Search Results (712)

Background: Brain tumours impose complex, spatially heterogeneous disturbances on neural circuits that extend far beyond the immediate lesion site. While gross anatomical displacement of the cortico-spinal tract (CST) has been extensively studied, the topological reorganization of the functionally informed structural connectome—and its dependence on tumour molecular phenotype—remains incompletely understood. Objectives: This study aimed to characterize upper-limb functionally informed network topology in brain tumour patients, identify histological and molecular patterns of structural reorganization at the cortical and subcortical level, and determine the impact on neurophysiological parameters. Methods: Forty-eight patients with supratentorial motor-eloquent tumours (MET’s) underwent diffusion-weighted imaging (DWI) as part of their preoperative motor mapping. Connectivity matrices based on streamline passing counts were extracted from 426 nodes of the HCPex atlas using DSI Studio^® upon seeding the structural connectome in the motor hotspot (best motor response) for the functional area of the upper limb identified using preoperative navigated transcranial magnetic stimulation (nTMS). Paired-sample t-tests compared tumour versus healthy hemispheres across network topology metrics. The impact of nTMS-derived excitability metrics—interhemispheric resting motor threshold ratio (iRMTr) and cortical silent period (CSP)—and tumour histological and molecular characteristics on the connectome was assessed. Results: The global network topology of the tumour hemisphere was preserved when compared to the healthy baseline hemisphere across all tumour types (p > 0.05). Subcortical analysis revealed significant hyper-connectivity in the tumour hemisphere, with elevated degree, strength, clustering coefficient, local efficiency, and eigenvector centrality (p < 0.05). Basal ganglia motor loop degree was increased in the tumour hemisphere (mean 7.37 versus 5.19; p = 0.0009). IDH-mutant tumours generated significantly more topologically organized compensatory networks than IDH-wildtype tumours (Clustering Coefficient 0.345 versus 0.273; p = 0.018). Of the cortical nodes on the side of the tumour, significant hyper-connectivity was seen in the supplementary motor area (p = 0.0011), premotor cortex (Area 6), with increased connection seen in 6 mp (medial premotor at p =0.0033) and 6 d (dorsal premotor at p = 0.025) and primary somatosensory cortex (p = 0.027). The presence of the tumour induced significant changes across all three domains: loss of CST volume (p < 0.001), prolongation of the cortical silent period indicative of intracortical inhibition (p < 0.0001), with significant prolongation in glioblastoma versus an oligodendroglioma. Conclusions: Brain tumours significantly impact the upper limb-centred structural connectome. While global network topology is preserved, tumours induce substantial subcortical and basal ganglia network reorganization by inducing compensatory hyper-connectivity. These findings suggest that structural connectomics offers a novel framework for non-invasive tumour characterization and surgical planning. Full article

Background/Objectives: Despite the clinical efficacy of cannabidiol (CBD) in treating certain epilepsies, its in vivo neuropharmacological mechanisms remain incompletely understood. This Phase 1 clinical trial aimed to evaluate the acute effects of a single oral dose of highly purified CBD (GWP42003-P) on cortical excitability. Transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) and electromyography (TMS-EMG) were utilized as assessment tools. Methods: In a randomized, double-blind, placebo-controlled crossover trial, 15 healthy male participants received a single 1500 mg dose of GWP42003-P or placebo. Cortical activity metrics, including resting and active motor thresholds (RMT, AMT), short intracortical inhibition (SICI), TMS-evoked potentials (TEPs), TMS-related spectral perturbations (TRSP), and inter-trial phase clustering (ITPC), were recorded pre-dose and at 1, 4, and 6 h post-dose. Results: RMT and AMT significantly decreased over time following CBD administration, though without a significant Condition × Time interaction. While primary analyses showed no condition-driven alterations for SICI, TEPs, or TRSP, secondary longitudinal modeling revealed a transient reduction in beta-band desynchronization 1 h post-dose, aligning with peak plasma concentration. The drug condition also exhibited a qualitative, non-significant trend toward increased alpha ITPC and decreased delta ITPC at 4 and 6 h post-dose compared to placebo. Conclusions: A single acute 1500 mg dose of GWP42003-P did not produce statistically significant alterations in widespread cortical excitability in healthy adult males. However, the transient blunting of beta desynchronization at peak concentration may reflect CBD’s distinct, non-classical neuromodulatory profile. Overall, these largely null findings suggest that acute CBD administration lacks a robust, direct modulatory effect on cortical networks. Capturing its precise neuropharmacological mechanisms will likely require future investigations utilizing chronic dosing paradigms or clinical patient populations. Full article

The photophysics of a series of Schiff base–BF₂ complexes was investigated using steady-state and femtosecond/nanosecond transient absorption spectroscopy, as well as theoretical computations. The native chromophore has a weak fluorescence and a short fluorescence lifetime (<30 ps, determined using the femtosecond fluorescence upconversion method). No triplet state formation was observed for the compounds. Moreover, attachment of a heavy atom (iodine) to the phenyl ring did not enhance intersystem crossing (ISC), which was different from that observed with Bodipy analogs. We attribute the lack of ISC to the short lifetime of the S₁ state, which decays rapidly through an efficient non-radiative decay channel, possibly geometry torsion. We also studied a Schiff base–BF₂ complex with a twisted molecular structure, which showed a similarly short S₁ state lifetime (<100 ps) and weak fluorescence. Using nanosecond transient absorption spectroscopy and intermolecular triplet–triplet energy transfer, we determined the triplet state lifetime of the Schiff base–BF₂ complexes to be ca. 20 μs, which is much shorter than that of the Bodipy chromophore (100–800 μs). Based on femtosecond transient absorption spectra, we inferred that the decay of the emissive S₁ state takes about 17–20 ps, leading to a non-emissive (dark) state, followed by the formation of a long-lived non-emissive singlet excited state. Theoretical computations demonstrated large spin–orbit coupling matrix elements (SOCMEs, up to 29 cm⁻¹), but the fast non-radiative relaxation of the S₁ state inhibits ISC. Thus, we propose that the fast internal conversion inhibits ISC of the iodo-containing molecules. A theoretical study of the zero-field splitting (ZFS) parameters of the triplet state indicates that the ZFS D parameter (45 cm⁻¹) was overestimated for the iodo-containing compounds, whereas a reasonable value was obtained for the iodo-free compounds (ca. 0.03–0.06 cm⁻¹). Full article

Gap junctions (GJs) are channels that enable exchange of ions and small molecules between cells, and have been implicated in the development and maintenance of neuropathic pain. Injury-induced glial activation in sensory ganglia is associated with increased coupling by GJs, which in turn enhances neuronal excitability, contributing to pain signaling. Tonabersat (TON) was suggested to act as a GJ blocker with analgesic actions, but these claims have been disputed. Here we examined whether TON blocks GJs and whether it influences pain behavior in a mouse pain model. Gap junctional coupling was assayed by the dye coupling method in mouse liver and trigeminal ganglia. Pain behavior was tested in a mouse model of chemotherapy-induced pain, using von Frey filaments (tactile sensitivity), the acetone method (cold sensitivity) and hot plate (heat sensitivity). Intracellular dye injection showed that TON and the GJ blocker carbenoxolone (both 50 µM) inhibited gap junctional coupling by 70% and 82%, respectively. In the trigeminal ganglia, TON and carbenoxolone inhibited gap junctional coupling by 74 and 77%, respectively. TON selectively reduced heat and cold hypersensitivity, but not mechanical threshold. Carbenoxolone reduced all hypersensitivity types. No sex differences were observed. We conclude that both TON and carbenoxolone reduced coupling, indicating their potential to influence GJ-mediated coupling. In behavioral tests TON showed a selective effect for thermal hypersensitivity, but the underlying mechanism is unclear. Carbenoxolone produced a somewhat greater reduction in coupling compared with TON. These findings suggest that GJs play a role in pain pathways and highlight the need to explore whether other pain-relieving drugs act by blocking GJs. Full article

The rodent prenatal valproate (VPA) treatment is a widely used animal model of idiopathic autism spectrum disorder (ASD). However, the presence of autistic-like symptoms is highly variable in treated offspring. The disruption of the excitation–inhibition balance of certain brain areas has been proposed as a main feature in both human ASD and the VPA model. The current study presents a detailed analysis of neural development, diverse behaviors, and neocortical excitability in a high number of individually identified VPA-treated rat offspring of both sexes. Neocortical excitability was assessed using electrophysiological and intrinsic optical imaging methods. Prenatal VPA treatment caused a delay in early postnatal sensorimotor development in rat pups of both sexes. Behavioral effects were associated with congenital morphological alterations (e.g., tail kink), as shown by stratification by principal component analysis and correlation analysis. Social deficits were evident only in the VPA-treated male offspring, while the females appear to be resistant to this effect. Prenatal VPA treatment was associated with sex- and region-dependent alterations in the excitability and seizure susceptibility of entorhinal and prefrontal cortical slices. Cortical excitability measures showed partial correlation with morphological and behavioral parameters. Thus, the current study further supports the validity of the rodent prenatal VPA model as a model of ASD for both sexes, but the variable degree of affectedness should be taken into account. Congenital malformation severity, including tail kink, may serve as a readily observable marker for subsequent physiological alterations, particularly in males. Full article

Halogenated ketones (HKs) and aldehydes (HAs) are prevalent emerging disinfection by-products (DBPs) threatening drinking water safety. Although pre-oxidation and coagulation are widely applied in drinking water treatment, critical knowledge gaps remain regarding the precursor-specific effects of KMnO₄ and O₃ pre-oxidation on chlorinated ketone/aldehyde formation potential, as well as the interaction between coagulation optimization and DBP yields. This study systematically investigates the effects of KMnO₄/O₃ pre-oxidation and optimized coagulation on the formation potential (FP) of 1,1-dichloroacetone (1,1-DCP), 1,1,1-trichloroacetone (1,1,1-TCP), and chloral hydrate (CH) from four typical precursors (fulvic acid, citric acid, L-threonine, L-asparagine). Batch pre-oxidation and chlorination experiments were performed; three-dimensional excitation–emission matrix (3D-EEM) fluorescence spectroscopy was used to characterize organic-precursor structural changes, while gas chromatography–mass spectrometry (GC-MS) was adopted to quantify target DBPs. Results show that KMnO₄ and O₃ pre-oxidation significantly promote (p < 0.05) DBP formation from fulvic acid but exert precursor-specific effects on small-molecule precursors: KMnO₄ enhances CKs while inhibiting CH from amino acids, and O₃ suppresses all three DBPs from small-molecule precursors. Coagulation pretreatment weakly inhibits DBP formation (reduction rate < 20%) by removing partial precursors. This study clarifies the mechanism of process-driven DBP modulation and provides a theoretical basis for optimizing water treatment processes to control chlorinated ketone/aldehyde DBPs. Full article

Hypertension is an important risk factor for cardiovascular and renal diseases, yet the mechanisms linking ion channel dysfunction to hypertension remain poorly understood. The voltage-gated potassium channel Kv1.3 (encoded by Kcna3) regulates membrane potential, but its role in the pathogenesis of hypertension remains unclear. In this study, we employed Kcna3 knockout (KO) mice, transcriptomic profiling, and pharmacological inhibition to investigate the role of Kv1.3. Kcna3-deficient mice showed increased blood pressure and renal fibrosis. Transcriptomic profiling showed activation of the renin–angiotensin–aldosterone system (RAAS), with increased renin expression in both Kcna3-deficient mice and Kv1.3 inhibitor-treated cells. Mechanistically, loss of Kv1.3 increased intracellular Ca²⁺ accumulation, activating the phosphoinositide 3-kinase (PI3K)-AKT and protein kinase A (PKA) pathways, leading to cAMP response element binding protein (CREB) phosphorylation and renin upregulation. Pharmacological inhibition of Ca²⁺ signaling or PKA reduced CREB phosphorylation and renin expression, confirming a causal signaling cascade. Thus, Kv1.3 links membrane excitability to RAAS activation via a Ca²⁺-dependent AKT–PKA–CREB signaling axis and represents a potential therapeutic target for hypertension and associated renal injury. Full article

Light-responsive materials enabling external modulation of bioactivity and spatial control are highly requested for photopharmacology—a booming research area of modern medicine. We present organo-inorganic hybrids of photoswitchable, bioactive symmetric diamine-phosphine oxides conjugated with luminescent carbon quantum dots (CQDs). The phosphonate compound was found to undergo Z-E isomerization upon 266 nm laser irradiation and exhibit butyrylcholinesterase (BChE) inhibition that increases twofold (15–30%) after photoconversion. Hybrids were fabricated via physical adsorption and chemisorption using different CQD surface groups, and characterized by UV-Vis, luminescence, and FTIR spectroscopy, confirming hybrid formation and retention of functional properties. In both binding modes, the molecules retained photoswitching capability despite steric constraints. All hybrids displayed orthogonal functions: luminescence (excitation at 350 nm) and photomodulation of BChE inhibition (at 266 nm). Remarkably, the binding mode dictated the bioactivity window—chemisorbed hybrids showed narrow 1.5-fold modulation, whereas physisorbed hybrids exhibited ultra-wide >10-fold modulation. This tunable responsiveness, achieved simply by altering the binding mode, demonstrates the exceptional potential of this hybrid design strategy for developing photoswitchable materials with tailored photopharmacological performance. Full article

Background/Objectives: Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are frequently co-occurring neurodevelopmental conditions with partially overlapping neurophysiological profiles. Electroencephalography (EEG) provides non-invasive access to candidate biomarkers, yet the literature remains largely organized around single-diagnosis frameworks, limiting comparison across conditions and constraining translation into intervention selection. This review compares EEG signatures across ASD and ADHD from a transdiagnostic perspective and examines how such signatures might inform the selection of non-pharmacological interventions. Methods: A structured search of PubMed, Scopus, IEEE Xplore and Web of Science identified peer-reviewed studies published between 2010 and 2026 reporting EEG findings in ASD and/or ADHD, spanning resting-state, task-based, connectivity, event-related potential, machine learning and intervention studies. Sixty-eight sources were synthesized thematically. Given substantial heterogeneity in acquisition parameters and analytic pipelines, evidence was integrated interpretively rather than pooled quantitatively, and no formal risk-of-bias assessment was undertaken. Results: Shared features across both conditions frequently included low-frequency theta excess, reduced alpha modulation under cognitive load, and flattened aperiodic (1/f) slopes—a pattern compatible with, though not a direct measurement of, altered excitation/inhibition balance. While substantial heterogeneity exists, disorder-specific signatures often comprised the ASD “U-shaped” spectral profile alongside elevated epileptiform activity, and frontally pronounced theta/beta ratio elevation in subsets of individuals with ADHD. Machine-learning studies increasingly emphasize interpretable, multidomain feature sets over binary classification. Mindfulness-based and neurofeedback interventions converge on theta reduction and alpha enhancement, although reported effects are frequently conditional on responder status, task context, or outcome-rater blinding. Conclusions: Convergent EEG features support a transdiagnostic account of neurodevelopmental dysregulation. A biomarker-informed framework for intervention selection is proposed, which requires prospective validation before clinical application. Full article

Parkinson’s disease (PD) is characterized by progressive dopaminergic degeneration and maladaptive motor cortical plasticity. However, the cellular pathways underlying cortical surface activity in the primary motor cortex (M1) remain unclear, despite serving as a potential target for electrotherapy. We investigated the excitatory–inhibitory (E-I) balance and synaptic plasticity of superficial M1 circuits in a unilateral 6-hydroxydopamine (6-OHDA)-induced rat model of PD. Using extracellular local field potential and whole-cell patch recordings from the contralateral and ipsilateral M1 hemispheres of hemi-parkinsonian rats, we observed a significantly elevated field excitatory postsynaptic potential (fEPSP) input–output function but unchanged intrinsic neuronal excitability in the M1 superficial layer. An altered relative contribution between alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)- and N-methyl-D-aspartate receptor (NMDAR)-mediated transmission was reflected by a significantly increased AMPA/NMDA ratio. Markedly reduced inhibitory synaptic tone was also evidenced by the decreased amplitude and frequency of spontaneous inhibitory postsynaptic currents (sIPSCs), supporting an E-I imbalance favoring excitation in PD. Furthermore, group I metabotropic glutamate receptor (mGluR_1/5)-dependent long-term depression (LTD) was abolished in the ipsilateral PD hemisphere, whereas NMDAR-dependent LTD remained intact. In summary, dopamine depletion appears to enhance network excitation and disrupt mGluR_1/5-mediated control of M1 surface circuitry. Our findings identify altered cortical surface mGluR-dependent plasticity in the hemi-parkinsonian model; however, the relationship between these electrophysiological alterations and individual motor outcomes remains to be determined. Full article

Background: Large yellow tea (LYT), a distinctive variety made from mature leaves, has recently gained attention for its remarkable health benefits. However, whether these benefits can be transmitted from mother to offspring remains unexplored. Purpose: This study investigated whether maternal LYT consumption confers intergenerational protection against metabolic and behavioral disorders induced by perinatal bisphenol A (BPA) exposure in F1 offspring. Methods: A mouse model of perinatal BPA exposure (0.03% in diet) was established with or without maternal LYT supplementation (2.5% in diet). Metabolic parameters were assessed through biochemical assays and gene expression analysis (RT-PCR). Energy expenditure and spontaneous activity were monitored using a Comprehensive Lab Animal Monitoring System (CLAMS). Hippocampal proteomic profiling was performed using label-free quantitative proteomics. Results: LYT significantly reduced maternal BPA body burden, potentially via limiting absorption, enhancing glucuronidation metabolism, and promoting excretion. Notably, LYT exhibited bidirectional metabolic regulation, alleviating gestational hyperglycemia in dams while restoring hypoglycemia in offspring, and normalizing underweight and hypolipidemia. Mechanistically, the SIRT6 (sirtuin 6)/FOXO1 and SIRT6/SREBP1 pathways may be involved in regulating gluconeogenesis and lipogenesis. Concurrently, LYT rectified BPA-induced hyperactivity and reduced excessive energy expenditure. Proteomic analysis revealed that LYT partially restores BPA-induced dysregulation of cholesterol metabolism and glutamatergic/GABAergic synaptic pathways, which may contribute to rebalancing synaptic homeostasis. Conclusions: These findings suggest that maternal LYT supplementation confers intergenerational protection against BPA-induced metabolic and behavioral disorders in mice, potentially acting through enhanced toxin clearance, bidirectional metabolic regulation, behavioral normalization, and partial restoration of hippocampal synaptic homeostasis. This study provides a theoretical basis for developing natural dietary interventions to mitigate developmental toxicant-induced health risks. Full article

Background/Objectives: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulatory approach with potential therapeutic value for cognitive impairment in Alzheimer’s disease (AD). Ferroptosis-related oxidative injury has been implicated in AD-associated neuronal dysfunction, but whether rTMS-induced functional improvement is accompanied by changes in ferroptosis-related oxidative injury remains unclear. This study evaluated the effects of high-frequency rTMS on cognitive function, hippocampal neuronal excitability, and ferroptosis-related oxidative injury in amyloid precursor protein/presenilin-1 (APP/PS1) mice, using Ferrostatin-1 (Fer-1) as a pharmacological comparator. Methods: Six-month-old female mice were used, including age-matched C57BL/6J controls and APP/PS1 mice assigned to the AD + Sham, AD + rTMS, and AD + Fer-1 groups (n = 6 per group). After 14 days of intervention, cognitive performance was assessed using behavioral tests. Whole-cell patch-clamp recordings were performed in hippocampal dentate gyrus granule neurons to evaluate neuronal excitability and voltage-gated sodium (Na⁺) and potassium (K⁺) channel properties. Biochemical assays and transmission electron microscopy were used to assess oxidative, iron-related, and mitochondrial changes, and mitochondrial ultrastructure was examined in an independent cohort (n = 3 per group) using transmission electron microscopy. Results: Compared with AD + Sham mice, high-frequency rTMS improved cognitive performance, increased evoked action potential firing, lowered the elevated action potential threshold, partially restored voltage-gated Na⁺ and K⁺ current amplitudes, and accelerated recovery of Na⁺ currents from inactivation. Fer-1 produced partially overlapping, but not identical, effects across behavioral, electrophysiological, biochemical, and ultrastructural outcomes. Both interventions increased hippocampal glutathione (GSH) levels, reduced malondialdehyde (MDA) and total iron levels, partially restored superoxide dismutase (SOD) activity, and improved mitochondrial ultrastructure and reduced the prevalence of mitochondrial profiles with small cross-sectional areas. Conclusions: High-frequency rTMS improved cognitive and hippocampal neuronal outcomes in female APP/PS1 mice. These improvements were accompanied by biochemical and mitochondrial changes compatible with attenuation of ferroptosis-related injury. However, the findings do not establish ferroptosis inhibition as either necessary or sufficient for the effects of rTMS. Full article

Disruption of neuronal excitation–inhibition balance and mitochondrial quality control may contribute importantly to lead (Pb)-induced neurotoxicity, but nutritional modulators targeting these processes remain poorly characterized. This study investigated the protective effects and underlying mechanisms of ginsenoside Rh1, a ginseng-derived bioactive compound, in Pb-exposed mice and Pb-treated HT22 hippocampal cells. Chronic Pb exposure caused spatial recognition deficits, reduced exploratory activity, anxiety-like behaviors, and marked neuronal injury, accompanied by Pb accumulation in blood and brain tissues, elevated IL-1β, TNF-α, and IL-6 levels, oxidative stress, reduced Gama-aminobutyric acid (GABA) content, and dysregulated NKCC1/KCC2 expression. In HT22 cells, Pb increased intracellular ROS generation and disrupted mitophagy-related signaling, as indicated by alterations in PINK1, Parkin, LC3, P62, and GABARAP. Rh1 treatment alleviated Pb-induced behavioral abnormalities and neuronal pathology, reduced Pb burden, suppressed neuroinflammatory responses, enhanced antioxidant defenses, improved Pb-associated alterations in GABAergic regulation, and modulated mitochondrial quality-control signaling in vivo and in vitro. These findings suggest that Rh1 may represent a promising nutritional intervention strategy for mitigating Pb-associated neurotoxicity. Full article

A previous investigation on limonene (LM), perillyl alcohol (POH), and carveol (CV), focused on the structure–activity relationship and hydroxyl group, documented that the presence of the hydroxyl group influences the pharmacodynamic potency of these agents, inhibiting smooth muscle contraction with the order of potency: POH > CV > LM. That investigation also suggested a mechanism of action, which importantly included activity on the voltage-dependent calcium channel. Here, we investigated whether this structure–activity relationship also applies to nerve excitability (an activity greatly dependent on sodium channels) using compound action potential (CAP) recordings from mouse sciatic nerves and in silico simulations. POH, CV, and LM inhibited both the positive amplitudes and conduction velocities of the two CAP components in a concentration-dependent manner, with IC₅₀ values of 0.8, 1.0, and 4.3 mM (1st component) and 0.6, 0.6, and 3.0 mM (2nd component) for amplitude, and 2.4, 2.4, and 7.1 mM (1st component) and 1.0, 2.6, and 4.3 mM (2nd component) for conduction velocity. The order of pharmacodynamic potency, thus, was POH = CV > LM. In silico simulation demonstrated that POH and CV penetrate the Nav 1.6 and accommodate in the channel at the interface between the selectivity filter and the central cavity, a position very favorable to block the channel pore. In contrast, LM exhibited a markedly different docking profile, suggesting that LM binding is less likely to directly obstruct sodium permeation. In conclusion, the three substances investigated inhibited nerve excitability, but those with a hydroxyl group demonstrated greater pharmacodynamic potency. Full article

Autism spectrum disorder (ASD) is characterized by persistent impairments in social communication together with restricted and repetitive patterns of behavior. Although ASD has traditionally been viewed primarily as a disorder of neural circuitry, increasing evidence indicates that interactions between the immune and nervous systems contribute substantially to brain development and cognitive function. This review develops a neuroimmune–cognitive–account of ASD by examining how immune signaling may influence neural organization and, in turn, cognitive function. Evidence from neuroimmunology, systems neuroscience, and experimental studies of neuromodulation is synthesized to examine relationships among immune signaling, neural network organization, and cognition. Disturbances in these processes have been associated with alterations in excitation–inhibition –balance and atypical large-scale connectivity, especially within networks supporting social cognition. We also examine the role of neuromodulatory systems, with particular emphasis on oxytocin and vasopressin, as intermediaries between biological regulation and cognitive processing. Experimental findings indicate that oxytocin can transiently modulate activity within social brain networks and increase the salience of socially relevant stimuli, although effects across clinical studies remain modest and inconsistent. The reviewed evidence suggests that disturbances in neuroimmune regulation may contribute to altered communication among distributed neural systems, providing one possible account of cognitive dysfunction in ASD. Social deficits, repetitive behaviors, and sensory differences reflect disturbances in the coordination of distributed neural systems rather than isolated impairments within single regions or pathways. This view has important implications for intervention, suggesting that approaches directed at individual molecular or neural targets alone are unlikely to produce broad or lasting effects. More effective strategies may require interventions that address interactions among immune function, neural dynamics, and cognitive processes. The resulting neuroimmune–cognitive account generates testable hypotheses concerning how immune processes may influence neural organization and cognition in ASD while providing a conceptual basis for future experimental and clinical research. Full article