scholarly journals Temporal emergence of age-associated changes in cognitive and physical function in vervets (Chlorocebus aethiops sabaeus)

2020 ◽  
Author(s):  
Brett M. Frye ◽  
Payton M. Valure ◽  
Suzanne Craft ◽  
Mark G. Baxter ◽  
Christie Scott ◽  
...  
Keyword(s):  
Working Memory ◽  
Executive Function ◽  
Cognitive Performance ◽  
Gait Speed ◽  
Integrative Approach ◽  
Delayed Response ◽  
Vervet Monkeys ◽  
Chlorocebus Aethiops ◽  
Increased Risk ◽  
Response Task

ABSTRACTDual declines in gait speed and cognitive performance are associated with increased risk of developing dementia. Characterizing the patterns of such impairments therefore is paramount to distinguishing healthy from pathological aging. Nonhuman primates such as vervet/African green monkeys (Chlorocebus aethiops sabaeus) are important models of human neurocognitive aging, yet the trajectory of dual decline has not been characterized. We therefore 1) assessed whether cognitive and physical performance (i.e., gait speed) are lower in older aged animals; 2) explored the relationship between performance in a novel task of executive function (Wake Forest Maze Task – WFMT) and a well-established assessment of working memory (Delayed Response Task – DR Task); and 3) examined the association between baseline gait speed with executive function and working memory at one-year follow-up. We found 1) physical and cognitive declines with age; 2) strong agreement between performance in the novel WFMT and DR task; and 3) that slow gait predicted poor cognitive performance in both domains. Our results suggest that older-aged vervets exhibit a coordinated suite of traits consistent with human aging and that slow gait may be a risk factor for cognitive decline. This integrative approach provides evidence that gait speed and cognitive function differ across the lifespan in female vervet monkeys, which advances them as a model that could be used to evaluate the trajectory of dual decline over time.

scholarly journals Co-Occurrence of Physical and Cognitive Decline in Vervet Monkeys (Chlorocebus aethiops sabaeus)

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 118-118
Author(s):  
Brett Frye ◽  
Carol Shively ◽  
Suzanne Craft ◽  
Thomas Register ◽  
Matthew Jorgensen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Executive Function ◽  
Social Cognition ◽  
Gait Speed ◽  
Short Term Memory ◽  
Middle Age ◽  
Vervet Monkeys ◽  
Short Term ◽  
Term Memory ◽  
Chlorocebus Aethiops

Abstract Age-related neurodegeneration associated with Alzheimer’s (AD) disease begins in middle age, well before the onset of symptoms. Therefore, translational models to identify modifiable risk factors in middle-age are needed to understand etiology and identify therapeutic targets. Vervet monkeys (Chlorocebus aethiops sabaeus), like humans, naturally develop several risk factors for AD with age, including obesity, prediabetes, and hypertension. Furthermore, older vervets exhibit accumulation of amyloid and tauopathies, decreased brain volumes, and physical declines in gait speed, suggesting that these NHPs may be useful models of early AD-like neuropathology. Currently, we are investigating the extent to which cognitive and physical decline co-occur in 20 elder (mean age=23 years, ~equivalent to a human age of 80 years) and 10 middle-aged (mean age=11 years) females through assessments of physical performance, executive function, social cognition, and short-term memory. These measures are part of a larger study to integrate physical, social, and cognitive function with measures of body composition, metabolic profiles, CSF, blood, neuroimages, and neuropathology. While tests of social cognition and short-term memory are ongoing, assessments of executive function indicate that performance declines with age (N=26; p<0.05; R-squared=0.23). Furthermore, animals that exhibit slower gait speed also perform poorly on the executive function task (N=26, p<0.05; R-squared=0.25). These preliminary results suggest that accelerated aging co-occurs in multiple systems in vervets. This study will enable examination of temporal relationships between physical and cognitive declines. Ultimately, this comprehensive, integrative whole-body approach will help clarify the mechanisms underlying divergent aging trajectories and inspire interventions that promote multi-system healthy aging.

Prefrontal Cortical Representation of Visuospatial Working Memory in Monkeys Examined by Local Inactivation With Muscimol

2001 ◽  
Vol 86 (4) ◽  
pp. 2041-2053 ◽  
Author(s):  
Toshiyuki Sawaguchi ◽  
Michiyo Iba
Keyword(s):  
Working Memory ◽  
Functional Organization ◽  
Visual Fields ◽  
Local Injection ◽  
Delayed Response ◽  
Visually Guided ◽  
Visuospatial Working Memory ◽  
Prefrontal Cortical ◽  
Response Task ◽  
Spatial Locations

In primates, dorsolateral areas of the prefrontal cortex (PFC) play a major role in visuospatial working memory. To examine the functional organization of the PFC for representing visuospatial working memory, we produced reversible local inactivation, with the local injection of muscimol (5 μg, 1 μl), at various sites ( n = 100) in the dorsolateral PFC of monkeys and observed the behavioral consequences in an oculomotor delayed-response task that required memory-guided saccades for locations throughout both visual fields. At 82 sites, the local injection of muscimol induced deficits in memory-guided saccades to a few specific, usually contralateral, target locations that varied with the location of the injection site. Such deficits depended on the delay length, and longer delays were associated with larger deficits in memory-guided saccades. The injection sites and affected spatial locations of the target showed a gross topographical relationship. No deficits appeared for a control task in which the subject was required to make a visually guided saccade to a visible target. These findings suggest that a specific site in the dorsolateral PFC is responsible for the working memory process for a specific visuospatial coordinate to guide goal-directed behavior. Further, memoranda for specific visuospatial coordinates appear to be represented in a topographical memory mapwithin the dorsolateral PFC to represent visuospatial working memory processes.

Spatial working memory assessment by a visual-manual delayed response task: a controlled study in schizophrenia

1999 ◽  
Vol 275 (1) ◽  
pp. 9-12 ◽  
Author(s):  
P Stratta ◽  
E Daneluzzo ◽  
P Prosperini ◽  
M Bustini ◽  
M.G Marinangeli ◽  
...  
Keyword(s):  
Working Memory ◽  
Spatial Working Memory ◽  
Controlled Study ◽  
Delayed Response ◽  
Memory Assessment ◽  
Response Task ◽  
Delayed Response Task

scholarly journals Association of Sleep Quality on Memory-Related Executive Functions in Middle Age

2017 ◽  
Vol 24 (1) ◽  
pp. 67-76 ◽  
Author(s):  
Brinda K. Rana ◽  
Matthew S. Panizzon ◽  
Carol E. Franz ◽  
Kelly M. Spoon ◽  
Kristen C. Jacobson ◽  
...  
Keyword(s):  
Working Memory ◽  
Executive Function ◽  
Episodic Memory ◽  
Sleep Quality ◽  
Executive Functions ◽  
Later Life ◽  
Set Shifting ◽  
Interference Control ◽  
Visual Spatial ◽  
Increased Risk

AbstractObjectives: Sleep quality affects memory and executive function in older adults, but little is known about its effects in midlife. If it affects cognition in midlife, it may be a modifiable factor for later-life functioning. Methods: We examined the association between sleep quality and cognition in 1220 middle-aged male twins (age 51–60 years) from the Vietnam Era Twin Study of Aging. We interviewed participants with the Pittsburgh Sleep Quality Index and tested them for episodic memory as well as executive functions of inhibitory and interference control, updating in working memory, and set shifting. Interference control was assessed during episodic memory, inhibitory control during working memory, and non-memory conditions and set shifting during working memory and non-memory conditions. Results: After adjusting for covariates and correcting for multiple comparisons, sleep quality was positively associated with updating in working memory, set shifting in the context of working memory, and better visual-spatial (but not verbal) episodic memory, and at trend level, with interference control in the context of episodic memory. Conclusions: Sleep quality was associated with visual-spatial recall and possible resistance to proactive/retroactive interference. It was also associated with updating in working memory and with set shifting, but only when working memory demands were relatively high. Thus, effects of sleep quality on midlife cognition appear to be at the intersection of executive function and memory processes. Subtle deficits in these age-susceptible cognitive functions may indicate increased risk for decline in cognitive abilities later in life that might be reduced by improved midlife sleep quality. (JINS, 2018, 24, 67–76)

scholarly journals Goal Setting Improves Cognitive Performance in a Randomized Trial of Chronic Stroke Survivors

Stroke ◽  
2021 ◽  
Vol 52 (2) ◽  
pp. 458-470
Author(s):  
Keera N. Fishman ◽  
Andrea R. Ashbaugh ◽  
Richard H. Swartz
Keyword(s):  
Working Memory ◽  
Cognitive Impairment ◽  
Executive Function ◽  
Cognitive Performance ◽  
Goal Setting ◽  
Verbal Learning ◽  
Chronic Phase ◽  
Vascular Cognitive Impairment ◽  
Stroke Survivors ◽  
Verbal Recall

Background and Purpose: Cognitive impairment after stroke, especially executive and attention dysfunction, is common, negatively affects daily functioning, and has limited treatment options. A single-blind, parallel-design, randomized controlled trial was used to examine the impact of goal setting on poststroke cognitive performance. Methods: Stroke survivors (n=72; mean age, 68.38 [SD=11.84] years; 69.4% men) in the chronic phase (≥3 months) after stroke from an academic stroke prevention clinic were randomly assigned to receive goal-setting instructions (n=36) or standard instructions (n=36) after completing baseline cognitive measures of executive function (primary outcome), attention/working memory, verbal learning, and verbal recall. Results: A one-way mixed multivariate analysis of covariance (MANCOVA) found a group by instructional manipulation interaction effect for executive function (Wilks λ=0.66; F [3,66]=11.30; P ≤0.001; η 2 p =0.34), after adjusting for age and years of education. After similar adjustment, attention/working memory (Wilks λ=0.86; F [5,63]=2.10; P =0.043; η 2 p =0.16) and verbal learning ( F [1,60]=5.81; P =0.019; η 2 p =0.09) also showed improvement after instruction but not verbal recall (Wilks λ=0.95; F [1,56]=2.82; P =0.099; η 2 p =0.05). There were no adverse events. Conclusions: Goal setting improved executive function, attention/working memory, and learning in a heterogeneous sample in the chronic phase after stroke. This suggests that >3 months after stroke, vascular cognitive impairment is not a fixed deficit; there is a motivational contributor. Brief treatments targeting goal-oriented behavior and motivation may serve as a novel approach or adjunct treatment to improve cognitive outcomes after stroke. Future research should investigate the use of goal setting on functional outcomes (eg, instrumental activities of daily living and vocational function) in this population, highlighting new potential avenues for treatment for vascular cognitive impairment. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03511300.

scholarly journals Do Cognitive Performance and Physical Function Differ between Individuals with Motoric Cognitive Risk Syndrome and those with Mild Cognitive Impairment?

2020 ◽  
Author(s):  
Fang-Yu Cheng ◽  
Yuanmay Chang ◽  
Shih-Jung Cheng ◽  
Jin-Siang Shaw ◽  
Chuo-Yu Lee ◽  
...  
Keyword(s):  
Working Memory ◽  
Cognitive Impairment ◽  
Executive Function ◽  
Mild Cognitive Impairment ◽  
Physical Function ◽  
Cognitive Performance ◽  
Assessment Scale ◽  
Timed Up And Go ◽  
Cognitive Risk ◽  
Cognitive Complaint

Abstract Background Motoric cognitive risk syndrome (MCR) is defined by slow gait speed combined with subjective cognitive complaint. MCR is a predementia syndrome, similar to mild cognitive impairment (MCI). However, there is currently no study comparing the differences in cognitive performance and physical function between these two types of cognitive impairment. Thus, the aim of this study is to compare cognitive performance and physical function in individuals with MCR versus MCI. Methods A total of 77 participants, free of dementia, were recruited from the neurological outpatient clinic of a medical center in Taiwan. Participants were separated into two groups, MCR (n=33) and MCI (n=44) groups, based on definition criteria from previous studies. The priority was to assign a diagnosis of MCR first, followed by MCI. Hence, “pure” MCI had no overlap with MCR syndrome. Cognitive performance, including executive function, attention, working memory, episode memory, visuospatial function, and language, were measured. Physical functions such as activities in daily living, the Tinetti Assessment Scale, and the Timed Up and Go test were also measured. Results Executive function, attention, working memory, episodic memory and language were all significantly lower in the MCR group than the MCI group. Abilities related to physical function, including those measured by the Tinetti Assessment Scale and the Timed Up and Go test, were significantly lower in the MCR group than the MCI group. Conclusions We noted that cognitive performance and physical function were lower in MCR individuals than MCI but without MCR syndrome. However, the conclusions were based on the enrollment procedure of participants prioritizes the MCR syndrome. Because of the overlap of MCR and MCI, future studies should use different enrollment strategies to further clarify the status of these two populations.

scholarly journals A theory of working memory without consciousness or sustained activity

2016 ◽  
Author(s):  
Darinka Trübutschek ◽  
Sébastien Marti ◽  
Andrés Ojeda ◽  
Jean-Rémi King ◽  
Yuanyuan Mi ◽  
...  
Keyword(s):  
Working Memory ◽  
Visual Masking ◽  
Target Location ◽  
Chance Level ◽  
Delayed Response ◽  
Conscious Perception ◽  
Neural Firing ◽  
Beta Band ◽  
Sustained Activity ◽  
Response Task

AbstractWorking memory and conscious perception are thought to share similar brain mechanisms, yet recent reports of non-conscious working memory challenge this view. Combining visual masking with magnetoencephalography, we demonstrate the reality of non-conscious working memory and dissect its neural mechanisms. In a spatial delayed-response task, participants reported the location of a subjectively unseen target above chance-level after a long delay. Conscious perception and conscious working memory were characterized by similar signatures: a sustained desynchronization in the alpha/beta band over frontal cortex, and a decodable representation of target location in posterior sensors. During non-conscious working memory, such activity vanished. Our findings contradict models that identify working memory with sustained neural firing, but are compatible with recent proposals of ‘activity-silent’ working memory. We present a theoretical framework and simulations showing how slowly decaying synaptic changes allow cell assemblies to go dormant during the delay, yet be retrieved above chance-level after several seconds.

scholarly journals Chemogenetic actuator drugs impair prefrontal cortex-dependent working memory in rhesus monkeys

2019 ◽  
Author(s):  
Nicholas A. Upright ◽  
Mark G. Baxter
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Rhesus Monkeys ◽  
Memory Performance ◽  
Memory Function ◽  
Muscarinic Acetylcholine Receptor ◽  
Designer Drugs ◽  
Delayed Response ◽  
Response Task ◽  
Delayed Response Task

AbstractThe most common chemogenetic neuromodulatory system, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), uses a non-endogenous actuator ligand to activate a modified muscarinic acetylcholine receptor that is no longer sensitive to acetylcholine. It is crucial in studies using these systems to test the potential effects of DREADD actuators prior to any DREADD transduction, so that effects of DREADDs can be attributed to the chemogenetic system rather than the actuator drug. We investigated working memory performance after injections of three DREADD agonists, clozapine, olanzapine, and deschloroclozapine, in male rhesus monkeys tested in a spatial delayed response task. Performance at 0.1 mg/kg clozapine and 0.1 mg/kg deschloroclozapine did not differ from mean performance after vehicle in any of the four subjects. Administration of 0.2 mg/kg clozapine impaired working memory function in three of the four monkeys. Two monkeys were impaired after administration of 0.1 mg/kg olanzapine and two monkeys were impaired after the 0.3 mg/kg dose of deschloroclozapine. We speculate that the unique neuropharmacology of prefrontal cortex function makes the primate prefrontal cortex especially vulnerable to off-target effects of DREADD actuator drugs with affinity for endogenous monoaminergic receptor systems. These findings underscore the importance of within-subject controls for DREADD actuator drugs to confirm that effects following DREADD receptor transduction are not due to the actuator drug itself, as well as validating the behavioral pharmacology of DREADD actuator drugs in the specific tasks under study.Significance StatementChemogenetic technologies, such as Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), allow for precise and remote manipulation of neuronal circuits. In the present study, we tested monkeys in a spatial delayed response task after injections of three actuator drugs – clozapine, olanzapine, and deschloroclozapine. We found that monkeys showed significant working memory impairments after 0.2 mg/kg clozapine, 0.1 mg/kg olanzapine, and 0.3 mg/kg deschloroclozapine compared to vehicle performance. In monkeys that showed impairments, these deficits were particularly apparent at longer delay periods. It is imperative to validate the drugs and dosages in the particular behavioral test to ensure any behavior after DREADD transduction can be attributed to activation of the receptors and not administration of the actuator drug itself.

scholarly journals Prescription Medications and Co-Morbidities in Late Middle-Age are Associated with Greater Cognitive Declines: Results from WRAP

2022 ◽  
Vol 2 ◽  
Author(s):  
Lianlian Du ◽  
Rebecca Langhough Koscik ◽  
Nathaniel A. Chin ◽  
Lisa C. Bratzke ◽  
Karly Cody ◽  
...  
Keyword(s):  
Executive Function ◽  
Cognitive Performance ◽  
Repeated Measures ◽  
Cognitive Change ◽  
Cognitive Domain ◽  
Objective Measures ◽  
Mixed Effect ◽  
Health History ◽  
Age Related ◽  
Increased Risk

The present study investigated: 1) sex differences in polypharmacy, comorbidities, self-rated current health (SRH), and cognitive performance, 2) associations between comorbidities, polypharmacy, SRH, and objective measures of health, and 3) associations of these factors with longitudinal cognitive performance. Analyses included 1039 eligible Wisconsin Registry for Alzheimer’s Prevention (WRAP) participants who were cognitively unimpaired at baseline and had ≥2 visits with cognitive composites, self-reported health history, and concurrent medication records. Repeated measures correlation (rmcorr) examined the associations between medications, co-morbidities, SRH, and objective measures of health (including LIfestyle for BRAin Health Index (LIBRA), and depression). Linear mixed-effect models examined associations between medications, co-morbidities, and cognitive change over time using a preclinical Alzheimer’s cognitive composite (PACC3) and cognitive domain z-scores (executive function, working memory, immediate learning, and delayed recall). In secondary analyses, we also examined whether the number of medications interacted with co-morbidities and whether they modified age-related cognitive trajectories. The number of prescribed medications was associated with worse SRH and a higher number of self-reported co-morbidities. More prescribed medications were associated with a faster decline in executive function, and more comorbidities were associated with faster PACC3 decline. Those with a non-elevated number of co-morbidities and medications performed an average of 0.26 SD higher (better) in executive function and an average of 0.18 SD higher on PACC3 than those elevated on both. Associations between medications, co-morbidities, and executive function, and PACC3 suggest that persons with more co-morbidities and medications may be at increased risk of reaching clinical levels of impairment earlier than healthier, less medicated peers.

scholarly journals Dissociative Effects of Methylphenidate in Nonhuman Primates: Trade-offs between Cognitive and Behavioral Performance

2012 ◽  
Vol 24 (6) ◽  
pp. 1371-1381 ◽  
Author(s):  
Abigail Z. Rajala ◽  
Jeffrey B. Henriques ◽  
Luis C. Populin
Keyword(s):  
Working Memory ◽  
Target Location ◽  
Memory Performance ◽  
Memory Task ◽  
Delayed Response ◽  
Impaired Performance ◽  
Healthy Humans ◽  
Trade Offs ◽  
Accuracy And Precision ◽  
Response Task

Low doses of methylphenidate reduce hyperactivity and improve attention in individuals with attention deficit hyperactivity disorder (ADHD) as well as in healthy humans and animals. Despite its extensive use, relatively little is known about its mechanisms of action. This study investigated the effects of methylphenidate on working memory performance, impulsivity, response accuracy and precision, and the ability to stay on task in rhesus monkeys using an oculomotor delayed response task. Methylphenidate affected task performance in an inverted-U manner in all three subjects tested. The improvements resulted from a reduction in premature responses and, importantly, not from improvement in the memory of target location. The length of time subjects participated in each session was also affected dose dependently. However, the dose at which the length of participation was maximally increased significantly impaired performance on the working memory task. This dissociation of effects has implications for the treatment of ADHD, for the nonprescription use of methylphenidate for cognitive enhancement, and for furthering the basic understanding of the neural substrate underlying these processes.

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