Publications by authors named "Philipp Arthur Thomann"

25 Publications

  • Page 1 of 1

Exploring joint patterns of brain structure and function in inflammatory bowel diseases using multimodal data fusion.

Neurogastroenterol Motil 2020 Dec 28:e14078. Epub 2020 Dec 28.

Department of General Psychiatry, Center for Psychosocial Medicine, Heidelberg University, Heidelberg, Germany.

Background: A growing number of neuroimaging studies suggest distinct neural changes in inflammatory bowel diseases (IBDs). Whether such changes may show similar spatial patterns across distinct neural features within and between specific IBD is unclear. To address this question, we used multivariate multimodal data fusion analysis to investigate structure/function modulation in remitted patients with Crohn's disease (CD) and ulcerative colitis (UC).

Methods: Patients with IBD (n = 46; n = 31 with CD, n = 15 with UC) in stable remission and 17 healthy controls (HC) underwent structural magnetic resonance imaging (sMRI) and resting-state functional magnetic resonance imaging (rs-fMRI) as well as cognitive testing. Anxiety, depression, and fatigue were assessed using self-rating questionnaires. sMRI data were analyzed via voxel-based morphometry (VBM) and rs-fMRI data via amplitude of low-frequency fluctuations (ALFFs) and regional homogeneity (ReHo). Detection of cross-information between VBM, ALFF, and ReHo was conducted by means of a joint independent component analysis (jICA), followed by group-inference statistics.

Key Results: Joint independent component analysis detected structural alterations in middle frontal and temporal regions (VBM), and functional changes in the superior frontal gyrus (ReHo) and the medial as well as inferior frontal, inferior temporal, rectal, and subcallosal gyrus (ALFF). One joint component of extracted features of the three modalities differed significantly between IBD patients and controls (p = 0.03), and most distinctly between HC and patients with UC.

Conclusions And Inferences: Using a multivariate data fusion technique, this study provides further evidence to brain alterations in IBD. The data suggest distinct neural differences between CD and UC, particularly in frontotemporal regions.
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http://dx.doi.org/10.1111/nmo.14078DOI Listing
December 2020

Transdiagnostic modulation of brain networks by electroconvulsive therapy in schizophrenia and major depression.

Eur Neuropsychopharmacol 2019 08 3;29(8):925-935. Epub 2019 Jul 3.

Center for Psychosocial Medicine, Department of General Psychiatry, Heidelberg University, 69115 Heidelberg, Germany. Electronic address:

Major depressive disorder (MDD) and schizophrenia (SCZ) share neurobiological and clinical commonalities. Altered functional connectivity of large-scale brain networks has been associated with both disorders. Electroconvulsive therapy (ECT) has proven to be an effective treatment in severe forms of MDD and SCZ. However, the role of ECT on the modulation of the dynamics of brain networks is still unknown. In this study, we used resting state functional magnetic resonance imaging (rs-fMRI) to investigate functional connectivity in 16 pharmacoresistant patients with SCZ or MDD and a matched group of normal controls. Patients were scanned before and after right-sided unilateral ECT. Group spatial independent component analysis was carried out with a multiple analysis of covariance (MANCOVA) approach to estimate the effects of ECT treatment on intrinsic components (INs). Functional network connectivity (FNC) was calculated between pairs of INs. Patients had reduced connectivity within a striato-thalamic network in the thalamus as well as increased low frequency oscillations in a striatal network. ECT reduced low frequency oscillations (LFOs) on a striatal network along with increasing functional connectivity in the medial prefrontal cortex within the DMN. Following ECT treatment, the FNC of the executive network was reduced with the DMN and increased with the salience network, respectively. Our findings suggest transnosological effects of ECT on the connectivity of large-scale networks as well as at the level of their interplay. Furthermore, they support a transnosological approach for the investigation not only of the neural correlates of the disease but also of the brain mechanism of treatment of mental disorders.
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http://dx.doi.org/10.1016/j.euroneuro.2019.06.002DOI Listing
August 2019

Neuromodulation in response to electroconvulsive therapy in schizophrenia and major depression.

Brain Stimul 2017 May - Jun;10(3):637-644. Epub 2017 Jan 16.

Charité - Universitätsmedizin Berlin, Department of Psychiatry and Psychotherapy, Charité Campus Mitte, 10117 Berlin, Germany.

Background: Electroconvulsive therapy (ECT) is one of the most effective treatments in severe and treatment-resistant major depressive disorder (MDD). ECT has been also shown to be effective in schizophrenia (SZ), particularly when rapid symptom reduction is needed or in cases of resistance to drug-treatment. However, its precise mechanisms of action remain largely unknown.

Objective/hypothesis: This study examined whether ECT exerts disorder-specific or unspecific modulation of brain structure and function in SZ and MDD.

Methods: We investigated neuromodulatory effects of right-sided unilateral ECT in pharmacoresistant patients with SZ or MDD. Magnetic resonance imaging was conducted before and after ECT to investigate treatment-related effects on brain structure and function. Imaging data were analyzed by means of Voxel Based Morphometry and Resting State Functional Connectivity (RSFC) methods.

Results: Right unilateral ECT induced transdiagnostic regional increases of limbic gray matter and modulations of neural coupling at rest. Structural effects were accompanied by a decrease in RSFC within temporoparietal, prefrontal and cortical midline structures, and an increase in hypothalamic RSFC. The extent of structural and functional change was partially inversely associated with the baseline measures.

Conclusion: The present findings provide first evidence for transdiagnostic changes of brain structure together with modulation of brain function after ECT. The data indicate diagnosis-unspecific mechanisms of action with respect to regional gray matter volume and resting-state functional connectivity.
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http://dx.doi.org/10.1016/j.brs.2017.01.578DOI Listing
December 2017

Structural network changes in patients with major depression and schizophrenia treated with electroconvulsive therapy.

Eur Neuropsychopharmacol 2016 09 12;26(9):1465-1474. Epub 2016 Jul 12.

Center for Psychosocial Medicine, Department of Psychiatry, University of Heidelberg, 69115 Heidelberg, Germany.

Electroconvulsive therapy (ECT) is one of the most effective treatments in severe and treatment-resistant major depressive disorder (MDD). In schizophrenia (SZ), ECT is frequently considered in drug-resistant cases, as an augmentation of antipsychotic treatment or in cases when rapid symptom relief is indicated. Accumulating neuroimaging evidence suggests modulation of medial temporal lobe and prefrontal cortical regions in MDD by ECT. In SZ, ECT-effects on brain structure have not been systematically investigated so far. In this study, we investigated brain volume in 21 ECT-naïve patients (12 with MDD, 9 with SZ) who received right-sided unilateral ECT. Twenty-one healthy controls were included. Structural magnetic resonance imaging data were acquired before and after ECT. Healthy participants were scanned once. Source-based morphometry was used to investigate modulation of structural networks pre/post ECT. ECT had an impact on distinct structural networks in MDD and SZ. In both MDD and SZ SBM revealed a medial temporal lobe (MTL) network (including hippocampus and parahippocampal cortex) which showed a significant increase after ECT. The increase in MTL network strength was not associated with clinical improvement in either MDD or SZ. In SZ a lateral prefrontal/cingulate cortical network showed a volume increase after ECT, and this effect was accompanied by clinical improvement. These findings provide preliminary evidence for structural network change in response to ECT in MDD and SZ. The data suggest both diagnosis-specific and transdiagnostic ECT-effects on brain volume. In contrast to SZ, in MDD structural network modulation by ECT was not associated with clinical improvement.
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http://dx.doi.org/10.1016/j.euroneuro.2016.06.008DOI Listing
September 2016

Evidence for Distinguishable Treatment Costs among Paranoid Schizophrenia and Schizoaffective Disorder.

PLoS One 2016 8;11(7):e0157635. Epub 2016 Jul 8.

Center for Psychosocial Medicine, Department of General Psychiatry, University of Heidelberg, Heidelberg, Germany.

Background: Schizophrenia spectrum disorders result in enormous individual suffering and financial burden on patients and on society. In Germany, there are about 1,000,000 individuals suffering from schizophrenia (SZ) or schizoaffective disorder (SAD), a combination of psychotic and affective symptoms. Given the heterogeneous nature of these syndromes, one may assume that there is a difference in treatment costs among patients with paranoid SZ and SAD. However, the current the national system of cost accounting in psychiatry and psychosomatics in Germany assesses all schizophrenia spectrum disorders within one category.

Methods: The study comprised a retrospective audit of data from 118 patients diagnosed with paranoid SZ (F20.0) and 71 patients with SAD (F25). We used the mean total costs as well as partial cost, i.e., mean costs for medication products, mean personal costs and mean infrastructure costs from each patient for the statistical analysis. We tested for differences in the four variables between SZ and SAD patients using ANCOVA and confirmed the results with bootstrapping.

Results: SAD patients had a longer duration of stay than patients with SZ (p = .02). Mean total costs were significantly higher for SAD patients (p = .023). Further, we found a significant difference in mean personnel costs (p = .02) between patients with SZ and SAD. However, we found no significant differences in mean pharmaceutical costs (p = .12) but a marginal difference of mean infrastructure costs (p = .05) between SZ and SAD. We found neither a common decrease of costs over time nor a differential decrease in SZ and SAD.

Conclusion: We found evidence for a difference of case related costs of inpatient treatments for paranoid SZ and SAD. The differences in mean total costs seem to be primarily related to the mean personnel costs in patients with paranoid SZ and SAD rather than mean pharmaceutical costs, possibly due to higher personnel effort and infrastructure.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0157635PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4938526PMC
July 2017

Novel gene variations in early-onset frontotemporal dementia with positive family history of neural ceroid lipofuscinosis-1.

Neurol Clin Pract 2015 Dec;5(6):484-487

Department of General Psychiatry (HJ, PAT, RCW), Heidelberg University Hospital; and Department of Psychiatry, Psychotherapy and Psychosomatics (RCW), Saarland University, Homburg, Germany.

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http://dx.doi.org/10.1212/CPJ.0000000000000134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802472PMC
December 2015

Neuropsychology, autobiographical memory, and hippocampal volume in "younger" and "older" patients with chronic schizophrenia.

Front Psychiatry 2015 21;6:53. Epub 2015 Apr 21.

Section of Geriatric Psychiatry, Department of General Psychiatry, University of Heidelberg , Heidelberg , Germany ; Institute of Gerontology, University of Heidelberg , Heidelberg , Germany.

Despite a wide range of studies on neuropsychology in schizophrenia, autobiographical memory (AM) has been scarcely investigated in these patients. Hence, less is known about AM in older patients and hippocampal contribution to autobiographical memories of varying remoteness. Therefore, we investigated hippocampal volume and AM along with important neuropsychological domains in patients with chronic schizophrenia and the respective relationships between these parameters. We compared 25 older patients with chronic schizophrenia to 23 younger patients and an older healthy control group (N = 21) with respect to AM, additional neuropsychological parameters, and hippocampal volume. Personal episodic and semantic memory was investigated using a semi-structured interview. Additional neuropsychological parameters were assessed by using a battery of standard neuropsychological tests. Structural magnetic resonance imaging data were analyzed with an automated region-of-interest procedure. While hippocampal volume reduction and neuropsychological impairment were more pronounced in the older than in the younger patients, both groups showed equivalent reduced AM performance for recent personal episodes. In the patient group, significant correlations between left hippocampal volume and recent autobiographical episodes as well as personal semantic memories arose. Verbal memory and working memory were significantly correlated with right hippocampal volume; executive functions, however, were associated with bilateral hippocampal volumes. These findings underline the complexity of AM and its impairments in the course of schizophrenia in comparison to rather progressive neuropsychological deficits and address the importance of hippocampal contribution.
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http://dx.doi.org/10.3389/fpsyt.2015.00053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4404739PMC
May 2015

Abnormal cerebellar volume and corticocerebellar dysfunction in early manifest Huntington's disease.

J Neurol 2015 28;262(4):859-69. Epub 2015 Jan 28.

Department of Psychiatry, Psychotherapy and Psychosomatics, Saarland University, Kirrberger Str. 1, 66421, Homburg, Germany,

Evidence from animal models and neuropathological data has revealed cerebellar pathology in Huntington's disease (HD). The extent of cerebellar dysfunction in preclinical stages and in early manifest HD is unclear. In this study, using MRI we investigated cerebellar changes in preclinical (preHD) and early manifest HD individuals. High-resolution structural MRI data at 3 Tesla were obtained from two independent preHD samples (n = 20/25 participants), from two independent cohorts of healthy controls (n = 20/24 participants) and from patients with early manifest HD (n = 20 participants). Resting-state functional MRI data were acquired from 20 healthy controls and 20 HD patients. Cerebellar volume was investigated using cerebellum-optimized voxel-based analysis methods. Corticocerebellar connectivity at rest was investigated by means of seed-region correlations. In both preHD samples, between-group analyses revealed no change of cerebellar volume. In contrast, early manifest HD patients exhibited lower right cerebellar lobule VIIa volume (p < 0.05 cluster-corrected). Within the control group regions functionally coupled to right cerebellar lobule VII comprised bilateral cerebellar regions, right prefrontal and cingulate areas, whereas within manifest HD, functional coupling was found in paracentral, lingual and inferior frontal areas. Paracentral connectivity strength in patients was associated with disease burden and motor symptoms. These data suggest intact cerebellar volume in preHD. In contrast, early manifest HD patients exhibit atrophy of specific cerebellar subregions and abnormal corticocerebellar functional coupling. In early HD, the association between paracentral lobule function and clinical parameters suggests that corticocerebellar connectivity strength is related to the evolution of HD biology and the severity of HD motor signs.
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http://dx.doi.org/10.1007/s00415-015-7642-6DOI Listing
January 2016

Neurological abnormalities in recent-onset schizophrenia and asperger-syndrome.

Front Psychiatry 2014 6;5:91. Epub 2014 Aug 6.

Department of General Psychiatry, Center for Psychosocial Medicine, University of Heidelberg , Heidelberg , Germany.

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.
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http://dx.doi.org/10.3389/fpsyt.2014.00091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123603PMC
August 2014

Longitudinal task-negative network analyses in preclinical Huntington's disease.

Eur Arch Psychiatry Clin Neurosci 2014 Sep 27;264(6):493-505. Epub 2013 Sep 27.

Center for Psychosocial Medicine, Department of General Psychiatry, University of Heidelberg, Voßstraße 4, 69115, Heidelberg, Germany,

Functional neuroimaging studies have reported task-related brain activation changes in preclinical individuals carrying the Huntington's disease (HD) gene mutation (preHD). Little is known about "task-negative" activity, i.e., patterns of task-related deactivation in preHD, and about the stability of any deactivation changes over the course of the disease. Here, we explored task-related deactivation and functional connectivity of "task-negative" networks (TNNs) in preHD followed over a time period of 2 years. Thirteen far-from-onset preHD (mean time to estimated motor onset = 19.5 years) and thirteen healthy controls were investigated. We used functional magnetic resonance imaging (fMRI), a verbal working memory task, and uni- and multivariate analysis techniques for fMRI data. Behavior was similar in preHD and controls at baseline and did not change 2 years later. At both time points, deactivation was similar in preHD and controls. Within two spatio-temporally distinct TNNs, preHD had lower functional connectivity in the posterior cingulate cortex and higher functional connectivity in the left anterior prefrontal cortex compared to controls (p < 0.05, cluster-corrected). These findings remained stable at follow-up. Anterior prefrontal connectivity correlated with disease burden scores both at baseline and at follow-up. Over time, preHD exhibited higher connectivity in a dorsal cingulate region. Functional connectivity differences within this region were inversely associated with changes of motor function. These data provide first evidence for TNN connectivity changes in preHD followed over a period of 2 years. The relationship between dorsal cingulate connectivity and motor function suggests that "task-negative" activity may capture time-sensitive neural and functional processes in preHD.
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http://dx.doi.org/10.1007/s00406-013-0447-7DOI Listing
September 2014

Disturbance of intentionality: a phenomenological study of body-affecting first-rank symptoms in schizophrenia.

PLoS One 2013 3;8(9):e73662. Epub 2013 Sep 3.

Section Phenomenological Psychopathology and Psychotherapy, Department of General Psychiatry, Center of Psychosocial Medicine, University of Heidelberg, Heidelberg, Germany ; Structural Neuroimaging Group, Department of General Psychiatry, Center of Psychosocial Medicine, University of Heidelberg, Heidelberg, Germany.

Objectives: In 1950, Kurt Schneider proposed that a considerable number of schizophrenia patients develop first-rank symptoms (FRS). In such cases, patients report made experiences, replaced control of will, thought insertion, broadcast or withdrawal and delusional perception, respectively. Although a number of recent studies tend to explain FRS in terms of neurobiological and neuropsychological processes, the origin of these symptoms still remains unknown. In this paper, we explore the subjective experience of patients with the following two FRS: (1) "made" impulses and (2) "made" volitional acts.

Method: The method applied for the study of two FRS consists first in the overview of psychiatric and philosophical literature and second in the further investigation of subjective experience in patients with FRS. Psychopathological and phenomenological aspects of FRS are discussed by means of patient cases.

Results: We discovered a profound transformation of intentionality and agency in schizophrenia patients with body-affecting FRS. This concept offers an insight into the interrelatedness between particular FRS.

Conclusion: We propose that the subjective experience of schizophrenia patients with body-affecting FRS is rooted in the disturbance of intentionality and diminished sense of agency. This theoretical account of body-affecting FRS will open up new directions in both phenomenological and neurobiological psychiatric research.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0073662PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3760919PMC
May 2014

Neurological soft signs and brainstem morphology in first-episode schizophrenia.

Neuropsychobiology 2013 19;68(2):91-9. Epub 2013 Jul 19.

Structural Neuroimaging Group, Department of General Psychiatry, University of Heidelberg, Heidelberg, Germany. dusan.hirjak @ med.uni-heidelberg.de

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.
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http://dx.doi.org/10.1159/000350999DOI Listing
October 2014

Abnormal gray and white matter volume in delusional infestation.

Prog Neuropsychopharmacol Biol Psychiatry 2013 Oct 19;46:19-24. Epub 2013 Jun 19.

Center for Psychosocial Medicine, Department of General Psychiatry, University of Heidelberg, Germany.

Little is known about the neural basis of delusional infestation (DI), the delusional belief to be infested with pathogens. Case series and the response to anti-dopaminergic medication indicate disruptions in dopaminergic neurotransmission in the striatum (caudate, putamen), but did not allow for population-based inference. Here, we report the first whole-brain structural neuroimaging study to investigate gray and white matter abnormalities in DI compared to controls. In this study, we used structural magnetic resonance imaging and voxel-based morphometry to investigate gray and white matter volume in 16 DI patients and 16 matched healthy controls. Lower gray matter volume in DI patients compared to controls was found in left medial, lateral and right superior frontal cortices, left anterior cingulate cortex, bilateral insula, left thalamus, right striatal areas and in lateral and medial temporal cortical regions (p<0.05, cluster-corrected). Higher white matter volume in DI patients compared to controls was found in right middle cingulate, left frontal opercular and bilateral striatal regions (p<0.05, cluster-corrected). This study shows that structural changes in prefrontal, temporal, insular, cingulate and striatal brain regions are associated with DI, supporting a neurobiological model of disrupted prefrontal control over somato-sensory representations.
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http://dx.doi.org/10.1016/j.pnpbp.2013.06.004DOI Listing
October 2013

Cortical signature of neurological soft signs in recent onset schizophrenia.

Brain Topogr 2014 Mar 10;27(2):296-306. Epub 2013 May 10.

Structural Neuroimaging Group, Department of General Psychiatry, University of Heidelberg, Voßstraße 4, 69115, Heidelberg, Germany,

Motor symptoms such as neurological soft signs (NSS) are characteristic phenomena of schizophrenia at any stage of the illness. Neuroimaging studies in schizophrenia patients have shown regional thinning of the cortical mantle, but it is unknown at present whether NSS are related to cortical thickness changes. Whole brain high-resolution magnetic resonance imaging at 3 Tesla was used to investigate cortical thickness in 28 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 cortical thickness. Age, education, and medication were considered as potential confounders. Higher NSS scores were associated with morphological changes of cortical thickness in multiple areas comprising paracentral gyrus, postcentral lobule, precuneus, inferior parietal lobule and temporal lobe. Our results confirm the hypothesis of a significant relationship between cortical thickness changes and the extent of NSS in schizophrenia. Investigation of cortical thickness may help to explain subtle motor symptoms such as NSS in schizophrenia.
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http://dx.doi.org/10.1007/s10548-013-0292-zDOI Listing
March 2014

Hippocampal and entorhinal cortex volume decline in cognitively intact elderly.

Psychiatry Res 2013 Jan 17;211(1):31-6. Epub 2012 Nov 17.

Section of Geriatric Psychiatry, University of Heidelberg, Germany.

Studying the distribution and chronological sequence of brain morphological changes that occur in normal aging is crucial for understanding the mechanisms underlying these alterations and for distinguishing them from pathological processes. Whether the hippocampal formation is subjected to or spared from age-related shrinkage still remains controversial. We used magnetic resonance imaging (MRI) in order to assess hippocampal and entorhinal morphology in two population-based cognitively unimpaired cohorts (aged 53-55 years and 73-75 years, respectively) matched for gender, education, handedness, and apolipoprotein E status. Voxel-based morphometry (VBM-DARTEL) and shape analysis (FSL-FIRST) revealed significant bihemispheric age-related shrinkage of subiculum and cornu ammonis as well as of the entorhinal cortex (investigated with VBM only). The results lend further support to an effect of aging on medial temporal lobe morphology and thus may be of importance for the interpretation of structural imaging findings, especially in those diseases that are typically related to advancing age, as well as for the interpretation of functional imaging studies, where age-related differences in hippocampal activation may--to a locally varying degree--be explained by morphometric alterations.
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http://dx.doi.org/10.1016/j.pscychresns.2012.06.002DOI Listing
January 2013

Hippocampal volume reduction and autobiographical memory deficits in chronic schizophrenia.

Psychiatry Res 2013 Mar 14;211(3):189-94. Epub 2012 Nov 14.

Section of Geriatric Psychiatry, University of Heidelberg, Voßstr. 4, 69115 Heidelberg, Germany.

Although autobiographical memory (AM) deficits and hippocampal changes are frequently found in schizophrenia, their actual association remained yet to be established. AM performance and hippocampal volume were examined in 33 older, chronic schizophrenic patients and 21 healthy volunteers matched for age, gender and education. Psychopathological symptoms and additional neuropsychological parameters were assessed by using appropriate rating scales; magnetic resonance imaging (MRI) 3-T data were analyzed via an automated region-of-interest procedure. When compared with the control subjects, patients showed significantly decreased left anterior and posterior hippocampal volumes. Episodic but not semantic AM performance was significantly lower in the patients than in the healthy controls. Both episodic and semantic AM deficits were significantly correlated with volume of the left hippocampus in the patient group. In contrast, deficits in verbal memory, working memory and remote semantic memory observed in the patients did not relate to hippocampal volume. Our findings indicate that AM deficits in chronic schizophrenia are associated with hippocampal volume reductions and underline the importance of this pathology in schizophrenia.
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http://dx.doi.org/10.1016/j.pscychresns.2012.04.002DOI Listing
March 2013

Brain structure in preclinical Huntington's disease: a multi-method approach.

Neurodegener Dis 2013 17;12(1):13-22. Epub 2012 Aug 17.

Center of Psychosocial Medicine, Department of General Psychiatry, University of Heidelberg, Heidelberg, Germany.

Background: Structural magnetic resonance imaging (MRI) of the brain could be a powerful tool for discovering early biomarkers in clinically presymptomatic carriers of the Huntington's disease gene mutation (preHD). So far, structural changes have been found mainly in preHD approaching the estimated motor onset of the disease (i.e., less than 15 years from onset), whereas structural findings in preHD far from the estimated motor onset have been inconclusive.

Objectives: The aims of this study were to investigate the sensitivity of different methodological approaches to structural data in far-from-onset preHD (mean estimated time to motor onset = 21.4 years) and to explore the relationship between brain structure, clinical variables and cognition.

Methods: High-resolution MRI data at 3 T were obtained from 20 preHD individuals and 20 healthy participants and subsequently analyzed using voxel-based morphometry (VBM), cortical surface modeling and subcortical segmentation analysis techniques.

Results: VBM analyses did not reveal significant between-group differences, whereas cortical surface modeling and subcortical segmentation analyses showed significant regional cortical thinning and striatal changes in preHD compared to controls. Significant correlations were found between striatal structure, estimated time to motor onset and executive performance, whereas cortical changes were not significantly correlated with these parameters.

Conclusion: These data suggest that a combined methodological approach to structural MRI data could increase the sensitivity for detecting subtle neurobiological changes in early preHD. As consistently shown across different methods, the association between striatal structure and clinical measures supports the notion that changes in striatal volume could represent a more robust marker of disease progression than cortical changes.
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http://dx.doi.org/10.1159/000338635DOI Listing
January 2014

Brain activation and functional connectivity in premanifest Huntington's disease during states of intrinsic and phasic alertness.

Hum Brain Mapp 2012 Sep 25;33(9):2161-73. Epub 2011 Aug 25.

Center of Psychosocial Medicine, Department of General Psychiatry, University of Heidelberg, Germany.

Previous functional neuroimaging studies have shown brain activation abnormalities in clinically presymptomatic carriers of the Huntington's disease (preHD) gene mutation when performing complex cognitive tasks. However, little is known about the neural correlates of attentional processes in preHD. In this study, we used functional magnetic resonance imaging to investigate basic aspects of attentional processing in preHD individuals (n = 18) compared to healthy participants (n = 18) during an alertness task. Uni- and multivariate statistical techniques were used to assess task-related regional brain activation and functional network connectivity. Compared to healthy controls, preHD individuals near to the estimated onset of clinical signs showed lower activation of right frontostriatal regions during phasic alertness (P < 0.001, uncorrected). Decreased striatal activation in this preHD subgroup was also evident when compared with those preHD individuals far from the estimated onset of HD signs. Lower putaminal activity was associated with longer reaction times and with proximity to onset. In addition, preHD participants near to onset had lower functional connectivity of motor regions when compared with controls and preHD individuals far from onset. Our data suggest that while alertness-related performance remains normal, the underlying frontostriatal activity and motor cortex connectivity decline only when approaching the onset of unequivocal signs of HD. However, these attentional network changes might not be the sole explanation for the differences in cognitive task performance previously observed in preHD.
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http://dx.doi.org/10.1002/hbm.21348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6870204PMC
September 2012

Default-mode network changes in preclinical Huntington's disease.

Exp Neurol 2012 Sep 25;237(1):191-8. Epub 2012 Jun 25.

Center for Psychosocial Medicine, Department of General Psychiatry, University of Heidelberg, Germany.

The default-mode network (DMN) refers to as a set of brain regions which are active when the brain does not engage in a cognitive task and which are deactivated with task-related cognitive effort. Altered function of the DMN has been associated with a decline of cognition in several neurodegenerative diseases and related at-risk conditions. In Huntington's disease, an autosomal dominant inherited neurodegenerative disorder, several studies so far have shown abnormal task-related brain activation patterns even in preclinical carriers of the Huntington's disease gene mutation (preHD). To date, however, the functional integrity of the DMN has not been addressed in this population. The aim of this study was to study the functional connectivity of the DMN in 18 preHD and 18 healthy controls who underwent functional magnetic resonance imaging during an attention task. A group independent component analysis identified spatiotemporally distinct patterns of two DMN subsystems. The spatial distribution of these components in preHD was similar to controls. However, preHD showed lower subsystem-specific connectivity in the anterior medial prefrontal cortex, the left inferior parietal and the posterior cingulate cortex (p<0.05, cluster-corrected). Connectivity between the two DMN subsystems was increased in preHD compared to controls. In preHD individuals lower functional connectivity of the left inferior parietal cortex was associated with shorter reaction times in the attention task. This suggests that some functionally critical regions of the DMN may have to remain active to maintain or optimise cognitive performance in preHD.
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http://dx.doi.org/10.1016/j.expneurol.2012.06.014DOI Listing
September 2012

Reduced gray to white matter tissue intensity contrast in schizophrenia.

PLoS One 2012 15;7(5):e37016. Epub 2012 May 15.

Structural Neuroimaging Group, Department of General Psychiatry, University of Heidelberg, Heidelberg, Germany.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0037016PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3352852PMC
January 2013

Orbitofrontal cortex and impulsivity in borderline personality disorder: an MRI study of baseline brain perfusion.

Eur Arch Psychiatry Clin Neurosci 2012 Dec 11;262(8):677-85. Epub 2012 Mar 11.

Center of Psychosocial Medicine, Department of General Psychiatry, University of Heidelberg, Heidelberg, Germany.

Behavioral and neuroimaging studies in patients with borderline personality disorder (BPD) have associated orbitofrontal cortex (OFC) dysfunction with distinct symptom clusters such as impulsivity. It is unclear, however, whether abnormal patterns of OFC activity are also present during resting-state conditions and whether OFC dysfunction is specifically associated with impulsivity in BPD. This study tested the hypothesis that BPD patients would exhibit changes of OFC baseline perfusion and explored the relationship between regional cerebral blood flow and distinct BPD symptom clusters, such as impulsivity, dissociation tension and depressive symptoms. Using continuous arterial spin labeling magnetic resonance imaging at 3 Tesla, we investigated 16 women with BPD according to DSM-IV criteria and 16 healthy female control participants during resting-state conditions. Between-group comparisons were conducted using an analysis of variance (p < 0.05 cluster corrected). Compared to controls, BPD patients exhibited decreased blood flow in the medial OFC, whereas increased blood flow was found in the left and right lateral OFC. Correlation analyses revealed a positive relationship between medial and lateral orbitofrontal blood flow and impulsivity scores, whereas measures of dissociation tension and depression did not exhibit a significant correlation with OFC perfusion. These data suggest that dysfunction of medial and lateral regions of the OFC could specifically mediate symptoms of impulsivity in BPD.
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http://dx.doi.org/10.1007/s00406-012-0303-1DOI Listing
December 2012

Dysconnectivity of multiple resting-state networks in patients with schizophrenia who have persistent auditory verbal hallucinations.

J Psychiatry Neurosci 2011 Nov;36(6):366-74

Central Institute of Mental Health, Department of Addictive Behavior and Addiction Medicine, Mannheim, Germany.

Background: Functional neuroimaging studies on schizophrenia have suggested abnormal task-related functional connectivity in patients with schizophrenia who have auditory verbal hallucinations (AVHs). However, little is known about intrinsic functional connectivity in these patients.

Methods: Between January 2009 and February 2010, we studied patients with schizophrenia who had persistent and treatment-refractory AVHs in comparison with healthy controls. Using functional magnetic resonance imaging, we studied the functional connectivity of multiple resting state networks (RSNs) and their relation to symptom severity. We analyzed the data using a spatial group independent component analysis, and we used random-effects t tests to compare spatial components between groups.

Results: There were 10 patients and 14 controls enrolled in this study. In total, 16 RSNs were identified, from which we selected 4 networks of interest for further analyses. Within a speech-related network, patients showed increased connectivity in bilateral temporal regions and decreased connectivity in the cingulate cortex. Within 2 additional RSNs associated with attention and executive control, respectively, patients exhibited abnormal connectivity in the precuneus and right lateral prefrontal areas. We found correlations between measures of AVH severity and functional connectivity of the left anterior cingulate, left superior temporal gyrus and right lateral prefrontal cortex.

Limitations: The relatively small sample size, the patients' use of antipsychotic medication and the lack of a clinical control group have to be considered as potential limitations.

Conclusion: Our findings indicate that disrupted intrinsic connectivity of a speech-related network could underlie persistent AVHs in patients with schizophrenia. In addition, the occurrence of hallucinatory symptoms seems to modulate RSNs associated with attention and executive control.
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http://dx.doi.org/10.1503/jpn.110008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3201990PMC
November 2011

Longitudinal functional magnetic resonance imaging of cognition in preclinical Huntington's disease.

Exp Neurol 2011 Oct 25;231(2):214-22. Epub 2011 Jun 25.

Center of Psychosocial Medicine, Department of General Psychiatry, University of Heidelberg, Germany.

Neuropsychological and functional neuroimaging studies have revealed early changes of cognition and brain function in individuals with the Huntington's disease (HD) gene mutation who are presymptomatic for the motor symptoms of the disease (preHD). However, little is known about whether changes of neural function progress over time. In this study, we used neuropsychological tests of attention, working memory and executive function, functional magnetic resonance imaging and voxel-based analyses of high-resolution structural data to explore the temporal dynamics of potential cognitive, functional and structural biomarkers in far from onset preHD (n=13, mean time to the estimated motor symptom onset=19.5 years) and healthy controls (n=13) followed over a 2-year period. Behavioral measures were similar in preHD individuals and controls at baseline and remained normal 2 years later. At both time points, the left dorsolateral prefrontal cortex was less active in preHD than in controls during working memory performance. The left dorsolateral prefrontal cortex did not exhibit further loss of activity over time. Regions showing less gray matter volume in preHD at baseline did not show further volume loss over time. These data indicate that the activity in brain regions contributing to working memory processing differs consistently in HD expansion mutation carriers while cognitive performance remains normal. However, the present data do not support the notion of a progressive decline of left prefrontal cortex activity in far from onset preHD followed over a 2-year period.
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http://dx.doi.org/10.1016/j.expneurol.2011.06.011DOI Listing
October 2011

Aberrant connectivity of resting-state networks in borderline personality disorder.

J Psychiatry Neurosci 2011 Nov;36(6):402-11

Center of Psychosocial Medicine, Department of General Psychiatry, University of Heidelberg, Germany.

Background: Several functional neuroimaging studies have reported regionally abnormal activation of the frontal cortex in individuals with borderline personality disorder (BPD) during cognitive and affective task performance. However, little is known about neural function in individuals with BPD during the resting state. Using functional magnetic resonance imaging (fMRI), this study investigated the functional connectivity of prefrontal and limbic networks in patients with BPD.

Methods: Between January 2009 and March 2010, we investigated patients with BPD according to DSM-IV criteria and healthy controls by means of resting-state fMRI. The data were analyzed using a spatial group independent component analysis, and random effects t tests were used to compare spatial components between groups (p < 0.005, uncorrected).

Results: There were 17 women with BPD and 17 female healthy controls enrolled in this study. Within a network comprising cortical midline regions ("default mode network"), patients with BPD showed an increase in functional connectivity in the left frontopolar cortex (FPC) and the left insula, whereas decreased connectivity was found in the left cuneus. Within a network comprising predominantly right lateral prefrontal and bilateral parietal regions, patients with BPD showed decreased connectivity of the left inferior parietal lobule and the right middle temporal cortex compared with healthy controls. Two networks comprising lateral prefrontal and cingulate regions did not exhibit significant between-group differences. We found correlations between functional connectivity of the FPC and measures of impulsivity as well as between connectivity of the insula/cuneus and dissociation tension.

Limitations: Co-occurrent axis I disorders and medication use in this sample of patients with BPD have to be considered as potential limitations.

Conclusion: These data suggest that abnormal functional connectivity of temporally coherent resting-state networks may underlie certain symptom clusters in patients with BPD.
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http://dx.doi.org/10.1503/jpn.100150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3201994PMC
November 2011