Cognitive Brain Research Articles

58 Cognitive and Brain Reserve Predict a Decline in Adverse Driving Behaviors Among Cognitively Normal Older Adults

Objective:Daily driving behavior is ultimate measure of cognitive functioning requiring multiple cognitive domains working synergistically to complete this complex instrumental activity of daily living. As the world’s population continues to grow and age older, motor vehicle crashes become more frequent. Cognitive and brain reserve are developing constructs that are frequently assessed in aging research. Cognitive reserve preserves functioning in the face of greater loss of brain structure as experienced during cognitive impairment or dementia. This study determined whether cognitive reserve and brain reserve predict changes in adverse driving behaviors in cognitively normal older adults.Participants and Methods:Cognitively normal participants (Clinical Dementia Rating 0) were enrolled from longitudinal studies at the Knight Alzheimer’s Disease Research Center at Washington University. Participants (n=186) were ≥ 65 years of age, required to have Magnetic Resonance Imaging (MRI) data, neuropsychological testing data, as well as one full year of naturalistic driving data prior to the beginning of COVID-19 lockdown in the United States (March 2020). Naturalistic driving behavior data was collected via the Driving Real World In-vehicle Evaluation System (DRIVES). DRIVES variables included idle time, over speeding, aggression, number of trips, including those at day and night. MRI was performed on 3T Tesla using a research imaging protocol based upon ADNI that includes a high-resolution T1 MPRAGE for assessment of brain structures to produce normalized whole brain volume (WBV) and hippocampal volume (HV). WBV and HV were each assessed using tertiles comparing the top 66% with the bottom 33% where the bottom represented increased atrophy. The Word Reading subtest of the Wide Range Achievement Test 4 (WRAT 4) was utilized as a proxy for cognitive reserve. WRAT 4 scores were compared with the top 66% and the bottom 33% where the bottom were poor performers. Linear-mixed-effect models adjusted for age, education, and sex.Results:Participants on average were older (73.7±4.9), college educated (16.6±2.2), and similar sex distribution (males=100, females=86). Analyses showed statistically significant differences in slopes where participants with increased hippocampal and whole brain atrophy were less likely to overspeed (p=0.0035; p=0.0003), drive aggressively (p=0.0016; p<0.0001), and drive during the daytime (p<0.0001; p<0.0001). However, they were more likely to spend more time idling (p=0.0005; p<0.0001) and drive during the nighttime (p=0.003; p=0.0002). Similar findings occurred with the WRAT 4 where participants with lower scores were less likely to overspeed (p=0.0035), drive aggressively (p=0.0024), hard brake (p=0.0180), and drive during the daytime (p<0.0001) while they were more likely to also spend more time idling (p=0.0012) and drive during the nighttime (p=0.0004).Conclusions:Numerous changes in driving behaviors over time were predicted by increased hippocampal and whole brain atrophy as well as lower cognitive reserve scores proxied by the WRAT 4. These changes show that those with lower brain and cognitive reserve are more likely to restrict their driving behavior and adapt their daily behaviors as they age. These results suggest older adults with lower brain and cognitive reserve are more likely to avoid highways where speeding and aggressive maneuvers are more frequent.

9 Connecting memory and functional brain networks in older adults: a resting state fMRI study

Objective:Nonpathological aging has been linked to decline in both verbal and visuospatial memory abilities in older adults. Disruptions in resting-state functional connectivity within well-characterized, higherorder cognitive brain networks have also been coupled with poorer memory functioning in healthy older adults and in older adults with dementia. However, there is a paucity of research on the association between higherorder functional connectivity and verbal and visuospatial memory performance in the older adult population. The current study examines the association between resting-state functional connectivity within the cingulo-opercular network (CON), frontoparietal control network (FPCN), and default mode network (DMN) and verbal and visuospatial learning and memory in a large sample of healthy older adults. We hypothesized that greater within-network CON and FPCN functional connectivity would be associated with better immediate verbal and visuospatial memory recall. Additionally, we predicted that within-network DMN functional connectivity would be associated with improvements in delayed verbal and visuospatial memory recall. This study helps to glean insight into whether within-network CON, FPCN, or DMN functional connectivity is associated with verbal and visuospatial memory abilities in later life.Participants and Methods:330 healthy older adults between 65 and 89 years old (mean age = 71.6 ± 5.2) were recruited at the University of Florida (n = 222) and the University of Arizona (n = 108). Participants underwent resting-state fMRI and completed verbal memory (Hopkins Verbal Learning Test - Revised [HVLT-R]) and visuospatial memory (Brief Visuospatial Memory Test - Revised [BVMT-R]) measures. Immediate (total) and delayed recall scores on the HVLT-R and BVMT-R were calculated using each test manual’s scoring criteria. Learning ratios on the HVLT-R and BVMT-R were quantified by dividing the number of stimuli (verbal or visuospatial) learned between the first and third trials by the number of stimuli not recalled after the first learning trial. CONN Toolbox was used to extract average within-network connectivity values for CON, FPCN, and DMN. Hierarchical regressions were conducted, controlling for sex, race, ethnicity, years of education, number of invalid scans, and scanner site.Results:Greater CON connectivity was significantly associated with better HVLT-R immediate (total) recall (ß = 0.16, p = 0.01), HVLT-R learning ratio (ß = 0.16, p = 0.01), BVMT-R immediate (total) recall (ß = 0.14, p = 0.02), and BVMT-R delayed recall performance (ß = 0.15, p = 0.01). Greater FPCN connectivity was associated with better BVMT-R learning ratio (ß = 0.13, p = 0.04). HVLT-R delayed recall performance was not associated with connectivity in any network, and DMN connectivity was not significantly related to any measure.Conclusions:Connectivity within CON demonstrated a robust relationship with different components of memory function as well across verbal and visuospatial domains. In contrast, FPCN only evidenced a relationship with visuospatial learning, and DMN was not significantly associated with memory measures. These data suggest that CON may be a valuable target in longitudinal studies of age-related memory changes, but also a possible target in future non-invasive interventions to attenuate memory decline in older adults.

‘’The Science Behind Raj Yoga Meditation-A Narrative Review’’

On invitation to write an article on Yoga here we decided to write on science of Raj yoga meditation (RM). Normally besides the classic asana-based meditations there are 3 kinds of meditations i) Contemplation/ Concentration based ii) Mindful based iii) Love kind of meditation. Despite so much scepticism the western world found results with meditation and according to them Mindful based meditation is the true one as they get results of increased Concentration, attention with them. Nevertheless, here we have focused on description of science behind RM. Here thus we have detailed a narrative review. The authors performed an extensive search on various platforms like PubMed; Google scholar; Web of Science; Embassy; Cochrane review library utilizing the MeSH terms; “Raj yoga meditation (RM)”; “Cognitive brain”; “attention systems ‘’emotional brain’ ’anandamide; coronary artery disease (CAD); drug addiction; obesity; neuropsychiatric disorders to assess the efficacy of RM in treatment of various diseases” from 2000 till date in 2023. We have detailed anandamide as it is the basic hormone liberated subsequent to bliss and helps in treatment of substance use disorders( SUD) .Further the basis of different neurotransmitters like serotonin, vasopressin ,GABA etc are detailed for laymen along with professionals to get insight into RM as well as its benefits which can aid in positive thinking and power of belief that I can do it can help one attain the impossible as I am possible. So much so that if 2 group of patients are told one that you will develop stomach cancer after 5 yrs, the one told of cancer actually develops it while say 2 patients knee surgery for pain both given anaesthesia one operated other also feels relief of pain despite no surgery with the power of mind, hence the role of positive thinking has kept a lot of cancer patients alive despite given a prognosis of 6mths life.

Circulating metabolites and risk of incident dementia: Aprospective cohort study.

Identifying circulating metabolites associated with dementia, cognition, and brain volume may improve the understanding of dementia pathogenesis and provide novel insights for preventive and therapeutic interventions. This cohort study included a total of 87 885 participants (median follow-up of 9.1 years, 54% female) without dementia at baseline from the UK Biobank. A total of 249 plasma metabolites were measured using nuclear magnetic resonance spectroscopy at baseline. Cox proportional regression was used to examine the associations of each metabolite with incident dementia (cases = 1134), Alzheimer's disease (AD; cases = 488), and vascular dementia (VD; cases = 257) during follow-up. Dementia-associated metabolites were further analyzed for association with cognitive deficits (N = 87 885) and brain volume (N = 7756) using logistic regression and linear regression. We identified 26 metabolites associated with incident dementia, of which 6 were associated with incident AD and 5 were associated with incident VD. These 26 dementia-related metabolites were subfractions of intermediate-density lipoprotein, large low-density lipoprotein (L-LDL), small high-density lipoprotein (S-HDL), very-low-density lipoprotein, fatty acids, ketone bodies, citrate, glucose, and valine. Among them, the cholesterol percentage in L-LDL (L-LDL-C%) was associated with lower risk of AD (HR [95% CI] = 0.92 [0.87-0.97], p = 0.002), higher brain cortical (β = 0.047, p = 3.91 × 10-6 ), and hippocampal (β = 0.043, p = 1.93 × 10-4 ) volume. Cholesteryl ester-to-total lipid ratio in L-LDL (L-LDL-CE%) was associated with lower risk of AD (HR [95% CI] = 0.93 [0.90-0.96], p = 1.48 × 10-4 ), cognitive deficits (odds ratio = 0.98, p = 0.009), and higher hippocampal volume (β = 0.027, p = 0.009). Cholesteryl esters in S-HDL (S-HDL-CE) were associated with lower risk of VD (HR [95% CI] = 0.81 [0.71-0.93], p = 0.002), but not AD. Taken together, circulating levels of L-LDL-CE% and L-LDL-C% were robustly associated with risk of AD and AD phenotypes, but not with VD. S-HDL-CE was associated with lower risk of VD, but not with AD or AD phenotypes. These metabolites may play a role in the advancement of future intervention trials. Additional research is necessary to gain a complete comprehension of the molecular mechanisms behind these associations.

The Neuroscience of Human and Artificial Intelligence Presence.

Two decades of social neuroscience and neuroeconomics research illustrate the brain mechanisms that are engaged when people consider human beings, often in comparison to considering artificial intelligence (AI) as a nonhuman control. AI as an experimental control preserves agency and facilitates social interactions but lacks a human presence, providing insight into brain mechanisms that are engaged by human presence and the presence of AI. Here, I review this literature to determine how the brain instantiates human and AI presence across social perception and decision-making paradigms commonly used to realize a social context. People behave toward humans differently than they do toward AI. Moreover, brain regions more engaged by humans compared to AI extend beyond the social cognition brain network to all parts of the brain, and the brain sometimes is engaged more by AI than by humans. Finally, I discuss gaps in the literature, limitations in current neuroscience approaches, and how an understanding of the brain correlates of human and AI presence can inform social science in the wild.

High Variability Periods in the EEG Distinguish Cognitive Brain States.

To describe a novel measure of EEG signal variability that distinguishes cognitive brain states. We describe a novel characterization of amplitude variability in the EEG signal termed "High Variability Periods" or "HVPs", defined as segments when the standard deviation of a moving window is continuously higher than the quartile cutoff. We characterize the parameter space of the metric in terms of window size, overlap, and threshold to suggest ideal parameter choice and compare its performance as a discriminator of brain state to alternate single channel measures of variability such as entropy, complexity, harmonic regression fit, and spectral measures. We show that the average HVP duration provides a substantially distinct view of the signal relative to alternate metrics of variability and, when used in combination with these metrics, significantly enhances the ability to predict whether an individual has their eyes open or closed and is performing a working memory and Raven's pattern completion task. In addition, HVPs disappear under anesthesia and do not reappear in early periods of recovery. HVP metrics enhance the discrimination of various brain states and are fast to estimate. HVP metrics can provide an additional view of signal variability that has potential clinical application in the rapid discrimination of brain states.

Biological Pathways Associated with Vitamins in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is characterized by early-appearing social communication deficits, with genetic and environmental factors potentially playing a role in its etiology, which remains largely unknown. During pregnancy, certain deficiencies in critical nutrients are mainly associated with central nervous system impairment. The vitamin B9 (folate) is primarily related to one-carbon and methionine metabolism, participating in methyl donor generation. In addition, supplementation with folic acid (FA) is recommended by the World Health Organization (WHO) in the first three gestational months to prevent neural tube defects. Vitamin B12 is related to folate regeneration, converting it into an active form. Deficiencies in this vitamin have a negative impact on cognitive function and brain development since it is involved in myelin synthesis. Vitamin D is intimately associated with Ca2+ levels, acting in bone development and calcium-dependent signaling. This vitamin is associated with ASD at several levels since it has a relation with ASD genes and oxidative stress environment. This review carries the recent literature about the role of folate, vitamin B12, and vitamin D in ASD. In addition, we discuss the possible impact of nutrient deficiency or hypersupplementation during fetal development. On the other hand, we explore the biases of vitamin supplementation studies such as the loss of participants in retrospective studies, as well as multiple variants that are not considered in the conclusion, like dietary intake or auto-medication during pregnancy. In this regard, we aim to contribute to the discussion about the role of vitamins in ASD currency, but also in pregnancy and fetal development as well. Furthermore, stress during pregnancy can be an ASD predisposition, with cortisol as a regulator. In this view, we propose that cortisol is the bridge of susceptibility between vitamin disorders and ASD prevalence.

The role of connection with nature in empirical studies with physiological measurements: a systematic literature review.

It is well described that exposure to nature reduces physiological stress, and connectedness to nature can have a moderating effect. However, few studies have so far examined the construction of the connection with nature in relation to physiological processes. In this systematic review, we collected studies that used a physiological measure and included a scale to measure connectedness to nature. Our aim was to assess the role of nature relatedness at the level of physiological processes and to summarize the results published so far. Our review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A literature search was conducted in 3 different databases (PubMed, ScienceDirect and Google Scholar). As keywords, we used all the different questionnaires that measure connectedness to nature, combined with terms related to physiological measures. After final screening, 28 articles met the inclusion criteria for the review. The studies were very diverse in terms of purpose, intervention and methods, so narrative synthesis was conducted without measures of effect. We found evidence for a mediating effect of nature connectedness on the associations between nature exposure and cognitive function, brain activity, blood pressure, cortisol level and mental health. Studies investigating nature relatedness as state-like characteristics have shown that exposure to nature increases the level of connection to nature. Eye-tracking studies have confirmed that this measurement method can be used to investigate nature relatedness at a physiological level, which could be a useful complement to self-report questionnaires in future studies.

Recombinant human brain natriuretic peptide attenuates ischemic brain injury in mice by inhibiting oxidative stress and cell apoptosis via activation of PI3K/AKT/Nrf2/HO-1 pathway.

Ischemic stroke followed by cerebral artery occlusion is a main cause of chronic disability worldwide. Recombinant human brain natriuretic peptide (rhBNP) has been reported to alleviate sepsis-induced cognitive dysfunction and brain I/R injury. However, the function and molecular mechanisms of rhBNP in ischemic brain injury have not been clarified. For establishment of an animal model of ischemic brain injury, C57BL/6 mice were treated with middle cerebral artery occlusion (MCAO) surgery for 1h and reperfusion for 24h. After subcutaneous injection of rhBNP into model mice, neurologic deficits were assessed by evaluating behavior of mice according to Longa scoring system, and TTC staining was utilized to determine the brain infarct size of mice. The levels of oxidative stress markers, superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and malondialdehyde (MDA), were detected in hippocampal tissues of mice by corresponding kits. Cell apoptosis in hippocampus tissues was examined by TUNEL staining. Protein levels of antioxidant enzymes (HO-1 and NQO1) in cerebral cortex, apoptotic markers (Bax, Bcl-2, and cleaved caspase), and PI3K/AKT pathway-associated factors in hippocampus were tested by western blot analysis. The results revealed that injection of rhBNP decreased neurologic deficit scores, the percent of brain water content, and infarct volume. Additionally, rhBNP downregulated MDA level, upregulated the levels of SOD, CAT, and GSH in hippocampus of mice, and increased protein levels of HO-1 and NQO1 in the cortex. Cell apoptosis in hippocampus tissues of model mice was inhibited by rhBNP which was shown as the reduced TUNEL-positive cells, the decreased Bax, cleaved caspase-3, and cleaved caspase-9 protein levels, and the enhanced Bcl-2 protein level. In addition, rhBNP treatment activated the PI3K/AKT signaling pathway and upregulated the protein levels of HO-1 and NRF2. Overall, rhBNP activates the PI3K/AKT/HO-1/NRF2 pathway to attenuate ischemic brain injury in mice after MCAO by suppression of cell apoptosis and oxidative stress.

Modeling naturalistic face processing in humans with deep convolutional neural networks.

Deep convolutional neural networks (DCNNs) trained for face identification can rival and even exceed human-level performance. The ways in which the internal face representations in DCNNs relate to human cognitive representations and brain activity are not well understood. Nearly all previous studies focused on static face image processing with rapid display times and ignored the processing of naturalistic, dynamic information. To address this gap, we developed the largest naturalistic dynamic face stimulus set in human neuroimaging research (700+ naturalistic video clips of unfamiliar faces). We used this naturalistic dataset to compare representational geometries estimated from DCNNs, behavioral responses, and brain responses. We found that DCNN representational geometries were consistent across architectures, cognitive representational geometries were consistent across raters in a behavioral arrangement task, and neural representational geometries in face areas were consistent across brains. Representational geometries in late, fully connected DCNN layers, which are optimized for individuation, were much more weakly correlated with cognitive and neural geometries than were geometries in late-intermediate layers. The late-intermediate face-DCNN layers successfully matched cognitive representational geometries, as measured with a behavioral arrangement task that primarily reflected categorical attributes, and correlated with neural representational geometries in known face-selective topographies. Our study suggests that current DCNNs successfully capture neural cognitive processes for categorical attributes of faces but less accurately capture individuation and dynamic features.

Application and Development of EEG Acquisition and Feedback Technology: A Review.

This review focuses on electroencephalogram (EEG) acquisition and feedback technology and its core elements, including the composition and principles of the acquisition devices, a wide range of applications, and commonly used EEG signal classification algorithms. First, we describe the construction of EEG acquisition and feedback devices encompassing EEG electrodes, signal processing, and control and feedback systems, which collaborate to measure faint EEG signals from the scalp, convert them into interpretable data, and accomplish practical applications using control feedback systems. Subsequently, we examine the diverse applications of EEG acquisition and feedback across various domains. In the medical field, EEG signals are employed for epilepsy diagnosis, brain injury monitoring, and sleep disorder research. EEG acquisition has revealed associations between brain functionality, cognition, and emotions, providing essential insights for psychologists and neuroscientists. Brain-computer interface technology utilizes EEG signals for human-computer interaction, driving innovation in the medical, engineering, and rehabilitation domains. Finally, we introduce commonly used EEG signal classification algorithms. These classification tasks can identify different cognitive states, emotional states, brain disorders, and brain-computer interface control and promote further development and application of EEG technology. In conclusion, EEG acquisition technology can deepen the understanding of EEG signals while simultaneously promoting developments across multiple domains, such as medicine, science, and engineering.

Effects of brain atrophy and altered functional connectivity on poststroke cognitive impairment

Background and PurposeBrain atrophy and disrupted functional connectivity are often present in patients with poststroke cognitive impairment (PSCI). This study aimed to explore the relationship between remote brain atrophy, connectional diaschisis and cognitive impairment in ischemic stroke patients to provide valuable information about the mechanisms underlying cognitive function recovery. MethodsForty first-time stroke patients with basal ganglia infarcts and twenty-nine age-matched healthy people were enrolled. All participants underwent T1-weighted and functional MRI scans, comprehensive cognitive function assessments at baseline, and 3-month follow-up. Brain volumes were calculated, and the atrophic regions were regarded as regions of interest in seed-based functional connectivity analyses. Pearson correlation analysis was used to explore the relationships among cognitive performance, brain atrophy, and functional connectivity alterations. ResultsCompared with healthy participants, stroke patients had worse cognitive performance at baseline and the 3-month follow-up. Worse cognitive performance was associated with smaller bilateral thalamus, left hippocampus, and left amygdala volumes, as well as lower functional connectivity between the left thalamus and the left medial superior frontal gyrus, between the right thalamus and the left median cingulate and paracingulate gyri, between the right hippocampus and the left medial superior frontal gyrus, and between the left amygdala and the right dorsolateral superior frontal gyrus. ConclusionsIn patients with basal ganglia infarction, connectional diaschisis between remote brain atrophy and the prefrontal lobe plays a significant role in PSCI. This finding provides new scientific evidence for understanding the mechanisms of PSCI and indicates that the prefrontal lobe may be a target to improve cognitive function after stroke.

Brain and Lifespan Science Homo sapiens: Energy, Quantum, Biophysical, Biochemical and Chronobiological Loss of Controllability Cognitive Brains of Healthy Aging Processes

Cognitive brain science is a new, modern, young multidisciplinary and multi-paradigm scientific platform involving nuclear medicine, neuroscience, neurophysiology, neuroendocrinology, neuroimmunology, etc., through the prism of fundamentally applied algorithms/tools/technologies for pathogenesis, diagnosis, treatment and prevention of neurodegenerative diseases. Cognitive brain science and longevity Homo sapiens: energy, quantum, biophysical and biochemical loss of cognitive brain controllability of aging processes. Circadian, electromagnetic, and nutriciological aging is the energy, quantum, biophysical, and biochemical loss of cognitive brain controllability of chronobiological processes associated with age-associated diseases (syndromes, symptoms). A new author’s multidisciplinary and multi-paradigm platform has been formed, through the prism of fundamental applied algorithms/tools/technologies for the pathogenesis, diagnosis, treatment and prevention of this neurodegeneration (Alzheimer’s disease, vascular dementia), which allows you to strategically simulate and predict the time (age) of onset of cognitive decline in Alzheimer’s disease. Homo sapiens: cognitive brains are biological, biophysical, neurophysiological, and medico-social information exchange paradigms. The achievement of research Romanchuk N. P. is the establishment of many genetic and epigenetic factors of cognitive decline and neurodegenerative diseases. Modern technologies of nuclear medicine make it possible to restore the structural-functional cognitive brain.

Correlation between low frequency fluctuation and cognitive performance in bipolar disorder patients with suicidal ideation

BackgroundPatients with bipolar disorder (BD) are at high risk of suicidal ideation (SI), and BD patients with suicidal ideation (BDSI) have shown marked abnormalities in spontaneous brain function. Cognitive impairment, on the other hand, is considered to be one of the core symptoms of BD. However, few studies have addressed the association between cognitive performance and abnormal spontaneous brain function in BDSI. MethodsIn the current study, the MATRICS Consensus Cognitive Battery (MCCB) was used to assess cognitive performance in BDSI (n = 20), BD subjects without suicidal ideation (BDNSI) (n = 24) and healthy controls (HC) (n = 30). Their cognitive performance was then correlated with amplitude of low frequency fluctuation (ALFF) values obtained by resting-state functional magnetic resonance imaging (rs-fMRI). ResultsWe found that ALFF was significantly higher in the left precuneus and right posterior cingulate cortex in the BDSI group and significantly lower in the right precuneus in the BDNSI group than in the HC group. In addition, in the BDSI group, visual learning performance was positively correlated with ALFF values in the left precuneus. ConclusionsOur findings support the notion that BD patients present with ALFF abnormalities, which are associated with cognitive performance in BDSI.

From the lab to the field: acceptability of using electroencephalography with Indian preschool children.

Background: Measurement of social and cognitive brain development using electroencephalography (EEG) offers the potential for early identification of children with elevated risk of developmental delay. However, there have been no published reports of how acceptable EEG technology is to parents and children within communities, especially in low-resource contexts such as in low and middle income countries (LMICs), which is an important question for the potential scalability of these assessments. We use a mixed-methods approach to examine whether EEG assessments are acceptable to children and their caregivers in a low resource community setting in India. Methods: We assessed the acceptability of neurophysiology research and Braintools (a novel neurodevelopmental assessment toolkit using concurrent EEG and eye-tracking technology) using: 1) a child engagement measure, 2) interviews with caregivers (n=8); 3) survey about caregiver's experience (n=36). Framework analysis was used to analyse interview data. Results: A high level of child engagement in EEG tasks was demonstrated, with children's gaze at the screen during the task averaging at 85.4% (±12.06%) of the task time. External distractions and noise during the tasks were measured, but not found to significantly effect child's attention to the screen during EEG tasks. Key topics were examined using the framework analysis: 1) parental experience of the assessment; and 2) the acceptability of research. From topic 1, four sub-themes were identified: i) caregivers' experience of the assessment, ii) caregivers' perception of child's experience of assessment, iii) logistical barriers and facilitators to participation, and iv) recommendations for improvement. Results from interviews and the survey indicated acceptability for gaze-controlled EEG research for parents and children. From topic 2, three themes were identified: i) caregivers' understanding of the research, ii) barriers to participation, and iii) facilitators to participation. Barriers to participation mainly included logistical challenges, such as geographic location and time, whereas involvement of the wider family in decision making was highlighted as an important facilitator to partake in the research. Conclusions: We demonstrate for the first time the acceptability of conducting neurodevelopmental assessments using concurrent EEG and eye-tracking in preschool children in uncontrolled community LMIC settings. This kind of research appears to be acceptable to the community and we identify potential barriers and facilitators of this research, thus allowing for future large scale research projects to be conducted investigating neurodevelopment and risk factors for suboptimal development in LMICs.

CDNF overexpression prevents motor-cognitive dysfunction by intrastriatal CPP-based delivery system in a Parkinson's disease animal model

Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compact (SNpc), and no effective treatment has yet been established to prevent PD. Neurotrophic factors, such as cerebral dopamine neurotrophic factor (CDNF), have shown a neuroprotective effect on dopaminergic neurons. Previously, we developed a cell-penetrating-peptide-based delivery system that includes Asn194Lys mutation in the rabies virus glycoprotein-9R peptide (mRVG9R), which demonstrated a higher delivery rate than the wild-type. In this study, using a mouse PD-like model, we evaluated the intrastriatal mRVG9R-KP-CDNF gene therapy through motor and cognitive tests and brain cell analysis. The mRVG9R-KP-CDNF complex was injected into the striatum on days 0 and 20. To induce the PD-like model, mice were intraperitoneally administered Paraquat (PQ) twice a week for 6weeks. Our findings demonstrate that mRVG9R-KP-CDNF gene therapy effectively protects brain cells from PQ toxicity and prevents motor and cognitive dysfunction in mice. We propose that the mRVG9R-KP-CDNF complex inhibits astrogliosis and microglia activation, safeguarding dopaminergic neurons and oligodendrocytes from PQ-induced damage. This study presents an efficient CDNF delivery system, protecting neurons and glia in the nigrostriatal pathway from PQ-induced damage, which is known to lead to motor and cognitive dysfunction in neurodegenerative diseases such as PD.

Glaucoma-associated abnormalities in cortical activity during a visuocognitive task

ObjectiveTo investigate neurophysiological dynamics during a visuocognitive task in glaucoma patients vs. healthy controls. MethodsFifteen patients with early-stage primary open-angle glaucoma (POAG) and fifteen age-matched healthy participants underwent a “go/no-go” task, monitored with EEG. Participants had to semantically categorize visual objects in central vision, with animal or furniture as targets according to the experimental block. ResultsEarly visual processing was delayed by 50 ms in patients with POAG compared to controls. The patients displayed a smaller difference between animal and furniture categorization during higher-level cognitive processing (at 400–600 ms). Regarding behavioral data, the groups differed in accuracy performance and decision criterion. As opposed to the control group, patients did not display facilitation and a higher accuracy rate for animal stimuli. However, patients maintained a consistent decision criterion throughout the experiment, whereas controls displayed a shift towards worse decision criteria in furniture trials, with higher error rate. ConclusionsThe comparative analysis of behavioral and neurophysiological data revealed in POAG patients a delay in early visual processing, and potential high-level cognitive compensation during late, task-dependent activations. SignificanceTo our knowledge, our findings provide the first evidence of modification in cognitive brain dynamics associated with POAG.

SAT143 Domains Of Cognitive Dysfunction In Patients With Post-Bariatric Hypoglycemia

Abstract Disclosure: A.M. Puleio: None. A.L. Sheehan: None. G.J. Musen: None. M. Patti: Consulting Fee; Self; AstraZeneca, Fractyl Laboratories. Other; Self; Eiger Pharmaceuticals - Consulting, MBX Biosceinces - Consulting, Hanmi Pharmaceutical - Consulting, Recordati - Consulting. Objective: Bariatric surgery is a highly effective treatment for obesity and associated comorbidities. Studies suggest bariatric surgery may result in improved cognitive function and brain volume in parallel with improved cardiometabolic function. However, some post-bariatric individuals develop post-bariatric hypoglycemia (PBH), which can be frequent and severe. Whether repeated episodes of hypoglycemia can impact cognitive function in PBH is unknown. The objective of this pilot study was to determine whether individuals with PBH display reduced cognitive function compared to surgical non-hypoglycemic counterparts. Inclusion/Exclusion Criteria: Adults aged 18-70 years, with a history of Roux-en-Y gastric bypass (RYGB), without a current diagnosis of diabetes, were recruited and enrolled into two groups: individuals with PBH (PBH+), and asymptomatic individuals with history of prior RYGB without hypoglycemia (RYGB non-hypo). Individuals with a history of traumatic brain injury or cerebrovascular accident, active treatment with any medications for diabetes (other than acarbose), active alcohol/substance abuse, known neuroendocrine tumor, or active depression (score >4 for Patient Health Questionnaire-2 (PHQ-2)) were excluded. Methods: Fourteen adults (PBH+, n=7; RYGB non-hypo, n=7) completed assessments of executive function (Delis Kaplan Executive Function System), working memory and attention (Wechsler Memory Scale Third Edition), as well as psychomotor speed (grooved pegboard). Premorbid intelligence was estimated using the National Adult Reading Test. Results: Individuals with PBH+ displayed significantly decreased performance on tests of category fluency (p <0.01), category switching (p <0.01), and category switching accuracy (p <0.01), compared to those in the RYGB non-hypo group. Performance in other verbal fluency measures, including the first (p =0.03) and third interval (p = 0.045), were significantly lower in PBH+ vs. RYGB non-hypo. All other assessments did not differ, including the estimation of premorbid intelligence (p=0.14). Conclusion: PBH+ individuals may be at greater risk for cognitive impairment compared to RYGB non-hypo individuals, as suggested by the impaired semantic processing and cognitive flexibility, as well as greater difficulty initiating and sustaining word retrieval in PBH+. Groups did not differ in cognitive assessments of psychomotor speed, memory, attention, and executive function. Clinicians should be alert for symptoms of cognitive dysfunction in PBH+ patients and consider neurocognitive testing in parallel with assessment of glycemic control, as well as other potential cognitive risk factors. Larger, longitudinal trials are necessary to further elucidate the impact of hypoglycemia on cognition and risk of dementia in patients with PBH. Presentation: Saturday, June 17, 2023

Bacillus Calmette-Guérin vaccination as defense against SARS-CoV-2 (BADAS): a randomized controlled trial to protect healthcare workers in the USA by enhanced trained immune responses

BackgroundA large epidemic, such as that observed with SARS-CoV-2, seriously challenges available hospital capacity, and this would be augmented by infection of healthcare workers (HCW). Bacillus Calmette-Guérin (BCG) is a vaccine against tuberculosis, with protective non-specific effects against other respiratory tract infections in vitro and in vivo. Preliminary analyses suggest that regions of the world with existing BCG vaccination programs have lower incidence and mortality from COVID-19. We hypothesize that BCG vaccination can reduce SARS-CoV-2 infection and disease severity.MethodsThis will be a placebo-controlled adaptive multi-center randomized controlled trial. A total of 1800 individuals considered to be at high risk, including those with comorbidities (hypertension, diabetes, obesity, reactive airway disease, smokers), racial and ethnic minorities, elderly, teachers, police, restaurant wait-staff, delivery personnel, health care workers who are defined as personnel working in a healthcare setting, at a hospital, medical center or clinic (veterinary, dental, ophthalmology), and first responders (paramedics, firefighters, or law enforcement), will be randomly assigned to two treatment groups. The treatment groups will receive intradermal administration of BCG vaccine or placebo (saline) with groups at a 1:1 ratio. Individuals will be tracked for evidence of SARS-CoV-2 infection and severity as well as obtaining whole blood to track immunological markers, and a sub-study will include cognitive function and brain imaging. The majority of individuals will be followed for 6 months, with an option to extend for another 6 months, and the cognitive sub-study duration is 2 years. We will plot Kaplan-Meier curves that will be plotted comparing groups and hazard ratios and p-values reported using Cox proportional hazard models.DiscussionIt is expected this trial will allow evaluation of the effects of BCG vaccination at a population level in high-risk healthcare individuals through a mitigated clinical course of SARS-CoV-2 infection and inform policy making during the ongoing epidemic.Trial registrationClinicalTrials.gov NCT04348370. Registered on April 16, 2020.

Relationship between baseline plasma p-tau181 and longitudinal changes in cognition and structural brain measures in a cohort of cognitively unimpaired older adults.

Preclinical Alzheimer's disease (AD) affects a significant proportion of cognitively unimpaired (CU) older adults. Currently, blood-based biomarkers detect very early changes in the AD continuum with great accuracy. We measured baseline plasma phosphorylated tau (p-tau)181 using electrochemiluminescence (ECL)-based assay (MesoScale Discovery) in 533 CU older adults. Follow-up lasted up to 18 months. Cognitive performance assessment included memory and cognitive control. Structural brain measures included cortical thickness, which includes the AD magnetic resonance imaging (AD MRI) signature, and hippocampal volume. In this cohort of CU older adults, baseline plasma p-tau181 levels were not associated with short-term changes in cognition and structural brain measures. Also, baseline plasma p-tau levels did not influence the effects of behavioral interventions (exercise or mindfulness) on cognitive and structural brain changes. The short follow-up and healthy status of this CU cohort might have limited the sensitivity of plasma p-tau181 in detecting changes associated with AD pathology.