Puerariae Lobatae Radix-Gastrodiae Rhizoma ameliorates nitroglycerin-induced chronic migraine by modulating p38 MAPK/CREB signaling pathway in the prefrontal cortex-thalamus neural circuit.

Reward motivation refers to the willingness to expend effort in pursuit of reward, which is believed to be affected by reward magnitude, effort level, and subjective value, but its neural basis remains unclear. The present study aims to identify brain regions associated with reward magnitude, effort level, and subjective value in healthy people. We performed an activation likelihood estimation meta-analysis. Moreover, we conducted meta-analytic connectivity modeling to examine the coactivation patterns associated with these regions. Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines and eligibility criteria, we included 33 task-based functional imaging studies with effort-based reward tasks. The activation likelihood estimation and meta-analytic connectivity modeling meta-analyses found that increased reward magnitude primarily elicited activation in the caudate head and putamen, with coactivation observed in the claustrum, insula, dorsal thalamus, and midbrain red nucleus. Moreover, elevated effort level predominantly engaged the medial frontal gyrus, showing coactivation with the insula and inferior frontal gyrus. Enhanced subjective value was chiefly associated with caudate head activation, coactivated with the thalamus, parahippocampal gyrus, and insula. Our findings provided a framework delineating the integrated insula-frontostriatal-thalamus network for the reward valuation system in healthy people. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

The ascending sensory projections from the dorsal thalamus to the pallium are one of the most distinctive features of the amniote brain. In mammals, these projections can be broadly classified into two main types: (1) those arising from "core" neurons, mostly located in the central region of sensory nuclei, which relay topographic inputs to the intermediate layers of primary sensory cortices, forming a reciprocal circuit with the reticular thalamic nucleus (RTN); and (2) those originating from "matrix" neurons, located in the periphery of sensory nuclei, which project to superficial layers of primary and higher order cortices. To date, both the reciprocal core-RTN circuitry and the matrix projections have only been described in mammals. In this study, we re-examined the organization of thalamic projections to the visual dorsal ventricular ridge (DVR) in pigeons using neural tracing techniques. In addition to the well-known projection from the thalamic nucleus rotundus (Rt) to the ventral layer of the visual DVR (entopallium), we described a reciprocal projection pattern between the Rt and the RTN. Moreover, we identified a second ascending thalamopallial projection, arising from neurons surrounding the Rt and terminating primarily in the intermediate layer of the visual DVR. These neurons form a continuous "matrix" of cells within the dorsal thalamus, which as a group also give rise to axons targeting several associative pallial areas. Furthermore, we found that this "matrix" region receives descending inputs from the motor arcopallium. Collectively, these findings indicate that the avian thalamopallial system is more complex than previously recognized and thus more comparable to its mammalian counterpart.

Background and objectivePostoperative cerebral hyperperfusion syndrome (CHS) remains a common and serious complication after extracranial-intracranial (EC-IC) bypass for moyamoya disease (MMD). This study aimed to identify preoperative hemodynamic predictors of CHS using quantitative whole-brain CT perfusion (WB-CTP) analysis.MethodsThe author retrospectively analyzed 103 hemispheres from 89 MMD patients who underwent direct bypass from January 2024 to December 2024. Preoperative WB-CTP scans based on the Alberta Stroke Program Early CT score (ASPECTS) topography were processed to quantify cerebral blood flow (CBF) and time to peak (Tmax) across various brain regions, with the cerebellum serving as the reference. CHS was diagnosed based on clinical and radiological criteria. Univariable and multivariable logistic regression analyses were performed to identify independent predictors, and receiver operating characteristic (ROC) analysis was used to evaluate predictive performance.ResultsPostoperative CHS occurred in 11.7% (12/103) of the included cases. Univariable analysis revealed Suzuki stage, moyamoya vessel density, and Tmax values in the thalamus (THAL) and posterior cerebral artery (PCA) regions as significant factors. Multivariable analysis confirmed advanced Suzuki stage (OR (95% CI), 8.87(1.44–54.45), p = 0.018), and lower PCA Tmax (OR (95% CI), 0.03 (0.00–0.69), p = 0.029) as independent predictors. ROC analysis demonstrated that combining Suzuki stage and PCA Tmax achieved an AUC of 0.83 (cut-off value = 0.060), indicating good discriminative performance for predicting postoperative CHS.ConclusionAdvanced Suzuki stage and reduced PCA Tmax are independent risk factors for postoperative CHS after direct bypass in MMD patients. Preoperative ASPECTS-based quantitative CTP analysis can effectively stratify CHS risk and support individualized surgical planning and perioperative management.

Hypergraph-Based Multimodal MRI Reveals Thalamus-Mediated Network Dyscoordination Underlying Motor Impairments in Parkinson's Disease.

The thalamus plays a crucial role in integrating subcortical inputs and relaying them to cortical circuits, yet the extent and specificity of dopaminergic innervation to human thalamic nuclei remain incompletely understood. Recent tractographybased studies suggest the existence of direct nigro-thalamic pathways, but direct histological evidence is still limited. In this study, we provide an ex vivo mapping of dopaminergic projections to the human thalamus using high-resolution immunohistochemistry and confocal microscopy. Human brain specimens were processed to detect multiple dopaminergic markers, including tyrosine hydroxylase (TH), vesicular monoamine transporter 2 (VMAT2), and aromatic L-amino acid decarboxylase (AADC), across anatomically defined thalamic nuclei. Multilabel immunofluorescence and 3D reconstruction allowed precise identification of axonal arborization and synaptic varicosities within the mediodorsal (MD), and ventral anterior (VA)/ventral lateral (VL) nuclei. Quantitative analysis revealed a significant expression of TH+/VMAT2+ fibers and D2R staining in the MD/VA/VL nuclei, supporting the notion of region-specific dopaminergic input. These results provide the first immunohistological confirmation of selective dopaminergic innervation of the human thalamus. This structural evidence complements prior neuroimaging findings and suggests a potential role for the nigro- thalamic pathway in modulating thalamo-cortical circuits involved in executive and cognitive functions.

BackgroundSelective cellular vulnerability is a hallmark of several late onset neurodegenerative disorders, including Alzheimer's Disease (AD). In AD, neurofibrillary tangles first accumulate in the transentorhinal cortex, subsequently spreading to the hippocampus and across the cerebrum. Consequently, existing research has primarily focused on these regions. However, other brain areas affected early in AD, such as the thalamus, remain underexplored. While the thalamus is well‐known as the brain's primary sensorimotor relay station, it's increasingly recognized as playing a crucial role in memory and spatial navigation. Postmortem studies reveal widespread amyloid and tau deposition across various thalamic nuclei early in the pathophysiology of AD. Furthermore, neuroimaging studies demonstrate significant thalamic atrophy, white matter alterations, and functional connectivity changes to occur in the initial stages of cognitive decline, prior to AD conversion. Despite these observations, little is known about selective cellular vulnerability within the thalamus and its contribution to cognitive and functional decline in AD.MethodImmunohistochemical neuropathological profiling was used to identify vulnerable thalamic nuclei in postmortem brain tissue from early AD donors. These regions were sub‐dissected, and nuclei were isolated from human control (Braak Stage 0) and early AD (Braak Stages I‐IV) postmortem brain tissues using established protocols. Fluorescence‐activated nuclear sorting (FANS) was employed to isolate specific thalamic cell types for bulk RNA sequencing. Analysis of gene expression profiles for each cell type confirmed the effectiveness of this approach in selectively and reproducibly isolating thalamic cell populations.ResultUsing FANS, we successfully isolated six distinct thalamic cell types from AD‐implicated nuclei in postmortem human brain tissue from both control and early AD donors. These cell types include glutamatergic thalamic projection neurons (TPNs), GABAergic inhibitory interneurons, astrocytes, microglia, oligodendrocytes, and oligodendrocyte precursor cells (OPCs). We will next perform comprehensive transcriptional and epigenetic profiling to investigate cell‐type specific changes in the human thalamus during early AD.ConclusionNeuropathological profiling of early AD donors supports previous studies indicating that the thalamus is affected early in AD. Our preliminary results indicate that our current dissection and sorting strategy will be valuable for uncovering AD‐related alterations in the thalamus and elucidating its role in disease progression.

IntroductionM4 muscarinic receptor (mAChR) knockout changed the female activity biological rhythm parameters. In this study, we focus on the biological rhythms of mAChRs (total + M1 mAChRs), acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) in M4 mAChR knockout (M4KO) and wild-type (WT) mice in specific brain areas.MethodsFemale mice were sacrificed every 4 hours, brains were removed, mAChRs were determined by autoradiography, and punching was used for the measurement of acetylcholinesterase and butyrylcholinesterase activity. The density of mAChRs was correlated with locomotor activity.ResultsAn ultradian rhythm in total mAChRs was found in the suprachiasmatic nucleus (SCN) (both M4KO and WT). M4KO had a positive correlation between the number of mAChRs and locomotor activity. This rhythm was changed to circadian in WT with a peak in the active phase and to circadian rhythm in M4KO with phase shifts to the inactive/active phase in the intergeniculate leaflet (IgL) (positive correlation in KO), subparaventricular zone (SPVZ) (negative correlation in WT), and posterior hypothalamic area (PHA) (positive correlation in WT). The thalamus (TH) reveals circadian rhythms in WT and M4KO, with a peak in the active phase (no correlation). The striatum (Str), i.e., caudate ncl-putamen (CPu) (decrease in M4KO, positive correlation in both WT and KO) and the motor cortex (MCx) (no correlation), showed circadian rhythms (peak in active phase). Caudate ncl-putamen M1 mAChRs rhythm in WT was circadian, while M4KO animals revealed an ultradian rhythm. Cholinesterases revealed ultradian and circadian rhythms in different areas.DiscussionWe conclude that muscarinic receptor-directed biological rhythm of activity is determined in the striatum (caudate ncl-putamen) as a key structure mainly by M4 mAChRs with a supportive role of M1 mAChRs.

Autism is a highly heritable neurodevelopmental condition that manifests across a wide phenotypic spectrum. Rare and de novo loss-of-function mutations strongly predispose to autism and co-occurring developmental and intellectual disabilities in over 10% of autistic individuals. Understanding whether these variants converge on specific regional brain circuits or widely alter human brain development is crucial to understanding the etiology of profound autism. To date, transcriptomic atlases have mainly implicated the developing cerebral cortex, yet other brain areas have received relatively little attention. Here, we present a single-cell resolution spatial transcriptomic atlas of 250 autism susceptibility genes during human brain development. Profiling over 10 million cells across the midgestation forebrain, we found convergence of these genes across a small number of regional programs. The developing thalamus showed the most prevalent expression of autism susceptibility genes, followed by germinal zones throughout the brain. Within the thalamus, excitatory neurons showed the most enriched expression, which varied across thalamic nuclei harboring distinct circuits. Across the germinal zones, neural progenitors in the medial ganglionic eminences that generate parvalbumin- and somatostanin-positive interneurons showed highest expression. Our findings reveal the prevalent expression of autism associated genes beyond the developing cerebral cortex and implicate the developing human thalamus as a major hub of autism susceptibility.

Minimal hepatic encephalopathy (MHE) is the initial stage of hepatic encephalopathy (HE), MHE patients have associated with widespread neuro-psychological impairment. Liver transplantation (LT) can restore metabolic abnormalities but the mechanisms are unclear. This study aimed to longitudinally evaluate brain function alteration in MHE patients one month after LT and their correlation with cognitive changes by using resting-state functional magnetic resonance imaging (rs-fMRI). Rs-fMRI data was collected from 32 healthy controls and 27 MHE before and 1 month after LT. Between-group comparisons of demographic data and neuropsychological scores were analyzed using SPSS 25.0. Functional imaging data were analyzed using RESTplus and SPM12 software based on MATLAB 2017b. Gender, age, and years of education were used as covariates to obtain low-frequency fluctuationd (ALFF) and dynamic low-frequency fluctuation (dALFF) dindices. Correlation analyses were performed to explore the relationship between the change of ALFF and dALFF with the change of clinical indexes pre- and post-LT. Compared to controls, ALFF values increased in the Left Cerebelum 8, right orbital part of the inferior frontal gyrus (ORBinf), right superior occipital gyrus (SOG) and decreased in right PreCG and left middle frontal gyrus (MFG) in patients post-LT; dALFF values increased in the right temporal pole and middle temporal gyrus (TPOmid), right ORBinf, left caudate nucleus (CAU), right SOG and decreased in left PreCG, left PCUN, left ANG, left SMA and left MFG in patients post-LT. Compared to pre-LT, ALFF values of post-LT patients increased in the right calcarine fissure and surrounding cortex (CAL), right MOG and decreased in right cerebelum 8, left PCUN; dALFF values of post-LT patients decreased in right thalamus (THA), left posterior cingulate gyrus (PCG) and left MFG. The changes of ALFF in the left PCUN, right CAL and right MOG were correlated with change of digit symbol test (DST) scores (P < 0.05). In summary, this study not only showcases the potential of ALFF/dALFF algorithms for assessing alterations in spontaneous neural activity in MHE, but also provides new insights into the altered brain functions in MHE patients 1 month after LT, which may facilitate the elucidation of elucidation of mechanisms underlying cognitive restoration post-LT in MHE patients.

Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) are two major global health challenges, both associated with increased incidence and mortality. Although their pathologies differ, mounting evidence points to a shared vascular dysfunction that may drive the onset and progression of both conditions. Ultrasound localization microscopy (ULM) offers a promising approach for high-resolution imaging and quantification of cerebral microvasculature. To investigate changes in cerebral micro-vessels induced by T2DM, AD, and their coexistence, aiming to uncover the underlying interactions between the two diseases. Twenty-four Sprague Dawley (SD) rats were randomly assigned into four groups: (1) normal, (2) DM combined with AD, (3) DM, and (4) AD. Cerebral vascular density in the caudate putamen (CPu), thalamus (TH), and hippocampus (HIP) was quantified using ULM. Statistical analysis was conducted using one-way ANOVA followed by Tukey's honestly significant difference (HSD) post-hoc test, after confirming normality and homogeneity of variance (Shapiro-Wilk and Levene's tests). A p-value<0.05 was considered statistically significant. To validate the model and examine the relationship between T2DM and AD, pathological staining was performed to assess cellular and neuronal changes, as well as Aβ deposition. Both single diseases and their combination led to a reduction in cerebral vascular density across all three brain regions. The blood glucose-vessel density distributions in the DM and DM&AD groups showed substantial overlap, indicating similar patterns of cerebrovascular changes. In the CPu region, vascular density in diabetic rats decreased by 34.13% compared to controls (p=0.003), while in the HIP of the DM&AD group, vascular density was reduced by 29.98% (p=0.002). T2DM triggers an increased risk of AD. ULM provides the possibility to be used as an emerging technological tool to detect early cerebral microangiopathy.

A quantitative analysis of TAAR1-positive cells in whole mouse brain by FDISCO technology.

Background/Objectives: Fibromyalgia causes chronic long-term pain, with symptoms lasting for months to years. Given the lack of evidence-based methods for diagnosing and assessing fibromyalgia, it ranks among the most difficult chronic pain conditions to treat. Programmed cell death ligand 1 (PD-L1) can inhibit acute and chronic pain transmission by inhibiting neuronal ion channels. Methods: Here, we aimed to explore the analgesic efficacy and mechanism of PD-L1/PD1 in an intermittent cold stress-induced fibromyalgia pain mouse model. Results: Von Frey and Hargreaves tests were performed, showing that the mouse model exhibited mechanical (day 4: 2.08 ± 0.13 g, n = 9) and thermal hyperalgesia (day 4: 3.93 ± 0.45 s, n = 9). Electroacupuncture (EA) or intraventricular PD-L1 injection effectively alleviated the nociceptive response and led to low PD-1 levels in the mouse dorsal root ganglia, spinal cord, thalamus, somatosensory cortex, and cerebellum, as measured through Western blots. In contrast, the pain-related kinase levels increased after fibromyalgia induction; these effects were reversed by EA and PD-L1 via the inhibition of microglia/astrocytes and Toll-like receptor 4. Conclusions: Our results show that EA can treat fibromyalgia pain in mice through effects on the PD-L1/PD1 pathway, indicating its potential as a therapeutic target in fibromyalgia.

Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus (TH) is an effective therapy for suppressing tremor. One of the critical challenges to optimizing VIM-DBS therapy is the lack of robust neural biomarkers that correlate well with tremor. To quantify biomarkers for tremor using intraoperative TH local field potential (LFP) recorded from DBS electrodes. Further, we used computational modeling to understand the biophysical basis of the recorded LFP signal. We simultaneously recorded intraoperative TH LFP and tremor from the hand dorsum (32 participants) and during DBS at different frequencies (16 participants). Then, we simulated the effects of DBS and spatial distribution of tremor cells on calculated LFPs in a TH model. There was a moderate correlation between tremor and LFP spectral power in the theta and alpha bands (r=0.445 and 0.389, respectively). There was a strong correlation between tremor and peak coherence between LFP and tremor signal (r=0.559). Postural tremor was decoded from the LFP signal with an area under the curve of ∼0.7. High frequency DBS reduced spectral power in the theta and alpha bands and tremor could be decoded from the LFP spectral power in the presence of DBS (0.429 goodness of fit R2). The theta power in the simulated LFP signal varied substantially with the specific location of the bipolar contact pair of the DBS electrode used for the LFP recordings as well as the spatial distribution of tremor cells. Theta power alone was not sufficient for prediction of tremor control. Simulations indicated that the number and distribution of tremor cells surrounding the DBS lead may explain the lack of a strong correlation between tremor and theta power.

The dorsal midline thalamus (DMT) is composed of the paraventricular (PV) and paratenial (PT) nuclei. While the anatomical and functional properties of PV are well-established, PT has remarkably received very little attention-even though the efferent projections of PV and PT are very similar. Using a combination of retrograde tracing and immunohistochemistry, we examined the anatomical inputs to PT and compared them with those to the anterior and posterior PV and to the anterodorsal nucleus of the thalamus. In addition, we examined orexinergic and serotonergic afferents to the PT, comparing them with those to other thalamic nuclei. We found that PT and PV receive input from a common set of structures, including the orbitomedial prefrontal cortex, nuclei of the diagonal band, septum, subiculum of the hippocampus, bed nucleus of the stria terminalis, hypothalamus, reticular nucleus of the thalamus, dorsal raphe nucleus, and periaqueductal gray. However, the pattern and density of these various afferents to PT and PV significantly differed. For instance, PT received much stronger inputs from the orbitofrontal cortex, while PV received stronger projections from the subiculum of the hippocampus and more widespread input from the hypothalamus and the brainstem. By comparison, afferents to AD differed from PT (and PV), as AD received substantial input from the retrosplenial and anterior cingulate cortices, and uniquely from the lateral mammillary nucleus. Further, orexinergic (ORX) and serotonergic (5-HT) fibers distributed at best modestly to PT, which contrasted with quite dense ORX and 5-HT innervation of PV. The present findings, essentially representing the first comprehensive examination of afferent projections to PT, show that the inputs to PT mainly arise from limbic forebrain structures-with pronounced projections from the orbitofrontal cortex, nuclei of the diagonal band, and the reticular nucleus of the thalamus. The functional properties of PT partially overlap with those of PV, but as described herein PT also participates in unique affective, cognitive, and motivational behaviors.

BackgroundObsessive-compulsive disorder (OCD) is significantly influenced by neurosteroidogenesis, which is mediated by the translocator protein 18 kDa (TSPO), a transmembrane protein located primarily in mitochondria.1 Despite numerous studies in the treatment of mood, anxiety, and stress-related disorders2,3, the TSPO ligands’ role in the treatment of OCD is yet to be elucidated.Aims & ObjectivesTo describe the short-term use of etifoxine, a TSPO ligand, in a patient with treatment-resistant OCD and to discuss the possible mechanisms of a rapid clinical response.MethodA case of treatment-resistant OCD who had a dramatic response to etifoxine was described, and a comprehensive literature search was conducted.ResultsA 36-year-old man was diagnosed with OCD since the age of 14. He had received numerous psychotropics, including maximum dosages of SSRIs (escitalopram, sertraline), SNRIs (venlafaxine), and TCAs (clomipramine, imipramine), and several previous augmentations (lithium, risperidone, aripiprazole, quetiapine), but failed to respond. He refused to receive psychotherapy, electroconvulsive therapy, and transcranial magnetic stimulation. Finally, he received neurosurgery twice at the ages of 30 (bilateral anterior cingulotomy) and 32 years old (subcaudate tractotomy). The responses were initially good, but then the OCD relapsed after 1.5 years and 6 months, respectively. His symptoms never remit. As the disease progressed, he became depressed and unable to work. His latest regimen included venlafaxine 375 mg/d, clomipramine 150 mg/d, aripiprazole 15 mg/d, and clonazepam 4 mg/d. The patient gradually developed suicidal ideation within a month but refused hospitalization because of contamination fear. However, he agreed to try etifoxine 150 mg/d along with the same ongoing medications. After one day of etifoxine use, his OC symptoms reduced dramatically, and the suicidal idea disappeared. He could sleep and join his family activity. Unfortunately, he developed an itchy skin rash and limb edema on Day 3. Despite this, he continued etifoxine, as it dramatically helped ameliorate his OC symptoms. On day 6, he came to the hospital for a psychiatric follow-up. At this point, the etifoxine was discontinued, resulting in resolution of the rash and limb edema, and all drug adverse reactions completely resolved within 2 weeks. The patient remained clinically stable after the etifoxine was discontinued and could be followed up in the outpatient setting.Discussion & ConclusionsThis is the first report of the use of a TSPO ligand in OCD treatment. This case illustrates the potential therapeutic option of etifoxine for treatment-resistant OCD. There are at least 2 possible mechanisms of the rapid response to etifoxine: (1) Increase endogenous neurosteroidogenesis. A TSPO-PET study in OCD patients has demonstrated increased TSPO expression in the dorsal caudate, orbitofrontal cortex, thalamus, ventral striatum, and dorsal putamen 1 and suggests a link of neurosteroid and OCD pathology. Etifoxine could increase endogenous neurosteroidogenesis, resulting in less anxiety. 4 (2) Gut-brain axis. Microbiome dysbiosis is linked with OCD pathology.5 A study in healthy human demonstrated that a five-day treatment with etifoxine reduced the number of some bacterial species. 6 TSPO can be a novel target for future research in OCD treatment.

Spatial-temporal lipidomics reveals dysregulated lipid metabolism in mouse brain during Alzheimer's disease progression.

The cold pressor task (CPT) is widely used to study tonic pain during acute and chronic conditions and is often used as a conditioning stimulus to activate descending pain control systems. However, logistical challenges in magnetic resonance imaging (MRI) limit its application, hindering the understanding of CPT's neural dynamics. To address this, we acquired resting-state functional MRI (fMRI) data from 30 healthy participants before, during and after immersion in gelled-cold water, the closest in-scanner alternative to date to CPT for prolonged stimulation. Participants provided subjective pain intensity ratings after each scan, as well as average pain perceived during noxious stimulation, using a numeric rating scale (NRS). Following fMRI, participants rated their pain continuously during identical tonic noxious stimulation of the contralateral hand using a visual analogue scale (VAS). We employed three complementary methods to examine changes in brain function across fMRI conditions: a data-driven approach via independent component analysis (ICA), seed-to-whole-brain connectivity analysis with the periaqueductal grey (PAG) as seed and spectral dynamic causal modelling (spDCM) to explore effective connectivity changes across the dorsal anterior cingulate cortex (dACC), anterior insulae (AI), thalamus and PAG. NRS scores were significantly higher following tonic cold compared to baseline and recovery conditions. Continuous VAS reflected sustained mild-to-moderate pain over 6 min, with average VAS scores not significantly differing from NRS ratings recorded in the scanner. ICA identified engagement of descending pain control and sensorimotor networks during pain, with the latter persisting during recovery. Seed-based analysis revealed a disengagement between the PAG and cortical/subcortical regions involved in pain processing, such as the dACC, midcingulate cortex, AI, intraparietal sulcus and precuneus. Finally, spDCM revealed tonic pain neural signature was most likely characterised by top-down inhibitory and bottom-up excitatory connections. This study establishes the cold gelled-water paradigm as a potential in-scanner alternative to CPT. By uncovering key neural dynamics of CPT, we provide new insights into the brain and brainstem mechanisms of tonic cold pain paradigms routinely used in psychophysical pain studies.

The long-term effect of superficial temporal artery-middle cerebral artery (STA-MCA) bypass and corresponding hemodynamics in hemorrhagic moyamoya disease (MMD) remained unclear. This study aimed to investigate the incidence of long-term rebleeding events, bypass patency, neovascularization, and changes in hemispheric prefusion in hemorrhagic MMD patients. Clinical and radiographic images for 35 hemorrhagic MMD patients (45 hemispheres) using STA-MCA bypass were recorded. The patients' demographic information, clinical presentation, associated medical conditions, hemispheric perfusion status, and clinical course were obtained from reviewing medical records, cerebral angiography, and CT perfusion (CTP) during long-term follow-up. Of the 45 cases with an average follow-up of 38 months, 7 cases (15.5%, 2.08% per year) experienced new cerebral hemorrhages. The latest cerebral angiography indicated patent bypass in 32 cases (71.1%) and Matsushima grade A in 16 cases (35.6%). Distribution analysis of modified Suzuki stages and moyamoya vessels patterns showed significant changes (P < 0.05), with a higher proportion of patients progressing to advanced stages and a decrease in moyamoya vessels. There was a significant improvement in neurological outcomes (P = 0.004), with 80.0% of cases achieving normal neurological function. Long-term CTP analysis revealed no significant differences in rCBF compared to preoperative values (P > 0.05). However, rCBV significantly decreased in the caudate nucleus, parietal lobe, and striatum (P < 0.05). Significant decrease in rMTT and rTmax parameters were noted in several regions, including the genu of the corpus callosum, caudate nucleus, dorsal thalamus, and multiple cortical regions, indicating a reduction in microcirculation time (P < 0.05). STA-MCA bypass could improve long-term neurological outcomes in hemorrhagic MMD patients, facilitating advancements in Suzuki stages and reducing moyamoya vessels. Long-term CTP results indicated a slight decrease in rCBF in several areas and shortened microcirculation time. Not applicable.

Understanding the neural mechanisms underlying associative threat learning is essential for advancing behavioral models of threat and adaptation. We investigated distinct activation patterns across thalamic pulvinar divisions, lateral geniculate nucleus (LGN), and mediodorsal thalamus (MD) during the acquisition of associative threat learning in the MRI. We revealed parallel thalamic learning systems within the anterior pulvinar and MD, supporting distinct mechanisms of automatic survival vs. more deliberate learning. Additionally, our findings support a novel hierarchical pulvinar model during fear conditioning: the medial pulvinar mediates basic threat information from the inferior and lateral divisions to the anterior pulvinar for integrative learning. Pulvinar divisions and MD support extinction learning. These regions also process salience and modulate safe/threat memory expression during extinction recall and threat renewal. The LGN sustains feedforward processing of anticipated visual input throughout all threat phases. This study extends dominant brain models of threat learning and memory, reframing our understanding of distinct thalamic roles in these psychological processes.