Influence of frontal-to-parietal connectivity in pseudoneglect: A cortico-cortical paired associative stimulation study.

Pseudoneglect is a set of visuospatial biases that entails a behavioral advantage for stimuli appearing in the left hemifield compared to the right one. Although right hemisphere dominance for visuospatial processing has been invoked to explain this phenomenon, its neurophysiological mechanisms are still debated, and the role of intra- and inter-hemispheric connectivity is yet to be defined. The present study explored the possibility of modulating pseudoneglect in healthy participants through a cortico-cortical paired associative stimulation protocol (ccPAS): a non-invasive brain stimulation protocol that manipulates the interplay between brain regions through the repeated, time-locked coupling of two transcranial magnetic stimulation (TMS) pulses. In the first experiment, healthy participants underwent a frontal-to-parietal (FP) and a parietal-to-frontal (PF) ccPAS. In the FP protocol, the first TMS pulse targeted the right frontal eye field (FEF), and the second pulse the right inferior parietal lobule (IPL), two critical areas for visuospatial and attentional processing. In the PF condition, the order of the pulses was reversed. In both protocols, the inter-stimulus interval (ISI) was 10 ms. Before and after stimulation, pseudoneglect was assessed with a landmark task and a manual line bisection task. A second experiment controlled for ccPAS timing dependency by testing FP-ccPAS with a longer ISI of 100 ms. Results showed that after administering the FP-ccPAS with the ISI of 10 ms, participants' leftward bias in the landmark task increased significantly, with no effects in the manual line bisection task. The other two protocols tested were ineffective. Our findings showed that ccPAS could be used to modulate pseudoneglect by exploiting frontal-to-parietal connectivity, possibly through increased top-down attentional control. FP-ccPAS could represent a promising tool to investigate connectivity properties within visuospatial and attentional networks in the healthy and as a potential rehabilitation protocol in patients suffering from severe visuospatial pathologies.

Connectivity alterations underlying the breakdown of pseudoneglect: New insights from healthy and pathological aging.

A right-hemisphere dominance for visuospatial attention has been invoked as the most prominent neural feature of pseudoneglect (i.e., the leftward visuospatial bias exhibited in neurologically healthy individuals) but the neurophysiological underpinnings of such advantage are still controversial. Previous studies investigating visuospatial bias in multiple-objects visual enumeration reported that pseudoneglect is maintained in healthy elderly and amnesic mild cognitive impairment (aMCI), but not in Alzheimer's disease (AD). In this study, we aimed at investigating the neurophysiological correlates sustaining the rearrangements of the visuospatial bias along the progression from normal to pathological aging. To this aim, we recorded EEG activity during an enumeration task and analyzed intra-hemispheric fronto-parietal and inter-hemispheric effective connectivity adopting indexes from graph theory in patients with mild AD, patients with aMCI, and healthy elderly controls (HC). Results revealed that HC showed the leftward bias and stronger fronto-parietal effective connectivity in the right as compared to the left hemisphere. A breakdown of pseudoneglect in patients with AD was associated with both the loss of the fronto-parietal asymmetry and the reduction of inter-hemispheric parietal interactions. In aMCI, initial alterations of the attentional bias were associated with a reduction of parietal inter-hemispheric communication, but not with modulations of the right fronto-parietal connectivity advantage, which remained intact. These data provide support to the involvement of fronto-parietal and inter-parietal pathways in the leftward spatial bias, extending these notions to the complex neurophysiological alterations characterizing pathological aging.

Responsiveness to left-prefrontal tDCS varies according to arousal levels.

Over the past two decades, the postulated modulatory effects of transcranial direct current stimulation (tDCS) on the human brain have been extensively investigated. However, recent concerns on reliability of tDCS effects have been raised, principally due to reduced replicability and to interindividual variability in response to tDCS. These inconsistencies are likely due to the interplay between the level of induced cortical excitability and unaccounted structural and state-dependent functional factors. On these grounds, we aimed at verifying whether the behavioural effects induced by a common tDCS montage (F3-rSOA) were influenced by the participants' arousal levels, as part of a broader mechanism of state-dependency. Pupillary dynamics were recorded during an auditory oddball task while applying either a sham or real tDCS. The tDCS effects were evaluated as a function of subjective and physiological arousal predictors (STAI-Y State scores and pre-stimulus pupil size, respectively). We showed that prefrontal tDCS hindered task learning effects on response speed such that performance improvement occurred during sham, but not real stimulation. Moreover, both subjective and physiological arousal predictors significantly explained performance during real tDCS, with interaction effects showing performance improvement only with moderate arousal levels; likewise, pupil response was affected by real tDCS according to the ongoing levels of arousal, with reduced dilation during higher arousal trials. These findings highlight the potential role of arousal in shaping the neuromodulatory outcome, thus emphasizing a more careful interpretation of null or negative results while also encouraging more individually tailored tDCS applications based on arousal levels, especially in clinical populations.

Targeting Default Mode Network Dysfunction in Persons at Risk of Alzheimer's Disease with Transcranial Magnetic Stimulation (NEST4AD): Rationale and Study Design.

BACKGROUND: Default mode network (DMN) dysfunction is well established in Alzheimer's disease (AD) and documented in both preclinical stages and at-risk subjects, thus representing a potential disease target. Multi-sessions of repetitive transcranial magnetic stimulation (rTMS) seem capable of modulating DMN dynamics and memory in healthy individuals and AD patients; however, the potential of this approach in at-risk subjects has yet to be tested. OBJECTIVE: This study will test the effect of rTMS on the DMN in healthy older individuals carrying the strongest genetic risk factor for AD, the Apolipoprotein E (APOE) ɛ4 allele. METHODS: We will recruit 64 older participants without cognitive deficits, 32 APOE ɛ4 allele carriers and 32 non-carriers as a reference group. Participants will undergo four rTMS sessions of active (high frequency) or sham DMN stimulation. Multimodal imaging exam (including structural, resting-state, and task functional MRI, and diffusion tensor imaging), TMS with concurrent electroencephalography (TMS-EEG), and cognitive assessment will be performed at baseline and after the stimulation sessions. RESULTS: We will assess changes in DMN connectivity with resting-state functional MRI and TMS-EEG, as well as changes in memory performance in APOE ɛ4 carriers. We will also investigate the mechanisms underlying DMN modulation through the assessment of correlations with measures of neuronal activity, excitability, and structural connectivity with multimodal imaging. CONCLUSION: The results of this study will inform on the physiological and cognitive outcomes of DMN stimulation in subjects at risk for AD and on the possible mechanisms. These results may outline the design of future non-pharmacological preventive interventions for AD.

Functional Imaging to Guide Network-Based TMS Treatments: Toward a Tailored Medicine Approach in Alzheimer's Disease.

A growing number of studies is using fMRI-based connectivity to guide transcranial magnetic stimulation (TMS) target identification in both normal and clinical populations. TMS has gained increasing attention as a potential therapeutic strategy also in Alzheimer's disease (AD), but an endorsed target localization strategy in this population is still lacking. In this proof of concept study, we prove the feasibility of a tailored TMS targeting approach for AD, which stems from a network-based perspective. Based on functional imaging, the procedure allows to extract individual optimal targets meanwhile accounting for functional variability. Single-subject resting-state fMRI was used to extract individual target coordinates of two networks primarily affected in AD, the default mode and the fronto-parietal network. The localization of these targets was compared to that of traditional group-level approaches and tested against varying degrees of TMS focality. The distance between individual fMRI-derived coordinates and traditionally defined targets was significant for a supposed TMS focality of 12 mm and in some cases up to 20 mm. Comparison with anatomical labels confirmed a lack of 1:1 correspondence between anatomical and functional targets. The proposed network-based fMRI-guided TMS approach, while accounting for inter-individual functional variability, allows to target core AD networks, and might thus represent a step toward tailored TMS interventions for AD.

Baseline levels of alertness influence tES effects along different age-related directions.

Normal aging is usually accompanied by several structural and functional physiological changes of the brain, which are closely related to alterations of cognitive functions (e.g., visual short-term memory). As the average age of the population increases, it has become crucial to identify cognitive-behavioural interventions to maintain a healthy level of cognitive performance. Among a variety of approaches, the targeting of specific intrinsic alertness mechanisms has shown a solid rationale and beneficial effects in both healthy and pathological ageing. In a similar vein, the use of non-invasive transcranial electrical stimulation (tES) represents another promising approach to induce an alerting state that can produce advantages in the information processing in the brain and therefore behaviour. Here, we investigated whether time-locked bursts of tES (i.e., transcranial random noise stimulation) were effective in inducing behavioural and physiological changes, consistently with an alertness increase, in both young and older healthy adults. Namely, we expected to find a beneficial alerting effect on visual short-term memory performance as a function of stimulus perceptual salience and tES. The initial results showed that the performance of younger adults was not affected by tES, while older adults scored lower correct responses for high-salience stimuli during real tES with respect to sham stimulation. However, after including a baseline measure of subjective level of alertness in the analyses, a tES-induced memory improvement did emerge in the less alerted younger adults, while only the more alerted older adults were subject to the worsening effect by tES. We discuss these results in consideration of the evidence on critical age-related differences as well as the interaction between neurostimulation and baseline alerting mechanisms.

Enhancing cognitive training effects in Alzheimer's disease: rTMS as an add-on treatment.

The treatment of Alzheimer's disease (AD) in the field of non-pharmacological interventions is a challenging issue, given the limited benefits of the available drugs. Cognitive training (CT) represents a commonly recommended strategy in AD. Recently, repetitive transcranial magnetic stimulation (rTMS) has gained increasing attention as a promising therapeutic tool for the treatment of AD, given its ability of enhancing neuroplasticity. In the present randomized, double-blind, sham-controlled study, we aimed at investigating the add-on effect of a high frequency rTMS protocol applied over the left dorsolateral prefrontal cortex (DLPFC) combined with a face-name associative memory CT in the continuum of AD pathology. Fifty patients from a very early to a moderate phase of dementia were randomly assigned to one of two groups: CT plus real rTMS or CT plus placebo rTMS. The results showed that the improvement in the trained associative memory induced with rTMS was superior to that obtained with CT alone. Interestingly, the extent of the additional improvement was affected by disease severity and levels of education, with less impaired and more educated patients showing a greater benefit. When testing for generalization to non-trained cognitive functions, results indicated that patients in CT-real group showed also a greater improvement in visuospatial reasoning than those in the CT-sham group. Interestingly, this improvement persisted over 12 weeks after treatment beginning. The present study provides important hints on the promising therapeutic use of rTMS in AD.

Does numerical similarity alter age-related distractibility in working memory?

Similarity between targets and distracters is a key factor in generating distractibility, and exerts a large detrimental effect on aging. The present EEG study tested the role of a new stimulus dimension in generating distractibility in visual Working Memory (vWM), namely numerical similarity. In a change detection paradigm a varying number of relevant and irrelevant stimuli were presented simultaneously in opposite hemifields. Behavioral results indicated that young participants outperformed older individuals; however, in both groups numerical similarity per se did not modulate performance. At the electrophysiological level, in young participants the Contralateral Delay Activity (CDA, a proxy for item maintenance in vWM) was modulated by the numerosity of the relevant items regardless of numerical similarity. In older participants, the CDA was modulated by target numerosity only in the same numerical condition, where the total number of (relevant and irrelevant) items increased with increasing target numerosities. No effect was present in the dissimilar numerical condition, where the total number of items did not vary substantially across target numerosity. This pattern was suggestive of an age-related effect of the total number of (relevant and irrelevant) items on vWM. The additional analyses on alpha-band lateralization measures support this interpretation by revealing that older adults lacked selective deployment of attentional and vWM resources towards the relevant hemifield. Overall, the results indicate that, while numerical similarity does not modulate distractibility, there is an age-related redistribution of vWM resources across the two visual fields, ultimately leading to a general decrease in task performance of older adults.

Pseudoneglect is maintained in aging but not in mild Alzheimer's disease: new insights from an enumeration task.

Neurologically healthy young adults display a behavioral bias, called pseudoneglect, which favors the processing of stimuli appearing in the left visual field. Pseudoneglect arises from the right hemisphere dominance for visuospatial attention. Previous studies investigating the effects of normal aging on pseudoneglect in line bisection and greyscale tasks have produced divergent results. In addition, scarce systematic investigations of visual biases in dementia have been reported. The aim of the present study was to evaluate whether the leftward bias appearing during an enumeration task in young adults would be preserved in normal aging and at different stages of severity of Alzheimer's disease. In Experiment 1, young and older healthy adults showed a comparable pseudoneglect, performing better when targets appeared in the left visual field. In Experiment 2, the leftward bias was maintained in amnesic mild cognitive impairment patients (aMCI), but it vanished in mild Alzheimer's disease patients (AD). The maintenance of pseudoneglect in normal aging and in aMCI patients is consistent with compensatory phenomena involving the right fronto-parietal network, which allow maintaining the right hemisphere dominance. Conversely, the lack of pseudoneglect in the sample of AD patients likely results from a loss of the right hemisphere dominance, caused by the selective degeneration of the right fronto-parietal network. These results highlight the need of further systematic investigations of visuospatial biases along the continuum of normal and pathological aging, both for a better understanding of the changes characterizing cognitive aging and for improvements in the evaluation of neglect in Alzheimer's disease.

Neural Dynamics of Multiple Object Processing in Mild Cognitive Impairment and Alzheimer's Disease: Future Early Diagnostic Biomarkers?

The aim of this study was to investigate the behavioral and electrophysiological dynamics of multiple object processing (MOP) in mild cognitive impairment (MCI) and Alzheimer's disease (AD), and to test whether its neural signatures may represent reliable diagnostic biomarkers. Behavioral performance and event-related potentials [N2pc and contralateral delay activity (CDA)] were measured in AD, MCI, and healthy controls during a MOP task, which consisted in enumerating a variable number of targets presented among distractors. AD patients showed an overall decline in accuracy for both small and large target quantities, whereas in MCI patients, only enumeration of large quantities was impaired. N2pc, a neural marker of attentive individuation, was spared in both AD and MCI patients. In contrast, CDA, which indexes visual short term memory abilities, was altered in both groups of patients, with a non-linear pattern of amplitude modulation along the continuum of the disease: a reduction in AD and an increase in MCI. These results indicate that AD pathology shows a progressive decline in MOP, which is associated to the decay of visual short-term memory mechanisms. Crucially, CDA may be considered as a useful neural signature both to distinguish between healthy and pathological aging and to characterize the different stages along the AD continuum, possibly becoming a reliable candidate for an early diagnostic biomarker of AD pathology.

The mismatch negativity as an index of cognitive decline for the early detection of Alzheimer's disease.

Evidence suggests that Alzheimer's disease (AD) is part of a continuum, characterized by long preclinical phases before the onset of clinical symptoms. In several cases, this continuum starts with a syndrome, defined as mild cognitive impairment (MCI), in which daily activities are preserved despite the presence of cognitive decline. The possibility of having a reliable and sensitive neurophysiological marker that can be used for early detection of AD is extremely valuable because of the incidence of this type of dementia. In this study, we aimed to investigate the reliability of auditory mismatch negativity (aMMN) as a marker of cognitive decline from normal ageing progressing from MCI to AD. We compared aMMN elicited in the frontal and temporal locations by duration deviant sounds in short (400 ms) and long (4000 ms) inter-trial intervals (ITI) in three groups. We found that at a short ITI, MCI showed only the temporal component of aMMN and AD the frontal component compared to healthy elderly who presented both. At a longer ITI, aMMN was elicited only in normal ageing subjects at the temporal locations. Our study provides empirical evidence for the possibility to adopt aMMN as an index for assessing cognitive decline in pathological ageing.

Assessing cortical synchronization during transcranial direct current stimulation: A graph-theoretical analysis.

Transcranial direct current stimulation (tDCS) is a neuromodulation technique that can alter cortical excitability and modulate behaviour in a polarity-dependent way. Despite the widespread use of this method in the neuroscience field, its effects on ongoing local or global (network level) neuronal activity are still not foreseeable. A way to shed light on the neuronal mechanisms underlying the cortical connectivity changes induced by tDCS is provided by the combination of tDCS with electroencephalography (EEG). In this study, twelve healthy subjects underwent online tDCS-EEG recording (i.e., simultaneous), during resting-state, using 19 EEG channels. The protocol involved anodal, cathodal and sham stimulation conditions, with the active and the reference electrodes in the left frontocentral area (FC3) and on the forehead over the right eyebrow, respectively. The data were processed using a network model, based on graph theory and the synchronization likelihood. The resulting graphs were analysed for four frequency bands (theta, alpha, beta and gamma) to evaluate the presence of tDCS-induced differences in synchronization patterns and graph theory measures. The resting state network connectivity resulted altered during tDCS, in a polarity-specific manner for theta and alpha bands. Anodal tDCS weakened synchronization with respect to the baseline over the fronto-central areas in the left hemisphere, for theta band (p<0.05). In contrast, during cathodal tDCS a significant increase in inter-hemispheric synchronization connectivity was observed over the centro-parietal, centro-occipital and parieto-occipital areas for the alpha band (p<0.05). Local graph measures showed a tDCS-induced polarity-specific differences that regarded modifications of network activities rather than specific region properties. Our results show that applying tDCS during the resting state modulates local synchronization as well as network properties in slow frequency bands, in a polarity-specific manner.

Electrophysiological Advances on Multiple Object Processing in Aging.

EEG research conducted in the past 5 years on multiple object processing has begun to define how the aging brain tracks the numerosity of the objects presented in the visual field for different goals. We review the recent EEG findings in healthy older individuals (age range: 65-75 years approximately) on perceptual, attentional and memory mechanisms-reflected in the N1, N2pc and contralateral delayed activity (CDA) components of the EEG, respectively-during the execution of a variety of cognitive tasks requiring simultaneous processing of multiple elements. The findings point to multiple loci of neural changes in multi-object analysis, and suggest the involvement of early perceptual mechanisms, attentive individuation and working memory (WM) operations in the neural and cognitive modification due to aging. However, the findings do not simply reflect early impairments with a cascade effect over subsequent stages of stimulus processing, but in fact highlight interesting dissociations between the effects occurring at the various stages of stimulus processing. Finally, the results on older adults indicate the occurrence of neural overactivation in association to good levels of performance in easy perceptual contexts, thus providing some hints on the existence of compensatory phenomena that are associated with the functioning of early perceptual mechanisms.

Object individuation and compensation in healthy aging.

Theories on neural compensation suggest that aged participants overactivate the brain areas involved in a task to compensate for the age-related decline. In this electrophysiological study, we investigated the temporal locus of neural overactivation in aging during multiple target processing. We measured performance and three event-related brain potential responses (N1, N2pc, and contralateral delay activity) in young and old adults, while they enumerated a variable number (1-4) of targets presented in an easy (distractor absent) or difficult (distractor present) condition. The main results indicated that although N2pc (∼200 ms) increased in amplitude in the distractor-present condition in the young group, no modulation occurred for the old group. Old participants were associated with larger N2pc amplitudes than young participants in the distractor-absent condition, where both groups had comparable levels of accuracy. These effects were not present for N1 and contralateral delay activity. Overall, the data suggest that in enumeration, aging is associated with compensatory effects that rely on the selection mechanism responsible for target individuation.

Effects of transcranial direct current stimulation on the functional coupling of the sensorimotor cortical network.

Transcranial direct current stimulation (tDCS) is well established-among the non-invasive brain stimulation techniques-as a method to modulate brain excitability. Polarity-dependent modulations of membrane potentials are detected after the application of anodal and cathodal stimulation, leading to changes in the electrical activity of the neurons. The main aim of the present study was to test the hypothesis that tDCS can affect-in a polarity-specific manner-the functional coupling of the sensorimotor areas during the eyes-open resting condition as revealed by total EEG coherence (i.e., coherence across the average of all combinations of the electrode pairs placed around the stimulation electrode). The changes in the total EEG coherence were evaluated pre-, during, and post-anodal and cathodal tDCS. While no differences were observed in the connectivity characteristics of the two pre-stimulation periods, a connectivity increase was observed in the alpha 2 band in the post-anodal tDCS with respect to pre-anodal and post-cathodal tDCS. The present study suggests that a specific approach based on the analyses of the functional coupling of EEG rhythms might enhance understanding of tDCS-induced effects on cortical connectivity. Moreover, this result suggests that anodal tDCS could possibly modify cortical connectivity more effectively with respect to cathodal tDCS.

The right inferior frontal cortex in response inhibition: A tDCS-ERP co-registration study.

In any given common situation, when an individual controls him/herself or obeys and stops a current action when asked to do, it is because the brain executes an inhibitory process. This ability is essential for adaptive behaviour, and it is also a requirement for accurate performance in daily life. It has been suggested that there are two main inhibitory functions related to behaviour, as inhibition is observed to affect behaviour at different time intervals. Proactive inhibition permits the subject to control his behavioural response over time by creating a response tendency, while reactive inhibition is considered to be a process that usually inhibits an already initiated response. In this context, it has been established that inhibitory function is implemented by specific fronto-basal-ganglia circuits. In the present study, we investigated the role of the right inferior frontal cortex (rIFC) in response inhibition by combining into a single task the Go-NoGo task and the Stop-Signal task. Concurrently, we applied transcranial direct current stimulation (tDCS) over the IFC and recorded electroencephalography (EEG). Thus, we obtained online EEG measurements of the tDCS-induced modifications in the IFC together with the participant's performance in a response inhibition task. We found that applying bilateral tDCS on the IFC (right anodal/left cathodal) significantly increased proactive inhibition, although the behavioural parameters indicative of reactive inhibition were unaffected by the stimulation. Finally, the inhibitory-P3 component reflected a similar modulation under both inhibitory conditions induced by the stimulation. Our data indicates that an online tDCS-ERP approach is achievable, but that a tDCS bilateral montage may not be the most efficient one for modulating the rIFC.

Electrophysiological Correlates of Subitizing in Healthy Aging.

To understand the nature of age-related changes in enumeration abilities we measured two ERP responses -N2pc and CDA, associated respectively to attentive individuation and VWM- and posterior alpha band (8-15 Hz) event-related desynchronization (ERD), traditionally linked to enhanced target processing. Two groups of old and young participants enumerated a variable number (1-6) of targets presented among distractors. Older participants were less accurate in enumerating targets. ERP results in old participants showed a suppression of N2pc amplitudes for all numerosities, and a decrease in CDA only for the largest set (4-6 targets). In contrast with the pattern for young adults, time/frequency results on older adults revealed neither a modulation of alpha oscillations as a function of target numerosity, nor an effect of ERD lateralization. These patterns indicate that both attention and working memory contribute to the age-related decline in enumeration, and point to an overall decrease in the activity of the visual areas responsible for the processing of the hemifield where the relevant objects are presented.

No causal effect of left hemisphere hyperactivity in the genesis of neglect-like behavior.

Spatial neglect is traditionally explained as an imbalance of the interhemispheric reciprocal inhibition exerted by the two hemispheres: after a right lesion, the contralesional hemisphere becomes disinhibited and its enhanced activity suppresses the activity in the lesioned one. Even though the hyperexcitability of the left hemisphere is the theoretical framework of several rehabilitation interventions using non-invasive brain stimulation protocols in neglect, no study has yet investigated directly the actual state of cortical excitability of the contralesional hemisphere immediately after the brain lesion. The present study represents the first attempt to directly assess the interhemispheric rivalry model adopting a novel approach based on the induction of neglect-like biases in healthy participants. Applying repetitive transcranial magnetic stimulation (rTMS) over the right posterior parietal cortex while concurrently recording the EEG activity allows to measure specific neurophysiological markers of cortical activity (i.e. TMS-evoked potentials, TEPs) both over the stimulated right hemisphere and over the contralateral homologous area. Besides the effectiveness of the protocol used in modulating behavior, our results show an inhibition of the cortical excitability of the directly stimulated parietal cortex (right hemisphere) and, most importantly, a comparable reduction of cortical excitability of the homologous contralateral (left) area. TEPs and additional electrophysiological measures reliably provide strong evidence for a bilateral hypo-activation following TMS induction of neglect-like biases. These results suggest that the parietal imbalance typically found in neglect patients could reflect a long-term maladaptive plastic reorganization that follows a brain lesion.

Bursts of transcranial electrical stimulation increase arousal in a continuous performance test.

Arousal reflects a state of generalised physiological activation, and its key role in cognition and behaviour has been extensively described. The regulation of arousal is controlled by specific nuclei located in the brainstem that contain widely distributed projections to the cortex and form the arousal systems. In humans, arousal has been commonly studied and modulated through behavioural paradigms, whereas in animals, direct electrical stimulation has been used to confirm the important role of these widely distributed structures. Recent evidence suggests that it might be possible to use transcranial electrical stimulation (tES) to non-invasively induce currents in the brainstem regions of the brain. Therefore, we hypothesise that, using a specific electrode arrangement, it might be possible to employ tES to stimulate subcortical-cortical neuromodulatory networks, inducing modulation of general arousal. The aim of the present study was to determine if it is possible to increase arousal during a discriminative reaction times (RTs) task, through the application of tES, to improve the subjects' performance. We developed 3 experiments: Experiment 1 validated the behavioural task, which was an adapted version of the continuous performance test. Experiment 2 aimed to show the task sensitivity to the level of activation. The results confirmed that the task was sensitive enough to reveal modulations of arousal. In Experiment 3, we applied bursts of tES concurrent with the onset of the relevant stimuli of the task to increase the physiological phasic activation of arousal. The skin conductance response was recorded during the experiment in addition to the RTs. The results showed a reduction of RTs and a concurrent increase in skin conductance during the real stimulation condition, which is consistent with a general increase in arousal. In all, these data support the effectiveness of bursts of tES in modulating arousal.

Automatic artifact suppression in simultaneous tDCS-EEG using adaptive filtering.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation method that can be used in cognitive and clinical protocols in order to modulate neural activity. Although some macro effects are known, the underlying mechanisms are still not clear. tDCS in combination with electroencephalography (EEG) could help to understand these mechanisms from a neural point of view. However, simultaneous tDCS-EEG still remains challenging because of the artifacts that affect the recorded signals. In this paper, an automated artifact cancellation method based on adaptive filtering is proposed. Using independent component analysis (ICA), the artifacts were characterized using data from both a phantom and a group of healthy subjects. The resulting filter can successfully remove tDCS-related artifacts during anodal and cathodal stimulations.