Locus coeruleus imaging as a biomarker for noradrenergic dysfunction in neurodegenerative diseases.

Pathological alterations to the locus coeruleus, the major source of noradrenaline in the brain, are histologically evident in early stages of neurodegenerative diseases. Novel MRI approaches now provide an opportunity to quantify structural features of the locus coeruleus in vivo during disease progression. In combination with neuropathological biomarkers, in vivo locus coeruleus imaging could help to understand the contribution of locus coeruleus neurodegeneration to clinical and pathological manifestations in Alzheimer's disease, atypical neurodegenerative dementias and Parkinson's disease.

Structural integrity in subjective cognitive decline, mild cognitive impairment and Alzheimer's disease based on multicenter diffusion tensor imaging.

Introduction: Subjective cognitive decline (SCD) can represent a preclinical stage of Alzheimer's disease. Diffusion tensor imaging (DTI) could aid an early diagnosis, yet only few monocentric DTI studies in SCD have been conducted, reporting heterogeneous results. We investigated microstructural changes in SCD in a larger, multicentric cohort.

Alzheimer's pathology targets distinct memory networks in the ageing brain.

Alzheimer's disease researchers have been intrigued by the selective regional vulnerability of the brain to amyloid-β plaques and tau neurofibrillary tangles. Post-mortem studies indicate that in ageing and Alzheimer's disease tau tangles deposit early in the transentorhinal cortex, a region located in the anterior-temporal lobe that is critical for object memory. In contrast, amyloid-β pathology seems to target a posterior-medial network that subserves spatial memory.

β-adrenergic modulation of discrimination learning and memory in the auditory cortex.

Despite vast literature on catecholaminergic neuromodulation of auditory cortex functioning in general, knowledge about its role for long-term memory formation is scarce. Our previous pharmacological studies on cortex-dependent frequency-modulated tone-sweep discrimination learning of Mongolian gerbils showed that auditory-cortical D -dopamine receptor activity facilitates memory consolidation and anterograde memory formation. Considering overlapping functions of D -dopamine receptors and β-adrenoceptors, we hypothesised a role of β-adrenergic signalling in the auditory cortex for sweep discrimination learning and memory.

Compulsivity and impulsivity traits linked to attenuated developmental frontostriatal myelination trajectories.

The transition from adolescence to adulthood is a period when ongoing brain development coincides with a substantially increased risk of psychiatric disorders. The developmental brain changes accounting for this emergent psychiatric symptomatology remain obscure. Capitalizing on a unique longitudinal dataset that includes in vivo myelin-sensitive magnetization transfer (MT) MRI scans, we show that this developmental period is characterized by brain-wide growth in MT trajectories within both gray matter and adjacent juxtacortical white matter.

Serotonin regulates mitochondrial biogenesis and function in rodent cortical neurons via the 5-HT receptor and SIRT1-PGC-1α axis.

Mitochondria in neurons, in addition to their primary role in bioenergetics, also contribute to specialized functions, including regulation of synaptic transmission, Ca homeostasis, neuronal excitability, and stress adaptation. However, the factors that influence mitochondrial biogenesis and function in neurons remain poorly elucidated. Here, we identify an important role for serotonin (5-HT) as a regulator of mitochondrial biogenesis and function in rodent cortical neurons, via a 5-HT receptor-mediated recruitment of the SIRT1-PGC-1α axis, which is relevant to the neuroprotective action of 5-HT.

Locus coeruleus MRI contrast is reduced in Alzheimer's disease dementia and correlates with CSF Aβ levels.

Introduction: This study aimed to assess how interindividual differences in locus coeruleus (LC) magnetic resonance imaging (MRI) contrast relate to cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD).

Methods: LC MRI contrast was quantified in 73 individuals from the DZNE Longitudinal Cognitive Impairment and Dementia Study (DELCODE) study comprising 25 healthy elderly adults and 21 individuals with subjective cognitive decline, 16 with mild cognitive impairment, and 11 participants with AD dementia using 3D T-weighted fast low-angle shot (FLASH) imaging (0.75 mm isotropic resolution).

Serotonergic, Dopaminergic, and Noradrenergic Modulation of Erotic Stimulus Processing in the Male Human Brain.

Human sexual behavior is mediated by a complex interplay of cerebral and spinal centers, as well as hormonal, peripheral, and autonomic functions. Neuroimaging studies identified central neural signatures of human sexual responses comprising neural emotional, motivational, autonomic, and cognitive components. However, empirical evidence regarding the neuromodulation of these neural signatures of human sexual responses was scarce for decades.

CSF total tau levels are associated with hippocampal novelty irrespective of hippocampal volume.

Introduction: We examined the association between cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease, neural novelty responses, and brain volume in predementia old age.

Methods: We conducted a cross-sectional analysis of the observational, multicentric DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) study. Seventy-six participants completed task functional magnetic resonance imaging and provided CSF (40 cognitively unimpaired, 21 experiencing subjective cognitive decline, and 15 with mild cognitive impairment).

High-fidelity multimode fibre-based endoscopy for deep brain in vivo imaging.

Progress in neuroscience relies on new techniques for investigating the complex dynamics of neuronal networks. An ongoing challenge is to achieve minimally invasive and high-resolution observations of neuronal activity in vivo inside deep brain areas. Recently introduced methods for holographic control of light propagation in complex media enable the use of a hair-thin multimode optical fibre as an ultranarrow imaging tool.

In vivo visualization of age-related differences in the locus coeruleus.

The locus coeruleus (LC), the major origin of noradrenergic modulation of the central nervous system, may play an important role in neuropsychiatric disorders including Parkinson's disease and Alzheimer's disease. The pattern of age-related change of the LC across the life span is unclear. We obtained normalized, mean LC signal intensity values, that is, contrast ratios (CRs), from magnetization transfer-weighted images to investigate the relationship between LC CR and age in cognitively normal healthy adults (N = 605, age range 18-88 years).

Older adults fail to form stable task representations during model-based reversal inference.

Older adults struggle in dealing with changeable and uncertain environments across several cognitive domains. This has been attributed to difficulties in forming adequate task representations that help navigate uncertain environments. Here, we investigate how, in older adults, inadequate task representations impact on model-based reversal learning.

Daily Intermittent Normobaric Hypoxia Over 2 Weeks Reduces BDNF Plasma Levels in Young Adults - A Randomized Controlled Feasibility Study.

The results from animal and human research indicate that acute intermittent hypoxia can enhance brain-derived neurotrophic factor (BDNF) plasma levels and gene expression. As BDNF is known to promote the differentiation of new neurons and the formation of synapses, it has been proposed to mediate adult neuroplasticity. Thus, the present study aimed to analyze the long-term effects of daily intermittent exposure to normobaric hypoxia (simulating high altitude exposure at approximately 4000-5000 m) over 2 weeks on BDNF levels in young adults.

Smaller medial temporal lobe volumes in individuals with subjective cognitive decline and biomarker evidence of Alzheimer's disease-Data from three memory clinic studies.

Introduction: Previous studies showed associations of brain volume differences and biomarker evidence for Alzheimer's disease (AD) in subjective cognitive decline (SCD). The consistency of this finding across SCD studies has not been investigated.

Methods: We studied gray matter volume differences between SCD subjects with and without cerebrospinal fluid biomarker evidence for AD across three European memory clinic samples (German Center for Neurodegenerative Diseases Longitudinal Cognitive Impairment and Dementia study, Amsterdam, Barcelona).

Memory Image Completion: Establishing a task to behaviorally assess pattern completion in humans.

For memory retrieval, pattern completion is a crucial process that restores memories from partial or degraded cues. Neurocognitive aging models suggest that the aged memory system is biased toward pattern completion, resulting in a behavioral preference for retrieval over encoding of memories. Here, we built on our previously developed behavioral recognition memory paradigm-the Memory Image Completion (MIC) task-a task to specifically target pattern completion.

Brain responses to different types of salience in antipsychotic naïve first episode psychosis: An fMRI study.

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.

Big-Loop Recurrence within the Hippocampal System Supports Integration of Information across Episodes.

Recent evidence challenges the widely held view that the hippocampus is specialized for episodic memory, by demonstrating that it also underpins the integration of information across experiences. Contemporary computational theories propose that these two contrasting functions can be accomplished by big-loop recurrence, whereby the output of the system is recirculated back into the hippocampus. We use ultra-high-resolution fMRI to provide support for this hypothesis, by showing that retrieved information is presented as a new input on the superficial entorhinal cortex-driven by functional connectivity between the deep and superficial entorhinal layers.

The Impact of Visual Cues, Reward, and Motor Feedback on the Representation of Behaviorally Relevant Spatial Locations in Primary Visual Cortex.

The integration of visual stimuli and motor feedback is critical for successful visually guided navigation. These signals have been shown to shape neuronal activity in the primary visual cortex (V1), in an experience-dependent manner. Here, we examined whether visual, reward, and self-motion-related inputs are integrated in order to encode behaviorally relevant locations in V1 neurons.

Progressive Compromise of Nouns and Action Verbs in Posterior Cortical Atrophy.

Processing of nouns and action verbs can be differentially compromised following lesions to posterior and anterior/motor brain regions, respectively. However, little is known about how these deficits in the course of neurodegeneration. To address this issue, we assessed productive lexical skills in a patient with posterior cortical atrophy (PCA) at two different stages of his pathology.

Differential Noradrenergic Modulation of Monetary Reward and Visual Erotic Stimulus Processing.

We recently investigated the effects of the noradrenergic antidepressant reboxetine and the antipsychotic amisulpride compared to placebo on neural correlates of primary reinforcers by visual erotic stimulation in healthy subjects. Whereas, amisulpride left subjective sexual functions and corresponding neural activations unimpaired, attenuated neural activations were observed under reboxetine within the nucleus accumbens (Nacc) along with diminished behavioral sexual functioning. However, a global dampening of the reward system under reboxetine seemed not intuitive considering the complementary role of the noradrenergic to the dopamine system in reward-related learning mediated by prediction error processing.

Action Semantics at the Bottom of the Brain: Insights From Dysplastic Cerebellar Gangliocytoma.

Recent embodied cognition research shows that access to action verbs in shallow-processing tasks becomes selectively compromised upon atrophy of the cerebellum, a critical motor region. Here we assessed whether cerebellar damage also disturbs explicit semantic processing of action pictures and its integration with ongoing motor responses. We evaluated a cognitively preserved 33-year-old man with severe dysplastic cerebellar gangliocytoma (Lhermitte-Duclos disease), encompassing most of the right cerebellum and the posterior part of the left cerebellum.

Scale-specific analysis of fMRI data on the irregular cortical surface.

To fully characterize the activity patterns on the cerebral cortex as measured with fMRI, the spatial scale of the patterns must be ascertained. Here we address this problem by constructing steerable bandpass filters on the discrete, irregular cortical mesh, using an improved Gaussian smoothing in combination with differential operators of directional derivatives. We demonstrate the utility of the algorithm in two ways.

Optimization of interneuron function by direct coupling of cell migration and axonal targeting.

Neural circuit assembly relies on the precise synchronization of developmental processes, such as cell migration and axon targeting, but the cell-autonomous mechanisms coordinating these events remain largely unknown. Here we found that different classes of interneurons use distinct routes of migration to reach the embryonic cerebral cortex. Somatostatin-expressing interneurons that migrate through the marginal zone develop into Martinotti cells, one of the most distinctive classes of cortical interneurons.

Multicenter Resting State Functional Connectivity in Prodromal and Dementia Stages of Alzheimer's Disease.

Background: Alterations of intrinsic networks from resting state fMRI (rs-fMRI) have been suggested as functional biomarkers of Alzheimer's disease (AD).

Objective: To determine the diagnostic accuracy of multicenter rs-fMRI for prodromal and preclinical stages of AD.

Methods: We determined rs-fMRI functional connectivity based on Pearson's correlation coefficients and amplitude of low-frequency fluctuation in people with subjective cognitive decline, people with mild cognitive impairment, and people with AD dementia compared with healthy controls.