Eye movements disrupt EEG alpha-band coding of behaviorally relevant and irrelevant spatial locations held in working memory.

Oscillations in the alpha frequency band (∼8-12 Hz) of the human electroencephalogram play an important role in supporting selective attention to visual items and maintaining their spatial locations in working memory (WM). Recent findings suggest that spatial information maintained in alpha is modulated by interruptions to continuous visual input, such that attention shifts, eye closure, and backward masking of the encoded item cause reconstructed representations of remembered locations to become degraded. Here, we investigated how another common visual disruption-eye movements-modulates reconstructions of behaviorally relevant and irrelevant item locations held in WM. Participants completed a delayed estimation task, where they encoded and recalled either the location or color of an object after a brief retention period. During retention, participants either fixated at the center or executed a sequence of eye movements. Electroencephalography (EEG) was recorded at the scalp and eye position was monitored with an eye tracker. Inverted encoding modeling (IEM) was applied to reconstruct location-selective responses across multiple frequency bands during encoding and retention. Location-selective responses were successfully reconstructed from alpha activity during retention where participants fixated at the center, but these reconstructions were disrupted during eye movements. Recall performance decreased during eye-movements conditions but remained largely intact, and further analyses revealed that under specific task conditions, it was possible to reconstruct retained location information from lower frequency bands (1-4 Hz) during eye movements. These results suggest that eye movements disrupt maintained spatial information in alpha in a manner consistent with other acute interruptions to continuous visual input, but this information may be represented in other frequency bands.NEW & NOTEWORTHY Neural oscillations in the alpha frequency band support selective attention to visual items and maintenance of their spatial locations in human working memory. Here, we investigate how eye movements disrupt representations of item locations held in working memory. Although it was not possible to recover item locations from alpha during eye movements, retained location information could be recovered from select lower frequency bands. This suggests that during eye movements, stored spatial information may be represented in other frequencies.

Probiotic Bifidobacterium longum NCC3001 Reduces Depression Scores and Alters Brain Activity: A Pilot Study in Patients With Irritable Bowel Syndrome.

BACKGROUND & AIMS: Probiotics can reduce symptoms of irritable bowel syndrome (IBS), but little is known about their effects on psychiatric comorbidities. We performed a prospective study to evaluate the effects of Bifidobacterium longum NCC3001 (BL) on anxiety and depression in patients with IBS. METHODS: We performed a randomized, double-blind, placebo-controlled study of 44 adults with IBS and diarrhea or a mixed-stool pattern (based on Rome III criteria) and mild to moderate anxiety and/or depression (based on the Hospital Anxiety and Depression scale) at McMaster University in Canada, from March 2011 to May 2014. At the screening visit, clinical history and symptoms were assessed and blood samples were collected. Patients were then randomly assigned to groups and given daily BL (n = 22) or placebo (n = 22) for 6 weeks. At weeks 0, 6, and 10, we determined patients' levels of anxiety and depression, IBS symptoms, quality of life, and somatization using validated questionnaires. At weeks 0 and 6, stool, urine and blood samples were collected, and functional magnetic resonance imaging (fMRI) test was performed. We assessed brain activation patterns, fecal microbiota, urine metabolome profiles, serum markers of inflammation, neurotransmitters, and neurotrophin levels. RESULTS: At week 6, 14 of 22 patients in the BL group had reduction in depression scores of 2 points or more on the Hospital Anxiety and Depression scale, vs 7 of 22 patients in the placebo group (P = .04). BL had no significant effect on anxiety or IBS symptoms. Patients in the BL group had a mean increase in quality of life score compared with the placebo group. The fMRI analysis showed that BL reduced responses to negative emotional stimuli in multiple brain areas, including amygdala and fronto-limbic regions, compared with placebo. The groups had similar fecal microbiota profiles, serum markers of inflammation, and levels of neurotrophins and neurotransmitters, but the BL group had reduced urine levels of methylamines and aromatic amino acids metabolites. At week 10, depression scores were reduced in patients given BL vs placebo. CONCLUSION: In a placebo-controlled trial, we found that the probiotic BL reduces depression but not anxiety scores and increases quality of life in patients with IBS. These improvements were associated with changes in brain activation patterns that indicate that this probiotic reduces limbic reactivity. ClinicalTrials.gov no. NCT01276626.

A qualitative study on the experiences of young adults with eating disorders transferring from pediatric to adult care.

The study's objective was to identify systemic facilitators and barriers of transferring young adults (ages 17-21) with eating disorders from pediatric to adult health and mental health services. Qualitative interviews were conducted and three themes emerged: (a) difficulties navigating care during the transfer period; (b) challenges achieving and maintaining recovery due to systemic barriers after the transfer of care;and (c) recommendations for facilitating the transfer between systems of care. From the perspective of young adults with eating disorders our study shows that the transition to adult care services may be improved with increased coordination, communication, and collaborative partnerships between pediatric and adult providers.

Effects of electroconvulsive therapy on cognitive functioning in patients with depression: protocol for a systematic review and meta-analysis.

INTRODUCTION: Depression is the leading cause of disability worldwide, affecting approximately 350 million people. Evidence indicates that only 60-70% of persons with major depressive disorder who tolerate antidepressants respond to first-line drug treatment; the remainder become treatment resistant. Electroconvulsive therapy (ECT) is considered an effective therapy in persons with treatment-resistant depression. The use of ECT is controversial due to concerns about temporary cognitive impairment in the acute post-treatment period. We will conduct a meta-analysis to examine the effects of ECT on cognition in persons with depression. METHODS: This systematic review and meta-analysis has been registered with PROSPERO (registration number: CRD42014009100). We developed our methods following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. We are searching MEDLINE, PsychINFO, EMBASE, CINAHL and Cochrane from the date of database inception to the end of October 2014. We are also searching the reference lists of published reviews and evidence reports for additional citations. Comparative studies (randomised controlled trials, cohort and case-control) published in English will be included in the meta-analysis. Three clinical neuropsychologists will group the cognitive tests in each included article into a set of mutually exclusive cognitive subdomains. The risk of bias of randomised controlled trials will be assessed using the Jadad scale. We will supplement the Jadad scale with additional questions based on the Cochrane risk of bias tool. The risk of bias of cohort and case-control studies will be assessed using the Newcastle-Ottawa Scale. We will employ the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to assess the strength of evidence. STATISTICAL ANALYSIS: Separate meta-analyses will be conducted for each ECT treatment modality and cognitive subdomain using Comprehensive Meta-Analysis V.2.0.

Combined vaccination and immunostimulatory antibodies provides durable cure of murine melanoma and induces transcriptional changes associated with positive outcome in human melanoma patients.

We have developed a recombinant adenovirus vaccine encoding dopachrome tautomerase (rHuAd5-hDCT) that produces robust DCT-specific immunity, but only provides modest suppression of murine melanoma. In the current study, an agonist antibody against 4-1BB was shown to enhance rHuAd5-hDCT efficacy and evoke tumor regression, but most tumors ultimately relapsed. The vaccine triggered upregulation of the immune inhibitory PD-1 signaling pathway and PD-1 blockade dramatically enhanced the rHuAd5-hDCT + anti-4-1BB strategy, resulting in complete regression of growing tumors in > 70% of recipients. The impact of the combined anti-4-1BB/anti-PD-1 treatment did not manifest as a dramatic enhancement in either the magnitude or functionality of DCT-specific tumor infiltrating lymphocytes relative to either treatment alone. Rather, a synergistic enhancement in intratumoral cytokine expression was observed, suggesting that the benefit of the combined therapy was a local event within the tumor. Global transcriptional analysis revealed immunological changes within the tumor following the curative vaccination, which extended beyond the T cell compartment. We identified an immune signature of 85 genes associated with clearance of murine melanoma that correlated with improved survival outcome in two independent cohorts of human melanoma patients. Our data reinforce the concept that successful vaccination must overcome local hurdles in the tumor microenvironment that are not manifest within the periphery. Further, tumor rejection following vaccination involves more than simply T cells. Finally, the association of our immune signature with positive survival outcome in human melanoma patients suggests that similar vaccination strategies may be promising for melanoma treatment.