The ability to flexibly switch between fast and accurate decisions is crucial in everyday life. Recent neuroimaging evidence suggested that left lateral prefrontal cortex plays a role in switching from a quick response strategy to an accurate one. However, the causal role of the left prefrontal cortex in this particular, non-verbal, strategy switch has never been demonstrated. To fill this gap, we administered a perceptual decision-making task to neuro-oncological prefrontal patients, in which the requirement to be quick or accurate changed randomly on a trial-by-trial basis. To directly assess hemispheric asymmetries in speed-accuracy regulation, patients were tested a few days before and a few days after surgical excision of a brain tumor involving either the left (N=13) or the right (N=12) lateral frontal brain region. A group of age- and education-matched healthy controls was also recruited. To gain more insight on the component processes implied in the task, performance data (accuracy and speed) were not only analyzed separately but also submitted to a diffusion model analysis. The main findings indicated that the left prefrontal patients were impaired in appropriately adopting stricter response criteria in speed-to-accuracy switching trials with respect to healthy controls and right prefrontal patients, who were not impaired in this condition. This study demonstrates that the prefrontal cortex in the left hemisphere is necessary for flexible behavioral regulations, in particular when setting stricter response criteria is required in order to successfully switch from a speedy strategy to an accurate one.

The ability to shift between different tasks according to internal or external demands, which is at the core of our behavioral flexibility, has been generally linked to the functionality of left fronto-parietal regions. Traditionally, the left and right hemispheres have also been associated with verbal and spatial processing, respectively. We therefore investigated with functional MRI whether the processes engaged during task-switching interact in the brain with the domain of the tasks to be switched, that is, verbal or spatial. Importantly, physical stimuli were exactly the same and participants' performance was matched between the two domains. The fMRI results showed a clearly left-lateralized involvement of fronto-parietal regions when contrasting task-switching versus single task blocks in the context of verbal rules. A more bilateral pattern, especially in the prefrontal cortex, was instead observed for switching between spatial tasks. Moreover, while a conjunction analysis showed that the core regions involved in task-switching, independently of the switching context, were localized both in left inferior prefrontal and parietal cortices and in bilateral supplementary motor area, a direct analysis of functional lateralization revealed that hemispheric asymmetries in the frontal lobes were more biased toward the left side for the verbal domain than for the spatial one and vice versa. Overall, these findings highlight the role of left fronto-parietal regions in task-switching, above and beyond the specific task requirements, but also show that hemispheric asymmetries may be modulated by the more specific nature of the tasks to be performed during task-switching.

Young and elderly adults performed a choice-RT task while scanned with functional magnetic resonance imaging. A foreperiod separated a warning and a response signal. In the variable condition, the foreperiod varied randomly between 1 and 3s. In the fixed conditions, it was kept constant at either 1 or 3s. Elderly subjects responded slower than controls in both task conditions. An interaction was observed between age and foreperiod in the variable condition only: in the young group, RT decreased with longer foreperiods, whereas the elderly participants showed the opposite tendency. This was accompanied by difference in brain activation. Right lateral prefrontal regions were more activated in the young than in the elderly group in the variable vs. fixed foreperiod contrast. These findings unveil the neural substrate of age-related preparation deficits, and confirm that the involvement of right lateral prefrontal cortex is essential for strategic preparation under uncertain timing conditions.

The brain predicts the timing of forthcoming events to optimize processes in response to them. Temporal predictions are driven by both our prior expectations on the likely timing of stimulus occurrence and the information conveyed by the passage of time. Specifically, such predictions can be described in terms of the hazard function, that is, the conditional probability that an event will occur, given it has not yet occurred. Events violating expectations cause surprise and often induce updating of prior expectations. While it is well-known that the brain is able to track the temporal hazard of event occurrence, the question of how prior temporal expectations are updated is still unsettled. Here we combined a Bayesian computational approach with brain imaging to map updating of temporal expectations in the human brain. Moreover, since updating is usually highly correlated with surprise, participants performed a task that allowed partially differentiating between the two processes. Results showed that updating and surprise differently modulated activity in areas belonging to two critical networks for cognitive control, the fronto-parietal (FPN) and the cingulo-opercular network (CON). Overall, these data provide a first computational characterization of the neural correlates associated with updating and surprise related to temporal expectation.

Different cortical regions respond with distinct rhythmic patterns of neural oscillations to Transcranial Magnetic Stimulation (TMS). We investigated natural frequencies induced by TMS in left and right homologous dorsolateral prefrontal cortices (DLPFC) and related hemispheric differences. In 12 healthy young adults, single-pulse TMS was delivered in different blocks close to F3 and F4 channels to target left and right DLPFC. An occipital site near PO3 was stimulated as control. TMS-related spectral perturbation analyses were performed on recorded EEG data. A widespread unspecific increase in theta power was observed for all stimulation sites. However, occipital TMS induced greater alpha activity and a 10.58 Hz natural frequency, while TMS over the left and right DLPFC resulted in similar beta band modulations and a natural frequency of 18.77 and 18.5 Hz, respectively. In particular, TMS-related specific increase in beta activity was stronger for the right than the left DLPFC. The right DLPFC is more specifically tuned to its natural beta frequency when it is directly stimulated by TMS than with TMS over the left counterpart (or a posterior region), while the left DLPFC increases its beta activity more similarly irrespective of whether it is directly stimulated or through right homologous stimulation. These results yield important implications for both basic neuroscience research on inter-hemispheric prefrontal interactions and clinical applications.

Many aspects of attention decline with aging. There is a current debate on how aging also affects sustained attention. In this study, we contribute to this debate by meta-analytically comparing performance on the go/no-go Sustained Attention to Response Task (SART) in younger and older adults. We included only studies in which the SART had a low proportion of no-go trials (5%-30%), there was a random or quasirandom stimulus presentation, and data on both healthy younger and older adults were available. A total of 12 studies were suitable with 832 younger adults and 690 older adults. Results showed that older adults were slower than younger adults on go trials (g = 1, 95% CI [.72, 1.27]) and more accurate than younger adults on no-go trials (g = .59, 95% CI [.32, .85]). Moreover, older adults were slower after a no-go error than younger adults (g = .79, 95% CI [.60, .99]). These results are compatible with an age-related processing speed deficit, mostly suggested by longer go RTs, but also with an increased preference for a prudent strategy, as demonstrated by fewer no-go errors and greater posterror slowing in older adults. An inhibitory deficit account could not explain these findings, as older adults actually outperformed younger adults by producing fewer false alarms to no-go stimuli. These findings point to a more prudent strategy when using attentional resources in aging that allows reducing the false-alarm rate in tasks producing a tendency for automatic responding.

Dementia with Lewy bodies (DLB) is a neurodegenerative disease characterized by cognitive, behavioral and motor symptoms and has a more challenging clinical management and poorer prognosis compared to other forms of dementia. The experience of lockdown leads to negative psychological outcomes for fragile people such as elderly with dementia, particularly for DLB, causing a worsening of cognitive and neuropsychiatric symptoms. Since an individual's feeling of time passage is strongly related to their cognitive and emotional state, it is conceivable to expect alterations of this construct in people with DLB during such a difficult period. We therefore assessed the subjective experience of the passage of time for present and past time intervals (Subjective Time Questionnaire, STQ) during the lockdown due to coronavirus disease (COVID-19) in 22 patients with DLB (17 of which were re-tested in a post-lockdown period) and compared their experience with that of 14 caregivers with similar age. Patients showed a significantly slower perception of present and past time spent under lockdown restrictions. We argue that these alterations might be related to the distinctive features of DLB and their exacerbation recorded by the patients' caregivers during the period of lockdown, though our results show that the patients' experience of time passage in a post-lockdown period remained similarly slow. Overall, we show an impairment of the subjective perception of time passage in DLB tested during the COVID-19 lockdown.

Temporal orienting (TO) is the allocation of attentional resources in time based on the a priori generation of temporal expectancy of relevant stimuli as well as the a posteriori updating of this expectancy as a function of both sensory-based evidence and elapsing time. These processes rely on dissociable cognitive mechanisms and neural networks. Yet, although there is evidence that TO may be a core mechanism for cognitive functioning in childhood, the developmental spatiotemporal neural dynamics of this mechanism are little understood. In this study we employed a combined approach based on the application of distributed source reconstruction on a high spatial resolution ERP data array obtained from eighteen 8- to 12-year-old children completing a TO paradigm in which both the cue (Temporal vs. Neutral) and the SOA (Short vs. Long) were manipulated. Results show both cue (N1) and SOA (CNV, Omission Detection Potential and Anterior Anticipatory Index) ERP effects, which were associated with expectancy generation and updating, respectively. Only cue-related effects were correlated with age, as revealed by a reduction of the N1 delta effect with increasing age. Our data suggest that the neural correlates underlying TO are already established at least from 8 to 12 years of age.

This study investigates whether the monitoring role that has been ascribed to the right lateral prefrontal cortex in various cognitive domains also applies to the spatial domain. Specific questions of the study were (i) what kind of spatial contingencies trigger the putative monitoring function of right lateral prefrontal cortex and (ii) which other brain regions are functionally connected to it in monitoring-related conditions. Participants had to track the trajectory of a car moving within a roundabout and detect when the car hit the crash-barrier. Four different trajectories were used with different degrees of regularity and predictability. The results showed that two regions in the right hemisphere, the lateral prefrontal and inferior parietal cortex, were maximally activated and functionally connected when monitoring regular predictable trajectories as compared with unpredictable ones, demonstrating that this fronto-parietal network plays a role in monitoring environmental contingencies that can inform expectancy in a meaningful way.

That the left prefrontal cortex has a critical role setting response criteria for numerous tasks has been well established, but gaps remain in our understanding of the brain mechanisms of task-setting. We aimed at (i) testing the involvement of this region in setting the criteria for a non-response and (ii) assessing functional connectivity between this and other brain regions involved in task-setting. Fourteen young participants performed a go/nogo task during functional magnetic resonance imaging. The task included two nogo visual stimuli which elicit a high (distractor) or a low (other) tendency to respond, respectively. Two task blocks were examined to assess learning the criteria. First, a multivariate Partial Least Squares (PLS) analysis identified brain regions that co-varied with task conditions, as expressed by two significant Latent Variables (LVs). One LV distinguished go and nogo stimuli. The other LV identified regions involved in the first block when the criteria not to respond to distractors were established. The left prefrontal region was prominently involved. Second, a left ventrolateral prefrontal area was selected from this LV as a seed region to perform functional connectivity using a multi-block PLS analysis. Results showed a distributed network functionally connected with the seed, including superior medial prefrontal and left superior parietal regions. These findings extend our understanding of task-setting along the following dimensions: 1) even when a task requires withholding a response, the left prefrontal cortex has a critical role in setting criteria, and 2) this region responds to the task demands within a distinctive functional network.

Cognitive control is particularly challenged when it is necessary to resolve interference and correct our behavior on-the-fly. To do this, it is necessary to inhibit the ongoing wrong action and reprogram a new motor plan as appropriate for the current task. This ability requires a complex interaction between cognitive and motor control. Here, we aimed at shedding light on this interplay. To do this, we administered a spatial version of the Stroop task comprising blocks with different Proportion Congruency (PC) manipulations (i.e., manipulating the percentage of congruent trials at 25%, 50% or 75%), to elicit different cognitive control demands. Moreover, we used two techniques with high-temporal resolution, as we simultaneously recorded EEG and mouse trajectories, that can be considered the real-time kinematic correlates of the ongoing cognitive processing. Specifically, we analyzed the Event Related Potentials (ERPs) locked to the peak deceleration time, which marks the suppression of ongoing erroneous trajectories, and we estimated their neural sources. We found three PC-dependent ERP components engaging distinct neural regions, which showed a reduction of the Stroop effect for low-PC blocks. By using a novel co-registration of mouse-trajectories and EEG, we suggest that the observed components may reflect different mechanisms engaged by reactive cognitive control to resolve the interference, including the suppression of an ongoing but no longer appropriate response, the selection of the new motor plan and its actual updating.

Homotopic functional connectivity reflects the degree of synchrony in spontaneous activity between homologous voxels in the two hemispheres. Previous studies have associated increased brain homotopy and decreased white matter integrity with performance decrements on different cognitive tasks across the life-span. Here, we correlated functional homotopy, both at the whole-brain level and specifically in fronto-parietal network nodes, with task-switching performance in young adults. Cue-to-target intervals (CTI: 300 vs. 1200 ms) were manipulated on a trial-by-trial basis to modulate cognitive demands and strategic control. We found that mixing costs, a measure of task-set maintenance and monitoring, were significantly correlated to homotopy in different nodes of the fronto-parietal network depending on CTI. In particular, mixing costs for short CTI trials were smaller with lower homotopy in the superior frontal gyrus, whereas mixing costs for long CTI trials were smaller with lower homotopy in the supramarginal gyrus. These results were specific to the fronto-parietal network, as similar voxel-wise analyses within a control language network did not yield significant correlations with behavior. These findings extend previous literature on the relationship between homotopy and cognitive performance to task-switching, and show a dissociable role of homotopy in different fronto-parietal nodes depending on task demands.

Resilience is the capacity of complex systems to persist in the face of external perturbations and retain their functional properties and performance. In the present study, we investigated how individual variations in brain resilience, which might influence response to stress, aging and disease, are influenced by genetics and/or the environment, with potential implications for the implementation of resilience-boosting interventions. Resilience estimates were derived from in silico lesioning of either brain regions or functional connections constituting the connectome of healthy individuals belonging to two different large and unique datasets of twins, specifically: 463 individual twins from the Human Connectome Project and 453 individual twins from the Colorado Longitudinal Twin Study. As has been reported previously, moderate heritability was found for several topological indexes of brain efficiency and modularity. Importantly, evidence of heritability was found for resilience measures based on removal of brain connections rather than specific single regions, suggesting that genetic influences on resilience are preferentially directed toward region-to-region communication rather than local brain activity. Specifically, the strongest genetic influence was observed for moderately weak, long-range connections between a specific subset of functional brain networks: the Default Mode, Visual and Sensorimotor networks. These findings may help identify a link between brain resilience and network-level alterations observed in neurological and psychiatric diseases, as well as inform future studies investigating brain shielding interventions against physiological and pathological perturbations.

Performance on tasks involving cognitive control such as the Stroop task is often associated with left lateralized brain activations. Based on this neuro-functional evidence, we tested whether leftward structural grey matter asymmetries would also predict inter-individual differences in combatting Stroop interference. To check for the specificity of the results, both a verbal Stroop task and a spatial one were administered to a total of 111 healthy young individuals, for whom T1-weighted magnetic resonance imaging (MRI) images were also acquired. Surface thickness and area estimations were calculated using FreeSurfer. Participants' hemispheres were registered to a symmetric template and Laterality Indices (LI) for the surface thickness and for the area at each vertex in each participant were computed. The correlation of these surface LI measures with the verbal and spatial Stroop effects (incongruent-congruent difference in trial performance) was assessed at each vertex by means of general linear models at the whole-brain level. We found a significant correlation between performance and surface area LI in an inferior posterior temporal cluster (overlapping with the so-called visual word form area, VWFA), with a more left-lateralized area in this region associated with a smaller Stroop effect only in the verbal task. These results point to an involvement of the VWFA for higher-level processes based on word reading, including the suppression of this process when required by the task, and could be interpreted in the context of cross-hemispheric rivalry.

Alzheimer's disease (AD) represents the most common type of neurodegenerative disorder. Although our knowledge on the causes of AD remains limited and no curative treatments are available, several interventions have been proposed in trying to improve patients' symptomatology. Among those, transcranial magnetic stimulation (TMS) has been shown a promising, safe and noninvasive intervention to improve global cognitive functioning. Nevertheless, we currently lack agreement between research studies on the optimal stimulation protocol yielding the highest efficacy in these patients. To answer this query, we conducted a systematic literature search in PubMed, PsycINFO and Scopus databases and meta-analysis of studies published in the last 10 years (2010-2021) according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Differently from prior published meta-analytic work, we investigated whether protocols that considered participants-specific neuroimaging scans for the selection of individualized stimulation targets held more successful outcomes compared to those relying on a generalized targeting selection criteria. We then compared the effect sizes of subsets of studies based on additional protocol characteristics (frequency, duration of intervention, number of stimulation sites, use of concomitant cognitive training and patients' educational level). Our results confirm TMS efficacy in improving global cognitive functioning in mild-to-moderate AD patients, but also highlight the flaws of current protocols characteristics, including a possible lack of sufficient personalization in stimulation protocols.

In our daily life, we constantly exert sustained and phasic cognitive control processes to manage multiple competing task sets and rapidly switch between them. Increasing research efforts are attempting to unveil how the brain mediates these processes, highlighting the importance of the prefrontal cortex. An intriguing question concerns the influence of hemispheric asymmetries and whether it may be generalized to different cognitive domains depending on lateralized processing. Another currently open question concerns the underlying causes of the observed huge inter-individual variability in cognitive control abilities. Here we tackle these issues by investigating whether participants' hemispheric asymmetry in intrinsic (i.e., resting-state-related) brain dynamics can reflect differences in their phasic and/or sustained cognitive control abilities regardless of the cognitive domain. To this aim, we recorded human participants' resting-state electroencephalographic activity and performed a source-based spectral analysis to assess their lateralized brain dynamics at rest. Moreover, we used three task-switching paradigms involving different cognitive domains to assess participants' domain-general phasic and sustained cognitive control abilities. By performing a series of correlations and an intersection analysis, we showed that participants with stronger left- and right-lateralized intrinsic brain activity in the middle frontal gyrus were more able, respectively, to exert phasic and sustained cognitive control. We propose that the variability in participants' prefrontal hemispheric asymmetry in the intrinsic electrophysiological spectral profile reflects individual differences in preferentially engaging either the left-lateralized, phasic or the right-lateralized, sustained cognitive control processes to regulate their behavior in response to changing task demands, regardless of the specific cognitive domain involved.

Although human flexible behavior relies on cognitive control, it would be implausible to assume that there is only one, general mode of cognitive control strategy adopted by all individuals. For instance, different reliance on proactive versus reactive control strategies could explain inter-individual variability. In particular, specific life experiences, like a highly demanding training for future Air Traffic Controllers (ATCs), could modulate cognitive control functions. A group of ATC trainees and a matched group of university students were tested longitudinally on task-switching and Stroop paradigms that allowed us to measure indices of cognitive control. The results showed that the ATCs, with respect to the control group, had substantially smaller mixing costs during long cue-target intervals (CTI) and a reduced Stroop interference effect. However, this advantage was present also prior to the training phase. Being more capable in managing multiple task sets and less distracted by interfering events suggests a more efficient selection and maintenance of task relevant information as an inherent characteristic of the ATC group, associated with proactive control. Critically, the training that the ATCs underwent improved their accuracy in general and reduced response time switching costs during short CTIs only. These results indicate a training-induced change in reactive control, which is described as a transient process in charge of stimulus-driven task detection and resolution. This experience-based enhancement of reactive control strategy denotes how cognitive control and executive functions in general can be shaped by real-life training and underlines the importance of experience in explaining inter-individual variability in cognitive functioning.

The ability to flexibly switch between tasks is a hallmark of cognitive control. Despite previous studies that have investigated whether different task-switching types would be mediated by distinct or overlapping neural mechanisms, no definitive consensus has been reached on this question yet. Here, we aimed at directly addressing this issue by recording the event-related potentials (ERPs) elicited by two types of task-switching occurring in the context of spatial and verbal cognitive domains. Source analysis was also applied to the ERP data in order to track the spatial dynamics of brain activity underlying task-switching abilities. In separate blocks of trials, participants had to perform either spatial or verbal switching tasks both of which employed the same type of stimuli. The ERP analysis, which was carried out through a channel- and time-uninformed mass univariate approach, showed no significant differences between the spatial and verbal domains in the modulation of switch and repeat trials. Specifically, relative to repeat trials, switch trials in both domains were associated with a first larger positivity developing over left parieto-occipital electrodes and with a subsequent larger negativity distributed over mid-left fronto-central sites. The source analysis reconstruction for the two ERP components complemented these findings by highlighting the involvement of left-lateralized prefrontal areas in task-switching. Overall, our results join and extend recent research confirming the existence of left-lateralized domain-general task-switching processes.

Functional hemispheric asymmetry can be lost with aging. In this electroencephalographic study, we assessed hemispheric asymmetries in regulating motor responses by analyzing oscillatory brain activity during a go/nogo task in younger and older right-handed participants. Three conditions were embedded in the task: go, high-conflict and low-conflict nogo. The hand used to respond to go stimuli was varied block-wise. Independently of the go/nogo conditions and responding hand, young participants showed asymmetric desynchronizations in the mu (10 Hz) and beta (18-22 Hz) frequency bands that was stronger in the scalp sensorimotor region contralateral to the hand used for the go responses, while older adults showed a more symmetric pattern of desynchronization. These findings indicate that a loss of hemispheric asymmetry is a hallmark of the aging motor system, consistent with a decline of inter-hemispheric motor inhibition in normal aging.

The ability to check and evaluate the environment over time with the aim to detect the occurrence of target stimuli is supported by sustained/tonic as well as transient/phasic control processes, which overall might be referred to as event monitoring. The neural underpinning of sustained attentional control processes involves a fronto-parietal network. However, it has not been well-defined yet whether this cortical circuit acts irrespective of the specific material to be monitored and whether this mediates sustained as well as transient monitoring processes. In the current study, the functional activity of brain during an event monitoring task was investigated and compared between two cognitive domains, whose processing is mediated by differently lateralized areas. Namely, participants were asked to monitor sequences of either faces (supported by right-hemisphere regions) or tools (left-hemisphere). In order to disentangle sustained from transient components of monitoring, a simultaneous EEG-fMRI technique was adopted within a block design. When contrasting monitoring versus control blocks, the conventional fMRI analysis revealed the sustained involvement of bilateral fronto-parietal regions, in both task domains. Event-related potentials (ERPs) showed a more positive amplitude over frontal sites in monitoring compared to control blocks, providing evidence of a transient monitoring component. The joint ERP-fMRI analysis showed that, in the case of face monitoring, this transient component relies on right-lateralized areas, including the inferior parietal lobule and the middle frontal gyrus. In the case of tools, no fronto-parietal areas correlated with the transient ERP activity, suggesting that in this domain phasic monitoring processes were masked by tonic ones. Overall, the present findings highlight the role of bilateral fronto-parietal regions in sustained monitoring, independently of the specific task requirements, and suggest that right-lateralized areas subtend transient monitoring processes, at least in some task contexts.