Decline In Cognitive Flexibility Research Articles

Age-related decline in cognitive flexibility and inadequate preparation: evidence from task-state network analysis.

Behavioral evidence showed decreased cognitive flexibility in older adults. However, task-based network mechanisms of cognitive flexibility in aging (CFA) remain unclear. Here, we provided the first task-state network evidence that CFA was associated with inadequate preparation for switching trials by revealing age-related changes in functional integration. We examined functional integration in a letter-number switch task that distinguished between the cue and target stages. Both young and older adults showed decreased functional integration from the cue stage to the target stage, indicating that control-related processes were executed as the task progressed. However, compared to young adults, older adults showed less cue-to-target reduction in functional integration, which was primarily driven by higher network integration in the target stage. Moreover, less cue-to-target reductions were correlated with age-related decreases in task performance in the switch task. To sum up, compared to young adults, older adults pre-executed less control-related processes in the cue stage and more control-related processes in the target stage. Therefore, the decline in cognitive flexibility in older adults was associated with inadequate preparation for the impending demands of cognitive switching. This study offered novel insights into network mechanisms underlying CFA. Furthermore, we highlighted that training the function of brain networks, in conjunction with providing more preparation time for older adults, may be beneficial to their cognitive flexibility.

Age-related decline in cognitive flexibility is associated with the levels of hippocampal neurogenesis.

Aging is associated with impairments in learning, memory, and cognitive flexibility, as well as a gradual decline in hippocampal neurogenesis. We investigated the performance of 6-and 14-month-old mice (considered mature adult and late middle age, respectively) in learning and memory tasks based on the Morris water maze (MWM) and determined their levels of preceding and current neurogenesis. While both age groups successfully performed in the spatial version of MWM (sMWM), the older mice were less efficient compared to the younger mice when presented with modified versions of the MWM that required a reassessment of the previously acquired experience. This was detected in the reversal version of MWM (rMWM) and was particularly evident in the context discrimination MWM (cdMWM), a novel task that required integrating various distal cues, local cues, and altered contexts and adjusting previously used search strategies. Older mice were impaired in several metrics that characterize rMWM and cdMWM, however, they showed improvement and narrowed the performance gap with the younger mice after additional training. Furthermore, we analyzed the adult-born mature and immature neurons in the hippocampal dentate gyrus and found a significant correlation between neurogenesis levels in individual mice and their performance in the tasks demanding cognitive flexibility. These results provide a detailed description of the age-related changes in learning and memory and underscore the importance of hippocampal neurogenesis in supporting cognitive flexibility.

Bifidobacterium animalis subsp. lactis and arginine mixture intake improves cognitive flexibility in mice.

The relationship between intestinal microbiota and cognitive function has been investigated as one of the major topics within the intestinal microbiota-gut-brain axis. Although an increasing number of studies have demonstrated an improvement in learning and memory when using probiotics or prebiotics, to date, there are no studies that target the cognitive flexibility observed in the early stages of several neuropsychiatric diseases, including dementia. We have recently developed a novel behavioral task using the touchscreen operant system to assess cognitive flexibility. We found that the disruption of the intestinal microbiota in mice induced a decline in cognitive flexibility. In the present study, we investigated the effects of treatments consisting of Bifidobacterium animalis subsp. lactis and arginine (Bifal + Arg), which promote the production of intestinal bacterial polyamine, on cognitive flexibility in the mouse model. Male C57BL6 mice orally treated with Bifal + Arg three times a week gradually decreased the 1st-choice incorrect diagonal rate with repeated reversals compared with the control group. Furthermore, in serial reversal phases, Bifal + Arg-treated mice shifted to the behavior of choosing a new correct spot more quickly after the reversal, and this was faster with repeated reversals. These results indicate that this treatment adapts to change and improves cognitive flexibility. This is the first report to show that intestinal environmental control, including probiotics and prebiotics, improves cognitive flexibility in mice.

Whole body vibration, an alternative for exercise to improve recovery from surgery?

Although exercise is usually associated with beneficial effects on physical and mental health, patients recovering from surgery may be hampered to perform active exercise. Whole body vibration (WBV) is suggested a passive alternative for physical training. Aim of the present study was to explore the therapeutic potential of WBV compared to physical exercise during early post-surgery recovery.Male three months old Wistar rats underwent major abdominal surgery. Starting the day after surgery, rats were subjected to either daily WBV or exercise (treadmill running) for 15 consecutive days. Control rats underwent pseudo treatment. During the first week after surgery, effects of interventions were obtained from continuous recording of hemodynamic parameters, body temperature and activity (via an implanted transducer). Behavioral tests were performed during the second post-surgical week to evaluate anxiety-like behavior, short and long-term memory functions, cognitive flexibility and motor performance. Animals were sacrificed 15 days after surgery and brain tissue was collected for analysis of hippocampal neuroinflammation and neurogenesis.Surgery significantly impacted all parameters measured during the first post-surgery week, irrespective of the type of surgery. Effect on cognitive performance was limited to cognitive flexibility; both WBV and exercise prevented the surgery-induced decline. Exercise, but not WBV increased anxiety-like behavior and grip strength. WBV as well as exercise prevented the surgery-induced declined neurogenesis, but surgery-associated hippocampal neuroinflammation was not affected.Our results indicated that active exercise and WBV share similar therapeutic potentials in the prevention of surgery induced decline in cognitive flexibility and hippocampal neurogenesis. In contrast to exercise, WBV did not increase anxiety-like behavior. Since neither intervention affected hippocampal neuroinflammation, other mechanisms and/or brain areas may be involved in the behavioral effects. Taken together, we conclude that WBV may provide a relevant alternative to active exercise during the early stage of post-operative recovery.

Impact of Intestinal Microbiota on Cognitive Flexibility by a Novel Touch Screen Operant System Task in Mice.

Cognitive flexibility is the ability to rapidly adapt to a constantly changing environment. It is impaired by aging as well as in various neurological diseases, including dementia and mild cognitive impairment. In rodents, although many behavioral test protocols have been reported to assess learning and memory dysfunction, few protocols address cognitive flexibility. In this study, we developed a novel cognitive flexibility test protocol using touch screen operant system. This test comprises a behavioral sequencing task, in which mice are required to discriminate between the “rewarded” and “never-rewarded” spots and shuttle between the two distantly positioned rewarded spots, and serial reversals, in which the diagonal spatial patterns of rewarded and never-rewarded spots were reversely changed repetitively. Using this test protocol, we demonstrated that dysbiosis treated using streptomycin induces a decline in cognitive flexibility, including perseveration and persistence. The relative abundances of Firmicutes and Bacteroides were lower and higher, respectively, in the streptomycin-treated mice with less cognitive flexibility than in the control mice. This is the first report to directly show that intestinal microbiota affects cognitive flexibility.

AGING-ASSOCIATED COGNITIVE DECLINE IS REVERSED BY D-SERINE SUPPLEMENTATION.

Brain aging is a natural process that involves structural and functional changes that lead to cognitive decline, even in healthy subjects. This detriment has been associated with NMDA receptor (NMDAR) hypofunction because of a reduction in the brain levels of D-serine, the endogenous NMDAR co-agonist. However, it is not clear whether D-serine supplementation could be used as an intervention to reduce or reverse age-related brain alterations. In the present work, we aimed to analyze the D-serine effect on aging-associated alterations in cellular and large-scale brain systems that could support cognitive flexibility in rats. We found that D-serine supplementation reverts the age-related decline in cognitive flexibility, frontal dendritic spine density, and partially restored large-scale functional connectivity without inducing nephrotoxicity; instead, D-serine restored the thickness of the renal epithelial cells that were affected by age. Our results suggest that D-serine could be used as a therapeutic target to reverse age-related brain alterations.

Vangl2, a Core Component of the WNT/PCP Pathway, Regulates Adult Hippocampal Neurogenesis and Age-Related Decline in Cognitive Flexibility.

Decline in episodic memory is one of the hallmarks of aging and represents one of the most important health problems facing Western societies. A key structure in episodic memory is the hippocampal formation and the dentate gyrus in particular, as the continuous production of new dentate granule neurons in this brain region was found to play a crucial role in memory and age-related decline in memory. As such, understanding the molecular processes that regulate the relationship between adult neurogenesis and aging of memory function holds great therapeutic potential. Recently, we found that Vang-Gogh like 2 (Vangl2), a core component of the Planar Cell Polarity (PCP) signaling pathway, is enriched in the dentate gyrus of adult mice. In this context, we sought to evaluate the involvement of this member of the Wnt/PCP pathway in both adult neurogenesis and memory abilities in adult and middle-aged mice. Using a heterozygous mouse model carrying a dominant-negative mutation in the Vangl2 gene, called Looptail (Vangl2Lp), we show that alteration in Vangl2 expression decreases the survival of adult-born granule cells and advances the onset of a decrease in cognitive flexibility. The inability of mutant mice to erase old irrelevant information to the benefit of new relevant ones highlights a key role of Vangl2 in interference-based forgetting. Taken together, our findings show that Vangl2 activity may constitute an interesting target to prevent age-related decline in hippocampal plasticity and memory.

Foreign Language Learning as Cognitive Training to Prevent Old Age Disorders? Protocol of a Randomized Controlled Trial of Language Training vs. Musical Training and Social Interaction in Elderly With Subjective Cognitive Decline.

Introduction: With aging comes a reduction of cognitive flexibility, which has been related to the development of late-life depression and progression of general cognitive decline. Several factors have been linked to attenuating such decline in cognitive flexibility, such as education, physical exercise and stimulating leisure activities. Speaking two or more languages has recently received abundant attention as another factor that may build up cognitive reserve, thereby limiting the functional implications of compromised cognition that accompany old age. With the number of older adults reaching record levels, it is important to attenuate the development of old-age disorders. Learning to speak a foreign language might offer a powerful tool in promoting healthy aging, but up to date effect studies are sparse. Here, the protocol that forms the foundation of the current study is presented. The present study aims to: (1) examine the effects of a foreign language training on cognitive flexibility and its neural underpinnings, and on mental health; and (2) assess the unique role of foreign language training vs. other cognitive or social programs.Method: One-hundred and ninety-eight Dutch elderly participants reporting subjective cognitive decline are included and randomized to either a language intervention, a music intervention, or a social control intervention. During 3 to 6 months, the language group learns English, the music group learns to play the guitar and the social group participates in social meetings where art workshops are offered. At baseline, at a 3-month follow-up, and at 6 months after termination of the training program, clinical, cognitive and brain activity measurements (combined EEG and fNIRS methods) are taken to assess cognitive flexibility and mental health.Discussion: This is the first trial addressing combined effects of language learning in elderly on cognition, language proficiency, socio-affective measures, and brain activity in the context of a randomized controlled trial. If successful, this study can provide insights into how foreign language training can contribute to more cognitively and mentally healthy years in older adulthood.Clinical Trial Registration: The trial is registered at the Netherlands Trial Register, July 2, 2018, trial number NL7137. https://www.trialregister.nl/trial/7137.

Combined cognitive and motor training improves the outcome in the early phase after stroke and prevents a decline of executive functions: A pilot study.

The negative impact of cognitive dysfunction on motor rehabilitation as a relearning-process is well known in stroke patients. However, evidence for combined cognitive and motor training (CMT) is lacking. To evaluate the effects of combined CMT in early stroke rehabilitation. In a controlled pilot study, 29 moderately affected stroke patients with low-level motor performance and cognitive impairment received motor therapy plus either cognitive (experimental group, EG) or low-frequency ergometer training (control group, CG) for eight days. Both groups improved their motor functioning significantly. After training, between-group comparison revealed significant differences for cognitive flexibility and trends for set-shifting, working memory, and reaction control in favor of the EG. Within-group effects showed improvement across all cognitive domains in the EG, which correlated with gains in bed-mobility, while the CG showed no significant improvement in cognition. Rather, a trend towards reaction control decline was observed, which correlated with less functional progression and recovery. Furthermore, a decline in cognitive flexibility, set-shifting, and working memory was descriptively observed. Combined CMT may enhance cognition and motor relearning early after stroke and is superior to single motor training. Further studies are needed to replicate these results and investigate long-term benefits.

Association of Marijuana Use with Changes in Cognitive Processing Speed and Flexibility for 17 Years in HIV-Seropositive and HIV-Seronegative Men

Background: The long-term effects of marijuana on cognition, particularly in the context of HIV is not clear, as extant research shows mixed findings. Objective: To determine associations between current and cumulative exposure to marijuana and changes in cognitive processing speed and flexibility in 788 HIV-seropositive (HIV+) and 1,132 HIV-seronegative (HIV−) men followed for up to 17 years in the Multicenter AIDS Cohort Study. Results: Among HIV+ men only, current daily marijuana use compared to none-use, was significantly associated with a greater annual percentage decline in cognitive processing speed assessed with the Trail Making Test A (TMTA) (β=−0.41, 95% confidence interval (CI): −0.88, −0.03, p=0.03)] and Symbol Digit Modalities Test (SDMT) (β= −0.14, 95% CI: −0.28, −0.01, p=0.04). Further, monthly marijuana use was associated with greater annual percentage decline in cognitive flexibility assessed with the Trail Making Test B (TMTB) (β= −0.70, 95% CI: −1.34, −0.05; p=0.03] and cognitive processing speed (SDMT) (β= −0.21, 95% CI: −0.40, −0.01, p=0.03). Among the HIV− men only, each 5-marijuana use-years (equivalent to 5-years of daily marijuana use) was significantly associated with a 0.17 annual percentage decline in cognitive processing speed only (TMTA) (β= −0.18, 95% CI: −0.36, −0.01; p=0.04). Conclusions: Our findings suggest that marijuana use, particularly current use, may be associated with worse cognitive processing speed, but the magnitude of the estimates was not clinically meaningful.

Identifying early diffusion imaging biomarkers of regional white matter injury as indicators of executive function decline following brain radiotherapy: A prospective clinical trial in primary brain tumor patients

Background and purposeExecutive function (EF) decline is common after brain radiation therapy (RT), yet the etiology is unclear. We analyzed the association between longitudinal changes in frontal lobe white matter microstructure and decline in EF following RT in brain tumor patients on a prospective clinical trial. Materials and methodsDiffusion tensor imaging was obtained on 22 patients with brain tumors prior to RT, as well as 3- and 6-months post-RT, in a prospective, observational trial. Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were calculated within the superficial white matter (SWM) of the anterior cingulate (AC) and dorsolateral prefrontal cortex. Measures of cognitive flexibility, verbal fluency, and verbal set-shifting were obtained pre- and post-RT. Reliable change indices were calculated to determine significant baseline to 6-month EF changes. ResultsDecreases in FA and increases in MD were observed in the caudal AC (CAC) at 3-months post-RT. CAC changes were characterized by increased RD bilaterally. From baseline to 6-months post-RT, decreased FA and increased MD and RD of the CAC was associated with decline in verbal set-shifting ability, whereas increased MD in the CAC was associated with a decline in cognitive flexibility. ConclusionWhite matter underlying the AC may be particularly vulnerable to radiation effects. Early microstructural loss within AC SWM represents an important biomarker for EF decline, and dose reduction in this region may represent a possibility for cognitive preservation for patients receiving radiotherapy.

One-year change in cognitive flexibility and fine motor function in middle-aged male and female marmosets (Callithrix jacchus).

The common marmoset (Callithrix jacchus) is uniquely suited for longitudinal studies of cognitive aging, due to a relatively short lifespan, sophisticated cognitive abilities, and patterns of brain aging that resemble those of humans. We examined cognitive function and fine motor skills in male and female marmosets (mean age ∼5 at study entry) followed longitudinally for 2 years. Each year, monkeys were tested on a reversal learning task with three pairs of stimuli (n = 18, 9 females) and a fine motor task requiring them to grasp small rewards from two staircases (Hill and Valley test, n = 12, 6 females). There was little evidence for a decline in cognitive flexibility between the two time points, in part because of practice effects. However, independent of year of testing, females took longer than males to reach criterion in the reversals, indicating impaired cognitive flexibility. Motivation was unlikely to contribute to this effect, as males refused a greater percentage of trials than females in the reversals. With regards to motor function, females were significantly faster than males in the Hill and Valley task. From Year 1 to Year 2, a slight slowing of motor function was observed in both sexes, but accuracy decreased significantly in males only. This study (1) demonstrates that marmosets exhibit sex differences in cognitive flexibility and fine motor function that resemble those described in humans; (2) that changes in fine motor function can already be detected at middle-age; and (3) that males may experience greater age-related changes in fine motor skills than females. Additional data points will determine whether these sex and age differences persist over time.

Age-related decline in cognitive flexibility in female chimpanzees.

Data on cognitive aging in chimpanzees are extremely sparse, yet can provide an invaluable phylogenetic perspective, especially because Alzheimer disease (AD)-like neuropathology has recently been described in the oldest chimpanzee brains. This finding underscores the importance of data on cognitive aging in this fellow hominin, our closest biological relative. We tested 30 female chimpanzees, 12-56years old, on a computerized analog of the Wisconsin Card Sort test. This test assesses cognitive flexibility, which is severely impaired in normal aging and AD. Subjects selected stimuli according to color or shape; the rewarded dimension (i.e., color or shape) switched without warning and the chimpanzee had to adapt her responses accordingly. We found that increasing age was associated with an increased number of perseverative errors and an increased number of trials to reach criterion in each switching dimension. The number of aborted trials was similar across age groups. These data show that similar to humans, chimpanzees show a clear age-related decline in cognitive flexibility that is already observed at middleage.

Cognitive Flexibility in Juvenile Anorexia Nervosain Relation to Comorbid Symptoms of Depression, Obsessive Compulsive Symptoms and Duration of Illness.

Whereas the evidence in adolescents is inconsistent, anorexia nervosa (AN) in adults is characterized by weak cognitive flexibility. This study investigates cognitive flexibility in adolescents with AN and its potential associations with symptoms of depression, obsessive compulsive disorder (OCD), and duration of illness. 69 patients and 63 age-matched healthy controls (HC) from 9 till 19 years of age were assessed using the Trail-Making Test (TMT) and self-report questionnaires. In hierarchical regression analyses, set-shifting ability did not differ between AN and HC, whereas AN patients reported significantly higher rates of depression symptoms and OCD symptoms. Age significantly predicted set-shifting in the total sample. Only among AN patients aged 14 years and older did set-shifting decline with increasing age. The presence of AN with depression or OCD symptoms or the duration of illness do not influence cognitive flexibility in children and adolescents. Early interventions may be helpful to prevent a decline in cognitive flexibility in adolescent AN with increasing age.

Promoting Cognitive Flexibility Under Attention-demanding Conditions in Aged Rats.

Age-related decline in cognitive flexibility and learning contributes to poorer quality of life. Thus, it is important to develop procedures that minimize age-related cognitive decline. Previous research has shown that, when young adult rats were trained in an attention-demanding task with a distracter, they learned a new task more quickly compared with rats trained in the same attention- demanding task without a distracter. The goal of the present experiment was to test whether this beneficial effect of distracter exposure was observed in aged rats. Male FBNF hybrid rats (n=20) trained in a two-lever visual sustained attention task that required discrimination of brief illumination of a centrally located panel light compared with trials when the light was not illuminated. At age 20 months, half of the animals received a flashing houselight distracter for the remaining testing sessions and the other animals did not. After 20 sessions, new task trials were interspersed within the sessions, when the rats received water access for pressing the lever under the left or right panel light after that light was illuminated. When 70% of the trials in a session were the new discrimination task, the distracter-exposed animals had higher accuracy in detecting the shortest signal in the remaining attention task trials compared with rats not exposed to the distracter. The present results suggest that aged animals' learning can benefit from overcoming distracter exposure, although not to the same extent as younger animals.

Diet and cognitive decline at middle age: the role of antioxidants.

To assess the relationship between dietary intake of antioxidants (vitamin C, vitamin E, β-carotene, lutein, flavonoids and lignans) and cognitive decline at middle age, analyses were performed on data from the population based Doetinchem Cohort Study. Habitual diet and cognitive function were assessed twice with a 5-year interval in 2613 persons aged 43-70 year at baseline (1995-2002). Diet was assessed with a validated 178-item semi-quantitative FFQ. Cognitive function was assessed with a neuropsychological test battery, consisting of the 15 Words Learning Test, the Stroop Test, the Word Fluency test, and the Letter Digit Substitution Test. Scores on global cognitive function, memory, processing speed, and cognitive flexibility were calculated. In regression analyses, quintiles of antioxidant intake were associated with change in cognitive domain scores. Results showed that higher lignan intake was linearly associated with less decline in global cognitive function (P= 0.01), memory (P< 0.01) and processing speed (P= 0.04), with about two times less declines in the highest v. the lowest quintile. In the lowest quintile of vitamin E intake, decline in memory was twice as fast as in all higher quintiles (P< 0.01). Global cognitive decline in the highest lutein intake group was greater than in the lowest intake group (P< 0.05). Higher flavonoid intake was associated with greater decline in cognitive flexibility (P for trend = 0.04). Intakes of other antioxidants were not associated with cognitive decline. We conclude that within the range of a habitual dietary intake, higher intake of lignans is associated with less cognitive decline at middle age.

Variability in Proactive and Reactive Cognitive Control Processes Across the Adult Lifespan

Task-switching paradigms produce a highly consistent age-related increase in mixing cost [longer response time (RT) on repeat trials in mixed-task than single-task blocks] but a less consistent age effect on switch cost (longer RT on switch than repeat trials in mixed-task blocks). We use two approaches to examine the adult lifespan trajectory of control processes contributing to mixing cost and switch cost: latent variables derived from an evidence accumulation model of choice, and event-related potentials (ERP) that temporally differentiate proactive (cue-driven) and reactive (target-driven) control processes. Under highly practiced and prepared task conditions, aging was associated with increasing RT mixing cost but reducing RT switch cost. Both effects were largely due to the same cause: an age effect for mixed-repeat trials. In terms of latent variables, increasing age was associated with slower non-decision processes, slower rate of evidence accumulation about the target, and higher response criterion. Age effects on mixing costs were evident only on response criterion, the amount of evidence required to trigger a decision, whereas age effects on switch cost were present for all three latent variables. ERPs showed age-related increases in preparation for mixed-repeat trials, anticipatory attention, and post-target interference. Cue-locked ERPs that are linked to proactive control were associated with early emergence of age differences in response criterion. These results are consistent with age effects on strategic processes controlling decision caution. Consistent with an age-related decline in cognitive flexibility, younger adults flexibly adjusted response criterion from trial-to-trial on mixed-task blocks, whereas older adults maintained a high criterion for all trials.

The role of cognitive flexibility and vocabulary abilities of younger and older users in searching for information on the web

AbstractThe present study investigated the role of cognitive flexibility and vocabulary abilities in explaining age‐related differences in information searching with a search engine. Nineteen older and 20 younger participants had to carry out nine searches and to complete a battery of cognitive tests. Older participants obtained poorer search performance with fewer correct answers, and lower task completion speed. They interacted little with the system, and showed specific difficulties in getting out of impasses and reformulating unfruitful requests. Regression analyses suggested that age differences in the number of requests were moderated by differences in cognitive flexibility and that the older participants did not leverage their increased vocabulary in producing new keywords. The findings suggest that the age‐related decline in cognitive flexibility plays a role in the age‐related differences observed in searching for information, especially in the way users get out of impasses. The results have implications for designing search engine tools. Copyright © 2010 John Wiley &amp; Sons, Ltd.

Encoding Changes in Orbitofrontal Cortex in Reversal-Impaired Aged Rats

Previous work in rats and primates has shown that normal aging can be associated with a decline in cognitive flexibility mediated by prefrontal circuits. For example, aged rats are impaired in rapid reversal learning, which in young rats depends critically on the orbitofrontal cortex. To assess whether aging-related reversal impairments reflect orbitofrontal dysfunction, we identified aged rats with reversal learning deficits and then recorded single units as these rats, along with unimpaired aged cohorts and young control rats, learned and reversed a series of odor discrimination problems. We found that the flexibility of neural correlates in orbitofrontal cortex was markedly diminished in aged rats characterized as reversal-impaired in initial training. In particular, although many cue-selective neurons in young and aged-unimpaired rats reversed odor preference when the odor-outcome associations were reversed, cue-selective neurons in reversal-impaired aged rats did not. In addition, outcome-expectant neurons in aged-impaired rats failed to become active during cue sampling after learning. These altered features of neural encoding could provide a basis for cognitive inflexibility associated with normal aging.