Hoarding Symptoms in Late Life Depression are Associated With Greater Executive Dysfunction and Disability and Poorer Response to Depression Treatment.

OBJECTIVES: Late life depression (LLD) and hoarding disorder (HD) are common in older adults and characterized by executive dysfunction and disability. We aimed to determine the frequency of co-occurring HD in LLD and examine hoarding severity as an additional contributor to executive dysfunction, disability, and response to psychotherapy for LLD. DESIGN: Cross-sectional. SETTING: Outpatient psychiatry program. PARTICIPANTS: Eighty-three community-dwelling adults ages 65-90 with LLD. INTERVENTION: Problem-solving therapy. MEASUREMENTS: Measures of executive function, disability, depression, and hoarding severity were completed at post-treatment. Pearson's chi-squared tests evaluated group differences in rates of cognitive impairment, disability, and depression treatment response between participants with HD (LLD+HD) and LLD only. Separate linear regressions assessed associations between hoarding severity and executive function, disability, and psychotherapy response. Covariates included age, education, gender, and depression severity. RESULTS: 30.1% (25/83) of LLD participants met HD criteria. Relative to LLD, LLD+HD participants demonstrated greater impairment rates on measures of executive function (Letter-Number-Sequencing, X2(1)=4.0, p = 0.045; Stroop-Interference, X2(1) = 4.8, p = 0.028). Greater hoarding severity was associated with poorer executive functioning performance (Letter-Number-Sequencing (t[70] = -2.1, ß = -0.05, p = 0.044), Digit-Span (t[71] = -2.4, ß = -0.07, p = 0.019), Letter-Fluency (t[ 71] = -2.8, ß = -0.24, p = 0.006)). Rates of disability were significantly higher for LLD+HD (88.0%) than LLD (62.3%), (X2[1] = 5.41, p = 0.020) and higher hoarding severity was related to greater disability (t[72] = 2.97, ß = 0.13, p = 0.004). Depression treatment response rates were significantly lower for LLD+HD (24.0%) compared to LLD (48.3%), X2(1) = 4.26, p = 0.039, and HD status predicted psychotherapy response, t(67) = -2.15, ß = -15.6, p = 0.035. CONCLUSIONS: We found 30.1% co-occurrence of HD in LLD, which was accompanied by greater executive dysfunction, disability, and poorer response to depression treatment. Results underscore the need for increased screening of hoarding behaviors in LLD and tailored interventions for this LLD+HD group.

Relationship of Hoarding and Depression Symptoms in Older Adults.

Hoarding disorder (HD) is a debilitating neuropsychiatric condition that affects 2%-6% of the population and increases in incidence with age. Major depressive disorder (MDD) co-occurs with HD in approximately 50% of cases and leads to increased functional impairment and disability. However, only one study to date has examined the rate and trajectory of hoarding symptoms in older individuals with a lifetime history of MDD, including those with current active depression (late-life depression; LLD). We therefore sought to characterize this potentially distinct phenotype. We determined the incidence of HD in two separate cohorts of participants with LLD (n = 73) or lifetime history of MDD (n = 580) and examined the reliability and stability of hoarding symptoms using the Saving Inventory-Revised (SI-R) and Hoarding Rating Scale-Self Report (HRS), as well as the co-variance of hoarding and depression scores over time. HD was present in 12% to 33% of participants with MDD, with higher rates found in those with active depressive symptoms. Hoarding severity was stable across timepoints in both samples (all correlations >0.75), and fewer than 30% of participants in each sample experienced significant changes in severity between any two timepoints. Change in depression symptoms over time did not co-vary with change in hoarding symptoms. These findings indicate that hoarding is a more common comorbidity in LLD than previously suggested, and should be considered in screening and management of LLD. Future studies should further characterize the interaction of these conditions and their impact on outcomes, particularly functional impairment in this vulnerable population.

Anxiety in late-life depression: Associations with brain volume, amyloid beta, white matter lesions, cognition, and functional ability.

OBJECTIVES: Late-life depression (LLD) is common and frequently co-occurs with neurodegenerative diseases of aging. Little is known about how heterogeneity within LLD relates to factors typically associated with neurodegeneration. Varying levels of anxiety are one source of heterogeneity in LLD. We examined associations between anxiety symptom severity and factors associated with neurodegeneration, including regional brain volumes, amyloid beta (Aß) deposition, white matter disease, cognitive dysfunction, and functional ability in LLD. PARTICIPANTS AND MEASUREMENTS: Older adults with major depression (N = 121, Ages 65-91) were evaluated for anxiety severity and the following: brain volume (orbitofrontal cortex [OFC], insula), cortical Aß standardized uptake value ratio (SUVR), white matter hyperintensity (WMH) volume, global cognition, and functional ability. Separate linear regression analyses adjusting for age, sex, and concurrent depression severity were conducted to examine associations between anxiety and each of these factors. A global regression analysis was then conducted to examine the relative associations of these variables with anxiety severity. RESULTS: Greater anxiety severity was associated with lower OFC volume (ß = -68.25, t = -2.18, p = .031) and greater cognitive dysfunction (ß = 0.23, t = 2.46, p = .016). Anxiety severity was not associated with insula volume, Aß SUVR, WMH, or functional ability. When examining the relative associations of cognitive functioning and OFC volume with anxiety in a global model, cognitive dysfunction (ß = 0.24, t = 2.62, p = .010), but not OFC volume, remained significantly associated with anxiety. CONCLUSIONS: Among multiple factors typically associated with neurodegeneration, cognitive dysfunction stands out as a key factor associated with anxiety severity in LLD which has implications for cognitive and psychiatric interventions.

Executive functioning moderates neural reward processing in youth.

Although executive functioning has traditionally been studied in "cool" settings removed from emotional contexts, it is highly relevant in "hot" emotionally salient settings such as reward processing. Furthermore, brain structures related to "cool" executive functioning and "hot" reward-related processes develop simultaneously, yet little is known about how executive functioning modulates neural processes related to reward processing during adolescence, a period of time when these systems are still developing. The present study examined how performance on "cool" behavioral executive functioning measures moderates neural reward processing. Youths (N = 43, Mage = 13.74 years, SD = 1.81 years) completed a child-friendly monetary incentive delay task during fMRI acquisition that captures neural responses to reward anticipation and to reward receipt and omission. Performance on inhibitory control and cognitive flexibility measures, captured outside the scanner, was used to predict brain activation and seed-based connectivity (ventral striatum and amygdala). Across analyses, we found that executive functioning moderated youths' neural responses during both reward anticipation and performance feedback, predominantly with respect to amygdala connectivity with prefrontal/frontal and temporal structures, supporting previous theoretical models of brain development during adolescence. Overall, youths with worse executive functioning had more pronounced differences in neural activation and connectivity between task conditions compared with youths with better executive functioning. This study contributes to elucidating the relationship between "cool" and "hot" processes and our findings demonstrate that simple executive functioning skills moderate more complex processes that involve incorporation of numerous skills in an emotionally salient context, such as reward processing.

Neural mechanisms of reward processing in adolescent irritability.

Irritability is impairing and prevalent across pediatric psychiatric disorders and typical development, yet its neural mechanisms are largely unknown. This study evaluated the relation between adolescent irritability and reward-related brain function as a candidate neural mechanism. Adolescents from intervention-seeking families in the community (N = 52; mean age = 13.80, SD = 1.94) completed a monetary incentive delay task to assess reward anticipation and feedback (reward receipt and omission) during fMRI acquisition. Whole-brain analyses, controlling for age, examined brain activation and striatal and amygdala connectivity in relation to irritability. Irritability was measured using the parent- and youth-reported Affective Reactivity Index. Irritability was associated with altered reward processing-related activation and connectivity in multiple networks during reward anticipation and feedback, including increased striatal activation and altered ventral striatum connectivity with prefrontal areas. Our findings suggest that irritability is associated with altered neural patterns during reward processing and that aberrant prefrontal cortex-mediated top-down control may be related to irritability. These findings inform our understanding of the etiology of youth irritability and the development of mechanism-based interventions.

Irritability-related neural responses to frustrative nonreward in adolescents with trauma histories: A preliminary investigation.

Irritability, conceptualized as a lowered frustration response threshold to blocked goal attainment (i.e., frustrative nonreward), is a common, detrimental symptom in adolescence. Yet, neural mechanisms of irritability are not well understood. This preliminary study aims to identify irritability-related neural patterns using a novel frustrative nonreward paradigm. Our study used a diverse sample of N = 31 non-White adolescent participants (mean age 14.53 years, SD = 1.74; 83.87% Hispanic/Latinx) to improve generalizability. During fMRI acquisition, participants performed a child-friendly monetary incentive delay task, modified to provide incorrect, negative feedback on performance. Irritability was associated with alterations in amygdala connectivity with basal ganglia, prefrontal, temporal, and parietal regions, and in activation of prefrontal and posterior cortical structures. Across clusters, youths with greater irritability showed activation/connectivity differences between reward blocked versus received conditions in the opposite direction compared to youths with lowered irritability. Alterations in amygdala-temporoparietal connectivity and lingual gyrus activation demonstrated an altered irritability-related recovery effect from the previous trial. These findings support the central role of frustrative nonreward as a key irritability pathway. Our work is one of the first to document neural correlates of difficult recovery from frustration characteristic of irritability and provides insight into novel treatment targets for irritability in diverse populations.

Attention shifting in the context of emotional faces: Disentangling neural mechanisms of irritability from anxiety.

BACKGROUND: Irritability predicts concurrent and prospective psychiatric disorders across the lifespan. Anxiety commonly co-occurs with irritability, and such comorbidity complicates care. Understanding the mechanisms of comorbid traits is necessary to inform treatment decisions. This study aimed to disentangle neural mechanisms of irritability from anxiety in the context of attentional shifting toward and away from emotional faces in youths from treatment-seeking families. METHODS: Youths (N = 45), mean age = 14.01 years (standard deviation = 1.89) completed a dot-probe task during functional magnetic resonance imaging acquisition. Whole-brain activation analyses evaluated the effect of irritability on neural reactivity in the context of varying attentional shifting toward and away from emotional faces, both depending on and above and beyond anxiety (i.e., with anxiety as [a] a moderator and [b] a covariate, respectively). RESULTS: Higher irritability levels related to distinct task-related patterns of cuneus activation, depending on comorbid anxiety levels. Increased irritability also related to distinct task-related patterns of parietal, temporal, occipital, and cerebellar activation, controlling for anxiety. Overall, youths with higher levels of irritability evinced more pronounced fluctuations in neural reactivity across task conditions. CONCLUSION: The present study contributes to a literature delineating the unique and shared neural mechanisms of overlapping symptom dimensions, which will be necessary to ultimately build a brain- and behavior-based nosology that forms the basis for more targeted and effective treatments.

Neural mechanisms of face emotion processing in youths and adults with bipolar disorder.

OBJECTIVES: Little is known about potential differences in the pathophysiology of bipolar disorder (BD) across development. The present study aimed to characterize age-related neural mechanisms of BD. METHODS: Youths and adults with and without BD (N = 108, age range = 9.8-55.9 years) completed an emotional face labeling task during fMRI acquisition. We leveraged three different fMRI analytic tools to identify age-related neural mechanisms of BD, investigating (a) change in neural responses over the course of the task, (b) neural activation averaged across the entire task, and (c) amygdala functional connectivity. RESULTS: We found converging Age Group × Diagnosis patterns across all three analytic methods. Compared to healthy youths vs adults, youths vs adults with BD show an altered pattern in response to repeated presentation of emotional faces in medial prefrontal, amygdala, and temporoparietal regions, as well as amygdala-temporoparietal connectivity. Specifically, medial prefrontal and lingual activation decreases over the course of repeated emotional face presentations in healthy youths vs adults but increases in youths with BD compared to adults with BD. Moreover, youths vs adults with BD show less medial prefrontal activation and amygdala-temporoparietal junction connectivity averaged over the task, but this difference is not found for healthy youths vs adults. CONCLUSION: Although longitudinal confirmation and replication will be necessary, these findings suggest that neural development may be aberrant in BD and that some neural mechanisms mediating BD may differ in adults vs children with the illness.

Longitudinal cognitive assessment in patients with primary CNS lymphoma treated with induction chemotherapy followed by reduced-dose whole-brain radiotherapy or autologous stem cell transplantation.

INTRODUCTION: The standard treatment for primary central nervous system lymphoma (PCNSL) involves induction methotrexate-based chemotherapy with or without consolidation whole brain radiotherapy (WBRT). As WBRT carries a substantial risk for cognitive impairment, alternative consolidation treatments have been used to reduce neurotoxicity, including reduced-dose WBRT (rdWBRT) or high-dose chemotherapy with autologous stem cell transplant (HDC-ASCT). In this study, we characterized cognitive functions in PCNSL patients achieving long-term remission following rdWBRT or HDC-ASCT. METHODS: PCNSL patients completed cognitive evaluations at diagnosis, post-induction chemotherapy, and yearly up to 5 years following rdWBRT or HDC-ASCT. Quality of life (QoL), white matter (WM) disease, and cortical atrophy (CA) on MRI were assessed at similar intervals. RESULTS: Performance was impaired on most cognitive tests at diagnosis. Linear mixed model analyses in each group showed statistically significant improvement from baseline up to year 3 in attention/executive functions, graphomotor speed, and memory; however, there was a decline in attention/executive functions and memory after year 3 in both groups. WM abnormalities increased over time in both groups, but more patients treated with rdWBRT developed CA and WM changes. There were no significant longitudinal group differences in cognitive performance or QoL. CONCLUSIONS: Results indicated improvement in cognitive function up to 3 years post-treatment, but a decline at later time points and an increase in brain structure abnormalities in both groups. The findings suggest that rdWBRT and HDC-ASCT may be associated with delayed neurotoxicity in progression-free patients and underscore the need for long-term follow-up to characterize cognitive dysfunction in PCNSL patients.

Patient-reported health-related quality of life outcomes in supportive-care interventions for adults with brain tumors: A systematic review.

OBJECTIVES: The objectives of this systematic review were to (a) identify supportive-care (psychosocial/behavioral, pharmacological, complementary, or alternative) interventions that have been evaluated via randomized controlled trials (RCTs) to improve patient-reported health-related quality of life (HRQoL) among adults with brain tumors, (b) evaluate the quality of the intervention studies, and (c) evaluate if developed interventions have been efficacious at improving HRQoL, as compared with control conditions in RCTs. METHODS: This systematic review was conducted using preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Four databases were searched for RCTs of supportive-care interventions for adults with brain tumors, primary or metastatic, that included a patient-reported HRQoL outcome. Quality of the included studies was assessed using the Effective Public Health Practice Project Quality Assessment Tool for Quantitative Studies. RESULTS: Ten RCTs involving 640 patients with either a primary or metastatic brain tumor investigating supportive-care interventions with a HRQoL outcome were identified. In terms of quality, three of the studies received a "strong" rating, three received a "moderate" rating, and four of the studies received a "weak" rating. Only two of the interventions (ie, a home-based psychosocial intervention and individualized acupuncture with standard rehabilitation) demonstrated improvements in HRQoL over control conditions. CONCLUSIONS: HRQoL is of the utmost importance when treating patients with brain tumors. Yet there is a notable paucity of research to inform clinical decisions and evidence-based practice. More high-quality studies of interventions aimed at improving HRQoL are needed.

Hedonic and Eudaimonic Motives: Associations with Academic Achievement and Negative Emotional States among Urban College Students.

College students from diverse ethnic and socioeconomic backgrounds are at risk for poorer academic outcomes and greater psychopathology and it is important to identify factors that are amenable to intervention and enhance college outcomes. Recent literature has entertained happiness as a potential predictor of various success outcomes and it has been suggested that parsing the concept of happiness into hedonia (seeking pleasure and relaxation) and eudaimonia (seeking meaning) may be particularly useful. This study examined the relations between hedonic and eudaimonic motives for action and student outcomes; that is, academic achievement and their negative emotional states, in an ethnically and socioeconomically diverse urban college population. Undergraduate students (N=119; mean age=21.24 [SD=3.16] years; 59.7 % female) completed self-reported measures of hedonic and eudaimonic motives for action, and depression, anxiety, and stress. Semester GPA was collected from school records. Hedonic motives for action ("Hedonia") were not associated with GPA or students' negative emotional states. Eudaimonic motives for action ("Eudaimonia"), however, were significantly positively associated with GPA, Individuals with high levels of both Hedonia and Eudaimonia (the Full Life) had higher GPAs compared to individuals with low Eudaimonia, but did not differ from students with high Eudaimonia and low Hedonia (Eudaimonic Life). Eudaimonia was also significantly negatively associated with Depression and Stress, and individuals high in Eudaimonia had the lowest levels of both of these outcomes compared to those with low Eudaimonia. Eudaimonic motives may be important for more desirable college outcomes, and interventions that promote development of this domain may hold promise.

Cognitive effects of donepezil therapy in patients with brain tumors: a pilot study.

Cognitive dysfunction is prevalent among brain tumor patients treated with radiotherapy (RT) and chemotherapy. However, there are no approved pharmacological interventions for cognitive dysfunction in cancer patients. The goal of this pilot study was to examine the efficacy of donepezil, an acetylcholinesterase inhibitor used to treat Alzheimer's disease, in improving cognitive functions in brain tumor patients previously treated with RT + chemotherapy or chemotherapy alone. Fifteen patients with a brain tumor received a single daily dose of donepezil for 24 weeks (5 mg for 4 weeks, then 10 mg for 20 weeks). Patients completed cognitive evaluations prior to initiating therapy (baseline), and about 12 weeks (mid-study) and 24 weeks (end-of-study) subsequent to initiation of donepezil therapy. The results of linear mixed models analysis, controlling for each patient's baseline cognitive test score, showed a significant post-baseline improvement in attention (WAIS-III digit span forward; p = 0.037), graphomotor speed (WAIS-III digit symbol; p = 0.035) and visual memory (BVMT-R-delay; p = 0.025). There was also an improvement in self-reported quality of life (FACT-Br, social well-being subscale; p = 0.01). The findings of this pilot study suggest that treatment with donepezil may improve some aspects of cognitive functions and quality of life in brain tumor patients. Similar findings were reported in two prior trials of donepezil in brain tumor survivors.

Amplification of positivity for depression and anxiety: Neural prediction of treatment response.

Psychosocial treatments targeting the positive valence system (PVS) in depression and anxiety demonstrate efficacy in enhancing positive affect (PA), but response to treatment varies. We examined whether individual differences in neural activation to positive and negative valence incentive cues underlies differences in benefitting from a PVS-targeted treatment. Individuals with clinically elevated depression and/or anxiety (N = 88, ages 18 to 55) participated in one of two randomized, waitlist-controlled trials of Amplification of Positivity (AMP; NCT02330627, NCT03196544), a cognitive and behavioral intervention targeting the PVS. Participants completed a monetary incentive delay (MID) task during fMRI acquisition at baseline measuring neural activation to the possibility of gaining or losing money. Change in PA from before to after treatment was assessed using the Positive and Negative Affect Schedule. No significant associations were observed between baseline neural activation during gain anticipation and AMP-related changes in PA in regions of interest (striatum and insula) or whole-brain analyses. However, higher baseline striatal and insula activation during loss anticipation was associated with greater increases in PA post-AMP. This study provides preliminary evidence suggesting neural reactivity to negative valence cues may inform who stands to benefit most from treatments targeting the PVS.

What I see, what you say: How cross-method variation sharpens characterization of irritability in early childhood.

OBJECTIVES: Identification of clinically significant irritability in preschool age is important to implement effective interventions. However, varying informant and measurement methods display distinct patterns. These patterns are associated with concurrent and future mental health concerns. Patterns across multi-informant methods in early-childhood irritability may have clinical utility, identifying risk for impaired psychosocial functioning. METHODS: Using data from the Multidimensional Assessment of Preschoolers Study (N = 425), latent profile analysis identified irritability patterns through the parent-reported Multidimensional Assessment Profile Scales-Temper Loss (MAPS-TL), parent-reported interviewer-rated Preschool Age Psychiatric Assessment (PAPA), and observer-rated Disruptive Behavior Diagnostic Observation Schedule (DB-DOS). These profiles were characterized on protective factors, global functioning, and mental health syndromes, concurrently and at early school age and preadolescent follow-up. RESULTS: Fit indices favored a five-class model: Low All, High Observation with Examiner (high DB-DOS Examiner Context), High All, High Parent Report (high MAPS-TL/PAPA), and Very High Parent Report (very high MAPS-TL/PAPA). Whereas Low All and High Observation with Examiner exhibited strong psychosocial functioning, remaining profiles showed impaired psychosocial functioning, with the Very High Parent Report group showing higher impairment at follow-ups, ds = 0.37-1.25. CONCLUSIONS: Multi-informant measurements of irritability may have utility for clinical prediction, and future studies should test utility for diagnostic precision.

Roads Diverged: Developmental Trajectories of Irritability From Toddlerhood Through Adolescence.

OBJECTIVE: Irritability is a dimensional trait that manifests from early life and is a robust transdiagnostic risk factor for psychopathology and impairment. A large, national dataset was leveraged to identify and broadly characterize trajectories from toddlerhood through adolescence, which is crucial for timely, targeted interventions. METHOD: Data on irritability and a broad array of potential factors affecting irritability development from 4,462 children assessed longitudinally at ages 3, 5, 9, and 15 were included. Latent class growth models identified groups of children based on their nonlinear irritability trajectories from toddlerhood to adolescence. LASSO regression then identified key characteristics differentiating trajectory groups. RESULTS: Five distinct irritability trajectories were identified, two of which were stable, maintaining medium or high irritability from age 3 to 15. Three trajectories showed undulating change over development, with an inflection point at the transition to adolescence (age 9): Most children had consistently low irritability. Two smaller groups started with high irritability at age 3 but diverged, sharply decreasing or increasing until a turning point at age 9. Developmental patterning of harsh/neglectful parenting and child internalizing symptoms most strongly differentiated trajectory groups. Sociodemographic characteristics, attachment style, neighborhood support, cognitive functioning, and genetic variation also differentiated trajectories. CONCLUSION: The results demonstrated the importance of the transition to adolescence as a critical inflection point for youths with fluctuating irritability trajectories. Identifying these patterns and multiple malleable factors associated with stably high or rising trajectories is an important step toward targeted interventions for the most vulnerable subgroups. DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper self-identifies as living with a disability. One or more of the authors of this paper received support from a program designed to increase minority representation in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group.

Irritability in early to middle childhood: Cross-sectional and longitudinal associations with resting state amygdala and ventral striatum connectivity.

BACKGROUND: Irritability is a common symptom that may affect children's brain development. This study aims to (1) characterize age-dependent and age-independent neural correlates of irritability in a sample of 4-8 year old children, and (2) examine early irritability as a predictor of change in brain connectivity over time. METHODS: Typically developing children, ages 4-8 years, with varying levels of irritability were included. Resting state fMRI and parent-rated irritability (via Child Behavior Checklist; CBCL) were collected at up to three time points, resulting in a cross-sectional sample at baseline (N = 176, M = 6.27, SD = 1.49), and two subsamples consisting of children who were either 4 or 6 years old at baseline that were followed longitudinally for two additional timepoints, one- and two-years post-baseline. That is, a "younger" cohort (age 4 at baseline, n = 34, M age = 4.44, SD = 0.25) and an "older" cohort (age 6 at baseline, n = 29, M age = 6.50, SD = 0.30). Across our exploratory analyses, we examined how irritability related to seed-based intrinsic connectivity via whole-brain connectivity ANCOVAs using the left and right amygdala, and left and right ventral striatum as seed regions. RESULTS: Cross-sectionally, higher levels of irritability were associated with greater amygdala connectivity with the posterior cingulate, controlling for child age. No age-dependent effects were observed in the cross-sectional analyses. Longitudinal analyses in the younger cohort revealed that early higher vs. lower levels of irritability, controlling for later irritability, were associated with decreases in amygdala and ventral striatum connectivity with multiple frontal and parietal regions over time. There were no significant findings in the older cohort. CONCLUSIONS: Findings suggest that irritability is related to altered neural connectivity during rest regardless of age in early to middle childhood and that early childhood irritability may be linked to altered changes in neural connectivity over time. Understanding how childhood irritability interacts with neural processes can inform pathophysiological models of pediatric irritability and the development of targeted mechanistic interventions.

Resting-State Connectivity Changes After Goal-Oriented Attentional Self-Regulation Training in Veterans With Mild Traumatic Brain Injury: Preliminary Findings from a Randomized Controlled Trial.

Mild traumatic brain injury (mTBI) can have lasting consequences on cognitive functioning and well-being. Goal-Oriented Attentional Self-Regulation (GOALS) training has been shown to improve attention and executive functioning, as well as emotional functioning, in veterans with chronic TBI. An ongoing clinical trial (NCT02920788) is further evaluating GOALS training, including underlying neural mechanisms of change. The present study aimed to examine training-induced neuroplasticity by resting-state functional connectivity (rsFC) changes in GOALS versus active control. Veterans with a history of mTBI ≥6 months post-injury (N = 33) were randomly assigned to GOALS (n = 19) or an intensity-matched active control group (Brain Health Education [BHE] training; n = 14). GOALS consists of attention regulation and problem solving applied to individually defined, relevant goals through a combination of group, individual, and home practice sessions. Participants underwent multi-band resting-state functional magnetic resonance imaging at baseline and post-intervention. Exploratory 2 × 2 mixed analyses of variance identified pre-to-post changes in seed-based connectivity for GOALS versus BHE in five significant clusters. GOALS versus BHE demonstrated a significant increase in right lateral pre-frontal cortex connectivity with the right frontal pole and right middle temporal gyrus, as well as increased posterior cingulate connectivity with the pre-central gyrus. Rostral pre-frontal cortex connectivity with the right precuneus and the right frontal pole decreased in GOALS versus BHE. These GOALS-related changes in rsFC point to potential neural mechanisms underlying the intervention. This training-induced neuroplasticity may play a role in improved cognitive and emotional functioning post-GOALS.

Executive functioning moderates neural mechanisms of irritability during reward processing in youth.

Pediatric irritability is the most robust indicator of transdiagnostic psychopathology risk. It is associated with altered neural reward processing, including neural networks related to cognitive control, and better cognitive control has been hypothesized to mitigate irritability. We evaluated the relationship of executive functioning (EF) with irritability-related neural correlates of reward processing in youths with varying levels of irritability. Participants (N = 51, mean age=13.80 years, SD=1.94) completed a monetary incentive delay task during multiband fMRI acquisition. Irritability and EF were measured via the Affective Reactivity Index and the NIH Toolbox cognition battery, respectively. Whole-brain analyses, controlling for age, examined the moderating role of EF on irritability-related brain activation and connectivity (seeds: striatum, amygdala) during reward anticipation and performance feedback. Irritability-related neural patterns during reward processing depended on EF, in occipital areas during reward anticipation and limbic, frontal, and temporal networks during performance feedback. Higher irritability combined with higher EF was associated with neural patterns opposite to those observed for higher irritability with lower co-occurring EF. Although preliminary, findings suggest that EF may buffer irritability-related reward processing deficits. Additionally, individual differences in EF and their relation to irritability may be related to varied etiologic mechanisms of irritability with important implications for personalized prevention and intervention.

Altered regional homogeneity in patients with ovarian cancer treated with chemotherapy: a resting state fMRI study.

Many patients treated with chemotherapy for non-central nervous system (CNS) cancers experience cognitive dysfunction. However, few studies have investigated treatment-related neurotoxicity in women with ovarian cancer. The goal of this study was to assess regional brain function in patients with ovarian cancer after first-line chemotherapy. Seventeen patients with ovarian cancer and seventeen healthy controls matched for gender, age and education participated in the study. The patients were evaluated 1-4 months after completion of first line taxane/platinum chemotherapy. All participants underwent resting state functional MRI (rsfMRI) and regional homogeneity (ReHo) indices were calculated. The results showed that patients had significantly decreased average ReHo values in the left middle frontal gyrus, medial prefrontal cortex, and right superior parietal lobule, compared to healthy controls. This is the first rsfMRI study showing ReHo alterations in frontal and parietal regions in patients with ovarian cancer treated with first-line chemotherapy. The findings are overall congruent with prior studies in non-CNS cancer populations and provide supporting evidence for the prevailing notion that frontal areas are particularly vulnerable to the adverse effects of chemotherapy.

Executive Functioning and the Pursuit of Happiness.

Executive functioning and happiness are each associated with successful learning and other desirable individual and societal outcomes; however, it is unclear whether a relation exists between them. Executive regulation of happiness pursuits in daily life, operationalized as hedonic (e.g., pursuing pleasure) and eudaimonic (e.g., pursuing personal growth) motives for action, may be a way the constructs relate to each other. In this initial investigation, we aimed to explore whether objectively measured executive functioning skills relate to happiness motives. A sample of 119 college students completed six objective neuropsychological measures of executive functioning and self-reported levels of hedonic and eudaimonic motives for action in daily life. Correlation and regression analyses examined the relations among temporal discounting and two latent executive functioning factors (inhibitory control and working memory) with hedonic and eudaimonic motives, as well as their interaction. Results suggested a possible association between higher levels of eudaimonic motives and preference for higher delayed rewards, as well as poorer working memory. Further analyses suggested that endorsing high levels of eudaimonic and hedonic motives simultaneously (i.e., the "full life") was associated with poorer inhibitory control and working memory performance, whereas endorsing low levels of both simultaneously (i.e., the "empty life") was associated with a preference for more immediate monetary rewards. Findings are discussed in the context of goal conflict and risk assessment among individuals who endorse the "full life". Overall, these findings suggest that complex relations may exist between executive functioning and trait-level happiness pursuits, and have implications for possible interventions aimed at enhancing happiness-related motives and cognitive processes to facilitate learning. Given the exploratory nature of the present study, further investigations are necessary.