The causal role of the subthalamic nucleus in the inhibitory network.

The neural network mediating successful response inhibition mainly includes right hemisphere activation of the pre-supplementary motor area, inferior frontal gyrus (IFG), subthalamic nucleus (STN), and caudate nucleus. However, the causal role of these regions in the inhibitory network is undefined. Five patients with Parkinson's disease were assessed prior to and after therapeutic thermal ablation of the right STN in two separate functional magnetic resonance imaging (fMRI) sessions while performing a stop-signal task.

Automatic Segmentation and Quantification of Nigrosome-1 Neuromelanin and Iron in MRI: A Candidate Biomarker for Parkinson's Disease.

Background: There is a lack of automated tools for the segmentation and quantification of neuromelanin (NM) and iron in the nigrosome-1 (N1). Existing tools evaluate the N1 sign, i.e.

Brainstem neuromelanin and iron MRI reveals a precise signature for idiopathic and LRRK2 Parkinson's disease.

Neuromelanin (NM) loss in substantia nigra pars compacta (SNc) and locus coeruleus (LC) reflects neuronal death in Parkinson's disease (PD). Since genetically-determined PD shows varied clinical expressivity, we wanted to accurately quantify and locate brainstem NM and iron, to discover whether specific MRI patterns are linked to Leucine-rich repeat kinase 2 G2019S PD (LRRK2-PD) or idiopathic Parkinson's disease (iPD). A 3D automated MRI atlas-based segmentation pipeline (3D-ABSP) for NM/iron-sensitive MRI images topographically characterized the SNc, LC, and red nucleus (RN) neuronal loss and calculated NM/iron contrast ratio (CR) and normalized volume (nVol).

Egocentric distance perception in older adults: Results from a functional magnetic resonance imaging and driving simulator study.

The ability to appropriately perceive distances in activities of daily living, such as driving, is necessary when performing complex maneuvers. With aging, certain driving behaviors and cognitive functions change; however, it remains unknown if egocentric distance perception (EDP) performance is altered and whether its neural activity also changes as we grow older. To that end, 19 young and 17 older healthy adults drove in a driving simulator and performed an functional magnetic resonance imaging (fMRI) experiment where we presented adults with an EDP task.

Brain Activity and Functional Connectivity Patterns Associated With Fast and Slow Motor Sequence Learning in Late Middle Adulthood.

The human brain undergoes structural and functional changes across the lifespan. The study of motor sequence learning in elderly subjects is of particularly interest since previous findings in young adults might not replicate during later stages of adulthood. The present functional magnetic resonance imaging (fMRI) study assessed the performance, brain activity and functional connectivity patterns associated with motor sequence learning in late middle adulthood.

The motor inhibitory network in patients with asymmetrical Parkinson's disease: An fMRI study.

Recent imaging studies with the stop-signal task in healthy individuals indicate that the subthalamic nucleus, the pre-supplementary motor area and the inferior frontal gyrus are key components of the right hemisphere "inhibitory network". Limited information is available regarding neural substrates of inhibitory processing in patients with asymmetric Parkinson's disease. The aim of the current fMRI study was to identify the neural changes underlying deficient inhibitory processing on the stop-signal task in patients with predominantly left-sided Parkinson's disease.

Neuroplasticity during the transition period: How the adolescent brain can recover from aphasia. A pilot study.

Background: Increasing clinical and scientific attention is given to the transition of neurological stages from child to adult. Data on brain plasticity during adolescence is interesting for providing adequate evidence-based medical attention to neurological conditions in this population. Acquired aphasia is well described in adults and children, but not in adolescence.

Exome-wide rare variant analysis in familial essential tremor.

Introduction: Essential tremor (ET) is one of the most common movement disorders. Despite its high prevalence and heritability, its genetic etiology remains elusive with only a few susceptibility genes identified and poorly replicated. Our aim was to find novel candidate genes involved in ET predisposition through whole exome sequencing.

Brain ventricular enlargement in human and murine acute intermittent porphyria.

The morphological changes that occur in the central nervous system of patients with severe acute intermittent porphyria (AIP) have not yet been clearly established. The aim of this work was to analyze brain involvement in patients with severe AIP without epileptic seizures or clinical posterior reversible encephalopathy syndrome, as well as in a mouse model receiving or not liver-directed gene therapy aimed at correcting the metabolic disorder. We conducted neuroradiologic studies in 8 severely affected patients (6 women) and 16 gender- and age-matched controls.

Central neurogenetic signatures of the visuomotor integration system.

Visuomotor impairments characterize numerous neurological disorders and neurogenetic syndromes, such as autism spectrum disorder (ASD) and Dravet, Fragile X, Prader-Willi, Turner, and Williams syndromes. Despite recent advances in systems neuroscience, the biological basis underlying visuomotor functional impairments associated with these clinical conditions is poorly understood. In this study, we used neuroimaging connectomic approaches to map the visuomotor integration (VMI) system in the human brain and investigated the topology approximation of the VMI network to the Allen Human Brain Atlas, a whole-brain transcriptome-wide atlas of cortical genetic expression.

An amygdala-cingulate network underpins changes in effort-based decision making after a fitness program.

When humans make decisions, objective rewards are mainly discounted by delay, risk and effort. Whereas recent research has demonstrated that several brain areas process costs and code subjective value in effort-based decision making, it remains obscure how neural activity patterns change when effort costs are reduced due to the acquisition of healthy habits, such as moving from sedentary to active lifestyles. Here, a sample of sedentary volunteers was behaviorally assessed and fMRI-scanned before and after completing a 3-month fitness plan.

A neural basis for food foraging in obesity.

Poverty-related food insecurity can be viewed as a form of economic and nutritional uncertainty that can lead, in some situations, to a desire for more filling and satisfying food. Given the current obesogenic food environment and the nature of the food supply, those food choices could engage a combination of sensory, neurophysiological, and genetic factors as potential determinants of obesity.

Neural correlates of effort-based behavioral inconsistency.

According to the theory of value-based decision making, subjects tend to choose the most valuable among a set of options. However, agents may not be consistent when facing the same decision several times. In this paper, Shannon's entropy (H) is employed as a measure of behavioral inconsistency: it is a central measure of information theory that, applied to decision making, allows the estimation of behavioral preferences among a set of options.

Kinematic and Kinetic Patterns Related to Free-Walking in Parkinson's Disease.

The aim of this study is to compare the properties of free-walking at a natural pace between mild Parkinson's disease (PD) patients during the ON-clinical status and two control groups. In-shoe pressure-sensitive insoles were used to quantify the temporal and force characteristics of a 5-min free-walking in 11 PD patients, in 16 young healthy controls, and in 12 age-matched healthy controls. Inferential statistics analyses were performed on the kinematic and kinetic parameters to compare groups' performances, whereas feature selection analyses and automatic classification were used to identify the signature of parkinsonian gait and to assess the performance of group classification, respectively.

Dynamic Atlas-Based Segmentation and Quantification of Neuromelanin-Rich Brainstem Structures in Parkinson Disease.

We present a dynamic atlas composed of neuromelanin-enhanced magnetic resonance brain images of 40 healthy subjects. The performance of this atlas is evaluated on the fully automated segmentation of two paired neuromelanin-rich brainstem healthy structures: the substantia nigra pars compacta and the locus coeruleus. We show that our dynamic atlas requires in average 60% less images and, therefore, 60% less computation time than a static multi-image atlas while achieving a similar segmentation performance.

Default-mode network dynamics are restricted during high speed discrimination in healthy aging: Associations with neurocognitive status and simulated driving behavior.

Numerous daily tasks, including car driving, require fine visuospatial tuning. One such visuospatial ability, speed discrimination, declines with aging but its neural underpinnings remain unknown. In this study, we use fMRI to explore the effect of aging during a high speed discrimination task and its neural underpinnings, along with a complete neuropsychological assessment and a simulated driving evaluation in order to examine how they interact with each other through a multivariate regression approach.

Pooled-DNA target sequencing of Parkinson genes reveals novel phenotypic associations in Spanish population.

Eighteen loci and several susceptibility genes have been related to Parkinson's disease (PD). However, most studies focus on single genes in small PD series. Our aim was to establish the genetic background of a large Spanish PD sample.

Target-enriched sequencing of chromosome 17q21.31 in sporadic tauopathies reveals no candidate variants.

The main genetic risk factors for progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are located at chromosome 17q21.31. The identification of risk H1 subhaplotypes suggests that disease-specific variants can be identified by resequencing the 17q21.

Common and rare TBK1 variants in early-onset Alzheimer disease in a European cohort.

TANK-binding kinase 1 (TBK1) loss-of-function (LoF) mutations are known to cause frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), often combined with memory deficits early in the disease course. We performed targeted resequencing of TBK1 in 1253 early onset Alzheimer's disease (EOAD) patients from 8 European countries to investigate whether pathogenic TBK1 mutations are enriched among patients with clinical diagnosis of EOAD. Variant frequencies were compared against 2117 origin-matched controls.

Translation and adaptation of the Disability Assessment for Dementia scale in the Spanish population.

Background And Objective: Functional assessment is especially relevant in patients with cognitive impairment (CI). The Disability Assessment for Dementia (DAD) scale assesses functional ability and its use is becoming increasingly popular. This study aims to perform the translation and cultural adaptation of the DAD scale in order to create a Spanish version: DAD-E.

Deleterious ABCA7 mutations and transcript rescue mechanisms in early onset Alzheimer's disease.

Premature termination codon (PTC) mutations in the ATP-Binding Cassette, Sub-Family A, Member 7 gene (ABCA7) have recently been identified as intermediate-to-high penetrant risk factor for late-onset Alzheimer's disease (LOAD). High variability, however, is observed in downstream ABCA7 mRNA and protein expression, disease penetrance, and onset age, indicative of unknown modifying factors. Here, we investigated the prevalence and disease penetrance of ABCA7 PTC mutations in a large early onset AD (EOAD)-control cohort, and examined the effect on transcript level with comprehensive third-generation long-read sequencing.

Motor sequence learning in the elderly: differential activity patterns as a function of hand modality.

Previous research on motor sequence learning (MSL) in the elderly has focused mainly on unilateral tasks, even though bilateral coordination might be impaired in this age group. In this fMRI study, 28 right-handed elderly subjects were recruited. The paradigm consisted of a Novel and a simple Control sequence executed with the right (R), left (L) and both hands (B).

Neuroimaging Correlates of Frontotemporal Dementia Associated with SQSTM1 Mutations.

Background: Frontotemporal lobar degeneration (FTLD) is a progressive dementia characterized by focal atrophy of frontal and/or temporal lobes caused by mutations in the gene coding for sequestosome 1 (SQSTM1), among other genes. Rare SQSTM1 gene mutations have been associated with Paget's disease of bone, amyotrophic lateral sclerosis, and, more recently, frontotemporal lobar degeneration (FTLD).

Objective: The aim of the study was to determine whether a characteristic pattern of grey and white matter loss is associated with SQSTM1 dysfunction.

A comprehensive study of the genetic impact of rare variants in SORL1 in European early-onset Alzheimer's disease.

The sortilin-related receptor 1 (SORL1) gene has been associated with increased risk for Alzheimer's disease (AD). Rare genetic variants in the SORL1 gene have also been implicated in autosomal dominant early-onset AD (EOAD). Here we report a large-scale investigation of the contribution of genetic variability in SORL1 to EOAD in a European EOAD cohort.