Marie-Anne Vanderhasselt

Working memory improvement with non-invasive brain stimulation of the dorsolateral prefrontal cortex: A systematic review and meta-analysis

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 meta-analyses 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 (RTs), higher percentage of correct responses and lower percentage of error responses. However, meta-regressions showed that tDCS (vs. rTMS) presented only an improvement in RT, and not in accuracy. This could have occurred in part because almost all tDCS studies employed a crossover design, possibly due to the reliable tDCS blinding. Study design was also associated with no improvement in correct responses in the active vs. sham groups. To conclude, rTMS of 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.

Cognitive control therapy and transcranial direct current stimulation for depression: A randomized, double-blinded, controlled trial

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 neurocognitive 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 those who 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.

Cognitive control moderates the association between stress and rumination

BACKGROUND AND OBJECTIVES A prospective design was used to examine whether inter-individual differences in cognitive control ability, for non-emotional and emotional material, play a moderating role in the association between the occurrence of a stressful event and the tendency to ruminate. METHODS At baseline, the Internal Switch Task (IST) was administered in an undergraduate sample to measure the ability to switch attention between items held in working memory. Six weeks after baseline, self-report questionnaires were administered at 4 fixed moments during their first examination period at university, measuring stressors, rumination and depressive symptoms. RESULTS Results revealed that impaired cognitive control, reflected in larger switch costs, moderated the association between stress and increased rumination. Interestingly, a larger switch cost when processing emotional material was specifically associated with increased depressive brooding in response to stress. No effects with reflective pondering were observed. CONCLUSIONS Implications for understanding the underlying mechanisms of rumination are discussed.

A Systematic Review and Meta-Analysis of the Effects of Transcranial Direct Current Stimulation (tDCS) Over the Dorsolateral Prefrontal Cortex in Healthy and Neuropsychiatric Samples: Influence of Stimulation Parameters

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 accurately. 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.

The influence of rTMS over the left dorsolateral prefrontal cortex on Stroop task performance.

Several studies have demonstrated that repetitive transcranial magnetic stimulation (rTMS) can improve cognitive processing. Neuroimaging studies have shown the engagement of the left dorsolateral prefrontal cortex (DLPFC) in executive functioning, and more specifically during selective attention. In the present study, the influence of high-frequency rTMS over the left DLPFC on Stroop task performance in healthy female volunteers was investigated. As expected, reaction time on both the incongruent and congruent trials decreased significantly after stimulation, and there was no difference with regard to the Stroop interference effect. Mood remained unchanged after rTMS. Such a pattern is consistent with the role of the left DLPFC in implementing top–down attentional control.

Accelerated HF-rTMS in treatment-resistant unipolar depression: Insights from subgenual anterior cingulate functional connectivity

Abstract Objectives. Intensified repetitive transcranial magnetic stimulation (rTMS) applied to the left dorsolateral prefrontal cortex (DLPFC) may result in fast clinical responses in treatment resistant depression (TRD). In these kinds of patients, subgenual anterior cingulate cortex (sgACC) functional connectivity (FC) seems to be consistently disturbed. So far, no de novo data on the relationship between sgACC FC changes and clinical efficacy of accelerated rTMS were available. Methods. Twenty unipolar TRD patients, all at least stage III treatment resistant, were recruited in a randomized sham-controlled crossover high-frequency (HF)-rTMS treatment study. Resting-state (rs) functional MRI scans were collected at baseline and at the end of treatment. Results. HF-rTMS responders showed significantly stronger resting-state functional connectivity (rsFC) anti-correlation between the sgACC and parts of the left superior medial prefrontal cortex. After successful treatment an inverted relative strength of the anti-correlations was observed in the perigenual prefrontal cortex (pgPFC). No effects on sgACC rsFC were observed in non-responders. Conclusions. Strong rsFC anti-correlation between the sgACC and parts of the left prefrontal cortex could be indicative of a beneficial outcome. Accelerated HF-rTMS treatment designs have the potential to acutely adjust deregulated sgACC neuronal networks in TRD patients.

Dorsolateral prefrontal cortex and Stroop performance: tackling the lateralization.

Neuroscience research has identified the involvement of the dorsolateral prefrontal cortex (DLPFC) in cognitive control. Questions remain, however, about its lateralization correlates during Stroop task performance, an experimental cornerstone on which a large amount of cognitive control research is based. After reviewing the literature, we find that three Stroop variants have been used in an attempt to uncover different aspects of cognitive control related to DLPFC involvement. In sum, rapid and sequential up-regulation of the attentional set seems to be related to the left DLPFC. These attentional adjustments are based on participants’ expectancies regarding the conflicting nature of the upcoming trial, and not on the conflict itself. In contrast, the right DLPFC is associated with an overall up-regulation of the attentional set when attentional conflict is experienced.

Neurocognitive effects of HF-rTMS over the dorsolateral prefrontal cortex on the attentional processing of emotional information in healthy women an event-related fMRI study

Current evidence concerning the neurocircuitry underlying the interplay between attention and emotion is mainly correlational. We used high-frequency repetitive Transcranial Magnetic Stimulation (HF-rTMS) to experimentally manipulate activity within the right or left dorsolateral prefrontal cortex (DLPFC) of healthy women and examined changes in attentional processing of emotional information using an emotional modification of the exogenous cueing task during event-related fMRI. Right prefrontal HF-rTMS resulted in impaired disengagement from angry faces, associated with decreased activation within the right DLPFC, dorsal anterior cingulate cortex (dACC) and left superior parietal gyrus, combined with increased activity within the right amygdala. Left prefrontal HF-rTMS resulted in diminished attentional engagement by angry faces and was associated with increased activity within the right DLPFC, dACC, right superior parietal gyrus and left orbitofrontal cortex. The present observations are in line with reports of a functionally interactive network of cortical-limbic pathways that play a central role in emotion regulation.

Why ruminators won't stop: The structural and resting state correlates of rumination and its relation to depression

BACKGROUND Rumination is a good predictor of major depression. The current study explores the structural and functional neural correlates of rumination. METHODS To explore structural correlates of rumination (RRS, Treynor et al., 2003) we used voxel-based morphometry. We relate these correlates of rumination to concurrence of grey matter reductions in depressed patients by means of a quantitative meta-analysis on 16 VBM studies. Resting state data was used to compute maps of the amplitude of low frequency fluctuations. RESULTS Rumination correlated negatively with grey matter volume in bilateral inferior frontal gyrus (IFG), left anterior cingulate cortex (ACC), and bilateral mid cingulate cortex. The volume reductions were within proximity of grey matter reductions identified in the meta-analysis on depressed patients in bilateral IFG and ACC. Moreover reductions in resting state activity were overlapping with volume reductions correlated with rumination in ACC and right IFG. LIMITATIONS The participants were all healthy control subjects. Future research is needed to explore the neural correlates of rumination in major depression. CONCLUSIONS The results show that rumination is associated with volume and resting state reductions in brain areas that have been related to cognitive control process of inhibition and thought suppression. We conclude that rumination not only qualifies as a behavioural predictor of major depression but also goes along with neuroanatomical abnormalities that are similar to those identified for depression.

Polarity- and valence-dependent effects of prefrontal transcranial direct current stimulation on heart rate variability and salivary cortisol

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 polarity-dependent 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 within-subject 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.