Brain Function Research Articles

Convergent functional effects of antidepressants in major depressive disorder: a neuroimaging meta-analysis.

Neuroimaging studies have provided valuable insights into the macroscale impacts of antidepressants on brain functions in patients with major depressive disorder. However, the findings of individual studies are inconsistent. Here, we aimed to provide a quantitative synthesis of the literature to identify convergence of the reported findings at both regional and network levels and to examine their associations with neurotransmitter systems. Through a comprehensive search in PubMed and Scopus databases, we reviewed 5258 abstracts and identified 36 eligible functional neuroimaging studies on antidepressant effects in major depressive disorder. Activation likelihood estimation was used to investigate regional convergence of the reported foci of antidepressant effects, followed by functional decoding and connectivity mapping of the convergent clusters. Additionally, utilizing group-averaged data from the Human Connectome Project, we assessed convergent resting-state functional connectivity patterns of the reported foci. Next, we compared the convergent circuit with the circuits targeted by transcranial magnetic stimulation therapy. Last, we studied the association of regional and network-level convergence maps with selected neurotransmitter receptors/transporters maps. No regional convergence was found across foci of treatment-associated alterations in functional imaging. Subgroup analysis in the Treated > Untreated contrast revealed a convergent cluster in the left dorsolateral prefrontal cortex, which was associated with working memory and attention behavioral domains. Moreover, we found network-level convergence of the treatment-associated alterations in a circuit more prominent in the frontoparietal areas. This circuit was co-aligned with circuits targeted by "anti-subgenual" and "Beam F3"transcranial magnetic stimulation therapy. We observed no significant correlations between our meta-analytic findings with the maps of neurotransmitter receptors/transporters. Our findings highlight the importance of the frontoparietal network and the left dorsolateral prefrontal cortex in the therapeutic effects of antidepressants, which may relate to their role in improving executive functions and emotional processing.

Functional MRI of imprinting memory in awake newborn domestic chicks

Filial imprinting, a crucial ethological paradigm, provides insights into the neurobiology of early learning and its long-term impact on behaviour. To date, invasive techniques like autoradiography or lesions have been used to study it, limiting the exploration of whole brain networks. Recent advances in fMRI for avian brains now open new windows to explore bird’s brain functions at the network level. We developed an fMRI technique for awake, newly hatched chicks, capturing BOLD signal changes during imprinting experiments. While early memory acquisition phases are understood, long-term storage and retrieval remain unclear. Our findings identified potential long-term storage of imprinting memories across a neural network, including the hippocampal formation, the medial striatum, the arcopallium, and the prefrontal-like nidopallium caudolaterale. This paradigm opens up new avenues for exploring the broader landscape of learning and memory in neonatal vertebrates, enhancing our understanding of behaviour and brain networks.

A (sub)field guide to quality control in hippocampal subfield segmentation on high-resolution T2-weighted MRI.

Inquiries into properties of brain structure and function have progressed due to developments in magnetic resonance imaging (MRI). To sustain progress in investigating and quantifying neuroanatomical details in vivo, the reliability and validity of brain measurements are paramount. Quality control (QC) is a set of procedures for mitigating errors and ensuring the validity and reliability of brain measurements. Despite its importance, there is little guidance on best QC practices and reporting procedures. The study of hippocampal subfields in vivo is a critical case for QC because of their small size, inter-dependent boundary definitions, and common artifacts in the MRI data used for subfield measurements. We addressed this gap by surveying the broader scientific community studying hippocampal subfields on their views and approaches to QC. We received responses from 37 investigators spanning 10 countries, covering different career stages, and studying both healthy and pathological development and aging. In this sample, 81% of researchers considered QC to be very important or important, and 19% viewed it as fairly important. Despite this, only 46% of researchers reported on their QC processes in prior publications. In many instances, lack of reporting appeared due to ambiguous guidance on relevant details and guidance for reporting, rather than absence of QC. Here, we provide recommendations for correcting errors to maximize reliability and minimize bias. We also summarize threats to segmentation accuracy, review common QC methods, and make recommendations for best practices and reporting in publications. Implementing the recommended QC practices will collectively improve inferences to the larger population, as well as have implications for clinical practice and public health.

A novel classification framework for genome-wide association study of whole brain MRI images using deep learning.

Genome-wide association studies (GWASs) have been widely applied in the neuroimaging field to discover genetic variants associated with brain-related traits. So far, almost all GWASs conducted in neuroimaging genetics are performed on univariate quantitative features summarized from brain images. On the other hand, powerful deep learning technologies have dramatically improved our ability to classify images. In this study, we proposed and implemented a novel machine learning strategy for systematically identifying genetic variants that lead to detectable nuances on Magnetic Resonance Images (MRI). For a specific single nucleotide polymorphism (SNP), if MRI images labeled by genotypes of this SNP can be reliably distinguished using machine learning, we then hypothesized that this SNP is likely to be associated with brain anatomy or function which is manifested in MRI brain images. We applied this strategy to a catalog of MRI image and genotype data collected by the Alzheimer's Disease Neuroimaging Initiative (ADNI) consortium. From the results, we identified novel variants that show strong association to brain phenotypes.

APPLICATION OF COMPUTERISED TECHNOLOGIES IN THE REHABILITATION OF PATIENTS WITH STROKE CONSEQUENCES

A stroke is a sudden onset of focal or generalized impairment of brain function due to vascular causes only, which is related to cerebral blood flow and lasts for more than 24 hours. Cerebral stroke remains the second leading cause of death and the third most significant cause of disability in the world. Over the past 30 years, the absolute number of cases of this disease has increased by 70%, the prevalence by 85%, with a 43% increase in mortality rates. According to the latest Global Burden of Disease (GBD) analysis, in 2019, there were about 12.2 million stroke cases, 143 million disability-adjusted life years and 6.6 million deaths worldwide, 86% of which occurred in low- and lower-middle-income countries. Purpose to analyse and systematise the use of computerised technologies in the rehabilitation of patients with stroke consequences. Materials and methods. To achieve the objectives of the research, the researchers analysed scientific literature and systematised information using electronic databases such as PubMed, Google Scholar and others. Research results. Traditional methods have proven their effectiveness and are widely used in the practice of rehabilitating patients after stroke. However, with the development of science and technology, there is a need to find new approaches to therapy that can provide a more comprehensive and effective treatment of this pathology. Today, computerized technologies deserve special attention in the rehabilitation of patients after stroke, namely robotic systems, specially designed video games and virtual reality, and TV rehabilitation. Robotic systems are devices that automate various tasks and processes. They can be programmed to perform certain functions with high accuracy and repeatability. In rehabilitation, such systems help to restore motor functions, support physical activity, and facilitate recovery from injuries or illnesses, including stroke. Video games and virtual reality technologies are examples of exciting and fun rehabilitation for stroke patients. Traditional therapies can be complex and tedious to repeat, making it less likely that patients will do them at home. Physical therapists are finding that video games are more engaging and easier to incorporate into home treatment regimens. Tele-rehabilitation after stroke is a form of remote medical care that allows patients to receive rehabilitation services via the Internet or other telecommunication technologies. This provides access to the necessary therapy regardless of the patient's place of residence. Conclusions. Computerized technology significantly improves the rehabilitation of patients with stroke. Robotic systems provide high precision and control during movements, which avoids incorrect exercise and reduces the risk of re-injury, regularity of training, and patient comfort. In addition, many robotic systems have built-in sensors that allow you to track the patient's progress and provide feedback to both the patient and the doctor. This helps to adjust the rehabilitation programme according to the patient's needs. The use of video games and virtual reality in stroke rehabilitation offers numerous benefits, including increased motivation, improved motor and cognitive function, psychological support, and social interaction. Tele-rehabilitation after stroke is an innovative approach to patient recovery, providing access to rehabilitation services regardless of where they live.

Adverse childhood experiences, brain function, and psychiatric diagnoses in a large adult clinical cohort.

Adverse childhood experiences (ACEs) are linked to higher rates of psychiatric disorders in adults. Previous neuroimaging studies with small samples have shown associations between ACEs and alterations in brain volume, connectivity, and blood flow. However, no study has explored these associations in a large clinical population to identify brain regions that may mediate the relationship between ACEs and psychiatric diagnoses. This study aims to evaluate how patient-reported ACEs are associated with brain function in adults, across diagnoses. We analyzed 7,275 adults using HMPAO SPECT scans at rest and during a continuous performance task (CPT). We assessed the impact of ACEs on brain function across psychiatric diagnoses and performed mediation analyses where brain functional regions of interest acted as mediators between patient-reported ACEs and specific psychiatric diagnoses. We further evaluated the risk of being diagnosed with specific classes of mental illnesses as a function of increasing ACEs and identified which specific ACE questions were statistically related to each diagnosis in this cohort. Increased ACEs were associated with higher activity in cognitive control and default mode networks and decreased activity in the dorsal striatum and cerebellum. Higher ACEs increased the risk of anxiety-related disorders, substance abuse, and depression. Several brain regions were identified as potential mediators between ACEs and adult psychiatric diagnoses. This study, utilizing a large clinical cohort, provides new insights into the neurobiological mechanisms linking ACEs to adult psychiatric conditions. The findings suggest that specific brain regions mediate the effects of ACEs on the risk of developing mental health disorders, highlighting potential targets for therapeutic interventions.

Unique Glycans in Synaptic Glycoproteins in Mouse Brain.

The synapse is an essential connection between neuronal cells in which the membrane and secreted glycoproteins regulate neurotransmission. The post-translational modifications of glycoproteins with carbohydrates, although essential for their functions as well as their specific localization, are not well understood. Oddly, whereas galactose addition to glycoproteins is required for neuronal functions, galactosylation is severely restricted for Asn-linked on N-glycans in the brain, and genetic evidence highlights the important roles of galactose in brain functions and development. To explore this novel glycosylation, we exploited an orthogonal technology in which a biotinylated sialic acid derivative (CMP-biotin-Sia) is transferred to terminally galactosylated proteins by a recombinant sialyltransferase (rST6Gal1). This approach allowed us to identify the carrier proteins as well as their localization on brain sections. Immunohistochemical analysis of the biotinylated glycoproteins in brain sections demonstrates that they are largely positioned in the pre- and postsynaptic membranes. Consistent with this positioning, glycoproteomic analyses of the labeled glycoproteins identified a number of them that are involved in synaptic function, cell adhesion, and extracellular matrix interactions. The discovery of these galactosylated N-glycoproteins and their relative confinement to synapses provide novel insights into the unusual and specific nature of protein glycosylation in the brain.

Sex Differences in Hierarchical and Modular Organization of Functional Brain Networks: Insights from Hierarchical Entropy and Modularity Analysis.

Existing studies have demonstrated significant sex differences in the neural mechanisms of daily life and neuropsychiatric disorders. The hierarchical organization of the functional brain network is a critical feature for assessing these neural mechanisms. But the sex differences in hierarchical organization have not been fully investigated. Here, we explore whether the hierarchical structure of the brain network differs between females and males using resting-state fMRI data. We measure the hierarchical entropy and the maximum modularity of each individual, and identify a significant negative correlation between the complexity of hierarchy and modularity in brain networks. At the mean level, females show higher modularity, whereas males exhibit a more complex hierarchy. At the consensus level, we use a co-classification matrix to perform a detailed investigation of the differences in the hierarchical organization between sexes and observe that the female group and the male group exhibit different interaction patterns of brain regions in the dorsal attention network (DAN) and visual network (VIN). Our findings suggest that the brains of females and males employ different network topologies to carry out brain functions. In addition, the negative correlation between hierarchy and modularity implies a need to balance the complexity in the hierarchical organization of the brain network, which sheds light on future studies of brain functions.

Disturbances of Interoception in Schizophrenia – Focus on Neuroimaging

Abstract: The current paper presents the most recent theoretical understanding of interoception (INTC) in light of the predictive processing framework and the Embodied Predictive Interoceptive Coding model and reviews recent experimental data on different interoceptive disturbances in schizophrenia (SCZ) such as lower interoceptive accuracy, nociceptive dysfunction reflected by reduced pain sensitivity, disturbed thermoregulation, impaired gastrointestinal regulation, cardiovascular and respiratory dysfunction, and immune disturbances. The immense clinical implications of these disturbances are discussed in the context of the high rates of morbidity and mortality in SCZ related to suicide and cardiac death. Next, the potential of INTC-related treatments is reviewed, and conclusions are made on the evidence for the use of vagus nerve stimulation, mindfulness-based interventions, and exercise therapy. The neuroimaging perspective is given in a brief account of the INTC-related findings in healthy individuals suggesting the right anterior insula and anterior cingulate cortex as key brain areas for interoceptive awareness, accuracy, and sensibility, by supporting higher-order representation and integration of visceral, and somatosensory interoception with exteroceptive information. In SCZ, on the other hand, neuroimaging research on specific interoceptive abilities is lacking but indirect evidence points to disrupted activation of major INTC network hubs. There is converging evidence of changes in these hubs in terms of both structure and function (volume reductions, aberrant activation, and connectivity). This narrative review identifies several gaps in contemporary INTC-related research in SCZ that need to be addressed in future experimental and clinical studies to elucidate the exact nature of the disturbances of interoceptive abilities in modalities other than cardioception; the interactions between different interoceptive modalities; the association between interoceptive abilities and other mental functions (such as emotion recognition and regulation, decision making, learning, memory, etc.); the efficacy of nonpharmacological and pharmacological INTC-based interventions; and the relation of disturbed interoceptive abilities with brain structure and function.

Impact of obesity on allergic respiratory diseases and on mental and cognitive performance

Summary Background Obesity and allergies are among the most common diseases of our civilization. Given the simultaneous rise in the prevalence of these diseases in recent years, a potential causal link between the two has been proposed. In particular, obese patients are at an increased risk of developing bronchial asthma, likely due to mechanical restrictions but also to metabolic changes that adversely affect immune function. Neuroscience studies have also shown that obesity can lead to impaired brain function and mental health. In the following review, we will take a closer look at our studies that focus on the influence of obesity on allergic diseases and cognitive performance. Results Both human studies and animal models (mice) have shown that obesity leads to increased allergic responses in the airways. Our studies in a mouse model of obesity confirm that an obese phenotype is associated with increased allergic sensitization and manifestation. These changes are associated with significant shifts in the composition of the gut microbial flora. The microbiome changes are further associated with allergic airway inflammation and an increased incidence of T helper 1 (Th1) type pulmonary macrophages. Interestingly, despite the changes in the microbiome, it is possible to effectively prevent allergy development by inducing oral tolerance. Furthermore, it was observed that obese mice show increased signs of anxiety and depression, as well as reduced cognitive performance. Conclusion Obesity is a complex metabolic disease that significantly impacts our body’s gut microbiome and immune system, resulting in an increased incidence of allergic asthma and neurological/psychological changes. Attention should be given to both the prophylactic and therapeutic measures to mitigate the impact of obesity, including oral tolerance for managing existing allergic diseases.

Intestinal endogenous metabolites affect neuroinflammation in 5×FAD mice by mediating “gut-brain” axis and the intervention with Chinese Medicine

BackgroundEmerging evidence suggested the association between gut dysbiosis and Alzheimer’s disease (AD) progression. However, it remained unclear how the gut microbiome and neuroinflammation in the brain mutually interact or how these interactions affect brain functioning and cognition. Here we hypothesized that “gut-brain” axis mediated by microbial derived metabolites was expected to novel breakthroughs in the fields of AD research and development.MethodsMultiple technologies, such as immunofluorescence, 16s rDNA sequencing, mass spectrometry-based metabolomics (LC-QQQ-MS and GC-MS), were used to reveal potential link between gut microbiota and the metabolism and cognition of the host.ResultsMicrobial depletion induced by the antibiotics mix (ABX) verified that “gut-brain” can transmit information bidirectionally. Short-chain fatty acid-producing (SCFAs-producing) bacteria and amino acid-producing bacteria fluctuated greatly in 5×FAD mice, especially the reduction sharply of the Bifidobacteriaceae and the increase of the Lachnospiraceae family. Concentrations of several Tryptophan-kynurenine intermediates, lactic acid, CD4+ cell, and CD8+ cells were higher in serum of 5×FAD mice, whilst TCA cycle intermediates and Th1/Th2 were lower. In addition, the levels of iso-butyric acid (IBA) in feces, serum, and brain of 5×FAD mice were increased compared with WT-M mice, especially in serum. And IBA in the brain was positively correlated with Aβ and proinflammatory factors.ConclusionTogether, our finding highlighted that the alternation in gut microbiota affected the effective communication between the “gut-brain” axis in 5×FAD mice by regulating the immune system, carbohydrate, and energy metabolism.

Translational research on cognitive impairment in chronic kidney disease.

Cognitive decline is common in patients with acute or chronic kidney disease. Several areas of brain function can be affected, including short and long-term memory, attention and inhibitory control, sleep, mood, eating control and motor function. Cognitive decline in kidney disease shares risk factors with cognitive dysfunction in people without kidney disease, such as diabetes, high blood pressure, sedentary lifestyle and unhealthy diet. However, additional kidney-specific risk factors may contribute, such as uremic toxins, electrolyte imbalances, chronic inflammation, acid-base disorders or endocrine dysregulation. Traditional and kidney-specific risk factors may interact to cause damage to the blood-brain barrier, induce vascular damage in the brain, and cause neurotoxicity or neuroinflammation. Here, we discuss recent insights into the pathomechanisms of cognitive decline from animal models and novel avenues for prevention and therapy. We focus on a several areas that influence cognition: blood-brain barrier disruption, the role of skeletal muscle, physical activity and the endocrine factor irisin, and the emerging therapeutic role of sodium-glucose transporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists. Taken together, these studies demonstrate the importance of animal models in providing a mechanistic understanding of this complex condition and their potential to explain the mechanisms of novel therapies.

Comparison of whole-brain task-modulated functional connectivity methods for fMRI task connectomics.

Higher brain functions require flexible integration of information across widely distributed brain regions depending on the task context. Resting-state functional magnetic resonance imaging (fMRI) has provided substantial insight into large-scale intrinsic brain network organisation, yet the principles of rapid context-dependent reconfiguration of that intrinsic network organisation are much less understood. A major challenge for task connectome mapping is the absence of a gold standard for deriving whole-brain task-modulated functional connectivity matrices. Here, we perform biophysically realistic simulations to control the ground-truth task-modulated functional connectivity over a wide range of experimental settings. We reveal the best-performing methods for different types of task designs and their fundamental limitations. Importantly, we demonstrate that rapid (100 ms) modulations of oscillatory neuronal synchronisation can be recovered from sluggish haemodynamic fluctuations even at typically low fMRI temporal resolution (2 s). Finally, we provide practical recommendations on task design and statistical analysis to foster task connectome mapping.

How Can Near‐Infrared Spectroscopy (NIRS) Help Understanding of the Psychotherapy Process? A Scoping Review of Therapeutic Interactions

AbstractIn recent years, near‐infrared spectroscopy (NIRS) has garnered significant attention for its potential clinical applications as a non‐invasive and straightforward method for measuring brain functions. While NIRS has become useful in psychiatric contexts by aiding in the differential diagnosis of depression, its application in clinical psychology is still developing. Due to its ecological validity, which allows for measurements in natural settings, NIRS shows promise in revealing the dynamic elements of the psychotherapy process. In this study, we conducted a scoping literature review of the use of NIRS in psychotherapeutic interactions, exploring its potential to unveil the complexities of psychotherapy settings involving interpersonal interactions. Employing a scoping review approach, we systematically searched the PubMed, PsycINFO, and Web of Science databases for articles published through October 19, 2023 about studies using NIRS as a measurement instrument: This yielded various therapeutic interactions. Of the 155 retrieved results that remained after the initial screening, seven met the inclusion criteria. Of these, six studies examined the synchronization of brain functions through the simultaneous brain activity measurements (hyperscanning) of two participants. The review revealed that, despite the anticipated potential of NIRS, it has become evident there is a dearth of research focusing on interactions during psychotherapy. Furthermore, the few available studies have not explored changes in line with the progression of psychotherapeutic interactions. Consequently, future studies should address whether NIRS can effectively assess alterations in brain function resulting from micro‐level events, such as the therapeutic interaction between therapists and clients during psychotherapy.

The different impacts of pain-related negative emotion and trait negative emotion on brain function in patients with inflammatory bowel disease

Inflammatory bowel diseases (IBD) are a group of chronic, non-specific intestinal diseases that could comorbid with varieties of negative emotional constructs, including pain-related negative emotions and trait negative emotions; however, the link between brain functions and different dimensions of negative emotions remains largely unknown. Ninety-eight patients with IBD and forty-six healthy subjects were scanned using a 3.0-T functional magnetic resonance imaging scanner. The amplitudes of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality (DC) were used to assess resting-state brain activity. Partial least squares (PLS) correlation was employed to assess the relationship among abnormal brain activities, pain-related and trait negative emotions. Compared to controls, patients with IBD exhibited higher values of ALFF in the right anterior cingulate cortex (ACC), lower values of ALFF in the left postcentral gyrus, and higher values of DC in the bilateral ACC. Multivariate PLS correlation analysis revealed the brain scores of the ACC were correlated with pain-related negative emotions, the brain salience in the left postcentral gyrus was associated with the higher-order trait depression. These findings can enhance our comprehension of how pain-related negative emotion and trait negative emotion affect the brains of patients with IBD in distinct ways.

Differential Resting-State Brain Characteristics of Skeleton Athletes and Non-Athletes: A Preliminary Resting-State fMRI Study.

(1) Background: This study investigates the resting-state brain characteristics of skeleton athletes compared to healthy age-matched non-athletes, using resting-state fMRI to investigate long-term skeleton-training-related changes in the brain. (2) Methods: Eleven skeleton athletes and twenty-three matched novices with no prior experience with skeleton were recruited. Amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity analyses were explored to investigate resting-state functional magnetic resonance imaging (rs-fMRI) data, aiming to elucidate differences in resting-state brain function between the two groups. (3) Results: Compared to the control group, skeleton athletes exhibited significantly higher ALFF in the left fusiform, left inferior temporal gyrus, right inferior frontal gyrus, left middle temporal gyrus, left and right insula, left Rolandic operculum, left inferior frontal gyrus, and left superior temporal gyrus. Skeleton athletes exhibit stronger functional connectivity in brain regions associated with cognitive and motor control (superior frontal gyrus, insula), as well as those related to reward learning (putamen), visual processing (precuneus), spatial cognition (inferior parietal), and emotional processing (amygdala), during resting-state brain function. (4) Conclusions: The study contributes to understanding how motor training history shapes skeleton athletes' brains, which have distinct neural characteristics compared to the control population, indicating potential adaptations in brain function related to their specialized training and expertise in the sport.

Mitochondrial Dysfunction as a Potential Mechanism Mediating Cardiac Comorbidities in Parkinson’s Disease

Individuals diagnosed with Parkinson’s disease (PD) often exhibit heightened susceptibility to cardiac dysfunction, reflecting a complex interaction between these conditions. The involvement of mitochondrial dysfunction in the development and progression of cardiac dysfunction and PD suggests a plausible commonality in some aspects of their molecular pathogenesis, potentially contributing to the prevalence of cardiac issues in PD. Mitochondria, crucial organelles responsible for energy production and cellular regulation, play important roles in tissues with high energetic demands, such as neurons and cardiac cells. Mitochondrial dysfunction can occur in different and non-mutually exclusive ways; however, some mechanisms include alterations in mitochondrial dynamics, compromised bioenergetics, biogenesis deficits, oxidative stress, impaired mitophagy, and disrupted calcium balance. It is plausible that these factors contribute to the increased prevalence of cardiac dysfunction in PD, suggesting mitochondrial health as a potential target for therapeutic intervention. This review provides an overview of the physiological mechanisms underlying mitochondrial quality control systems. It summarises the diverse roles of mitochondria in brain and heart function, highlighting shared pathways potentially exhibiting dysfunction and driving cardiac comorbidities in PD. By highlighting strategies to mitigate dysfunction associated with mitochondrial impairment in cardiac and neural tissues, our review aims to provide new perspectives on therapeutic approaches.

Impact of Heavy Metals on Alzheimer Disease, Using Artificial Intelligence

There is no doubt that Alzheimer disease (AD) is one of the most deadly and expensive diseases in the world today. It accounts for the majority of patients with dementia. The disease is caused by a combination of environmental and genetic factors, and identifying effective environmental factors can play a significant role in controlling and preventing this disease. Heavy metals (HMs) can be ingested, inhaled, or absorbed through the skin by the human body. As a result of HM accumulation in the body, many organs, including the nervous system, are adversely affected. Accordingly, memory, cognition, and learning functions may be negatively affected. In recent years, there has been considerable interest in the effect of HMs on AD, and several studies have examined how HMs affect brain function and AD. During this study, we will review these studies and examine how HMs may influence AD development. As a result of the limitations of traditional methods in identifying HM toxicity, this study discusses artificial intelligence (AI) and its advantages and limitations as a tool for determining HMs associated with AD.

Role of ACSBG1 in Brain Lipid Metabolism and X-Linked Adrenoleukodystrophy Pathogenesis: Insights from a Knockout Mouse Model.

"Bubblegum" acyl-CoA synthetase (ACSBG1) is a pivotal player in lipid metabolism during mouse brain development, facilitating the activation of long-chain fatty acids (LCFA) and their incorporation into lipid species that are crucial for brain function. ACSBG1 converts LCFA into acyl-CoA derivatives, supporting vital metabolic processes. Fruit fly mutants lacking ACSBG1 exhibited neurodegeneration and had elevated levels of very long-chain fatty acids (VLCFA), characteristics of human X-linked adrenoleukodystrophy (XALD). To explore ACSBG1's function and potential as a therapeutic target in XALD, we created an ACSBG1 knockout (Acsbg1-/-) mouse and examined the effects on brain FA metabolism during development. Phenotypically, Acsbg1-/- mice resembled wild type (w.t.) mice. ACSBG1 expression was found mainly in tissue affected pathologically in XALD, namely the brain, adrenal gland and testis. ACSBG1 depletion did not significantly reduce the total ACS enzyme activity in these tissue types. In adult mouse brain, ACSBG1 expression was highest in the cerebellum; the low levels detected during the first week of life dramatically increased thereafter. Unexpectedly, lower, rather than higher, saturated VLCFA levels were found in cerebella from Acsbg1-/- vs. w.t. mice, especially after one week of age. Developmental changes in monounsaturated ω9 FA and polyunsaturated ω3 FA levels also differed between w.t. and Acsbg1-/- mice. ACSBG1 deficiency impacted the developmental expression of several cerebellar FA metabolism enzymes, including those required for the synthesis of ω3 polyunsaturated FA, precursors of bioactive signaling molecules like eicosanoids and docosanoids. These changes in membrane lipid FA composition likely affect membrane fluidity and may thus influence the body's response to inflammation. We conclude that, despite compelling circumstantial evidence, it is unlikely that ACSBG1 directly contributes to the pathology of XALD, decreasing its potential as a therapeutic target. Instead, the effects of ACSBG1 knockout on processes regulated by eicosanoids and/or docosanoids should be further investigated.

Predictive Representations: Building Blocks of Intelligence.

Adaptive behavior often requires predicting future events. The theory of reinforcement learning prescribes what kinds of predictive representations are useful and how to compute them. This review integrates these theoretical ideas with work on cognition and neuroscience. We pay special attention to the successor representation and its generalizations, which have been widely applied as both engineering tools and models of brain function. This convergence suggests that particular kinds of predictive representations may function as versatile building blocks of intelligence.