Cognitive Markers Research Articles

A postpartum enriched environment rescues impaired cognition and oxidative markers in aged mice with gestational inflammation.

Previous studies have shown that gestational inflammation can accelerate age-associated cognitive decline (AACD) in maternal mice; enriched environments (EEs) have been reported to protect normally aging mice from AACD and improve mitochondrial function. However, it is unclear whether the nitrosative stress-related proteins tet methylcytosine dioxygenase 1 (TET1) and S-nitrosoglutathione reductase (GSNOR) are involved in the accelerated aging process of gestational inflammation and whether EEs can slow this process. In this study, CD-1 female mice on the 15th day of pregnancy were injected with bacterial lipopolysaccharide (50μg/kg; LPS group) or an equivalent amount of normal saline (CON group) from the abdominal cavity for 4 consecutive days. Twenty-one days after delivery, half of the LPS-treated mice were randomly selected for EE until the end of the behavioral experiment (LPS-E group). When the female rats were raised to 6 months and 18 months of age, the Morris water maze (MWM) was used to detect spatial learning and memory ability; RT-PCR and Western blots were used to measure the mRNA and protein levels of hippocampal TET1 and GSNOR. As for the control group, compared with 6-month-old mice, the spatial learning and memory ability of 18-month-old mice decreased, and the hippocampal TET1 and GSNOR mRNA and protein levels were decreased. Gestational inflammation exacerbated these age-related changes, but an EE alleviated the effects. Pearson's correlation analysis indicated that performance during the learning and memory periods in the MWM correlated with the levels of hippocampal TET1 and GSNOR. Our findings suggest that gestational inflammation accelerates age-related learning and memory impairments and that postpartum EE exposure could alleviate these changes. These effects may be related to hippocampal TET1 and GSNOR expression.

Subjective cognitive complaints are important in PD-MCI criteria: Associations with CSF markers and cognitive decline

IntroductionAccording to the Movement Disorder Society (MDS), subjective cognitive complaints (SCC) are a diagnostic criterion for PD-mild cognitive impairment (PD-MCI); however, studies often do not incorporate SCC when classifying PD-MCI. This inconsistent use may reflect mixed findings regarding the association between SCC and objective measures of cognitive impairment. Our study aimed to describe the extent that inclusion/exclusion of SCC affects the occurrence of PD-MCI, and if the inclusion of SCC is associated with faster cognitive decline and cerebrospinal fluid markers (CSF) of alpha-synuclein, amyloid beta, total tau, and phophorylated-tau. MethodsIndividuals with PD (N = 358) from the PPMI cohort whom completed measures of neuropsychological performance, subjective cognitive complaints, motor severity, and CSF markers were included. Participants were classified as cognitively normal (CN), PD-MCI with subjective cognitive complaints (PD-MCI + SCC) and PD-MCI without subjective cognitive complaints (PD-MCI –SCC). ResultsPD-MCI rates were consistently higher (16.5–19.1%) across the 5 years when SCC was not included in the diagnostic criteria as opposed to when SCC was included (4.4–11.0%). PD-MCI + SCC experienced greater cognitive decline and had significantly higher levels of tau/ab and p-tau/ab relative to both the CN and PD-MCI - SCC groups. ConclusionsInconsistent implementation of an SCC requirement in PD-MCI classifications may have important implications in terms of the occurrence of PD-MCI and its prognostic value. Classifying PD-MCI only using neuropsychological cut-off criterion, without regard to SCC, may lead to higher rates of PD-MCI. Inclusions of SCC in PD-MCI criteria in newly diagnosed PD participants may strengthen the ability to detect individuals at risk for future cognitive decline, though it is possible that this decline is related to Alzheimer's disease changes rather than worse PD pathology.

Subjective socioeconomic status is associated with risk aversion in a community-based cohort of older adults without dementia.

Attitudes towards risk impact financial decisions that are critical in older adulthood. Socioeconomic status (SES) influences an individual's level of risk aversion; however, the association of subjective SES (i.e., social standing relative to others) with risk aversion has not been explored. We examined whether subjective SES is associated with risk aversion independent of objective SES (i.e., income, education). Participants were 933 older adults without dementia from the Rush Memory and Aging Project (MAP) or Minority Aging Research Study (MARS), two longitudinal epidemiologic studies of aging. Participants completed assessments of risk aversion, subjective SES, and cognition. We examined associations of subjective SES with risk aversion using mixed models adjusting for participant characteristics, objective markers of SES and global cognition. In bivariate analyses, lower global cognitive functioning, lower income, female sex, Black race, and lower subjective SES were associated with greater risk aversion. Results of the nonlinear mixed effects model revealed that higher subjective SES was associated with less risk aversion (Estimate = -0.238, SE = 0.083, p = 0.004), after controlling for covariates. Age, sex, race, and global cognition were also associated with risk aversion in the mixed effects model (ps 0.03), although income and education were not (ps 0.27) The relationship between subjective SES and risk aversion did not differ by sex or race (ps 0.31). Findings suggest that subjective SES contributes to risk aversion regardless of sex or race. Findings support the importance of considering subjective indicators of SES as they may impact an older adult's economic preferences.

International depiction of the cost of functional independence limitations among older adults living in the community: a systematic review and cost-of-impairment study

BackgroundFunctional independence limitations restrict older adult self-sufficiency and can reduce quality of life. This systematic review and cost of impairment study examined the costs of functional independence limitations among community dwelling older adults to society, the health care system, and the person.MethodsFollowing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines this systematic review included community dwelling older adults aged 60 years and older with functional independence limitations. Databases (Cochrane Database of Systematic Reviews, EconLit, NHS EED, Embase, CINAHL, AgeLine, and MEDLINE) were searched between 1990 and June 2020. Two reviewers extracted information on study characteristics and cost outcomes including mean annual costs of functional independence limitations per person for each cost perspective (2020 US prices). Quality was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist.Results85 studies were included. The mean annual total costs per person (2020 US prices) were: $27,380.74 (95% CI: [$4075.53, $50,685.96]) for societal, $24,195.52 (95% CI: [$9679.77, $38,711.27]) for health care system, and $7455.49 (95% CI: [$2271.45, $12,639.53]) for personal. Individuals with cognitive markers of functional independence limitations accounts for the largest mean costs per person across all perspectives. Variations across studies included: cost perspective, measures quantifying functional independence limitations, cost items reported, and time horizon.ConclusionsThis study sheds light on the importance of targeting cognitive markers of functional independence limitations as they accounted for the greatest costs across all economic perspectives.

Axiological characteristics of the concept of cruelty in modern English-language humorous discourse

This article is devoted to the study of the features of the comic objectification of the concept of cruelty in terms of axiological linguistics. The concept of cruelty is considered as a value of modern English humorous discourse. The present article is based on the axiological approach to the study of humor that consists of assessing the reaction embracing viewers response to cruelty through comically significant cognitive markers related to identifying language and non-language means of actualizing the concept of cruelty. The corpus of the research comprises recordings and scripts of more than 70 episodes from stand-up comedies and more than 500 episodes of various situational comedies. Besides laughter during the manifestation of cruelty is also often accompanied by applauding from the audience. The main key cognitive markers of the value cruelty concept within the framework of humorous type of discourse are: lack of compassion and sympathy; causing physical or mental pain; manifestation of injustice or dishonesty. Lack of compassion and sympathy is usually expressed through: taking pleasure in the pain caused; unreasonable, intentional and regular causing of severe pain or suffering; misunderstanding (misidentification) of their own cruelty. Causing physical or mental pain is usually actualized through: physical impact on a person; infliction of mental suffering; murder. In modern humorous English discourse, unfair manifestation of cruelty relates mainly to concerns mostly physically weak people. In humorous discourse the value concept of cruelty is expressed both verbally (description of cruel actions; statement of positive emotions derived from cruelty; enumeration of committed or alleged acts; manifestation of cruelty; etc.) and non-verbally (demonstration of the intention to commit a cruel act or the result of this act, the performance of cruelty).

ATTENUATION OF OXIDATIVE STRESS AND NEUROTOXICITY BY MK-801 (DIZOCILPINE) ON DIPENTYLPHTHALATE-INDUCED COGNITIVE DYSFUNCTION IN MICE

Objectives: The aim of our research is to study the effect of dipentylphthalate (DPeP), a plasticizer on cognition and various oxidative stress markers in mice, and to explore the modulatory effects of MK-801. Methods: In the present study, experimental mice were orally treated with two doses (33 and 100 mg/kg) of DPeP for 28 days. Cognitive functions were assessed using spatial navigation task on Morris water maze (MWM) and step-down latency (SDL) in passive avoidance apparatus. Oxidative stress was assessed by examining the levels of malondialdehyde (MDA), glutathione (GSH), ferric-reducing antioxidant power (FRAP), and 8-hydroxy-deoxyguanosine (8-OH-dG) levels in whole brain of mice. Results: DPeP exposure led to a statistically significant increase of latency in spatial navigation task and significant decline in the SDL in passive avoidance apparatus when compared to the control groups. Oxidative stress markers showed a significant increase following DPeP administration as seen with rise in levels of MDA, 8-OH-dG, and a fall in GSH and FRAP levels. Conclusion: The present data suggest that DPeP could adversely affect learning and memory functions in mice by an oxidative stress-mediated neuronal damage and pre-administration of MK-801 has the potential to attenuate these effects.

Association of Red Blood Cell Omega-3 Fatty Acids With MRI Markers and Cognitive Function in Midlife: The Framingham Heart Study.

Diet may be a key contributor to brain health in midlife. In particular, omega-3 fatty acids have been related to better neurologic outcomes in older adults. However, studies focusing on midlife are lacking. We investigated the cross-sectional association of red blood cell (RBC) omega-3 fatty acid concentrations with MRI and cognitive markers of brain aging in a community-based sample of predominantly middle-aged adults and further explore effect modification by APOE genotype. We included participants from the Third-Generation and Omni 2 cohorts of the Framingham Heart Study attending their second examination. Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) concentrations were measured from RBC using gas chromatography, and the Omega-3 index was calculated as EPA + DHA. We used linear regression models to relate omega-3 fatty acid concentrations to brain MRI measures (i.e., total brain, total gray matter, hippocampal, and white matter hyperintensity volumes) and cognitive function (i.e., episodic memory, processing speed, executive function, and abstract reasoning) adjusting for potential confounders. We further tested for interactions between omega-3 fatty acid levels and APOE genotype (e4 carrier vs noncarrier) on MRI and cognitive outcomes. We included 2,183 dementia-free and stroke-free participants (mean age of 46 years, 53% women, 22% APOE-e4 carriers). In multivariable models, higher Omega-3 index was associated with larger hippocampal volumes (standard deviation unit beta ±standard error; 0.003 ± 0.001, p = 0.013) and better abstract reasoning (0.17 ± 0.07, p = 0.013). Similar results were obtained for DHA or EPA concentrations individually. Stratification by APOE-e4 status showed associations between higher DHA concentrations or Omega-3 index and larger hippocampal volumes in APOE-e4 noncarriers, whereas higher EPA concentrations were related to better abstract reasoning in APOE-e4 carriers. Finally, higher levels of all omega-3 predictors were related to lower white matter hyperintensity burden but only in APOE-e4 carriers. Our results, albeit exploratory, suggest that higher omega-3 fatty acid concentrations are related to better brain structure and cognitive function in a predominantly middle-aged cohort free of clinical dementia. These associations differed by APOE genotype, suggesting potentially different metabolic patterns by APOE status. Additional studies in middle-aged populations are warranted to confirm these findings.

Changes in sensory, postural stability and gait functions depending on cognitive decline, and possible markers for detection of cognitive status

BackgroundNumerous people never receive a formal dementia diagnosis. This issue can be addressed by early detection systems that utilize alternative forms of classification, such as gait, balance, and sensory function parameters. In the present study, said functions were compared between older adults with healthy cognition, older adults with low executive function, and older adults with cognitive impairment, to determine which parameters can be used to distinguish these groups.ResultsA group of cognitively healthy older men was found to have a significantly greater gait cadence than both the low executive function group (113.1 ± 6.8 vs. 108.0 ± 6.3 steps/min, p = 0.032) and the cognitively impaired group (113.1 ± 6.8 vs. 107.1 ± 7.4 steps/min, p = 0.009). The group with low executive function was found to have more gait stability than the impaired cognition group, represented by the single limb support phase (39.7 ± 1.2 vs. 38.6 ± 1.3%, p = 0.027). Additionally, the healthy cognition group had significantly greater overall postural stability than the impaired cognition group (0.6 ± 0.1 vs. 1.1 ± 0.1, p = 0.003), and the low executive function group had significantly greater mediolateral postural stability than the impaired cognition group (0.2 ± 0.1 vs. 0.6 ± 0.6, p = 0.012). The low executive function group had fewer mistakes on the sentence recognition test than the cognitively impaired (2.2 ± 3.6 vs. 5.9 ± 6.4, p = 0.005). There were no significant differences in visual capacity, however, the low executive function group displayed an overall greatest ability.ConclusionsOlder adults with low executive function showcased a lower walking pace, but their postural stability and sensory functions did not differ from those of the older adults with healthy cognition. The variables concluded as good cognitive status markers were (1) gait cadence for dividing cognitively healthy from the rest and (2) single limb support portion, mediolateral stability index, and the number of mistakes on the sentence recognition test for discerning between the low executive function and cognitive impairment groups.

Multilayer Exponential Family Factor models for integrative analysis and learning disease progression.

Current diagnosis of neurological disorders often relies on late-stage clinical symptoms, which poses barriers to developing effective interventions at the premanifest stage. Recent research suggests that biomarkers and subtle changes in clinical markers may occur in a time-ordered fashion and can be used as indicators of early disease. In this article, we tackle the challenges to leverage multidomain markers to learn early disease progression of neurological disorders. We propose to integrate heterogeneous types of measures from multiple domains (e.g., discrete clinical symptoms, ordinal cognitive markers, continuous neuroimaging, and blood biomarkers) using a hierarchical Multilayer Exponential Family Factor (MEFF) model, where the observations follow exponential family distributions with lower-dimensional latent factors. The latent factors are decomposed into shared factors across multiple domains and domain-specific factors, where the shared factors provide robust information to perform extensive phenotyping and partition patients into clinically meaningful and biologically homogeneous subgroups. Domain-specific factors capture remaining unique variations for each domain. The MEFF model also captures nonlinear trajectory of disease progression and orders critical events of neurodegeneration measured by each marker. To overcome computational challenges, we fit our model by approximate inference techniques for large-scale data. We apply the developed method to Parkinson's Progression Markers Initiative data to integrate biological, clinical, and cognitive markers arising from heterogeneous distributions. The model learns lower-dimensional representations of Parkinson's disease (PD) and the temporal ordering of the neurodegeneration of PD.

Spotlight on the September 20 Issue

![Graphic][1]</img>#### Notable in Neurology This Week This issue features an article that investigates the moderating role of cognitive reserve markers in the association between childhood cognition and cognitive aging; another examines longitudinal dopamine D2 receptor changes and cerebrovascular health in aging. A featured article explores the association of plasma eicosanoid levels with immune, viral, and cognitive outcomes in people with HIV. ### APOE and Cerebral Small Vessel Disease Markers in Patients With Intracerebral Hemorrhage ![Graphic][2]</img> This study investigated the association between apolipoprotein E ( APOE ) genotype, intracerebral hemorrhage (ICH), and neuroimaging markers of cerebral … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif

Effects of a Liquefied Petroleum Gas Stove and Continuous Fuel Distribution Intervention on Anthropometric Outcomes at Birth

Background and Aims: Air pollution may contribute to childhood stunting and impaired cognitive development. Potential anthropometric markers of poor growth and cognition include head circumference and length at birth. The Household Air Pollution Intervention Network (HAPIN) trial in India, Guatemala, Peru, and Rwanda was a randomized controlled field trial among 3200 pregnant women that assessed the effect of liquefied petroleum gas (LPG) stove and continuous free fuel intervention compared to cooking with biomass on health outcomes. We conducted an intention-to-treat analysis of the LPG intervention delivered during pregnancy starting at 9-19 weeks of gestation on head circumference and length at birth among offspring. Methods: Length and head circumference were measured in centimeters within 24 hours of birth. Birth length and head circumference z-scores were calculated using INTERGROWTH-21st standards which accounts for gestational age at birth. Separate linear regression models (adjusted for 10 strata, representing settings in Guatemala (1 site), Rwanda (1 site), India (2 sites) and Peru (six sites)) were created for head circumference, head circumference z-score, birth length and birth length z-score. Results: A total of 3060 live births were included in the analysis. The intervention had small or no effect on birth length (β=0.14, 95% CI -0.01 to 0.29), birth length Z-scores (β=0.09, 95% CI 0.01 to 0.16), head circumference (β= -0.01, 95% CI -0.11 to 0.09) and head-circumference Z-scores (β= -0.01, 95% CI -0.08 to 0.07). More than 90% of the women had a full-term pregnancy (94.6% in control and 94.1% in intervention group), and the mean (SD) time with the intervention was 21.23 weeks (3.67 weeks). Conclusion: Our intervention strategy aimed at reducing household air pollution during pregnancy had small or no effects on length and head circumference at birth among offspring. Keywords: Household air pollution, liquefied petroleum gas, biomass fuel, head circumference, birth length, newborn

Exposure to metal mixtures and neuropsychological functioning in middle childhood

Elevated exposure to multiple trace metals can be neurotoxic even at relatively low levels. These findings are primarily evident from adult occupational studies as well as in children exposed prenatally or in early childhood. Less research has focused on the neurodevelopmental impacts of exposure to metals among school-aged children. We examined associations between exposure to a mixture of four metals (arsenic, cadmium, manganese, lead) measured in hair and markers of cognition, attention, and behavior among 222 6–12 year old children who participated in a 2009–2010 neurodevelopmental follow-up to the C8 Health Project. Using quantile-based g-computation we estimated the adjusted overall metal mixture effect ψ (95 % CI) as the change in outcome per decile increase in all metals in the mixture. Hair metal levels varied by metal, with cadmium being lowest (median 0.007, interquartile range (IQR) 0.013 μg/g) and lead the highest concentration (median 0.152, IQR 0.252 μg/g). Children’s cognitive skills and development, attention/impulsivity, and behavior were all close to standardized population means. Each decile increase in all metals was associated with a Full Scale IQ reduction of 1.01 points (95 % confidence interval (CI) –1.88, –0.15) and Verbal IQ reduction of 1.11 points (95 % CI –1.97, –0.25), adjusted for child age, sex, secondhand smoke exposure, HOME score, maternal education, maternal IQ, and examiner. Maternal report of ADHD-like behaviors and executive functioning also showed adverse associations with the metal mixture. Our findings suggest that similar to exposure during prenatal and early childhood periods, recent exposure to metals during middle childhood is associated with adverse neurodevelopmental consequences. Middle childhood may also be a developmental window of susceptibility to the negative consequences of exposure to environmental neurotoxicants.

Intuitive assessment of spatial navigation beyond episodic memory: Feasibility and proof of concept in middle-aged and elderly individuals.

Deficits in spatial navigation in three-dimensional space are prevalent in various neurological disorders and are a sensitive cognitive marker for prodromal Alzheimer's disease, but are also associated with non-pathological aging. However, standard neuropsychological tests used in clinical settings lack ecological validity to adequately assess spatial navigation. Experimental paradigms, on the other hand, are often too difficult for seniors or patients with cognitive or motor impairments since most require operating a human interface device (HID) or use complex episodic memory tasks. Here, we introduce an intuitive navigation assessment, which is conceptualized using cognitive models of spatial navigation and designed to account for the limited technical experience and diverging impairments of elderly participants and neurological patients. The brief computer paradigm uses videos of hallways filmed with eye tracking glasses, without employing an episodic memory task or requiring participants to operate a HID. Proof of concept data from 34 healthy, middle-aged and elderly participants (56-78 years) provide evidence for the assessment's feasibility and construct validity as a navigation paradigm. Test performance showed normal distribution and was sensitive to age and education, which needs to be considered when investigating the assessment's psychometric properties in larger samples and clinical populations. Correlations of the navigation assessment with other neuropsychological tests confirmed its dependence on visuospatial skills rather than visual episodic memory, with age driving the association with working memory. The novel paradigm is suitable for a differentiated investigation of spatial navigation in elderly individuals and promising for experimental research in clinical settings.

The language marker hypothesis

According to the language marker hypothesis language has provided homo sapiens with a rich symbolic system that plays a central role in interpreting signals delivered by our sensory apparatus, in shaping action goals, and in creating a powerful tool for reasoning and inferencing. This view provides an important correction on embodied accounts of language that reduce language to action, perception, emotion and mental simulation. The presence of a language system has, however, also important consequences for perception, action, emotion, and memory. Language stamps signals from perception, action, and emotional systems with rich cognitive markers that transform the role of these signals in the overall cognitive architecture of the human mind. This view does not deny that language is implemented by means of universal principles of neural organization. However, language creates the possibility to generate rich internal models of the world that are shaped and made accessible by the characteristics of a language system. This makes us less dependent on direct action-perception couplings and might even sometimes go at the expense of the veridicality of perception. In cognitive (neuro)science the pendulum has swung from language as the key to understand the organization of the human mind to the perspective that it is a byproduct of perception and action. It is time that it partly swings back again.

Editors' Note: Association of Loneliness With 10-Year Dementia Risk and Early Markers of Vulnerability for Neurocognitive Decline

Dr. Salinas and colleagues examined the association of loneliness at baseline with 10-year all-cause dementia risk and early cognitive and neuroanatomic imaging markers of Alzheimer disease and related dementia (ADRD) vulnerability in 2,308 participants in the population-based Framingham study cohorts. They found that loneliness was associated with increased dementia risk, with the risk tripling in adults whose baseline risk would otherwise be fairly low on the basis of age and genetic risk and that loneliness was also associated with worse markers of ADRD vulnerability, implying a potential early pathogenetic role. In response, Dr. Daly notes that a similar association was seen between frailty and 10-year dementia risk. He suggests studying the relationship between longitudinal changes in loneliness and neuroanatomical or neuropathologic measures, and the relationship of loneliness to frailty. He also emphasizes the importance of taking action against loneliness in society, which was aggravated by the COVID-19 pandemic especially among lower socioeconomic strata, to mitigate further social disparities in dementia risk. Responding to these comments, Dr. Salinas notes that the study team has begun exploring longitudinal associations of loneliness with dementia-related measures in another cohort, and points to compelling findings of greater cortical amyloid and entorhinal tau accumulation in patients with loneliness in the Harvard Aging Brain Study. Dr. Salinas echoes the need for interventions targeting loneliness and social isolation. This correspondence underscores our growing understanding of the role that psychosocial determinants of health play in the development of dementia. Although it seems clear that a social brain fares better than a lonely one over time, the question remains as to whether the lonely brain can be “rescued” by social interventions. Dr. Salinas and colleagues examined the association of loneliness at baseline with 10-year all-cause dementia risk and early cognitive and neuroanatomic imaging markers of Alzheimer disease and related dementia (ADRD) vulnerability in 2,308 participants in the population-based Framingham study cohorts. They found that loneliness was associated with increased dementia risk, with the risk tripling in adults whose baseline risk would otherwise be fairly low on the basis of age and genetic risk and that loneliness was also associated with worse markers of ADRD vulnerability, implying a potential early pathogenetic role. In response, Dr. Daly notes that a similar association was seen between frailty and 10-year dementia risk. He suggests studying the relationship between longitudinal changes in loneliness and neuroanatomical or neuropathologic measures, and the relationship of loneliness to frailty. He also emphasizes the importance of taking action against loneliness in society, which was aggravated by the COVID-19 pandemic especially among lower socioeconomic strata, to mitigate further social disparities in dementia risk. Responding to these comments, Dr. Salinas notes that the study team has begun exploring longitudinal associations of loneliness with dementia-related measures in another cohort, and points to compelling findings of greater cortical amyloid and entorhinal tau accumulation in patients with loneliness in the Harvard Aging Brain Study. Dr. Salinas echoes the need for interventions targeting loneliness and social isolation. This correspondence underscores our growing understanding of the role that psychosocial determinants of health play in the development of dementia. Although it seems clear that a social brain fares better than a lonely one over time, the question remains as to whether the lonely brain can be “rescued” by social interventions.

Objective Neurophysiologic Markers of Cognition After Pediatric Brain Injury.

Following brain injury, clinical assessments of residual and emerging cognitive function are difficult and fraught with errors. In adults, recent American Academy of Neurology (AAN) practice guidelines recommend objective neuroimaging and neurophysiologic measures to support diagnosis. Equivalent measures are lacking in pediatrics-an especially great challenge due to the combined heterogeneity of both brain injury and pediatric development. Therefore, we aim to establish quantitative, clinically practicable measures of cognitive function following pediatric brain injury. Participants with and without brain injury were aged 8-18 years, clinically classified according to cognitive recovery state: N = 8 in disorders of consciousness (DoC), N = 7 in confusional state, N = 19 cognitively impaired, and N = 13 typically developing uninjured controls. We prospectively measured electroencephalographic markers of sensory processing and attention in an auditory oddball paradigm, and of covert movement attempts in a command-following paradigm. In 3 participants with DoC, EEG markers of active attempted command following revealed cognitive function that clinical assessment had failed to detect. These same 3 individuals could also be distinguished from the rest of their group by 2 event-related potentials that correlate with sensory processing and orienting attention in the oddball paradigm. Considered across the whole participant group, magnitudes of these 2 ERP markers significantly increased as cognitive recovery progressed (ANOVA: each p < 0.001); viewed jointly, the 2 ERP markers cleanly delineated the 4 cognitive states. Despite heterogeneity of brain injuries and brain development, our objective EEG markers reflected cognitive recovery independent of motor function. Two of these markers required no active participation. Together, they allowed us to identify 3 individuals who meet the criteria for cognitive-motor dissociation. To diagnose, prognose, and track cognitive recovery accurately, such markers should be used in pediatrics.

COVID-19 Infection and Risk for Neuropsychiatric Symptoms

COVID-19 Infection and Risk for Neuropsychiatric Symptoms

Changes In Cognitive Function, Neurotrophin Concentrations, And Both Brain And Systemic Inflammatory Markers Following A Game Of American Football

PURPOSE: This investigation examined the effect of a simulated American football game on cognitive function, neurotrophin concentrations and markers of both systemic and brain inflammation. METHODS: Members of the Israel national team players (six linemen and nine skill position players) were examined one-week prior to (PRE), immediately-post (IP) and 24-hours-post (24P) game. Blood was obtained and cognitive function was measured at each assessment. RESULTS:No head injuries to any of the players participating in the study occurred. Significant (p < 0.001) decreases in acute memory and a trend (p = 0.066) towards a decrease in delayed memory were noted at IP. Significant negative correlations were observed between playing time (number of plays) and concentration changes from PRE to IP (r = -0.801, p = 0.001) and from PRE to 24P (r = -0.549, p = 0.034). All cognitive function measures returned to PRE levels by 24P. Increases from PRE were noted in TNF-α (p = 0.041) at IP, and in BDNF (p = 0.009) and CRP (p = 0.019) concentrations at 24P. Circulating CRP concentrations, and the cytokine markers IL-4, IL-6, IL10 and TNF-α, were significantly elevated in linemen compared to skill players. Brain inflammatory markers (S100B and GFAP) and total tau protein (a marker of brain injury) were not elevated from PRE. No change from PRE was noted in either myoglobin or creatine kinase-mm concentrations. CONCLUSIONS: Muscle damage and inflammatory marker responses observed from the scrimmage game were consistent with muscle desensitization associated with football participation. In addition, the systemic inflammatory marker results observed in linemen were suggestive of chronic low-grade inflammation.

A Support Vector Machine Application for the Detection of Pupillary Markers of Cognitive Workload

The visual system is a core processing system and an assessment of the cognitive workload generated by vision-related tasks is made possible through pupillometry. Pupillometry, the study of pupil dimensions and their reactivity to mental effort, proposes that the diameter of the pupil expands concomitantly with the amount of mental resources mobilized (Beatty, 1982). However, considering the pupil’s responsiveness to the brightness of the surrounding, an application of pupillometry in the absence of controlled illumination represents a challenge. Overcoming this challenge is the objective of the present study. Using a head-mounted eye-tracking device, the present investigation induces transient levels of brightness in the continuous performance of cognitive tasks. Most importantly, the novel implementation of Support Vector Machine algorithms suited for recognition across intermittent time series enables the discrimination of frequency-specific pupillary markers of cognition from frequency-specific pupillary markers of brightness.

On the Spatial Distribution of Temporal Complexity in Resting State and Task Functional MRI

Measuring the temporal complexity of functional MRI (fMRI) time series is one approach to assess how brain activity changes over time. In fact, hemodynamic response of the brain is known to exhibit critical behaviour at the edge between order and disorder. In this study, we aimed to revisit the spatial distribution of temporal complexity in resting state and task fMRI of 100 unrelated subjects from the Human Connectome Project (HCP). First, we compared two common choices of complexity measures, i.e., Hurst exponent and multiscale entropy, and observed a high spatial similarity between them. Second, we considered four tasks in the HCP dataset (Language, Motor, Social, and Working Memory) and found high task-specific complexity, even when the task design was regressed out. For the significance thresholding of brain complexity maps, we used a statistical framework based on graph signal processing that incorporates the structural connectome to develop the null distributions of fMRI complexity. The results suggest that the frontoparietal, dorsal attention, visual, and default mode networks represent stronger complex behaviour than the rest of the brain, irrespective of the task engagement. In sum, the findings support the hypothesis of fMRI temporal complexity as a marker of cognition.