2026-04-02
Wei Meng, Qingyu Xu, Qi Shi, Yi Song, Jiafu Hou
Abdominal epilepsy (AE) is a type of focal autonomic epilepsy characterized by recurrent paroxysmal abdominal pain as the primary clinical manifestation. It is relatively more common in children and adolescents and is often accompanied by autonomic nervous system dysfunction and altered consciousness. Due to its atypical clinical presentation and symptom overlap with gastrointestinal disorders, AE is frequently misdiagnosed or overlooked in clinical practice. Advances in neuroimaging, electroencephalography (EEG), and molecular biology have deepened the understanding of AE’s pathogenesis and diversified its diagnostic and therapeutic strategies. This article systematically reviews and critically appraises recent research on AE in children, covering epidemiology, pathogenesis, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis. By evaluating the strengths and limitations of the existing evidence (predominantly from case reports, small case series, and a limited number of controlled studies), it aims to highlight reliable conclusions, identify knowledge gaps, and inform future clinical practice and research priorities.
DOI: 10.3389/fnins.2026.17912612026-04-01
Shifang Luo, Linao Zhang, Xue Wu, Jiying Wang, Qing Li, Wentao Chen, Rongyu Li, Lingli Zhou, Na Zhou, Rong Chen, Yuhuan Xie, Peixin Guo
ObjectiveThis review aims to summarize the application and mechanisms of plant extracts with neuroprotective effects in Parkinson’s disease (PD), emphasizing their therapeutic potential in PD management.BackgroundParkinson’s disease is a widespread neurodegenerative disorder, predominantly affecting middle-aged and elderly populations. Characterized by varied etiologies, clinical presentations, and complex pathogenesis, its hallmark symptoms include tremor and bradykinesia. Despite the availability of limited pharmacological treatments, current approaches primarily focus on symptom management rather than modifying disease progression. Recent research have increasingly investigates the use of neuroprotective plant extracts, which have shown demonstrating promising therapeutic effects, garnering significant attention in the field.MethodsA systematic review was conducted on preclinical and clinical studies published from 2000 to 2025, sourced from PubMed, ScienceDirect, Google Scholar, and China National Knowledge Infrastructure (CNKI), to evaluate the effects of neuroprotective plant extracts in PD treatment.ResultsThe review reveals that plant extracts with neuroprotective properties exert anti-PD effects through mechanisms including antioxidant and anti-inflammatory actions, inhibition of α-synuclein (α-syn) aggregation, enhancement of dopaminergic neuron survival, and restoration of synaptic function.ConclusionThis review outlines research directions for the development of neuroprotective plant extracts as novel PD therapies, suggesting their potential as complementary treatments alongside conventional pharmacological interventions.
DOI: 10.3389/fnins.2026.18131332026-04-01
Xu Li, Wenke Zhou, Shuran Yang, Xiangkai Huang, Kuihong Zheng
The microbiota–gut–brain axis represents a complex bidirectional communication network linking the gastrointestinal system and the central nervous system and has been increasingly recognized as a key contributor to neurological and psychiatric disorders. Growing evidence indicates that alterations in gut microbiota composition and function can influence brain development and function through neural, immune, endocrine, and metabolic pathways, thereby modulating neuroinflammation, neurotransmission, and blood–brain barrier integrity. Dysregulation of this axis has been implicated in a range of conditions, including Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, autism spectrum disorder, depression, anxiety, and stroke. Recent pharmacological advances have identified the microbiota–gut–brain axis as a promising therapeutic target. Current strategies focus on modulating shared pathophysiological mechanisms rather than disease-specific endpoints and include microbiota-directed interventions, immune–inflammatory modulators, neurotransmitter-targeting agents, and approaches aimed at restoring intestinal and blood–brain barrier function. In this review, we summarize the core mechanisms underlying microbiota–gut–brain axis dysfunction and organize existing pharmacological strategies according to their primary targets. By integrating evidence across multiple disorders, we provide a mechanism-oriented framework to support future drug development and precision therapeutic approaches for brain disorders.
DOI: 10.3389/fnins.2026.18065322026-04-01
Elizabeth B. Torres, Mona Elsayed
IntroductionThe sensation of pain varies from person to person. These patterns of individual variation are difficult to capture using coarse subjective self-reports. However, they are important when prescribing therapies and tailoring them to each person’s own sensations. Pain can be experienced differently by the same person and can fluctuate based on context; yet, most analyses treat the problem with a one-size-fits-all model.MethodsIn this work, we introduce a series of assays to assess pressure pain across tasks with different motoric and cognitive demands, in relation to a resting state. In a cohort of healthy individuals, we examine pain-free vs. pain states at rest, during drawing with heavy cognitive demands, during pointing to a visual target, and during a grooved peg task, such as inserting a grooved key into a matching keyhole. We adopt a standardized data type called micro-movement spikes (MMS) to characterize the biorhythmic activities of facial micro-expressions and the micro-fluctuations in the heart’s inter-beat interval timings.ResultsUsing the MMS peaks, we find that the continuous Gamma family of probability distribution functions best fits the frequency histograms of both the facial and heart data. Furthermore, we find that the Gamma shape and scale parameters in both signals span a scaling power law whereby, as the noise-to-signal ratio (Gamma scale parameter) increases, so does the randomness of the stochastic process. We find that as the heart IBI becomes more erratic (noisier and more random), the facial ophthalmic region also increases in noise and randomness, with higher linear correlation for tasks requiring haptic feedback (R2 0.84) and lower correlation for tasks requiring greater cognitive and memory loads (R2 0.77).ConclusionIncreases in transfer entropy show that recent past activity (~167 ms back) of the heart IBI and facial data combined lower the uncertainty in predicting the present ophthalmic facial activity, suggesting that this facial region may serve as a proxy for the increasingly dysregulated heart. These results have implications for the detection and monitoring of pressure pain.
DOI: 10.3389/fnins.2026.17021242026-04-01
Weibo Xiao, Feng Xiao, Yingying Zhang, Lei Zeng
IntroductionMorphine antinociceptive tolerance remains a critical problem in the clinical management of pain. Spinal cord glial cell activation and neuroinflammation appear to play a crucial role in the development and maintenance of this tolerance. BTP2, a potent store-operated calcium channel inhibitor, has anti-inflammatory properties in the central nervous system. This study aimed to investigate the effect of BTP2 on the development of morphine antinociceptive tolerance and glial cell-derived pro-inflammatory cytokines production by chronic morphine treatment.MethodsA rat model of morphine antinociceptive tolerance was made by intrathecal injection of morphine (15 μg/d). Two separate studies were conducted: Firstly, to investigate whether BTP2 could attenuate the development of tolerance, BTP2 (2 and 10 nmol) was given intrathecally 30 min before each intrathecal delivery of morphine for consecutive 7 days. Secondly, to investigate whether BTP2 could reverse the established tolerance, BTP2 administration was initiated on day 8 after 7 days of morphine treatment and continued for 4 days.ResultsThe results showed that BTP2 not only attenuated the development of morphine tolerance but also partially reversed the established tolerance. Immunohistochemistry revealed that chronic morphine-induced activation of astrocytes in the spinal cord, while BTP2 was shown to suppress the activation of astrocytes. Moreover, the administration of BTP2 alleviated the activation of astrocytic ERK and the production of proinflammatory cytokines (e.g., TNF-α and Il-1β) in the spinal cord.DiscussionThese findings suggest that BTP2 can be a potential therapeutic drug for morphine antinociceptive tolerance, and the store-operated calcium channel may play an important role in morphine antinociceptive tolerance.
DOI: 10.3389/fnins.2026.17583522026-04-01
Bin Yu, Jian-Min Lv, Ge Lei, Jing-Li Wu, Ding-Xu Li, Xuan-Yue Song, Xi-Ning He, Na Zhao, Qian Shu, Hong-Xia Li
ObjectiveChildren with High-Functioning Autism (HFA) often show marked deficits in executive functioning, particularly during verbal fluency tasks (VFTs). These behavioral impairments are believed to stem from neurophysiological abnormalities in the prefrontal cortex (PFC) functioning, characterized by atypical activation patterns and disrupted functional connectivity. This study utilized functional near-infrared spectroscopy (fNIRS) to investigate hemodynamic responses and connectivity metrics during VFT performance. By comparing children with HFA to age-matched typically developing (TD) controls, this study aimed to clarify the neural mechanisms underlying the executive control of language production in HFA.MethodsThe sample included 29 children who met diagnostic criteria for HFA and 26 TD controls. All participants had a Full-Scale Intelligence Quotient of 70 or higher and were matched for age and cognitive ability. During a standardized phonemic VFT, cortical hemodynamics were continuously monitored using a 19-channel fNIRS system, with analyses focusing on changes in oxygenated hemoglobin concentration within PFC regions.ResultsCompared with TD controls, children with HFA exhibited reduced cortical activation across multiple prefrontal regions, including channels 1 (t = −2.975, p = 0.017), 2 (t = −4.320, p = 0.001), 3 (t = −3.381, p = 0.012), 9 (t = −3.127, p = 0.014), and 19 (t = −3.279, p = 0.012). These regions correspond anatomically to the inferior prefrontal gyrus, frontopolar cortex, and dorsolateral PFC. Functional connectivity analyses demonstrated significantly reduced interregional coupling in the HFA group (p < 0.001), with mean connectivity values of 0.512 (SD = 0.076) compared with 0.566 (SD = 0.069) in TD participants. Furthermore, Oxy-Hb changes in prefrontal channels 1 (r = −0.424, p = 0.022), 2 (r = −0.432, p = 0.019), and 3 (r = −0.394, p = 0.034) were negatively correlated with Social Responsiveness Scale total scores, indicating that weaker prefrontal activation was associated with greater social impairment.ConclusionThe results reveal distinct cortical activation and functional connectivity alterations in children with HFA during VFTs. These findings support the hypothesis that disrupted interregional brain coordination underlies executive difficulties in language production in HFA children, who exhibit reduced PFC activation and weaker interregional functional connectivity during the VFT.
DOI: 10.3389/fnins.2026.17364152026-03-31
George R. Uhl, Balaji Kannan, Sarah Jung, Joungil Choi, Ian Henderson, Kevin Schultz
Densities of neurofibrillary tangles (NFTs), a major Alzheimer’s disease (AD) pathology, display genetic associations with variants in the receptor type protein tyrosine phosphatase D (PTPRD) gene. NFTs are rich in tau protein that is hyperphosphorylated, prominently by the glycogen synthase kinases (GSK) 3α/β. PTPRD dephosphorylates GSK3s, reducing their activities and providing an attractive candidate molecular mechanism for PTPRD/NFT associations. We have used AT-8 and Aβ immunohistochemistry to assess hyperphosphorylated tau/NFT and Aβ/senile plaque pathologies, developed and characterized 3xTg-AD mice with wildtype or reduced PTPRD expression and assessed results of treatments with our (a) PTPRD phosphatase inhibitor pentilludin, (b) lead PTPRD positive allosteric modulator (PAM) quercetin and (c) drug candidate PTPRD PAM active metabolite 6BrQ. Four-month 3xTg-AD/PTPRD +/− mice display AT-8 immunoreactivity in hippocampal neurons, much earlier than 3xTg-AD/PTPRD +/+ mice. There are modest effects of reducing PTPRD expression on densities of Aβ/senile plaque structures assessed at 21 months. 3xTg-AD (but not wildtype C57) mice treated (weeks 6–16) with pentilludin display abundant hyperphosphorylated tau at 4 months. 3xTg-AD/PTPRD+/− mice treated (weeks 6–16) with quercetin or 6BrQ display >50% and >95% reductions in AT-8 immunoreactive hippocampal neuron counts, respectively. These results support roles for PTPRD in AD neurofibrillary pathophysiology and for orally-bioavailable drugs that can be metabolized to 6BrQ to slow development of this pathology.
DOI: 10.3389/fnins.2026.18033322026-03-30
Christopher K. Nguyen, Brandon S. Sturgill, Balaji Srikanthan, Behnoush Dousti, Madhav Bhatt, Mahasty Khajehzadeh, Soham Mangarolia, Nashita Hasan, Ana G. Hernandez-Reynoso, Sandeep Negi, Stuart F. Cogan
This study presents methods for evaluating the long-term electrochemical stability of Utah electrode arrays (UEAs) encapsulated with amorphous silicon carbide (a-SiC) or Parylene-C for intracortical microstimulation (ICMS). UEAs were implanted in rat motor cortex and monitored for 25 weeks using electrochemical impedance spectroscopy (EIS) to observe device impedance, cyclic voltammetry (CV) to obtain cathodic charge-storage capacity (Qstor,c), and voltage transient (VT) measurements to derive maximum charge-injection capacity (Qinj). Observed shifts in the open-circuit potential of the return electrode during stimulation, from in vitro to in vivo conditions, highlight the need to adjust potential limits when using a quasi-reference electrode. Both encapsulation materials exhibited stable impedance and maximum (Qinj) trends in vivo, becoming similar after approximately 16 weeks post-implant. High-scan rate CV (up to 500,000 mV/s) was used to assess similarities between Qstor,c and maximum Qinj and determine if it can be used to estimate the maximum Qinj. These methods can be used to evaluate the encapsulation and stimulation properties of chronically implanted neural electrodes.
DOI: 10.3389/fnins.2026.1789112