Propranolol Reduces Parkinson's Tremor and Inhibits Tremor-Related Activity in the Motor Cortex: A Placebo-Controlled Crossover Trial.

Objective: Parkinson's disease (PD) resting tremor is thought to be initiated in the basal ganglia and amplified in the cerebello-thalamo-cortical circuit. Because stress worsens tremor, the noradrenergic system may play a role in amplifying tremor. We tested if and how propranolol, a non-selective beta-adrenergic receptor antagonist, reduces PD tremor and whether or not this effect is specific to stressful conditions.

Changes in Action Tremor in Parkinson's Disease over Time: Clinical and Neuroimaging Correlates.

Background: The various symptoms of Parkinson's disease (PD) may change differently over time as the disease progresses. Tremor usually manifests early in the disease, but unlike other motor symptoms, its severity may diminish over time. The cerebral mechanisms underlying these symptom-specific longitudinal trajectories are unclear.

A worldwide study of subcortical shape as a marker for clinical staging in Parkinson's disease.

Alterations in subcortical brain regions are linked to motor and non-motor symptoms in Parkinson's disease (PD). However, associations between clinical expression and regional morphological abnormalities of the basal ganglia, thalamus, amygdala and hippocampus are not well established. We analyzed 3D T1-weighted brain MRI and clinical data from 2525 individuals with PD and 1326 controls from 22 global sources in the ENIGMA-PD consortium.

A worldwide study of white matter microstructural alterations in people living with Parkinson's disease.

The progression of Parkinson's disease (PD) is associated with microstructural alterations in neural pathways, contributing to both motor and cognitive decline. However, conflicting findings have emerged due to the use of heterogeneous methods in small studies. Here we performed a large diffusion MRI study in PD, integrating data from 17 cohorts worldwide, to identify stage-specific profiles of white matter differences.

Cerebellar Volume and Disease Staging in Parkinson's Disease: An ENIGMA-PD Study.

Background: Increasing evidence points to a pathophysiological role for the cerebellum in Parkinson's disease (PD). However, regional cerebellar changes associated with motor and non-motor functioning remain to be elucidated.

Objective: To quantify cross-sectional regional cerebellar lobule volumes using three dimensional T1-weighted anatomical brain magnetic resonance imaging from the global ENIGMA-PD working group.

The role of laboratory investigations in the classification of tremors.

Introduction: Tremor is the most common movement disorder. Although clinical examination plays a significant role in evaluating patients with tremor, laboratory tests are useful to classify tremors according to the recent two-axis approach proposed by the International Parkinson and Movement Disorders Society.

Methods: In the present review, we will discuss the usefulness and applicability of the various diagnostic methods in classifying and diagnosing tremors.

Integrative Brain States Facilitate the Expression of Parkinson's Tremor.

Background: Parkinson's disease (PD) rest tremor emerges from pathological activity in the basal ganglia and cerebello-thalamo-cortical circuits. A well-known clinical feature is the waxing and waning of PD tremor amplitude, but the mechanisms that drive this variability are unclear. Previous work has shown that arousal amplifies PD tremor by increasing between-network connectivity.

The pathophysiology of Parkinson's disease tremor.

Tremor is one of the primary motor symptoms of Parkinson's disease (PD), and it is characterized by a highly phenomenological heterogeneity. Clinical and experimental observations suggest that tremor in PD cannot be interpreted merely as an expression of dopaminergic denervation of the basal ganglia. Accordingly, other neurotransmitter systems and brain areas are involved.

The clinical and electrophysiological investigation of tremor.

The various forms of tremor are now classified in two axes: clinical characteristics (axis 1) and etiology (axis 2). Electrophysiology is an extension of the clinical exam. Electrophysiologic tests are diagnostic of physiologic tremor, primary orthostatic tremor, and functional tremor, but they are valuable in the clinical characterization of all forms of tremor.

Cerebello-thalamic activity drives an abnormal motor network into dystonic tremor.

Dystonic tremor syndromes are highly burdensome and treatment is often inadequate. This is partly due to poor understanding of the underlying pathophysiology. Several lines of research suggest involvement of the cerebello-thalamo-cortical circuit and the basal ganglia in dystonic tremor syndromes, but their role is unclear.

International Multicenter Analysis of Brain Structure Across Clinical Stages of Parkinson's Disease.

Background: Brain structure abnormalities throughout the course of Parkinson's disease have yet to be fully elucidated.

Objective: Using a multicenter approach and harmonized analysis methods, we aimed to shed light on Parkinson's disease stage-specific profiles of pathology, as suggested by in vivo neuroimaging.

Methods: Individual brain MRI and clinical data from 2357 Parkinson's disease patients and 1182 healthy controls were collected from 19 sources.

Effects of dopamine on reinforcement learning in Parkinson's disease depend on motor phenotype.

Parkinson's disease is clinically defined by bradykinesia, along with rigidity and tremor. However, the severity of these motor signs is greatly variable between individuals, particularly the presence or absence of tremor. This variability in tremor relates to variation in cognitive/motivational impairment, as well as the spatial distribution of neurodegeneration in the midbrain and dopamine depletion in the striatum.

Dopamine-responsive and dopamine-resistant resting tremor in Parkinson disease.

Objective: We tested the hypothesis that there are 2 distinct phenotypes of Parkinson tremor, based on interindividual differences in the response of resting tremor to dopaminergic medication. We also investigated whether this pattern is specific to tremor by comparing interindividual differences in the dopamine response of tremor to that of bradykinesia.

Methods: In this exploratory study, we performed a levodopa challenge in 76 tremulous patients with Parkinson tremor.

Systematic clinical approach for diagnosing upper limb tremor.

Tremor is the most common movement disorder worldwide, but diagnosis is challenging. In 2018, the task force on tremor of the International Parkinson and Movement Disorder Society published a consensus statement that proposes a tremor classification along two independent axes: a clinical tremor syndrome and its underlying aetiology. In line with this statement, we here propose a stepwise diagnostic approach that leads to the correct clinical and aetiological classification of upper limb tremor.

Cognitive load amplifies Parkinson's tremor through excitatory network influences onto the thalamus.

Parkinson's tremor is related to cerebral activity in both the basal ganglia and a cerebello-thalamo-cortical circuit. It is a common clinical observation that tremor markedly increases during cognitive load (such as mental arithmetic), leading to serious disability. Previous research has shown that this tremor amplification is associated with reduced efficacy of dopaminergic treatment.

GABAergic changes in the thalamocortical circuit in Parkinson's disease.

Parkinson's disease is characterized by bradykinesia, rigidity, and tremor. These symptoms have been related to an increased gamma-aminobutyric acid (GABA)ergic inhibitory drive from globus pallidus onto the thalamus. However, in vivo empirical evidence for the role of GABA in Parkinson's disease is limited.

Cerebral differences between dopamine-resistant and dopamine-responsive Parkinson's tremor.

Rest tremor in Parkinson's disease is related to cerebral activity in both the basal ganglia and a cerebello-thalamo-cortical circuit. Clinically, there is strong interindividual variation in the therapeutic response of tremor to dopaminergic medication. This observation casts doubt on the idea that Parkinson's tremor has a dopaminergic basis.

The nature of postural tremor in Parkinson disease.

Objective: To disentangle the different forms of postural tremors in Parkinson disease (PD).

Methods: In this combined observational and intervention study, we measured resting and postural tremor characteristics in 73 patients with tremulous PD by using EMG of forearm muscles. Patients were measured both "off" medication (overnight withdrawal) and after dispersible levodopa-benserazide 200/50 mg.

Pathophysiology and Management of Parkinsonian Tremor.

Parkinson's tremor is one of the cardinal motor symptoms of Parkinson's disease. The pathophysiology of Parkinson's tremor is different from that of other motor symptoms such as bradykinesia and rigidity. In this review, the authors discuss evidence suggesting that tremor is a network disorder that arises from distinct pathophysiological changes in the basal ganglia and in the cerebellothalamocortical circuit.

Dopamine controls Parkinson's tremor by inhibiting the cerebellar thalamus.

Parkinson's resting tremor is related to altered cerebral activity in the basal ganglia and the cerebello-thalamo-cortical circuit. Although Parkinson's disease is characterized by dopamine depletion in the basal ganglia, the dopaminergic basis of resting tremor remains unclear: dopaminergic medication reduces tremor in some patients, but many patients have a dopamine-resistant tremor. Using pharmacological functional magnetic resonance imaging, we test how a dopaminergic intervention influences the cerebral circuit involved in Parkinson's tremor.

Cognitive Stress Reduces the Effect of Levodopa on Parkinson's Resting Tremor.

Aims: Resting tremor in Parkinson's disease (PD) increases markedly during cognitive stress. Dopamine depletion in the basal ganglia is involved in the pathophysiology of resting tremor, but it is unclear whether this contribution is altered under cognitive stress. We test the hypothesis that cognitive stress modulates the levodopa effect on resting tremor.

The patient's perspective: The effect of levodopa on Parkinson symptoms.

Background: Dopaminergic medication adjustments in Parkinson's disease are often solely based on patient reports. However, it is unclear how well patient-based ratings of the levodopa response correlate with clinician-based ratings, and whether this correlation differs between motor symptoms. Here we compare patient-clinician agreement for the effect of levodopa on resting tremor and bradykinesia/rigidity.

The Cerebral Network of Parkinson's Tremor: An Effective Connectivity fMRI Study.

Unlabelled: Parkinson's resting tremor has been linked to pathophysiological changes both in the basal ganglia and in a cerebello-thalamo-cortical motor loop, but the role of those circuits in initiating and maintaining tremor remains unclear. Here, we test whether and how the cerebello-thalamo-cortical loop is driven into a tremor-related state by virtue of its connectivity with the basal ganglia. An internal replication design on two independent cohorts of tremor-dominant Parkinson patients sampled brain activity and tremor with concurrent EMG-fMRI.

Consensus Paper: Towards a Systems-Level View of Cerebellar Function: the Interplay Between Cerebellum, Basal Ganglia, and Cortex.

Despite increasing evidence suggesting the cerebellum works in concert with the cortex and basal ganglia, the nature of the reciprocal interactions between these three brain regions remains unclear. This consensus paper gathers diverse recent views on a variety of important roles played by the cerebellum within the cerebello-basal ganglia-thalamo-cortical system across a range of motor and cognitive functions. The paper includes theoretical and empirical contributions, which cover the following topics: recent evidence supporting the dynamical interplay between cerebellum, basal ganglia, and cortical areas in humans and other animals; theoretical neuroscience perspectives and empirical evidence on the reciprocal influences between cerebellum, basal ganglia, and cortex in learning and control processes; and data suggesting possible roles of the cerebellum in basal ganglia movement disorders.