Biology subjects

Dechent, P.

Publications and source records attributed to Dechent, P..

14 recordsLinked to original sources

bioRxiv2026

Automated quantification of white matter hyperintensity confluence: A measure of spatial organisation beyond volume and visual rating scales

White matter hyperintensities (WMH) are a highly prevalent finding on FLAIR MRI scans and a prominent feature of white matter pathology across cerebrovascular and neurodegenerative diseases. Currently, WMH are assessed with visual rating scales such as the Fazekas scale or with their volume, as calculated from automatic or manual segmentations. Both methods have limitations: Visual rating scales are rater-dependent and coarse, while WMH volume does not take the confluence of lesions into account and thus disregards their spatial organisation. As an alternative, here we propose a novel automated method for quantifying the confluence of white matter hyperintensities on a continuous standardised scale between 0 and 1. The metric is based on WMH segmentations from routine MRI and quantifies the extent to which individual WMH merge into coherent lesions, independently of total lesion volume. We apply the method to QMIN-MC, a large UK memory clinic cohort, and show associations of the confluence metric with age, cognitive performance across domains, and Fazekas ratings. Participants with vascular and mixed dementia showed higher confluence than other diagnostic groups, whereas cognitively unimpaired participants showed lower confluence. However, confluence did not explain additional cognitive variance after accounting for log-transformed WMH volume. Findings were validated in DELCODE, an independent cohort of individuals with neurodegenerative disorders, replicating our original results. In this validation cohort, periventricular WMH confluence remained associated with cognition after adjustment for WMH volume. These findings introduce WMH confluence as a reproducible, automated, and fine-grained measure of lesion spatial organisation. It provides complementary information about morphological WMH severity beyond volume and is an alternative to visual rating scales. Although related to WMH volume in memory-clinic populations, confluence captures clinically interpretable information and may complement existing WMH measures for improved lesion characterisation in studies of white matter disease, ageing, and cognitive impairment.

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bioRxiv2025

Disrupted Forward Connectivity in Parieto-temporal Network Impairs Memory Performance in Alzheimer's Disease

Alzheimers disease (AD) is characterised by the accumulation of beta-amyloid (A{beta}) and tau proteins, leading to neurodegeneration and cognitive decline. While A{beta} and tau are known to disrupt synaptic function, the mechanisms linking these molecular pathologies to network-level dysfunction and memory impairment remain poorly understood. Here we investigated the effects of A{beta} and tau pathology (CSF A{beta}42/40 ratio and tau phosphorylated at position 181, p-tau-181, respectively) on effective connectivity (EC) related to memory encoding, which may constitute a link between synaptic pathology and cognitive outcomes. Functional magnetic resonance imaging (fMRI) during visual memory encoding was acquired from participants of the multicentric DZNE Longitudinal Cognitive Impairment and Dementia Study (DELCODE), including 203 cognitively normal older participants (CN) as well as individuals with subjective cognitive decline (SCD; N = 204), mild cognitive impairment (MCI; N = 65), and early dementia due to AD (DAT; N = 21). EC was assessed by applying Dynamic causal modelling (DCM) to the fMRI data, using brain regions previously implicated in memory-encoding: the parahippocampal place area (PPA), the hippocampus (HC) and the precuneus (PCU). Disruptions in forward connectivity from the PPA to the HC and PCU were associated with both memory impairment and indices of AD pathology. Specifically, reduced excitatory EC from the PPA to the HC was associated with higher p-tau-181 levels and correlated with poorer memory performance. Diminished inhibitory EC from the PPA to the PCU was driven by both tau and amyloid pathology and was likewise linked to memory decline. Our findings suggest that disrupted forward connectivity within the temporo-parietal memory network constitutes a candidate mechanism mediating the relationship between molecular pathology and cognitive dysfunction.

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bioRxiv2025

Optic Ataxia in Patients with Thalamic Lesions

Lesions in parietal cortex can strongly impair visually guided reach-grasping behaviour. A specific reaching deficit termed Optic Ataxia (OA) occurs when eye and hand position are dissociated. Optic ataxia has typically been studied in patients with lesions in parietal cortex, neglecting potential thalamic contributions. We here examined 28 acute stroke patients (age 58.9 {+/-} 12.6 years) with circumscribed thalamic lesions for the presence of optic ataxia. We leveraged MRI-based lesion-symptom mapping to address the contributions of specific thalamic nuclei to visually-guided reaching deficits under foveal and peripheral viewing conditions. Based on the cortical literature, we hypothesized that lesions in thalamic nuclei with strong connections to the inferior and superior parietal cortex, such as the ventrolateral nucleus and pulvinar might lead to optic ataxia. In comparison with aged-matched healthy subjects (n = 40, age 60.6 {+/-} 9.1 years), we identified five thalamic patients with optic ataxia, most pronounced for reaches with the contralesional hand into the contralesional space. While motor and grasping deficits and optic ataxia occurred frequently together, they did not always co-occur, and visual attention deficits could not account for the optic ataxia either. Comparing the lesion maps of patients with and without optic ataxia, the critical lesion site for optic ataxia was not restricted to one circumscribed thalamic region within the Morel atlas. Instead, it encompassed several medial and lateral nuclei within and around the internal medullary laminar (IML) complex. Interestingly, this region matches the so-called central thalamus, a functionally defined thalamic region that is considered a higher-order nucleus complex. It receives afferent inputs from the cerebellum and brainstem regions and connects to fronto-parietal regions involved in eye movement control. Taken together, our results suggest the critical importance of thalamic nuclei for the spatial transformation from eye-into body-centered coordinates.

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bioRxiv2024

SMAS: Structural MRI-Based AD Score using Bayesian VAE

This study introduces the Structural MRI-based Alzheimers Disease Score (SMAS), a novel index intended to quantify Alzheimers Disease (AD)-related morphometric patterns using a deep learning Bayesian-supervised Variational Autoencoder (Bayesian-SVAE). SMAS index was constructed using baseline structural MRI data from the DELCODE study and evaluated longitudinally in two independent cohorts: DEL-CODE (n=415) and ADNI (n=190). Our findings indicate that SMAS has strong associations with cognitive performance (DELCODE: r=-0.83; ADNI: r=-0.62), age (DEL-CODE: r=0.50; ADNI: r=0.28), hippocampal volume (DEL-CODE: r=-0.44; ADNI: r=-0.66), and total grey matter volume (DELCODE: r=-0.42; ADNI: r=-0.47), suggesting its potential as a biomarker for AD-related brain atrophy. Moreover, our longitudinal studies suggest that SMAS may be useful for early identification and tracking of AD. The model demonstrated significant predictive accuracy in distinguishing cognitively healthy individuals from those with AD (DELCODE: AUC=0.971 at baseline, 0.833 at 36 months; ADNI: AUC=0.817 at baseline, improving to 0.903 at 24 months). Notably, over a 36-month period, SMAS index outperformed existing measures such as SPARE-AD and hippocampal volume. Relevance map analysis revealed significant morphological changes in key AD-related brain regions--including the hippocampus, posterior cingulate cortex, precuneus, and lateral parietal cortex--highlighting that SMAS is a sensitive and interpretable biomarker of brain atrophy, suitable for early AD detection and longitudinal monitoring of disease progression.

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bioRxiv2024

Dysfunction of the episodic memory network in the Alzheimer's disease cascade

Alzheimers disease (AD) is a major cause of dementia and cognitive decline. Here we assessed how episodic memory circuit dysfunction, a hallmark of AD, is related to the longitudinal cascade of AD biomarkers, neurodegeneration and cognition using data from the DZNE Longitudinal Cognitive Impairment and Dementia study. This data set is unique by including over 1000 longitudinal functional magnetic resonance imaging (fMRI) measurements during episodic memory encoding. We leveraged a disease progression model (DPM) to obtain AD progression scores. Voxel-wise analyses revealed widespread loss of deactivation (hyperactivation) and activation (hypoactivation) with increasing disease stage. Hyperactivation trajectories were nonlinear and visually preceded trajectories of cognition. Overall, hyperactivation was independently associated with co-occurrence of amyloid- and tau-positivity and neurodegeneration, suggesting synaptic dysfunction and neurodegeneration as two independent drives of cognitive decline. Our results therefore provide evidence for a critical time window in which pharmacological treatments targeting the synapse may improve cognition.

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bioRxiv2024

Cerebellar Ex Vivo Magnetic Resonance Imaging at its Feasibility Limit: Up to 77-Microns Isotropic Resolution using Low-Bandwidth Balanced Steady State Free Precession (LoBa-bSSFP) Sequences and 3T Standard Equipment

BackgroundUltra-high-resolution magnetic resonance imaging of the ex vivo brain is increasingly becoming an indispensable tool for studying the morphology and potential pathology of the brain. Despite the important role of the cerebellum in nervous system functions and motor control, as well as its potential damage in neurological diseases, it remains relatively understudied compared to other brain regions. One major reason is the even finer structures. MethodsA balanced steady state free precession approach with receiver bandwidths as low as 50Hz/pixel and long repetition times of 36ms is suggested and optimized, called "LoBa-bSSFP", which enhances the signal-to-noise ratio and alleviates strain on the gradient system for the ultra-high spatial resolutions. A radiofrequency phase cycle scheme is used to reduce potential artifacts. Only 3T MRI standard equipment is utilized for acquisition and basic image reconstruction of the ex vivo brain immersed in perfluoropolyether. ResultsThe presented LoBa-bSSFP approach provides images with very good soft tissue contrast and a detailed visualization of cerebellar morphology. It enables isotropic resolutions of 98-microns for the entire cerebellum, a further refinement allows even up to 77-microns isotropic on a purely clinical MR system. The acquisitions preserved the integrity of the ex vivo cerebellum, so maintaining its connection to the cerebrum and brainstem. ConclusionsOur findings demonstrate the feasibility of employing 3T based LoBa-bSSFP for true ultra-high-resolution ex vivo imaging of the cerebellum, reaching resolutions up to 77-microns isotropic and the potential to reveal subtle microscopic abnormalities of the cerebellar cortex. LoBa-bSSFP may be superior to conventional FLASH sequences in terms of acquisition efficiency and - in some cases - even contrast.

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bioRxiv2023

Diagnostic images for mild cognitive impairment reveal biomarker status and abnormal scene processing

Research on the impairment of episodic memory in Alzheimers disease often focuses on the processes of memory rather than the content of the specific images being remembered. We recently showed that patients with mild cognitive impairment (MCI), Stage 3 of Alzheimers disease, can memorize certain images quite well, suggesting that episodic memory is not uniformly impaired. Certain images, on the other hand, could not be memorized by MCI patients and were instead diagnostic for distinguishing MCI from healthy older adults. In this study, we investigate whether poor memory for diagnostic images is related to impaired neural processing in specific brain regions due to Alzheimers biomarker pathology. 64 healthy controls and 48 MCI participants in the DELCODE dataset performed a visual scene memory task during fMRI, with CSF Alzheimers disease biomarker data collected (i.e., amyloid and tau biomarkers). We found that diagnostic images have larger behavior-biomarker correlations for total tau, phospho-tau, A{beta}42/A{beta}40, A{beta}42/phospho-tau compared to non-diagnostic images, suggesting that memory for these specific images are more affected by Alzheimers disease pathology. The fMRI data revealed an interaction effect between group membership (healthy control / MCI) and image diagnosticity (diagnostic / non-diagnostic scene images), with MCI participants having higher activation in scene processing regions (parahippocampal place area, retrosplenial cortex and occipital place area) for diagnostic images than non-diagnostic images. In contrast, healthy controls showed no differences in processing between diagnostic and non-diagnostic images. These results suggest that MCI individuals may engage in inefficiently heightened encoding activation for these diagnostic images. Our results show that special "diagnostic" images exist that can reveal amyloid and tau pathology and differences in neural activity in scene regions.

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bioRxiv2023

Cognitive Reserve Against Alzheimer's Pathology Is Linked to Brain Activity During Memory Formation

The cognitive reserve (CR) hypothesis posits that individuals can differ in how their brain function is disrupted by pathology associated with aging and neurodegeneration. Here, we tested this hypothesis in the Alzheimers disease continuum using longitudinal data from 490 participants of the DELCODE multicentric observational study. Brain function was measured using task fMRI of visual memory encoding. Using a multivariate moderation analysis we identified a CR-related activity pattern underlying successful memory encoding that moderated the detrimental effect of AD pathological load on cognitive performance. CR was mainly represented by a more pronounced expression of the task-active network encompassing the default mode network (DMN), anterior cingulate cortex (ACC) and inferior temporal regions including the fusiform gyrus. We devised personalized fMRI-based CR scores that moderated the impact of AD pathology on cognitive performance and were positively associated with years of education. Furthermore, higher CR scores were associated with slower cognitive decline over time. Our findings suggest maintenance of core cognitive circuits including the DMN and ACC as the primary mechanism of CR. Individual brain activity levels of these areas during memory encoding have prognostic value for future cognitive decline.

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bioRxiv2023

Fornix fractional anisotropy mediates the association between Mediterranean diet adherence and memory four years later in older adults without dementia

Here, we investigated whether fractional anisotropy (FA) of hippocampus-relevant white-matter tracts mediates the association between baseline Mediterranean diet adherence (MeDiAd) and verbal episodic memory over four years. Participants were healthy older adults with and without subjective cognitive decline and patients with amnestic mild cognitive impairment from the DELCODE cohort study (n = 376; age: 71.47 {+/-} 6.09 years; 48.7% female). MeDiAd and diffusion data were obtained at baseline. Verbal episodic memory was assessed at baseline and four yearly follow-ups. The associations between baseline MeDiAd and white matter, and verbal episodic memorys mean and rate of change over four years were tested with latent growth curve modeling. Baseline MeDiAd was associated with verbal episodic memory four years later (95% confidence interval, CI [0.01, 0.32]) but not with its rate of change over this period. Baseline Fornix FA mediated - and, thus, explained - that association (95% CI [0.002, 0.09]). Fornix FA may be an appropriate response biomarker of Mediterranean diet interventions on verbal memory in older adults.

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bioRxiv2021

Lifelong musical activity is associated with multi-domain cognitive and brain benefits in older adults

1AO_SCPLOWBSTRACTC_SCPLOWRegular musical activity as a highly-stimulating lifestyle activity is proposed to be protective against age-related cognitive decline and Alzheimers disease (AD). This study investigated associations between lifelong regular musical instrument playing, late-life cognitive abilities and brain morphology in older adults. We show that musical activity over the life course is associated with better global cognition, working memory, executive functions, language, and visuospatial abilities accounting for reserve proxies. Playing music is not significantly associated with gray matter volume in regions most affected by aging and AD. Selectively in the musically active participants, multi-domain cognitive abilities were enhanced with preserved gray matter volume in frontal and temporal regions. Our correlational findings suggest that playing a musical instrument may improve the recruitment of existing brain resources to facilitate late-life cognitive capacities. We propose that engaging in regular musical activity could serve as a low-threshold multimodal enrichment strategy that may promote cognitive resilience in advanced age.

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bioRxiv2021

Imaging Multiple Sclerosis Pathology at 160μm Isotropic Resolution by Human Whole-Brain Ex Vivo Magnetic Resonance Imaging at 3T

Postmortem magnetic resonance imaging (MRI) of the fixed healthy and diseased human brain facilitates spatial resolutions and image quality that is not achievable with in vivo MRI scans. Though challenging - and almost exclusively performed at 7T field strength - depicting the tissue architecture of the entire brain in fine detail is invaluable since it enables the study of neuroanatomy and uncovers important pathological features in neurological disorders. The objectives of the present work were (i) to develop a 3D isotropic ultra-high-resolution imaging approach for human whole-brain ex vivo acquisitions working on a standard clinical 3T MRI system, and (ii) to explore the sensitivity and specificity of this concept for specific pathoanatomical features of multiple sclerosis. The reconstructed images demonstrate unprecedented resolution and soft tissue contrast of the diseased human brain at 3T, thus allowing visualization of sub-millimetric lesions in the different cortical layers and in the cerebellar cortex, as well as unique cortical lesion characteristics such as the presence of incomplete / complete iron rims, and patterns of iron accumulation. Further details such as the subpial molecular layer, the line of Gennari, and some intrathalamic nuclei are also well distinguishable.

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bioRxiv2020

Two cortical representations of voice control are differentially involved in speech fluency

Recent studies have identified two distinct cortical representations of voice control in humans, the ventral and the dorsal laryngeal motor cortex. Strikingly, while persistent developmental stuttering has been linked to a white matter deficit in the ventral laryngeal motor cortex, intensive fluency shaping intervention modulated the functional connectivity of the dorsal laryngeal motor cortical network. Currently, it is unknown whether the underlying structural network organization of these two laryngeal representations is distinct or differently shaped by stuttering intervention. Using probabilistic diffusion tractography in 22 individuals who stutter and participated in a fluency shaping intervention, in 18 individuals who stutter and did not participate in the intervention, and in 28 control participants, we here compare structural networks of the dorsal laryngeal motor cortex and the ventral laryngeal motor cortex and test intervention-related white matter changes. We show (i) that all participants have weaker ventral laryngeal motor cortex connections compared to the dorsal laryngeal motor cortex network, regardless of speech fluency, (ii) connections of the ventral laryngeal motor cortex were stronger in fluent speakers, (iii) the connectivity profile of the ventral laryngeal motor cortex predicted stuttering severity, (iv) but the ventral laryngeal motor cortex network is resistant to a fluency shaping intervention. Our findings substantiate a weaker structural organization of the ventral laryngeal motor cortical network in developmental stuttering and imply that assisted recovery supports neural compensation rather than normalization. Moreover, the resulting dissociation provides evidence for functionally segregated roles of the ventral laryngeal motor cortical and dorsal laryngeal motor cortical networks.

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bioRxiv2020

Fluent speech: neural basis of sensorimotor plasticity in developmental stuttering

Fluency-shaping enhances the speech fluency of persons who stutter, yet underlying conditions and neuroplasticity-related mechanisms are largely unknown. While speech production-related brain activity in stuttering is well studied, it is unclear whether therapy repairs networks of altered sensorimotor integration, imprecise neural timing and sequencing, faulty error monitoring, or insufficient speech planning. Here, we tested the impact of one-year fluency-shaping therapy on resting-state fMRI connectivity within sets of brain regions subserving these speech functions. We analyzed resting-state data of 22 patients who participated in a fluency-shaping program, 18 patients not participating in therapy, and 28 fluent control participants, measured one year apart. Improved fluency was accompanied by an increased synchronization within the sensorimotor integration network. Specifically, two connections were strengthened; the left inferior frontal gyrus showed increased connectivity with the precentral gyrus at the representation of the left laryngeal motor cortex, and the left inferior frontal gyrus showed increased connectivity with the right superior temporal gyrus. Thus, therapy-associated neural remediation was based on a strengthened integration of the command-to-execution pathway together with an increased auditory-to-motor coupling. Since we investigated task-free brain activity, we assume that our findings are not biased to network activity involved in compensation but represent long-term focal neuroplasticity effects.

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bioRxiv2019

Intermittent theta burst stimulation at personalized targets reduces the functional connectivity of the default mode network in healthy subjects

Understanding the mechanisms by which transcranial magnetic stimulation protocols exert changes in the default mode network (DMN) is paramount to develop therapeutically more effective approaches in the future. A full session (3000 pulses) of 10 Hz repetitive transcranial magnetic stimulation (HF-rTMS) reduces the functional connectivity (FC) of the DMN and the subgenual anterior cingulate cortex but current understanding of the effects of a single session of intermittent theta burst stimulation (iTBS) on the DMN in healthy subjects is limited. To reduce the effects of inter-individual variability in functional architectures, we used a novel personalized target selection approach based on each subjects resting state fMRI for an unprecedented investigation into the effects of a single session (1800 pulses) of iTBS over the DMN in healthy controls. 26 healthy subjects participated in a double-blind, crossover, sham-controlled study. After iTBS to the personalized left dorsolateral prefrontal cortex (DLPFC) targets, we investigated the time lapse of effects in the DMN and its relationship to the harm avoidance (HA) personality trait measure (Temperament and Character Inventory/TCI). Approx. 25-30 minutes after stimulation, we observed reduced FC between the DMN and the rostral anterior cingulate cortex (rACC). About 45 minutes after stimulation the FC of rACC strongly decreased further, as did the FC of right anterior insula (rAI) with the DMN. We also report a positive correlation between the FC decrease in the rACC and the HA domain of TCI. Our results show how iTBS at personalized left-DLPFC targets reduces the FC between DMN and the rACC and rAI, regions typically described as nodes of the salience network. We find that HA scores can potentially predict iTBS response, as has been observed for HF-rTMS.

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