural signature of DI. HighlightsDI patients have higher cortical thickness in the medial orbitofrontal cortex.DI patients have lower surface area and LGI in temporo‐parietal regions.Cortical features of distinct evolutionary origin differently contribute to DI.