Associations between brain imaging-derived phenotypes and cognitive functions.

We aimed to evaluate the potential causal relationship between brain imaging-derived phenotypes and cognitive functions via Mendelian randomization analyses. Genetic instruments for 470 brain imaging-derived phenotypes were selected from a genome-wide association study based on the UK Biobank (n = 33,224). Statistics for cognitive functions were obtained from the genome-wide association study based on the UK Biobank. We used the inverse variance weighted Mendelian randomization method to investigate the associations between brain imaging-derived phenotypes and cognitive functions, and reverse Mendelian randomization analyses were performed for significant brain imaging-derived phenotypes to examine the reverse causation for the identified associations. We identified three brain imaging-derived phenotypes to be associated with verbal-numerical reasoning, including cortical surface area of the left fusiform gyrus (beta, 0.18 [95% confidence interval, 0.11 to 0.25], P = 4.74 × 10-7), cortical surface area of the right superior temporal gyrus (beta, 0.25 [95% confidence interval, 0.15 to 0.35], P = 6.30 × 10-7), and orientation dispersion in the left superior longitudinal fasciculus (beta, 0.14 [95% confidence interval, 0.09 to 0.20], P = 8.37 × 10-7). The reverse Mendelian randomization analysis indicated that verbal-numerical reasoning had no effect on these three brain imaging-derived phenotypes. This Mendelian randomization study identified cortical surface area of the left fusiform gyrus, cortical surface area of the right superior temporal gyrus, and orientation dispersion in the left superior longitudinal fasciculus as predictors of verbal-numerical reasoning.

Dodecyl creatine ester therapy: from promise to reality.

Pathogenic variants in SLC6A8, the gene which encodes creatine transporter SLC6A8, prevent creatine uptake in the brain and result in a variable degree of intellectual disability, behavioral disorders (e.g., autism spectrum disorder), epilepsy, and severe speech and language delay. There are no treatments to improve neurodevelopmental outcomes for creatine transporter deficiency (CTD). In this spotlight, we summarize recent advances in innovative molecules to treat CTD, with a focus on dodecyl creatine ester, the most promising drug candidate.

Anterior thalamic circuits crucial for working memory.

Alterations in the structure and functional connectivity of anterior thalamic nuclei (ATN) have been linked to reduced cognition during aging. However, ATN circuits that contribute to higher cognitive functions remain understudied. We found that the anteroventral (AV) subdivision of ATN is necessary specifically during the maintenance phase of a spatial working memory task. This function engages the AV→parasubiculum (PaS)→entorhinal cortex (EC) circuit. Aged mice showed a deficit in spatial working memory, which was associated with a decrease in the excitability of AV neurons. Activation of AV neurons or the AV→PaS circuit in aged mice was sufficient to rescue their working memory performance. Furthermore, rescued aged mice showed improved behavior-induced neuronal activity in prefrontal cortex (PFC), a critical site for working memory processes. Although the direct activation of PFC neurons in aged mice also rescued their working memory performance, we found that these animals exhibited increased levels of anxiety, which was not the case for AV→PaS circuit manipulations in aged mice. These results suggest that targeting AV thalamus in aging may not only be beneficial for cognitive functions but that this approach may have fewer unintended effects compared to direct PFC manipulations.

Comprehensive investigation of predictive processing: A cross- and within-cognitive domains fMRI meta-analytic approach.

Predictive processing (PP) stands as a predominant theoretical framework in neuroscience. While some efforts have been made to frame PP within a cognitive domain-general network perspective, suggesting the existence of a "prediction network," these studies have primarily focused on specific cognitive domains or functions. The question of whether a domain-general predictive network that encompasses all well-established cognitive domains exists remains unanswered. The present meta-analysis aims to address this gap by testing the hypothesis that PP relies on a large-scale network spanning across cognitive domains, supporting PP as a unified account toward a more integrated approach to neuroscience. The Activation Likelihood Estimation meta-analytic approach was employed, along with Meta-Analytic Connectivity Mapping, conjunction analysis, and behavioral decoding techniques. The analyses focused on prediction incongruency and prediction congruency, two conditions likely reflective of core phenomena of PP. Additionally, the analysis focused on a prediction phenomena-independent dimension, regardless of prediction incongruency and congruency. These analyses were first applied to each cognitive domain considered (cognitive control, attention, motor, language, social cognition). Then, all cognitive domains were collapsed into a single, cross-domain dimension, encompassing a total of 252 experiments. Results pertaining to prediction incongruency rely on a defined network across cognitive domains, while prediction congruency results exhibited less overall activation and slightly more variability across cognitive domains. The converging patterns of activation across prediction phenomena and cognitive domains highlight the role of several brain hubs unfolding within an organized large-scale network (Dynamic Prediction Network), mainly encompassing bilateral insula, frontal gyri, claustrum, parietal lobules, and temporal gyri. Additionally, the crucial role played at a cross-domain, multimodal level by the anterior insula, as evidenced by the conjunction and Meta-Analytic Connectivity Mapping analyses, places it as the major hub of the Dynamic Prediction Network. Results support the hypothesis that PP relies on a domain-general, large-scale network within whose regions PP units are likely to operate, depending on the context and environmental demands. The wide array of regions within the Dynamic Prediction Network seamlessly integrate context- and stimulus-dependent predictive computations, thereby contributing to the adaptive updating of the brain's models of the inner and external world.

Neuropsychological Changes in Isolated REM Sleep Behavior Disorder: A Systematic Review and Meta-analysis of Cross-sectional and Longitudinal Studies.

The aim of this meta-analysis is twofold: (a) to assess cognitive impairments in isolated rapid eye movement (REM) sleep behavior disorder (iRBD) patients compared to healthy controls (HC); (b) to quantitatively estimate the risk of developing a neurodegenerative disease in iRBD patients according to baseline cognitive assessment. To address the first aim, cross-sectional studies including polysomnography-confirmed iRBD patients, HC, and reporting neuropsychological testing were included. To address the second aim, longitudinal studies including polysomnography-confirmed iRBD patients, reporting baseline neuropsychological testing for converted and still isolated patients separately were included. The literature search was conducted based on PRISMA guidelines and the protocol was registered at PROSPERO (CRD42021253427). Cross-sectional and longitudinal studies were searched from PubMed, Web of Science, Scopus, and Embase databases. Publication bias and statistical heterogeneity were assessed respectively by funnel plot asymmetry and using I2. Finally, a random-effect model was performed to pool the included studies. 75 cross-sectional (2,398 HC and 2,460 iRBD patients) and 11 longitudinal (495 iRBD patients) studies were selected. Cross-sectional studies showed that iRBD patients performed significantly worse in cognitive screening scores (random-effects (RE) model = -0.69), memory (RE model = -0.64), and executive function (RE model = -0.50) domains compared to HC. The survival analyses conducted for longitudinal studies revealed that lower executive function and language performance, as well as the presence of mild cognitive impairment (MCI), at baseline were associated with an increased risk of conversion at follow-up. Our study underlines the importance of a comprehensive neuropsychological assessment in the context of iRBD.

Cerebellar Roles in Motor and Social Functions and Implications for ASD.

The cerebellum, traditionally linked to voluntary motor coordination, is now recognized for its role in nonmotor functions, including cognitive and social behaviors. This expanded understanding is vital for identifying neurodevelopmental disorders such as autism spectrum disorder (ASD), where cerebellar abnormalities are common. Recent research has identified specific cerebellar circuits contributing to these diverse functions, revealing interconnected pathways that regulate both motor and social behaviors. The cerebellum communicates extensively with the cerebral cortex, thalamus, and limbic structures through converging and diverging pathways, integrating sensory and motor information to fine-tune outputs and influence higher-order functions. Mouse models have been instrumental in dissecting cerebellar functions, with studies using genetic and neuroanatomical techniques to manipulate specific circuits and observe behavioral outcomes. Disruptions in cerebellar pathways can lead to motor deficits and social impairments, mirroring human neurodevelopmental disorders. This review explores the anatomical and functional organization of cerebellar pathways in mice, their role in behavior, and the implications of cerebellar dysfunction in disorders such as ASD. Understanding these pathways enhances knowledge of cerebellar contributions to behavior and informs therapeutic strategies for cerebellar and neurodevelopmental disorders, emphasizing the integral role of the cerebellum in motor and social functions.

Morus Alba Fruit Extract and its Fractions Ameliorate Streptozotocin Induced Cognitive Deficit in Mice via Modulating Oxidative and Cholinergic Systems.

Increased oxidative stress and acetylcholinesterase (AChE) activity are key pathological characters contributing to the memory disorders. Thus, drugs targeting both oxidative stress and AChE are being explored for the management of cognitive dysfunction. Morus alba fruits (commonly consumed for its high nutritious value) are known to have antioxidant and AChE inhibitory effects. However, the role of Morus alba fruits in the management of memory disorders has not reported yet. This investigation was conducted to assess the antioxidant and AChE inhibitory potential of Morus alba fruit extracts in-vitro and to identify the components responsible for such effects. Further, the obtained bioactive component was studied for possible memory improvement effects against streptozotocin (STZ) induced dementia. To isolate the bioactive component in-vitro DPPH and AChE assays guided fractionation was performed. Memory functions in mice were determined using Morris Water Maze test while brain biochemical parameters were measured to understand the mechanism of action. In-vitro assays revealed strong AChE and DPPH inhibitory potential of methanol extract (ME), therefore, it was further fractionated. Among various fractions obtained, ethyl-acetate fraction (EAF) was found to possess marked AChE and DPPH inhibitory activities. On subsequent fractionation of EAF, bioactivity of obtained sub-fractions was found to be inferior to EAF. Further, both ME and EAF improved STZ (intracerebroventricular) induced cognitive dysfunction in animals by restoring endogenous antioxidant status (superoxide dismutase and reduced glutathione) and reducing thiobarbituric acid reactive species and nitric oxide levels along with brain AChE and myeloperoxidase activity. TLC densitometric studies showed appreciable levels of phenolic acids and quercetin in both EAF and ME. It can be concluded that Morus alba fruit extract has the ability to modulate cholinergic and oxidative system due to presence of phenolic and flavonoid compounds and hence, could aid in the management of memory disorders.

The role of fatigue in attentional processing in multiple sclerosis: data from event-related potentials.

Fatigue is an extremely common symptom in in people with multiple sclerosis (PwMS) and has a severe impact on quality of life. The purpose of the present study was to verify whether fatigue in PwMS is associated with a selective covert attention impairment, as measured by event-related potentials and to assess whether it is more associated with an impairment of top-down or bottom-up attentional control. Twenty-two PwMS and fatigue-MSF, 17 without fatigue-MSnF and 35 healthy volunteers underwent a three-stimulus P300 novelty task that elicits both the P3a and the P3b components. P3b latency was comparable between groups, but PwMS, independently from the presence of fatigue displayed significantly greater P3b amplitudes. P3a latency was significantly prolonged in MSF alone, while P3a amplitude in MSnF group was greater than controls. MSF were able to categorize the task-relevant target stimulus but the orienting response to a novel salient stimulus was delayed, indicating an impairment in bottom-up attentional control mechanism related to ventral attention network. Fatigue is selectively associated with a covert attentional deficit related to the ability to reallocate attentional resources to salient stimuli, a crucial function of adaptive decision-making behaviour.

Enhanced audiovisual associative pair learning in migraine without aura in adult patients: An unexpected finding.

BACKGROUND: Altered sensory processing in migraine has been demonstrated by several studies in unimodal, and especially visual, tasks. While there is some limited evidence hinting at potential alterations in multisensory processing among migraine sufferers, this aspect remains relatively unexplored. This study investigated the interictal cognitive performance of migraine patients without aura compared to matched controls, focusing on associative learning, recall, and transfer abilities through the Sound-Face Test, an audiovisual test based on the principles of the Rutgers Acquired Equivalence Test. MATERIALS AND METHODS: The performance of 42 volunteering migraine patients was compared to the data of 42 matched controls, selected from a database of healthy volunteers who had taken the test earlier. The study aimed to compare the groups' performance in learning, recall, and the ability to transfer learned associations. RESULTS: Migraine patients demonstrated significantly superior associative learning as compared to controls, requiring fewer trials, and making fewer errors during the acquisition phase. However, no significant differences were observed in retrieval error ratios, generalization error ratios, or reaction times between migraine patients and controls in later stages of the test. CONCLUSION: The results of our study support those of previous investigations, which concluded that multisensory processing exhibits a unique pattern in migraine. The specific finding that associative audiovisual pair learning is more effective in adult migraine patients than in matched controls is unexpected. If the phenomenon is not an artifact, it may be assumed to be a combined result of the hypersensitivity present in migraine and the sensory threshold-lowering effect of multisensory integration.

Protecting the Brain While Healing Hearts: The Protective Role of Cognitive Reserve in Cardiac Surgery.

OBJECTIVE: One of the most significant complications following coronary artery bypass grafting (CABG) is postoperative cognitive decline (POCD). CABG patients frequently experience considerable postoperative cognitive dysfunction (POCD), including decline in attention, orientation, memory, judgment, and social functioning. DESIGN: These negative effects may potentially be resolved by a protective factor, cognitive reserve (CR) that has been considered to function as a buffer against the consequences of neuropathology. SETTING: We explored the frequency of POCD and CR in coronary artery disease patients undergoing CABG. We hypothesized that high levels of CR would protect against POCD after cardiac surgery. PARTICIPANTS: We assessed 101 patients before surgery, and 4 months after cardiopulmonary bypass surgery with the use of extracorporeal circulation. MEASUREMENTS: Measures of cognitive functions, CR, anxiety, and depression were included in the assessment. RESULTS: Each patient was placed in the high (n = 50) or low CR (n = 51) group, based on median split. Chi-square tests effect showed that patients with low CR were more likely to a great extend to demonstrate postsurgical cognitive decline in attention, memory, visuospatial perception and executive functions than patients with high CR upon postsurgery neuropsychological assessment. CONCLUSIONS: Our results suggest that CR can forecast neuropsychological outcomes of cardiac surgery, recognizing the patients with low CR and help them to participate to interventions programs that could slow cognitive aging or reduce the risk of dementia and enhance their overall postsurgical functional outcome.

An embodied approach to fetal and newborn perceptual and sensorimotor development.

The embodied approach argues that interaction with the environment plays a crucial role in brain development and that the presence of sensory effects generated by movements is fundamental. The movement of the fetus is initially random. Then, the repeated execution of the movement creates a link between it and its sensory effects, allowing the selection of movements that produce expected sensations. During fetal life, the brain develops from a transitory fetal circuit to the permanent cortical circuit, which completes development after birth. Accordingly, this process must concern the interaction of the fetus with the intrauterine environment and of the newborn with the new aerial environment, which provides a new sensory stimulation, light. The goal of the present review is to provide suggestions for neuroscientific research capable of shedding light on brain development process by describing from a functional point of view the relationship between the motor and sensory abilities of fetuses and newborns and the increasing complexity of their interaction with objects in the womb and outside of it.

The impacts of early environmental adversity on cognitive functioning, body mass, and life-history behavioral profiles.

Early adverse experiences or exposures have a profound impact on neurophysiological, cognitive, and somatic development. Evidence across disciplines uncovers adversity-induced alternations in cortical structures, cognitive functions, and related behavioral manifestations, as well as an energetic trade-off between the brain and body. Based on the life history (LH) framework, the present research aims to explore the adversity-adapted cognitive-behavioral mechanism and investigate the relation between cognitive functioning and somatic energy reserve (i.e., body mass index; BMI). A structural equation modeling (SEM) analysis was performed with longitudinal self-reported, anthropometric, and task-based data drawn from a cohort of 2,607 8- to 11-year-old youths and their primary caregivers recruited by the Adolescent Brain Cognitive Development (ABCDSM) study. The results showed that early environmental adversity was positively associated with fast LH behavioral profiles and negatively with cognitive functioning. Moreover, cognitive functioning mediated the relationship between adversity and fast LH behavioral profiles. Additionally, we found that early environmental adversity positively predicted BMI, which was inversely correlated with cognitive functioning. These results revealed an adversity-adapted cognitive-behavioral mechanism and energy-allocation pathways, and add to the existing knowledge of LH trade-off and developmental plasticity.

Activation of D2-like dopamine receptors improves the neuronal network and cognitive function of PPT1KI mice.

Palmitoyl-protein thioesterase 1 (PPT1) is a lysosomal depalmitoylation enzyme that mediates protein posttranslational modifications. Loss-of-function mutation of PPT1 causes a failure of the lysosomal degradation of palmitoylated proteins and results in a congenital disease characterized by progressive neuronal degeneration referred to as infantile neuronal ceroid lipofuscinosis (INCL). A mouse knock-in model of PPT1 (PPT1-KI) was established by introducing the R151X mutation into exon 5 of the PPT1 gene, which exhibited INCL-like pathological lesions. We previously reported that hippocampal γ oscillations were impaired in PPT1 mice. Hippocampal γ oscillations can be enhanced by selective activation of the dopamine D4 receptor (DR4), a dopamine D2-like receptor. In this study, we investigated the changes in DR expression and the effects of dopamine and various DR agonists on neural network activity, cognition and motor function in PPT1KI mice. Cognition and motor defects were evaluated via Y-maze, novel object recognition and rotarod tests. Extracellular field potentials were elicited in hippocampal slices, and neuronal network oscillations in the gamma frequency band (γ oscillations) were induced by perfusion with kainic acid (200 nM). PPT1KI mice displayed progressive impairments in γ oscillations and hippocampus-related memory, as well as abnormal expression profiles of dopamine receptors with preserved expression of DR1 and 3, increased membrane expression of DR4 and decreased DR2 levels. The immunocytochemistry analysis revealed the colocalization of PPT1 with DR4 or DR2 in the soma and large dendrites of both WT and PPT1KI mice. Immunoprecipitation confirmed the interaction between PPT1 and DR4 or DR2. The impaired γ oscillations and cognitive functions were largely restored by the application of exogenous dopamine, the selective DR2 agonist quinpirole or the DR4 agonist A412997. Furthermore, the administration of A412997 (0.5 mg/kg, i.p.) significantly upregulated the activity of CaMKII in the hippocampus of 5-month-old PPT1KI mice. Collectively, these results suggest that the activation of D2-like dopamine receptors improves cognition and network activity in PPT1KI mice and that specific DR subunits may be potential targets for the intervention of neurodegenerative disorders, such as INCL.

White matter microstructural variability linked to differential attentional skills and impulsive behavior in a pediatric population.

Structural and functional magnetic resonance imaging (MRI) studies have suggested a neuroanatomical basis that may underly attention-deficit-hyperactivity disorder (ADHD), but the anatomical ground truth remains unknown. In addition, the role of the white matter (WM) microstructure related to attention and impulsivity in a general pediatric population is still not well understood. Using a state-of-the-art structural connectivity pipeline based on the Brainnetome atlas extracting WM connections and its subsections, we applied dimensionality reduction techniques to obtain biologically interpretable WM measures. We selected the top 10 connections-of-interests (located in frontal, parietal, occipital, and basal ganglia regions) with robust anatomical and statistical criteria. We correlated WM measures with psychometric test metrics (Conner's Continuous Performance Test 3) in 171 children (27 Dx ADHD, 3Dx ASD, 9-13 years old) from the population-based GESTation and Environment cohort. We found that children with lower microstructural complexity and lower axonal density show a higher impulsive behavior on these connections. When segmenting each connection in subsections, we report WM alterations localized in one or both endpoints reflecting a specific localization of WM alterations along each connection. These results provide new insight in understanding the neurophysiology of attention and impulsivity in a general population.

Understanding treatment preferences and cognitive outcomes in patients with gliomas.

OBJECTIVE: Understanding how glioma patients value cognitive outcomes is essential to personalizing their treatment plans. The purpose of this study was to identify the modifiable cognitive functions most affected by treatment and most important to patient quality of life. METHODS: Patients with gliomas were prospectively enrolled in focus groups and individual interviews using a standardized guide focusing on cognitive functions until saturation was achieved. Patient values and treatment preferences were elicited and compared to the frequency of reported deficits. NVivo natural language processing software was used to perform thematic qualitative analyses. Quantitative analysis with Fischer's exact test was used for each cognitive function to assess for an association between experiencing a deficit and rating that function as important to quality of life. RESULTS: Twenty participants participated, of whom 60% were female. Racial identification consisted of 75% White, 15% Black/African American, and 10% Other Racial Identification. The cognitive functions most essential to the quality of life in this cohort were sense of self (80% of participants), memory (70% of participants), and communication (25% of participants). The functions that experienced the most deficits because of treatment were memory (65% of participants), concentration (65% of participants), and special senses (40% of participants). "Dealbreakers" to treatment were complete loss of independence, sense of self, and/or the ability to interact with loved ones. Fischer's exact test showed no associations between experiencing a cognitive function deficit and rating that function as important to quality of life. CONCLUSIONS: Glioma patients in this study prioritized cognitive functions according to memory, personal identity, and their ability to communicate with loved ones independently of experiencing deficits in these functions. Further study should compare patient prioritization and decision-making between surgically curable and noncurable grade gliomas as well as investigate the quality of life benefits of incorporating the connectomics of highly valued cognitive functions in surgical planning.

Bi-directional association between outdoor or social activities and cognitive function: do the PM2.5 exposure catalyze the detrimental inactivity-poor cognition cycle?

BACKGROUND: Previous research has shown that lack of leisure activities, either outdoor or social activities, impedes cognitive function. However, the interrelationship between poor cognition and deficient activities is understudied. In addition, whether exposure to air pollution, such as PM2.5, can accelerate the detrimental 'inactivity-poor cognition' cycle, is worthy of investigation. METHODS: We used data from the 2008, 2011, 2014, and 2018 waves of the Chinese Longitudinal Healthy Longevity Survey (CLHLS). We assessed the frequency of outdoor or social activities at each wave. The cognitive function was examined using a China-Modified Mini-mental State Examination. We estimated the residential exposure to fine particular matter (PM2.5) via a satellite-based model. We applied cross-lagged panel (CLP) model to examine the bi-directional relationship between outdoor or social activities and cognitive function. We then examined the effect of PM2.5 exposure with sequent cognitive function and activities using generalized estimation equation (GEE) model. FINDINGS: Overall, we observed significant bi-directional associations between outdoor or social activities and cognitive function. Participants with better cognitive function in the last wave were more likely to engage in outdoor or social activities in the following wave (outdoor activities: ß = 0.37, 95% CI [0.27,0.48], P < 0.01; social activities: ß = 0.05, 95% CI [0.02,0.09] P < 0.01). Meanwhile, higher engagement in outdoor or social activities in the last wave was associated with more favorable cognitive function in the following wave (outdoor activities: ß = 0.06, 95% CI [0.03,0.09], P < 0.01; social activities: ß = 0.10, 95% CI [0.03,0.18], P < 0.01). Notably, an increase in PM2.5 exposure during the preceding year was significantly associated with a declining cognitive function (ß = -0.05, 95% CI [-0.08,-0.03], P < 0.01), outdoor activities (ß = -0.02, 95% CI [-0.04, -0.01], P < 0.01) and social activities (ß = -0.02, 95% CI [-0.02, -0.01], P < 0.01) in the current year; the lagged effects of the PM2.5 exposure in the past year of the last wave on activities and cognitive function of the following wave were also observed. INTERPRETATION: Our findings not only indicate the bi-directional links between the frequency of outdoor or social activities and cognitive function, but also report that PM2.5 exposure plays a role in catalyzing the detrimental inactivity-poor cognition cycle. Future research should investigate whether the policy-driven interventions, such as clean air policies, can break the unfavorable activity-cognition cycle, and thereby promoting health from the dual gains in leisure activities and cognition.

Effect of L-theanine on selective attention in a traffic-related reaction task in sleep-deprived young adults: a double-blind placebo-controlled, crossover study.

BACKGROUND: L-theanine is a non-protein-forming amino acid found in tea. Limited evidence suggests that it improves selective attention. Sleep deprivation impairs attention and psychomotor reactions, affecting automobile driving. We aimed to determine whether L-theanine improves neurobehavioral measures of visual attention in acutely sleep-deprived healthy adults in a traffic-scene-based attention task. METHODS: In a double-blind, placebo-controlled, counterbalanced, two-way crossover study, we compared the effects of a 200-mg dose of L-theanine with a placebo (150 ml of distilled water) on a computerised, traffic-scene-based visual recognition reaction task in 24 healthy volunteers (age 20-25 years; 13 males) sleep-deprived overnight. The participants made speeded button-presses to imminent accident scenes (i.e. hits), while ignoring safe scenes. They were tested pre-dose and 45 min post-dose, each treatment administered one week apart. RESULTS: Hit rates were more than 90% in all sessions, and were similar in two treatments, pre- vs post-dose. L-theanine significantly reduced false alarms (i.e. responses to safe scenes) (p = 0.014) and increased A' (i.e. target-distractor discriminability) (p = 0.009), whereas placebo did not (p > 0.05). L-theanine reduced hit reaction time by 38.65 ms (p = 0.007), and placebo by 19.08 ms (p = 0.016), however reaction time changes from baseline were not significantly different between treatments (p > 0.05). CONCLUSIONS: L-theanine in high doses appears to improve selective visual attention by concurrently improving information processing speed and target-distractor discriminability in acutely sleep-deprived individuals. This is consistent with previous functional neuroimaging findings, where L-theanine suppressed distractor-processing and default-mode-network activity in visual selective attention tasks.

Virtual reality-based training may improve visual memory and some aspects of sustained attention among healthy older adults - preliminary results of a randomized controlled study.

BACKGROUND/AIMS: Older age and cognitive inactivity have been associated with cognitive impairment, which in turn is linked to economic and societal burdens due to the high costs of care, especially for care homes and informal care. Emerging non-pharmacological interventions using new technologies, such as virtual reality (VR) delivered on a head-mounted display (HMD), might offer an alternative to maintain or improve cognition. The study aimed to evaluate the efficacy and safety of a VR-based Digital Therapeutics application for improving cognitive functions among healthy older adults. METHODS: Seventy-two healthy seniors (experimental group N = 35, control group N = 37), aged 65-85 years, were recruited by the Medical University of Lodz (Poland). Participants were randomly allocated to the experimental group (a VR-based cognitive training which consists of a warm-up module and three tasks, including one-back and dual-N-back) or to the control group (a regular VR headset app only showing nature videos). The exercises are performed in different 360-degree natural environments while listening to a preferred music genre and delivered on a head-mounted display (HMD). The 12-week intervention of 12 min was delivered at least three times per week (36 sessions). Compliance and performance were followed through a web-based application. Primary outcomes included attention and working memory (CNS-Vital Signs computerized cognitive battery). Secondary outcomes comprised other cognitive domains. Mixed linear models were constructed to elucidate the difference in pre- and post-intervention measures between the experimental and control groups. RESULTS: The users performed, on average, 39.8 sessions (range 1-100), and 60% performed more than 36 sessions. The experimental group achieved higher scores in the visual memory module (B = 7.767, p = 0.011) and in the one-back continuous performance test (in terms of correct responses: B = 2.057, p = 0.003 and omission errors: B = -1.950, p = 0.007) than the control group in the post-test assessment. The results were independent of participants' sex, age, and years of education. The differences in CNS Vital Signs' global score, working memory, executive function, reaction time, processing speed, simple and complex attention, verbal memory, cognitive flexibility, motor speed, and psychomotor speed were not statistically significant. CONCLUSIONS: VR-based cognitive training may prove to be a valuable, efficacious, and well-received tool in terms of improving visual memory and some aspect of sustainability of attention among healthy older adults. This is a preliminary analysis based on part of the obtained results to that point. Final conclusions will be drawn after the analysis of the target sample size. TRIAL REGISTRATION: Clinicaltrials.gov ID NCT05369897.

Intraoperative mapping and preservation of executive functions in awake craniotomy: a systematic review.

Awake craniotomy (AC) allows intraoperative brain mapping (ioBM) for maximum lesion resection while monitoring and preserving neurological function. Conventionally, language, visuospatial assessment, and motor functions are mapped, while the assessment of executive functions (EF) is uncommon. Impaired EF may lead to occupational, personal, and social limitations, thus, a compromised quality of life. A comprehensive literature search was conducted through Scopus, Medline, and Cochrane Library using a pre-defined search strategy. Articles were selected after duplicate removal, initial screening, and full-text assessment. The demographic details, ioBM techniques, intraoperative tasks, and their assessments, the extent of resection (EOR), post-op EF and neurocognitive status, and feasibility and potential adverse effects of the procedure were reviewed. The correlations of tumor locations with intraoperative EF deficits were also assessed. A total of 13 studies with intraoperative EF assessment of 351 patients were reviewed. Awake-asleep-awake protocol was most commonly used. Most studies performed ioBM using bipolar stimulation, with a frequency of 60 Hz, pulse durations ranging 1-2 ms, and intensity ranging 2-6 mA. Cognitive function was monitored with the Stroop task, spatial-2-back test, line-bisection test, trail-making-task, and digit-span tests. All studies reported similar or better EOR in patients with ioBM for EF. When comparing the neuropsychological outcomes of patients with ioBM of EF to those without it, all studies reported significantly better EF preservation in ioBM groups. Most authors reported EF mapping as a feasible tool to obtain satisfactory outcomes. Adverse effects included intraoperative seizures which were easily controlled. AC with ioBM of EF is a safe, effective, and feasible technique that allows satisfactory EOR and improved neurocognitive outcomes with minimal adverse effects.

Is High-Intensity Interval Training More Effective Than Moderate Continuous Training in Rehabilitation of Multiple Sclerosis: A Comprehensive Systematic Review and Meta-analysis.

OBJECTIVES: The present study aimed to conduct meta-analysis to determine whether the high intensity interval training (HIIT) protocol is more beneficial in improving outcome measures compared to moderate continuous training (MCT) in people with multiple sclerosis (PwMS). It also aimed to systematically review the exercise protocols differences. DATA SOURCES: A search strategy, locating HIIT in PwMS, was executed in six databases, PubMed, EMBASE, Web of Science, Central Cochrane, Pedro, and Ovid MEDLine. STUDY SELECTION: Randomized control trials of HIIT utilizing cycle ergometer or recumbent stepper as exercise modalities were included in analysis. Intervention arms should include at least two intervention arms, including HIIT in one arm, and MCT in the other group. DATA EXTRACTION: Data extracted from each study includes the following items: basic details of the study (such as author, date of publication, location, and study design), participant characteristics (sample size, mean age, sex, mean disease duration, and extended disability status scale), specifications of the HITT protocol (exercise modality, session duration, number of intervals/session, interval intensity, recovery intensity, recovery interval, and adverse effect), as well as primary outcomes at baseline and post-intervention (cardiorespiratory fitness, fatigue, body composition, cognitive functions, and blood biomarkers). DATA SYNTHESIS: 22 studies included in the systematic review, 11 were included in random effects model pooled analysis. There was a significant effect in favor of HIIT for VO2max of cardiorespiratory functions compared to MCT (ES=0.45 95%, CI [0.14, 0.76], P=.004), and for memory domain of cognitive functions (ES=0.34 95% CI [0.05, 0.63], P=.02). Statistical significance was not achieved for the other variables. CONCLUSION: HIIT and MCT yield similar results in terms of fatigue, body composition, cognitive functions, and blood biomarkers. However, VO2max of cardiorespiratory functions and memory domain of cognitive functions were in favor of HIIT protocol.