Functional network topology in drug resistant and well-controlled idiopathic generalized epilepsy:a resting state functional MRI study

Despite an increasing number of drug treatment options for people with idiopathic generalized epilepsy (IGE), drug resistance remains a significant issue and the mechanisms underlying it remain poorly understood. Previous studies have largely focused on potential cellular or genetic explanations for drug resistance. However, epilepsy is understood to be a network disorder and there is a growing body of literature suggesting altered topology of large-scale resting networks in people with epilepsy compared with controls. We hypothesize that network alterations may also play a role in seizure control. The aim of this study was to compare resting state functional network structure between well-controlled IGE (WC-IGE), drug resistant IGE (DR-IGE) and healthy controls. Thirty-three participants with IGE (10 with WC-IGE and 23 with DR-IGE) and 34 controls were included. Resting state functional MRI networks were constructed using the Functional Connectivity Toolbox (CONN). Global graph theoretic network measures of average node strength (an equivalent measure to mean degree in a network that is fully connected), node strength distribution variance, characteristic path length, average clustering coefficient, small-world index and average betweenness centrality were computed. Graphs were constructed separately for positively weighted connections and for absolute values. Individual nodal values of strength and betweenness centrality were also measured and 'hub nodes' were compared between groups. Outcome measures were assessed across the three groups and between both groups with IGE and controls. The IGE group as a whole had a higher average node strength, characteristic path length and average betweenness centrality. There were no clear differences between groups according to seizure control. Outcome metrics were sensitive to whether negatively correlated connections were included in network construction. There were no clear differences in the location of 'hub nodes' between groups. The results suggest that, irrespective of seizure control, IGE interictal network topology is more regular and has a higher global connectivity compared to controls, with no alteration in hub node locations. These alterations may produce a resting state network that is more vulnerable to transitioning to the seizure state. It is possible that the lack of apparent influence of seizure control on network topology is limited by challenges in classifying drug response. It is also demonstrated that network topological features are influenced by the sign of connectivity weights and therefore future methodological work is warranted to account for anticorrelations in graph theoretic studies

Study protocol for a randomised pilot study of a computer-based, non-pharmacological cognitive intervention for motor slowing and motor fatigue in Parkinson’s disease

Abstract Background Parkinson’s disease (PD) is a chronic, neurodegenerative disorder affecting over 137,000 people in the UK and an estimated five million people worldwide. Treatment typically involves long-term dopaminergic therapy, which improves motor symptoms, but is associated with dose-limiting side effects. Developing effective complementary, non-pharmacological interventions is of considerable importance. This paper presents the protocol for a three-arm pilot study to test the implementation of computer-based cognitive training that aims to produce improvements or maintenance of motor slower and motor fatigue symptoms in people with PD. The primary objective is to assess recruitment success and usability of external data capture devices during the intervention. The secondary objectives are to obtain estimates of variance and effect size for changes in primary and secondary outcome measures to inform sample size calculations and study design for a larger scale trial. Methods The study aims to recruit between 40 and 60 adults with early- to middle-stage PD (Hoehn and Yahr 1–3) from National Health Service (NHS) outpatients’ clinics and support groups across North Wales, UK. Participants will be randomised to receive training over five sessions in either a spatial grid navigation task, a sequential subtraction task or a spatial memory task. Patient-centred outcome measures will include motor examination scores from part 3 of the UPDRS-III and data from movement kinematic and finger tapping tasks. Discussion The results of this study will provide information regarding the feasibility of conducting a larger randomised control trial of non-pharmacological cognitive interventions of motor symptoms in PD. Trial registration ISRCTN, ISRCTN12565492. Registered 4 April 2018—retrospectively registered, in accordance with the WHO Trial Registration Data Set

Does transcranial direct current stimulation to prefrontal cortex affect mood and emotional memory retrieval in healthy individuals?

Studies using transcranial direct current stimulation (tDCS) of prefrontal cortex to improve symptoms of depression have had mixed results. We examined whether using tDCS to change the balance of activity between left and right dorsolateral prefrontal cortex (DLPFC) can alter mood and memory retrieval of emotional material in healthy volunteers. Participants memorised emotional images, then tDCS was applied bilaterally to DLPFC while they performed a stimulus-response compatibility task. Participants were then presented with a set of images for memory retrieval. Questionnaires to examine mood and motivational state were administered at the beginning and end of each session. Exploratory data analyses showed that the polarity of tDCS to DLPFC influenced performance on a stimulus-response compatibility task and this effect was dependent on participants' prior motivational state. However, tDCS polarity had no effect on the speed or accuracy of memory retrieval of emotional images and did not influence positive or negative affect. These findings suggest that the balance of activity between left and right DLPFC does not play a critical role in the mood state of healthy individuals. We suggest that the efficacy of prefrontal tDCS depends on the initial activation state of neurons and future work should take this into account. © 2014 Morgan et al

Brain stimulation studies of non-motor cerebellar function: A systematic review

Evidence for a cerebellar role in non-motor functions has been demonstrated by clinical and neuroimaging research. These approaches do not allow causal relationships to be inferred though the experimental manipulation of the cerebellum. Transcranial magnetic and current stimulation may allow better understanding of the cerebellum via the temporary alteration of its operation in healthy volunteers. This review examined all studies of the cerebellar role in non-motor functions using non-invasive brain stimulation. Of 7585 papers captured by an initial search, 26 met specific selection criteria. Analysis revealed behavioural effects across learning, memory, cognition, emotional processing, perception and timing, though the results were not sufficiently similar as to offer a definitive statement of the cerebellum's role. The non-invasive application of stimulation to the cerebellum presents challenges due to surrounding anatomy and the relatively small target areas involved. This review analysed the methods used to address these challenges with a view to suggesting methodological improvements for the establishment of standards for the location of cerebellar stimulation targets and appropriate levels of stimulation. © 2013 Elsevier Ltd

Cerebellar contributions to spatial memory

There is mounting evidence for a role for the cerebellum in working memory (WM). The majority of relevant studies has examined verbal WM and has suggested specialisation of the right cerebellar hemisphere for language processing. Our study used theta burst stimulation (TBS) to examine whether there is a converse cerebellar hemispheric specialisation for spatial WM. We conducted two experiments to examine spatial WM performance before and after TBS to mid-hemispheric and lateral locations in the posterior cerebellum. Participants were required to recall the order of presentation of targets on a screen or the targets' order of presentation and their locations. We observed impaired recollection of target order after TBS to the mid left cerebellar hemisphere and reduced response speed after TBS to the left lateral cerebellum. We suggest that these results give evidence of the contributions of the left cerebellar cortex to the encoding and retrieval of spatial information

Hemispheric specialisation in haptic processing

This study investigated the organising principles of touch. We examined specialisations within the haptic system and their hemispheric distribution. Haptic processing consists of the integration of data from multiple sources to form a single percept. Previous research provides strong support for a hierarchical and functional distribution within haptic processing. We investigated hemispheric asymmetry in haptic discrimination of objects with differing textures and centres of mass. By analogy with vision it was hypothesised that participants would demonstrate a left-hand advantage for centre of mass discrimination (a 'global', presumed right hemisphere, judgement) and a right-hand advantage for surface texture judgements (a 'local', presumed left hemisphere discrimination). We found that left-handed participants showed these effects to a lesser degree than did the right-handers, consistent with the notion that left-handed people generally show weaker asymmetries in bimanual tasks. In a second experiment the effect of conflicting information on haptic percept formation was investigated. Following from the previous hypotheses it was predicted that participants would be more accurate with their right hands at judging conflicting surfaces. Contrary to predictions an advantage was demonstrated for the left hand for texture discrimination and for the right hand for centre of mass judgement