Recent studies have used non-invasive brain stimulation (NIBS) techniques, such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), to increase dorsolateral prefrontal cortex (DLPFC) activity and, consequently, working memory (WM) performance.. However, such experiments have yielded mixed results, possibly due to small sample sizes and heterogeneity of outcomes. Therefore, our aim was to perform a systematic review and metaanalyses on NIBS studies assessing the n-back task, which is a reliable index for WM. From the first data available to February 2013, we looked for sham-controlled, randomized studies that used NIBS over the DLPFC using the n-back task in PubMed/MEDLINE and other databases. Twelve studies (describing 33 experiments) matched our eligibility criteria. Active vs. sham NIBS was significantly associated with faster response times (RT), higher percentage of correct responses and lower percentage of error responses. However, meta-regressions showed that tDCS (vs. rTMS) presented an improvement only in RT. This could have occurred in part because almost all tDCS studies employed a crossover design (possibly more employed in tDCS over rTMS due to the reliable tDCS blinding) -this factor (study design) was also associated with no improvement in correct responses in the active vs. sham groups. To conclude, rTMS over the DLPFC significantly improved all measures of WM performance whereas tDCS significantly improved RT, but not the percentage of correct and error responses. Mechanistic insights on the role of DLPFC in WM are further discussed, as well as how NIBS techniques could be used in neuropsychiatric samples presenting WM deficits, such as major depression, dementia and schizophrenia.

Background:Research into the effects of transcranial direct current stimulation of the dorsolateral prefrontal cortex on cognitive functioning is increasing rapidly. However, methodological heterogeneity in prefrontal tDCS research is also increasing, particularly in technical stimulation parameters that might influence tDCS effects.Objective: To systematically examine the influence of technical stimulation parameters on DLPFC-tDCS effects. Methods:We performed a systematic review and meta-analysis of tDCS studies targeting the DLPFC published from the first data available to February 2016. Only single-session, sham-controlled, within-subject studies reporting the effects of tDCS on cognition in healthy controls and neuropsychiatric patients were included. Results:Evaluation of 61 studies showed that after single-session a-tDCS, but not c-tDCS, participants responded faster and more accurately on cognitive tasks. Sub-analyses specified that following a-tDCS, healthy subjects responded faster, while neuropsychiatric patients responded more accurate. Importantly, different stimulation parameters affected a-tDCS effects, but not c-tDCS effects, on accuracy in healthy samples vs. patients: increased current density and density charge resulted in improved accuracy in healthy samples, most prominently in females; for neuropsychiatric patients, task performance during a-tDCS resulted in stronger increases in accuracy rates compared to task performance following a-tDCS. Conclusions:Healthy participants respond faster, but not more accurate on cognitive tasks after a-tDCS.However, increasing the current density and/or charge might be able to enhance response accuracy, particularly in females. In contrast, online task performance leads to greater increases in response accuracy than offline task performance in neuropsychiatric patients. Possible implications and practical recommendations are discussed.

Background: Based on findings that major depressive disorder (MDD) is associated to decreased dorsolateral prefrontal cortical (DLPFC) activity; interventions that increase DLPFC activity might theoretically present antidepressant effects. Two of them are cognitive control therapy (CCT), a neurobehavioral intervention that uses computer-based working memory exercises, and transcranial direct current stimulation (tDCS), which delivers weak, electric direct currents over the scalp. Methods:We investigated whether tDCS enhanced the effects of CCT in a double-blind trial, in which participants were randomized to sham tDCS and CCT (n=17) vs. active tDCS and CCT (n=20). CCT and tDCS were applied for 10 consecutive workdays. Clinicaltrials.gov identifier:NCT01434836.Results: Both CCT alone and combined with tDCS ameliorated depressive symptoms after the acute treatment period and at follow-up, with a response rate of approximately 25%. Older patients and those who presented better performance in the task throughout the trial (possibly indicating greater engagement and activation of the DLPFC) had greater depression improvement in the combined treatment group.Limitations: Our exploratory findings should be further confirmed in prospective controlled trials.Discussion: CCT and tDCS combined might be beneficial for older depressed patients, particularly for thosewho have cognitive resources to adequately learn and improve task performance over time.This combined therapy might be specifically relevant in this subgroup that is more prone to present cognitive decline and prefrontal cortical atrophy. KeywordsMajor depressive disorder; transcranial direct current stimulation; control cognitive therapy; noninvasive brain stimulation; randomized clinical trial; geriatric depression. 3

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Recent evidence has supported the notion that the hypothalamic-pituitary-adrenal (HPA) and the sympatho-adreno-medullary (SAM) systems are modulated by cortical structures such as the prefrontal cortex. This top-down modulation may play a major role in the neuroendocrine changes associated with stressful events. We aimed to investigate further this hypothesis by modulating directly prefrontal cortex excitability using transcranial direct current stimulation (tDCS) -a non-invasive, neuromodulatory tool that induces polaritydependent changes in cortical excitability -and measuring effects on salivary cortisol and heart rate variability as proxies of the HPA and SAM systems. Twenty healthy participants with no clinical and neuropsychiatric conditions were randomized to receive bifrontal tDCS (left anodal/right cathodal or left cathodal/right anodal) or sham stimulation, in a withinsubject design. During each stimulation session, after a resting period, subjects were shown images with neutral or negative valence. Our findings showed that excitability enhancing left anodal tDCS induced a decrease in cortisol levels. This effect is more pronounced during emotional negative stimuli. Moreover, vagal activity was higher during left anodal tDCS and emotional negative stimuli, as compared to sham stimulation and neutral images. We also observed an association between higher mood scores, higher vagal activation and lower cortisol levels for anodal stimulation. Subjective mood and anxiety evaluation revealed no specific changes after stimulation. Our findings suggest that tDCS induced transient, polarity specific modulatory top-down effects with anodal tDCS leading to a down-regulation of HPA and SAM systems. Further research using tDCS and neuroendocrine markers should explore the mechanisms of stress regulation in healthy and clinical samples.3

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AND CHRIS BAEKENUniversity Hospital Brussels (UZ Brussel), Brussels, Belgium Neuroscience research has identified the involvement of the dorsolateral prefrontal cortex (DLPFC) Theoretical BackgroundCognitive control can be conceptualized as the capacity to suppress prepotent but incorrect responses and the ability to filter out irrelevant information within a stimulus set (Botvinick, Braver, Barch, Carter, & Cohen, 2001). Experimental conflict situations that require cognitive control have been found in tasks that demand overriding of prepotent responses, such as in the Stroop (1935) paradigm. The Stroop interference effect is one of the most frequently used tasks in cognitive psychology, clinical neuropsychology, and cognitive neuroscience. In a Stroop color-naming task, participants have to name the ink color of a printed color word, and greater conflict occurs for incongruent (e.g., the word RED in green ink) than for congruent (e.g., the word RED in red ink) trials-in other words, the Stroop interference effect.Neuroimaging techniques can be used to investigate the brain correlates of cognitive control during experiments. Such activation techniques include PET (positron emission tomography), fMRI (functional magnetic resonance imaging), and ERPs (event-related potentials). These neuroimaging techniques face the critical problem, though, of distinguishing cause from effect, because no interference with brain activity is provoked. As a noninvasive tool for stimulation of the human cerebral cortex, repetitive transcranial magnetic stimulation (rTMS) induces alterations of neuronal activity that have an effect on cognition; this is becoming a promising technique for investigating whether a particular area is essential for task performance.

Cognitive control plays a key role in both adaptive emotion regulation, such as positive reappraisal, and maladaptive emotion regulation, such as rumination, with both strategies playing a major role in resilience and well-being. As a result, cognitive control training targeting working memory functioning (CCT) may have the potential to reduce maladaptive emotion regulation and increase adaptive emotion regulation. The current study explored the effects of CCT on positive reappraisal ability in a lab context, and deployment and efficacy of positive appraisal and rumination in daily life. A sample of undergraduates (n = 83) was allocated to CCT or an active control condition, performing 10 online training sessions over a period of 14 days. Effects on regulation of affective states in daily life were assessed using experience sampling over a seven-day post-training period. Results revealed a positive association between baseline cognitive control and self-reported use of adaptive emotion regulation strategies, whereas maladaptive emotion regulation strategies showed a negative association. CCT showed transfer to working memory functioning on the dual n-back task.Overall, effects of CCT on emotion regulation were limited to reducing deployment of rumination in low positive affective states. However, we did not find beneficial effects on indicators of adaptive emotion regulation. These findings are in line with previous studies targeting maladaptive emotion regulation, but suggest limited use in enhancing adaptive emotion regulation in a healthy sample.Keywords: positive reappraisal, rumination, resilience, cognitive control, training COGNITIVE CONTROL AND EMOTION REGULATION 3 How people respond to stressful events and negative emotions has important consequences for their mental health. For instance, responding with negative and repetitive moody pondering (i.e., brooding, a subtype of rumination; Treynor, Gonzalez, & NolenHoeksema, 2003) to negative affect following a stressful event such as loss of job is known to be an important risk factor for developing mood disorders (D'Avanzato, Joormann, Siemer, & Gotlib, 2013; Nolen-Hoeksema, Wisco, & Lyubomirsky, 2008). In contrast, applying a strategy such as cognitive (re-)appraisal in which the emotion-eliciting value of a stressful situation is reduced through cognitive strategies (Gross, 2002) is known to have beneficial effects on well-being and mental health (Gross & John, 2003; Haga, Kraft, & Corby, 2009; Hu et al., 2014). This process of influencing which emotions one has, when one experiences these emotions, and how these emotions are experienced and expressed is known as emotion regulation (p. 275; Gross, 1998) and plays an important role in maintaining and ameliorating mental health (Gross & Jazaieri, 2014). Given their differential effects on mental health, rumination (among strategies such as catastrophizing, self-blame, etc.) has been conceptualized as a maladaptive emotion regulation strategy, whereas cognitive reappraisal (among strategies su...