搜索结果：Behavioural brain research

Repetitive behaviour, resulting from impaired inhibitory control and error monitoring, represents a core manifestation of autism, with a poorly understood neural basis. Our primary hypothesis was that a striatum-midbrain framework could provide a theoretical basis for understanding neural changes underlying response inhibition in autism. This conceptual approach considered two critical neurobehavioural factors: (a) inhibition as a dynamic process requiring trial-and-error learning, and (b) efficient error learning relying on the striatum receiving dopaminergic signals from the midbrain-a framework analogous to an 'actor-critic' architecture. Eighteen adults with a diagnosis of autism spectrum disorder and 21 age-matched healthy controls performed a stop-signal task adjusted for functional MRI (fMRI). To dissect domain-dependent correlates of neural inhibition, we measured brain activation and connectivity as a function of task phases in the dorsal striatum and dopaminergic midbrain nuclei. Repetitive behaviour severity was assessed using the observer-reported Repetitive Behaviours Scale-Revised. A striking hypoactivation in the midbrain during failed inhibition events was observed in relation with the severity of repetitive behaviours. We also identified, in the autism group, reduced functional connectivity between the midbrain-striatum hubs and regions involved in cognitive control (prefrontal cortex) and error monitoring (bilateral insula), during response preparation periods. Finally, although both groups achieved similar final performance levels, neurodivergent subjects learned slower and displayed delayed striatal engagement when behavioural adjustment was required. These results reveal a novel autism profile characterized by midbrain hypoactivation mediating repetitive behaviour manifestations and reduced long-range mesocortical hypoconnectivity during inhibitory response preparation phases. Accordingly, we suggest that individuals with autism exhibit midbrain-dependent reduced motivational arousal, limiting their ability to develop proactive strategies for trial-and-error learning and regulate out-of-context behaviours. By highlighting the key role of dopaminergic midbrain structures and related long-range pathways, we challenge the view autism as solely a cortical dysfunction condition and provide evidence for promising targets for neurobiologically-driven interventions based on dopaminergic mechanisms.

Chemotherapy-induced cognitive impairment, widely known as chemobrain, has emerged as a pressing concern as cancer incidence and treatment success continue to rise worldwide. Patients frequently report persistent deficits in memory, attention, affective regulation, and executive function, which significantly diminish quality of life. While early explanations emphasized psychological causes, evidence now supports a biological basis involving oxidative stress, neuroinflammation, synaptic alterations, and blood-brain barrier disruption. Yet, the precise molecular mechanisms remain incompletely understood, in part due to methodological limitations of conventional neuroscience approaches. Recent advances in multi-omics technologies have opened new avenues to dissect the complexity of chemobrain at genomic, transcriptomic, proteomic, metabolomic, and lipidomic levels. Studies employing both untargeted discovery workflows and targeted validation strategies have revealed convergent disruptions in mitochondrial function, neurotransmitter pathways, and inflammatory signaling, despite differences across chemotherapeutic agents. Integrative analyses further highlight how these molecular perturbations align with behavioural deficits observed in preclinical and clinical settings. This review synthesizes current multi-omics evidence, emphasizing not only the shared downstream neurotoxic pathways across diverse chemotherapies but also the variability introduced by experimental design, tissue selection, and validation practices. Importantly, multi-omics profiling underscores the need for combination neuroprotective strategies, as chemotherapy-induced cognitive impairment arises from intertwined molecular insults rather than a single pathway. By consolidating mechanistic insights from multi-omics, this review aims to inform biomarker discovery, therapeutic innovation, and ultimately the development of precision strategies to mitigate the burden of chemobrain in cancer survivors.

Background/Goals: Traumatic brain injury (TBI) is increasingly recognised as an important risk factor for delayed neurodegeneration and has been implicated in the modulation of Alzheimer's disease (AD)-related amyloid pathology. However, experimental evidence remains equivocal, suggesting that the effects of TBI on amyloidogenesis are context-dependent and influenced by factors including disease stage, injury severity, and the pre-existing neurodegenerative background. This study aimed to comprehensively assess the effects of TBI on cognitive function, synuclein-family gene expression, neuroinflammatory gene expression and amyloid plaque morphology in APPswe/PS1dE9/Blg mice. Methods: Wild-type and APP/PS1 mice were assigned to four experimental groups: WT, WT-TBI, APP/PS1 and APP/PS1-TBI. TBI was induced at 6 months of age using a controlled cortical impact device (precision impactor). Behavioural assessments were conducted at two post-injury time points to evaluate locomotor activity, object recognition memory, short-term spatial memory and spatial learning. Cortex and hippocampus samples were analysed by qRT-PCR to evaluate synuclein-family gene expression and neuroinflammation-related markers. Amyloid plaque pathology was evaluated in Congo red-stained brain sections using QuPath-based image analysis. Results: TBI did not induce a consistent increase in amyloid plaque burden in APP/PS1 mice. Instead, TBI was associated with changes in plaque-size distribution, particularly at the later post-injury time point. Behavioural assessments revealed early trauma-associated cognitive impairmen; whereas, impairments observed at later stages appeared to be driven predominantly by progression of the APP/PS1 phenotype. Gene expression analysis revealed region- and genotype-dependent alterations in synuclein-family transcripts and inflammatory markers with the most pronounced changes observed in the cortex. Conclusions: These findings indicate that TBI does not uniformly accelerate β-amyloid deposition in APP/PS1 mice with established amyloid pathology. Rather, TBI appears to modify the temporal progression and morphological characteristics of amyloid pathology while interacting with genotype-dependent transcriptional responses involving synuclein-family genes and neuroinflammatory pathways. These results highlight the complex interplay between traumatic injury and pre-existing neurodegenerative processes and warrant further studies at the protein-level and over extended follow-up periods to elucidate the underlying mechanisms.

Studying the transcriptional changes in the brain following sleep deprivation has provided insight into the molecular mechanisms that differ between sleep and wake. Individual studies are limited in their ability to detect differentially expressed genes due to small sample size. Here we performed a meta-analysis of published brain expression data, totalling 173 microarrays across 245 mice. 498 genes were identified as significantly changing with sleep-deprivation at q&#x202f;<&#x202f;0.01, 96 of which were previously identified by the original studies. Of the remaining 402 novel candidate sleep genes, 14 were associated with human sleep traits and 3 with sleep phenotypes in knockout mice. Candidate gene validation showed significant upregulation of Rasd1 (Dexras1) following sleep deprivation, and phenotyping of Rasd1 KO mice revealed changes in the amount and distribution of behavioural sleep duration and sleep bout structure. These results provide a greater understanding of the molecular correlates of sleep and provide a resource for the sleep research community.

The gut microbiota has emerged as a key regulator of central nervous system development and function. Accumulating experimental and clinical evidence demonstrates that microbial signals influence brain activity through integrated neural, immune, neuroendocrine, and metabolic pathways. These pathways converge on core mechanisms of synaptic plasticity, including neurotrophic signaling, glutamatergic transmission, dendritic remodeling, and adult neurogenesis, thereby shaping learning, memory, executive function, and emotional regulation. Disruption of microbiota-brain communication is implicated in a range of neurodevelopmental and neurodegenerative disorders, including autism spectrum disorder (ASD), major depressive disorder (MDD), Alzheimer's disease (AD), and Parkinson's disease (PD), suggesting shared systems-level vulnerabilities across conditions and highlighting the translational potential of microbiota-targeted interventions such as probiotics, dietary modulation, postbiotics, and precision microbiome-based strategies. Overall, the gut microbiota functions as a dynamic regulator of brain plasticity and cognitive resilience across the lifespan. Future progress will require identification of causal mechanisms at the level of specific microbial metabolites, neural circuits, and developmental windows using integrated multi-omics and spatially resolved approaches, alongside translation into targeted therapeutic strategies.

Perfluorobutane sulfonate (PFBS) is a widely used short-chain per- and polyfluoroalkyl substance (PFAS) associated with neurodevelopmental disturbances, yet the underlying maternal-fetal mechanisms remain poorly understood. Herein, a gestational PFBS exposure rat model (0, 5, or 50&#x202f;mg/kg) was established to assess placental alterations, offspring behavioral outcomes, and the molecular pathways linking placental dysfunction to neurodevelopmental effects. Prenatal PFBS exposure induced anxiety-like behaviors in offspring, as evidenced by reduced central area exploration (50&#x202f;mg/kg) in the open field test and decreased open-arm time (5 and 50&#x202f;mg/kg) in the elevated plus maze, without affecting general locomotion. At 50&#x202f;mg/kg, PFBS caused histological damage on the maternal side of the placenta, characterized by cellular necrosis and intranuclear vacuolization, along with downregulation of monocarboxylate transporter 1 (MCT1) in the labyrinth zone, indicating impaired placental nutrient transport. Multi-omics analyses revealed disrupted placental transcriptomic and metabolomic profiles, particularly involving downregulation of PI3K-Akt signaling pathway genes and enrichment of neurodevelopment-related pathways. Integrative analysis revealed that decreased placental levels of acetylcholine chloride and N-carbamoylputrescine were positively correlated with anxiety-like behavior in offspring. Protein validation confirmed reduced PI3K and p-AKT expression in offspring brains, supporting involvement of PI3K-Akt signaling in placenta-brain crosstalk. Collectively, these findings suggest that prenatal PFBS exposure is associated with placental PI3K-Akt signaling disruption, altered placental metabolic profiles, and anxiety-like behavior in offspring. These results identify placental molecular and metabolic alterations as potential pathways linking prenatal PFBS exposure to neurodevelopmental outcomes and highlight the importance of incorporating placental assessments into developmental toxicity evaluations of PFAS compounds.

Among myrmecophilous insects, beetles represent the most specialised and diverse group. Myrmecophily is a complex evolutionary strategy encompassing a wide spectrum of interactions with ants, ranging from occasional to obligate relationships, and from mutualistic associations (e.g., trophobionts) to fully parasitic symbioses (social parasites). One of the most remarkable examples of an obligate ant parasite is Paussus favieri Fairmaire,1851 (Carabidae, Paussinae, Paussini), a West-Mediterranean ant-nest beetle. This species spends most of its life inside the nests of Pheidole pallidula (Nylander, 1849) (Hymenoptera, Formicidae), where it exploits the colony's most valuable resources (ant larvae, pupae, and tenerals) through a suite of sophisticated chemical and structural adaptations that allow it to evade detection and integrate seamlessly into the host colony. For these reasons, P. favieri has recently emerged as a key model organism for studying host-parasite interactions in eusocial systems. In this study, we investigated possible correlations between the nervous system of P. favieri and its remarkable morphological and behavioural adaptations, shedding light on how an extreme environment such as the ant nest may have shaped the beetle's brain. Our results, although requiring more in-depth analysis, reveal an exceptional development of the central body and the antennal lobes, which rank among the largest recorded across all insect species studied to date. We also report two previously undescribed morphological asymmetries affecting the optic lobes and mushroom bodies. Together, these findings provide new insights into the neuroanatomy of carabid beetles and, more broadly, into the biology of a unique model of ant parasitism, advancing our understanding of the evolutionary adaptations that characterise the highly specialised Paussinae subfamily, laying down the basis for further analysis.

Falls are a common and debilitating feature of Parkinson's Disease (PD) patients. Prefrontal acetylcholine (ACh) deficits, as well as nigrostriatal dopamine deficits, are implicated in vulnerability to falls. PD patients with loss of cortical ACh and associated cognitive dysfunction experience a higher rate of falls than PD patients without cortical ACh loss. In addition, chemogenetic inhibition of basal forebrain (BF) neurons in rats increases the vulnerability to falls on a balance beam task. Here, the impact of transient optogenetic inhibition specifically of BF cholinergic neurons was assessed in rats with dorsomedial striatal dopamine lesions during traversal of straight or zig-zag balance beams using the Michigan Complex Movement Control Task (MCMCT). Adding transient optogenetic inhibition of BF cholinergic neurons with striatal dopamine lesions elevated falls above the level produced by striatal dopamine lesions or BF ACh inhibition alone, especially on the challenging zig-zag task. These results support the critical role of BF-cortical cholinergic circuits in alleviating vulnerability to falls in PD patients with striatal dopamine loss, suggesting that it is combined loss of BF cholinergic activity and striatal dopamine that leads to greatest vulnerability to falls and related complex movement impairments.

A major subpopulation of 5-hydroxytryptamine (5-HT) neurons expresses the vesicular glutamate transporter 3 (VGLUT3) allowing the co-release of glutamate. Previous evidence has implicated VGLUT3 in 5-HT neurons in mechanisms of anxiety and reward. Here we examined mice with a genetic loss of VGLUT3 targeted to 5-HT neurons (VGLUT3 cKO5-HT) and littermate controls in a battery of behavioural tests, including paradigms assessing levels of anxiety and learning with appetitive rewards. Compared to littermate controls, VGLUT3 cKO5-HT mice displayed no evidence of altered anxiety-like behaviour in the elevated plus maze, light/dark box, marble burying and social interaction tests. However, VGLUT3 cKO5-HT mice showed reduced preference for low (but not high) sucrose-containing solution and reduced correct responses in an appetitively motivated spatial reference memory task. Similarly, in an appetitively motivated operant task, VGLUT3 cKO5-HT mice displayed evidence of reduced responding to cues associated with reward. These effects appeared specific in that VGLUT3 cKO5-HT mice did not differ from controls in terms of home cage food consumption, performance in a spatial novelty preference test, as well as contextual and cued fear memory tests. These findings support a role for VGLUT3 in 5-HT neurons in some aspects of learning, here in association with learning for reward, although not anxiety-like behaviour.

Alzheimer's Disease (AD) is neurodegenerative disorder characterized by deposition of A&#x3b2; plaques, tau-positive neurofibrillary tangles, neuroinflammation and clinical dementia. Epidemiological and experimental evidence suggest that peripheral immune inflammation is a risk factor for age-related neurodegeneration but whether its sustained activation is sufficient to drive behavioural, molecular and cellular changes consistent with AD-associated neurodegenerative vulnerability remains unclear. Here we investigated whether prenatal immune stimulation followed by an adult systemic re-challenge with Polyinosinic-polycytidylic acid (Poly(I:C)) induces persistent cognitive/motivational/social deficits and hippocampal neurodegeneration in wild-type mice, consistent with long-lasting neuroimmune priming mechanism(s). Pregnant C57Bl/6J dams received intravenously Poly(I:C) at gestational day 17 and male offspring received intraperitoneal Poly(I:C) at 9 months (single- or double-hit design) and were analyzed at 12 months. Recognition memory, working memory, reward-related learning, and social interaction were assessed followed by hippocampal Western blotting and immunofluorescence. Poly(I:C)-exposed mice exhibited impaired recognition and working memory, reduced palatable food-induced conditioned place preference, and blunted social investigation. These behavioral abnormalities were accompanied by increased amyloidogenic APP processing (BACE1/PSEN1 upregulation and &#x3b2;-CTF accumulation), tau dysregulation (AT8 hyperphosphorylation), microglial activation (Iba1/CD68 upregulation and process retraction), synaptic alterations (&#x3b1;-synuclein reduction), and bioenergetic impairment (reduced mitochondrial and glycolytic markers) in the hippocampus. Overall, these findings indicate that repeated prenatal and postnatal peripheral activation of innate immunity may act as a contributing factor to neurodegenerative phenotype with features relevant to AD-related susceptibility, paving the way for the development of next-generation therapeutical interventions affecting systemic-to-brain inflammatory signaling.

Neuro-emotional technique (NET) is a structured mind-body intervention used by certified practitioners to identify and address stress-related emotional patterns associated with physiological and behavioural responses. Published NET research has described changes in psychological symptoms, pain, quality of life, brain physiology, inflammatory markers, and blood chemistry, yet the mechanisms underlying these effects remain incompletely defined. This narrative review and conceptual synthesis propose that memory reconsolidation theory and predictive processing provide complementary frameworks for understanding how NET may influence stress-linked somatic-emotional patterns. Reconsolidation research suggests that previously consolidated emotional memories may become temporarily labile following reactivation if a sufficient prediction error occurs, permitting updating before restabilisation. Predictive processing models propose that emotional learning may be expressed as embodied predictions about threat, safety, self, action, and physiological demand, rather than solely as conscious narrative recall. Taken together, these frameworks suggest that the clinically relevant target of NET may be a body-brain prediction pattern rather than a discrete memory or a fixed physiological state. This article introduces somatic-emotional updating to describe the proposed modification of emotionally encoded physiological prediction patterns through concurrent emotional activation and contradictory embodied experience. Within this model, NET may create clinical conditions in which a stress-linked somatic-emotional pattern is reactivated while the patient simultaneously experiences a sense of present-time safety, interoceptive attention, practitioner support, and non-threatening somatosensory input. This combination is proposed to constitute embodied mismatch, the clinical expression of prediction error, which may provide conditions consistent with reconsolidation-relevant updating. The model does not propose that NET has been proven to induce memory reconsolidation. Rather, it identifies structural parallels between the NET clinical sequence and reconsolidation phases and proposes somatic-emotional updating as a theoretically coherent and falsifiable hypothesis for future research. Proposed research priorities include measuring durable changes in target emotional reactivity, autonomic regulation, biological stress markers, and adaptive function following NET, as well as comparing full NET with modified protocols that isolate key procedural elements.

What makes some people willing to help strangers at a personal cost, while others are more hesitant or selective? Early life adversity - such as neglect or abuse - may shape how we respond to strangers in need later in life, yet the underlying neural mechanisms remain unclear. In this study we tested whether the neuropeptide oxytocin, a key modulator for a rich repertoire of social behaviours, influences altruistic decisions in adults with different childhood experiences. Using functional magnetic resonance imaging (fMRI) and a validated altruistic donation task, the study showed that oxytocin increased donations among individuals with greater childhood adversity, while reducing them in those with lower adversity. These behavioural effects were mirrored by changes in functional connectivity between the medial prefrontal cortex and middle cingulate cortex - core circuits involved in social evaluation and empathy. Our findings suggest that early life experiences sensitize neural pathways for social processing, and that oxytocin dynamically modulates these circuits to influence altruistic behaviour in adulthood.

Attention impairment constitutes a primary cognitive deficit following subconcussive head impacts. However, the underlying neural mechanisms remain unclear. This study investigated neural alterations in attention networks associated with repetitive subconcussive exposure by integrating source-level electroencephalography (EEG) functional connectivity analysis with the Attention Network Test (ANT). Source-level functional connectivity matrices were constructed using the phase-locking value (PLV) to characterize connectivity patterns across multiple frequency bands (delta, theta, alpha, and beta), and graph-theoretical analysis was subsequently performed to assess network topological properties. At the behavioral level, attention network efficiency did not differ significantly between groups; however, compared with healthy controls, the subconcussion group exhibited increased functional connectivity across attention networks. Specifically: (1) Within the alerting network, connectivity increased in the delta and alpha bands; exploratory correlations analyses indicated that stronger connectivity between the rolandic operculum (ROL) and the inferior parietal lobule, as well as between the ROL and the angular gyrus, was associated with better alerting efficiency, whereas stronger connectivity between the middle frontal gyrus and the supplementary motor area (SMA) was associated with poorer alerting efficiency. (2) Within the orienting network, widespread increases in connectivity were observed across the delta, alpha, and beta bands, and stronger connectivity between the supramarginal gyrus and the middle temporal pole was associated with better orienting efficiency. (3) Within the executive control network, right-hemisphere-predominant enhancement of connectivity in the alpha and beta bands was accompanied by significant alterations in network topological organization. Collectively, these findings reveal frequency-specific functional hyperconnectivity and selective topological reorganization within attention networks following repetitive subconcussion, providing insights into subconcussion-related neural alterations and potential neurophysiological signatures for further investigation.

暂无摘要（点击查看详情）

BackgroundHistorically, OFF burden in Parkinson's disease has been primarily attributed to motor features. Recent studies highlight that non-motor symptoms, and the predictability of OFF episodes also drive functional impairment, yet they are rarely measured in clinical practice.ObjectiveTo identify which clinical features are most closely associated with OFF time and OFF impact, and to quantify the added explanatory value of temporal predictability, non-motor, and behavioural domains beyond a core motor model.MethodsWe analysed 1252 OFF-only visits from 430 PPMI participants. Outcomes were MDS-UPDRS IV 4.3 (OFF time) and 4.4 (OFF impact). Linear mixed-effects models with a participant random intercept were fitted. The core motor model included OFF-state motor severity, freezing, tremor, levodopa responsiveness, and dyskinesia, plus covariates. Predictability (IV&#x202f;4.5), non-motor (mood, fatigue/sleep, autonomic/GI), and behavioural (impulse-control behaviours) domains were then added to assess added influence beyond motor. Analyses were stratified by time since diagnosis (Pooled; &#x2264;&#x202f;4&#x202f;y; &#x2265;&#x202f;6&#x202f;y).ResultsClinical features explained more variance in OFF impact than OFF time (25.9% vs 8.1%). OFF time was primarily linked to OFF-state motor severity/freezing, with levodopa responsiveness important early. For OFF impact, predictability produced the largest increment in marginal R2 beyond the core motor model (pooled and Late). Within the core motor model, tremor was the largest contributor to OFF impact.ConclusionsPredictability is a prominent correlate of OFF impact. Asking about predictability may help tailor therapy, from timing optimisation to on-demand rescue for unpredictable episodes. Understanding OFF Periods in Parkinson's Disease: Why Predictability Matters for Daily Life and Treatment ChoicesPeople with Parkinson's disease often experience &#x201c;OFF periods,&#x201d; when their usual medication stops working and symptoms return. These episodes can make everyday activities difficult. Traditionally, OFF periods have been measured by how much time they last, but patients often say that unpredictability, when OFF episodes happen without warning, is even more disruptive.Our study looked at data from over 1200 clinic visits in a large international research project. We examined two aspects of OFF burden: OFF time &#x2013; how much of the day is spent in an OFF state.OFF impact &#x2013; how much OFF episodes interfere with daily life.We correlated these with motor symptoms (such as tremor and freezing), non-motor symptoms (such as anxiety and fatigue), and a measure of predictability (how regular or irregular OFF episodes are).We found that OFF impact was strongly linked to predictability. However, this does not mean unpredictability alone makes OFF worse, it may reflect a different type of OFF episode. Predictable &#x201c;wearing-off&#x201d; usually occurs gradually as medication wears off, while &#x201c;on&#x2013;off fluctuations&#x201d; can happen suddenly and are often more severe. Our findings suggest that patients who experience these abrupt changes report greater disruption to daily life.Why does this matter? Asking patients whether they can predict their OFF episodes may help doctors choose the right treatment. Predictable wearing-off can often be managed by adjusting medication timing or adding long-acting drugs. On&#x2013;off fluctuations may need fast-acting rescue treatments. In some cases, frequent unpredictable OFF episodes may signal the need to consider advanced options like infusion therapies or deep brain stimulation earlier in care.Our findings suggest that predictability should be part of routine assessment, alongside motor symptoms. Future research should explore whether improving predictability or targeting these more severe fluctuations can reduce the impact of OFF periods.

The substantia nigra is the critical part of the midbrain responsible for movement-related functions. Nigral alterations have been associated with neurological conditions related to movement disorders, including Parkinson's disease (PD). 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a toxin commonly used as a model of PD due to its selective nature of destroying dopaminergic neurons. However, toxicity varies among different animals and strains. Therefore, this study aimed to assess a comprehensive multi-level profile of early dopaminergic dysfunction by evaluating behavioural, biochemical, mitochondrial, neuroinflammatory, and histological assessments to characterise early nigrostriatal alterations in Swiss mice following subacute MPTP exposure. Twelve (12) adult male mice were randomly divided into two groups of six (6) mice each. Group I (control) was administered normal saline (1&#x202f;ml/kg i.p.), while group II was administered MPTP (30&#x202f;mg/kg i.p.) daily for 5 consecutive days. Twenty-four (24) hours following the last MPTP administration, the mice were assessed for neurobehavioural performance using the beam walk, pole, and traction test. Assessments of oxidative stress biomarkers [malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH)], mitochondrial complex 1 activity, neuroinflammatory markers (IL-1&#x3b2; and TNF-&#x3b1;), brain-derived neurotrophic factor (BDNF), monoamine oxidase B (MAO-B), dopamine level, and histological examination of the substantia nigra were conducted following subacute MPTP exposure. Exposure to MPTP altered neurobehavioural performance, oxidative stress biomarkers, neuroinflammatory markers (IL-1&#x3b2;, TNF-&#x3b1;), and other assessed biochemical parameters, as evidenced by increased beam performance latency, bradykinesia, and a lower traction score. Significant (p&#x202f;<&#x202f;0.05) increase in MDA level and decrease in SOD, CAT, and GSH were also observed. A significant (p&#x202f;<&#x202f;0.05) increase was observed in IL-1&#x3b2; and TNF-&#x3b1; levels, and a decrease (p&#x202f;<&#x202f;0.05) was observed in mitochondrial complex 1 activity, BDNF and dopamine levels. Nigral histological distortions were observed following MPTP exposure. These findings confirm the established alterations in neurobehavioral, physiological and morphological features in the substantia nigra of MPTP-exposed Swiss mice. The study assesses early nigral alterations after subacute MPTP exposure and supports the use of this model for investigating MPTP-induced neurotoxicity.

Recent studies have focused on characterising the brain's intrinsic connectivity networks during fear learning, going beyond traditional brain activation analyses, to study the acquisition of fearful associations as a model for clinical anxiety onset. Given the sharp increase in prevalence of affective disorders during puberty, a period marked by heightened affective sensitivity and fronto-amygdala circuitry development, the current study compares the connectivity within and between the salience network, executive control network and default mode network throughout fear learning, between young adults with and without mild mixed affective complaints. We hereby aim to identify potential neural targets for promising novel treatment options, such as functional magnetic resonance imaging (fMRI)-guided neurofeedback or transcranial magnetic stimulation. Generalised psychophysiological interaction analysis was used to assess connectivity changes within and between the salience network, executive control network and default mode network during an fMRI fear-conditioning paradigm (habituation, early, mid and late acquisition phase). Results were compared between healthy controls (n = 44), spider phobics (n = 44) and a group with subclinical mixed psychopathology (n = 52; 21 males), all aged 16-25 years. Task-induced changes in functional connectivity were specifically found in the default mode network (F(6, 792) = 4.170, p < 0.001). Overall, the default mode network showed less functional connectivity during conditioned threat stimulus than neutral 'safe' stimulus trials. Notably, a subset of connections within the default mode network of the subclinical mixed psychopathology group failed to differentiate between the stimuli (F(27, 377.39) = 2.01, false discovery rate-adjusted p-value = 0.014), which is in line with fear-conditioning research showing impaired (behavioural) stimuli differentiation in affective disorders. Stimulus-specific temporal dynamics of the default mode network during fear learning differentiated young adults with and without mild psychopathology. These results add up to a growing body of research identifying deficient default mode network functionality in affective disorders.

Children and young people with intellectual and developmental disability have long been known to suffer from inequities in accessing safe and quality health care. These challenges are most felt within the emergency department due to its busy, crowded, and overstimulating environments with staff that are not trained to provide reasonably adjusted care. The study is an evaluation using qualitative and quantitative methods of a continuing education and quality improvement programme designed to increase the knowledge, skills, and confidence of healthcare staff in providing reasonable adjustments to children and young people with intellectual disability in hospitals. This study evaluated the Motivated for Change programme, which uses Behavioural change, Adult Learning, and Quality Improvement strategies to drive practice change and service improvement. A hundred and thirty-one and 89 staff participated in a pre- and post-intervention survey. Interviews were conducted with parents of children and young people with intellectual and developmental disability attending the emergency department. Observational studies were also conducted in the pre- and post-intervention phase. These were transcribed, categorised, and coded with themes derived. Consensus was reached through meetings with the research team. The Motivated for Change programme has demonstrated significant increases in staff knowledge, skills, and experience in providing safe and quality care for these children and young people. Evidence of change is reflected in the parent and staff interview and observational study themes. In addition, staff were further motivated to undertake quality improvement projects, develop an in-house training programme to provide ongoing training for new staff, and make further improvements in the department. The Motivated for Change programme has demonstrated its efficacy in enabling changes in the practice of reasonable adjustments and the emergence of local champions for sustained efforts for ongoing improvements in safety and quality of care. The development of the research question and outcome measures was informed by data from previous research publications involving parents and staff. We sought input from a parent advisory committee in the design of the study. Parents were not involved in the recruitment and conduct of the study. Results were presented to the parent advisory at the end of the study.

The glymphatic system is a brain-wide perivascular clearance pathway that facilitates cerebrospinal fluid-interstitial fluid (CSF-ISF) exchange and the removal of metabolic waste from the brain parenchyma. Increasing evidence indicates that glymphatic transport is critically dependent on the integrity and function of cerebral small vessels, suggesting a close link with cerebral small vessel disease (cSVD). Structural and functional alterations of small vessels may disrupt glymphatic flow, while impaired glymphatic clearance may in turn exacerbate small vessel-related brain injury, indicating a bidirectional interaction between these two processes.In this review, we synthesize current evidence on the relationship between cSVD and glymphatic dysfunction, integrating findings from experimental models and in vivo human studies. We discuss shared pathophysiological mechanisms linking small vessel pathology to impaired perivascular fluid transport, summarize associations between glymphatic dysfunction and established cSVD imaging markers, and evaluate emerging therapeutic strategies aimed at restoring or enhancing glymphatic function. We highlight areas of convergence and inconsistency in the existing literature and identify key knowledge gaps that warrant further investigation. If glymphatic failure does play a causal role in cSVD this raises the exciting possibility that therapies improving glymphatic function could treat cSVD, and we review potential therapeutic approaches, both behavioural and pharmacological.