Neuromodulation of Spatial Associations: Evidence from Choice Reaction Tasks During Transcranial Direct Current Stimulation

Various portions of human behavior and cognition are influenced by covert implicit processes without being necessarily available to intentional planning. Implicit cognitive biases can be measured in behavioral tasks yielding SNARC effects for spatial associations of numerical and non-numerical sequences, or yielding the implicit association test effect for associations between insect-flower and negative-positive categories. By using concurrent neuromodulation with transcranial direct current stimulation (tDCS), subthreshold activity patterns in prefrontal cortical regions can be experimentally manipulated to reduce implicit processing. Thus, the application of tDCS can test neurocognitive hypotheses on a unique neurocognitive origin of implicit cognitive biases in different spatial-numerical and non-numerical domains. However, the effects of tDCS are not only determined by superimposed electric fields, but also by task characteristics. To outline the possibilities of task-specific targeting of tDCS, task characteristics and instructions can be varied systematically when combined with neuromodulation. In the present thesis, implicit cognitive processes are assessed in different paradigms concurrent to left-hemispheric prefrontal tDCS to investigate a verbal processing hypothesis for implicit associations in general. In psychological experiments, simple choice reaction tasks measure implicit SNARC and SNARC-like effects as relative left-hand vs. right-hand latency advantages for responding to smaller number or ordinal sequence targets. However, different combinations of polarity-dependent tDCS with stimuli and task procedures also reveal domain-specific involvements and dissociations. Discounting previous unified theories on the SNARC effect, polarity-specific neuromodulation effects dissociate numbers and weekday or month ordinal sequences. By considering also previous results and patient studies, I present a hybrid and augmented working memory account and elaborate the linguistic markedness correspondence principle as one critical verbal mechanism among competing covert coding mechanisms. Finally, a general stimulation rationale based on verbal working memory is tested in separate experiments extending also to non-spatial implicit association test effects. Regarding cognitive tDCS effects, the present studies show polarity asymmetry and task-induced activity dependence of state-dependent neuromodulation. At large, distinct combinations of the identical tDCS electrode configuration with different tasks influences behavioral outcomes tremendously, which will allow for improved task- and domain-specific targeting

Efficacy of non-invasive brain stimulation on cognitive functioning in brain disorders:a meta-analysis

Background Cognition is commonly affected in brain disorders. Non-invasive brain stimulation (NIBS) may have procognitive effects, with high tolerability. This meta-analysis evaluates the efficacy of transcranial magnetic stimulation (TMS) and transcranial Direct Current Stimulation (tDCS) in improving cognition, in schizophrenia, depression, dementia, Parkinson's disease, stroke, traumatic brain injury, and multiple sclerosis. Methods A PRISMA systematic search was conducted for randomized controlled trials. Hedges' g was used to quantify effect sizes (ES) for changes in cognition after TMS/tDCS v. sham. As different cognitive functions may have unequal susceptibility to TMS/tDCS, we separately evaluated the effects on: attention/vigilance, working memory, executive functioning, processing speed, verbal fluency, verbal learning, and social cognition. Results We included 82 studies (n = 2784). For working memory, both TMS (ES = 0.17, p = 0.015) and tDCS (ES = 0.17, p = 0.021) showed small but significant effects. Age positively moderated the effect of TMS. TDCS was superior to sham for attention/vigilance (ES = 0.20, p = 0.020). These significant effects did not differ across the type of brain disorder. Results were not significant for the other five cognitive domains. Conclusions Our results revealed that both TMS and tDCS elicit a small trans-diagnostic effect on working memory, tDCS also improved attention/vigilance across diagnoses. Effects on the other domains were not significant. Observed ES were small, yet even slight cognitive improvements may facilitate daily functioning. While NIBS can be a well-tolerated treatment, its effects appear domain specific and should be applied only for realistic indications (i.e. to induce a small improvement in working memory or attention)

Attentional modulation of the carry over of eye-movements between tasks

Task demands that influence scanning behaviour in one task can cause that behaviour to persist to a second unrelated task (carry over). This can also affect performance on a second task (e.g., hazard perception ratings), and has been attributed to a process of attentional bias that is modulated by top-down influences (Thompson & Crundall, 2011). In a series of experiments we explored how these top-down influences impact upon carry over. In all experiments, participants searched letters that were presented horizontally, vertically, or in a random array. They were then presented with a driving scene and rated the hazardousness of the scene. Carry over of eye-movements from the letter search to the scene was observed in all experiments. Furthermore, it was demonstrated that this carry over effect influenced hazard perception accuracy. The magnitude of carry over was correlated with task switching abilities, attentional conflicting, and attentional orienting (Experiment 1), and was affected by predictability of the primary task (Experiment 2). Furthermore, direct current stimulation of the left dorsolateral prefrontal cortex and parietal areas affected the magnitude of the effect (Experiment 3). These results indicate that carry over is modulated by the specific ability to orient attention and disengage from this orientation. Over orienting leads to increased carry over and insufficient task switching is detrimental to task performance. As a result the current experiments provide evidence that the carry over effect is strongly influenced by attentional processes, namely orienting, inhibition, and task switching

Neurophysiological and functional neuroanatomical coding of statistical and deterministic rule information during sequence learning

Humans are capable of acquiring multiple types of information presented in the same information stream. It has been suggested that at least two parallel learning processes are important during learning of sequential patterns—statistical learning and rule‐based learning. Yet, the neurophysiological underpinnings of these parallel learning processes are not fully understood. To differentiate between the simultaneous mechanisms at the single trial level, we apply a temporal EEG signal decomposition approach together with sLORETA source localization method to delineate whether distinct statistical and rule‐based learning codes can be distinguished in EEG data and can be related to distinct functional neuroanatomical structures. We demonstrate that concomitant but distinct aspects of information coded in the N2 time window play a role in these mechanisms: mismatch detection and response control underlie statistical learning and rule‐based learning, respectively, albeit with different levels of time‐sensitivity. Moreover, the effects of the two learning mechanisms in the different temporally decomposed clusters of neural activity also differed from each other in neural sources. Importantly, the right inferior frontal cortex (BA44) was specifically implicated in visuomotor statistical learning, confirming its role in the acquisition of transitional probabilities. In contrast, visuomotor rule‐based learning was associated with the prefrontal gyrus (BA6). The results show how simultaneous learning mechanisms operate at the neurophysiological level and are orchestrated by distinct prefrontal cortical areas. The current findings deepen our understanding on the mechanisms of how humans are capable of learning multiple types of information from the same stimulus stream in a parallel fashion

Activation of the pro-resolving receptor Fpr2 attenuates inflammatory microglial activation

Poster number: P-T099 Theme: Neurodegenerative disorders & ageing Activation of the pro-resolving receptor Fpr2 reverses inflammatory microglial activation Authors: Edward S Wickstead - Life Science & Technology University of Westminster/Queen Mary University of London Inflammation is a major contributor to many neurodegenerative disease (Heneka et al. 2015). Microglia, as the resident immune cells of the brain and spinal cord, provide the first line of immunological defence, but can become deleterious when chronically activated, triggering extensive neuronal damage (Cunningham, 2013). Dampening or even reversing this activation may provide neuronal protection against chronic inflammatory damage. The aim of this study was to determine whether lipopolysaccharide (LPS)-induced inflammation could be abrogated through activation of the receptor Fpr2, known to play an important role in peripheral inflammatory resolution. Immortalised murine microglia (BV2 cell line) were stimulated with LPS (50ng/ml) for 1 hour prior to the treatment with one of two Fpr2 ligands, either Cpd43 or Quin-C1 (both 100nM), and production of nitric oxide (NO), tumour necrosis factor alpha (TNFα) and interleukin-10 (IL-10) were monitored after 24h and 48h. Treatment with either Fpr2 ligand significantly suppressed LPS-induced production of NO or TNFα after both 24h and 48h exposure, moreover Fpr2 ligand treatment significantly enhanced production of IL-10 48h post-LPS treatment. As we have previously shown Fpr2 to be coupled to a number of intracellular signaling pathways (Cooray et al. 2013), we investigated potential signaling responses. Western blot analysis revealed no activation of ERK1/2, but identified a rapid and potent activation of p38 MAP kinase in BV2 microglia following stimulation with Fpr2 ligands. Together, these data indicate the possibility of exploiting immunomodulatory strategies for the treatment of neurological diseases, and highlight in particular the important potential of resolution mechanisms as novel therapeutic targets in neuroinflammation. References Cooray SN et al. (2013). Proc Natl Acad Sci U S A 110: 18232-7. Cunningham C (2013). Glia 61: 71-90. Heneka MT et al. (2015). Lancet Neurol 14: 388-40

Change blindness: eradication of gestalt strategies

Arrays of eight, texture-defined rectangles were used as stimuli in a one-shot change blindness (CB) task where there was a 50% chance that one rectangle would change orientation between two successive presentations separated by an interval. CB was eliminated by cueing the target rectangle in the first stimulus, reduced by cueing in the interval and unaffected by cueing in the second presentation. This supports the idea that a representation was formed that persisted through the interval before being 'overwritten' by the second presentation (Landman et al, 2003 Vision Research 43149–164]. Another possibility is that participants used some kind of grouping or Gestalt strategy. To test this we changed the spatial position of the rectangles in the second presentation by shifting them along imaginary spokes (by ±1 degree) emanating from the central fixation point. There was no significant difference seen in performance between this and the standard task [F(1,4)=2.565, p=0.185]. This may suggest two things: (i) Gestalt grouping is not used as a strategy in these tasks, and (ii) it gives further weight to the argument that objects may be stored and retrieved from a pre-attentional store during this task

The effect of anodal transcranial direct current stimulation on spatial motor skill learning in healthy and spinal cord injured humans

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.Anodal transcranial direct current stimulation (tDCS) is an intervention which is thought to enhance motor learning in healthy and stroke-injured states, when applied adjunctively during skill learning. We set out to investigate whether anodal tDCS might enhance functional rehabilitation from incomplete tetraplegic SCI. To address current limitations in the measurement of task-dependent skill, a novel integrated skill training and measurement task, the Motor Skill Rehabilitation Task (MSRT) was designed and developed. Measures of performance from this task delivered the functional measure of spatial motor skill learning, Task Productivity Rate (TPR). TPR was analysed and validated as a univariate dependent outcome, which is of potential importance to the future development of clinical measures measuring goal-directed motor skills. The MSRT was included alongside conventional behavioural measures in a repeated-measures RCT pilot study, the first to investigate the effect of anodal tDCS on rehabilitation of motor skill from chronic spinal cord injury. Adjunctive application of anodal tDCS had a statistically significant benefit upon retention of skill in the incomplete spinal cord injured population, but only when the independent factor of sensory acuity was included in the analysis. Differences between the development of task-dependent skill and generic dexterity over time suggested that spatial skill development was subject to an interaction of short-term and lasting effects. A larger study in healthy persons further investigated these phenomena, also applying Transcranial Magnetic Stimulation (TMS)–evoked measurements to investigate intervention-dependent effects upon the excitability of projections between the primary motor cortex and muscles involved in the prehension task. The findings revealed that active tDCS did not enhance skill learning at 7 days beyond the training period, but did significantly alter the development of motor skill following a period of learning and subsequent skill consolidation which was associated with underlying perturbation of motor control strategy. Significant and divergent patterns of cortical plasticity were evoked in projections to muscles necessary for reaching and grasping. The main findings of this thesis do not support anodal tDCS as an effective adjunctive means of enhancing spatial motor skill in rehabilitation from incomplete tetraplegic SCI. If applied in patient populations, the clinical benefits of anodal tDCS may be contingent both on the nature of the sensorimotor deficit affecting upper limb function and the spatial demands of the behavioural task. The findings of this project serve to inform further research in relation to the effect of anodal tDCS on the brain and behavioural outcomes, the potential for efficacy in target patient groups and the sensitivity of outcome measures to spatial and temporal dimensions of practical motor skills.This study was partly supported by The Brunel University Isambard Research Scholarship, and The Orthotist Education and Training Trust

Attention Restraint, Working Memory Capacity, and Mind Wandering: Do Emotional Valence or Intentionality Matter?

Attention restraint appears to mediate the relationship between working memory capacity (WMC) and mind wandering (Kane et al., 2016). Prior work has identifed two dimensions of mind wandering—emotional valence and intentionality. However, less is known about how WMC and attention restraint correlate with these dimensions. Te current study examined the relationship between WMC, attention restraint, and mind wandering by emotional valence and intentionality. A confrmatory factor analysis demonstrated that WMC and attention restraint were strongly correlated, but only attention restraint was related to overall mind wandering, consistent with prior fndings. However, when examining the emotional valence of mind wandering, attention restraint and WMC were related to negatively and positively valenced, but not neutral, mind wandering. Attention restraint was also related to intentional but not unintentional mind wandering. Tese results suggest that WMC and attention restraint predict some, but not all, types of mind wandering