Extratemporale Veränderungen der Hirnstruktur nach der operativen Behandlung der mesialen Temporallappenepilepsie und ihre kognitiven Korrelate

Die Epilepsiechirurgie ist im Laufe der letzten Jahrzehnte zu Operationsstrategien übergegangen, bei denen immer mehr die Schonung von Gewebe im Vordergrund steht. So werden bei der SAH nur die temporo-mesialen Strukturen entfernt. Hierzu zählen der Hippokampus, die Amygdala und der Gyrus parahippocampalis. Die vorliegende Arbeit geht der Frage nach, ob sich Regionen in ihrer Neuronendichte verändern, die außerhalb des Temporallappens liegen und dadurch nicht unmittelbar durch die Operation betroffen sind. Des Weiteren wird untersucht, welche extratemporalen Strukturveränderungen mit signifikanten Kognitionsveränderungen der betroffenen TLE-Patienten nach einer SAH zusammenhängen. Um die Fragestellung zu untersuchen, wurden die Verhaltens- und MRT-Daten von 69 mTLE-Patienten untersucht, bei denen eine AHS diagnostiziert wurde und die sich einer SAH unterzogen haben. Die Auswertung der MRT-Daten fand unter Zuhilfenahme der Voxel-basierten Morphometrie statt. Diese Methode ermöglicht eine objektive Ganzhirnanalyse, durch die regionale Unterschiede in der Neuronendichte dargestellt werden können. Als kognitive Funktionen gingen die Daten des verbalen und figuralen Gedächtnisses, der Aufmerksamkeitsleistung und die der phonematischen Wortflüssigkeit in die Analyse ein. Als Ergebnis der reinen MRT-Analyse zeigte sich eine signifikante Abnahme der extratemporalen Neuronendichte im ipsi- und kontralateralen Thalamus und Nucleus caudatus nach einer rechten SAH. Bei den Patienten, die einen linksseitigen epilepsiechirurgischen Eingriff erhalten haben, ergab sich eine Dichteabnahme der grauen Substanz im Bereich des ipsilateralen Pallidum, Putamen und Nucleus caudatus. Die Dichteabnahme lässt sich gut mit der Annahme einer Deafferenzierung diskutieren. Eine Dichtezunahme der Neuronen konnte im linken Gyrus praecentralis nach einer linksseitigen SAH sowie im beidseitigen Cerebellum und im rechten supplementär-motorische Areal (SMA) nach einer SAH der rechten Seite beobachtet werden. Eine Erklärung für diese Dichtezunahme lässt sich bei der vorliegenden Datenlage nicht finden. Die kombinierte Analyse der Verhaltens- und MRT-Daten ergab bei einer signifikanten Verschlechterung des Verbalgedächtnisses eine Neuronendichteabnahme außerhalb der temporalen Strukturen im ipsilateralen Gyrus cinguli, Thalamus und rolandischen Operculum sowie ipsi- und kontralateral im Nucleus caudatus, Gyrus frontalis superior und Gyrus orbitofrontalis bei linksseitig betroffenen Patienten. Damit einhergehende Gedächtnisverschlechterung lassen sich durch die Annahme erklären, dass extratemporale Areale atrophieren, die innerhalb eines funktionalen Netzwerkes mit den resezierten mesio-limbischen Strukturen verknüpft sind. Die signifikante Verbesserung in der Aufmerksamkeitsleistung ging hingegen mit einer Dichtezunahme der grauen Substanz im ipsilateralen Gyrus frontalis triangularis inferior, Gyrus frontalis opercularis, Gyrus praecentralis und Cerebellum sowie im kontralateralen Precuneus einher. Bei rechtsseitig operierten TLE-Patienten zeigte sich eine signifikante Aufmerksamkeitsverbesserung zusammen mit einer Dichtezunahme der Neuronen im Bereich des ipsilateralen rolandischen Operculums. Erklärt wird hierbei die Aufmerksamkeitsverbesserung als Folge der Dichteerhöhung der grauen Substanz in Arealen, welche diese exekutive Funktion generieren. Zudem wird die Annahme der Beteiligung des Kleinhirns an kognitiven Funktionen im Sinne einer Vorbereitungsfunktion zur Diskussion der Aufmerksamkeitsverbesserung herangezogen. Die Arbeit zeigt, dass die Selektivität der SAH insofern eingeschränkt ist, als dass der chirurgische Eingriff nicht nur zu Strukturveränderungen im Resektionsbereich führt, sondern auch zu Änderungen, welche Areale des gesamten Gehirns betreffen. Damit gehen Veränderungen von neuropsychologischen Funktionen einher, die wiederum nicht lediglich auf die Entfernung der mesialen Strukturen zurückzuführen sind, sondern auf das Eingreifen in ein komplexes Netzwerk aus Hirnstrukturen, welche funktionell in verschiedene Kognitionen eingebunden sind

Phylogenetic relationships of species of Raymunida (Decapoda: Galatheidae) based on morphology and mitochondrial cytochrome oxidase sequences, with the recognition of four new species

19 pages.-- RECEIVED: 10 April 2000, ACCEPTED: 8 November 2000.The species of the genus Raymunida from the Pacific and Indian oceans are revised using morphological characters and the mitochondrial cytochrome oxidase subunit I sequences. Four new species are described (R. confundens, R. dextralis, R. erythrina, and R. insulata), and the status of R. bellior and R. elegantissima are revised. The species of Raymunida can be identified by subtle morphological characters, which match differences in mitochondrial nucleotide sequences. Therefore, the sequence divergences confirm the specific and phylogenetic value of some morphological characters (e.g., length of the mesial spine on the basal antennal segment, length of the walking legs). Furthermore, they confirm the importance of the color pattern as a diagnostic character. The widespread species (R. elegantissima), known from the Philippines to Fiji, shows minimal divergence between specimens from different localities (maximum of 3 nucleotide differences or 0.2% mean divergence). The phylogenetic reconstruction agreed with the monophyletic condition of Raymunida and its differentiation with respect to the genus Munida (in which Raymunida species had previously been included) and Agononida.Peer reviewe

Cholinergic white matter pathways along the Alzheimer's disease continuum

Nemy et al. investigate cholinergic white matter projections along the Alzheimer's disease continuum. They show that alterations are already present in individuals with subjective cognitive decline, preceding the more widespread alterations seen in mild cognitive impairment and Alzheimer's disease dementia. Previous studies have shown that the cholinergic nucleus basalis of Meynert and its white matter projections are affected in Alzheimer's disease dementia and mild cognitive impairment. However, it is still unknown whether these alterations can be found in individuals with subjective cognitive decline, and whether they are more pronounced than changes found in conventional brain volumetric measurements. To address these questions, we investigated microstructural alterations of two major cholinergic pathways in individuals along the Alzheimer's disease continuum using an in vivo model of the human cholinergic system based on neuroimaging. We included 402 participants (52 Alzheimer's disease, 66 mild cognitive impairment, 172 subjective cognitive decline and 112 healthy controls) from the Deutsches Zentrum für Neurodegenerative Erkrankungen Longitudinal Cognitive Impairment and Dementia Study. We modelled the cholinergic white matter pathways with an enhanced diffusion neuroimaging pipeline that included probabilistic fibre-tracking methods and prior anatomical knowledge. The integrity of the cholinergic white matter pathways was compared between stages of the Alzheimer's disease continuum, in the whole cohort and in a CSF amyloid-beta stratified subsample. The discriminative power of the integrity of the pathways was compared to the conventional volumetric measures of hippocampus and nucleus basalis of Meynert, using a receiver operating characteristics analysis. A multivariate model was used to investigate the role of these pathways in relation to cognitive performance. We found that the integrity of the cholinergic white matter pathways was significantly reduced in all stages of the Alzheimer's disease continuum, including individuals with subjective cognitive decline. The differences involved posterior cholinergic white matter in the subjective cognitive decline stage and extended to anterior frontal white matter in mild cognitive impairment and Alzheimer's disease dementia stages. Both cholinergic pathways and conventional volumetric measures showed higher predictive power in the more advanced stages of the disease, i.e. mild cognitive impairment and Alzheimer's disease dementia. In contrast, the integrity of cholinergic pathways was more informative in distinguishing subjective cognitive decline from healthy controls, as compared with the volumetric measures. The multivariate model revealed a moderate contribution of the cholinergic white matter pathways but not of volumetric measures towards memory tests in the subjective cognitive decline and mild cognitive impairment stages. In conclusion, we demonstrated that cholinergic white matter pathways are altered already in subjective cognitive decline individuals, preceding the more widespread alterations found in mild cognitive impairment and Alzheimer's disease. The integrity of the cholinergic pathways identified the early stages of Alzheimer's disease better than conventional volumetric measures such as hippocampal volume or volume of cholinergic nucleus basalis of Meynert

Novelty-Related fMRI Responses of Precuneus and Medial Temporal Regions in Individuals at Risk for Alzheimer Disease

BACKGROUND AND OBJECTIVES: We assessed whether novelty-related fMRI activity in medial temporal lobe regions and the precuneus follows an inverted U-shaped pattern across the clinical spectrum of increased Alzheimer disease (AD) risk as previously suggested. Specifically, we tested for potentially increased activity in individuals with a higher AD risk due to subjective cognitive decline (SCD) or mild cognitive impairment (MCI). We further tested whether activity differences related to diagnostic groups were accounted for by CSF markers of AD or brain atrophy. METHODS: We studied 499 participants aged 60-88 years from the German Center for Neurodegenerative Diseases Longitudinal Cognitive Impairment and Dementia Study (DELCODE) who underwent task-fMRI. Participants included 163 cognitively normal (healthy control, HC) individuals, 222 SCD, 82 MCI, and 32 patients with clinical diagnosis of mild AD. CSF levels of β-amyloid 42/40 ratio and phosphorylated-tau181 were available from 232 participants. We used region-based analyses to assess novelty-related activity (novel > highly familiar scenes) in entorhinal cortex, hippocampus, and precuneus as well as whole-brain voxel-wise analyses. First, general linear models tested differences in fMRI activity between participant groups. Complementary regression models tested quadratic relationships between memory impairment and activity. Second, relationships of activity with AD CSF biomarkers and brain volume were analyzed. Analyses were controlled for age, sex, study site, and education. RESULTS: In the precuneus, we observed an inverted U-shaped pattern of novelty-related activity across groups, with higher activity in SCD and MCI compared with HC, but not in patients with AD who showed relatively lower activity than MCI. This nonlinear pattern was confirmed by a quadratic relationship between memory impairment and precuneus activity. Precuneus activity was not related to AD biomarkers or brain volume. In contrast to the precuneus, hippocampal activity was reduced in AD dementia compared with all other groups and related to AD biomarkers. DISCUSSION: Novelty-related activity in the precuneus follows a nonlinear pattern across the clinical spectrum of increased AD risk. Although the underlying mechanism remains unclear, increased precuneus activity might represent an early signature of memory impairment. Our results highlight the nonlinearity of activity alterations that should be considered in clinical trials using functional outcome measures or targeting hyperactivity

Short communication: Lifetime musical activity and resting-state functional connectivity in cognitive networks

Background Participation in multimodal leisure activities, such as playing a musical instrument, may be protective against brain aging and dementia in older adults (OA). Potential neuroprotective correlates underlying musical activity remain unclear. Objective This cross-sectional study investigated the association between lifetime musical activity and resting-state functional connectivity (RSFC) in three higher-order brain networks: the Default Mode, Fronto-Parietal, and Salience networks. Methods We assessed 130 cognitively unimpaired participants (≥ 60 years) from the baseline cohort of the DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) study. Lifetime musical activity was operationalized by the self-reported participation in musical instrument playing across early, middle, and late life stages using the Lifetime of Experiences Questionnaire (LEQ). Participants who reported musical activity during all life stages (n = 65) were compared to controls who were matched on demographic and reserve characteristics (including education, intelligence, socioeconomic status, self-reported physical activity, age, and sex) and never played a musical instrument (n = 65) in local (seed-to-voxel) and global (within-network and between-network) RSFC patterns using pre-specified network seeds. Results Older participants with lifetime musical activity showed significantly higher local RSFC between the medial prefrontal cortex (Default Mode Network seed) and temporal as well as frontal regions, namely the right temporal pole and the right precentral gyrus extending into the superior frontal gyrus, compared to matched controls. There were no significant group differences in global RSFC within or between the three networks. Conclusion We show that playing a musical instrument during life relates to higher RSFC of the medial prefrontal cortex with distant brain regions involved in higher-order cognitive and motor processes. Preserved or enhanced functional connectivity could potentially contribute to better brain health and resilience in OA with a history in musical activity. Trial registration German Clinical Trials Register (DRKS00007966, 04/05/2015)

IN/OUTsiderArt: Studierende der Kunstpädagogik im Dialog mit der Sammlung Prinzhorn

In der Publikation "IN/OUTsiderArt" wird der Dialog von Studierenden der Kunstpädagogik (Lehrstuhl für Kunstpädagogik der Friedrich-Alexander-Universität Erlangen-Nürnberg) mit Werken aus der Sammlung Prinzhorn (Heidelberg) dokumentiert. In der Sammlung Prinzhorn werden Werke psychiatrieerfahrener Menschen vom Ende des 19. Jahrhunderts bis heute aufbewahrt. Diese Arbeiten entstanden außerhalb des gewöhnlichen Kunstbetriebs und werden deswegen als Outsider Art bezeichnet. Die künstlerischen Werke der gesellschaftlichen Außenseiter zeigen ungewöhnliche bildnerische Ausdrucksformen und weisen einen starken biografischen Bezug auf. Das Buch folgt nicht nur inhaltlich, sondern auch formal dem Dialog. Die Arbeiten aus der Sammlung Prinzhorn sind den jeweiligen Arbeiten der Studierenden gegenübergestellt. So lässt sich eindrücklich den Dialogen der Studierenden nachspüren, die von Texten des Leiters der Sammlung Prinzhorn, Dr. Thomas Röske, der Lehrstuhlinhaberin Prof. Dr. Susanne Liebmann-Wurmer sowie des Dozenten Tobias Loemke gerahmt werden

Relevance of Subjective Cognitive Decline in Older Adults with a First-Degree Family History of Alzheimer's Disease

Background: It is unclear whether subjective cognitive decline (SCD) is a relevant clinical marker of incipient Alzheimer's disease (AD) and future cognitive deterioration in individuals with a family history of AD (FHAD). Objective: To investigate the association of SCD with cross-sectional cerebrospinal fluid (CSF) AD biomarker levels and cognitive decline in cognitively normal older adults with or without a first-degree FHAD. Methods: We analyzed data from cognitively normal individuals with first-degree FHAD (n = 82 AD relatives; mean age: 65.7 years (SD = 4.47); 59% female) and a similar group of n = 236 healthy controls without FHAD from the DELCODE study. We measured SCD with an in-depth structured interview from which we derived a SCD score, capturing features proposed to increase likelihood of underlying AD (SCD-plus score). We tested whether higher SCD-plus scores were associated with more pathological CSF AD biomarker levels and cognitive decline over time and whether this association varied by group. Results: AD relatives showed higher SCD-plus scores than healthy controls and more cognitive decline over time. Higher SCD-plus scores also related stronger to cognitive change and abnormal CSF AD biomarker levels in the AD relatives as compared to the healthy controls group. Conclusion: Quantification of specific SCD features can provide further information on the likelihood of early AD pathology and cognitive decline among AD relatives. FHAD and SCD appear as synergistically acting enrichment strategies in AD research, the first one as a permanent indicator of genetic risk, the latter one as a correlate of disease progression

Musical Activity During Life Is Associated With Multi-Domain Cognitive and Brain Benefits in Older Adults

Regular musical activity as a complex multimodal lifestyle activity is proposed to be protective against age-related cognitive decline and Alzheimer’s disease. This cross-sectional study investigated the association and interplay between musical instrument playing during life, multi-domain cognitive abilities and brain morphology in older adults (OA) from the DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) study. Participants reporting having played a musical instrument across three life periods (n = 70) were compared to controls without a history of musical instrument playing (n = 70), well-matched for reserve proxies of education, intelligence, socioeconomic status and physical activity. Participants with musical activity outperformed controls in global cognition, working memory, executive functions, language, and visuospatial abilities, with no effects seen for learning and memory. The musically active group had greater gray matter volume in the somatosensory area, but did not differ from controls in higher-order frontal, temporal, or hippocampal volumes. However, the association between gray matter volume in distributed frontal-to-temporal regions and cognitive abilities was enhanced in participants with musical activity compared to controls. We show that playing a musical instrument during life relates to better late-life cognitive abilities and greater brain capacities in OA. Musical activity may serve as a multimodal enrichment strategy that could help preserve cognitive and brain health in late life. Longitudinal and interventional studies are needed to support this notion

Resulting clusters of the seed-to-voxel connectivity analysis for the DMN seed.

Resulting clusters of the seed-to-voxel connectivity analysis for the DMN seed.</p