Electrophysiological Advances on Multiple Object Processing in Aging

EEG research conducted in the past five 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 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 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

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

A simultaneous modulation of reactive and proactive inhibition processes by anodal tDCS on the right inferior frontal cortex

Proactive and reactive inhibitory processes are a fundamental part of executive functions, allowing a person to stop inappropriate responses when necessary and to adjust performance in in a long term in accordance to the goals of a task. In the current study, we manipulate, in a single task, both reactive and proactive inhibition mechanisms, and we investigate the within-subjects effect of increasing, by means of anodal transcranial direct current stimulation (tDCS), the involvement of the right inferior frontal cortex (rIFC). Our results show a simultaneous enhancement of these two cognitive mechanisms when modulating the neural activity of rIFC. Thus, the application of anodal tDCS increased reaction times on Go trials, indicating a possible increase in proactive inhibition. Concurrently, the stop-signal reaction time, as a covert index of the inhibitory process, was reduced, demonstrating an improvement in reactive inhibition. In summary, the current pattern of results validates the engagement of the rIFC in these two forms of inhibitory processes, proactive and reactive inhibition and it provides evidence that both processes can operate concurrently in the brain

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

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