Jesús Cespón

Age-related changes in ERP correlates of visuospatial and motor processes.

Although previous ERP studies have demonstrated slowing of visuospatial and motor processes with age, such studies frequently included only young and elderly participants, and lacked information about age-related changes across the adult lifespan. The present research used a Simon task with two irrelevant dimensions (position and direction of an arrow) to study visuospatial (N2 posterior contralateral, N2pc) and motor (response-locked lateralized readiness potential, LRP-r) processes in young, middle-aged, and elderly adults. The reaction time and motor execution stage (LRP-r) increased gradually with age, while visuospatial processes (N2pc latency) were similarly delayed in the older groups. No age-related increase in interference was observed, probably related to a delay in processing the symbolic meaning of the direction in older groups, which was consistent with age-related differences in distributional analyses and N2pc amplitude modulations.

The Simon effect modulates N2cc and LRP but not the N2pc component.

Previous studies have reported that the horizontal arrangement of the stimuli in Simon tasks elicits three different components: LRP, N2pc and N2cc. Although N2cc may play a key role in Simon tasks, as it is involved in preventing responses based on stimulus position, modulation of the N2cc component according to the experimental conditions has not previously been investigated because of N2cc/LRP overlap in similar regions and temporal window. The aim of the present study was to investigate how the Simon effect modulates N2pc, N2cc and LRP components. For this purpose, participants were asked to respond to an arrow according to its colour. Three conditions, which depended on the congruency between stimulus position and the required response, were analysed: compatible position (CP), incompatible position (IP), and neutral position (NP). The LRP peak latency was delayed in IP with respect to CP and NP conditions. Lateralized minus neutral position (L-NP) subtractions were carried out to remove the common motor activity and isolate the N2cc and N2pc components in the lateralized conditions. The N2cc amplitude in L-NP waveforms was larger in IP than in CP, in accordance with the greater effort required to monitor selection of the correct response in the first condition. eLORETA analysis also revealed greater premotor activity at 150-200 ms in IP and CP, than in NP, which was attributed to the N2cc component present in IP/CP conditions. Evidence of functional dissociation between N2pc and N2cc components was obtained, because N2cc, but not N2pc, was affected by the experimental conditions.

Electrophysiological Correlates of Amnestic Mild Cognitive Impairment in a Simon Task

Amnestic mild cognitive impairment (aMCI) represents a prodromal stage of Alzheimer`s disease (AD), especially when additional cognitive domains are affected (Petersen et al., 2009). Thus, single-domain amnestic MCI (sdaMCI) and multiple-domain-amnestic MCI (mdaMCI) biomarkers are important for enabling early interventions to help slow down progression of the disease. Recording event-related potentials (ERPs) is a non-invasive and inexpensive measure of brain activity associated with cognitive processes, and it is of interest from a clinical point of view. The ERP technique may also be useful for obtaining early sdaMCI and mdaMCI biomarkers because ERPs are sensitive to impairment in processes that are not manifested at behavioral or clinical levels. In the present study, EEG activity was recorded in 25 healthy participants and 30 amnestic MCI patients (17 sdaMCI and 13 mdaMCI) while they performed a Simon task. The ERPs associated with visuospatial (N2 posterior-contralateral – N2pc -) and motor (lateralized readiness potential – LRP –) processes were examined. The N2pc amplitude was smaller in participants with mdaMCI than in healthy participants, which indicated a decline in the correlates of allocation of attentional resources to the target stimulus. In addition, N2pc amplitude proved to be a moderately good biomarker of mdaMCI subtype (0.77 sensitivity, 0.76 specificity). However, the LRP amplitude was smaller in the two MCI groups (sdaMCI and mdaMCI) than in healthy participants, revealing a reduction in the motor resources available to execute the response in sdaMCI and mdaMCI patients. Furthermore, the LRP amplitude proved to be a valid biomarker (0.80 sensitivity, 0.92 specificity) of both amnestic MCI subtypes.

Differences between Mild Cognitive Impairment Subtypes as Indicated by Event-Related Potential Correlates of Cognitive and Motor Processes in a Simon Task

Mild cognitive impairment (MCI) may represent a prodromal stage of Alzheimers disease (AD), although the clinical manifestations of MCI are heterogeneous. Consequently, MCI subtypes are differentiated since amnestic decline (particularly when combined with decline on multiple cognitive domains) increases the probability of progression to AD. In the present study, event-related potential (ERP) correlates of stimulus evaluation (N2), visuospatial attention (negativity posterior-contralateral, N2pc), stimulus categorization (P3b), executive control (pre-response positivity, PP, and medial frontal negativity), and motor (lateralized readiness potential, LRP) processes were studied in 53 participants while they performed a Simon task. Participants were divided into control group (CG), multiple-domain non-amnestic MCI (mdnaMCI), single-domain amnestic MCI (sdaMCI), and multiple-domain amnesic MCI (mdaMCI). Although there were no differences in reaction times and percentage of errors in the performed Simon-type task, a differential pattern of electrophysiological correlates was observed in MCI compared to CG. Concretely, amnestic MCI (sdaMCI and mdaMCI) showed reduced motor activity (LRP amplitude; AUC: 0.84); impairment in executive control (PP amplitude; AUC: 0.80) was observed in multiple-domain MCI (mdaMCI and mdnaMCI); finally, stimulus evaluation (N2 latency; AUC: 0.86) and visuospatial attention (N2pc amplitude; AUC: 0.78) was affected in mdaMCI. Overall, results linked the poorer prognosis of the mdaMCI subtype with a greater number of differences in ERP correlates regarding CG. Therefore, the present results enable us to suggest possible ERP biomarkers for specific MCI subtypes.

Inhibition deficit in the spatial tendency of the response in multiple-domain amnestic mild cognitive impairment. An event-related potential study

Longitudinal studies have shown that a high percentage of people with amnestic mild cognitive impairment (MCI) develop Alzheimer’s disease (AD). Prodromal AD is known to involve deficits in executive control processes. In the present study, we examined such deficits by recording EEG in 13 single-domain amnestic MCI (sdaMCI), 12 multiple-domain amnestic MCI (mdaMCI) and 18 healthy elderly (control group, CG) participants while they performed a Simon task. The Simon task demands deployment of executive processes because participants have to respond to non-spatial features of a lateralized stimulus and inhibit the more automatic spatial tendency of the response. We specifically focused on the negativity central contralateral (N2cc), an event-related potential (ERP) component related to brain activity that prevents the cross-talk between direction of spatial attention and manual response preparation. The reaction time (RT) was not significantly different among the three groups of participants. The percentage of errors (PE) was higher in mdaMCI than in CG and sdaMCI participants. In addition, N2cc latency was delayed in mdaMCI (i.e., delayed implementation of mechanisms for controlling the spatial tendency of the response). The N2cc latency clearly distinguished among mdaMCI and CG/sdaMCI participants (area under curve: 0.91). Longer N2cc was therefore associated with executive control deficits, which suggests that N2cc latency is a correlate of mdaMCI.

Similarities and differences between interference from stimulus position and from direction of an arrow: Behavioral and event-related potential measures

Studies with stimulus-response compatibility (SRC) tasks used the stimulus position (SRC-p) and/or the direction indicated by a central arrow (SRC-d) as irrelevant dimensions. Despite behavioral differences revealed by the distributional analysis (DA), both interferences were established at similar loci on the basis of modulations in the lateralized readiness potential (LRP) and P3b components. Consequently, similar underlying mechanisms were proposed for both interferences. However, comparison of motor processes associated with each task is problematical because each involves different components. In addition, previous studies have frequently used different proportions of trials between conditions, which complicate interpretation of the results because the stimulus probability may modulate P3b. Taking these problems into account, the present study investigated the effects of interference in SRC-p and SRC-d tasks, in which the participants responded to the color of a stimulus while ignoring the position and the direction indicated by a central arrow, respectively. The interference was greater in the SRC-p than in the SRC-d task. The DA showed that stimulus position affected the performance more quickly than the direction of the arrow. The P3b latency was longer and the P3b amplitude was smaller when stimulus position was incompatible. However, no differences in P3b were found in the SRC-d task. Moreover, both types of interference affected response-related processes (LRP-r) similarly. Therefore, the stimulus position and the direction indicated by the stimulus may share a common locus of interference (response execution), but only stimulus position affects P3b component, which constitutes a link between stimulus evaluation and the response selection.

N2pc is modulated by stimulus-stimulus, but not by stimulus-response incompatibilities.

Studies of the N2pc in Simon-type tasks have revealed inconsistent results. That is, N2pc was only modulated when a stimulus-stimulus (S-S) overlap covaries with the stimulus-response (S-R) overlap. The present study aimed to establish whether N2pc is modulated by the S-R or by the S-S overlap. Therefore, we designed a Simon task requiring response to a colour stimulus (an arrow) with two irrelevant dimensions (position and direction). The following conditions were thus generated: compatible direction-compatible position (CDCP); incompatible direction-compatible position (IDCP); compatible direction-incompatible position (CDIP); and incompatible direction-incompatible position (IDIP). In IDCP and CDIP, both irrelevant dimensions conveyed contradictory spatial information (S-S incompatibility), while compatibility between both irrelevant dimensions occurred in CDCP and IDIP (the direction indicated was compatible with stimulus position). The N2pc amplitude was smaller in IDCP and CDIP than in CDCP and IDIP, what suggests that N2pc was modulated by S-S incompatibility and not by S-R incompatibilities.

Interventional programmes to improve cognition during healthy and pathological ageing: Cortical modulations and evidence for brain plasticity

A growing body of evidence suggests that healthy elderly individuals and patients with Alzheimers disease retain an important potential for neuroplasticity. This review summarizes studies investigating the modulation of neural activity and structural brain integrity in response to interventions involving cognitive training, physical exercise and non-invasive brain stimulation in healthy elderly and cognitively impaired subjects (including patients with mild cognitive impairment (MCI) and Alzheimers disease). Moreover, given the clinical relevance of neuroplasticity, we discuss how evidence for neuroplasticity can be inferred from the functional and structural brain changes observed after implementing these interventions. We emphasize that multimodal programmes, which combine several types of interventions, improve cognitive function to a greater extent than programmes that use a single interventional approach. We suggest specific methods for weighting the relative importance of cognitive training, physical exercise and non-invasive brain stimulation according to the functional and structural state of the brain of the targeted subject to maximize the cognitive improvements induced by multimodal programmes.

Effects of mild cognitive impairment on the event-related brain potential components elicited in executive control tasks

We summarize here the findings of several studies in which we analyzed the event-related brain potentials (ERPs) elicited in participants with mild cognitive impairment (MCI) and in healthy controls during performance of executive tasks. The objective of these studies was to investigate the neural functioning associated with executive processes in MCI. With this aim, we recorded the brain electrical activity generated in response to stimuli in three executive control tasks (Stroop, Simon, and Go/NoGo) adapted for use with the ERP technique. We found that the latencies of the ERP components associated with the evaluation and categorization of the stimuli were longer in participants with amnestic MCI than in the paired controls, particularly those with multiple-domain amnestic MCI, and that the allocation of neural resources for attending to the stimuli was weaker in participants with amnestic MCI. The MCI participants also showed deficient functioning of the response selection and preparation processes demanded by each task.

Cognitive control activity is modulated by the magnitude of interference and pre-activation of monitoring mechanisms.

The Simon task is used to study interference from irrelevant spatial information. Interference is manifested by longer reaction times when the required response –based on non-spatial features- is spatially incompatible with stimulus position. Interference is greater when incompatible trials are preceded by compatible trials (compatible-incompatible sequence) than when they are preceded by incompatible trials (incompatible-incompatible sequence). However, the relationships between spatial attention, interference and cognitive control have not been investigated. In the present study, we distinguished three experimental conditions according to sequential effects: same mappings (SM, compatible-compatible/incompatible-incompatible sequences: low interference), opposite mappings (OM, compatible-incompatible/incompatible-compatible sequences: high interference) and unrelated mappings (UM, central-compatible/central-incompatible sequences: intermediate interference). The negativity central contralateral (N2cc, a correlate of prevention of spatial response tendencies) was larger in OM than in SM, indicating greater cognitive control for greater interference. Furthermore, N2cc was larger in UM than in SM/OM, indicating lower neural efficiency for suppressing spatial tendencies of the response after central trials. Attentional processes (negativity posterior contralateral) were also delayed in UM relative to SM/OM, suggesting attentional facilitation by similar sets of attentional shifts in successive trials. Overall, the present findings showed that cognitive control is modulated by the magnitude of interference and pre-activation of monitoring mechanisms.