Web addiction in the brain: Cortical oscillations, autonomic activity, and behavioral measures

Background and aims Internet addiction (IA) was recently defined as a disorder tagging both the impulse control and the reward systems. Specifically, inhibitory deficits and reward bias were considered highly relevant in IA. This research aims to examine the electrophysiological correlates and autonomic activity [skin conductance response (SCR) and heart rate] in two groups of young subjects (N = 25), with high or low IA profile [tested by the Internet Addiction Test (IAT)], with specific reference to gambling behavior. Methods Oscillatory brain activity (delta, theta, alpha, beta, and gamma) and autonomic and behavioral measures [response times (RTs) and error rates (ERs)] were acquired during the performance of a Go/NoGo task in response to high-rewarding (online gambling videos and video games) or neutral stimuli. Results A better performance (reduced ERs and reduced RTs) was revealed for high IAT in the case of NoGo trials representing rewarding cues (inhibitory control condition), probably due to a “gain effect” induced by the rewarding condition. In addition, we also observed for NoGo trials related to gambling and video games stimuli that (a) increased low-frequency band (delta and theta) and SCR and (b) a specific lateralization effect (more left-side activity) delta and theta in high IAT. Discussion Both inhibitory control deficits and reward bias effect were considered to explain IA

Treatment of resistant depression : a pilot study assessing the efficacy of a tDCS-mindfulness program compared with a tDCS-relaxation program

Background: This pilot study explores a therapeutic setting combining transcranial direct current stimulation (tDCS) and mindfulness-based cognitive therapy (MBCT) for patients with drug-resistant depression. tDCS has shown efficacy for depression treatment and improvement could be maintained with the combination with mindfulness, which has shown depression relapse-prevention properties. Methods: Thirty-one treatment-resistant depressed patients have been assigned to our experimental treatment condition [tDCS combined with MBCT (n = 15)] or to a control condition [tDCS combined with relaxation (n = 16)]. Patients have completed both an intensive treatment block (eight consecutive days) and a single remind session 2 weeks after the intensive treatment. Clinical (depression, anxiety, and rumination) and cognitive (general cognitive functioning, mental flexibility, and working memory) symptoms of depression have been assessed through different questionnaires at baseline (t0), after the first block of treatment (t1), and after the remind session (t2). Results: Results seem to indicate a positive impact of both treatment conditions on clinical and cognitive symptoms of depression at t1. However, the treatment condition combining tDCS with mindfulness has been found to better maintain clinical improvements at t2 regarding some clinical [Montgomery-angstrom sberg Depression Rating Scale (MADRS) and Sadness and Anger Ruminative Inventory (SARI)] and cognitive variables (Digit Span-F and Digit Span-B). Conclusion: Based on the current observations, a multi-disciplinary treatment approach combining tDCS and MBCT might be effective in resistant depressed patients in the long run, even though further clinical research is necessary

Editorial: Binge Drinking in the Adolescent and Young Brain

This study was supported by the project POCI-01-0145-FEDER-028672, funded by the Portuguese Foundation for Science and Technology (FCT) and the European Regional Development Fund (FEDER). EL-C was supported by a Postdoctoral Fellowship of the FCT (SFRH/BPD/109750/2015), as well as by the Psychology Research Centre (UID/PSI/01662/2013), co-financed by FEDER through COMPETE2020 under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007653)S

Addiction: Brain and Cognitive Stimulation for Better Cognitive Control and Far Beyond

Addiction behaviors are characterized by conditioned responses responsible for craving and automatic actions as well as disturbances within the supervisory network, one of the key elements of which is the inhibition of prepotent response. Interventions such as brain stimulation and cognitive training targeting this imbalanced system can potentially be a positive adjunct to treatment as usual. The relevance of several invasive and noninvasive brain stimulation techniques in the context of addiction as well as several cognitive training protocols is reviewed. By reducing cue-induced craving and modifying the pattern of action, memory associations, and attention biases, these interventions produced significant but still limited clinical effects. A new refined definition of response inhibition, including automatic inhibition of response and a more consistent approach to cue exposure capitalizing on the phase of reconsolidation of pre-activated emotional memories, all associated with brain and cognitive stimulation, opens new avenues for clinical research

Increased Neural Activity in Hazardous Drinkers During High Workload in a Visual Working Memory Task: A Preliminary Assessment Through Event-Related Potentials

Despite equated behavioral performance levels, hazardous drinkers generally exhibited increased neural activity while performing simple cognitive tasks compared to light drinkers. Here, 49 participants (25 hazardous and 24 light drinkers) participated in an event-related potentials (ERPs) study while performing an n-back working memory task. In the control zero-back (N0) condition, the subjects were required to press a button when the number “2” or “6” was displayed. In the two-back and three-back (N2; N3) conditions, the subjects had to press a button when the displayed number was identical to the number shown two/three trials earlier. To assess for the impact of alcohol consumption on the updating of working memory processes under various cognitive loads, difference waveforms of “N2 minus N0” and “N3 minus N0” were computed by subtracting waveforms in the N0 condition from waveforms in the N2 and N3 conditions, for the light and the hazardous drinkers. Three main ERP components were noted for both groups: a P200/N200 complex, a P300 component, and an N400/P600 activity. The results show that, to perform the task at the same level as the light drinkers, the hazardous drinkers exhibited larger amplitude differences, mainly around the P300 and P600 components. These data may be considered, at the preventive level, as vulnerability factors for developing adult substance use disorders, and they stress the importance, at a clinical level, to consider such working memory processes in the management of alcohol dependence

Epidermal growth factor receptor gene copy number in 101 advanced colorectal cancer patients treated with chemotherapy plus cetuximab

<p>Abstract</p> <p>Background</p> <p>Responsiveness to Cetuximab alone can be mediated by an increase of Epidermal Growth factor Receptor (EGFR) Gene Copy Number (GCN). Aim of this study was to assess the role of EGFR-GCN in advanced colorectal cancer (CRC) patients receiving chemotherapy plus Cetuximab.</p> <p>Methods</p> <p>One hundred and one advanced CRC patients (43 untreated- and 58 pre-treated) were retrospectively studied by fluorescence in situ hybridization (FISH) to assess EGFR-GCN and by immunohistochemistry (IHC) to determine EGFR expression. Sixty-one out of 101 patients were evaluated also for k-ras status by direct sequencing. Clinical end-points were response rate (RR), progression-free survival (PFS) and overall survival (OS).</p> <p>Results</p> <p>Increased EGFR-GCN was found in 60/101 (59%) tumor samples. There was no correlation between intensity of EGFR-IHC and EGFR-GCN (p = 0.43). Patients receiving chemotherapy plus Cetuximab as first line treatment had a RR of 70% (30/43) while it was 18% (10/56) in the group with previous lines of therapy (p < 0.0001). RR was observed in 29/60 (48%) of patients with increased EGFR-GCN and in 6/28 (21%) in those without (p = 0.02). At multivariate analyses, number of chemotherapy lines and increased EGFR-GCN were predictive of response; EGFR-IHC score, increased EGFR-GCN and number of chemotherapy lines were significantly associated with a significant better PFS. Response to therapy was the only prognostic predictive factor for OS. In the 60 patients analyzed for k-ras mutations, number of chemotherapy lines, increased EGFR-GCN and k-ras wild type status predicted a better PFS.</p> <p>Conclusion</p> <p>In metastatic CRC patients treated with chemotherapy plus Cetuximab number of chemotherapy lines and increased EGFR-GCN were significantly associated with a better clinical outcome, independent of k-ras status.</p

Differentially methylated microRNAs in prediagnostic samples of subjects who developed breast cancer in the european prospective investigation into nutrition and cancer (EPIC-Italy) cohort

The crosstalk between microRNAs (miRNAs) and other epigenetic factors may lead to novel hypotheses about carcinogenesis identifying new targets for research. Because a single miRNA can regulate multiple downstream target genes, its altered expression may potentially be a sensitive biomarker to detect early malignant transformation and improve diagnosis and prognosis. In the current study, we tested the hypothesis that altered methylation of miRNA encoding genes, associated with deregulated mature miRNA expression, may be related to dietary and lifestyle factors and may contribute to cancer development. In a case-control study nested in a prospective cohort (EPIC-Italy), we analysed DNA methylation levels of miRNA encoding genes (2191 CpG probes related to 517 genes) that are present in the Infinium Human Methylation450 BeadChip array in prediagnostic peripheral white blood cells of subjects who developed colorectal cancer (CRC, n = 159) or breast cancer (BC, n = 166) and matched subjects who remained clinically healthy. In the whole cohort, several differentially methylated miRNA genes were observed in association with age, sex, smoking habits and physical activity. Interestingly, in the case-control study, eight differentially methylated miRNAs were identified in subjects who went on to develop BC (miR-328, miR-675, miR-1307, miR-1286, miR-1275, miR-1910, miR-24-1 and miR-548a-1; all Bonferroni-adjusted P < 0.05). No significant associations were found with CRC. Assuming that altered methylation of miRNAs detectable in blood may be present before diagnosis, it may represent a biomarker for early detection or risk of cancer and may help to understand the cascade of events preceding tumour onset

Life-course socioeconomic status and DNA methylation of genes regulating inflammation

Background: In humans, low socioeconomic status (SES) across the life course is associated with greater diurnal cortisol production, increased inflammatory activity and higher circulating antibodies for several pathogens, all suggesting a dampened immune response. Recent evidence suggests that DNA methylation of pro-inflammatory genes may be implicated in the biological embedding of the social environment. Methods: The present study examines the association between life-course SES and DNA methylation of candidate genes, selected on the basis of their involvement in SES-related inflammation, in the context of a genome-wide methylation study. Participants were 857 healthy individuals sampled from the EPIC Italy prospective cohort study. Results: Indicators of SES were associated with DNA methylation of genes involved in inflammation. NFATC1, in particular, was consistently found to be less methylated in individuals with low vs high SES, in a dose-dependent manner. IL1A, GPR132 and genes belonging to the MAPK family were also less methylated among individuals with low SES. In addition, associations were found between SES and CXCL2 and PTGS2, but these genes were consistently more methylated among low SES individuals. Conclusions: Our findings support the hypothesis that the social environment leaves an epigenetic signature in cells. Although the functional significance of SES-related DNA methylation is still unclear, we hypothesize that it may link SES to chronic disease ris

Biological marks of early-life socioeconomic experience is detected in the adult inflammatory transcriptome.

Consistent evidence is accumulating to link lower socioeconomic position (SEP) and poorer health, and the inflammatory system stands out as a potential pathway through which socioeconomic environment is biologically embedded. Using bloodderived genome-wide transcriptional profiles from 268 Italian participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we evaluated the association between early life, young and later adulthood SEP and the expression of 845 genes involved in human inflammatory responses. These were examined individually and jointly using several inflammatory scores. Our results consistently show that participants whose father had a manual (as compared to nonmanual) occupation exhibit, later in life, a higher inflammatory score, hence indicating an overall increased level of expression for the selected inflammatory-related genes. Adopting a life course approach, these associations remained statistically significant upon adjustment for later-in-life socioeconomic experiences. Sensitivity analyses indicated that our findings were not affected by the way the inflammatory score was calculated, and were replicated in an independent study. Our study provides additional evidence that childhood SEP is associated with a sustainable upregulation of the inflammatory transcriptome, independently of subsequent socioeconomic experiences. Our results support the hypothesis that early social inequalities impacts adult physiology