Changes in task‐evoked pupil dilation as a marker of locus coeruleus function in healthy aging and Alzheimer’s disease.

Background: Locus coeruleus (LC) is a primary source of noradrenalin in the brain and plays a complex role in human behavior. In healthy aging and Alzheimer’s disease (AD), LC cell loss has been linked to a decline in overall cognitive function. This study aimed to explore age‐ and AD‐related differences in a proxy measure of LC activity.

Brainstem and midbrain structures involved in memory encoding in healthy aging and mild cognitive impairment, a 3T task‐fMRI study.

Background: Memory decline, which is especially prevalent in Alzheimer’s disease (AD), has been studied via fMRI, primarily focusing on the prefrontal cortex and hippocampus. However, emerging evidence suggests that the brainstem, alongside various midbrain regions, is an initial target for pathological processes like hyperphosphorylated TAU protein accumulation. Among these, the locus coeruleus, a noradrenergic nucleus in the pons, projects to critical midbrain areas supporting memory encoding.

Quantitative multi‐parameter mapping of locus coeruleus in aging and Alzheimer’s disease.

Background: The Locus Coeruleus (LC) is prominently affected by neuronal loss in the earliest stages of Alzheimer’s disease (AD). Assessing LC integrity can serve as an important early biomarker for assessing AD progression. Neuromelanin (NM) accumulates in LC neurons and NM imaging has therefore been proposed as a means of imaging the LC.

Functional locus coeruleus imaging to investigate an ageing noradrenergic system.

The locus coeruleus (LC), our main source of norepinephrine (NE) in the brain, declines with age and is a potential epicentre of protein pathologies in neurodegenerative diseases (ND). In vivo measurements of LC integrity and function are potentially important biomarkers for healthy ageing and early ND onset. In the present study, high-resolution functional MRI (fMRI), a reversal reinforcement learning task, and dedicated post-processing approaches were used to visualise age differences in LC function (N = 50).

Insights and improvements in correspondence between axonal volume fraction measured with diffusion-weighted MRI and electron microscopy.

Biophysical diffusion-weighted imaging (DWI) models are increasingly used in neuroscience to estimate the axonal water fraction ( ), which in turn is key for noninvasive estimation of the axonal volume fraction ( ). These models require thorough validation by comparison with a reference method, for example, electron microscopy (EM). While EM studies often neglect the unmyelinated axons and solely report the fraction of myelinated axons, in DWI both myelinated and unmyelinated axons contribute to the DWI signal.

Expectation Cues and False Percepts Generate Stimulus-Specific Activity in Distinct Layers of the Early Visual Cortex.

Perception has been proposed to result from the integration of feedforward sensory signals with internally generated feedback signals. Feedback signals are believed to play an important role in driving false percepts, that is, seeing things that are not actually there. Feedforward and feedback influences on perception can be studied using layer-specific fMRI, which we used here to interrogate neural activity underlying high-confidence false percepts while healthy human participants ( = 25, male and female) performed a perceptual orientation discrimination task.

Fiber-orientation independent component of R* obtained from single-orientation MRI measurements in simulations and a post-mortem human optic chiasm.

The effective transverse relaxation rate (R*) is sensitive to the microstructure of the human brain like the g-ratio which characterises the relative myelination of axons. However, the fibre-orientation dependence of R* degrades its reproducibility and any microstructural derivative measure. To estimate its orientation-independent part (R*) from single multi-echo gradient-recalled-echo (meGRE) measurements at arbitrary orientations, a second-order polynomial in time model (hereafter M2) can be used.

Statistical analyses of motion-corrupted MRI relaxometry data computed from multiple scans.

Background: Consistent noise variance across data points (i.e. homoscedasticity) is required to ensure the validity of statistical analyses of MRI data conducted using linear regression methods.

Mitigating susceptibility-induced distortions in high-resolution 3DEPI fMRI at 7T.

Geometric distortion is a major limiting factor for spatial specificity in high-resolution fMRI using EPI readouts and is exacerbated at higher field strengths due to increased B field inhomogeneity. Prominent correction schemes are based on B field-mapping or acquiring reverse phase-encoded (reversed-PE) data. However, to date, comparisons of these techniques in the context of fMRI have only been performed on 2DEPI data, either at lower field or lower resolution.

Coherent, time-shifted patterns of microstructural plasticity during motor-skill learning.

Motor skill learning relies on neural plasticity in the motor and limbic systems. However, the spatial and temporal characteristics of these changes-and their microstructural underpinnings-remain unclear. Eighteen healthy males received 1 h of training in a computer-based motion game, 4 times a week, for 4 consecutive weeks, while 14 untrained participants underwent scanning only.

Transcranial direct current stimulation with functional magnetic resonance imaging: a detailed validation and operational guide.

: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique used to modulate human brain and behavioural function in both research and clinical interventions. The combination of functional magnetic resonance imaging (fMRI) with tDCS enables researchers to directly test causal contributions of stimulated brain regions, answering questions about the physiology and neural mechanisms underlying behaviour. Despite the promise of the technique, advances have been hampered by technical challenges and methodological variability between studies, confounding comparability/replicability.

In vivo multi-parameter mapping of the habenula using MRI.

The habenula is a small, epithalamic brain structure situated between the mediodorsal thalamus and the third ventricle. It plays an important role in the reward circuitry of the brain and is implicated in psychiatric conditions, such as depression. The importance of the habenula for human cognition and mental health make it a key structure of interest for neuroimaging studies.

Neuroimaging in Leber Hereditary Optic Neuropathy: State-of-the-art and future prospects.

Leber Hereditary Optic Neuropathy (LHON) is an inherited mitochondrial retinal disease that causes the degeneration of retinal ganglion cells and leads to drastic loss of visual function. In the last decades, there has been a growing interest in using Magnetic Resonance Imaging (MRI) to better understand mechanisms of LHON beyond the retina. This is partially due to the emergence of gene-therapies for retinal diseases, and the accompanying expanded need for reliably quantifying and monitoring visual processing and treatment efficiency in patient populations.

Conduction velocity along a key white matter tract is associated with autobiographical memory recall ability.

Conduction velocity is the speed at which electrical signals travel along axons and is a crucial determinant of neural communication. Inferences about conduction velocity can now be made in vivo in humans using a measure called the magnetic resonance (MR) g-ratio. This is the ratio of the inner axon diameter relative to that of the axon plus the myelin sheath that encases it.

Mitigating the impact of flip angle and orientation dependence in single compartment R2* estimates via 2-pool modeling.

Purpose: The effective transverse relaxation rate ( ) is influenced by biological features that make it a useful means of probing brain microstructure. However, confounding factors such as dependence on flip angle (α) and fiber orientation with respect to the main field ( ) complicate interpretation. The α- and -dependence stem from the existence of multiple sub-voxel micro-environments (e.

Error quantification in multi-parameter mapping facilitates robust estimation and enhanced group level sensitivity.

Multi-Parameter Mapping (MPM) is a comprehensive quantitative neuroimaging protocol that enables estimation of four physical parameters (longitudinal and effective transverse relaxation rates R and R, proton density PD, and magnetization transfer saturation MT) that are sensitive to microstructural tissue properties such as iron and myelin content. Their capability to reveal microstructural brain differences, however, is tightly bound to controlling random noise and artefacts (e.g.

Universal pulses for homogeneous excitation using single channel coils.

Purpose: Universal Pulses (UPs) are excitation pulses that reduce the flip angle inhomogeneity in high field MRI systems without subject-specific optimization, originally developed for parallel transmit (PTX) systems at 7 T. We investigated the potential benefits of UPs for single channel (SC) transmit systems at 3 T, which are widely used for clinical and research imaging, and for which flip angle inhomogeneity can still be problematic.

Methods: SC-UPs were designed using a spiral nonselective k-space trajectory for brain imaging at 3 T using transmit field maps (B) and off-resonance maps (B) acquired on two different scanner types: a 'standard' single channel transmit system and a system with a PTX body coil.

Combining navigator and optical prospective motion correction for high-quality 500 μm resolution quantitative multi-parameter mapping at 7T.

Purpose: High-resolution quantitative multi-parameter mapping shows promise for non-invasively characterizing human brain microstructure but is limited by physiological artifacts. We implemented corrections for rigid head movement and respiration-related B0-fluctuations and evaluated them in healthy volunteers and dementia patients.

Methods: Camera-based optical prospective motion correction (PMC) and FID navigator correction were implemented in a gradient and RF-spoiled multi-echo 3D gradient echo sequence for mapping proton density (PD), longitudinal relaxation rate (R1) and effective transverse relaxation rate (R2*).

Correcting inter-scan motion artifacts in quantitative R mapping at 7T.

Purpose: Inter-scan motion is a substantial source of error in estimation methods based on multiple volumes, for example, variable flip angle (VFA), and can be expected to increase at 7T where fields are more inhomogeneous. The established correction scheme does not translate to 7T since it requires a body coil reference. Here we introduce two alternatives that outperform the established method.

Restoring statistical validity in group analyses of motion-corrupted MRI data.

Motion during the acquisition of magnetic resonance imaging (MRI) data degrades image quality, hindering our capacity to characterise disease in patient populations. Quality control procedures allow the exclusion of the most affected images from analysis. However, the criterion for exclusion is difficult to determine objectively and exclusion can lead to a suboptimal compromise between image quality and sample size.

Reassessing associations between white matter and behaviour with multimodal microstructural imaging.

Several studies have established specific relationships between White Matter (WM) and behaviour. However, these studies have typically focussed on fractional anisotropy (FA), a neuroimaging metric that is sensitive to multiple tissue properties, making it difficult to identify what biological aspects of WM may drive such relationships. Here, we carry out a pre-registered assessment of WM-behaviour relationships in 50 healthy individuals across multiple behavioural and anatomical domains, and complementing FA with myelin-sensitive quantitative MR modalities (MT, R1, R2∗).

Reducing Susceptibility Distortion Related Image Blurring in Diffusion MRI EPI Data.

Diffusion magnetic resonance imaging (MRI) is an increasingly popular technique in basic and clinical neuroscience. One promising application is to combine diffusion MRI with myelin maps from complementary MRI techniques such as multi-parameter mapping (MPM) to produce g-ratio maps that represent the relative myelination of axons and predict their conduction velocity. Statistical Parametric Mapping (SPM) can process both diffusion data and MPMs, making SPM the only widely accessible software that contains all the processing steps required to perform group analyses of g-ratio data in a common space.

Interruptions of the GAA Repeat Tract Delay the Age at Onset of Friedreich's Ataxia in a Location Dependent Manner.

Friedreich's ataxia (FRDA) is a comparatively rare autosomal recessive neurological disorder primarily caused by the homozygous expansion of a GAA trinucleotide repeat in intron 1 of the gene. The repeat expansion causes gene silencing that results in deficiency of the frataxin protein leading to mitochondrial dysfunction, oxidative stress and cell death. The GAA repeat tract in some cases may be impure with sequence variations called interruptions.

Model-based multi-parameter mapping.

Quantitative MR imaging is increasingly favoured for its richer information content and standardised measures. However, computing quantitative parameter maps, such as those encoding longitudinal relaxation rate (R), apparent transverse relaxation rate (R) or magnetisation-transfer saturation (MT), involves inverting a highly non-linear function. Many methods for deriving parameter maps assume perfect measurements and do not consider how noise is propagated through the estimation procedure, resulting in needlessly noisy maps.