Previous neuroimaging studies in schizophrenia have shown that neurological soft signs (NSS) are ... more Previous neuroimaging studies in schizophrenia have shown that neurological soft signs (NSS) are associated with abnormal brain structure and function, but it remains unclear whether these findings truly reflect pathological processes or if they may be confounded by antipsychotics. To address these issues, structural neuroimaging studies conducted in healthy populations have shown an association between NSS and cortical regions but to date, studies of brain function in healthy participants are scarce. In this study, using functional magnetic resonance imaging we investigated 37 healthy adults under "resting-state" conditions. Functional connectivity of motor cortical and subcortical neural networks was assessed using a group spatial independent component analysis (ICA). NSS were measured using the "Heidelberg Scale". The relationship between functional connectivity at rest and NSS was analyzed using a regression model where age, gender and movement parameters wer...
Patients with psychiatric disorders of significant neurodevelopmental origin such as schizophreni... more 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 studies 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, education, and medication were considered as potential confounders. In summary, higher NSS scores were positively associated with morphological changes of LGI predominantly in parietal and occipital areas. In conclusion, 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.
Progress in neuro-psychopharmacology & biological psychiatry, Jan 29, 2015
Previous structural neuroimaging studies linked cerebellar deficits to neurological soft signs (N... more Previous structural neuroimaging studies linked cerebellar deficits to neurological soft signs (NSS) in schizophrenia. However, no studies employed a methodology specifically designed to assess cerebellar morphology. In this study, we evaluated the relationship between NSS levels and abnormalities of the human cerebellum in patients with recent-onset schizophrenia and healthy individuals using an exclusive cerebellar atlas. A group of 26 patients with recent-onset schizophrenia and 26 healthy controls were included. All participants underwent a high-resolution T1-weighted MRI scan on a 3 Tesla scanner. We used a voxel-based morphometry (VBM) approach utilizing the Spatially Unbiased Infratentorial (SUIT) toolbox to provide an optimized and fine-grained exploration of cerebellar structural alterations associated with NSS. Compared with healthy controls, patients had significantly smaller cerebellar volumes for both hemispheres. In the patients' group, we identified a significant ...
At the beginning of the twentieth century, many authors proposed that a considerable number of sc... more At the beginning of the twentieth century, many authors proposed that a considerable number of schizophrenic patients experience genuine motor abnormalities (GMA). In the era of antipsychotic treatment, GMA became a scientifically and clinically challenging characteristic of schizophrenia. Over the past 10Â years, several magnetic resonance imaging (MRI) studies suggested a crucial role of the motor system in this disorder. Constituting a major relay center in the extrapyramidal motor system and being involved in the automatic execution of motor plans, an involvement of the basal ganglia with GMA and schizophrenia is plausible. However, the precise morphological correlates of GMA have remained controversial. The aim of this paper is to systematically review structural neuroimaging findings on GMA and basal ganglia in individuals with schizophrenia. Nineteen structural MRI studies were identified for inclusion in the review. Considering the extant data, there is some evidence for volumetric and shape alterations of basal ganglia in schizophrenia being in part determined by psychopathology and GMA, and not entirely explained by antipsychotic medication effects.
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2014
Abnormal structure of frontal and temporal brain regions has been suggested to occur in patients ... more Abnormal structure of frontal and temporal brain regions has been suggested to occur in patients with schizophrenia who have frequent auditory verbal hallucinations (AVH). However, it is unknown whether this is specific to this patient subgroup. This study tested the hypothesis that frontotemporal gray matter volume changes would characterize patients with persistent AVH (pAVH) in contrast to healthy controls and patients without AVH. Using structural magnetic resonance imaging at 3T, we studied 20 patients with schizophrenia and 14 matched healthy controls. Ten patients were classified as having chronic and treatment resistant AVH, whereas the remaining 10 patients either never had AVH in the past or were in full remission with regard to AVH (nAVH). Using a multivariate statistical technique for structural data, i.e. "source-based morphometry" (SBM), we investigated naturally grouping patterns of gray matter volume variation among individuals, the magnitude of their expression between-groups and the relationship between gray matter volume and AVH-specific measures. SBM identified a reduction of medial and inferior frontal, insular and bilateral temporal gray matter volume between pAVH and nAVH. This pattern did not differ between nAVH patients and controls and was associated with "physical" AVH characteristics (such as symptom duration, location, frequency and intensity) in the pAVH patient group. These results suggest that a pattern of lower gray matter volume in medial frontal, insular and bilateral temporal cortical regions differentiates between patients with persistent AVH and non-hallucinating patients. Moreover, the data support a specific role of this neural pattern in AVH symptom expression.
A considerable number of schizophrenic patients develop delusions of technical alien control. In ... more 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. 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. 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. 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.
Minor motor and sensory deficits or neurological soft signs (NSS) have frequently been reported i... more 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. 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. 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. 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.
Clinicians are confronted with considerable difficulties in diagnosing conversion disorders such ... more Clinicians are confronted with considerable difficulties in diagnosing conversion disorders such as dissociative paraplegia. In the literature, there is still no sufficient evidence regarding a typical pattern or general characteristics for this neuropsychiatric syndrome. Over the last decades case reports have described patients with similar personality traits, psychopathological characteristics, history and symptoms. We present the case of a 67-year-old Caucasian woman of high economic status and educational level with no psychopathological symptoms and no history of mental disorders who developed dissociative paraplegia after epidural anesthesia. The neurological examination revealed incongruous features, and repeated spine magnetic resonance imaging was normal. Three years earlier the patient had transient paralysis of her left lower limb without detectable cause. We identified an association between stressful life events and neurological anomalies. Crucial for the diagnosis of dissociative paraplegia is the neurological examination. Our case demonstrates that lack of psychopathological features and previous psychiatric diagnosis are not sufficient to exclude dissociative paraplegia. In patients with incongruous neurological findings and absent neurobiological correlates, clinicians should consider the presence of conversion disorders such as dissociative paraplegia.
Previous neuroimaging studies in schizophrenia have shown that neurological soft signs (NSS) are ... more Previous neuroimaging studies in schizophrenia have shown that neurological soft signs (NSS) are associated with abnormal brain structure and function, but it remains unclear whether these findings truly reflect pathological processes or if they may be confounded by antipsychotics. To address these issues, structural neuroimaging studies conducted in healthy populations have shown an association between NSS and cortical regions but to date, studies of brain function in healthy participants are scarce. In this study, using functional magnetic resonance imaging we investigated 37 healthy adults under "resting-state" conditions. Functional connectivity of motor cortical and subcortical neural networks was assessed using a group spatial independent component analysis (ICA). NSS were measured using the "Heidelberg Scale". The relationship between functional connectivity at rest and NSS was analyzed using a regression model where age, gender and movement parameters wer...
Patients with psychiatric disorders of significant neurodevelopmental origin such as schizophreni... more 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 studies 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, education, and medication were considered as potential confounders. In summary, higher NSS scores were positively associated with morphological changes of LGI predominantly in parietal and occipital areas. In conclusion, 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.
Progress in neuro-psychopharmacology & biological psychiatry, Jan 29, 2015
Previous structural neuroimaging studies linked cerebellar deficits to neurological soft signs (N... more Previous structural neuroimaging studies linked cerebellar deficits to neurological soft signs (NSS) in schizophrenia. However, no studies employed a methodology specifically designed to assess cerebellar morphology. In this study, we evaluated the relationship between NSS levels and abnormalities of the human cerebellum in patients with recent-onset schizophrenia and healthy individuals using an exclusive cerebellar atlas. A group of 26 patients with recent-onset schizophrenia and 26 healthy controls were included. All participants underwent a high-resolution T1-weighted MRI scan on a 3 Tesla scanner. We used a voxel-based morphometry (VBM) approach utilizing the Spatially Unbiased Infratentorial (SUIT) toolbox to provide an optimized and fine-grained exploration of cerebellar structural alterations associated with NSS. Compared with healthy controls, patients had significantly smaller cerebellar volumes for both hemispheres. In the patients' group, we identified a significant ...
At the beginning of the twentieth century, many authors proposed that a considerable number of sc... more At the beginning of the twentieth century, many authors proposed that a considerable number of schizophrenic patients experience genuine motor abnormalities (GMA). In the era of antipsychotic treatment, GMA became a scientifically and clinically challenging characteristic of schizophrenia. Over the past 10Â years, several magnetic resonance imaging (MRI) studies suggested a crucial role of the motor system in this disorder. Constituting a major relay center in the extrapyramidal motor system and being involved in the automatic execution of motor plans, an involvement of the basal ganglia with GMA and schizophrenia is plausible. However, the precise morphological correlates of GMA have remained controversial. The aim of this paper is to systematically review structural neuroimaging findings on GMA and basal ganglia in individuals with schizophrenia. Nineteen structural MRI studies were identified for inclusion in the review. Considering the extant data, there is some evidence for volumetric and shape alterations of basal ganglia in schizophrenia being in part determined by psychopathology and GMA, and not entirely explained by antipsychotic medication effects.
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2014
Abnormal structure of frontal and temporal brain regions has been suggested to occur in patients ... more Abnormal structure of frontal and temporal brain regions has been suggested to occur in patients with schizophrenia who have frequent auditory verbal hallucinations (AVH). However, it is unknown whether this is specific to this patient subgroup. This study tested the hypothesis that frontotemporal gray matter volume changes would characterize patients with persistent AVH (pAVH) in contrast to healthy controls and patients without AVH. Using structural magnetic resonance imaging at 3T, we studied 20 patients with schizophrenia and 14 matched healthy controls. Ten patients were classified as having chronic and treatment resistant AVH, whereas the remaining 10 patients either never had AVH in the past or were in full remission with regard to AVH (nAVH). Using a multivariate statistical technique for structural data, i.e. "source-based morphometry" (SBM), we investigated naturally grouping patterns of gray matter volume variation among individuals, the magnitude of their expression between-groups and the relationship between gray matter volume and AVH-specific measures. SBM identified a reduction of medial and inferior frontal, insular and bilateral temporal gray matter volume between pAVH and nAVH. This pattern did not differ between nAVH patients and controls and was associated with "physical" AVH characteristics (such as symptom duration, location, frequency and intensity) in the pAVH patient group. These results suggest that a pattern of lower gray matter volume in medial frontal, insular and bilateral temporal cortical regions differentiates between patients with persistent AVH and non-hallucinating patients. Moreover, the data support a specific role of this neural pattern in AVH symptom expression.
A considerable number of schizophrenic patients develop delusions of technical alien control. In ... more 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. 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. 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. 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.
Minor motor and sensory deficits or neurological soft signs (NSS) have frequently been reported i... more 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. 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. 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. 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.
Clinicians are confronted with considerable difficulties in diagnosing conversion disorders such ... more Clinicians are confronted with considerable difficulties in diagnosing conversion disorders such as dissociative paraplegia. In the literature, there is still no sufficient evidence regarding a typical pattern or general characteristics for this neuropsychiatric syndrome. Over the last decades case reports have described patients with similar personality traits, psychopathological characteristics, history and symptoms. We present the case of a 67-year-old Caucasian woman of high economic status and educational level with no psychopathological symptoms and no history of mental disorders who developed dissociative paraplegia after epidural anesthesia. The neurological examination revealed incongruous features, and repeated spine magnetic resonance imaging was normal. Three years earlier the patient had transient paralysis of her left lower limb without detectable cause. We identified an association between stressful life events and neurological anomalies. Crucial for the diagnosis of dissociative paraplegia is the neurological examination. Our case demonstrates that lack of psychopathological features and previous psychiatric diagnosis are not sufficient to exclude dissociative paraplegia. In patients with incongruous neurological findings and absent neurobiological correlates, clinicians should consider the presence of conversion disorders such as dissociative paraplegia.
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Papers by Dusan Hirjak