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ABSTRACT: The planum temporale (PT) is a highly lateralized brain area associated with auditory and language processing. In schizophrenia, reduced structural and functional laterality of the PT has been suggested, which is of clinical interest because of its potential role in the generation of auditory verbal hallucinations. We investigated whether resting-state functional imaging (fMRI) of the PT reveals aberrant functional connectivity and laterality in patients with schizophrenia (SZ) and unaffected relatives, and examined possible associations between altered intrinsic functional organization of auditory networks and hallucinations. We estimated functional connectivity between bilateral PT and whole-brain in 24 SZ patients, 22 unaffected first-degree relatives and 24 matched healthy controls. The results indicated reduced functional connectivity between PT and temporal, parietal, limbic and subcortical regions in SZ patients and relatives in comparison with controls. Altered functional connectivity correlated with predisposition towards hallucinations (measured with the Revised Hallucination Scale [RHS]) in both patients and relatives. We also observed reduced functional asymmetry of the superior temporal gyrus in patients and relatives, which correlated significantly with acute severity of hallucinations in the patient group. To conclude, SZ patients and relatives showed abnormal asymmetry and aberrant connectivity in the planum temporale during resting-state, which was related to psychopathology. These results are in line with results from auditory processing and symptom-mapping studies that suggest that the PT is a central node in the generation of hallucinations. Our findings support reduced intrinsic functional hemispheric asymmetry of the auditory network as a possible trait marker in schizophrenia.
Biological Psychiatry 05/2013; · 8.28 Impact Factor
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Gilberto Sousa Alves,
Laurence O'Dwyer,
Alina Jurcoane,
Viola Oertel-Knöchel, Christian Knöchel,
David Prvulovic,
Felipe Sudo,
Carlos Eduardo Alves,
Letice Valente,
Denise Moreira,
Fabian Fußer,
Tarik Karakaya,
Johannes Pantel,
Eliasz Engelhardt,
Jerson Laks
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ABSTRACT: Alzheimer´s disease (AD) represents the most prevalent neurodegenerative disorder that causes cognitive decline in old age. In its early stages, AD is associated with microstructural abnormalities in white matter (WM). In the current study, multiple indices of diffusion tensor imaging (DTI) and brain volumetric measurements were employed to comprehensively investigate the landscape of AD pathology. The sample comprised 58 individuals including cognitively normal subjects (controls), amnestic mild cognitive impairment (MCI) and AD patients. Relative to controls, both MCI and AD subjects showed widespread changes of anisotropic fraction (FA) in the corpus callosum, cingulate and uncinate fasciculus. Mean diffusivity and radial changes were also observed in AD patients in comparison with controls. After controlling for the gray matter atrophy the number of regions of significantly lower FA in AD patients relative to controls was decreased; nonetheless, unique areas of microstructural damage remained, e.g., the corpus callosum and uncinate fasciculus. Despite sample size limitations, the current results suggest that a combination of secondary and primary degeneration occurrs in MCI and AD, although the secondary degeneration appears to have a more critical role during the stages of disease involving dementia.
PLoS ONE 12/2012; 7(12):e52859. · 4.09 Impact Factor
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Gilberto Sousa Alves,
Tarik Karakaya,
Fabian Fußer,
Martha Kordulla,
Laurence O'Dwyer,
Julia Christl,
Jörg Magerkurth,
Viola Oertel-Knöchel, Christian Knöchel,
David Prvulovic,
Alina Jurcoane,
Jerson Laks,
Eliasz Engelhardt,
Harald Hampel,
Johannes Pantel
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ABSTRACT: Major depression disorder (MDD) is one of the most common causes of disability in people over 60years of age. Previous studies have linked affective and cognitive symptoms of MDD to white matter (WM) disruption in limbic-cortical circuits. However, the relationship between clinical cognitive deficits and loss of integrity in particular WM tracts is poorly understood. Fractional anisotropy (FA) as a measure of WM integrity was investigated in 17 elderly MDD subjects in comparison with 18 age-matched controls using tract-based spatial statistics (TBSS) and correlated with clinical and cognitive parameters. MDD patients revealed significantly reduced FA in the right posterior cingulate cluster (PCC) compared with controls. FA in the right PCC (but not in the left PCC) showed a significant positive correlation with performance in a verbal naming task, and showed a non-significant trend toward a correlation with verbal fluency and episodic memory performance. In control subjects, no correlations were found between cognitive tasks and FA values either in the right or left PCC. Results provide additional evidence supporting the neuronal disconnection hypothesis in MDD and suggest that cognitive deficits are related to the loss of integrity in WM tracts associated with the disorder.
Psychiatry research. 09/2012; 203(2-3):194-200.
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ABSTRACT: In this study, we investigate whether aberrant integrity of white matter (WM) fiber tracts represents a genetically determined biological marker of schizophrenia (SZ), and its relation with clinical symptoms. We collected brain DTI data from 28 SZ patients, 18 first-degree relatives and 22 matched controls and used voxel-based analysis with tract-based spatial statistics (TBSS) in order to compare fractional anisotropy (FA) between groups. Mean voxel-based FA values from the entire skeleton of each group were compared. We did a multiple regression analysis, followed by single post-hoc contrasts between groups. FA values were extracted from the statistically significant areas. The results showed significantly smaller FA values for SZ patients in comparison with controls in cortico-spinal tracts, in commissural fibers, in thalamic projections, in association fibers and in cingulum bundles. A significant increase of FA in SZ patients in comparison with healthy controls was only found in the arcuate fasciculus. Relatives had intermediate values between patients and controls which were deemed significant in the comparison to patients and controls in association fibers, arcuate fasciculus and cingulum bundles. Lower FA values in association fibers were significantly associated with predisposition toward hallucinations (in SZ patients and relatives), with higher PANSS scores of positive symptoms and with duration of illness (SZ patients). Our results suggest that clinical and subclinical presentations of psychotic symptoms are associated with aberrant integrity of multiple WM tracts. This association may represent an endophenotype of schizophrenia, since it is present in unaffected relatives as well. Such endophenotypes may serve as quantitative traits for future genetic studies and as candidate markers for early and preclinical identification of subjects at risk.
Biological Psychiatry 07/2012; 140(1-3):129-35. · 8.28 Impact Factor
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Viola Oertel-Knöchel,
Britta Reinke,
Alexandra Hornung, Christian Knöchel,
Silke Matura,
Monika Knopf,
David Prvulovic,
Laurence O'Dwyer,
Michael Lindner,
Alexandra Rau,
Harald Hampel,
Corinna Haenschel,
David E J Linden
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ABSTRACT: This is the first study to combine psychometric and functional neuroimaging methods to study altered patterns of autobiographical memory in bipolar disorder (BD). All participants were interviewed with an expanded version of the Bielefelder Autobiographical Memory Inventory (Bielefelder Autobiographisches Gedächtnis Inventar 2004;Lisse: Swets and Zeitlinger). We then acquired functional magnetic resonance imaging data during a task of individually designed autobiographical recall. Compared with healthy controls, BD patients reported a stronger emotionality of autobiographical memories and more frequent recollections of autobiographical events during their everyday life. Furthermore, they failed to deactivate areas in the cuneus and lingual gyrus and showed decreased activation in the inferior frontal and precentral areas compared with the control group. More frequent intrusions from a person's past, which had a neural correlate in the lack of deactivation in some default mode network areas in BD patients, may contribute to manic or depressive symptoms.
The Journal of nervous and mental disease 04/2012; 200(4):296-304. · 1.77 Impact Factor
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ABSTRACT: The current study provides a complete magnetic resonance imaging (MRI) analysis of thickness throughout the cerebral cortical mantle in patients with schizophrenia (SZ) and rigorously screened and matched unaffected relatives and controls and an assessment of its relation to psychopathology and subjective cognitive function. We analyzed 3D-anatomical MRI data sets, obtained at 3 T, from 3 different subject groups: 25 SZ patients, 29 first-degree relatives, and 37 healthy control subjects. We computed whole-brain cortical thickness using the Freesurfer software and assessed group differences. We also acquired clinical and psychometric data. The results showed markedly reduced cortical thickness in SZ patients compared with controls, most notably in the frontal and temporal lobes, in the superior parietal lobe and several limbic areas, with intermediate levels of cortical thickness in relatives. In both patients and relatives, we found an association between subjective cognitive dysfunction and reduced thickness of frontal cortex, and predisposition toward hallucinations and reduced thickness of the superior temporal gyrus. Our findings suggest that changes in specific cortical areas may predispose to specific symptoms, as exemplified by the association between temporal cortex thinning and hallucinations.
Cerebral Cortex 01/2012; · 6.54 Impact Factor
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ABSTRACT: The current review outlines the under-appreciated effects of physical exercise on the course of psychiatric disorders, focussing on recent findings from animal and human research. Several studies have shown that regular physical exercise is significantly beneficial for psychiatric patients both on a biological and a psychological level. Positive effects of controlled exercise include improved metabolic responses, neuro-protection, increased quality of life, and reduced psychopathological symptoms. Studies investigating the effectiveness of various physical training interventions in alleviating severe mental diseases, such as Alzheimer's dementia (AD), schizophrenia (SZ) or major depressive disorder (MDD) indicate that physical exercise can relieve symptoms of depression, psychosis and dementia and more importantly can curtail further progression of these diseases. This review assesses the most effective methods of physical training for specific psychiatric symptoms. Introducing physical exercise in therapeutic regimes would be an innovative approach that could significantly reduce the severity of psychopathological and cognitive symptoms in patients. The positive biological and molecular outcomes associated with physical exercise render it a concrete therapeutic strategy for improving the quality of live and reducing physical illness in psychiatric patients. Therefore, integrating physical activity into a patient's social life may be an effective treatment strategy. Furthermore, exercise might have the potential to be a preventative treatment within the context of multi-modal therapeutic programs.
Progress in Neurobiology 11/2011; 96(1):46-68. · 8.87 Impact Factor
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Christian Knöchel,
Viola Oertel-Knöchel,
Ralf Schönmeyer,
Anna Rotarska-Jagiela,
Vincent van de Ven,
David Prvulovic,
Corinna Haenschel,
Peter Uhlhaas,
Johannes Pantel,
Harald Hampel,
David E J Linden
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ABSTRACT: Changes in hemispheric asymmetry and inter-hemispheric connectivity have been reported in schizophrenia. However, the genetic contribution to these alterations is still unclear. In the current study, we applied an automatic segmentation method to structural MRI and diffusion tensor imaging (DTI) data and examined volume and fiber integrity of the corpus callosum (CC), the main interhemispheric fiber tract, in 16 chronic schizophrenia (SZ) patients, matched first degree relatives and controls. SZ patients and relatives had smaller CC volumes than controls, particularly in the posterior genu, isthmus and splenium. Fractional anisotropy (FA), an indicator of fiber integrity, was reduced in patients and relatives in the whole CC, the inferior genu, the superior genu and the isthmus. Correspondingly, the mean diffusivity (MD) values of the whole CC and the isthmus were higher in patients and their unaffected relatives, indicating decreased compactness and increased intercellular space. Relatives had intermediate values in the volumetric and fiber integrity measurements between patients and controls. Lower CC volume and fiber integrity in SZ patients were associated with more severe auditory hallucinations. These results support the connectivity hypothesis of SZ (Friston, 1998) and particularly highlight the altered interhemispheric connectivity, which appears to be a genetic feature of SZ risk.
NeuroImage 09/2011; 59(2):926-34. · 5.89 Impact Factor
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ABSTRACT: Major depressive disorders (MDD) are among the most debilitating diseases worldwide and occur with a high prevalence in elderly individuals. Neurodegenerative diseases (in particular Alzheimer's disease, AD) do also show a strong age-dependent increase in incidence and prevalence among the elderly population. A high number of geriatric patients with MDD show cognitive deficits and a very high proportion of AD patients present co-morbid MDD, which poses difficult diagnostic and prognostic questions. Especially in prodromal and in very early stages of AD, it is almost impossible to differentiate between pure MDD and MDD with underlying AD. Here, we give a comprehensive review of the literature on the current state of candidate biomarkers for MDD ("positive MDD markers") and briefly refer to established and validated diagnostic AD biomarkers in order to rule out underlying AD pathophysiology in elderly MDD subjects with cognitive impairments ("negative MDD biomarkers"). In summary, to date there is no evidence for positive diagnostic MDD biomarkers and the only way to delineate MDD from AD is to use "negative MDD" biomarkers. Because of this highly unsatisfactory current state of MDD biomarker research, we propose a research strategy targeting to detect and validate positive MDD biomarkers, which is based on a complex (genetic, molecular and neurophysiological) biological model that incorporates current state of the art knowledge on the pathobiology of MDD. This model delineates common pathways and the intersection between AD and MDD. Applying these concepts to MDD gives hope that positive MDD biomarkers can be successfully identified in the near future.
Progress in Neurobiology 08/2011; 95(4):703-17. · 8.87 Impact Factor
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ABSTRACT: Schizophrenia is one of the most disabling forms of mental illness. One of the most important challenges is to establish biological markers which can accurately identify at-risk individuals in preclinical stages and thus improve the effects of early intervention strategies. Here, we review recent findings in the field of molecular genetics, CSF (cerebrospinal fluid) based markers as well as structural and functional neuroimaging in the light of their relevance for schizophrenia biomarker research. We also examine evidence supporting the hypothesis that schizophrenia and neurodegenerative disorders such as Alzheimer's disease may share certain pathophysiological features, e.g. chronic inflammation and oxidative stress, and discuss their possible role in schizophrenia. The heterogeneous, multifaceted and multifactorial nature of the traditionally clinically operationalized entity "schizophrenia" presents an enormous challenge towards the identification of single diagnostic or surrogate markers. We propose that abnormal neural coordination is a major point of convergence of a number of crucial pathophysiological pathways. Therefore, functional markers reflecting disturbed neural coordination might be particularly attractive biomarker candidates, because of their ability to integrate the influence of diverse pathophysiological mechanisms. Similarly, combinatorial and multimodal approaches may be a promising way to more accurately capture the complex biological underpinnings schizophrenia. We consider the development of such integrative biomarkers to be essential in order to facilitate a timely diagnosis of schizophrenia. They should also advance our understanding of the subtle and intricate biological nature of schizophrenia.
Progress in Neurobiology 06/2011; 95(4):686-702. · 8.87 Impact Factor
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ABSTRACT: Laterality is a characteristic principle of the organization of the brain systems for language, and reduced hemispheric asymmetry has been considered a risk factor for schizophrenia. Here we sought support for the risk factor hypothesis by investigating whether reduced asymmetry of temporal lobe structure and function is also present in unaffected relatives. Sixteen schizophrenia patients, 16 age-matched first-degree relatives, and 15 healthy controls underwent high-resolution three-dimensional anatomical imaging and functional magnetic resonance imaging during auditory stimulation. Both the overall auditory cortex and planum temporale volumes and the lateralization to the left hemisphere were markedly reduced in patients. The decrease of lateralization correlated with increased severity of symptoms. In addition, both the overall functional activation in response to auditory stimulation and its asymmetry were reduced in the patients. Relatives had intermediate values between patients and controls on both structural and functional measures. This study provides added support for the idea that reduced hemispheric asymmetry is a biological risk factor for schizophrenia.
Journal of Neuroscience 02/2010; 30(6):2289-99. · 7.11 Impact Factor
