Neural correlates of true and false memory in mild cognitive impairment

The goal of this research was to investigate the changes in neural processing in mild cognitive impairment. We measured phase synchrony, amplitudes, and event-related potentials in veridical and false memory to determine whether these differed in participants with mild cognitive impairment compared with typical, age-matched controls. Empirical mode decomposition phase locking analysis was used to assess synchrony, which is the first time this analysis technique has been applied in a complex cognitive task such as memory processing. The technique allowed assessment of changes in frontal and parietal cortex connectivity over time during a memory task, without a priori selection of frequency ranges, which has been shown previously to influence synchrony detection. Phase synchrony differed significantly in its timing and degree between participant groups in the theta and alpha frequency ranges. Timing differences suggested greater dependence on gist memory in the presence of mild cognitive impairment. The group with mild cognitive impairment had significantly more frontal theta phase locking than the controls in the absence of a significant behavioural difference in the task, providing new evidence for compensatory processing in the former group. Both groups showed greater frontal phase locking during false than true memory, suggesting increased searching when no actual memory trace was found. Significant inter-group differences in frontal alpha phase locking provided support for a role for lower and upper alpha oscillations in memory processing. Finally, fronto-parietal interaction was significantly reduced in the group with mild cognitive impairment, supporting the notion that mild cognitive impairment could represent an early stage in Alzheimer’s disease, which has been described as a ‘disconnection syndrome’

Anterior Thalamic High Frequency Band Activity Is Coupled with Theta Oscillations at Rest

Cross-frequency coupling (CFC) between slow and fast brain rhythms, in the form of phase–amplitude coupling (PAC), is proposed to enable the coordination of neural oscillatory activity required for cognitive processing. PAC has been identified in the neocortex and mesial temporal regions, varying according to the cognitive task being performed and also at rest. PAC has also been observed in the anterior thalamic nucleus (ATN) during memory processing. The thalamus is active during the resting state and has been proposed to be involved in switching between task-free cognitive states such as rest, in which attention is internally-focused, and externally-focused cognitive states, in which an individual engages with environmental stimuli. It is unknown whether PAC is an ongoing phenomenon during the resting state in the ATN, which is modulated during different cognitive states, or whether it only arises during the performance of specific tasks. We analyzed electrophysiological recordings of ATN activity during rest from seven patients who received thalamic electrodes implanted for treatment of pharmacoresistant focal epilepsy. PAC was identified between theta (4–6 Hz) phase and high frequency band (80–150 Hz) amplitude during rest in all seven patients, which diminished during engagement in tasks involving an external focus of attention. The findings are consistent with the proposal that theta–gamma coupling in the ATN is an ongoing phenomenon, which is modulated by task performance

Modulation of Working Memory Using Transcranial Electrical Stimulation: A Direct Comparison Between TACS and TDCS

Transcranial electrical stimulation (TES) has been considered a promising tool for improving working memory (WM) performance. Recent studies have demonstrated modulation of networks underpinning WM processing through application of transcranial alternating current (TACS) as well as direct current (TDCS) stimulation. Differences between study designs have limited direct comparison of the efficacy of these approaches, however. Here we directly compared the effects of theta TACS (6 Hz) and anodal TDCS on WM, applying TACS to the frontal-parietal loop and TDCS to the dorsolateral prefrontal cortex (DLPFC). WM was evaluated using a visual 2-back WM task. A within-subject, crossover design was applied (N = 30) in three separate sessions. TACS, TDCS, and sham stimulation were administered in a counterbalanced order, and the WM task was performed before, during, and after stimulation. Neither reaction times for hits (RT-hit) nor accuracy differed according to stimulation type with this study design. A marked practice effect was noted, however, with improvement in RT-hit irrespective of stimulation type, which peaked at the end of the second session. Pre-stimulation RT-hits in session three returned to the level observed pre-stimulation in session two, irrespective of stimulation type. The participants who received sham stimulation in session one and had therefore improved their performance due to practice alone, had thus reached a plateau by session two, enabling us to pool RT-hits from sessions two and three for these participants. The pooling allowed implementation of a within-subject crossover study design, with a direct comparison of the effects of TACS and TDCS in a subgroup of participants (N = 10), each of whom received both stimulation types, in a counterbalanced order, with pre-stimulation performance the same for both sessions. TACS resulted in a greater improvement in RT-hits than TDCS (F(2,18) = 4.31 p = 0.03). Our findings suggest that future work optimizing the application of TACS has the potential to facilitate WM performance

Functional electrical stimulation driven by a brain–computer interface in acute and subacute stroke patients impacts beta power and long-range temporal correlation

Functional electrical stimulation (FES) is a standard rehabilitation approach applied by therapists to aid motor recovery in a paretic limb post-stroke. Information pertaining to the timing of a movement attempt can be obtained from changes in the power of oscillatory electrophysiological activity in motor cortical regions, derived from scalp electroencephalographic (EEG) recordings. The use of a brain–computer interface (BCI), to enable delivery of FES within a tight temporal window with a movement attempt detected in scalp EEG, is associated with greater motor recovery than conventional FES application in patients in the chronic phase post-stroke. We hypothesized that the heightened neural plasticity early post-stroke could further enhance motor recovery and that motor improvements would be accompanied by changes in the motor cortical sensorimotor rhythm after compared with before treatment. Here we assessed clinical outcome and changes in the sensorimotor rhythm in patients following subcortical stroke affecting the non-dominant hemisphere from a study comparing timing of FES delivery using a BCI, with a Sham group, receiving FES with no such temporal relationship. The BCI group showed greater clinical improvement following the treatment, particularly early post-stroke, and a greater decrease in beta oscillatory power and long-range temporal correlation over contralateral (ipsilesional) motor cortex. The electrophysiological changes are consistent with a reduction in compensatory processes and a transition towards a subcritical state when movement is triggered at the time of movement detection based on motor cortical oscillations

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

Testing for significance of phase synchronisation dynamics in the EEG

A number of tests exist to check for statistical significance of phase synchronisation within the Electroencephalogram (EEG); however, the majority suffer from a lack of generality and applicability. They may also fail to account for temporal dynamics in the phase synchronisation, regarding synchronisation as a constant state instead of a dynamical process. Therefore, a novel test is developed for identifying the statistical significance of phase synchronisation based upon a combination of work characterising temporal dynamics of multivariate time-series and Markov modelling. We show how this method is better able to assess the significance of phase synchronisation than a range of commonly used significance tests. We also show how the method may be applied to identify and classify significantly different phase synchronisation dynamics in both univariate and multivariate datasets

A toolbox for decoding BCI commands based on event-related potentials

Commands in brain-computer interface (BCI) applications often rely on the decoding of event-related potentials (ERP). For instance, the P300 potential is frequently used as a marker of attention to an oddball event. Error-related potentials and the N2pc signal are further examples of ERPs used for BCI control. One challenge in decoding brain activity from the electroencephalogram (EEG) is the selection of the most suitable channels and appropriate features for a particular classification approach. Here we introduce a toolbox that enables ERP-based decoding using the full set of channels, while automatically extracting informative components from relevant channels. The strength of our approach is that it handles sequences of stimuli that encode multiple items using binary classification, such as target vs. nontarget events typically used in ERP-based spellers. We demonstrate examples of application scenarios and evaluate the performance of four openly available datasets: a P300-based matrix speller, a P300-based rapid serial visual presentation (RSVP) speller, a binary BCI based on the N2pc, and a dataset capturing error potentials. We show that our approach achieves performances comparable to those in the original papers, with the advantage that only conventional preprocessing is required by the user, while channel weighting and decoding algorithms are internally performed. Thus, we provide a tool to reliably decode ERPs for BCI use with minimal programming requirements

CSF macrophage migration inhibitory factor levels did not predict steroid treatment response after optic neuritis in patients with multiple sclerosis.

Glucocorticoid (GC) refractory relapses in patients with multiple sclerosis (MS) or clinically isolated syndrome (CIS), who are in potential need of treatment escalation, are a key challenge in routine clinical practice. The pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) has been shown to be an endogenous counter-regulator of GC, and potentiates autoimmune-mediated neuroinflammation. In order to evaluate whether MIF levels are elevated in the cerebrospinal fluid (CSF) of MS patients (CSF-MIF), and whether they are higher still during a GC refractory relapse, we compared CSF-MIF concentrations of CIS/MS patients with acute optic neuritis as their first inflammatory episode (ON, n = 20), CIS/MS patients with a stable disease progression/without relapse (CIS/MS w/o, n = 18), and healthy controls (HC, n = 20) using ANOVA. Mean CSF-MIF concentrations in CIS/MS w/o patients were significantly higher than in ON patients and HCs, whereas ON patients and HCs did not differ. A subgroup analysis of the ON group revealed 10 patients to be responsive to GC-treatment (GC-ON) and 10 patients refractory under GC-treatment (rGC-ON). However, mean CSF-MIF concentrations did not differ between GC-ON and rGC-ON cases. We therefore conclude that MIF is not suitable for distinguishing GC responders from non-responders in a group of patients with acute optic neuritis, but it rather mirrors the ongoing inflammation in long-term MS disease progression

Table_1_A toolbox for decoding BCI commands based on event-related potentials.XLSX

Commands in brain-computer interface (BCI) applications often rely on the decoding of event-related potentials (ERP). For instance, the P300 potential is frequently used as a marker of attention to an oddball event. Error-related potentials and the N2pc signal are further examples of ERPs used for BCI control. One challenge in decoding brain activity from the electroencephalogram (EEG) is the selection of the most suitable channels and appropriate features for a particular classification approach. Here we introduce a toolbox that enables ERP-based decoding using the full set of channels, while automatically extracting informative components from relevant channels. The strength of our approach is that it handles sequences of stimuli that encode multiple items using binary classification, such as target vs. nontarget events typically used in ERP-based spellers. We demonstrate examples of application scenarios and evaluate the performance of four openly available datasets: a P300-based matrix speller, a P300-based rapid serial visual presentation (RSVP) speller, a binary BCI based on the N2pc, and a dataset capturing error potentials. We show that our approach achieves performances comparable to those in the original papers, with the advantage that only conventional preprocessing is required by the user, while channel weighting and decoding algorithms are internally performed. Thus, we provide a tool to reliably decode ERPs for BCI use with minimal programming requirements.</p

Table_1_A toolbox for decoding BCI commands based on event-related potentials.XLSX

Commands in brain-computer interface (BCI) applications often rely on the decoding of event-related potentials (ERP). For instance, the P300 potential is frequently used as a marker of attention to an oddball event. Error-related potentials and the N2pc signal are further examples of ERPs used for BCI control. One challenge in decoding brain activity from the electroencephalogram (EEG) is the selection of the most suitable channels and appropriate features for a particular classification approach. Here we introduce a toolbox that enables ERP-based decoding using the full set of channels, while automatically extracting informative components from relevant channels. The strength of our approach is that it handles sequences of stimuli that encode multiple items using binary classification, such as target vs. nontarget events typically used in ERP-based spellers. We demonstrate examples of application scenarios and evaluate the performance of four openly available datasets: a P300-based matrix speller, a P300-based rapid serial visual presentation (RSVP) speller, a binary BCI based on the N2pc, and a dataset capturing error potentials. We show that our approach achieves performances comparable to those in the original papers, with the advantage that only conventional preprocessing is required by the user, while channel weighting and decoding algorithms are internally performed. Thus, we provide a tool to reliably decode ERPs for BCI use with minimal programming requirements.</p