Effects of home-based EEG neurofeedback training as a non-pharmacological intervention for Parkinson's disease.

OBJECTIVES: Aberrant movement-related cortical activity has been linked to impaired motor function in Parkinson's disease (PD). Dopaminergic drug treatment can restore these, but dosages and long-term treatment are limited by adverse side-effects. Effective non-pharmacological treatments could help reduce reliance on drugs. This experiment reports the first study of home-based electroencephalographic (EEG) neurofeedback training as a non-pharmacological candidate treatment for PD. Our primary aim was to test the feasibility of our EEG neurofeedback intervention in a home setting. METHODS: Sixteen people with PD received six home visits comprising symptomology self-reports, a standardised motor assessment, and a precision handgrip force production task while EEG was recorded (visits 1, 2 and 6); and 3 × 1-hr EEG neurofeedback training sessions to supress the EEG mu rhythm before initiating handgrip movements (visits 3 to 5). RESULTS: Participants successfully learned to self-regulate mu activity, and this appeared to expedite the initiation of precision movements (i.e., time to reach target handgrip force off-medication pre-intervention = 628 ms, off-medication post-intervention = 564 ms). There was no evidence of wider symptomology reduction (e.g., Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III Motor Examination, off-medication pre-intervention = 29.00, off-medication post intervention = 30.07). Interviews indicated that the intervention was well-received. CONCLUSION: Based on the significant effect of neurofeedback on movement-related cortical activity, positive qualitative reports from participants, and a suggestive benefit to movement initiation, we conclude that home-based neurofeedback for people with PD is a feasible and promising non-pharmacological treatment that warrants further research.

Midbrain structure volume, estimated myelin and functional connectivity in idiopathic generalised epilepsy.

BACKGROUND: Structural and functional neuroimaging studies often overlook lower basal ganglia structures located in and adjacent to the midbrain due to poor contrast on clinically acquired T1-weighted scans. Here, we acquired T1-weighted, T2-weighted, and resting-state fMRI scans to investigate differences in volume, estimated myelin content and functional connectivity of the substantia nigra (SN), subthalamic nuclei (SubTN) and red nuclei (RN) of the midbrain in IGE. METHODS: Thirty-three patients with IGE (23 refractory, 10 non-refractory) and 39 age and sex-matched healthy controls underwent MR imaging. Midbrain structures were automatically segmented from T2-weighted images and structural volumes were calculated. The estimated myelin content for each structure was determined using a T1-weighted/T2-weighted ratio method. Resting-state functional connectivity analysis of midbrain structures (seed-based) was performed using the CONN toolbox. RESULTS: An increased volume of the right RN was found in IGE and structural volumes of the right SubTN differed between patients with non-refractory and refractory IGE. However, no volume findings survived corrections for multiple comparisons. No myelin alterations of midbrain structures were found for any subject groups. We found functional connectivity alterations including significantly decreased connectivity between the left SN and the thalamus and significantly increased connectivity between the right SubTN and the superior frontal gyrus in IGE. CONCLUSIONS: We report volumetric and functional connectivity alterations of the midbrain in patients with IGE. We postulate that potential increases in structural volumes are due to increased iron deposition that impacts T2-weighted contrast. These findings are consistent with previous studies demonstrating pathophysiological abnormalities of the lower basal ganglia in animal models of generalised epilepsy.

Spatial Binding Impairments in Visual Working Memory following Temporal Lobectomy.

Disorders of the medial temporal lobe (MTL) adversely affect visual working memory (vWM) performance, including feature binding. It is unclear whether these impairments generalize across visual dimensions or are specifically spatial. To address this issue, we compared performance in two tasks of 13 epilepsy patients, who had undergone a temporal lobectomy, and 15 healthy controls. In the vWM task, participants recalled the color of one of two polygons, previously displayed side by side. At recall, a location or shape probe identified the target. In the perceptual task, participants estimated the centroid of three visible disks. Patients recalled the target color less accurately than healthy controls because they frequently swapped the nontarget with the target color. Moreover, healthy controls and right temporal lobectomy patients made more swap errors following shape than space probes. Left temporal lobectomy patients, showed the opposite pattern of errors instead. Patients and controls performed similarly in the perceptual task. We conclude that left MTL damage impairs spatial binding in vWM, and that this impairment does not reflect a perceptual or attentional deficit.

Altered Structural Brain Networks in Refractory and Nonrefractory Idiopathic Generalized Epilepsy.

Introduction: Idiopathic generalized epilepsy (IGE) is a collection of generalized nonlesional epileptic network disorders. Around 20-40% of patients with IGE are refractory to antiseizure medication, and mechanisms underlying refractoriness are poorly understood. Here, we characterize structural brain network alterations and determine whether network alterations differ between patients with refractory and nonrefractory IGE. Methods: Thirty-three patients with IGE (10 nonrefractory and 23 refractory) and 39 age- and sex-matched healthy controls were studied. Network nodes were segmented from T1-weighted images, while connections between these nodes (edges) were reconstructed from diffusion magnetic resonance imaging (MRI). Diffusion networks of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and streamline count (Count) were studied. Differences between all patients, refractory, nonrefractory, and control groups were computed using network-based statistics. Nodal volume differences between groups were computed using Cohen's d effect size calculation. Results: Patients had significantly decreased bihemispheric FA and Count networks and increased MD and RD networks compared with controls. Alterations in network architecture, with respect to controls, differed depending on treatment outcome, including predominant FA network alterations in refractory IGE and increased nodal volume in nonrefractory IGE. Diffusion MRI networks were not influenced by nodal volume. Discussion: Although a nonlesional disorder, patients with IGE have bihemispheric structural network alterations that may differ between patients with refractory and nonrefractory IGE. Given that distinct nodal volume and FA network alterations were observed between treatment outcome groups, a multifaceted network analysis may be useful for identifying imaging biomarkers of refractory IGE.

Automated subcortical volume estimation from 2D MRI in epilepsy and implications for clinical trials.

PURPOSE: Most techniques used for automatic segmentation of subcortical brain regions are developed for three-dimensional (3D) MR images. MRIs obtained in non-specialist hospitals may be non-isotropic and two-dimensional (2D). Automatic segmentation of 2D images may be challenging and represents a lost opportunity to perform quantitative image analysis. We determine the performance of a modified subcortical segmentation technique applied to 2D images in patients with idiopathic generalised epilepsy (IGE). METHODS: Volume estimates were derived from 2D (0.4 × 0.4 × 3 mm) and 3D (1 × 1x1mm) T1-weighted acquisitions in 31 patients with IGE and 39 healthy controls. 2D image segmentation was performed using a modified FSL FIRST (FMRIB Integrated Registration and Segmentation Tool) pipeline requiring additional image reorientation, cropping, interpolation and brain extraction prior to conventional FIRST segmentation. Consistency between segmentations was assessed using Dice coefficients and volumes across both approaches were compared between patients and controls. The influence of slice thickness on consistency was further assessed using 2D images with slice thickness increased to 6 mm. RESULTS: All average Dice coefficients showed excellent agreement between 2 and 3D images across subcortical structures (0.86-0.96). Most 2D volumes were consistently slightly lower compared to 3D volumes. 2D images with increased slice thickness showed lower agreement with 3D images with lower Dice coefficients (0.55-0.83). Significant volume reduction of the left and right thalamus and putamen was observed in patients relative to controls across 2D and 3D images. CONCLUSION: Automated subcortical volume estimation of 2D images with a resolution of 0.4 × 0.4x3mm using a modified FIRST pipeline is consistent with volumes derived from 3D images, although this consistency decreases with an increased slice thickness. Thalamic and putamen atrophy has previously been reported in patients with IGE. Automated subcortical volume estimation from 2D images is feasible and most reliable at using in-plane acquisitions greater than 1 mm x 1 mm and provides an opportunity to perform quantitative image analysis studies in clinical trials.

Probabilistic mapping of thalamic nuclei and thalamocortical functional connectivity in idiopathic generalised epilepsy.

It is well established that abnormal thalamocortical systems play an important role in the generation and maintenance of primary generalised seizures. However, it is currently unknown which thalamic nuclei and how nuclear-specific thalamocortical functional connectivity are differentially impacted in patients with medically refractory and non-refractory idiopathic generalised epilepsy (IGE). In the present study, we performed structural and resting-state functional magnetic resonance imaging (MRI) in patients with refractory and non-refractory IGE, segmented the thalamus into constituent nuclear regions using a probabilistic MRI segmentation method and determined thalamocortical functional connectivity using seed-to-voxel connectivity analyses. We report significant volume reduction of the left and right anterior thalamic nuclei only in patients with refractory IGE. Compared to healthy controls, patients with refractory and non-refractory IGE had significant alterations of functional connectivity between the centromedian nucleus and cortex, but only patients with refractory IGE had altered cortical connectivity with the ventral lateral nuclear group. Patients with refractory IGE had significantly increased functional connectivity between the left and right ventral lateral posterior nuclei and cortical regions compared to patients with non-refractory IGE. Cortical effects were predominantly located in the frontal lobe. Atrophy of the anterior thalamic nuclei and resting-state functional hyperconnectivity between ventral lateral nuclei and cerebral cortex may be imaging markers of pharmacoresistance in patients with IGE. These structural and functional abnormalities fit well with the known importance of thalamocortical systems in the generation and maintenance of primary generalised seizures, and the increasing recognition of the importance of limbic pathways in IGE.

Academic factors in medical recruitment: evidence to support improvements in medical recruitment and retention by improving the academic content in medical posts.

There is a major problem with medical recruitment and retention in the UK. The 2018 General Medical Council (GMC) report 'The state of medical education and practice in the UK' has indicated that a high proportion of doctors are thinking of either giving up medical practice or reducing their hours in the next 3 years. If this trend continues the shortage of doctors in the UK will increase despite a modest increase in the supply of doctors.This paper investigates the evidence that increasing the academic component of medical posts may help retain doctors in practice by providing experience and support in an area of medical practice, which appears to fulfil a significant number of doctors' aspirations. The paper shows that this aspect of medical practice is poorly represented in medical workforce strategic thinking and should be considered as an integral aspect of policy and practice in medical workforce delivery.