Anne K. Thomann

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

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

Brain Structure in Preclinical Huntington's Disease: A Multi-Method Approach

Background: Structural magnetic resonance imaging (MRI) of the brain could be a powerful tool for discovering early biomarkers in clinically presymptomatic carriers of the Huntingtons 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.

Hippocampal formation alterations differently contribute to autobiographic memory deficits in mild cognitive impairment and Alzheimer's disease

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 Alzheimers 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.

Cortical folding patterns are associated with impulsivity in healthy young adults

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.

Prevalence of inflammatory bowel disease in alcoholic, non-alcoholic and autoimmune pancreatitis: Inflammatory bowel disease in pancreatitis

OBJECTIVES Patients with inflammatory bowel disease (IBD) frequently reveal features of pancreatic inflammation. However, the prevalence of IBD in patients with alcoholic pancreatitis (AP) and nonalcoholic pancreatitis (NAP) has not yet been determined, and the prevalence of IBD in patients with autoimmune pancreatitis (AiP) from Germany is unknown. AIMS Thus, we aimed, first, to determine the prevalence of IBD in AP, NAP, and AiP from a tertiary center in Germany and, second, to characterize patients with AiP and IBD. METHODS We performed a retrospective cross-sectional study to determine the prevalence of IBD in patients with different forms of pancreatitis presenting to our clinic. RESULTS Compared to the general population and to a control group with viral hepatitis from our clinic, we observed the most significant increase of IBD in patients with AiP (n = 3/28; p < 0.0001 vs. general population, binomial proportion test; p = 0.0112 vs. hepatitis group, Fishers exact test), followed by a significant increase in subjects with NAP (n = 11/278; p < 0.0001 vs. general population, binomial proportion test; p = 0.0338 vs. hepatitis group, Fishers exact test). A review of previous studies on the prevalence of IBD among patients with AiP revealed a combined prevalence of 12 % (n = 43/355). Type 2 AiP is significantly more often associated with IBD than type 1 AiP (n = 28/48, 58 % vs. n = 7/129, 5 %; combined patient cohort, p < 10E - 12; Fishers exact test). CONCLUSIONS Immune-mediated mechanisms related to IBD may participate in the development of AiP, especially AiP type 2, and may also increase the risk for the development of other forms of pancreatic inflammation.

The relevance of hippocampal subfield integrity and clock drawing test performance for the diagnosis of Alzheimer’s disease and mild cognitive impairment

Abstract 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.

Intrinsic neural network dysfunction in quiescent Crohn’s Disease

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.

G02 Brain structure in preclinical Huntington's disease: a multi-method approach

Background Structural MRI of the brain could be a powerful tool for discovering early biomarkers in clinically pre-symptomatic carriers of the Huntingtons disease gene mutation (preHD). Aims The aim of this study was to investigate the sensitivity of different methodological approaches to structural data in far-from onset preHD (mean time to motor onset = 21.4 years) and to explore the relationship between the time to motor onset, cognition and brain structure. Methods High-resolution MRI data at 3 Tesla were obtained from 20 preHD individuals and 20 healthy participants and subsequently analysed using voxel-based morphometry (VBM), cortical surface modelling and subcortical segmentation analysis techniques. Results VBM analyses did not reveal significant between-group differences. In contrast, cortical surface modelling and subcortical segmentation analyses showed significant regional cortical thinning and striatal changes in preHD compared to controls (p<0.05, corrected for multiple comparisons). Significant correlations were found between striatal structure, time-to-motor-onset and behavioural performance during card sorting, whereas cortical changes were not significantly correlated with time-to-motor-onset or behavioural parameters. Conclusions These data suggest that a combined methodological approach to structural MRI data could increase sensitivity to very early neurobiological changes in far-from-onset preHD. As demonstrated across different methodological modalities, the association between striatal structure and clinical measures supports the notion that striatal volume might represent a more robust marker of change than cortical alterations.