2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:Tc1b, Objective This systematic review evaluates the safety, feasibility, tolerability, and efficacy outcomes of intranasally administered stem cells and their derivatives (MSCs, NSCs, secretome, and EVs) for the treatment of neurological and respiratory disorders. Methods A literature search was conducted across PubMed, Google Scholar, Web of Science, Scopus, and ClinicalTrials.gov for published research from January 2011 to December 2025. A total of 19 studies were included (7 published articles, 12 registry-only or grey literature records). Risk of bias was assessed using two complementary Cochrane tools, the RoB 2 tool for all 19 studies and the ROBINS-I tool for the 6 n-RCTs. Sources of heterogeneity were systematically characterized across 5 clinical dimensions, and structural publication bias was evaluated against a 30% registry-only threshold. A random-effects model was selected for pooled analyses, with a planned subgroup analysis of treatment dosage against adverse events. Effect sizes were extracted using SMD, mean differences, risk ratios, and odds ratios as appropriate per outcome type. Results This systematic review was conducted in accordance with PRISMA 2020 guidelines. A total of 104 participants were enrolled in 7 published studies, with one completed registry trial (NCT04602104) confirming actual enrolment of an additional 18 participants. No study achieved an overall low risk of bias under either assessment tool. Under RoB 2, 1 published study was rated as having some concerns, others were rated high risk or some concerns. Under ROBINS-I, 3 n-RCT studies were rated critical overall. The remaining 3 were rated serious. Across the 7 published studies, 98 participants contributed to the analyzed outcomes. Structural publication bias was confirmed. Substantial clinical heterogeneity was identified across 9 conditions, multiple cell product categories, and mixed intranasal and intravenous delivery routes. Conclusion Although current evidence suggests that intranasal administration of stem cells, particularly MSCs and NSCs, in humans is a safe and feasible approach, with possible therapeutic improvements in CNS disorders. However, there is a serious risk of bias, critically small sample sizes, and pervasive publication bias in the available literature. Adequately powered, quadruple-blinded, placebo-controlled randomized trials need to be conducted before clinical translation can be considered. 31:T540,In 2021, of the US population of 332.7 million, disorders affecting nervous system health impacted 180.3 million (95% UI, 170.7 million to 190.4 million) US individuals and were the top cause of disability, with 16.6 million (95% UI, 12.9 million to 20.9 million) DALYs. The most prevalent conditions were tension-type headache (121.9 million; 95% UI, 109.4 million to 135.1 million), migraine (57.7 million; 95% UI, 50.1 million to 66.1 million), and diabetic neuropathy (17.1 million; 95% UI, 14.4 million to 19.9 million). Conditions with the greatest collective disability were stroke (3.9 million DALYs; 95% UI, 3.5 million to 4.2 million DALYs), Alzheimer disease and other dementias (3.3 million DALYs; 95% UI, 1.6 million to 6.9 million DALYs), diabetic neuropathy (2.2 million DALYs; 95% UI, 1.5 million to 3.0 million DALYs), and migraine (2.1 million DALYs; 95% UI, 0.4 million to 4.6 million DALYs). Compared with age-standardized metrics in 1990, the prevalence of disorders affecting the nervous system was nearly identical (-0.2%; 95% UI, -1.5% to 1.9%), with decreased attributable deaths (-14.6%; 95% UI, -18.3% to -11.3%) but increased YLDs (9.8%; 95% UI, 4.6% to 16.6%). By state, Mississippi, Alabama, and Louisiana had the largest age-standardized DALY rates, while New York, Massachusetts, and New Jersey had the smallest.32:Ta77,Nervous system health is a major contributor to population health, which is directly affected by neurological conditions and other disorders where nervous system damage occurs. To quantify aggregated health loss from diseases affecting the nervous system, including neurological disorders; neurodevelopmental disorders; congenital, neonatal, and systemic illnesses; and infectious diseases in the United States. This is a cross-sectional study of the Global Burden of Disease 2021 study data for nervous system health loss confined to the United States from 1990 through 2021 among the entire US population. Data analysis was performed from December 2021 to January 2025. Thirty-six unique conditions that cause harm to the nervous system. Totals and age-standardized estimates with 95% uncertainty intervals (UIs) for disability-adjusted life-years (DALYs), years lived with disability (YLDs), years of life lost (YLLs), total attributable deaths (where applicable), and prevalence. In 2021, of the US population of 332.7 million, disorders affecting nervous system health impacted 180.3 million (95% UI, 170.7 million to 190.4 million) US individuals and were the top cause of disability, with 16.6 million (95% UI, 12.9 million to 20.9 million) DALYs. The most prevalent conditions were tension-type headache (121.9 million; 95% UI, 109.4 million to 135.1 million), migraine (57.7 million; 95% UI, 50.1 million to 66.1 million), and diabetic neuropathy (17.1 million; 95% UI, 14.4 million to 19.9 million). Conditions with the greatest collective disability were stroke (3.9 million DALYs; 95% UI, 3.5 million to 4.2 million DALYs), Alzheimer disease and other dementias (3.3 million DALYs; 95% UI, 1.6 million to 6.9 million DALYs), diabetic neuropathy (2.2 million DALYs; 95% UI, 1.5 million to 3.0 million DALYs), and migraine (2.1 million DALYs; 95% UI, 0.4 million to 4.6 million DALYs). Compared with age-standardized metrics in 1990, the prevalence of disorders affecting the nervous system was nearly identical (-0.2%; 95% UI, -1.5% to 1.9%), with decreased attributable deaths (-14.6%; 95% UI, -18.3% to -11.3%) but increased YLDs (9.8%; 95% UI, 4.6% to 16.6%). By state, Mississippi, Alabama, and Louisiana had the largest age-standardized DALY rates, while New York, Massachusetts, and New Jersey had the smallest. Disorders affecting the nervous system are highly prevalent and cause disability for millions of US individuals, with reduced mortality leading to more YLDS. The United States should prioritize efforts to combat these conditions with development and implementation of new and effective prevention strategies, therapeutics, and focused rehabilitation.33:Tf54, Importance Nervous system health is a major contributor to population health, which is directly affected by neurological conditions and other disorders where nervous system damage occurs. Objective To quantify aggregated health loss from diseases affecting the nervous system, including neurological disorders; neurodevelopmental disorders; congenital, neonatal, and systemic illnesses; and infectious diseases in the United States. Design, Setting, and Participants This is a cross-sectional study of the Global Burden of Disease 2021 study data for nervous system health loss confined to the United States from 1990 through 2021 among the entire US population. Data analysis was performed from December 2021 to January 2025. Exposure Thirty-six unique conditions that cause harm to the nervous system. Main Outcomes and Measures Totals and age-standardized estimates with 95% uncertainty intervals (UIs) for disability-adjusted life-years (DALYs), years lived with disability (YLDs), years of life lost (YLLs), total attributable deaths (where applicable), and prevalence. Results In 2021, of the US population of 332.7 million, disorders affecting nervous system health impacted 180.3 million (95% UI, 170.7 million to 190.4 million) US individuals and were the top cause of disability, with 16.6 million (95% UI, 12.9 million to 20.9 million) DALYs. The most prevalent conditions were tension-type headache (121.9 million; 95% UI, 109.4 million to 135.1 million), migraine (57.7 million; 95% UI, 50.1 million to 66.1 million), and diabetic neuropathy (17.1 million; 95% UI, 14.4 million to 19.9 million). Conditions with the greatest collective disability were stroke (3.9 million DALYs; 95% UI, 3.5 million to 4.2 million DALYs), Alzheimer disease and other dementias (3.3 million DALYs; 95% UI, 1.6 million to 6.9 million DALYs), diabetic neuropathy (2.2 million DALYs; 95% UI, 1.5 million to 3.0 million DALYs), and migraine (2.1 million DALYs; 95% UI, 0.4 million to 4.6 million DALYs). Compared with age-standardized metrics in 1990, the prevalence of disorders affecting the nervous system was nearly identical (−0.2%; 95% UI, −1.5% to 1.9%), with decreased attributable deaths (−14.6%; 95% UI, −18.3% to −11.3%) but increased YLDs (9.8%; 95% UI, 4.6% to 16.6%). By state, Mississippi, Alabama, and Louisiana had the largest age-standardized DALY rates, while New York, Massachusetts, and New Jersey had the smallest. Conclusions and Relevance Disorders affecting the nervous system are highly prevalent and cause disability for millions of US individuals, with reduced mortality leading to more YLDS. The United States should prioritize efforts to combat these conditions with development and implementation of new and effective prevention strategies, therapeutics, and focused rehabilitation. 25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Neurological Disorders: condition Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Neurological Disorders (condition). Clinician-written summaries and actionable practice insights. 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Monitoring CMRO2 could serve as a meaningful biomarker of disease severity across multiple neurological conditions."}},{"doi":"10.1038/s41380-026-03819-6","pmid":"42595835","title":"Glial-neuronal crosstalk via GABA signaling: mechanistic insights into neuropsychiatric and neurological pathophysiology","journal_title":"Molecular Psychiatry","journal_issn":"1359-4184","published_at":"2026-08-13T00:00:00.000Z","url":"https://doi.org/10.1038/s41380-026-03819-6","source_score":10,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-19T06:28:49.475Z","updated_at":"2026-08-19T06:28:49.475Z","tags":[{"paper_doi":"10.1038/s41380-026-03819-6","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03819-6","tag_type":"category","value":"Psychiatry","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03819-6","tag_type":"condition","value":"Neurological Disorders","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03819-6","tag_type":"condition","value":"Neuropsychiatric Disorders","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03819-6","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03819-6","tag_type":"level_of_evidence","value":"7","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03819-6","tag_type":"modality","value":"GABAergic Signaling","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03819-6","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03819-6","tag_type":"warning","value":"No specific neuropsychiatric or neurological diseases are listed individually in the abstract — the review appears to cover multiple conditions but the abstract does not enumerate them; tags reflect the broad scope as described.","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03819-6","tag_type":"warning","value":"Published date (2026-08-13) is recent; the review may cite preprints or emerging findings not yet independently replicated.","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03819-6","tag_type":"warning","value":"Study design classification as 'Narrative Review' is inferred from abstract language; no explicit systematic review methodology is described.","value_numeric":null}],"summaries":{"what_studied":"This review examines how GABA mediates glial-neuronal crosstalk — covering how astrocytes, microglia, oligodendrocytes, and oligodendrocyte progenitor cells sense, synthesize, uptake, and release GABA — and how disruptions in GABAergic signaling and GABA mitochondrial metabolism contribute to neurological and neuropsychiatric disorders.","key_result":"Glial cells express diverse GABA receptor subtypes and actively participate in GABA synthesis and release; GABA metabolism is primarily mitochondrial, so perturbations in these pathways can impair glial bioenergetics, trigger pathological glial state transitions, and disrupt circuit homeostasis across multiple CNS disease states.","limitations":"As a narrative review, no original data are presented and no systematic search strategy or risk-of-bias assessment is reported; causal directionality between GABA metabolic disruption and disease progression remains largely inferential.","practice_takeaway":"Clinicians managing neuropsychiatric or neurological conditions should be aware that GABAergic dysfunction may involve glial biology and mitochondrial metabolism — not just neuronal signaling — which could inform future therapeutic targets beyond classic GABA receptor agonists/antagonists."}},{"doi":"10.1038/s41583-026-01061-1","pmid":"42443461","title":"Brain mitochondria as key drivers of cognition and behaviour","journal_title":"Nature Reviews Neuroscience","journal_issn":"1471-003X","published_at":"2026-07-13T00:00:00.000Z","url":"https://doi.org/10.1038/s41583-026-01061-1","source_score":21,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-22T13:37:32.645Z","updated_at":"2026-07-22T13:37:32.645Z","tags":[{"paper_doi":"10.1038/s41583-026-01061-1","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1038/s41583-026-01061-1","tag_type":"category","value":"Neurosciences","value_numeric":null},{"paper_doi":"10.1038/s41583-026-01061-1","tag_type":"condition","value":"Anxiety Disorders","value_numeric":null},{"paper_doi":"10.1038/s41583-026-01061-1","tag_type":"condition","value":"Cognitive Dysfunction","value_numeric":null},{"paper_doi":"10.1038/s41583-026-01061-1","tag_type":"condition","value":"Neurological Disorders","value_numeric":null},{"paper_doi":"10.1038/s41583-026-01061-1","tag_type":"condition","value":"Psychiatric Disorders","value_numeric":null},{"paper_doi":"10.1038/s41583-026-01061-1","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1038/s41583-026-01061-1","tag_type":"level_of_evidence","value":"7","value_numeric":null},{"paper_doi":"10.1038/s41583-026-01061-1","tag_type":"modality","value":"Mitochondrial Therapeutics","value_numeric":null},{"paper_doi":"10.1038/s41583-026-01061-1","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1038/s41583-026-01061-1","tag_type":"warning","value":"No specific drugs, generics, or brands are evaluated; the modality tag reflects the broader therapeutic direction discussed, not a specific intervention.","value_numeric":null},{"paper_doi":"10.1038/s41583-026-01061-1","tag_type":"warning","value":"The 'practice_changing' impact flag reflects the conceptual framework proposed (two-mode mitochondrial support model) rather than a clinical trial result — the translational implications are speculative at this stage.","value_numeric":null},{"paper_doi":"10.1038/s41583-026-01061-1","tag_type":"warning","value":"This is a high-level narrative review published in July 2026; no primary experimental data or sample population are presented, so effect sizes and clinical applicability cannot be quantified.","value_numeric":null}],"summaries":{"what_studied":"This review examines how mitochondria in neurons and glia drive cognition and behaviour by supporting neural circuit function — covering bioenergetics, Ca²⁺ dynamics, reactive oxygen species, neurotransmitter synthesis, and quality control programmes across two modes: a baseline mode (long-term circuit architecture) and an activity-evoked mode (synaptic transmission and plasticity).","key_result":"The authors propose that mitochondrial support operates in two distinct modes — baseline (sustaining circuit readiness over long timescales) and activity-evoked (supporting active synaptic engagement) — and that behavioural modulators such as stress hormones, immune activity, and metabolic signals shape cognition by altering one or both modes.","limitations":"As a narrative review, no primary data are presented and causal claims rely on synthesis of heterogeneous experimental evidence; mechanistic links between mitochondrial function and specific behaviours (e.g., anxiety, motivation) remain correlative in many cited studies.","practice_takeaway":"Clinicians managing conditions tied to stress, metabolic dysregulation, or neuroinflammation should be aware that mitochondrial dysfunction may be a shared upstream driver of cognitive and behavioural symptoms. Targeting mitochondrial health may represent a future therapeutic lever across psychiatric and neurological disorders."}},{"doi":"10.1016/j.ajog.2026.07.008","pmid":"42431247","title":"Ischemic Placental Disease and Hospitalization for Neurological and Psychiatric Disorders","journal_title":"American Journal of Obstetrics and Gynecology","journal_issn":"0002-9378","published_at":"2026-07-10T00:00:00.000Z","url":"https://doi.org/10.1016/j.ajog.2026.07.008","source_score":10,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-25T13:57:45.287Z","updated_at":"2026-07-25T13:57:45.287Z","tags":[{"paper_doi":"10.1016/j.ajog.2026.07.008","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.ajog.2026.07.008","tag_type":"category","value":"Obstetrics & Gynecology","value_numeric":null},{"paper_doi":"10.1016/j.ajog.2026.07.008","tag_type":"condition","value":"Fetal Growth Restriction","value_numeric":null},{"paper_doi":"10.1016/j.ajog.2026.07.008","tag_type":"condition","value":"Ischemic Placental Disease","value_numeric":null},{"paper_doi":"10.1016/j.ajog.2026.07.008","tag_type":"condition","value":"Neurological Disorders","value_numeric":null},{"paper_doi":"10.1016/j.ajog.2026.07.008","tag_type":"condition","value":"Placental Abruption","value_numeric":null},{"paper_doi":"10.1016/j.ajog.2026.07.008","tag_type":"condition","value":"Postpartum Depression","value_numeric":null},{"paper_doi":"10.1016/j.ajog.2026.07.008","tag_type":"condition","value":"Post-Traumatic Stress Disorder","value_numeric":null},{"paper_doi":"10.1016/j.ajog.2026.07.008","tag_type":"condition","value":"Preeclampsia","value_numeric":null},{"paper_doi":"10.1016/j.ajog.2026.07.008","tag_type":"condition","value":"Psychiatric Disorders","value_numeric":null},{"paper_doi":"10.1016/j.ajog.2026.07.008","tag_type":"condition","value":"Stroke","value_numeric":null},{"paper_doi":"10.1016/j.ajog.2026.07.008","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/j.ajog.2026.07.008","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1016/j.ajog.2026.07.008","tag_type":"sample_size","value":"n=17368071","value_numeric":17368071},{"paper_doi":"10.1016/j.ajog.2026.07.008","tag_type":"sex","value":"female","value_numeric":null},{"paper_doi":"10.1016/j.ajog.2026.07.008","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1016/j.ajog.2026.07.008","tag_type":"warning","value":"Brain disorder diagnoses are based on administrative ICD codes, which may undercount or misclassify conditions; the authors applied quantitative bias analysis but residual misclassification is possible.","value_numeric":null},{"paper_doi":"10.1016/j.ajog.2026.07.008","tag_type":"warning","value":"The 'impact_flag' of practice_changing reflects the large sample size and dose-response finding, but causality cannot be established from this observational design.","value_numeric":null},{"paper_doi":"10.1016/j.ajog.2026.07.008","tag_type":"warning","value":"The study uses calendar-year follow-up rather than a fixed postpartum window (e.g., 12 months from delivery date), which may introduce variability in follow-up duration across patients.","value_numeric":null}],"summaries":{"what_studied":"This population-based retrospective cohort study used the US Nationwide Readmissions Database (2010–2020) to examine whether ischemic placental disease (preeclampsia, placental abruption, and/or fetal growth restriction) is associated with postpartum hospitalization for neurological and psychiatric disorders in women aged 15–54, within the calendar year of delivery.","key_result":"Among 17,368,071 deliveries, 10.7% had ischemic placental disease. Brain disorder hospitalization rates were 1,219 vs. 730 per 10,000 deliveries (with vs. without ischemic placental disease; adjusted HR 1.50, 95% CI 1.48–1.51). Risk rose in a dose-dependent fashion: HR 1.47 with 1 condition, 1.66 with 2, and 1.85 with all 3.","limitations":"- Administrative claims data rely on coded diagnoses, introducing potential outcome misclassification (though quantitative bias analysis was applied).\n- Unmeasured confounding cannot be fully excluded despite bias corrections.\n- Follow-up was limited to the calendar year of delivery, so longer-term outcomes are not captured.","practice_takeaway":"Women with ischemic placental disease face a ~50% higher risk of hospitalization for brain disorders—including stroke, depression, PTSD, and suicide attempt—within the postpartum year. Clinicians should treat ischemic placental disease as a neurological and psychiatric risk signal, prompting closer postpartum mental health and neurological surveillance."}},{"doi":"10.1037/neu0001063","pmid":"41359566","title":"Differential diagnosis in clinical neuropsychology: A case example of assessment without testing.","journal_title":"Neuropsychology","journal_issn":"1931-1559","published_at":"2026-07-01T00:00:00.000Z","url":"https://doi.org/10.1037/neu0001063","source_score":13,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-17T13:24:17.588Z","updated_at":"2026-07-17T13:24:17.588Z","tags":[{"paper_doi":"10.1037/neu0001063","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1037/neu0001063","tag_type":"category","value":"Psychology, Clinical","value_numeric":null},{"paper_doi":"10.1037/neu0001063","tag_type":"condition","value":"Cognitive Impairment","value_numeric":null},{"paper_doi":"10.1037/neu0001063","tag_type":"condition","value":"Neurological Disorders","value_numeric":null},{"paper_doi":"10.1037/neu0001063","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1037/neu0001063","tag_type":"level_of_evidence","value":"6","value_numeric":null},{"paper_doi":"10.1037/neu0001063","tag_type":"modality","value":"Neuropsychological Assessment","value_numeric":null},{"paper_doi":"10.1037/neu0001063","tag_type":"sample_size","value":"n=1","value_numeric":1},{"paper_doi":"10.1037/neu0001063","tag_type":"study_design","value":"Case Report","value_numeric":null},{"paper_doi":"10.1037/neu0001063","tag_type":"warning","value":"Sex of the patient is not reported in the abstract or methods; sex tag omitted.","value_numeric":null},{"paper_doi":"10.1037/neu0001063","tag_type":"warning","value":"Study design is a single case/educational case example rather than a traditional case report; findings are illustrative and not meant to be generalizable.","value_numeric":null},{"paper_doi":"10.1037/neu0001063","tag_type":"warning","value":"The specific neurological or psychiatric conditions considered in the differential diagnosis are not detailed in the available text, limiting condition tagging precision.","value_numeric":null}],"summaries":{"what_studied":"This case example explores how neuropsychological differential diagnosis can be conducted using only clinical history and behavioral observations — without standardized testing or brain imaging — in a patient unable to participate in formal assessment.","key_result":"History and behavioral observations, analyzed in the context of disease base rates, were sufficient to rule in/rule out differential diagnoses involving both the peripheral and central nervous systems, demonstrating that assessment can occur independent of standardized testing.","limitations":"Single case example with no standardized test data or neuroimaging, severely limiting generalizability and diagnostic precision; findings cannot be quantified or statistically validated.","practice_takeaway":"When standardized testing is not possible, clinicians can still conduct meaningful neuropsychological assessment by systematically applying history-taking, behavioral observation, and disease base rates. This approach is a core competency that practitioners should be prepared to use in real-world, uncontrolled clinical settings."}},{"doi":"10.1016/j.tins.2026.05.002","pmid":"42336722","title":"The neural basis of laughter","journal_title":"Trends in Neurosciences","journal_issn":"0166-2236","published_at":"2026-06-23T00:00:00.000Z","url":"https://doi.org/10.1016/j.tins.2026.05.002","source_score":389,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-28T13:27:07.482Z","updated_at":"2026-06-28T13:27:07.482Z","tags":[{"paper_doi":"10.1016/j.tins.2026.05.002","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.tins.2026.05.002","tag_type":"category","value":"Neurosciences","value_numeric":null},{"paper_doi":"10.1016/j.tins.2026.05.002","tag_type":"condition","value":"Gelastic Seizures","value_numeric":null},{"paper_doi":"10.1016/j.tins.2026.05.002","tag_type":"condition","value":"Neurological Disorders","value_numeric":null},{"paper_doi":"10.1016/j.tins.2026.05.002","tag_type":"condition","value":"Pathological Laughter","value_numeric":null},{"paper_doi":"10.1016/j.tins.2026.05.002","tag_type":"condition","value":"Pseudobulbar Affect","value_numeric":null},{"paper_doi":"10.1016/j.tins.2026.05.002","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1016/j.tins.2026.05.002","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1016/j.tins.2026.05.002","tag_type":"modality","value":"Direct Electrical Stimulation","value_numeric":null},{"paper_doi":"10.1016/j.tins.2026.05.002","tag_type":"modality","value":"Intracranial Recording","value_numeric":null},{"paper_doi":"10.1016/j.tins.2026.05.002","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1016/j.tins.2026.05.002","tag_type":"warning","value":"No primary data or sample size is reported — this is a theoretical/framework review based on synthesis of prior invasive studies.","value_numeric":null},{"paper_doi":"10.1016/j.tins.2026.05.002","tag_type":"warning","value":"Study design label 'Narrative Review' is inferred from abstract language; the paper does not explicitly state whether it follows systematic review methodology.","value_numeric":null},{"paper_doi":"10.1016/j.tins.2026.05.002","tag_type":"warning","value":"The dual-system framework is a proposed model, not yet empirically validated as a standalone construct; clinical applications should be interpreted cautiously.","value_numeric":null}],"summaries":{"what_studied":"This review examines the neural circuitry underlying laughter, drawing on invasive methods such as direct electrical stimulation and intracranial recordings to map the brain networks involved in both spontaneous and volitional laughter.","key_result":"The authors propose a dual-system framework: (1) an evolutionarily ancient cingulo-temporal network acting as the gateway for involuntary, spontaneous laughter; and (2) a lateral motor-opercular system that recruits speech-production networks for volitional, conversational laughter — with parallel cortico-subcortical pathways driving both.","limitations":"As a narrative review, no primary data or statistical outcomes are reported. The authors acknowledge that reproducing spontaneous laughter in controlled laboratory settings remains a core methodological challenge, which may limit the completeness of the circuitry mapped so far.","practice_takeaway":"Clinicians evaluating neurological disorders featuring pathological laughter (e.g., pseudobulbar affect, gelastic seizures) can use this dual-system framework to better localize lesions or stimulation targets. The cingulo-temporal vs. motor-opercular distinction may help differentiate involuntary from volitional laughter deficits at the bedside."}},{"doi":"10.1038/s41562-026-02503-7","pmid":"42332113","title":"Potential mechanisms and functional significance of aperiodic neural activity","journal_title":"Nature Human Behaviour","journal_issn":"2397-3374","published_at":"2026-06-22T00:00:00.000Z","url":"https://doi.org/10.1038/s41562-026-02503-7","source_score":19,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-28T13:27:10.588Z","updated_at":"2026-06-28T13:27:10.588Z","tags":[{"paper_doi":"10.1038/s41562-026-02503-7","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1038/s41562-026-02503-7","tag_type":"category","value":"Neurosciences","value_numeric":null},{"paper_doi":"10.1038/s41562-026-02503-7","tag_type":"condition","value":"Neurodevelopmental Disorders","value_numeric":null},{"paper_doi":"10.1038/s41562-026-02503-7","tag_type":"condition","value":"Neurological Disorders","value_numeric":null},{"paper_doi":"10.1038/s41562-026-02503-7","tag_type":"condition","value":"Psychiatric Disorders","value_numeric":null},{"paper_doi":"10.1038/s41562-026-02503-7","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1038/s41562-026-02503-7","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1038/s41562-026-02503-7","tag_type":"modality","value":"Electrophysiology","value_numeric":null},{"paper_doi":"10.1038/s41562-026-02503-7","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1038/s41562-026-02503-7","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1038/s41562-026-02503-7","tag_type":"warning","value":"No sample size is applicable — this is a review article with no primary dataset.","value_numeric":null},{"paper_doi":"10.1038/s41562-026-02503-7","tag_type":"warning","value":"Study design labeled as 'Narrative Review' rather than 'Systematic Review' or 'Meta-Analysis' based on the absence of any described systematic search or pooled quantitative analysis.","value_numeric":null},{"paper_doi":"10.1038/s41562-026-02503-7","tag_type":"warning","value":"The 'practice_changing' impact flag is applied cautiously: the review synthesizes emerging evidence that reframes how neural noise should be interpreted, which has broad methodological implications, but direct clinical protocols are not yet established.","value_numeric":null}],"summaries":{"what_studied":"This review examines aperiodic neural activity — the broadband, non-oscillatory component of electrophysiological signals — covering its physiological generators, relationship to other neural measures, and relevance to cognition, development, ageing, and disease.","key_result":"Computational modelling and empirical evidence converge on postsynaptic transmembrane currents across neuronal populations as the primary source of aperiodic activity; the review also links aperiodic measures to functional and clinical outcomes across development, ageing, and neurological/psychiatric conditions.","limitations":"As a narrative review, it does not perform quantitative meta-analysis, so effect-size estimates across studies are not synthesized; many mechanistic claims rest on computational models whose assumptions may not fully capture in vivo complexity.","practice_takeaway":"Aperiodic neural activity — long dismissed as noise — carries physiologically meaningful information about excitation/inhibition balance and may serve as a clinically useful biomarker across neurological and psychiatric conditions. Clinicians and researchers should be aware of new analysis methods that separate aperiodic from periodic (oscillatory) signal components before drawing conclusions from EEG or LFP data."}},{"doi":"10.1038/s41593-026-02301-4","pmid":"42225897","title":"Deep brain stimulation induces white matter remodeling and functional changes to brain-wide networks","journal_title":"Nature Neuroscience","journal_issn":"1097-6256","published_at":"2026-06-01T00:00:00.000Z","url":"https://doi.org/10.1038/s41593-026-02301-4","source_score":109,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-11T13:42:53.826Z","updated_at":"2026-06-11T13:42:53.826Z","tags":[{"paper_doi":"10.1038/s41593-026-02301-4","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02301-4","tag_type":"category","value":"Neurosciences","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02301-4","tag_type":"condition","value":"Neurological Disorders","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02301-4","tag_type":"condition","value":"Treatment-Resistant Depression","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02301-4","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02301-4","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02301-4","tag_type":"modality","value":"Deep Brain Stimulation","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02301-4","tag_type":"study_design","value":"Controlled Animal Study","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02301-4","tag_type":"warning","value":"Full page text was not extractable from the PDF; sample sizes, exact statistical results, and stimulation parameters could not be confirmed and are not included in the summary.","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02301-4","tag_type":"warning","value":"Level of evidence set to 5 (animal/experimental study) given the preclinical macaque model design.","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02301-4","tag_type":"warning","value":"Study was conducted in macaques — generalizability to human clinical DBS practice should be interpreted with caution.","value_numeric":null}],"summaries":{"what_studied":"This study examined the anatomical and functional effects of subcallosal anterior cingulate cortex deep brain stimulation (SCC-DBS) in macaques, modeling the white matter-targeted approach used in treatment-resistant depression in humans. Outcomes included white matter microstructure (fractional anisotropy), cellular changes (myelination, oligodendrocytes), and brain-wide functional connectivity.","key_result":"SCC-DBS selectively increased fractional anisotropy in the cingulum bundle, associated with increased myelinated oligodendrocytes and greater myelination in the mid-cingulum. Functional connectivity was also altered brain-wide, with notable changes in interactions between the SCC and the default mode network.","limitations":"- Animal model only (macaques); direct translation to human DBS outcomes is uncertain.\n- Full text pages were not extractable, so sample sizes, stimulation parameters, and statistical details could not be verified from the source.\n- Causal link between white matter remodeling and clinical antidepressant efficacy remains inferred, not directly tested.","practice_takeaway":"SCC-DBS may work partly by remodeling white matter and reshaping default mode network connectivity — not just by acute neuromodulation. Clinicians should consider that structural brain changes may be part of DBS's therapeutic mechanism in depression."}},{"doi":"10.3389/fnagi.2026.1834543","pmid":null,"title":"Intranasal administration of stem cells and their derivatives for neurological and respiratory disorders: a systematic review of human clinical trials","journal_title":"Frontiers in Aging Neuroscience","journal_issn":"1663-4365","published_at":"2026-05-07T00:00:00.000Z","url":"https://doi.org/10.3389/fnagi.2026.1834543","source_score":184,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-05-10","doi":"10.3389/fnagi.2026.1834543","days":"7","issn":"1663-4365","rank":"2","field":"Clinical Medicine","score":"184","category":"Neurosciences","categories":["Neurosciences"],"_categories":["Neurosciences"]},"pubmed":null,"crossref":{"DOI":"10.3389/fnagi.2026.1834543","URL":"https://doi.org/10.3389/fnagi.2026.1834543","ISSN":["1663-4365"],"link":[{"URL":"https://www.frontiersin.org/articles/10.3389/fnagi.2026.1834543/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":null,"score":1,"title":["Intranasal administration of stem cells and their derivatives for neurological and respiratory disorders: a systematic review of human clinical trials"],"author":[{"given":"Umm E.","family":"Habiba","sequence":"first","affiliation":[{"name":"Research and Development (R&D) Department, R3 Stem Cell LLC"},{"name":"Research and Development (R&D) Department, R3 Medical Research LLC"}]},{"given":"Roshini","family":"Sathyanarayanan","sequence":"additional","affiliation":[{"name":"Research and Development (R&D) Department, R3 Medical Research LLC"}]},{"given":"Sabiha","family":"Shamim","sequence":"additional","affiliation":[{"name":"Research and Development (R&D) Department, R3 Medical Research LLC"}]},{"given":"Aishwarya","family":"Manian","sequence":"additional","affiliation":[{"name":"Research and Development (R&D) Department, R3 Medical Research LLC"}]},{"given":"Ammar","family":"Haider","sequence":"additional","affiliation":[{"name":"Research and Development (R&D) Department, R3 Medical Research LLC"}]},{"given":"Iqra","family":"Sarwar","sequence":"additional","affiliation":[{"name":"Research and Development (R&D) Department, R3 Medical Research LLC"}]},{"given":"David Lawrence","family":"Greene","sequence":"additional","affiliation":[{"name":"Research and Development (R&D) Department, R3 Stem Cell LLC"},{"name":"Research and Development (R&D) Department, R3 Medical Research LLC"}]}],"issued":{"date-parts":[[2026,5,7]]},"member":"1965","prefix":"10.3389","source":"Crossref","volume":"18","created":{"date-time":"2026-05-07T05:41:35Z","timestamp":1778132495000,"date-parts":[[2026,5,7]]},"indexed":{"date-time":"2026-05-07T06:14:44Z","timestamp":1778134484033,"date-parts":[[2026,5,7]]},"license":[{"URL":"https://creativecommons.org/licenses/by/4.0/","start":{"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000,"date-parts":[[2026,5,7]]},"delay-in-days":0,"content-version":"vor"}],"subject":[],"abstract":"$30","relation":{},"resource":{"primary":{"URL":"https://www.frontiersin.org/articles/10.3389/fnagi.2026.1834543/full"}},"subtitle":[],"deposited":{"date-time":"2026-05-07T05:41:36Z","timestamp":1778132496000,"date-parts":[[2026,5,7]]},"issn-type":[{"type":"electronic","value":"1663-4365"}],"published":{"date-parts":[[2026,5,7]]},"publisher":"Frontiers Media SA","reference":[{"DOI":"10.1186/s13287-025-04254-0","key":"ref1","year":"2025","issue":null,"author":"Allouh","volume":"16","first-page":"127","unstructured":null,"article-title":"Mesenchymal stromal/stem cells from perinatal sources: biological facts, molecular biomarkers, and therapeutic promises","journal-title":"Stem Cell Res Ther","doi-asserted-by":"publisher"},{"DOI":"10.3390/pharmaceutics14020381","key":"ref2","year":"2022","issue":null,"author":"Alvites","volume":"14","first-page":"381","unstructured":null,"article-title":"Mesenchymal stem/stromal cells and their paracrine activity—immunomodulation mechanisms and how to influence the therapeutic potential","journal-title":"Pharmaceutics","doi-asserted-by":"publisher"},{"DOI":"10.25259/SNI_233_2020","key":"ref3","year":"2020","issue":null,"author":"Boika","volume":"11","first-page":"380","unstructured":null,"article-title":"Mesenchymal stem cells in Parkinson’s disease: motor and nonmotor symptoms in the early posttransplant period","journal-title":"Surg. 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Structural publication bias was confirmed (63% registry-only or grey literature, exceeding the 30% threshold). Across 98 analyzed participants from 7 published studies, intranasal delivery was consistently reported as safe with no serious adverse events, and preliminary signals of benefit appeared in cerebral palsy, perinatal stroke, and Alzheimer's disease — but no efficacy conclusion is interpretable due to open-label design, absent sham controls, and unblinded outcome assessment in every published trial.","limitations":"- Every published study lacked randomization, sham/placebo intranasal control, and blinded outcome assessment, making efficacy estimates uninterpretable as biological activity.\n- Multiple studies combined intranasal and intravenous delivery, preventing route-specific attribution of any observed effect.\n- The review itself was not pre-registered in PROSPERO, and several authors have direct conflicts of interest (employment by the stem cell manufacturer whose products were evaluated).","practice_takeaway":"Do not adopt intranasal stem cell or exosome therapy for any neurological or respiratory condition based on current evidence — no adequately powered, blinded, sham-controlled trial has been completed or published. 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Disability was highest for stroke 3.9 million DALYs (95% UI, 3.5–4.2), Alzheimer disease and other dementias 3.3 million (95% UI, 1.6–6.9), diabetic neuropathy 2.2 million (95% UI, 1.5–3.0), and migraine 2.1 million (95% UI, 0.4–4.6); since 1990, age-standardized prevalence was flat (-0.2%; 95% UI, -1.5 to 1.9), deaths fell (-14.6%; 95% UI, -18.3 to -11.3), and YLDs rose (9.8%; 95% UI, 4.6–16.6), with the highest DALY rates in Mississippi, Alabama, and Louisiana and the lowest in New York, Massachusetts, and New Jersey.","practice_takeaway":"Disorders affecting the nervous system are widespread and now the top cause of disability in the US; falling mortality means more people are living with disability. Health systems should prioritize prevention, effective therapies, and focused rehabilitation for these conditions."}}],"initialOffset":10,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"condition","value":"Neurological Disorders"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Conditions","href":"/hub/tag/condition"},{"name":"Neurological Disorders"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"condition","hub_tag_value":"Neurological Disorders"}}}]]

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