Phase dependent modulation of tremor amplitude in essential tremor through thalamic stimulation.

High frequency deep brain stimulation of the thalamus can help ameliorate severe essential tremor. Here we explore how the efficacy, efficiency and selectivity of thalamic deep brain stimulation might be improved in this condition. We started from the hypothesis that the effects of electrical stimulation on essential tremor may be phase dependent, and that, in particular, there are tremor phases at which stimuli preferentially lead to a reduction in the amplitude of tremor.

The nucleus basalis of Meynert: a new target for deep brain stimulation in dementia?

Dementia is a major cause of disability amongst the elderly and represents a serious global health issue. Current treatments for dementia are limited; at best they provide inadequate symptomatic relief. In contrast, there are a plethora of approaches that provide symptomatic relief for abnormalities of movement including surgical approaches.

Subthalamic nucleus local field potential activity during the Eriksen flanker task reveals a novel role for theta phase during conflict monitoring.

The subthalamic nucleus (STN) is thought to play a central role in modulating responses during conflict. Computational models have suggested that the location of the STN in the basal ganglia, as well as its numerous connections to conflict-related cortical structures, allows it to be ideally situated to act as a global inhibitor during conflict. Additionally, recent behavioral experiments have shown that deep brain stimulation to the STN results in impulsivity during high-conflict situations.

Influence of single nucleotide polymorphisms in COMT, MAO-A and BDNF genes on dyskinesias and levodopa use in Parkinson's disease.

Background: Clinical heterogeneity in the development of levodopa-induced dyskinesias (LID) suggests endogenous factors play a significant role in determining their overall prevalence.

Objective: We hypothesised that single nucleotide polymorphisms (SNPs) in specific genes may result in a clinical phenotype conducive to an increased risk of LID.

Methods: We examined the influence of SNPs in the catechol-O-methyltransferase (COMT), monoamine oxidase A (MAO-A) and brain-derived neurotrophic factor (BDNF) genes on LID in a cohort of 285 pathologically confirmed Parkinson's disease patients, using data from their complete disease course.

Dopamine agonists rather than deep brain stimulation cause reflection impulsivity in Parkinson's disease.

Background: Dopamine agonist therapy is the main risk factor for impulse control disorders in Parkinson's disease (PD). However, it is unclear whether bilateral deep brain stimulation of the subthalamic nucleus also causes impairment in decision making.

Objectives: To assess the role of dopamine agonist therapy and deep brain stimulation on reflection impulsivity in non-demented patients with PD.

Dopaminergic neuronal imaging in genetic Parkinson's disease: insights into pathogenesis.

Objectives: To compare the dopaminergic neuronal imaging features of different subtypes of genetic Parkinson's Disease.

Methods: A retrospective study of genetic Parkinson's diseases cases in which DaTSCAN (123I-FP-CIT) had been performed. Specific non-displaceable binding was calculated for bilateral caudate and putamen for each case.

Pallidal stimulation for cervical dystonia does not correct abnormal temporal discrimination.

Background: We investigated whether clinical improvement observed after deep brain stimulation (DBS) of the globus pallidus internus (GPi) in cervical dystonia (CD) is paralleled by the normalisation of temporal discrimination thresholds (TDTs), a marker of abnormal sensory processing in CD.

Methods: TDT was tested in 11 patients with CD after they received DBS and was compared with TDT scores from 24 patients with CD and a group of 61 controls.

Results: A clear clinical response to GPi-DBS was demonstrated (total Toronto Western Spasmodic Torticollis Rating Scale scores fell from 50 to 18; P < 0.

Adaptive deep brain stimulation in advanced Parkinson disease.

Objective: Brain-computer interfaces (BCIs) could potentially be used to interact with pathological brain signals to intervene and ameliorate their effects in disease states. Here, we provide proof-of-principle of this approach by using a BCI to interpret pathological brain activity in patients with advanced Parkinson disease (PD) and to use this feedback to control when therapeutic deep brain stimulation (DBS) is delivered. Our goal was to demonstrate that by personalizing and optimizing stimulation in real time, we could improve on both the efficacy and efficiency of conventional continuous DBS.

Understanding DCM: ten simple rules for the clinician.

Despite almost a decade since the introduction of Dynamic Causal Modelling (DCM), there remains some confusion within the wider neuroimaging, neuroscience and clinical communities as to what DCM studies are probing, and what all the jargon means. We provide ten simple rules, and a theoretical example to gently introduce the reader to the rationale behind DCM analyses, and how one should consider neuroimaging data and experiments that use DCM. It is deliberately written as a primer or orientation for non-technical imaging neuroscientists or clinicians who have had to contend with the technical intricacies of understanding DCM.

Genotype and phenotype in Parkinson's disease: lessons in heterogeneity from deep brain stimulation.

Variation in the genetic risk(s) of developing Parkinson's disease (PD) undoubtedly contributes to the subsequent phenotypic heterogeneity. Although patients with PD who undergo deep brain stimulation (DBS) are a skewed population, they represent a valuable resource for exploring the relationships between heterogeneous phenotypes and PD genetics. In this series, 94 patients who underwent DBS were screened for mutations in the most common genes associated with PD.

The CamPaIGN study of Parkinson's disease: 10-year outlook in an incident population-based cohort.

Background: Prognosis in Parkinson's disease (PD) remains poorly understood due to a lack of unbiased data on the natural history of treated PD. The CamPaIGN study has been the first to prospectively track disease evolution from diagnosis in an unselected population-representative incident cohort. We now report the 10-year follow-up data, focusing on three key irreversible milestones: postural instability (Hoehn and Yahr 3), dementia and death.

Complementary roles of different oscillatory activities in the subthalamic nucleus in coding motor effort in Parkinsonism.

The basal ganglia may play an important role in the control of motor scaling or effort. Recently local field potential (LFP) recordings from patients with deep brain stimulation electrodes in the basal ganglia have suggested that local increases in the synchronisation of neurons in the gamma frequency band may correlate with force or effort. Whether this feature uniquely codes for effort and whether such a coding mechanism holds true over a range of efforts is unclear.

Exenatide and the treatment of patients with Parkinson's disease.

Unlabelled: BACKGROUND. There is increasing interest in methods to more rapidly and cost-efficiently investigate drugs that are approved for clinical use in the treatment of another condition. Exenatide is a type 2 diabetes treatment that has been shown to have neuroprotective/neurorestorative properties in preclinical models of neurodegeneration.

Parkinson's disease: an update on pathogenesis and treatment.

The Parkinson's disease research field is a rapidly moving one, as many of the relevant processes underlying PD neurodegeneration are being deciphered, enabling novel approaches to treatment to be assessed both in the laboratory and in the clinic. This review aims to highlight the most relevant updates in the PD field, with emphasis on research that may help lead towards an improvement in the treatment of this condition.

Gender differences in quality of life following subthalamic stimulation for Parkinson's disease.

Objectives: Surveys of subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinson's disease (PD) have shown that this procedure is roughly twice more common in men than in women. Here, we investigate possible differences between women and men undergoing STN DBS, with respect to health-related quality of life.

Materials And Methods: Forty-nine consecutive patients (18 women) received STN DBS.

Impact of Duodopa on Quality of Life in Advanced Parkinson's Disease: A UK Case Series.

Treatment options in advanced Parkinson's disease (PD) include subcutaneous apomorphine, pallidal or subthalamic nucleus Deep Brain Stimulation (DBS), or levodopa/carbidopa intestinal gel (LCIG/Duodopa). In this study, we describe the outcome of 12 PD patients with PD related complications started on LCIG, with respect to their quality of life measured by a disease specific validated scale-the PDQ39, together with diaries recording time spent "On," "Off," "Dyskinetic," or "Asleep." At the time of latest follow up, improvements were observed in both the PDQ39 Summary index as well as diary reports of PD symptom control following introduction of LCIG, supporting its use in well selected patients.

Glucocerebrosidase mutations influence the natural history of Parkinson's disease in a community-based incident cohort.

Carriers of mutations in the glucocerebrosidase gene (GBA) are at increased risk of developing Parkinson's disease. The frequency of GBA mutations in unselected Parkinson's disease populations has not been established. Furthermore, no previous studies have investigated the influence of GBA mutations on the natural history of Parkinson's disease using prospective follow-up.

Therapeutic subthalamic nucleus deep brain stimulation reverses cortico-thalamic coupling during voluntary movements in Parkinson's disease.

Deep brain stimulation of the subthalamic nucleus (STN DBS) has become an accepted treatment for patients experiencing the motor complications of Parkinson's disease (PD). While its successes are becoming increasingly apparent, the mechanisms underlying its action remain unclear. Multiple studies using radiotracer-based imaging have investigated DBS-induced regional changes in neural activity.

The glucocerobrosidase E326K variant predisposes to Parkinson's disease, but does not cause Gaucher's disease.

Background: Heterozygous loss-of-function mutations in the acid beta-glucocerebrosidase (GBA1) gene, responsible for the recessive lysosomal storage disorder, Gaucher's disease (GD), are the strongest known risk factor for Parkinson's disease (PD). Our aim was to assess the contribution of GBA1 mutations in a series of early-onset PD.

Methods: One hundred and eighty-five PD patients (with an onset age of ≤50) and 283 age-matched controls were screened for GBA1 mutations by Sanger sequencing.

The risk of hardware infection in deep brain stimulation surgery is greater at impulse generator replacement than at the primary procedure.

Background/aims: Infection of implanted hardware after deep brain stimulation (DBS) has a significant impact on patient morbidity. We examined all patients who underwent DBS procedures over the last 9 years in our centre to assess the infection rate and possible factors related to surgery that may predispose to infection.

Methods: Surgical reports and clinical notes were reviewed in 273 consecutive patients who underwent a total of 519 DBS-related procedures in our institute between November 2002 and September 2011.

Frequency specific activity in subthalamic nucleus correlates with hand bradykinesia in Parkinson's disease.

Local field potential recordings made from the basal ganglia of patients undergoing deep brain stimulation have suggested that frequency specific activity is involved in determining the rate of force development and the peak force at the outset of a movement. However, the extent to which the basal ganglia might be involved in motor performance later on in a sustained contraction is less clear. We therefore recorded from the subthalamic nucleus region (STNr) in patients with Parkinson's disease (PD) as they made maximal voluntary grips.