The extracellular matrix regulates cortical layer dynamics and cross-columnar frequency integration in the auditory cortex.

In the adult vertebrate brain, enzymatic removal of the extracellular matrix (ECM) is increasingly recognized to promote learning, memory recall, and restorative plasticity. The impact of the ECM on translaminar dynamics during cortical circuit processing is still not understood. Here, we removed the ECM in the primary auditory cortex (ACx) of adult Mongolian gerbils using local injections of hyaluronidase (HYase).

Detection of Cerebral Microbleeds With Venous Connection at 7-Tesla MRI.

Objective: Cerebral microbleeds (MBs) are a common finding in patients with cerebral small vessel disease (CSVD) and Alzheimer disease as well as in healthy elderly people, but their pathophysiology remains unclear. To investigate a possible role of veins in the development of MBs, we performed an exploratory study, assessing in vivo presence of MBs with a direct connection to a vein.

Methods: 7-Tesla (7T) MRI was conducted and MBs were counted on quantitative susceptibility mapping (QSM).

Age impairs mnemonic discrimination of objects more than scenes: A web-based, large-scale approach across the lifespan.

Recent findings suggest that the effect of aging on recognition memory is modality-dependent, affecting memory for objects and scenes differently. However, the lifespan trajectory of memory decline in these domains remains unclear. A major challenge for assessing domain-specific trajectories is the need to utilize different types of stimuli for each domain (objects and scenes).

Advances in neuroimaging to support translational medicine in dementia.

Advances in neuroimaging are ideally placed to facilitate the translation from progress made in cellular genetics and molecular biology of neurodegeneration into improved diagnosis, prevention and treatment of dementia. New positron emission tomography (PET) ligands allow one to quantify neuropathology, inflammation and metabolism in vivo safely and reliably, to examine mechanisms of human disease and support clinical trials. Developments in MRI-based imaging and neurophysiology provide complementary quantitative assays of brain function and connectivity, for the direct testing of hypotheses of human pathophysiology.

Reconciling the object and spatial processing views of the perirhinal cortex through task-relevant unitization.

The perirhinal cortex is situated on the border between sensory association cortex and the hippocampal formation. It serves an important function as a transition area between the sensory neocortex and the medial temporal lobe. While the perirhinal cortex has traditionally been associated with object coding and the "what" pathway of the temporal lobe, current evidence suggests a broader function of the perirhinal cortex in solving feature ambiguity and processing complex stimuli.

Dynamics of Cortical Degeneration Over a Decade in Huntington's Disease.

Background: Characterizing changing brain structure in neurodegeneration is fundamental to understanding long-term effects of pathology and ultimately providing therapeutic targets. It is well established that Huntington's disease (HD) gene carriers undergo progressive brain changes during the course of disease, yet the long-term trajectory of cortical atrophy is not well defined. Given that genetic therapies currently tested in HD are primarily expected to target the cortex, understanding atrophy across this region is essential.

Longitudinal Reproducibility of Neurite Orientation Dispersion and Density Imaging (NODDI) Derived Metrics in the White Matter.

Diffusion-weighted magnetic resonance imaging (DWI) is undergoing constant evolution with the ambitious goal of developing in-vivo histology of the brain. A recent methodological advancement is Neurite Orientation Dispersion and Density Imaging (NODDI), a histologically validated multi-compartment model to yield microstructural features of brain tissue such as geometric complexity and neurite packing density, which are especially useful in imaging the white matter. Since NODDI is increasingly popular in clinical research and fields such as developmental neuroscience and neuroplasticity, it is of vast importance to characterize its reproducibility (or reliability).

Multimodal MRI analysis of basal forebrain structure and function across the Alzheimer's disease spectrum.

Background: Dysfunction of the cholinergic basal forebrain (cBF) is associated with cognitive decline in Alzheimer's disease (AD). Multimodal MRI allows for the investigation of cBF changes in-vivo. In this study we assessed alterations in cBF functional connectivity (FC), mean diffusivity (MD), and volume across the spectrum of AD.

Association between composite scores of domain-specific cognitive functions and regional patterns of atrophy and functional connectivity in the Alzheimer's disease spectrum.

Background: Cognitive decline has been found to be associated with gray matter atrophy and disruption of functional neural networks in Alzheimer's disease (AD) in structural and functional imaging (fMRI) studies. Most previous studies have used single test scores of cognitive performance among monocentric cohorts. However, cognitive domain composite scores could be more reliable than single test scores due to the reduction of measurement error.

Abnormal Regional and Global Connectivity Measures in Subjective Cognitive Decline Depending on Cerebral Amyloid Status.

Background: Amyloid-β accumulation was found to alter precuneus-based functional connectivity (FC) in mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia, but its impact is less clear in subjective cognitive decline (SCD), which in combination with AD pathologic change is theorized to correspond to stage 2 of the Alzheimer's continuum in the 2018 NIA-AA research framework.

Objective: This study addresses how amyloid pathology relates to resting-state fMRI FC in SCD, especially focusing on the precuneus.

Methods: From the DELCODE cohort, two groups of 24 age- and gender-matched amyloid-positive (SCDAβ+) and amyloidnegative SCD (SCDβ-) patients were selected according to visual [18F]-Florbetaben (FBB) PET readings, and studied with resting-state fMRI.

MRI phenotyping of underlying cerebral small vessel disease in mixed hemorrhage patients.

Objective: To investigate underlying cerebral small vessel disease (CSVD) in patients with mixed cerebral hemorrhages patterns and phenotype them according to the contribution of the two most common sporadic CSVD subtypes: cerebral amyloid angiopathy (CAA) vs. hypertensive arteriopathy (HA).

Methods: Brain MRIs of patients with intracerebral hemorrhages (ICHs) and/or cerebral microbleeds (CMBs) were assessed for the full spectrum of CSVD markers using validated scales: ICHs, CMBs, cortical superficial siderosis (cSS), white matter hyperintensities, MRI-visible perivascular spaces (PVS).

Neuropsychiatric symptoms in at-risk groups for AD dementia and their association with worry and AD biomarkers-results from the DELCODE study.

Background: Early identification of individuals at risk of dementia is mandatory to implement prevention strategies and design clinical trials that target early disease stages. Subjective cognitive decline (SCD) and neuropsychiatric symptoms (NPS) have been proposed as potential markers for early manifestation of Alzheimer's disease (AD). We aimed to investigate the frequency of NPS in SCD, in other at-risk groups, in healthy controls (CO), and in AD patients, and to test the association of NPS with AD biomarkers, with a particular focus on cognitively unimpaired participants with or without SCD-related worries.

Moral Cognition About Harm in Anxiety Disorders: The Importance of Experienced Emotion.

Recent work has shown that emotional arousal influences decision-making in sacrificial moral dilemmas, with heightened levels of arousal associated with increased aversion to committing moral transgressions to maximize utilitarian outcomes. Patients with anxiety disorders experience pathologically heightened states of arousal and thus may be expected to exhibit reduced utilitarian responding on such dilemmas. Extant evidence has been mixed, however, regarding whether anxious patients differ in their moral decisions from controls, and no study has conducted a careful examination of emotions experienced during decision-making.

Learning in anticipation of reward and punishment: perspectives across the human lifespan.

Learning to act to receive reward and to withhold to avoid punishment has been found to be easier than learning the opposite contingencies in young adults. To what extent this type of behavioral adaptation might develop during childhood and adolescence and differ during aging remains unclear. We therefore tested 247 healthy individuals across the human life span (7-80 years) with an orthogonalized valenced go/no-go learning task.

Small vessel disease more than Alzheimer's disease determines diffusion MRI alterations in memory clinic patients.

Introduction: Microstructural alterations as assessed by diffusion tensor imaging (DTI) are key findings in both Alzheimer's disease (AD) and small vessel disease (SVD). We determined the contribution of each of these conditions to diffusion alterations.

Methods: We studied six samples (N = 365 participants) covering the spectrum of AD and SVD, including genetically defined samples.

Disynaptic cerebrocerebellar pathways originating from multiple functionally distinct cortical areas.

The cerebral cortex and cerebellum both play important roles in sensorimotor processing, however, precise connections between these major brain structures remain elusive. Using anterograde mono-trans-synaptic tracing, we elucidate cerebrocerebellar pathways originating from primary motor, sensory, and association cortex. We confirm a highly organized topography of corticopontine projections in mice; however, we found no corticopontine projections originating from primary auditory cortex and detail several potential extra-pontine cerebrocerebellar pathways.

Forecasting memory function in aging: pattern-completion ability and hippocampal activity relate to visuospatial functioning over 25 years.

Heterogeneity in episodic memory functioning in aging was assessed with a pattern-completion functional magnetic resonance imaging task that required reactivation of well-consolidated face-name memory traces from fragmented (partial) or morphed (noisy) face cues. About half of the examined individuals (N = 101) showed impaired (chance) performance on fragmented faces despite intact performance on complete and morphed faces, and they did not show a pattern-completion response in hippocampus or the examined subfields (CA1, CA23, DGCA4). This apparent pattern-completion deficit could not be explained by differential hippocampal atrophy.

Minor neuropsychological deficits in patients with subjective cognitive decline.

Objective: To determine the nature and extent of minor neuropsychological deficits in patients with subjective cognitive decline (SCD) and their association with CSF biomarkers of Alzheimer disease (AD).

Method: We analyzed data from n = 449 cognitively normal participants (n = 209 healthy controls, n = 240 patients with SCD) from an interim data release of the German Center for Neurodegenerative Diseases Longitudinal Cognitive Impairment and Dementia Study (DELCODE). An extensive neuropsychological test battery was applied at baseline for which we established a latent, 5 cognitive domain factor structure comprising learning and memory, executive functions, language abilities, working memory, and visuospatial functions.

Neurocan genome-wide psychiatric risk variant affects explicit memory performance and hippocampal function in healthy humans.

Alterations of the brain extracellular matrix (ECM) can perturb the structure and function of brain networks like the hippocampus, a key region in human memory that is commonly affected in psychiatric disorders. Here, we investigated the potential effects of a genome-wide psychiatric risk variant in the NCAN gene encoding the ECM proteoglycan neurocan (rs1064395) on memory performance, hippocampal function and cortical morphology in young, healthy volunteers. We assessed verbal memory performance in two cohorts (N = 572, 302) and found reduced recall performance in risk allele (A) carriers across both cohorts.

Altered subcortical emotional salience processing differentiates Parkinson's patients with and without psychotic symptoms.

Objective: Current research does not provide a clear explanation for why some patients with Parkinson's Disease (PD) develop psychotic symptoms. The 'aberrant salience hypothesis' of psychosis has been influential and proposes that dopaminergic dysregulation leads to inappropriate attribution of salience to irrelevant/non-informative stimuli, facilitating the formation of hallucinations and delusions. The aim of this study is to investigate whether non-motivational salience is altered in PD patients and possibly linked to the development of psychotic symptoms.

Correction to: Relevance of biomarkers across different neurodegenerative diseases.

An amendment to this paper has been published and can be accessed via the original article.

Dietary patterns are related to cognitive functioning in elderly enriched with individuals at increased risk for Alzheimer's disease.

Purpose: To investigate cross-sectional associations between dietary patterns and cognitive functioning in elderly free of dementia.

Methods: Data of 389 participants from the German DELCODE study (52% female, 69 ± 6 years, mean Mini Mental State Score 29 ± 1) were included. The sample was enriched with elderly at increased risk for Alzheimer's disease (AD) by including participants with subjective cognitive decline, mild cognitive impairment (MCI) and siblings of AD patients.

Childhood socio-economic disadvantage predicts reduced myelin growth across adolescence and young adulthood.

Socio-economic disadvantage increases exposure to life stressors. Animal research suggests early life stressors impact later neurodevelopment, including myelin developmental growth. To determine how early life disadvantage may affect myelin growth in adolescence and young adulthood, we analysed data from an accelerated longitudinal neuroimaging study measuring magnetisation transfer (MT), a myelin-sensitive marker, in 288 participants (149 female) between 14 and 25 years of age at baseline.

Relevance of biomarkers across different neurodegenerative diseases.

Background: The panel of fluid- and imaging-based biomarkers available for neurodegenerative disease research is growing and has the potential to close important gaps in research and the clinic. With this growth and increasing use, appropriate implementation and interpretation are paramount. Various biomarkers feature nuanced differences in strengths, limitations, and biases that must be considered when investigating disease etiology and clinical utility.