Working memory (WM) refers to a set of cognitive processes that allows for the temporary storage and manipulation of information, crucial for everyday life skills. WM deficits are present in several neurological, psychiatric, and neurodevelopmental disorders, thus making the full understanding of its neural correlates a key aspect for the implementation of cognitive training interventions. Here, we present a quantitative meta‐analysis focusing on the underlying neural substrates upon which the n‐back, one of the most commonly used tasks for WM assessment, is believed to rely on, as highlighted by functional magnetic resonance imaging and positron emission tomography findings. Relevant published work was scrutinized through the activation likelihood estimate (ALE) statistical framework in order to generate a set of task‐specific activation maps, according to n‐back difficulty. Our results confirm the known involvement of frontoparietal areas across different types of n‐back tasks, as well as the recruitment of subcortical structures, cerebellum and precuneus. Specific activations maps for four stimuli types, six presentation modalities, three WM loads and their combination are provided and discussed. Moreover, functional overlap with resting‐state networks highlighted a strong similarity between n‐back nodes and the Dorsal Attention Network, with less overlap with other networks like Salience, Language, and Sensorimotor ones. Additionally, neural deactivations during n‐back tasks and their functional connectivity profile were examined. Clinical and functional implications are discussed in the context of potential noninvasive brain stimulation and cognitive enhancement/rehabilitation programs.

Coping abilities represent the individual set of mental and behavioral strategies adopted when facing stress or traumatic experiences. Coping styles related to avoidance have been linked to a disposition to develop psychiatric disorders such as PTSD, anxiety, and major depression, whereas problem-oriented coping skills have been positively correlated with well-being and high quality of life. Even though coping styles constitute an important determinant of resilience and can impact many aspects of everyday living, no study has investigated their brain functional connectivity underpinnings in humans. Here we analyzed both psychometric scores of coping and resting-state fMRI data from 102 healthy adult participants. Controlling for personality and problem-solving abilities, we identified significant links between the propensity to adopt different coping styles and the functional connectivity profiles of regions belonging to the default mode (DMN) and anterior salience (AS) networks-namely, the anterior cingulate cortex, left frontopolar cortex, and left angular gyrus. Also, a reduced negative correlation between AS and DMN nodes explained variability in one specific coping style, related to avoiding problems while focusing on the emotional component of the stressor at hand, instead of relying on cognitive resources. These results might be integrated with current neurophysiological models of resilience and individual responses to stress, in order to understand the propensity to develop clinical conditions (e.g., PTSD) and predict the outcomes of psychotherapeutic interventions.

Human cognitive abilities and behavior are linked to functional coupling of many brain regions organized in distinct networks. Gaining insights on the role those networks' dynamics play in cognition and pathology requires their selective, reliable, and reversible manipulation. Here we document the possibility to manipulate the interplay between two brain networks in a controlled manner, by means of a Transcranial Magnetic Stimulation (TMS) protocol inducing spike timing dependent plasticity (STDP). Pairs of TMS pulses at specific inter-stimulus intervals, repeatedly delivered over two negatively correlated nodes of the default mode network (DMN) and the task-positive network (TPN) defined on the basis of individual functional magnetic resonance imaging (fMRI) data, induced a modulation of network-to-network connectivity, even reversing correlation from negative to slightly positive in 30% of cases. Results also suggest a baseline-dependent effect, with a greater connectivity modulation observed in participants with weaker between-networks connectivity strength right before TMS. Finally, modulation of task-evoked fMRI activity patterns during a sustained attention task was also observed after stimulation, with a faster or slower switch between rest and task blocks according to the timing of TMS pulses. The present findings promote paired associative TMS as a promising technique for controlled manipulation of fMRI connectivity dynamics in humans, as well as the causal investigation of brain-behavior relations.

Background: Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique able to transiently modulate brain activity, is surging as one of the most promising therapeutic solutions in many neurological and psychiatric disorders. However, profound limitations exist in current placebo (sham) protocols that limit single-and double-blinding, especially in non-naïve subjects. Objective: To ensure better blinding and strengthen reliability of tDCS studies and trials, we tested a new optimization algorithm aimed at creating an "active" sham tDCS condition (ActiSham hereafter) capable of inducing the same scalp sensations perceived during real stimulation while preventing currents from reaching the cortex and cause changes in brain excitability. Methods: A novel model-based multielectrode technique d optimizing the location and currents of a set of small electrodes placed on the scalp d was used to control the relative amount of current delivered transcranially in real and placebo multichannel tDCS conditions. The presence, intensity and localization of scalp sensations during tDCS was evaluated by means of a specifically designed questionnaire administered to the participants. We compared blinding ratings by directly addressing subjects' ability to discriminate across conditions for both traditional (Bifocal-tDCS and Sham, using sponge electrodes) and our novel multifocal approach (both real Multifocal-tDCS and ActiSham). Changes in corticospinal excitability were monitored based on Motor Evoked Potentials (MEPs) recorded via concurrent Transcranial Magnetic Stimulation (TMS) and electromyography (EMG). Results: Participants perceived Multifocal-tDCS and ActiSham similarly in terms of both localization and intensity of scalp sensations, whereas traditional Bifocal stimulation was rated as more painful and annoying compared to its Sham counterpart. Additionally, differences in scalp localization were reported for active/sham Bifocal-tDCS, with Sham tDCS inducing more widespread itching and burning sensations. As for MEPs amplitude, a main effect of stimulation was found when comparing Bifocal-Sham and ActiSham (F (1,13) ¼ 6.67, p ¼ .023), with higher MEPs amplitudes after the application of Bifocal-Sham. Conclusions: Compared to traditional Bifocal-tDCS, ActiSham offers better participants' blinding by inducing very similar scalp sensations to those of real Multifocal tDCS both in terms of intensity and localization, while not affecting corticospinal excitability.

Abstract Fluid intelligence (gf) represents a crucial component of human cognition, as it correlates with academic achievement, successful aging, and longevity. However, it has strong resilience against enhancement interventions, making the identification of gf enhancement approaches a key unmet goal of cognitive neuroscience. Here, we applied a spike-timing-dependent plasticity (STDP)-inducing brain stimulation protocol, named cortico-cortical paired associative stimulation (cc-PAS), to modulate gf in 29 healthy young subjects (13 females—mean ± standard deviation, 25.43 years ± 3.69), based on dual-coil transcranial magnetic stimulation (TMS). Pairs of neuronavigated TMS pulses (10-ms interval) were delivered over two frontoparietal nodes of the gf network, based on individual functional magnetic resonance imaging data and in accordance with cognitive models of information processing across the prefrontal and parietal lobe. cc-PAS enhanced accuracy at gf tasks, with parieto-frontal and fronto-parietal stimulation significantly increasing logical and relational reasoning, respectively. Results suggest the possibility of using SPTD-inducing TMS protocols to causally validate cognitive models by selectively engaging relevant networks and manipulating inter-regional temporal dynamics supporting specific cognitive functions.