Assessing age-related changes in brain activity during isometric upper and lower limb force control tasks.

Despite the widespread use of older adults (OA) as controls in movement disorder studies, the specific effects of aging on the neural control of upper and lower limb movements remain unclear. While functional MRI paradigms focusing on hand movements are widely used to investigate age-related brain changes, research on lower limb movements is limited due to technical challenges in an MRI environment. This study addressed this gap by examining both upper and lower limb movements in healthy young adults (YA) vs.

Acute hypernatremia increases functional connectivity of NaCl sensing regions in the human brain: An fMRI pilot study.

Rodent studies demonstrated specialized sodium chloride (NaCl) sensing neurons in the circumventricular organs, which mediate changes in sympathetic nerve activity, arginine vasopressin, thirst, and blood pressure. However, the neural pathways involved in NaCl sensing in the human brain are incompletely understood. The purpose of this pilot study was to determine if acute hypernatremia alters the functional connectivity of NaCl-sensing regions of the brain in healthy young adults.

Free water imaging unravels unique patterns of longitudinal structural brain changes in Parkinson's disease subtypes.

Background: Research shows that individuals with Parkinson's disease (PD) who have a postural instability and gait difficulties (PIGD) subtype have a faster disease progression compared to those with a tremor dominant (TD) subtype. Nevertheless, our understanding of the structural brain changes contributing to these clinical differences remains limited, primarily because many brain imaging techniques are only capable of detecting changes in the later stages of the disease.

Objective: Free water (FW) has emerged as a robust progression marker in several studies, showing increased values in the posterior substantia nigra that predict symptom worsening.

Imaging the lower limb network in Parkinson's disease.

Background: Despite the significant impact of lower limb symptoms on everyday life activities in Parkinson's disease (PD), knowledge of the neural correlates of lower limb deficits is limited.

Objective: We ran an fMRI study to investigate the neural correlates of lower limb movements in individuals with and without PD.

Methods: Participants included 24 PD and 21 older adults who were scanned while performing a precisely controlled isometric force generation task by dorsiflexing their ankle.

Rate control deficits during pinch grip and ankle dorsiflexion in early-stage Parkinson's disease.

Background: Much of our understanding of the deficits in force control in Parkinson's disease (PD) relies on findings in the upper extremity. Currently, there is a paucity of data pertaining to the effect of PD on lower limb force control.

Objective: The purpose of this study was to concurrently evaluate upper- and lower-limb force control in early-stage PD and a group of age- and gender-matched healthy controls.

Development and Validation of Automated Magnetic Resonance Parkinsonism Index 2.0 to Distinguish Progressive Supranuclear Palsy-Parkinsonism From Parkinson's Disease.

Background: Differentiating progressive supranuclear palsy-parkinsonism (PSP-P) from Parkinson's disease (PD) is clinically challenging.

Objective: This study aimed to develop an automated Magnetic Resonance Parkinsonism Index 2.0 (MRPI 2.

Diffusion Magnetic Resonance Imaging Detects Progression in Parkinson's Disease: A Placebo-Controlled Trial of Rasagiline.

Background: Rasagiline has received attention as a potential disease-modifying therapy for Parkinson's disease (PD). Whether rasagiline is disease modifying remains in question.

Objective: The main objective of this study was to determine whether rasagiline has disease-modifying effects in PD over 1 year.

A New MRI Measure to Early Differentiate Progressive Supranuclear Palsy From De Novo Parkinson's Disease in Clinical Practice: An International Study.

Background: Enlargement of the third ventricle has been reported in atypical parkinsonism. We investigated whether the measurement of third ventricle width could distinguish Parkinson's disease (PD) from progressive supranuclear palsy (PSP).

Methods: We assessed a new MR T1-weighted measurement (third ventricle width/internal skull diameter) in a training cohort of 268 participants (98 PD, 73 PSP, 98 controls from our center) and in a testing cohort of 291 participants (82 de novo PD patients and 133 controls from the Parkinson's Progression Markers Initiative, 76 early-stage PSP from an international research group).

Magnetic Resonance Imaging and Neurofilament Light in the Differentiation of Parkinsonism.

Objective: Accurate diagnosis is particularly challenging in Parkinson's disease (PD), multiple system atrophy (MSAp), and progressive supranuclear palsy (PSP). We compare the utility of 3 promising biomarkers to differentiate disease state and explain disease severity in parkinsonism: the Automated Imaging Differentiation in Parkinsonism (AID-P), the Magnetic Resonance Parkinsonism Index (MRPI), and plasma-based neurofilament light chain protein (NfL).

Methods: For each biomarker, the area under the curve (AUC) of receiver operating characteristic curves were quantified for PD versus MSAp/PSP and MSAp versus PSP and statistically compared.

Development and Validation of the Automated Imaging Differentiation in Parkinsonism (AID-P): A Multi-Site Machine Learning Study.

Background: There is a critical need to develop valid, non-invasive biomarkers for Parkinsonian syndromes. The current 17-site, international study assesses whether non-invasive diffusion MRI (dMRI) can distinguish between Parkinsonian syndromes.

Methods: We used dMRI from 1002 subjects, along with the Movement Disorders Society Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III), to develop and validate disease-specific machine learning comparisons using 60 template regions and tracts of interest in Montreal Neurological Institute (MNI) space between Parkinson's disease (PD) and Atypical Parkinsonism (multiple system atrophy - MSA, progressive supranuclear palsy - PSP), as well as between MSA and PSP.

Automated MRI Classification in Progressive Supranuclear Palsy: A Large International Cohort Study.

Background: The Magnetic Resonance Parkinsonism Index is listed as one of the most reliable imaging morphometric markers for diagnosis of progressive supranuclear palsy (PSP). However, the use of this index in diagnostic workup has been limited until now by the low generalizability of published results because of small monocentric patient cohorts, the lack of data validation in independent patient series, and manual measurements used for index calculation. The objectives of this study were to investigate the generalizability of Magnetic Resonance Parkinsonism Index performance validating previously established cutoff values in a large international cohort of PSP patients subclassified into PSP-Richardson's syndrome and PSP-parkinsonism and to standardize the use of the automated Magnetic Resonance Parkinsonism Index by providing a web-based platform to obtain homogenous measures around the world.

Temporal Invariance in SCA6 Is Related to Smaller Cerebellar Lobule VI and Greater Disease Severity.

Regulating muscle force and timing are fundamental for accurate motor performance. In spinocerebellar ataxia type 6 (SCA6), there is evidence that individuals have greater force dysmetria but display better temporal accuracy during fast goal directed contractions. Here, we test whether greater temporal accuracy occurs in all individuals with SCA6, and can be explained by lesser temporal variability.

Development and validation of the automated imaging differentiation in parkinsonism (AID-P): a multicentre machine learning study.

Background: Development of valid, non-invasive biomarkers for parkinsonian syndromes is crucially needed. We aimed to assess whether non-invasive diffusion-weighted MRI can distinguish between parkinsonian syndromes using an automated imaging approach.

Methods: We did an international study at 17 MRI centres in Austria, Germany, and the USA.

Multimodal dopaminergic and free-water imaging in Parkinson's disease.

Introduction: When using free-water diffusion imaging or positron emission tomography (PET), it is established that substania nigra microstructure and presynaptic dopamine activity are impaired in early PD. It is not well understood if these two forms of degeneration are redundant, or if they each provide a unique contribution to the clinical motor and cognitive symptoms.

Methods: A total of 129 PD and 75 control individuals underwent motor and cognitive evaluations, and in vivo [11C]dihydrotetrabenazine (DTBZ) monoaminergic brain PET imaging and diffusion imaging.

Imaging of Motor Cortex Physiology in Parkinson's Disease.

There is abundant evidence that the pathophysiology of Parkinson's disease (PD) is not confined to the nigrostriatal dopaminergic pathway but propagates along the cortico-basal ganglia-thalamo-cortical neural network. A critical node in this functional circuit impacted by PD is the primary motor cortex (M1), which plays a key role in generating neural impulses that regulate movements. The past several decades have lay witness to numerous in vivo neuroimaging techniques that provide a window into the function and structure of M1.

Longitudinal Progression Markers of Parkinson's Disease: Current View on Structural Imaging.

Purpose Of Review: Advances in neuroimaging techniques pave a rich avenue for in vivo progression biomarkers, which can objectively and noninvasively assess the long-term dynamic alterations in the brain of Parkinson's disease (PD) patients. This article reviews recent progress in structural magnetic resonance imaging (MRI) tools to track disease progression in PD, and discusses specific criteria a neuroimaging tool needs to meet to be a progression biomarker of PD and the potential applications of these techniques in PD based on current evidence.

Recent Findings: Recent longitudinal studies showed that quantitative structural MRI markers derived from T1-weighted, diffusion-weighted, neuromelanin-sensitive, and iron-sensitive imaging have the potential to track disease progression in PD.

Beta-band oscillations in the supplementary motor cortex are modulated by levodopa and associated with functional activity in the basal ganglia.

We investigated the effect of acute levodopa administration on movement-related cortical oscillations and movement velocity in Parkinson's disease (PD). Patients with PD on and off medication and age- and sex-matched healthy controls performed a ballistic upper limb flexion movement as fast and accurately as possible while cortical oscillations were recorded with high-density electroencephalography. Patients off medication were also studied using task-based functional magnetic resonance imaging (fMRI) using a force control paradigm.

Multimodal neuroimaging and behavioral assessment of α-synuclein polymorphism rs356219 in older adults.

The single-nucleotide polymorphism rs356219 in the α-synuclein (SNCA) gene has been shown to significantly contribute to an earlier age at onset of Parkinson's disease (PD), and regulates SNCA expression in PD brain regions, blood, and plasma. Here, we used multimodal magnetic resonance imaging (MRI) to study healthy adults with and without the rs356219 risk genotype. Motor and cognitive tests were administered, and all participants underwent functional and structural MRI.

A widespread visually-sensitive functional network relates to symptoms in essential tremor.

Essential tremor is a neurological syndrome of heterogeneous pathology and aetiology that is characterized by tremor primarily in the upper extremities. This tremor is commonly hypothesized to be driven by a single or multiple neural oscillator(s) within the cerebello-thalamo-cortical pathway. Several studies have found an association of blood-oxygen level-dependent (BOLD) signal in the cerebello-thalamo-cortical pathway with essential tremor, but there is behavioural evidence that also points to the possibility that the severity of tremor could be influenced by visual feedback.

Progression marker of Parkinson's disease: a 4-year multi-site imaging study.

Progression markers of Parkinson's disease are crucial for successful therapeutic development. Recently, a diffusion magnetic resonance imaging analysis technique using a bitensor model was introduced allowing the estimation of the fractional volume of free water within a voxel, which is expected to increase in neurodegenerative disorders such as Parkinson's disease. Prior work demonstrated that free water in the posterior substantia nigra was elevated in Parkinson's disease compared to controls across single- and multi-site cohorts, and increased over 1 year in Parkinson's disease but not in controls at a single site.

Free water improves detection of changes in the substantia nigra in parkinsonism: A multisite study.

Background: Imaging markers that are sensitive to parkinsonism across multiple sites are critically needed for clinical trials. The objective of this study was to evaluate changes in the substantia nigra using single- and bi-tensor models of diffusion magnetic resonance imaging in PD, MSA, and PSP.

Methods: The study cohort (n = 425) included 107 healthy controls and 184 PD, 63 MSA, and 71 PSP patients from 3 movement disorder centers.

Forebrain knock-out of torsinA reduces striatal free-water and impairs whole-brain functional connectivity in a symptomatic mouse model of DYT1 dystonia.

Multiple lines of evidence implicate striatal dysfunction in the pathogenesis of dystonia, including in DYT1, a common inherited form of the disease. The impact of striatal dysfunction on connected motor circuits and their interaction with other brain regions is poorly understood. Conditional knock-out (cKO) of the DYT1 protein torsinA from forebrain cholinergic and GABAergic neurons creates a symptomatic model that recapitulates many characteristics of DYT1 dystonia, including the developmental onset of overt twisting movements that are responsive to antimuscarinic drugs.