Neural correlates of working memory function in pediatric cancer survivors treated with chemotherapy: an fMRI study.

The goal of this study is to investigate the neural correlates of working memory function associated with chemotherapy in pediatric cancer survivors using event-related functional MRI (fMRI) analysis. Fifteen pediatric cancer survivors treated with chemotherapy and 15 healthy controls were studied. Blood oxygenation level dependent (BOLD) fMRI was acquired. A visual n-back task was used to test working memory function during the fMRI scan. Responses were recorded via an MRI compatible button box for analysis. fMRI scans were analyzed using statistical parametric mapping software. All statistics were corrected for multiple comparisons by false discovery rate, with p < 0.05 as significance. Patients however gave more incorrect responses (p < 0.05), more no responses (p < 0.05), and longer response times (p < 0.05) compared with healthy controls. Correct responses generated significantly lower BOLD responses in the posterior cingulate for pediatric cancer survivors compared with controls (p < 0.05). Incorrect responses generated significantly greater BOLD responses in the angular gyrus in survivors (p < 0.05), and no response trials generated greater BOLD responses within the superior parietal lobule (p < 0.05) compared with controls. Working memory impairment appears to be due to an inability to manipulate information and to retrieve information from memory. The ability to delineate the affected neural circuits associated with chemotherapy-induced cognitive impairment could inform treatment strategies, identify patients at high risk of developing cognitive deficits, and pre-emptively tailor behavioral enrichment to overcome specific cognitive deficits.

Language mapping using electrocorticography versus stereoelectroencephalography: A case series.

Direct electrical stimulation (DES) is sometimes used in epilepsy surgery to identify areas that may result in language deficits if resected. Extraoperative language mapping is usually performed using electrocorticography (ECOG) - grids and strip electrodes; however, given the better safety profile of stereoelectroencephalogaphy (SEEG), it would be desirable to determine if mapping using SEEG is also effective. We report a case series of fifteen patients that underwent language mapping with either ECOG (5), SEEG (9), or both (1). Six patients in the SEEG group underwent resection or ablation with only mapping via SEEG. No patients in the SEEG group that underwent resective or ablative surgery experienced persistent language deficits. These results suggest that language mapping with SEEG may be considered as a clinically useful alternative to language mapping with ECOG.

The Reciprocal Relationship between Sleep and Epilepsy.

The relationship between sleep and epilepsy is bidirectional. Certain epilepsy syndromes predominantly or exclusively manifest during sleep, with seizures frequently originating from non-rapid eye movement (NREM) sleep. Interictal epileptiform discharges observed on electroencephalograms are most likely to be activated during the deep NREM sleep stage known as N3. Conversely, epileptiform discharges, anti-seizure medications (ASMs), as well as other anti-seizure therapies can exert detrimental effects on sleep architecture. Moreover, the co-occurrence of sleep disorders has the potential to exacerbate seizure control. Understating the relationship between sleep and epilepsy is crucial for healthcare providers. Addressing and managing sleep-related problems in individuals with epilepsy can potentially contribute to improved seizure control and overall well-being. At the same time, improving seizure control can improve sleep quality and quantity, thus further improving the health of individuals with epilepsy.

Neurocognitive, Sociocultural, and Psychological Factors Impacting Medication Beliefs Among HIV-Seropositive Latinx Adults.

Among Latinx people living with HIV (PLWH), neurocognitive (NC) function, culture, and mental health impact medication adherence. Similarly, health beliefs and attitudes play a role in health care barriers and health behaviors. Research has not examined the effect that compromised neurocognition, sociocultural factors, and mental health have on health beliefs and attitudes. This is especially relevant for Latinx PLWH who are disproportionately impacted by HIV, given that sociocultural factors may uniquely impact HIV-related NC and psychological sequelae. This study investigated the associations between neurocognition, sociocultural factors, mental health, health beliefs, and health attitudes among Latinx HIV-seropositive adults. Within a sample of 100 Latinx PLWH, better verbal learning and executive functioning abilities were associated with more positive attitudes about the benefits of medications and memory for medications. In terms of sociocultural factors, higher English language competence was related to better self-reported memory for medications, and overall, higher US acculturation was associated with more positive attitudes toward health professionals. Depressive symptomatology was negatively associated with attitudes toward medications and health professionals, as well as with self-reported memory for medications. These findings highlight the important interplay between NC, sociocultural, psychological factors, and health beliefs among Latinx PLWH. Adherence intervention strategies and suggestions for dispensing medical information are presented for clinicians and health care practitioners.

Underrepresentation of diverse populations and clinical characterization in opioid agonist treatment research: A systematic review of the neurocognitive effects of buprenorphine and methadone treatment.

INTRODUCTION: The relative neurocognitive effects of the two most common opioid agonist treatments (OAT; buprenorphine and methadone) for opioid use disorder (OUD) are poorly understood. The aim of this systematic review is to examine the neurocognitive effects of OAT (buprenorphine and methadone) and the clinical and sociodemographic characteristics of study samples. METHODS: The research team queried PubMed, PsycINFO and Cochrane Reviews for articles (01/1980-01/2020) with terms related to neurocognitive testing in adults (age ≥ 18) prescribed OAT. The team extracted neurocognitive data and grouped them by domain (e.g., executive functioning, learning/memory), and assessed study quality. RESULTS: The search retrieved 2341 abstracts, the team reviewed 278 full articles, and 32 met inclusion criteria. Of these, 31 were observational designs and one was an experimental design. Healthy controls performed better across neurocognitive domains than OAT-treated persons (buprenorphine or methadone). Compared to those with active OUD, OAT-treated persons had better neurocognition in various domains. However, in seven studies comparing buprenorphine- and methadone-treated persons, buprenorphine was associated with better neurocognition than was methadone, with moderate to large effect sizes in executive functioning, attention/working memory, and learning/memory. Additionally, OAT research underreports clinical characteristics and underrepresents Black and Latinx adults, as well as women. CONCLUSIONS: Findings suggest that compared to active opioid use, both buprenorphine and methadone treatment are associated with better neurocognitive functioning, but buprenorphine is associated with better executive functioning, attention/working memory, and learning/memory. These findings should be interpreted with caution given widespread methodological heterogeneity, and limited representation of ethnoracially diverse adults and women. Rigorous longitudinal comparisons with more diverse, better characterized samples will help to inform treatment and policy recommendations for persons with OUD.

Neurocognitive intra-individual variability within HIV+ adults with and without current substance use.

OBJECTIVE: HIV infection and current substance use (SU) are linked to cognitive and functional deficits, yet findings on their combined effects are mixed. Neurocognitive intraindividual variability, measured as dispersion of scores across a neuropsychological battery, is associated with worse cognitive outcomes and functional deficits among HIV+ adults but has not been studied in the context of HIV+ adults with current SU. We hypothesized that, among HIV+ adults, current SU would be associated with greater dispersion, that greater dispersion would be associated with worse medication adherence, and that this relationship would be worse among substance users. METHOD: Forty HIV+ adults completed neuropsychological, psychiatric, SU, and medical evaluations and an electronic medication adherence measure. General linear models evaluated the main effect of SU status on neurocognitive dispersion, and models stratified by SU status evaluated the effect of dispersion on medication adherence, adjusting for relevant covariates. RESULTS: The SU+ group showed greater dispersion than did the SU- group, t(38) = 2.74, p = .049, d = 0.81, but this association did not survive multiple comparisons. Stratified analyses indicated a negative relationship between dispersion and medication adherence among the SU+ group but not in the SU- group; however, this effect was reduced after accounting for depressive symptoms. CONCLUSIONS: We found preliminary evidence that current SU is associated with greater neurocognitive dispersion among HIV+ adults. SU and neurocognitive dispersion may have a synergistic effect on medication adherence; however, this effect is largely accounted for by depressive symptoms. Future research should examine progression of dispersion in HIV and consequent neurocognitive and functional deficits in those with current SU. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Anatomical brain MRI study of pediatric cancer survivors treated with chemotherapy: Correlation with behavioral measures.

The negative impacts of chemotherapy on pediatric patients treated with chemotherapy during the formative years of brain development are understudied compared to adult chemotherapy cancer patients. This work investigated the morphometry, cortical thickness, and subcortical volumes using MRI and their correlations with behavioral measures in pediatric oncology survivors treated with chemotherapy. Chemotherapy-treated childhood cancer survivors (N = 15, 15.12 ± 5.98 years old) diagnosed with a non-central nervous system malignancy and healthy age-matched controls (N = 15, 15.13 ± 4.21 years old) were studied. MRI was acquired at 3 Tesla. Behavioral Rating Inventory of Executive Functioning (BRIEF) Parental Rating, Purdue Pegboard manual dexterity and n-back working memory measures were administered. Structural MRI scans at 3 Tesla were acquired. Voxel-based morphometry, cortical thickness and subcortical volumes were analyzed and correlated with behavioral scores. Parametric statistics with a p < .05 and adjusted for multiple comparison corrections were performed. Patients exhibited significantly smaller gray-matter volumes in the left globus pallidum, bilateral thalami, left caudate and left nucleus accumbens (p < .05) and thinner cortex in the right parahippocampal gyrus (p < .05) compared to controls. BRIEF scores were similar to normative values. Purdue Pegboard revealed manual dexterity deficits compared to normative values, and the n-back task showed working-memory deficits in patients compared to controls. Left thalamus volume positively correlated with dexterity performance (p = .029). The number of correct answers positively correlated and the number of incorrect answers negatively correlated with total-brain and white-matter volume (p < .05), but not gray-matter volume (p > .05). Our results support the hypothesis that the neurotoxicity of systemic chemotherapy has widespread negative effects on brain development in pediatric oncology patients with relatively mild cognitive deficits. MRI identified neuroanatomical changes have the potential to provide neural correlates of the sequelae associated with pediatric chemotherapy.

The Combined Roles of Nonsomatic Depressive Symptomatology, Neurocognitive Function, and Current Substance Use in Medication Adherence in Adults Living With HIV Infection.

Depression, global neurocognitive (GNC) function, and substance use disorders (SUDs) are each associated with medication adherence in persons living with HIV (PLWH). Because somatic symptoms can inflate depression scores in PLWH, the role of nonsomatic depressive symptomatology (NSDS) should be considered in adherence. However, the combined roles of NSDS, GNC function, and current SUDs in predicting combined antiretroviral therapy (cART) adherence remain poorly understood. Forty PLWH (70% Latina/o; 30% non-Hispanic White) completed psychiatric/SUD, neurocognitive, and self-report cART adherence evaluations. Higher NSDS was associated with suboptimal adherence (p < .01), but optimal and suboptimal adherers did not differ in GNC function or current SUDs. Only NSDS was associated with suboptimal adherence, after accounting for GNC function and SUDs (p = .01). NSDS uniquely predicted self-reported adherence, beyond GNC function and current SUDs among ethnically diverse PLWH. Methodological issues between present and prior studies should also be considered.

Neuropsychological function is improved among opioid dependent adults who adhere to opiate agonist treatment with buprenorphine-naloxone: a preliminary study.

BACKGROUND: Among persons with opioid use disorder (OUD), neuropsychological dysfunction is associated with depression, and better neuropsychological function is associated with opioid abstinence. However, it is unknown whether depressive symptomatology or adherence to opiate agonist treatment are associated with neuropsychological change over time. METHODS: We recruited 20 buprenorphine/naloxone-treated adults with OUD (M Age = 45.2 years [SD = 8.1]; 25% female) to complete baseline and 6 month visits containing a neuropsychological test battery and self-reported measures of depressive symptomatology and medication adherence. RESULTS: Depressive symptomatology was not significantly related to neuropsychological change (p's > .05). Greater adherence to buprenorphine/naloxone was associated with improvements in learning, memory, and global functioning (r's = .52-60; p's < .05). CONCLUSIONS: Among OUD patients, greater adherence to buprenorphine/naloxone is associated with improved neuropsychological functioning over time. In contrast, depressive symptomatology is not associated with neuropsychological functioning over time. Supporting adherence to buprenorphine/naloxone may improve and/or preserve learning and memory functioning in individuals treated for OUD. TRIAL REGISTRATION: NCT01108679 . Registered 21 April 2010.

Cognitive estimations as a measure of executive dysfunction in childhood epilepsy.

Children and adolescents with epilepsy are known to demonstrate executive function deficits. Despite prior work that has shown that cognitive estimation tasks are sensitive to executive dysfunction in children, such tasks have not been studied in children with epilepsy. This is particularly important given the fact that executive tasks have heretofore shown poor ecological validity, and it has been speculated that estimation tasks may show stronger ecological validity than other executive tests. One hundred and thirteen clinically referred children and adolescents with epilepsy were included. The Biber Cognitive Estimations Test was sensitive to cognitive dysfunction, with about half showing impairments on this task in comparison to age-matched normative data; the most frequently impaired subscales were quantity estimation and time estimation. Moreover, the Biber Cognitive Estimation Test showed moderate correlations with not only overall intellectual functions and academic achievement but also other commonly administered tests of executive functions, including digit span, Trailmaking, and the Tower of London but not with the contingency naming test. Cognitive estimations were also modestly correlated with age of epilepsy onset but not other epilepsy-severity variables such as number of antiepilepsy drugs (AEDs) or seizure frequency. Unfortunately, the hypothesis that the Biber Cognitive Estimation Test would show strong ecological validity was not supported, as it showed weak relations with parent-reported executive function deficits. The significance and limitations of this investigation are discussed.

[Formula: see text]The Relative Utility of Three English Language Dominance Measures in Predicting the Neuropsychological Performance of HIV+ Bilingual Latino/a Adults.

OBJECTIVE: Given the disproportionate impact of neurologic disorders such as HIV on racial/ethnic minorities, neuropsychologists are increasingly evaluating individuals of diverse linguistic backgrounds. This study compares the utility of two brief and one comprehensive language measure to account for variation in English neuropsychological performance within a bilingual population. METHOD: Sixty-two HIV+ English/Spanish bilingual Latino adults completed three language measures in English and Spanish: Self-Reported Language Ability; Verbal Fluency (FAS/PMR); and the Woodcock Munoz Language Survey-Revised (WMLS-R). All participants also completed an English language neuropsychological (NP) battery. RESULTS: It was hypothesized that the comprehensive English/Spanish WMLS-R language dominance index (LDI) would be significantly correlated with NP performance, as well as the best predictor of NP performance over and above the two brief language measures. Contrary to our hypothesis, the WMLS-R LDI was not significantly correlated to NP performance, whereas the easily administered Verbal Fluency and Self-Report LDIs were each correlated with global NP performance and multiple NP domains. After accounting for Verbal Fluency and Self-Report LDI in a multivariate regression predicting NP performance, the WMLS-R LDI did not provide a unique contribution to the model. CONCLUSIONS: These findings suggest that the more comprehensive WMLS-R does not improve understanding of the effects of language on NP performance in an HIV+ bilingual Latino population.

Neurocognitive, psychiatric, and substance use characteristics in opioid dependent adults.

AIMS: To describe neurocognitive function among opioid-dependent adults seeking buprenorphine treatment and to explore the impact of lifetime psychiatric conditions on neurocognitive function. To explore the additive interaction of patient-based characteristics that may help to inform treatment. DESIGN: Cross-sectional assessment of neurocognitive function, substance use, and psychiatric characteristics of adults seeking buprenorphine treatment within substance use treatment centers in New York City. PARTICIPANTS: Thirty-eight opioid-dependent adults seeking buprenorphine treatment. MEASUREMENTS: A comprehensive battery, which included measures of executive functioning, learning, memory, verbal fluency, attention, processing speed, and motor functioning were administered. The Wide Range Achievement Test-Third Edition, the Composite International Diagnostic Interview, and an audio computer assisted structured interview were also completed. Correlations and independent sample t-tests were used to ascertain group differences. FINDINGS: Thirty-nine percent of participants were impaired in global neurocognitive function (n=15). Over one third were impaired in either: learning (n=28), memory (n=26), executive functioning (n=17), motor functioning (n=17), attention/working memory (n=14) or verbal fluency (n=12). Lifetime history of alcohol dependence was associated with impairment in global neurocognitive, executive functioning, and motor functioning. Lifetime history of cocaine dependence was associated with impairment in executive functioning and motor functioning (all p's<0.05). Major depressive disorder history was not associated with neurocognitive impairment. CONCLUSIONS: Among this sample of opioid-dependent adults, there were high rates of global and domain-specific neurocognitive impairment, with severe impairment in learning and memory. Lifetime alcohol and cocaine dependence were associated with greater neurocognitive impairment, particularly in executive functioning. Because executive functioning is critical for decision-making and learning/memory dysfunction may interfere with information encoding, these findings suggest that opioid-dependent adults may require enhanced support for medical decision-making.

Socioeconomic Status and Neuropsychological Functioning: Associations in an Ethnically Diverse HIV+ Cohort.

OBJECTIVE: There is limited research examining the relationship between socioeconomic status (SES) and neuropsychological functioning, particularly in racial/ethnic minority and HIV+ populations. However, there are complex associations between poverty, education, HIV disease, race/ethnicity, and health outcomes in the US. METHOD: We explored these relationships among an ethnically diverse sample of 134 HIV+ adults using a standardized SES measure (i.e., the Hollingshead scale), a comprehensive NP test battery, and a functional evaluation (i.e., Patient's Assessment of Own Functioning Inventory and Modified Instrumental Activities of Daily Living Scale). RESULTS: Bivariate analyses showed that adult SES was significantly, positively correlated with neuropsychological performance on specific tests within the domains of verbal fluency, attention/concentration, learning, memory, processing speed, and executive functioning, and childhood SES was significantly linked to measures of verbal fluency, processing speed, and executive functioning. In a series of linear regressions, controlling for SES significantly attenuated group differences in NP test scores between racial/ethnic minority individuals and non-Hispanic White individuals. Finally, SES scores significantly differed across HIV-Associated Neurocognitive Disorder (HAND) diagnoses. In a binary logistic regression, SES was the only independent predictor of HAND diagnosis. CONCLUSIONS: HIV+ individuals with lower SES may be more vulnerable to HIV-associated neuropsychological sequelae due to prominent health disparities, although the degree to which this is influenced by factors such as test bias remains unclear. Overall, our results suggest that SES is significantly linked to neuropsychological test performance in HIV+ individuals, and is an important factor to consider in clinical practice.

The role of decision-making ability in HIV/AIDS: impact on prospective memory.

BACKGROUND: Prospective memory (ProM), a form of episodic memory related to execution of future intentions, is important for everyday functioning. Among persons living with HIV (PLWH), executive dysfunction is implicated in ProM impairments. However, specific subcomponents of executive functioning involved in ProM deficits remain poorly understood. Unlike more "traditional" neurocognitive (NC) measures of executive functioning associated with dorsolateral prefrontal cortex (i.e., conceptual reasoning, abstraction), those associated with medial orbitofrontal/ventromedial prefrontal (mOF/vmP) cortex (i.e., decision making, inhibitory control, goal-oriented behavior) have yet to be examined in ProM. METHOD: This study characterized ProM ability in a sample of 89 HIV-seropositive adults and examined the unique role of decision-making ability in ProM. Participants completed a standard NC battery, the Iowa Gambling Task (IGT; a decision-making measure), and the Memory for Intentions Screening Test (MIST; a ProM measure). RESULTS: Correlational analyses revealed that both traditional executive functioning measures and the IGT were associated with ProM. Regression analyses revealed that the IGT significantly predicted ProM, even after accounting for NC measures. Among all NC measures, only executive functioning significantly contributed to ProM. DISCUSSION: Further examination of mOF/vmP-sensitive executive dysfunction within this population is needed as PLWH may require more tailored treatment recommendations due to specific decision-making difficulties that can impact medication management.

Multidimensional effects of acculturation on English-language neuropsychological test performance among HIV+ Caribbean Latinas/os.

Acculturation has been linked to neuropsychological performance in several ethnic groups. However, research among Latina/o samples has examined primarily Mexicans/Mexican Americans and has not examined Latina/o clinical populations of Caribbean descent. This study examined associations between a multidimensional acculturation measure and neuropsychological performance among 82 HIV+ Caribbean Latina/o adults. Multivariate results showed that US acculturation significantly predicted 11-14% of the variance in global neuropsychological functioning, verbal fluency, and processing speed, whereas Latina/o acculturation predicted 6-8% of the variance in motor and executive function (trend level associations). Both linguistic and nonlinguistic cultural factors had distinct effects on neuropsychological performance.

Visuospatial and verbal fluency relative deficits in 'complicated' late-preterm preschool children.

BACKGROUND: Late-preterm children constitute a majority of all preterm deliveries (75%). Their immature brain development at birth has been associated with an increased risk for morbidities. Data have been sparse regarding neuropsychological outcomes in the preschool years. AIM: To examine general cognition, attention/working memory, language, manual coordination/motor dexterity, visuomotor, visuospatial, and executive functions in preschoolers born late-preterm (LPT; 34-36 gestational weeks) who required NICU admission compared to term-born participants. DESIGN: Single-center retrospective cohort study of 95 three-year-old children; 60 born LPT in 2004-2005 and admitted to the NICU compared to 35 healthy term-born participants born > or =37 gestational weeks and > or =2500 g. RESULTS: LPT birth was associated with visuospatial (p=.005), visuomotor (p=.012), and executive function (noun [p=.018] and action-verb [p=.026] fluency) relative deficits, but not attention/working memory, receptive or expressive language, nonverbal reasoning, or manual coordination/dexterity deficit. CONCLUSIONS: Late-preterm birth is likely to be associated with negative neuropsychological sequelae, although subtle and selective compared to effects reported for children born at an earlier gestational age. Visuospatial function appears to be especially vulnerable to disruption even at preschool age, and verbal fluency may be useful as an early predictor of executive dysfunction in childhood. Routine preschool neuropsychological evaluation is recommended to identify delay or deficit in LPT children preparing for school entry, and may highlight underlying vulnerable neural networks in LPT children.