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Background: Fatigue and psychosocial impairments are highly prevalent in IBD, particularly during active disease. Disturbed brain-gut interactions may contribute to these symptoms. This study examined associations between brain structure, faecal calprotectin, and symptoms of fatigue, depression, and anxiety in persons with Crohn's disease [CD] in different disease states., Methods: In this prospective observational study, n = 109 participants [n = 67 persons with CD, n = 42 healthy controls] underwent cranial magnetic resonance imaging, provided stool samples for analysis of faecal calprotectin, and completed questionnaires to assess symptoms of fatigue, depression, and anxiety. We analysed differences in grey matter volume [GMV] between patients and controls, and associations between regional GMV alterations, neuropsychiatric symptoms, and faecal calprotectin., Results: Symptoms of fatigue, depression, and anxiety were increased in patients with CD compared with controls, with highest scores in active CD. Patients exhibited regionally reduced GMV in cortical and subcortical sensorimotor regions, occipitotemporal and medial frontal areas. Regional GMV differences showed a significant negative association with fatigue, but not with depression or anxiety. Subgroup analyses revealed symptom-GMV associations for fatigue in remitted but not in active CD, whereas fatigue was positively associated with faecal calprotectin in active but not in remitted disease., Conclusion: Our findings support disturbed brain-gut interactions in CD which may be particularly relevant for fatigue during remitted disease. Reduced GMV in the precentral gyrus and other sensorimotor areas could reflect key contributions to fatigue pathophysiology in CD. A sensorimotor model of fatigue in CD could also pave the way for novel treatment approaches., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: Inflammatory bowel diseases (IBD) are accompanied by symptoms that can vastly affect patients' representations of their bodies. The aim of this study was to investigate alterations in body evaluation and body ownership in IBD and their link to interoceptive sensibility, gastrointestinal-specific anxiety, and history of childhood maltreatment., Methods: Body evaluation and ownership was assessed in 41 clinically remitted patients with IBD and 44 healthy controls (HC) using a topographical self-report method. Interoceptive sensibility, gastrointestinal-specific anxiety and a history of childhood maltreatment were assessed via self-report questionnaires., Results: Patients reporting higher interoceptive sensibility perceived their bodies in a more positive manner. Higher gastrointestinal-specific anxiety was linked to a more negative body evaluation particularly of the abdomen in patients with IBD. Childhood maltreatment severity strengthened the positive association between interoceptive sensibility and body ownership only in those patients reporting higher trauma load., Conclusion: Altered body representations of areas associated with abdominal pain are linked to higher symptom-specific anxiety and lower levels of interoceptive sensibility in IBD. Particularly in patients with a history of childhood maltreatment, higher levels of interoceptive sensibility might have a beneficial effect on the patients' sense of body ownership., (© 2024. The Author(s).)

Introduction: Fatigue is a common symptom in patients with inflammatory bowel diseases (IBD). To date, there is no instrument to assess IBD-specific fatigue in German. The aim of this study was to translate the IBD Fatigue (IBD-F) scale and to test its psychometric properties in a German IBD population., Methods: After completing the translation process, 20 IBD patients participated in a pilot testing phase. For further analyses, 180 IBD patients with fatigue answered the IBD-F (Sections I, II, III) and the IBD Questionnaire (IBDQ-D). Reliability was tested by using Cronbach's alpha and corrected item-total correlation. Exploratory factor analyses (EFA) were carried out. Spearman's correlation was calculated between the IBD-F and IBDQ-D . 78 patients could be included to calculate the test-retest reliability., Results: The German version of the IBD-F shows high face and content validity. Internal consistency was excellent, with a Cronbach's alpha of 0.93-0.98. Corrected item-total correlations ranged from 0.51 to 0.89. The correlation between the IBD-F and the IBDQ-D was statistically significant for Section I (rs=-0.59; p<0.01) and Section II (rs=-0.76; p<0.01) of the IBD-F. The EFA identified one relevant factor for each section. Test-retest reliability was acceptable for Section I (intraclass correlation coefficient (ICC)=0.73) and Section II (ICC=0.84)., Conclusion: The German version of the IBD-F is a reliable and valid tool to assess fatigue in IBD., Competing Interests: U.v.A. received consulting and/or speaker fees from ESOCAP, Abbvie, MSD, Takeda, Falk Pharma; R.R. received speaker fee from Abbvie; A.K.T. received speaker and consulting fees from Janssen Cilag, speaker fees from Pfizer and MSD and travel support from Abbvie and Takeda; J.W. received consulting and/or speaker fees from Abbvie Deutschland, Takeda Pharma, Janssen-Cilag GmbH; N.T. received personal fees from AbbVie, MSD, Falk, Janssen, Takeda and Vifor outside the submitted work., (Thieme. All rights reserved.)

Goal: The aim of this study was to investigate the network of biopsychosocial factors and quality of life (QoL) in persons with inflammatory bowel diseases (IBDs) and explore the influence of psychological factors on the course of the disease., Background: QoL of persons with IBD depends on disease activity but also on numerous interacting psychosocial factors. The influence of psychosocial factors on the disease course in controversially discussed., Materials and Methods: In 2 independent IBD samples (sample 1: n=209, anonymous internet survey; sample 2: n=84, outpatients with active disease), we measured QoL, anxiety, depression, illness identity, self-esteem, loneliness, childhood trauma, and visceral sensitivity with questionnaires. In addition, fatigue, hemoglobin levels, and response to therapy were assessed in sample 2. We estimated multiple regularized partial correlation networks and conducted accuracy and stability tests of the networks., Results: In both samples, QoL had the strongest relationships with visceral sensitivity and the illness identity engulfment. Depression was the most central factor in the networks. Baseline depression scores, visceral sensitivity, and engulfment were associated with response to therapy in sample 2., Conclusions: This first network study to assess the interplay between biopsychosocial factors and QoL in IBD reveals a comparable network structure in 2 samples. Results partly replicate findings from previous studies with regard to the importance of depression and yield information on the central role of the newly introduced concepts of illness identity and visceral sensitivity. Preliminary findings point to an influence of these parameters on the disease course, which indicates their role as a possible target in individualized therapy., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Extraintestinal symptoms are common in inflammatory bowel diseases (IBD) and include depression and fatigue. These are highly prevalent especially in active disease, potentially due to inflammation-mediated changes in the microbiota-gut-brain axis. The aim of this study was to investigate the associations between structural and functional microbiota characteristics and severity of fatigue and depressive symptoms in patients with active IBD., Methods: We included clinical data of 62 prospectively enrolled patients with IBD in an active disease state. Patients supplied stool samples and completed the questionnaires regarding depression and fatigue symptoms. Based on taxonomic and functional metagenomic profiles of faecal gut microbiota, we used Bayesian statistics to investigate the associative networks and triangle motifs between bacterial genera, functional modules and symptom severity of self-reported fatigue and depression., Results: Associations with moderate to strong evidence were found for 3 genera (Odoribacter, Anaerotruncus and Alistipes) and 3 functional modules (pectin, glycosaminoglycan and central carbohydrate metabolism) with regard to depression and for 4 genera (Intestinimonas, Anaerotruncus, Eubacterium and Clostridiales g.i.s) and 2 functional modules implicating amino acid and central carbohydrate metabolism with regard to fatigue., Conclusions: This study provides the first evidence of association triplets between microbiota composition, function and extraintestinal symptoms in active IBD. Depression and fatigue were associated with lower abundances of short-chain fatty acid producers and distinct pathways implicating glycan, carbohydrate and amino acid metabolism. Our results suggest that microbiota-directed therapeutic approaches may reduce fatigue and depression in IBD and should be investigated in future research., (© 2022. The Author(s).)

Quality of life (QoL) of persons with inflammatory bowel diseases (IBD) is often impaired by symptoms that do not primarily relate to intestinal inflammation. Among the most challenging extraintestinal symptoms are depression and fatigue, which are also frequent in other chronic diseases like multiple sclerosis, rheumatoid arthritis and cancer. Yoga as an ancient Indian tradition containing postures, breathing exercises and meditation may positively influence those symptoms. This review evaluates the current literature with regard to the effect of yoga-based interventions in persons with IBD and with regard to QoL, depression and fatigue in other somatic disorders. A systematic literature search yielded three trials examining the effects of yoga in patients with IBD and 37 trials addressing depressive syndromes or fatigue in somatic disorders. In summary, both in-person and video-based yoga classes are feasible, acceptable and safe as complementary treatment in patients with IBD and significantly improve anxiety and impaired quality of life. Current literature does not provide information on the effect of yoga on depression and fatigue in patients with IBD, but research from other somatic disorders or patients with depressive disorders implies the potential of yoga in this regard for persons with IBD. This should be specifically addressed in interventional trials with standardized yoga modules including patients with IBD suffering from fatigue, depression and/or impaired QoL., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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., (© 2020 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Background & Aims: The pathogenesis of chronic inflammatory bowel diseases (Crohn's disease [CD] and ulcerative colitis) involves dysregulated TH1 and TH17 cell responses, which can be targeted therapeutically by the monoclonal antibody Ustekinumab directed against the joint p40 subunit of IL-12 and IL-23. These cytokines may also regulate the differentiation of T follicular helper (TFH) cells, which promote B cell function in germinal centers. However, the role of TFH cells in CD pathogenesis and impact of Ustekinumab therapy on TFH cell fate in patients are poorly defined., Methods: Lymphocytes were isolated from peripheral blood (n=45) and intestinal biopsies (n=15) of CD patients or healthy controls (n=21) and analyzed by flow cytometry to assess TFH cell phenotypes and functions ex vivo. In addition, TFH cell differentiation was analyzed in the presence of Ustekinumab in vitro., Results: TFH cell frequencies in the intestine as well as peripheral blood were associated with endoscopic as well as biochemical evidence of CD activity. CD patients with clinical response to Ustekinumab, but not those with response to anti-TNF antibodies, displayed reduced frequencies of circulating TFH cells in a concentration-dependent manner while the TFH phenotype was not affected by Ustekinumab therapy. In keeping with this notion, TFH cell differentiation was inhibited by Ustekinumab in vitro while TFH cell maintenance was not affected. Moreover, Ustekinumab therapy resulted in reduced germinal center activity in CD patients in vivo., Conclusions: These data implicate TFH cells in the pathogenesis of CD and indicate that Ustekinumab therapy affects TFH cell differentiation, which may influence TFH-mediated immune functions in UST-treated CD patients., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

(1) Background: Tofacitinib is approved in Europe for the treatment of adults with moderately to severely active ulcerative colitis since 2018. Real-world efficacy and safety data are currently scarce. (2) Methods: We performed a retrospective multicenter study at three German tertiary outpatient clinics for inflammatory bowel diseases and included all patients who started tofacitinib therapy between August 2018 and March 2020. The primary endpoint was a combined endpoint of steroid-free clinical remission, steroid-free clinical response, or clinical response at week 8. Secondary endpoints were biochemical response at week 8, as well as steroid-free clinical remission, steroid-free clinical response or clinical response at week 24, respectively, adverse events by week 24, and need for colectomy by the end of follow-up. (3) Results: Thirty-eight patients with moderate-to-severe ulcerative colitis were included. Eleven patients (28.9%) achieved steroid-free clinical remission at week 8. Fifty-three percent of the patients were primary non-responders at week 8. Three severe adverse events (pneumonia, hospitalization for aggravation of ulcerative colitis, emergency colectomy due to colon perforation), and 12 adverse events were documented by week 8 of therapy. By the end of follow-up, seven patients (18.4%) had undergone colectomy.

Background: Psychiatric co-morbidities including depression and anxiety are common in inflammatory bowel diseases (IBD). Emerging evidence suggests that interactions between the gut microbiota and brain may play a role in the pathogenesis of psychiatric symptoms in IBD., Aim: To review the literature on microbiota-brain-gut interactions in gut inflammation, psychosocial stress and mental disorders and to discuss the putative mediating role of gut microbiota in the development of psychiatric symptoms or co-morbidities in IBD., Methods: A literature search was conducted on Ovid and Pubmed to select relevant animal and human studies reporting an association between IBD, mental disorders and gut microbiota., Results: Gut microbial alterations are frequently reported in subjects with IBD and with mental disorders. Both have been associated with reduced faecal bacterial diversity, decreased taxa within the phylum Firmicutes and increased Gammaproteobacteria. In animal studies, microbial perturbations induce behavioural changes and modulate inflammation in mice. Anxiety- and depression-like behaviours in animals can be transferred via faecal microbiota. In humans, modulation of the gut microbiota with probiotics is associated with behavioural and mood changes. Recent data show correlations in changes of faecal and mucosal microbiota and psychological distress in patients with IBD independent of disease activity., Conclusion: Both IBD and mental disorders are associated with gut microbial alterations. Preclinical and preliminary human studies have shown a mediating role of the gut microbiota in intestinal inflammation and anxiety, depression and stress. Targeting the gut microbiota may represent a useful therapeutic approach for the treatment of psychiatric co-morbidities in IBD., (© 2020 John Wiley & Sons Ltd.)

Background and Aim:  The role of therapeutic drug monitoring (TDM) in ustekinumab (UST) therapy for Crohn's disease (CD) has not been established, as only few studies have analyzed the relationship between UST serum concentrations and clinical outcome. In this pilot study, we retrospectively examined the potential of UST-concentrations (cUST) 8 weeks after induction (cUSTw8) to predict clinical response at week 16., Methods:  Serum samples and clinical data from patients (n = 72) with moderate to severely active CD who received intravenous induction with UST were retrospectively analyzed. cUST were quantitated using liquid chromatography-tandem mass spectrometry (LC-MSMS). A receiver-operating characteristic (ROC) curve and area under ROC curve (AUROC) was computed to analyze the predictive potential of cUSTw8 for clinical response at week 16 and to determine the minimal therapeutic UST trough concentration., Results:  Forty-four patients (61 %) achieved clinical response to UST therapy at week 16. cUSTw8 was moderately effective to predict clinical response with a minimal therapeutic cUSTw8 of 2.0 mg/l (AUC 0.72, p = 0.001)., Conclusion:  Trough concentrations of UST 8 weeks after induction predict clinical response to therapy in week 16 with moderate sensitivity and specificity. TDM using LC-MSMS could prove beneficial in personalized UST therapy of patients with CD by identifying individuals with subtherapeutic concentrations who might benefit from dose escalation., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht.The authors report no conflict of interest related to this work. Outside of this project, the authors report the following disclosures:AKT: Speakers honorary or travel support from Abbvie, MSD and TakedaAMG: Travel support from Abbvie and JanssenPHo: Speakers honorary and travel support from JanssenTK: Speakers honorary and/or consultant fees from AbbVie, Janssen, MSD, Novartis, Takeda and PfizerJW: Speakers honorary and/or consultant fees from AbbVie, Ardeypharm, Ferring, Janssen, MSD, Novartis, Pfizer, Roche and TakedaAG: Speakers honorary, travel support and/or consultant fees from Abbvie, Amgen, Janssen, MSD, Pfizer, Takeda and TillotsPHa: Speakers honorary, travel support and/or consultant fees from Abbvie, Falk, Janssen, MSD and TakedaJK: Speakers honorary, travel support and/or consultant fees from Abbvie, BMS, Celltrion, Falk, Janssen, MSD, Pharmacosmos, Shield, Takeda, Tillots and ViforWR: Speakers honorary and/or consultant fees from Abbvie, Janssen and TakedaLAS, TI, AT, RS, NS and MPE report no disclosures or conflicts of interest for this project, (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Approximately one-third of all patients suffering from Crohn's disease (CD) undergo surgery within the first 10 years after diagnosis and another 20% will have a second operation in the 10 years after their first operation. Surgery will remain an essential part of managing CD and therefore it is crucial to prevent perioperative complications by optimizing perioperative management., Methods: We reviewed the current literature on managing immunomodulating therapy, nutritional support, and thromboembolic prophylaxis in the perioperative situation., Results: CD patients with serious nutritional deficits (weight loss >10% in the last 3-6 months, body mass index <18.5 kg/m 2 , or albumin levels <30 g/L) benefit from intensive enteral or parenteral nutritional support, thereby reducing the risk of surgical-site infections and post-operative septic complications. Immunosuppressive therapy with prednisolone doses >20 mg should be avoided. The risk of therapy with anti-TNFα agents, vedolizumab, and ustekinumab for surgical complications has not been fully established. Analysis of currently available data suggests that an interval of 4-8 weeks is prudent to avoid complications and reduce risk by performing protective ostomy in the emergency setting. Finally, due to the high risk of venous thromboembolism, prophylactic therapy with heparin is recommended., Conclusion: As most cases of CD-related surgery are performed in a non-emergency setting, careful planning and risk management can reduce the rate of surgical complications, increase quality of life, and also reduce costs., Competing Interests: W.R. received speaker's fees from AbbVie, Falk, Janssen, and Takeda., (Copyright © 2019 by S. Karger AG, Basel.)

Background: Disturbed brain-gut interactions and a bidirectional relationship between inflammation and psychiatric symptoms such as anxiety and depression are being discussed in patients with inflammatory bowel diseases (IBD). Alterations of brain structure and function in IBD have been reported with heterogeneous results. Whether these changes reflect independent localized deficits or rather a systematic disruption in the anatomical organization of large-scale brain networks remains unclear. The present study investigated the gray matter structural connectome in patients with Crohn's disease (CD)., Methods: Sixty participants (30 with quiescent CD and 30 matched healthy controls [HC]) underwent high-resolution brain MRI at 3 Tesla. Well-established graph theoretical metrics were analyzed at the global and regional network level and compared between groups., Key Results: The networks in both groups followed a small-world organization, that is, an architecture that is simultaneously highly segregated and integrated. However, transitivity, a measure of global network segregation, was significantly reduced in patients (P = 0.003). Regionally, patients showed a reduction of nodal betweenness centrality in the right insula and cuneus and the left superior frontal cortex and reduced nodal degree within the left-hemispheric cingulate and the left lateral and right medial orbitofrontal cortex., Conclusion and Inferences: These findings lend support to the hypothesis that CD is accompanied by alterations in both global network organization and regional connectivity. A deeper understanding of neural central networks in IBD may facilitate the development of complementary strategies in the treatment of "extraintestinal" comorbid conditions such as depression or anxiety., (© 2019 John Wiley & Sons Ltd.)

Objectives: The clock drawing test (CDT) is one of the worldwide most used screening tests for Alzheimer's disease (AD). MRI studies have identified temporo-parietal regions being involved in CDT impairment. However, the contributions of specific hippocampal subfields and adjacent extrahippocampal structures to CDT performance in AD and mild cognitive impairment (MCI) have not been investigated so far. It is unclear whether morphological alterations or CDT score, or a combination of both, are able to predict AD., Methods: 38 AD patients, 38 MCI individuals and 31 healthy controls underwent neuropsychological assessment and MRI at 3 Tesla. FreeSurfer 5.3 was used to perform hippocampal parcellation. We used a collection of statistical methods to better understand the relationship between CDT and hippocampal formation. We also tested the clinical feasibility of this relationship when predicting AD., Results: Impaired CDT performance in AD was associated with widespread atrophy of the cornu ammonis, presubiculum, and subiculum, whereas MCI subjects showed CDT-related alterations of the CA4-dentate gyrus and subiculum. CDT correlates in AD and MCI showed regional and quantitative overlap. Importantly, CDT score was the best predictor of AD., Conclusions: Our findings lend support for an involvement of different hippocampal subfields in impaired CDT performance in AD and MCI. CDT seems to be more efficient than subfield imaging for predicting AD.

Impulsivity is associated with distinct mental disorders but is also considered as a personality trait exhibited by healthy individuals. Current studies suggest that early stressful life events might cause higher impulsivity in the adulthood. Morphological features, which reflect early brain development, could provide valuable information regarding the origin of impulsive behavior. However, none of the previous MRI studies employed a methodology specifically designed to investigate the relationship between impulsivity and markers of brain development. In this regard, we aimed to investigate the relationship between cortical folding and the three distinct factors of impulsivity (attention, motor, and non-planning) in young healthy adults. Fifty-four right-handed healthy individuals were recruited for the study and underwent magnetic resonance imaging (MRI) at 3 Tesla. A surface-based analysis was used to calculate a local gyrification index (LGI). Impulsivity was examined by the Barratt Impulsiveness Scale (BIS-11) and related to LGI. Associations between LGI and BIS-11 scores were assessed using within-group correlations (p < 0.05, "cluster-wise probability" [CWP] corr.). BIS subscores were positively correlated with cortical folding in several distinct areas: Total and attention scores were positively correlated with LGI in the left postcentral gyrus, cingulate gyrus, precentral gyrus, pars opercularis of the inferior frontal gyrus, right middle temporal gyrus, superior parietal gyrus, pericalcarine gyrus, and lateral occipital gyrus (each p < 0.05 CWP corr.). BIS motor score was positively correlated with LGI in the left superior temporal, lingual and supramarginal gyrus (each p < 0.05 CWP corr.). BIS non-planning score showed a positive correlation with LGI in the pars opercularis of the right inferior frontal gyrus and the left middle temporal, precentral and superior parietal gyrus (each p < 0.05 CWP corr.). Furthermore, we found gender-specific differences in BIS-11-LGI-correlation in the middle and inferior frontal gyrus. Our findings illustrate the advantages of cortical folding as a marker of early brain development when investigating structural brain correlates of impulsivity in young adulthood. Further, they lend additional support to the notion that alterations in early neurodevelopment comprising fronto-temporo-parietal regions might give rise to higher impulsivity in healthy individuals.

Psychological factors and comorbidities play an important role in inflammatory bowel diseases. Such comorbidity could be associated with a specific neural phenotype. Brain regions associated with emotion regulation and self-referential processing, including areas assigned to the "default mode network" (DMN), could be promising candidates in this regard. We investigated the functional integrity of multiple intrinsic neural networks in remitted patients with Crohn's disease (CD) and sought to establish relationships between neural network connectivity and psychiatric symptoms. Fifteen CD patients in remission and 14 controls were investigated. We employed resting-state functional magnetic resonance imaging (fMRI) at 3 Tesla followed by a spatial Independent Component Analysis for fMRI data. Abnormal connectivity in CD patients was observed in DMN subsystems only (p < 0.05, cluster-corrected). Increased connectivity was found in the anterior cingulate and left superior medial frontal gyrus (aDMN) and the middle cingulate cortex (pDMN). Middle cingulate activity showed a significant association with anxiety scores in patients (p = 0.029). This study provides first evidence of selectively disrupted intrinsic neural network connectivity in CD and suggests abnormalities of self-referential neural networks. An increased sensitivity to self-related affective and somatic states in CD patients could account for these findings and explain a higher risk for anxiety symptoms.

It is unclear whether clock drawing test (CDT) performance relies on a widely distributed cortical network, or whether this test predominantly taps into parietal cortex function. So far, associations between cortical integrity and CDT impairment in Alzheimer's disease (AD) and mild cognitive impairment (MCI) largely stem from cortical volume analyses. Given that volume is a product of thickness and surface area, investigation of the relationship between CDT and these two cortical measures might contribute to better understanding of this cognitive screening tool for AD. 38 patients with AD, 38 individuals with MCI and 31 healthy controls (HC) underwent CDT assessment and MRI at 3 Tesla. The surface-based analysis via Freesurfer enabled calculation of cortical thickness and surface area. CDT was scored according to the method proposed by Shulman and related to the two distinct cortical measurements. Higher CDT scores across the entire sample were associated with cortical thickness in bilateral temporal gyrus, the right supramarginal gyrus, and the bilateral parietal gyrus, respectively (p < 0.001 CWP corr.). Significant associations between CDT and cortical thickness reduction in the parietal lobe remained significant when analyses were restricted to AD individuals. There was no statistically significant association between CDT scores and surface area (p < 0.001 CWP corr.). In conclusion, CDT performance may be driven by cortical thickness alterations in regions previously identified as "AD vulnerable", i.e. regions predominantly including temporal and parietal lobes. Our results suggest that cortical features of distinct evolutionary and genetic origin differently contribute to CDT performance., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Autobiographical memory (AM) is part of declarative memory and includes both semantic and episodic aspects. AM deficits are among the major complaints of patients with Alzheimer's disease (AD) even in early or preclinical stages. Previous MRI studies in AD patients have showed that deficits in semantic and episodic AM are associated with hippocampal alterations. However, the question which specific hippocampal subfields and adjacent extrahippocampal structures contribute to deficits of AM in individuals with mild cognitive impairment (MCI) and AD patients has not been investigated so far. Hundred and seven participants (38 AD patients, 38 MCI individuals and 31 healthy controls [HC]) underwent MRI at 3 Tesla. AM was assessed with a semi-structured interview (E-AGI). FreeSurfer 5.3 was used for hippocampal parcellation. Semantic and episodic AM scores were related to the volume of 5 hippocampal subfields and cortical thickness in the parahippocampal and entorhinal cortex. Both semantic and episodic AM deficits were associated with bilateral hippocampal alterations. These associations referred mainly to CA1, CA2-3, presubiculum, and subiculum atrophy. Episodic, but not semantic AM loss was associated with cortical thickness reduction of the bilateral parahippocampal and enthorinal cortex. In MCI individuals, episodic, but not semantic AM deficits were associated with alterations of the CA1, presubiculum and subiculum. Our findings support the crucial role of CA1, presubiculum, and subiculum in episodic memory. The present results implicate that in MCI individuals, semantic and episodic AM deficits are subserved by distinct neuronal systems., (© 2017 Wiley Periodicals, Inc.)

Background and Objective: Alterations of brain morphology in Crohn's disease have been reported, but data is scarce and heterogenous and the possible impact of disease predisposition on brain development is unknown. Assuming a systemic course of the disease, brain involvement seems more probable in presence of extraintestinal manifestations, but this question has not yet been addressed. The present study examined the relationship between Crohn's disease and brain structure and focused on the connection with extraintestinal manifestations and markers of brain development., Methods: In a pilot study, brains of 15 patients with Crohn's disease (of which 9 had a history of extraintestinal manifestations, i.e. arthritis, erythema nodosum and primary sclerosing cholangitis) were compared to matched healthy controls using high resolution magnetic resonance imaging. Patients and controls were tested for depression, fatigue and global cognitive function. Cortical thickness, surface area and folding were determined via cortical surface modeling., Results: The overall group comparison (i.e. all patients vs. controls) yielded no significant results. In the patient subgroup with extraintestinal manifestations, changes in cortical area and folding, but not thickness, were identified: Patients showed elevated cortical surface area in the left middle frontal lobe (p<0.05) and hypergyrification in the left lingual gyrus (p<0.001) compared to healthy controls. Hypogyrification of the right insular cortex (p<0.05) and hypergyrification of the right anterior cingulate cortex (p<0.001) were detected in the subgroup comparison of patients with against without extraintestinal manifestations. P-values are corrected for multiple comparisons., Conclusions: Our findings lend further support to the hypothesis that Crohn's disease is associated with aberrant brain structure and preliminary support for the hypothesis that these changes are associated with a systemic course of the disease as indicated by extraintestinal manifestations. Changes in cortical surface area and folding suggest a possible involvement of Crohn's disease or its predisposition during brain development., Competing Interests: The authors have declared that no competing interests exist.

Neurological soft signs (NSS) are frequently found in psychiatric disorders of significant neurodevelopmental origin. Previous MRI studies in schizophrenia have shown that NSS are associated with abnormal cortical, thalamic and cerebellar structure and function. So far, however, no neuroimaging studies investigated brain correlates of NSS in individuals with Asperger-Syndrome (AS) and the question whether the two disorders exhibit common or disease-specific cortical correlates of NSS remains unresolved. High-resolution MRI data at 3 T were obtained from 48 demographically matched individuals (16 schizophrenia patients, 16 subjects with AS and 16 healthy individuals). The surface-based analysis via Freesurfer enabled calculation of cortical thickness, area and folding (local gyrification index, LGI). NSS were examined on the Heidelberg Scale and related to cortical measures. In schizophrenia, higher NSS were associated with reduced cortical thickness and LGI in fronto-temporo-parietal brain areas. In AS, higher NSS were associated with increased frontotemporal cortical thickness. This study lends further support to the hypothesis that disorder-specific mechanisms contribute to NSS expression in schizophrenia and AS. Pointing towards dissociable neural patterns may help deconstruct the complex processes underlying NSS in these neurodevelopmental disorders.

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., (Copyright © 2015 Elsevier B.V. All rights reserved.)

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., (Copyright © 2012 S. Karger AG, Basel.)