Devika R. Jutagir

Resting-State Functional Connectivity Indexes Reading Competence in Children and Adults

Task-based neuroimaging studies face the challenge of developing tasks capable of equivalently probing reading networks across different age groups. Resting-state fMRI, which requires no specific task, circumvents these difficulties. Here, in 25 children (8–14 years) and 25 adults (21–46 years), we examined the extent to which individual differences in reading competence can be related to resting-state functional connectivity (RSFC) of regions implicated in reading. In both age groups, reading standard scores correlated positively with RSFC between the left precentral gyrus and other motor regions, and between Brocas and Wernickes areas. This suggests that, regardless of age group, stronger coupling among motor regions, as well as between language/speech regions, subserves better reading, presumably reflecting automatized articulation. We also observed divergent RSFC–behavior relationships in children and adults, particularly those anchored in the left fusiform gyrus (FFG) (the visual word form area). In adults, but not children, better reading performance was associated with stronger positive correlations between FFG and phonology-related regions (Brocas area and the left inferior parietal lobule), and with stronger negative relationships between FFG and regions of the “task-negative” default network. These results suggest that both positive RSFC (functional coupling) between reading regions and negative RSFC (functional segregation) between a reading region and default network regions are important for automatized reading, characteristic of adult readers. Together, our task-independent RSFC findings highlight the importance of appreciating developmental changes in the neural correlates of reading competence, and suggest that RSFC may serve to facilitate the identification of reading disorders in different age groups.

Cortical Signatures of Dyslexia and Remediation: An Intrinsic Functional Connectivity Approach

This observational, cross-sectional study investigates cortical signatures of developmental dyslexia, particularly from the perspective of behavioral remediation. We employed resting-state fMRI, and compared intrinsic functional connectivity (iFC) patterns of known reading regions (seeds) among three dyslexia groups characterized by (a) no remediation (current reading and spelling deficits), (b) partial remediation (only reading deficit remediated), and (c) full remediation (both reading and spelling deficits remediated), and a group of age- and IQ-matched typically developing children (TDC) (total N = 44, age range = 7–15 years). We observed significant group differences in iFC of two seeds located in the left posterior reading network – left intraparietal sulcus (L.IPS) and left fusiform gyrus (L.FFG). Specifically, iFC between L.IPS and left middle frontal gyrus was significantly weaker in all dyslexia groups, irrespective of remediation status/literacy competence, suggesting that persistent dysfunction in the fronto-parietal attention network characterizes dyslexia. Additionally, relative to both TDC and the no remediation group, the remediation groups exhibited stronger iFC between L.FFG and right middle occipital gyrus (R.MOG). The full remediation group also exhibited stronger negative iFC between the same L.FFG seed and right medial prefrontal cortex (R.MPFC), a core region of the default network These results suggest that behavioral remediation may be associated with compensatory changes anchored in L.FFG, which reflect atypically stronger coupling between posterior visual regions (L.FFG-R.MOG) and greater functional segregation between task-positive and task-negative regions (L.FFG-R.MPFC). These findings were bolstered by significant relationships between the strength of the identified functional connections and literacy scores. We conclude that examining iFC can reveal cortical signatures of dyslexia with particular promise for monitoring neural changes associated with behavioral remediation.

Long-term psychological benefits of cognitive-behavioral stress management for women with breast cancer: 11-year follow-up of a randomized controlled trial.

Breast cancer survivors experience long‐term physical and psychological sequelae after their primary treatment that negatively influence their quality of life (QOL) and increase depressive symptoms. Group‐based cognitive‐behavioral stress management (CBSM) delivered after surgery for early‐stage breast cancer was previously associated with better QOL over a 12‐month follow‐up and with fewer depressive symptoms up to 5 years after study enrollment. This 8‐ to 15‐year follow‐up (median, 11 years) of a previously conducted trial (NCT01422551) evaluated whether women in this cohort receiving CBSM had fewer depressive symptoms and better QOL than controls at an 8‐ to 15‐year follow‐up.

Intrinsic brain indices of verbal working memory capacity in children and adolescents

Highlights • Digit span forward and backward performance has unique intrinsic neural correlates.• Dorsal anterior cingulate gyrus plays distinctive roles in forward and backward span.• Angular gyrus and subcallosum associated with forward digit span performance depending on age.• Visual cortex and ventrolateral PFC linked to backward digit span performance depending on age.• Age-related brain–behavior relationship changes are more robust for forward span.

Brief cognitive-behavioral and relaxation training interventions for breast cancer: A randomized controlled trial

OBJECTIVE Women with breast cancer (BCa) report elevated distress postsurgery. Group-based cognitive-behavioral stress management (CBSM) following surgery improves psychological adaptation, though its key mechanisms remain speculative. This randomized controlled dismantling trial compared 2 interventions featuring elements thought to drive CBSM effects: a 5-week cognitive-behavioral training (CBT) and 5-week relaxation training (RT) versus a 5-week health education (HE) control group. METHOD Women with stage 0-III BCa (N = 183) were randomized to CBT, RT, or HE condition 2-10 weeks postsurgery. Psychosocial measures were collected at baseline (T1) and postintervention (T2). Repeated-measures analyses of variance (ANOVAs) tested whether CBT and RT treatments improved primary measures of psychological adaptation and secondary measures of stress management resource perceptions from pre- to postintervention relative to HE. RESULTS Both CBT and RT groups reported reduced depressive affect. The CBT group reported improved emotional well-being/quality of life and less cancer-specific thought intrusions. The RT group reported improvements on illness-related social disruption. Regarding stress management resources, the CBT group reported increased reliability of social support networks, while the RT group reported increased confidence in relaxation skills. Psychological adaptation and stress management resource constructs were unchanged in the HE control group. CONCLUSIONS Nonmetastatic breast cancer patients participating in 2 forms of brief, 5-week group-based stress management intervention after surgery showed improvements in psychological adaptation and stress management resources compared with an attention-matched control group. Findings provide preliminary support suggesting that using brief group-based stress management interventions may promote adaptation among nonmetastatic breast cancer patients.

Postsurgical Depressive Symptoms and Proinflammatory Cytokine Elevations in Women Undergoing Primary Treatment for Breast Cancer

Objective Depression and inflammation may independently promote breast cancer (BCa) disease progression and poorer clinical outcomes. Depression has been associated with increased levels of inflammatory markers in medically healthy individuals and patients with cancer. However, inconsistencies in study time frames complicate interpretation of results within specific cancer types. This study examined relationships between depressive symptoms and inflammation in women with early-stage BCa before beginning adjuvant treatment. Methods Women with Stage 0-III BCa were recruited approximately 4 to 8 weeks after surgery. Depressive symptoms were assessed using the Hamilton Rating Scale for Depression, and blood samples were collected to quantify circulating levels of interleukin (IL)-1&bgr;, IL-6, and tumor necrosis factor &agr; (TNF-&agr;) by enzyme-linked immunosorbent assay. Analyses of covariance were used to test for group differences (elevated versus low depressive symptoms) in levels of cytokines. Multiple regression analyses were used to examine relationships between continuous severity of depressive symptoms and levels of cytokines adjusting for relevant biobehavioral covariates. Results Thirty-six (40%) of 89 patients showed elevated levels of depressive symptoms and, in adjusted models, had marginally higher levels of IL-1&bgr; (mean [M] = 14.49 [95% confidence interval {CI} = 6.11–32.65] versus M = 4.68 [95% CI = 1.96–9.86] and IL-6 [M = 88.74 {95% CI = 33.28–233.96} versus M = 61.52 {95% CI = 27.44–136.40}]) significantly higher levels of TNF-&agr; (M = 17.07 [95% CI = 8.27–34.32] versus M = 6.94 [95% CI = 3.58–12.80]) than did women with low depressive symptoms. Across the spectrum of depressive symptoms, greater magnitude of depressive symptoms was related to greater levels of IL-1&bgr; (&bgr; = 0.06, p = .006, R2 = 0.25) and TNF-&agr; (&bgr; = 0.06, p = .003, R2 = 0.27). Conclusions Postsurgery and preadjuvant treatment for early-stage BCa, depressive symptoms covary with elevated levels of multiple proinflammatory cytokines. Findings have implications for psychosocial and biological interventions concurrently focusing on depression and inflammation. Trial Registration: NCT01422551.

Poor sleep quality is associated with greater circulating pro-inflammatory cytokines and severity and frequency of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) symptoms in women

OBJECTIVE Poor sleep quality has been linked to inflammatory processes and worse disease outcomes in the context of many chronic illnesses, but less is known in conditions such as chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). This study examines the relationships between sleep quality, pro-inflammatory cytokines, and CFS/ME symptoms. METHODS Sixty women diagnosed with CFS/ME were assessed using the Pittsburgh Sleep Quality Index (PSQI), Fatigue Symptom Inventory (FSI) and Center for Disease Control and Prevention (CDC)-based CFS/ME symptom questionnaires. Circulating plasma pro-inflammatory cytokine levels were measured by ELISA. Multiple regression analyses examined associations between sleep, cytokines and symptoms, controlling for age, education, and body mass index. RESULTS Poor sleep quality (PSQI global score) was associated with greater pro-inflammatory cytokine levels: interleukin-1β (IL-1β) (β=0.258, p=0.043), IL-6 (β=0.281, p=0.033), and tumor necrosis factor-alpha (TNF-α) (β=0.263, p=0.044). Worse sleep quality related to greater fatigue severity (β=0.395, p=0.003) and fatigue-related interference with daily activities (β=0.464, p<0.001), and more severe and frequent CDC-defined core CFS/ME symptoms (β=0.499, p<0.001, and β=0.556, p<0.001, respectively). CONCLUSIONS Results underscore the importance of managing sleep-related difficulties in this patient population. Further research is needed to identify the etiology of sleep disruptions in CFS/ME and mechanistic factors linking sleep quality to symptom severity and inflammatory processes.

Stress management, leukocyte transcriptional changes and breast cancer recurrence in a randomized trial: An exploratory analysis

PURPOSE Cognitive behavioral stress management (CBSM) is an empirically-validated group-based psychosocial intervention. CBSM is related to decreased self-reported indicators of psychological adversity during breast cancer treatment and greater disease-free survival (DFS) vs. a control condition. This study examined relationships between CBSM, DFS, and a potential biobehavioral pathway linking these variables in breast cancer patients through a gene expression composite representing the leukocyte conserved transcriptional response to adversity (CTRA). DESIGN Women with stage 0-IIIb breast cancer completed questionnaires and provided blood samples post-surgery. Participants were randomized to 10-week group-based CBSM or a psychoeducation control group and followed at 6 months, 12 months, and median 11 years. In total, 51 participants provided blood data for longitudinal analyses (CBSM n=28; Control n=23). Mixed model analyses examined CBSM effects on 6-12 month changes in CTRA expression (53 indicator genes representing pro-inflammatory, anti-viral and antibody production signaling). Cox regression models assessed the relationship between 6 and 12 month changes in CTRA expression and 11-year DFS. RESULTS Patients randomized to CBSM showed attenuated 6-12 month change in CTRA gene expression, whereas patients randomized to control showed increased CTRA expression (p=0.014). Average DFS was 5.92 years (SD=3.90). Greater 6-12 month CTRA increases predicted shorter 11-year DFS controlling for covariates (p=0.007). CONCLUSIONS CBSM attenuated CTRA gene expression during the initial year of breast cancer treatment. In turn, greater increases in CTRA gene expression predicted shorter long-term DFS. These findings identify a biobehavioral oncology pathway to examine in future work.

Ethnic differences in types of social support from multiple sources after breast cancer surgery

ABSTRACT Objectives. Diagnosis of and treatment for breast cancer (BCa) may require psychological adaptation and often involve heightened distress. Several types of social support positively relate to psychological adaptation to BCa, and negative support is associated with poorer adaptation. Although Hispanic women report greater distress than non-Hispanic White (NHW) women after diagnosis of BCa, no studies have examined ethnic differences in types of social support received from varying sources after surgery for BCa. Design. Hispanic (N = 61) and NHW (N = 150) women diagnosed with early-stage BCa self-reported emotional, informational, instrumental, and negative support from five sources. Ethnic differences in levels of social support were compared using multiple regression analysis. Results. When controlling for age, income, days since surgery, and stage of disease in multivariable models there were no ethnic differences in levels of emotional support from any source. Hispanic women reported greater informational support from adult women family members and children and male adult family members than did NHW women. Instrumental support from adult women family members was also greater among Hispanic than NHW women. Hispanic women reported higher negative support from husbands/partners and from children and male adult family members. When the number of years in the USA was controlled, Hispanic women showed greater informational support from adult women family members, children and male adult family members, and friends. Instrumental support from adult women family members remained greater in Hispanic women, but negative support no longer differed. Conclusion. Family is a greater source of informational and instrumental support for Hispanic than NHW women. Hispanic women reported higher negative support from male sources than did NHW women. Level of support from different sources may also depend on time spent in the USA. Longitudinal studies are needed to determine whether patterns and sources of social support shift over the course of BCa treatment.

Post-surgical depressive symptoms and long-term survival in non-metastatic breast cancer patients at 11-year follow-up

BACKGROUND Mild to moderate depressive symptoms are common during treatment for non-metastatic breast cancer. The goal of this secondary analysis was to determine if depressive symptoms predict clinical outcomes at long-term follow-up. METHODS From 1998 to 2005, we interviewed 231 women with the Hamilton Rating Scale for Depression who were participating in a psychosocial study 2-10weeks post-surgery for non-metastatic breast cancer (Stage 0-IIIb). We conducted Kaplan Meier (K-M) curves and Cox proportional hazards (PH) models to examine associations between depressive symptoms, overall survival, and disease-free survival at 8-15-year follow-up. RESULTS A total of 95 women (41.1%) scored in the mild-moderately depressed range. Non-depressed women had longer overall survival (M=13.56years; SE=0.26) than those in the mild/moderate depressed group (M=11.45years; SE=0.40), Log-rank χ2(1)=4.41, p=0.036. Cox PH models, adjusting for covariates, showed comparable results: mild/moderate depressive symptoms hazard ratio=2.56, [95% CI, 1.11 to 5.91], p=0.027. Similar results were observed in a subsample with invasive disease (n=191). Depression category did not predict disease-free survival in the overall or invasive sample. CONCLUSIONS Screening and referrals for treatment of depressive symptoms, even at subclinical levels, is important early in treatment. A randomized trial is warranted to determine effects of depressive symptoms on clinical outcomes.