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Item Associations of brain-derived neurotrophic factor rs6265 polymorphism and cognitive function in breast cancer survivors from a cross-sectional study(Wiley, 2024) Goto, Taichi; Saligan, Leorey N.; Li, Xiaobai; Xiang, Lichen; Kwiat, Catherine; Nguyen, Christopher; Crouch, Adele; Von Ah, Diane; School of NursingBackground: Breast cancer survivors (BCS) often complain of cancer-related cognitive impairment (CRCI) during and even months after completing primary cancer treatments, particularly chemotherapy. The etiology of CRCI is unknown, but associations of CRCI with germline genetic polymorphisms have been reported, including Brain-Derived Neurotrophic Factor (BDNF) rs6265 polymorphism. The current study investigated the associations of specific BDNF rs6265 with CRCI. Methods: Cancer-related cognitive impairment was assessed using subjective reports of cognitive symptoms (the version 1.0, 8-item short-forms of the Patient-Reported Outcomes Measurement Information System®) and computerized objective cognitive function scores (CANTAB®). BDNF rs6265 genotypes were determined from buccal swabs. The associations of specific BDNF rs6265 with CRCI were examined by either one-way analysis of variance or the Kruskal–Wallis test followed by post hoc tests and rank-based regression analysis. Results: We examined 356 female BCS. The mean (SD) age was 55.6 (9.8) years old, the median (IQR) years since cancer diagnosis were 4.0 (6.0), and 331 (92.7%) were self-described as White. BCS carrying the Met/Met genotype showed poorer results on ‘visual episodic memory and new learning’ and ‘spatial working memory and executive function.’ This relationship was observed regardless of prior chemotherapy. Conclusion: Our findings suggest that carrying the BDNF rs6265 Met/Met genotype increases the risk for CRCI in BCS. These results are foundational in nature and provide important information to identify mechanisms underpinning CRCI.Item Estradiol treatment in young postmenopausal women with self-reported cognitive complaints: Effects on cholinergic-mediated cognitive performance(Wiley, 2022) Conley, Alexander C.; Albert, Kimberly M.; McDonald, Brenna C.; Saykin, Andrew J.; Dumas, Julie A.; Newhouse, Paul A.; Radiology and Imaging Sciences, School of MedicineObjective: Older women are at increased risk of developing Alzheimer's disease compared to men. One proposed reason is that following menopause there is a decline in estrogens. Estrogens are important for cholinergic functioning and attenuate the impact of cholinergic antagonists on cognitive performance in postmenopausal women. Self-reported or subjective cognitive complaints in middle or older age may represent a harbinger of cognitive decline and those who endorse cognitive complaints appear more likely to develop future cognitive impairment. However, the response of individuals with cognitive complaints after menopause to estrogen and the relationship to cholinergic functioning has not been investigated. This study investigated the effect of estrogen treatment using 17β-estradiol on cognitive performance following anticholinergic blockade in postmenopausal women and the relationship of this interaction with the level of self-reported (subjective) postmenopausal cognitive complaints. Methods: Forty postmenopausal women (aged 50-60 years) completed a 3-month treatment regimen of either 1 mg oral estradiol or placebo. Participants then completed four challenge days in which they completed cognitive and behavioral tasks after one of four cholinergic antagonist drug conditions (oral mecamylamine (MECA), intravenous scopolamine, combined MECA and scopolamine, or PLC). Results: Compared to PLC, the estradiol treated group performed worse on attention tasks under cholinergic challenge including the choice reaction time task and the critical flicker fusion task. In addition, participants who endorsed greater cognitive complaints showed reduced performance on the N-back working memory task, regardless of whether they received estradiol treatment. Conclusions: The findings of this study indicate that estradiol treatment was unable to mitigate anticholinergic blockade in postmenopausal women with subjective cognitive complaints, and worsened performance on attention tasks. Moreover, the present study suggests that greater levels of cognitive complaints following menopause may be associated with an underlying decline in cholinergic function that may manifest as an inability to compensate during working memory tasks.Item Examining the Role of Dysfunctional Beliefs in Individuals with Schizotypy(2015) Luther, Lauren; Salyers, Michelle; Minor, Kyle; Rand, KevinIn accord with the cognitive model of poor functioning in schizophrenia, defeatist performance beliefs, or overgeneralized negative beliefs about one’s ability to perform tasks, have been linked to poor functional outcomes, cognitive impairment, and negative symptoms in schizophrenia and are a suggested therapeutic target in Cognitive Therapy for Schizophrenia. However, there is a paucity of research investigating these beliefs in schizotypy, or those exhibiting traits reflecting a putative genetic liability for schizophrenia. This study had three aims: to examine whether defeatist performance beliefs 1) are elevated in schizotypy compared to non-schizotypy, 2) are associated with functioning-related outcomes (i.e., quality of life, working memory, negative schizotypy traits), and 3) mediate the relationships between working memory and both negative schizotypy traits and quality of life. Schizotypy (n = 43) and non-schizotypy (n = 45) groups completed measures of schizotypy traits, defeatist performance beliefs, quality of life, and working memory. Results revealed that the schizotypy group reported significantly more defeatist performance beliefs than the non-schizotypy group. Within the schizotypy group, defeatist performance beliefs were significantly positively associated with negative schizotypy traits and significantly inversely associated with quality of life. No associations were observed between defeatist performance beliefs and positive schizotypy traits and working memory. Further, defeatist performance beliefs did not mediate the relationships between working memory and either quality of life or negative schizotypy traits. Findings are generally consistent with the cognitive model of poor functioning in schizophrenia and suggest that defeatist performance beliefs may be an important therapeutic target in early intervention services.Item Language processing fluency and verbal working memory in prelingually deaf long-term cochlear implant users: A pilot study(Taylor & Francis, 2018-11) Kronenberger, William G.; Henning, Shirley C.; Ditmars, Allison M.; Pisoni, David B.; Psychiatry, School of MedicineOBJECTIVE: Verbal working memory (WM) is more strongly correlated with spoken language skills in prelingually deaf, early-implanted cochlear implant (CI) users than in normal-hearing (NH) peers, suggesting that CI users access WM in order to support and compensate for their slower, more effortful spoken language processing. This pilot study tested the feasibility and validity of a dual-task method for establishing the causal role of WM in basic language processing (lexical access speed) in samples of 9 CI users (ages 8-26 years) and 9 NH peers. METHODS: Participants completed tests of lexical access speed (rapid automatized picture naming test and lexical decision test) under two administration conditions: a standard condition and a dual-task WM condition requiring participants to hold numerals in WM during completion of the lexical access speed tests. RESULTS: CI users showed more dual-task interference (decline in speed during the WM condition compared to the standard condition) than NH peers, indicating that their lexical access speed was more dependent on engagement of WM resources. Furthermore, dual-task interference scores were significantly correlated with several measures of speed-based executive functioning (EF), consistent with the hypothesis that the dual-task method reflects the involvement of EF in language processing. CONCLUSION: These pilot study results support the feasibility and validity of the dual-task WM method for investigating the influence of WM in the basic language processing of CI users. Preliminary findings indicate that CI users are more dependent on the use of WM as a compensatory strategy during slow-effortful basic language processing than NH peers.Item Loneliness Interacts With Cognition in Relation to Healthcare and Financial Decision Making Among Community-Dwelling Older Adults(Oxford University Press, 2020-11-23) Stewart, Christopher C.; Yu, Lei; Glover, Crystal M.; Mottola, Gary; Bennett, David A.; Wilson, Robert S.; Boyle, Patricia A.; Neurology, School of MedicineBackground and objectives: Cognition is a known determinant of healthcare and financial decision making in old age. Social vulnerabilities also might play a role in such decisions; however, the evidence for this is less clear. Here, we examined the association of loneliness with decision making and tested the hypothesis that loneliness is associated with decision making via its interaction with global cognition. Research design and methods: Participants were 1,121 nondemented older adults from the Rush Memory and Aging Project. Healthcare and financial decision making was assessed via a performance-based measure; loneliness was assessed via the De Jong Gierveld Loneliness Scale; and cognition was assessed via a 19-test neuropsychological battery. Results: In a regression model adjusted for age, sex, and education, global cognition was associated with decision making (B = 2.43, SE = 0.14, p < .001) but loneliness was not (B = -0.04, SE = 0.11, p = .72). However, in a model including the interaction of loneliness with global cognition, the interaction was significant (B = 0.44, SE = 0.20, p = .03), such that the detrimental effect of loneliness on decision making was stronger when cognition was low. In secondary analyses examining the interaction of loneliness with 5 specific cognitive domains, the interaction between loneliness and working memory with decision making was significant (B = 0.35, SE = 0.15, p = .02). Discussion and implications: Our results suggest that loneliness compromises healthcare and financial decision making among older adults with lower global cognition and, more specifically, lower working memory.Item Questionnaire-based assessment of executive functioning: Case studies(Taylor & Francis, 2018-01) Kronenberger, William G.; Castellanos, Irina; Pisoni, David B.; Psychiatry, School of MedicineDelays in the development of executive functioning skills are frequently observed in pediatric neuropsychology populations and can have a broad and significant impact on quality of life. As a result, assessment of executive functioning is often relevant for the development of formulations and recommendations in pediatric neuropsychology clinical work. Questionnaire-based measures of executive functioning behaviors in everyday life have unique advantages and complement traditional neuropsychological measures of executive functioning. Two case studies of children with spina bifida are presented to illustrate the clinical use of a new questionnaire measure of executive and learning-related functioning, the Learning, Executive, and Attention Functioning Scale (LEAF). The LEAF emphasizes clinical utility in assessment by incorporating four characteristics: brevity in administration, breadth of additional relevant content, efficiency of scoring and interpretation, and ease of availability for use. LEAF results were consistent with another executive functioning checklist in documenting everyday behavior problems related to working memory, planning, and organization while offering additional breadth of assessment of domains such as attention, processing speed, and novel problem-solving. These case study results demonstrate the clinical utility of questionnaire-based measurement of executive functioning in pediatric neuropsychology and provide a new measure for accomplishing this goal.Item The Rat Medial Prefrontal Cortex Exhibits Flexible Neural Activity States during the Performance of an Odor Span Task(Society for Neuroscience, 2019-03-26) De Falco, Emanuela; An, Lei; Sun, Ninglei; Roebuck, Andrew J.; Greba, Quentin; Lapish, Christopher C.; Howland, John G.; Psychology, School of ScienceMedial prefrontal cortex (mPFC) activity is fundamental for working memory (WM), attention, and behavioral inhibition; however, a comprehensive understanding of the neural computations underlying these processes is still forthcoming. Toward this goal, neural recordings were obtained from the mPFC of awake, behaving rats performing an odor span task of WM capacity. Neural populations were observed to encode distinct task epochs and the transitions between epochs were accompanied by abrupt shifts in neural activity patterns. Putative pyramidal neuron activity increased earlier in the delay for sessions where rats achieved higher spans. Furthermore, increased putative interneuron activity was only observed at the termination of the delay thus indicating that local processing in inhibitory networks was a unique feature to initiate foraging. During foraging, changes in neural activity patterns associated with the approach to a novel odor, but not familiar odors, were robust. Collectively, these data suggest that distinct mPFC activity states underlie the delay, foraging, and reward epochs of the odor span task. Transitions between these states likely enables adaptive behavior in dynamic environments that place strong demands on the substrates of working memory.Item Recognizing spoken words in semantically-anomalous sentences: Effects of executive control in early-implanted deaf children with cochlear implants(Taylor & Francis, 2021) Pisoni, David B.; Kronenberger, William G.; Otolaryngology -- Head and Neck Surgery, School of MedicineTo investigate differences in speech, language, and neurocognitive functioning in normal hearing (NH) children and deaf children with cochlear implants (CIs) using anomalous sentences. Anomalous sentences block the use of downstream predictive coding during speech recognition, allowing for investigation of rapid phonological coding and executive functioning. Methods: Extreme groups were extracted from samples of children with CIs and NH peers (ages 9 to 17) based on the 7 highest and 7 lowest scores on the Harvard-Anomalous sentence test (Harvard-A). The four groups were compared on measures of speech, language, and neurocognitive functioning. Results: The 7 highest-scoring CI users and the 7 lowest-scoring NH peers did not differ in Harvard-A scores but did differ significantly on measures of neurocognitive functioning. Compared to low-performing NH peers, high performing children with CIs had significantly lower nonword repetition scores but higher nonverbal IQ scores, greater verbal WM capacity, and excellent EF skills related to inhibition, shifting attention/mental flexibility and working memory updating. Discussion: High performing deaf children with CIs are able to compensate for their sensory deficits and weaknesses in automatic phonological coding of speech by engaging in a slow effortful mode of information processing involving inhibition, working memory and executive functioning.Item Speed of Information Processing and Verbal Working Memory in Children and Adolescents With Cochlear Implants(Wolters Kluwer, 2023) Herran, Reid M.; Montgomery, Caitlin J.; Henning, Shirley C.; Herbert, Carolyn J.; Ditmars, Allison M.; Yates, Catherine J.; Pisoni, David B.; Kronenberger, William G.; Otolaryngology -- Head and Neck Surgery, School of MedicineBackground: Verbal working memory delays are found in many deaf children with cochlear implants compared with normal-hearing peers, but the factors contributing to these delays are not well understood. This study investigated differences between cochlear implant users and normal-hearing peers in memory scanning speed during a challenging verbal working memory task. To better understand variability in verbal working memory capacity within each sample, associations between memory scanning speed, speech recognition, and language were also investigated. Methods: Twenty-five prelingually deaf, early implanted children (age, 8-17 yr) with cochlear implants and 25 normal-hearing peers completed the Wechsler Intelligence Scale for Children, Fifth Edition, Letter-Number Sequencing (LNS) working memory task. Timing measures were made for response latency and average pause duration between letters/numbers recalled during the task. Participants also completed measures of speech recognition, vocabulary, and language comprehension. Results: Children with cochlear implants had longer pause durations than normal-hearing peers during three-span LNS sequences, but the groups did not differ in response latencies or in pause durations during two-span LNS sequences. In the sample of cochlear implant users, poorer speech recognition was correlated with longer pause durations during two-span sequences, whereas poorer vocabulary and weaker language comprehension were correlated with longer response latencies during two-span sequences. Response latencies and pause durations were unrelated to language in the normal-hearing sample. Conclusion: Children with cochlear implants have slower verbal working memory scanning speed than children with normal hearing. More robust phonological-lexical representations of language in memory may facilitate faster memory scanning speed and better working memory in cochlear implant users.Item Verbal learning and memory in prelingually deaf children with cochlear implants(Taylor & Francis, 2018-10) Kronenberger, William G.; Henning, Shirley C.; Ditmars, Allison M.; Roman, Adrienne S.; Pisoni, David B.; Psychiatry, School of MedicineOBJECTIVE: Deaf children with cochlear implants (CIs) show poorer verbal working memory compared to normal-hearing (NH) peers, but little is known about their verbal learning and memory (VLM) processes involving multi-trial free recall. DESIGN: Children with CIs were compared to NH peers using the California Verbal Learning Test for Children (CVLT-C). STUDY SAMPLE: Participants were 21 deaf (before age 6 months) children (6-16 years old) implanted prior to age 3 years, and 21 age-IQ matched NH peers. RESULTS: Results revealed no differences between groups in number of words recalled. However, CI users showed a pattern of increasing use of serial clustering strategies across learning trials, whereas NH peers decreased their use of serial clustering strategies. In the CI sample (but not in the NH sample), verbal working memory test scores were related to resistance to the build-up of proactive interference, and sentence recognition was associated with performance on the first exposure to the word list and to the use of recency recall strategies. CONCLUSIONS: Children with CIs showed robust evidence of VLM comparable to NH peers. However, their VLM processing (especially recency and proactive interference) was related to speech perception outcomes and verbal WM in different ways from NH peers.