Movement-related potentials in Parkinson's disease

To date, many different approaches have been used to study the impairment of motor function in Parkinson's disease (PD). Event-related potentials (ERPs) are averaged amplitude fluctuations of the ongoing EEG activity that are time locked to specific sensory, motor or cognitive events, and as such can be used to study different brain processes with an excellent temporal resolution. Movement-related potentials (MRPs) are ERPs associated with processes of voluntary movement preparation and execution in different paradigms. In this review we concentrate on MRPs in PD. We review studies recording the Bereitschaftspotential, the Contingent Negative Variation, and the lateralized readiness potential in PD to highlight the contributions they have made to further understanding motor deficits in PD. Possible directions for future research are also discussed

Event-related potentials and cognition in Parkinson's disease: An integrative review

Cognitive impairment is a common non-motor symptom of Parkinson’s disease (PD), but the nature of cognitive changes varies considerably between individuals. According to the dual-syndrome hypothesis, one cluster of patients is characterized by deficits in executive function that may be related to fronto-striatal dysfunction. Other patients primarily show non-frontal cognitive impairments that progress rapidly to PD dementia (PDD). We provide a comprehensive review of event-related potential (ERP) studies to identify ERP measures substantiating the heterogeneity of cognitive impairment in PD. Our review revealed evidence for P3b and mismatch-negativity alterations in PDD, but not in non-demented PD, indicating that alterations of these ERPs constitute electrophysiological markers for PDD. In contrast, ERP correlates of executive functions, such as NoGo-P3, N2, and error(-related) negativity (Ne/ERN), appear to be attenuated in non-demented PD patients in a dopamine-dependent manner. Hence, ERP measures confirm and yield distinct electrophysiological markers for the heterogeneity of cognitive impairment in PD. We discuss limitations and open questions of the ERP approach and provide directions and predictions for future ERP research

In Parkinson's disease on a probabilistic Go/NoGo task deep brain stimulation of the subthalamic nucleus only interferes with withholding of the most prepotent responses

The evidence on the impact of subthalamic nucleus deep brain stimulation (STN-DBS) on action restraint on Go/NoGO reaction time (RT) tasks in Parkinson's disease (PD) is inconsistent; with some studies reporting no effect and others finding that STN stimulation interferes with withholding of responses and results in more commission errors relative to STN-DBS off. We used a task in which the probability of Go stimuli varied from 100 % (simple RT task) to 80, 50 and 20 % (probabilistic Go/NoGo RT task), thus altering the prepotency of the response and the difficulty in withholding it on NoGo trials. Twenty PD patients with STN-DBS, ten unoperated PD patients and ten healthy controls participated in the study. All participants were tested twice; the order of on versus off stimulation for STN-DBS PD patients was counterbalanced. Both STN-DBS and unoperated PD patients were tested on medication. The results indicated that STN-DBS selectively decreased discriminability when the response was most prepotent (high-80 %, as compared to low Go probability trials-50 and 20 %). Movement times were faster with STN stimulation than with DBS off across different Go probability levels. There was neither an overall nor a selective effect of STN-DBS on RTs depending on the level of Go probability. Furthermore, compared to healthy controls, both STN-DBS and unoperated PD patients were more prone to making anticipatory errors; which was not influenced by STN stimulation. The results provide evidence for 'load-dependent' effects of STN stimulation on action restraint as a function of the prepotency of the Go response

Continuous Theta Burst Stimulation Over the Dorsolateral Prefrontal Cortex and the Pre-SMA Alter Drift Rate and Response Thresholds Respectively During Perceptual Decision-Making

BACKGROUND: The speed-accuracy trade-off (SAT) refers to the balancing of speed versus accuracy during decision-making. SAT is very commonly investigated with perceptual decision-making tasks such as the moving dots task (MDT). The dorsolateral prefrontal cortex (DLPFC) and the pre-supplementary motor area (pre-SMA) are two brain regions considered to be involved in the control of SAT. OBJECTIVES/HYPOTHESES: The study tested whether the DLPFC and the pre-SMA play an essential role in the control of SAT. We hypothesized that continuous theta burst stimulation (cTBS) over the right DLPFC would primarily alter the rate of accumulation of evidence, whereas stimulation of the pre-SMA would influence the threshold for reaching a decision. METHODS: Fifteen (5 females; mean age = 30, SD =5.40) healthy volunteers participated in the study. We used two versions of the MDT and cTBS over the right DLPFC, pre-SMA and sham stimulation. The drift diffusion model was fit to the behavioural data (reaction time and error rate) in order to calculate the drift rate, boundary separation (threshold) and non-decision time. RESULTS: cTBS over the right DLPFC decreased the rate of accumulation of evidence (i.e. the drift rate from the diffusion model) in high (0.35 and 0.5) but not in low coherence trials. cTBS over the pre-SMA changed the boundary separation/threshold required to reach a decision on accuracy, but not on speed trials. CONCLUSIONS: The results suggest for the first time that both the DLPFC and the pre-SMA make essential but distinct contributions to the modulation of SAT

Deep Brain Stimulation of the Subthalamic Nucleus Does Not Affect the Decrease of Decision Threshold during the Choice Process When There Is No Conflict, Time Pressure, or Reward

During a decision process, the evidence supporting alternative options is integrated over time, and the choice is made when the accumulated evidence for one of the options reaches a decision threshold. Humans and animals have an ability to control the decision threshold, that is, the amount of evidence that needs to be gathered to commit to a choice, and it has been proposed that the subthalamic nucleus (STN) is important for this control. Recent behavioral and neurophysiological data suggest that, in some circumstances, the decision threshold decreases with time during choice trials, allowing overcoming of indecision during difficult choices. Here we asked whether this within-trial decrease of the decision threshold is mediated by the STN and if it is affected by disrupting information processing in the STN through deep brain stimulation (DBS). We assessed 13 patients with Parkinson's disease receiving bilateral STN DBS six or more months after the surgery, 11 age-matched controls and 12 young healthy controls. All participants completed a series of decision trials, in which the evidence was presented in discrete time points, which allowed more direct estimation of the decision threshold. The participants differed widely in the slope of their decision threshold, ranging from constant threshold within a trial to steeply decreasing. However, the slope of the decision threshold did not depend on whether STN DBS was switched on or off and did not differ between the patients and controls. Furthermore, there was no difference in accuracy and RT between the patients in the on and off stimulation conditions and healthy controls. Previous studies that have reported modulation of the decision threshold by STN DBS or unilateral subthalamotomy in Parkinson's disease have involved either fast decision-making under conflict or time pressure or in anticipation of high reward. Our findings suggest that, in the absence of reward, decision conflict, or time pressure for decision-making, the STN does not play a critical role in modulating the within-trial decrease of decision thresholds during the choice process

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. However, little is known about the effect of DBS on connectivity within neural networks; in other words, whether DBS impacts upon functional integration of specialized regions of cortex. In this work, we report the first findings of fMRI in 10 subjects with PD and fully implanted DBS hardware receiving efficacious stimulation. Despite the technical demands associated with the safe acquisition of fMRI data from patients with implanted hardware, robust activation changes were identified in the insula cortex and thalamus in response to therapeutic STN DBS. We then quantified the neuromodulatory effects of DBS and compared sixteen dynamic causal models of effective connectivity between the two identified nodes. Using Bayesian model comparison, we found unequivocal evidence for the modulation of extrinsic (between region), i.e. cortico-thalamic and thalamo-cortical connections. Using Bayesian model parameter averaging we found that during voluntary movements, DBS reversed the effective connectivity between regions of the cortex and thalamus. This casts the therapeutic effects of DBS in a fundamentally new light, emphasising a role in changing distributed cortico-subcortical interactions. We conclude that STN DBS does impact upon the effective connectivity between the cortex and thalamus by changing their sensitivities to extrinsic afferents. Furthermore, we confirm that fMRI is both feasible and is tolerated well by these patients provided strict safety measures are adhered to

Visual change detection on tunnel linings

We describe an automated system for detecting, localising, clustering and ranking visual changes on tunnel surfaces. The system is designed to provide assistance to expert human inspectors carrying out structural health monitoring and maintenance on ageing tunnel networks. A three-dimensional tunnel surface model is first recovered from a set of reference images using Structure from Motion techniques. New images are localised accurately within the model and changes are detected versus the reference images and model geometry. We formulate the problem of detecting changes probabilistically and evaluate the use of different feature maps and a novel geometric prior to achieve invariance to noise and nuisance sources such as parallax and lighting changes. A clustering and ranking method is proposed which efficiently presents detected changes and further improves the inspection efficiency. System performance is assessed on a real data set collected using a low-cost prototype capture device and labelled with ground truth. Results demonstrate that our system is a step towards higher frequency visual inspection at a reduced cost.The authors gratefully acknowledge the support by Toshiba Research Europe.This is the accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s00138-014-0648-8

E-commerce adoption by SMEs in developing countries: evidence from Indonesia

This study aims to provide an overview of e-commerce adoption by SMEs in developing countries and, in particular, the extent of the adoption of e-commerce by Indonesian SMEs. It identifies the e-commerce benefits realized by these SMEs and investigates the relationship between the levels of e-commerce adoption and the benefits thus realized. The study was motivated by the limited studies related to e-commerce adoption by SMEs, especially in developing countries. In addition, it seems that most e-commerce studies are focused more on upstream issues: to see the factors that facilitate, or barriers faced regarding e-commerce adoption, rather than downstream issues: to see post-adoption benefits. This certainly limits our understanding about e-commerce adoption by SMEs in developing countries, as well as the post-adoption benefits of e-commerce. Indonesia was chosen as the place in which to conduct the study. A survey of 292 SMEs shows that the majority of them are still at an early stage in their adoption of e-commerce. Their use of e-commerce is dominated by marketing and purchasing and procurement activities. “Extending market reach”, “increased sales”, “improved external communication”, “improved company image”, “improved speed of processing”, and “increased employee productivity” are reported as the top six e-commerce benefits perceived by these SMEs. This study also shows that SMEs at the higher level of e-commerce adoption experience greater e-commerce benefits than those at other levels of adoption

Translational considerations for the design of untethered nanomaterials in human neural stimulation

Neural stimulation is a powerful tool to study brain physiology and an effective treatment for many neurological disorders. Conventional interfaces use electrodes implanted in the brain. As these are often invasive and have limited spatial targeting, they carry a potential risk of side-effects. Smaller neural devices may overcome these obstacles, and as such, the field of nanoscale and remotely powered neural stimulation devices is growing. This review will report on current untethered, injectable nanomaterial technologies intended for neural stimulation, with a focus on material-tissue interface engineering. We will review nanomaterials capable of wireless neural stimulation, and discuss their stimulation mechanisms. Taking cues from more established nanomaterial fields (e.g., cancer theranostics, drug delivery), we will then discuss methods to modify material interfaces with passive and bioactive coatings. We will discuss methods of delivery to a desired brain region, particularly in the context of how delivery and localization are affected by surface modification. We will also consider each of these aspects of nanoscale neurostimulators with a focus on their prospects for translation to clinical use

Cerebral activations related to ballistic, stepwise interrupted and gradually modulated movements in parkinson patients

Patients with Parkinson's disease (PD) experience impaired initiation and inhibition of movements such as difficulty to start/stop walking. At single-joint level this is accompanied by reduced inhibition of antagonist muscle activity. While normal basal ganglia (BG) contributions to motor control include selecting appropriate muscles by inhibiting others, it is unclear how PD-related changes in BG function cause impaired movement initiation and inhibition at single-joint level. To further elucidate these changes we studied 4 right-hand movement tasks with fMRI, by dissociating activations related to abrupt movement initiation, inhibition and gradual movement modulation. Initiation and inhibition were inferred from ballistic and stepwise interrupted movement, respectively, while smooth wrist circumduction enabled the assessment of gradually modulated movement. Task-related activations were compared between PD patients (N = 12) and healthy subjects (N = 18). In healthy subjects, movement initiation was characterized by antero-ventral striatum, substantia nigra (SN) and premotor activations while inhibition was dominated by subthalamic nucleus (STN) and pallidal activations, in line with the known role of these areas in simple movement. Gradual movement mainly involved antero-dorsal putamen and pallidum. Compared to healthy subjects, patients showed reduced striatal/SN and increased pallidal activation for initiation, whereas for inhibition STN activation was reduced and striatal-thalamo-cortical activation increased. For gradual movement patients showed reduced pallidal and increased thalamo-cortical activation. We conclude that PD-related changes during movement initiation fit the (rather static) model of alterations in direct and indirect BG pathways. Reduced STN activation and regional cortical increased activation in PD during inhibition and gradual movement modulation are better explained by a dynamic model that also takes into account enhanced responsiveness to external stimuli in this disease and the effects of hyper-fluctuating cortical inputs to the striatum and STN in particular