Biology subjects

Bunzeck, N.

Publications and source records attributed to Bunzeck, N..

6 recordsLinked to original sources

bioRxiv2023

Structural Degeneration of the Nucleus basalis of Meynert in Mild Cognitive Impairment and Alzheimer's Disease - Evidence from an MRI-based Meta-Analysis

Recent models of Alzheimers Disease (AD) suggest that neuropathological changes of the medial temporal lobe, especially entorhinal cortex, are preceded by degenerations of the cholinergic Nucleus basalis of Meynert (NbM). Evidence from imaging studies in humans, however, is limited. Therefore, we performed an activation-likelihood estimation meta-analysis on whole brain voxel-based morphometry (VBM) MRI data from 54 experiments and 2581 subjects in total. It revealed, compared to healthy older controls, reduced gray matter in the bilateral NbM in AD, but only limited evidence for such an effect in patients with mild cognitive impairment (MCI), which typically precedes AD. Both patient groups showed less gray matter in the amygdala and hippocampus, with hints towards more pronounced amygdala effects in AD. We discuss our findings in the context of studies that highlight the importance of the cholinergic basal forebrain in learning and memory throughout the life span, and conclude that they are partly compatible with pathological staging models suggesting initial and pronounced structural degenerations within the NbM in the progression of AD.

neuroscience↗

bioRxiv2023

Basal forebrain activity predicts functional degeneration in the entorhinal cortex and decreases with Alzheimer's Disease progression

BACKGROUND AND OBJECTIVESRecent models of Alzheimers Disease (AD) suggest the nucleus basalis of Meynert (NbM) as the origin of structural degeneration followed by the entorhinal cortex (EC). However, the functional properties of NbM and EC regarding amyloid-{beta} and hyperphosphorylated tau remain unclear. METHODSWe analyzed resting-state (rs)fMRI data with CSF assays from the Alzheimers Disease Neuroimaging Initiative (ADNI, n=71) at baseline and two years later. RESULTSAt baseline, local activity, as quantified by fractional amplitude of low-frequency fluctuations (fALFF), differentiated between normal and abnormal CSF groups in the NbM but not EC. Further, NbM activity linearly decreased as a function of CSF ratio, resembling the disease status. Finally, NbM activity predicted the annual percentage signal change in EC, but not the reverse, independent from CSF ratio. DISCUSSIONOur findings give novel insights into the pathogenesis of AD by showing that local activity in NbM is affected by proteinopathology and predicts functional degeneration within the EC.

neuroscience↗

bioRxiv2022

Contextual incongruency triggers memory reinstatement and the disruption of neural stability

Schemas, or internal representation models of the environment, are thought to be central in organising our everyday life behaviour by giving stability and predictiveness to the structure of the world. However, when an element from an unfolding event mismatches the schema-derived expectations, the coherent narrative is interrupted and an update to the current event model representation is required. Here, we asked whether the perceived incongruence of an item from an unfolding event and its impact on memory relied on the disruption of neural stability patterns preceded by the neural reactivation of the memory representations of the just-encoded event. Our study includes data from 3 different experiments whereby participants encoded images of target objects preceded by trial-unique sequences of events depicting daily routine. We found that neural stability patterns gradually increased throughout the ongoing exposure to a schema-consistent episodic narrative and that the brain stability pattern was interrupted when the encoding of an object of the event was lowly congruent within the ongoing schema representation. We found that the decrease in neural stability for low-congruence items was best seen at [~]1000 ms from object encoding onset when compared to high-congruence items and that this effect was preceded by an enhanced N400 ERP and an increased degree of neural reactivation of the just-encoded episode for low-congruence items. Current results offer new insights into the neural mechanisms and their temporal orchestration that are engaged during online encoding of schema-consistent episodic narratives and the detection of incongruencies.

neuroscience↗

bioRxiv2018

Age-related impairment of semantic integration into long-term memory is related to theta-alpha and low beta oscillations

Long-term memory can improve when incoming information is congruent with known semantic information. This so-called congruence effect has widely been shown in younger adults but age-related changes and neural mechanisms remain unclear. Here, congruence improved recognition memory in younger and older adults (i.e. congruency effect), but - importantly - this effect decreased with age. Electroencephalography data show that, in both groups, congruence led to widespread differences in event-related potentials (ERPs) and alpha-beta oscillations (8-30 Hz), known to support semantic processing. Importantly, these ERP differences predicted increases in memory performance, especially for congruent items. Finally, age-related differences in memory were accompanied by a positive ERP and later decrease in theta-alpha (5-13 Hz) during encoding, which were greater in the younger group. Together, although semantic congruence generally increases long-term memory, the effect is less pronounced in the elderly. At the neural level, theta-alpha oscillations, previously linked to memory and attentional processes, provide a mechanistic explanation for such an age-related effect.

neuroscience↗

bioRxiv2018

Dopamine is a double-edged sword: Enhancing memory retrieval performance at the expense of metacognition

While memory encoding and consolidation processes have been linked with dopaminergic signaling for a long time, the role of dopamine in episodic memory retrieval remained mostly unexplored. Based on previous observations of striatal activity during memory retrieval, we used pharmacological fMRI to investigate the effects of dopamine on retrieval performance and metacognitive memory confidence in healthy humans. Dopaminergic modulation by the D2 antagonist haloperidol administered acutely during the retrieval phase improved recognition accuracy of previously learned pictures significantly and was associated with increased activity in the SN/VTA, locus coeruleus, hippocampus and amygdala during retrieval. In contrast, confidence for new-decisions was impaired by unsystematically increased activity of the striatum across confidence levels and restricted range of responsiveness in frontostriatal networks under haloperidol. These findings offer new insights into the mechanisms underlying memory retrieval and metacognition and provide a broader perspective on the presence of memory problems in dopamine-related diseases and the treatment of memory disorders.

neuroscience↗

bioRxiv2018

Altered cingulate and substantia nigra/ventral tegmental activation to novelty and emotional salience in antipsychotic naive first episode psychosis patients

Abnormal salience processing has been suggested to contribute to the formation of positive psychotic symptoms in schizophrenia and related conditions. Previous research utilising reward learning or anticipation paradigms has demonstrated cortical and subcortical abnormalities in people with psychosis, specifically in the prefrontal cortex, the dopaminergic midbrain and the striatum. In these paradigms, reward prediction errors attribute motivational salience to stimuli. However, little is known about possible abnormalities across different forms of salience processing in psychosis patients, and whether any such abnormalities involve the dopaminergic midbrain. The aim of our study was, therefore, to investigate possible alterations in psychosis in neural activity in response to various forms of salience: novelty, negative emotion, targetness (task-driven salience) and rareness/deviance. We studied 14 antipsychotic naive participants with first episode psychosis, and 37 healthy volunteers. During fMRI scanning, participants performed a visual oddball task containing these four forms of salience. Psychosis patients showed abnormally reduced signalling in the substantia nigra/ventral tegmental area (SN/VTA) for novelty, negative emotional salience and targetness; reduced striatal and occipital (lingual gyrus) signalling to novelty and negative emotional salience, reduced signalling in the amygdala, anterior cingulate cortex and parahippocamal gyrus to negative emotional salience, and reduced cerebellar signalling to novelty and negative emotional salience. Our results indicate alterations of several forms of salience processing in patients with psychosis in the midbrain SN/VTA, with additional subcortical and cortical regions also showing alterations in salience signalling, the exact pattern of alterations depending on the form of salience in question.

neuroscience↗