Brain Research Bulletin[JOURNAL]
Sun
200 papers
Evaluation of glymphatic system activity by using diffusion tensor image analysis along the perivascular space in patients with differential suicidality.
Ho MHC, Chen VC, Tsai YH … +2 more , Chang YE, Weng JC
Brain Res Bull · 2026 Jul · PMID 42128141 · Publisher ↗
PURPOSE: Glymphatic dysfunction is linked to various neurological conditions, yet its longitudinal role in Major Depressive Disorder (MDD) and suicidal ideation remains unclear. This study used the non-invasive Diffusion...
PURPOSE: Glymphatic dysfunction is linked to various neurological conditions, yet its longitudinal role in Major Depressive Disorder (MDD) and suicidal ideation remains unclear. This study used the non-invasive Diffusion Tensor Image Analysis Along the Perivascular Space (DTI-ALPS) index to evaluate the association between glymphatic function and suicidal ideation over time. METHODOLOGY: In this prospective longitudinal study, we enrolled 85 patients (31 male and 54 females) comprising 26 healthy controls (HC; mean age: 40.04 ± 10.4 years [95% CI: 35.85-44.22]) and 59 patients with MDD. The patient cohort was categorized by clinical trajectory into three groups: non-suicidal (NS, n = 28; 44.75 ± 10.1 [40.82-48.68]), suicidal ideation (SI, n = 18; 38.56 ± 11.6 [32.81-44.30]), and improved (IM, n = 13; 42.15 ± 13.1 [34.21-50.10]), the latter of which transitioned from an SI to a non-suicidal state between timepoints. Clinical assessments, including the Hamilton Depression Rating Scale (HAM-D), Ruminative Responses Scale (RRS), Hospital Anxiety and Depression Scale-Anxiety (HADS-A), and Beck Scale for Suicide Ideation (BSS), were analyzed alongside diffusion MRI. Research is structured for a longitudinal study that includes (1) healthy controls at two time points, (2) depression without suicidal ideation at two time points, (3) depression with suicidal ideation at two time points, and (4) depression with suicidal ideation converting to depression without suicidal ideation. By calculating the DTI-ALPS index, we aim to obtain estimates of glymphatic activity and its association with clinical assessment. All patients, including healthy controls, were also rescanned at TP2. KEY RESULTS: At TP1, a significant difference in the DTI-ALPS index (b=1500) was observed between the SI and IM groups, suggesting its potential as a predictor of treatment response. Over two years, the IM group was characterized by a stabilization of glymphatic activity. Notably, differential analysis revealed a significant negative correlation between the DTI-ALPS index and HADS-A scores at follow-up. This inverse relationship indicates that maintained glymphatic function is associated with the reduction of anxiety and depressive symptoms. CONCLUSIONS: The DTI-ALPS index is closely associated with anxiety-related measures in MDD. These findings highlight glymphatic activity as a potential biological marker for monitoring clinical improvement and the impact of treatment on suicidal ideation.
The nigrostriatal dopaminergic pathway mediates state-dependent emergence from propofol anesthesia in mice.
Chen Y, Bai S, Liu X … +9 more , Li Y, Ba Y, Wang Y, Zhang P, Zhang L, Xue L, Sun P, Li W, Wang X
Brain Res Bull · 2026 Jul · PMID 42119827 · Publisher ↗
The endogenous arousal pathway, centered around the midbrain dopaminergic (DA) system, plays a crucial role in regulating consciousness transitions. However, the role of substantia nigra pars compacta (SNc) DA neurons, p...
The endogenous arousal pathway, centered around the midbrain dopaminergic (DA) system, plays a crucial role in regulating consciousness transitions. However, the role of substantia nigra pars compacta (SNc) DA neurons, particularly their projections to the dorsal striatum (DS), in propofol-induced unconsciousness and wakefulness is not yet clear. This study combines fiber optic recording, optogenetics, and chemogenetics to manipulate SNc DA cell bodies or their terminals towards DS in C57BL/6 J mice. The results showed that SNc DA manipulation had no effect on the induction period; however, during the awakening period, activation can accelerate the recovery of the righting reflex (RORR) and induce awakening related EEG features, while inhibition delays RORR and enhances slow wave activity. Importantly, this awakening effect is state dependent: it occurs when SNc DA neurons are activated during anesthesia maintenance and recovery phases but not during induction phase activation. In addition, the effect of SNc DA manipulation is time-dependent, that is, it regulates the awakening period without affecting the induction period. Pathway specific manipulation indicates that photoactivation of DS terminals can promote wakefulness, while inhibition prolongs RORR without affecting the induction period. Therefore, it is believed that SNc DA neurons mainly exert time-dependent and pathway specific effects on propofol awakening through the substantia nigra striatum, and participate in the process of propofol anesthesia awakening.
Functional connectivity disruptions and topological structure alterations centered around the sensorimotor network in disorders of consciousness: A functional near-infrared spectroscopy study.
Wang Y, Yao P, Liu Y … +3 more , Zou L, Bai Y, Feng Z
Brain Res Bull · 2026 Jul · PMID 42119826 · Publisher ↗
OBJECTIVE: The neural network mechanisms of consciousness are not fully understood. This study aimed to construct resting-state whole-brain functional networks using functional near-infrared spectroscopy (fNIRS) to explo...
OBJECTIVE: The neural network mechanisms of consciousness are not fully understood. This study aimed to construct resting-state whole-brain functional networks using functional near-infrared spectroscopy (fNIRS) to explore the functional network mechanisms underlying disorders of consciousness (DOC) and to identify potential neural network biomarkers for diagnosis and prognosis. METHODS: Resting-state fNIRS data were collected from healthy controls (HC) and patients in vegetative state (VS) or minimally conscious state (MCS). Whole-brain weighted functional networks were constructed for each participant, and group differences in functional connectivity (FC) and global/local topological properties were analyzed, along with their correlation with Glasgow Outcome Scale-Extended (GOS-E) scores in DOC patients. RESULTS: DOC patients (both VS and MCS) had significantly lower average FC strength than HC, with the VS group showing significantly lower FC than the MCS group-differences most prominent within the sensorimotor network. Globally, both DOC groups exhibited reduced clustering coefficient, global efficiency (Eglob), and local efficiency (Eloc), as well as increased characteristic path length (Lp) compared to HC. Furthermore, the VS group had significantly lower Eglob and Eloc and higher Lp than the MCS group. Local topological differences were also mainly found in sensorimotor regions. Several network metrics, including average FC, Lp, Eglob, Eloc, and nodal efficiency, were significantly correlated with GOS-E scores in DOC patients. CONCLUSION: Global connectivity disruption centered around the sensorimotor network, along with reduced functional integration and segregation capabilities, may underlie DOC. Resting-state functional network characteristics could serve as neurobiological markers to differentiate VS from MCS and predict patient prognosis.
Shouhui Tongbian capsule is associated with antidepressant-like effects and gut-brain axis-related biological improvements in mouse models of depression.
Wang B, Huang Y, Yang W … +6 more , Xu N, Li Y, Du C, Zhang X, Wang H, Lou H
Brain Res Bull · 2026 Jul · PMID 42119658 · Publisher ↗
BACKGROUND: Major depressive disorder (MDD) is a global health challenge with complex etiology. The gut-brain axis, particularly neuroinflammation and synaptic dysfunction, has emerged as a critical therapeutic target. S...
BACKGROUND: Major depressive disorder (MDD) is a global health challenge with complex etiology. The gut-brain axis, particularly neuroinflammation and synaptic dysfunction, has emerged as a critical therapeutic target. Shouhui Tongbian Capsule (SHTB), a clinically used Chinese patent medicine for constipation, has shown potential in modulating gut microbiota and alleviating comorbid mood symptoms, yet its systemic antidepressant mechanisms remain unexplored. PURPOSE: This study aimed to evaluate the antidepressant-like effects of SHTB in mouse models and characterize accompanying gut- and brain-related biological changes. STUDY DESIGN AND METHODS: Network pharmacology was used to assess whether reported SHTB constituents were relevant to depression-related gene networks. Subsequent in vivo validation was conducted in lipopolysaccharide (LPS)-induced and chronic unpredictable mild stress (CUMS) mouse models of depression. Behavioral phenotypes, neuroinflammation, hippocampal neuronal and synaptic integrity, intestinal barrier function, and mRNA expression of selected predicted targets were evaluated. RESULTS: Exploratory network analysis indicated potential associations between reported SHTB constituents and depression-related gene networks, providing a preliminary rationale for animal experiments. In vivo, SHTB administration was associated with significant improvements in depressive- and anxiety-like behaviors in both LPS and CUMS-induced mouse models of depression. These behavioral effects were accompanied by attenuation of neuroinflammatory responses, preservation of hippocampal neuronal and synaptic features, maintenance of intestinal barrier integrity, and altered hippocampal expression of several neurotransmitter-related genes. CONCLUSION: SHTB showed significant antidepressant-like effects accompanied by gut-brain axis-related biological improvements. This study provides a novel, multi-evidence rationale for repurposing SHTB as a promising multi-target therapeutic agent for MDD, mediated via the gut-brain axis.
Corrigendum to "TCF7L2 transcriptionally regulates C1QB to exacerbate synaptic pruning-dependent neuronal injury in the epileptic hippocampus" [Brain Res. Bull. 235 (2026) 111730].
Wu L, Huang Y, Wang X … +3 more , Tian T, Feng D, Zhou G
Brain Res Bull · 2026 Jun · PMID 42115012 · Publisher ↗
Abstract loading — click title to view on PubMed.
Corrigendum to "Identifying neuroimaging-based biomarkers for obsessive-compulsive disorder: A resting-state fMRI and machine learning study in patients and unaffected first-degree relatives" [Brain Res. Bull. 239 (2026) 111894/BRB_111894].
Suo X, Zhang Y, Li X … +9 more , Liu J, Xu Z, Zeng L, Lei L, Zhang M, Luo Z, Min Y, Zeng X, Hu M
Brain Res Bull · 2026 Jun · PMID 42108163 · Publisher ↗
Abstract loading — click title to view on PubMed.
Anatomical input-output streams within mouse orbitofrontal cortex subdivisions.
Tripathi A, Censoni L, Medini P
Brain Res Bull · 2026 Jul · PMID 42107475 · Publisher ↗
The orbitofrontal cortex (OFC) supports flexible value representation and decision making and its dysfunction is implicated in affective disorders. In rodents and primates different OFC subdivisions fulfill different fun...
The orbitofrontal cortex (OFC) supports flexible value representation and decision making and its dysfunction is implicated in affective disorders. In rodents and primates different OFC subdivisions fulfill different functions, like encoding rewarding/aversive stimuli. Although recent anatomical and functional investigations have been performed in mice, species differences in reward and value-encoding physiology call for deeper investigation of mouse OFC connectivity to better support translational research. Here, we compare density of retrograde inputs, axonal outputs and inter-subdivision connectivity, focusing on MO (medial-orbital), VO (ventral-orbital), (D)LO ((dorso)lateral-orbital) and AI (agranular insula). Central subdivisions (LO, VO) received dominant inputs from mediodorsal and submedius thalamic nuclei and projected respectively to medial prefrontal areas and sensory cortices. The striatal output was directed towards dorsal striatum, with reciprocal connection to/from brainstem dopaminergic areas. Input sources were more distributed for MO and AI, with reciprocal innervation to medial prefrontal cortices and amygdala, respectively. Striatal output was mainly to ventral striatum, and AI also received strong serotonergic innervation. Cluster analysis revealed that VO/LO, and to lesser extent MO/DLO, shared strong similar input distributions, distinct from AI. Output clustering separated VO targeting sensory areas and AI targeting amygdala. Intra-OFC connectivity suggested information flow preferentially from (D)LO (entry nodes), to VO, MO and finally AI (output node). We suggest a putative model integrating preferentially in-series, sensory-motor plans (at (D)LO), motivational state and cue-uncertainty (at VO/LO) and current goals (at MO), via AI modulating the amygdaloidal and ventral striatal outputs, thus proposing a prototype circuit to control emotional reactivity and decision-making in mouse OFC.
Efficacy associated with repetitive transcranial magnetic stimulation targeting the medial superior frontal gyrus in schizophrenia: A pilot randomized controlled study.
Ding Z, Li Z, Li M … +2 more , Fan F, Liang J
Brain Res Bull · 2026 Jul · PMID 42107474 · Publisher ↗
Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising adjunctive therapy for schizophrenia (SCZ). The medial superior frontal gyrus (mSFG) is a key network hub and a novel therapeutic target. The...
Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising adjunctive therapy for schizophrenia (SCZ). The medial superior frontal gyrus (mSFG) is a key network hub and a novel therapeutic target. Therefore, this study investigated the clinical and neuroimaging changes associated with left mSFG-targeted rTMS augmentation in SCZ. Patients were prospectively enrolled and randomly assigned to either the Conventional Therapy (CT, n = 15) group or the CT combined with a 4-week course of 10 Hz rTMS to the left mSFG (rTMS group, n = 14). The changes in Positive and Negative Syndrome Scale (PANSS) scores, Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scores, and bilateral mSFG volume/fractional amplitude of low-frequency fluctuations (fALFF) from pre- to post-treatment were compared within and between groups. Both groups showed significant within-group improvements in PANSS total score and several RBANS domains. The reduction in PANSS total score was significantly greater in the rTMS group compared to the CT group (p = 0.049). However, no significant between-group differences were found for PANSS positive/negative subscales or RBANS Total Score change. Within-group analyses revealed volumetric increases in the mSFG bilaterally in the rTMS group and in the right hemisphere in the CT group. However, direct between-group comparisons of the magnitude of volume change (Δ volume) revealed no statistically significant differences for either the left or right mSFG. These structural observations should therefore be considered strictly exploratory. No significant changes in fALFF were detected in either group. In this pilot study, augmentation with left mSFG-targeted rTMS was associated with a greater reduction in overall symptom burden compared to conventional therapy alone and with a bilateral pattern of structural change in the target region. These preliminary findings warrant confirmation in larger, sham-controlled trials.
Exosomes from joints mediate depressive-like behaviors in MIA arthritis mice.
Li Z, Gao Y, Ma H … +3 more , Xiong Y, Wang J, Ning G
Brain Res Bull · 2026 Jun · PMID 42107473 · Publisher ↗
Arthritis-related mood disturbances suggest pathogenic communication between inflamed joints and the brain, yet the causal mediators remain unclear. Here we show that exosomes released from mono-iodoacetate (MIA)-injured...
Arthritis-related mood disturbances suggest pathogenic communication between inflamed joints and the brain, yet the causal mediators remain unclear. Here we show that exosomes released from mono-iodoacetate (MIA)-injured knees transmit surface-displayed high mobility group box 1 (HMGB1) to the brain, where they activate neuronal NF-κB and senescence programs that culminate in depressive-like behavior. In mice with MIA arthritis, depressive-like behaviours (reduced sucrose/saccharin preference) coincided with increased neuronal pp65 and senescence markers. Pharmacologic exosomes inhibition (GW4869) prevented both molecular and behavioral phenotypes, while intravenous transfer of purified joint-derived exosomes from MIA donors recapitulated them in naïve recipients. A proteinase-K protection assay localized HMGB1 to the exosomes exterior, and neutralizing HMGB1 with 2G7 abrogated exosome-induced neuronal pp65/senescence and restored behavioral performance without altering joint histopathology. In vitro, joint-derived exosomes triggered HMGB1-dependent NF-κB activation and senescence signatures in primary neurons, supporting neuron-intrinsic responsiveness to vesicular DAMP signaling. These data identify a joint-to-brain exosome/HMGB1 axis as both necessary and sufficient to drive affective dysfunction after MIA. Our findings propose a tractable therapeutic framework-intercepting exosomes biogenesis/trafficking or neutralizing circulating HMGB1-to mitigate mood symptoms associated with arthritis. More broadly, the work illustrates how tissue-restricted inflammation can remodel distant neural circuits via vesicle-borne danger signals, offering biomarker and intervention opportunities for inflammatory disorders complicated by affective disturbances.
Disproportionately elevated sulcal index (DESI): An automatically driven index representing disproportionate subarachnoid space enlargement in brain MRI scans.
Shirzadeh Barough S, Ohno S, Bilgel M … +4 more , Moghekar A, Sair HI, Luciano MG, Moghekar A
Brain Res Bull · 2026 Jul · PMID 42105919 · Full text
INTRODUCTION: Idiopathic normal pressure hydrocephalus (iNPH) is frequently underdiagnosed due to non-specific symptoms and the risks of invasive testing. While disproportionately enlarged subarachnoid space hydrocephalu...
INTRODUCTION: Idiopathic normal pressure hydrocephalus (iNPH) is frequently underdiagnosed due to non-specific symptoms and the risks of invasive testing. While disproportionately enlarged subarachnoid space hydrocephalus (DESH) is a hallmark imaging feature, manual assessment is subjective and qualitative. We developed the Disproportionately Elevated Sulcal Index (DESI), a fully automated deep learning-based volumetric biomarker, to objectively quantify these morphological changes. METHODS: We trained a U-Net model with an EfficientNet-B0 encoder on T1-weighted MRI scans from the Baltimore Longitudinal Study of Aging and Johns Hopkins Clinic (n = 1248) to segment Sylvian fissures and superior sulcal spaces. DESI was defined as the volumetric ratio of the Sylvian fissure to superior sulci within an AC-PC aligned wedge. The model was externally validated on the multi-site PENS trial dataset (n = 94), comparing NPH patients against healthy controls and participants with Alzheimer's disease and vascular dementia. RESULTS: In external validation, DESI demonstrated high diagnostic accuracy. The index distinguished NPH patients with DESH features from non-DESH NPH cases with an Area Under the Curve (AUC) of 0.97. When differentiating NPH with DESH from a pooled group of healthy controls and neurodegenerative mimics, DESI achieved an AUC of 0.99 (sensitivity 98%, specificity 100%). In a broad comparison of all NPH cases versus all non-NPH groups, DESI maintained an AUC of 0.94. CONCLUSIONS: DESI provides a robust, fully automated quantification of sulcal disproportion that effectively differentiates iNPH from normal aging and neurodegenerative mimics. This continuous, non-invasive metric offers a scalable tool for accurate iNPH screening and patient stratification in clinical settings.
Neural substrates of apathy in Parkinson's disease: A systematic review of structural and functional neuroimaging studies.
Marafioti G, Culicetto L, Blundo C … +5 more , Susinna C, Restuccia G, Di Lorenzo G, Quartarone A, Lo Buono V
Brain Res Bull · 2026 Jun · PMID 42103035 · Publisher ↗
BACKGROUND: Apathy is a frequent and disabling non-motor symptom in Parkinson's disease (PD), characterized by diminished motivation, reduced goal-directed behavior, and emotional indifference. Growing evidence suggests...
BACKGROUND: Apathy is a frequent and disabling non-motor symptom in Parkinson's disease (PD), characterized by diminished motivation, reduced goal-directed behavior, and emotional indifference. Growing evidence suggests that apathy in PD represents a distinct neuropsychiatric syndrome that may coexist with depression and global cognitive impairment, while also showing partially dissociable clinical and neural correlates. OBJECTIVE: This systematic review aimed to investigate the neural substrates of apathy in PD by synthesizing evidence from structural and functional neuroimaging studies. METHODS: Following PRISMA guidelines, we searched PubMed, Embase, Web of Science, and Scopus for studies assessing apathy in PD through neuroimaging techniques, including structural MRI, resting-state functional MRI, diffusion tensor imaging, PET/SPECT molecular imaging, and connectivity analyses. Apathy severity was evaluated using validated clinical scales, and findings were compared between PD population with and without apathy, as well as healthy controls. RESULTS: Across 16 heterogeneous studies, recurrent findings implicated structural, functional, and molecular alterations within fronto-striatal-limbic networks. However, differences in apathy measures and neuroimaging modalities limit direct comparability across studies and do not support a single unified imaging signature of apathy in PD. Apathetic PD subjects consistently exhibited reduced gray matter volume and altered spontaneous activity in the dorsolateral, inferior frontal gyri, anterior cingulate cortex (ACC), and nucleus accumbens, alongside disrupted functional and structural connectivity in fronto-limbic tracts. These alterations were significantly correlated with apathy severity and, in several studies, remained detectable after accounting for depressive symptoms or global cognitive status. Furthermore, the available findings suggest that apathy in PD may involve heterogeneous neurobiological mechanisms, including variable involvement of frontal, striatal, and limbic circuits; however, current evidence remains insufficient to support firm transmitter-based subtyping or treatment stratification. CONCLUSIONS: Current evidence suggests that apathy in PD involves partially dissociable neural correlates across prefrontal, striatal, and limbic systems. However, methodological heterogeneity across studies limits strong generalization, and future harmonized longitudinal studies are needed to clarify which findings are robust and clinically meaningful.
Network toxicology, molecular docking, and molecular dynamics to explore the epilepsy mechanism induced by tetramine poisoning.
Liu MW, Peng HD, Cun YF … +4 more , Gao SJ, Zhu YL, Li X, Li CR
Brain Res Bull · 2026 Jun · PMID 42103034 · Publisher ↗
Tetramine poisoning commonly leads to epilepsy, with complex underlying mechanisms and poor treatment outcomes. This study aimed to explore the mechanisms of epilepsy induced by tetramine poisoning via network toxicology...
Tetramine poisoning commonly leads to epilepsy, with complex underlying mechanisms and poor treatment outcomes. This study aimed to explore the mechanisms of epilepsy induced by tetramine poisoning via network toxicology and molecular docking approaches. Tetramine poisoning targets were obtained from the SuperPred database, whereas epilepsy-related gene targets were identified through the GeneCards and OMIM databases. The intersection of tetramine targets and epilepsy-related genes revealed candidate targets. A proteinprotein interaction (PPI) network for these candidate targets was constructed via the String platform, after which the core functional modules were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted via the Metascape platform. Additionally, a targetpathway network involving Tetramine and brain injury was constructed via Cytoscape 3.8.2 software, enabling network topology analysis and screening of key components and targets. The results found that a total of 118 candidate targets for tetramine-induced epilepsy were identified. Pathway enrichment analysis indicated that tetramine-induced epilepsy is likely associated with the HIF-1, PI3K-Akt, Ras, Toll-like receptor, chemokine, and neurotrophin signaling pathways. The core targets include SRC, STAT3, HSP90AB1, MMP9, and HIF1A. To verify the above findings experimentally, this study established an epilepsy rat model by intragastric administration of different doses (0.1, 0.25, 0.5 mg/kg) of tetramine. The seizure behavior was evaluated using the Racine scoring system, and hippocampal tissues were collected for subsequent tests. Real-time fluorescence quantitative PCR and Western Blot were used to detect the mRNA and protein expression levels of five core targets, as well as the phosphorylation levels of STAT3, SRC, Akt, and ERK. Immunofluorescence staining was used to observe the expression and distribution of p-STAT3 and HIF1A in brain tissues, and HE staining was used to assess the histopathological changes. The results showed that tetramine induced severe epileptic seizures in a dose-dependent manner. At the same time, the mRNA and protein expression levels of core targets HIF1A, MMP9, HSP90AB1, SRC, and STAT were all upregulated, and the phosphorylation levels of STAT3, SRC, Akt, and ERK were increased. Immunofluorescence and HE staining further confirmed the protein activation and pathological changes induced by tetramine. Network toxicology methods suggest that tetramine may induce epilepsy through multiple targets and signaling pathways. The above experimental results have preliminarily verified the key targets for network toxicology identification. However, the specific mechanism still needs to be further studied and confirmed.
Astrocyte-mediated angiogenesis in CNS diseases: Mechanisms and therapeutic implications.
He Z, Mao Y, Chi L … +1 more , Sun J
Brain Res Bull · 2026 Jun · PMID 42103033 · Publisher ↗
Astrocytes are central, yet often underappreciated, regulators of angiogenesis in the central nervous system (CNS), exhibiting a profound context-dependent duality. They can foster restorative vascular repair after ische...
Astrocytes are central, yet often underappreciated, regulators of angiogenesis in the central nervous system (CNS), exhibiting a profound context-dependent duality. They can foster restorative vascular repair after ischemic injury while simultaneously driving pathological vessel formation in tumors and other neurological disorders. This review synthesizes current knowledge on astrocyte-mediated angiogenesis across major CNS diseases, critically examining how disease-specific cues-such as hypoxia, tumor-derived factors, or Aβ plaques-are integrated to produce distinct vascular outcomes. We move beyond the binary A1/A2 paradigm to introduce a framework of "disease-associated astrocyte subsets" (e.g., ischemia-associated, glioma-associated, and Alzheimer's disease-associated astrocytes), as revealed by emerging single-cell studies. Key mechanisms are dissected, including the tightly regulated VEGF/Ang axis, HMGB1 signaling, the Sonic Hedgehog pathway, and the growing role of exosomal miRNA transfer. A central challenge highlighted is the temporal dichotomy of VEGF action, which transitions from acutely detrimental to beneficial during recovery. We explore therapeutic implications, from promoting reparative angiogenesis in ischemia to inhibiting pathological angiogenesis in glioblastoma. By identifying critical knowledge gaps, we propose future directions-such as astrocyte-specific gene editing and engineered exosomes-that aim to translate these insights into effective, context-specific CNS therapies.
Subclinical gray matter damage: Macro- and microstructural findings in stroke-free unilateral middle cerebral artery occlusion patients.
Liu Z, Wan X, Xiao Y
Brain Res Bull · 2026 Jul · PMID 42097515 · Publisher ↗
OBJECTIVE: This study aimed to investigate macrostructural and microstructural damage in the gray matter of stroke-free patients with unilateral middle cerebral artery (MCA) occlusion using three-dimensional T1-weighted...
OBJECTIVE: This study aimed to investigate macrostructural and microstructural damage in the gray matter of stroke-free patients with unilateral middle cerebral artery (MCA) occlusion using three-dimensional T1-weighted imaging (3D T1WI) and Neurite Orientation Dispersion and Density Imaging (NODDI) sequences. METHOD: A total of 56 patients with unilateral MCA occlusion and 60 age- and sex-matched healthy controls underwent 3.0 T MRI with 3D T1WI and NODDI sequences. Voxel-based morphometry was applied to quantify regional brain volumes from 3D T1WI data, while Neurite Density Index (NDI) and Orientation Dispersion Index (ODI) were derived from NODDI data. Voxel-wise statistical comparisons assessed differences in regional gray matter volume, cortical thickness, NDI, and ODI between groups. RESULTS: Compared with healthy controls, individuals with unilateral MCA occlusion exhibited significant reductions in global gray matter volume and average cortical thickness. Specifically, unilateral MCA occlusion was linked to more extensive regional gray matter volume decreases. Notably, right MCA occlusion was uniquely associated with volume loss in the hippocampus, parahippocampal gyrus, and limbic system. Microstructural analysis revealed that, relative to controls, patients showed reduced NDI primarily in bilateral white matter tracts and decreased ODI in specific cortical regions of the frontal and occipital lobes. CONCLUSIONS: In stroke-free individuals with unilateral MCA occlusion, widespread macrostructural and microstructural damage to the gray matter is observed, affecting bilateral cerebral and cerebellar regions beyond the classic MCA vascular territory. Notably, the limbic system exhibits marked susceptibility, particularly involving the hippocampus, parahippocampal gyrus, and other limbic structures.
Getting in touch with ourselves: Self-Compassion is associated with subcortical brain structures.
Scheiwe GS, König P, Zwiky E … +10 more , Schöniger K, Küttner A, Andreev J, Fleischer L, Hamann JE, Wohlgemuth WA, Deistung A, Kamrla R, Selle J, Redlich R
Brain Res Bull · 2026 Jun · PMID 42092707 · Publisher ↗
The concept of Self-Compassion has recently gained significant importance in research and psychotherapy. However, little is known about its neural correlates. Related constructs, such as compassion for others, empathy, a...
The concept of Self-Compassion has recently gained significant importance in research and psychotherapy. However, little is known about its neural correlates. Related constructs, such as compassion for others, empathy, and emotion regulation, have been repeatedly associated with structural correlates in subcortical brain regions - including the amygdala, hippocampus, and insula - but corresponding associations with Self-Compassion have not been examined yet. Therefore, this study investigated the potential association between Self-Compassion and brain structure. Structural MRI data from N = 301 (gender (m/f): 106/195) healthy participants were analyzed. Threshold-free cluster enhancement (TFCE) corrected voxel-wise multiple regression analyses of the Self-Compassion Scale and its two subscales (Self-Compassionate Attitude and Self-Critical Attitude) on gray matter volume (GMV) were conducted separately within the bilateral amygdala, hippocampus, and insula as regions of interest (ROIs). An exploratory whole-brain analysis was performed for all three models. Significance threshold for all analyses was p < .05. The analysis revealed a significant negative association between Self-Compassion and the GMV in the left amygdala (k 94, t = 2.53, p =.042). Further, a significant negative association was found between Self-Compassionate Attitude and GMV in the bilateral amygdala (k = 196, t = 2.59, p =.032; k = 63, t = 2.53, p =.043). No other significant associations were observed (all p ≥ .080). The findings indicate initial evidence that Self-Compassion, as well as Self-Compassionate Attitude, is associated with subcortical brain structures involved in emotion processing, indicating a relevance of Self-Compassion with regard to emotional encoding and appraisal.
Brain microstructural alterations on quantitative synthetic MRI and correlation with cognitive dysfunction in patients with β-thalassemia major.
Bu M, Deng X, Yang X … +6 more , Zheng H, Li L, Ye B, Cui W, Jiang M, Chen BT
Brain Res Bull · 2026 Jun · PMID 42092706 · Publisher ↗
BACKGROUND: To investigate microstructural brain alterations and their relationship with cognitive dysfunction in patients with β-thalassemia major (β-TM) using quantitative synthetic MRI (SyMRI). METHODS: Ninety-six β-T...
BACKGROUND: To investigate microstructural brain alterations and their relationship with cognitive dysfunction in patients with β-thalassemia major (β-TM) using quantitative synthetic MRI (SyMRI). METHODS: Ninety-six β-TM patients and 47 healthy controls (HCs) underwent brain SyMRI, Montreal Cognitive Assessment (MoCA), and Modified Mini-Mental State Examination (MMMSE). Quantitative SyMRI parameters (T1, T2, and T1/T2 ratio) were measured in gray matter (GM) and white matter (WM). Group differences were analyzed using general linear models. Pearson correlation assessed associations between SyMRI metrics, cognitive scores, and blood test results in the β-TM group. Mediation analyses were conducted using the PROCESS macro to explore indirect effects of hematological variables on cognition via regional T1 values. RESULTS: Compared to HCs, β-TM patients showed significantly increased T1 values in GM regions of the default mode and frontoparietal networks, as well as WM regions (e.g., anterior corona radiata, cingulum, corpus callosum) (P < 0.001). Compared with HCs, patients with β-TM exhibited both decreased and increased T1 values across multiple GM and WM regions. Specifically, decreased T1 values were observed in frontal, cingulate, striatal, and temporal regions, as well as major WM tracts (e.g., anterior corona radiata, cingulum, superior longitudinal fasciculus), whereas increased T1 values were identified in parietal and temporal cortices and the corpus callosum (tapetum) (P < 0.001). T1 values in GM and WM were negatively correlated with cognitive scores (P < 0.05). There were negative correlations of the SyMRI quantitative parameters with cognitive scores and with blood laboratory values for white blood cell, platelet count and direct bilirubin (r = -0.270, P = 0.031; r = -0.287, P = 0.021; r = -0.263, P = 0.036, respectively). Blood test results such as the mean corpuscular volume (MCV) and mean corpuscular hemoglobin concentration (MCHC) were associated with cognitive function ((r = -0.257, P = 0.040; r = - 0.247, P = 0.049). No significant mediation effects were detected. CONCLUSIONS: SyMRI revealed T1 alterations in GM and WM in β-TM patients, associated with cognitive impairment and hematological markers. These findings implicated the neural correlates using SyMRI and potential neuroimaging biomarker of cognitive functioning in patients with β-TM.
Hypothalamic microstructure and function are associated with mild cognitive impairment in aging.
Sun M, Zhao X, Gao K … +2 more , Ding G, Yu J
Brain Res Bull · 2026 Jun · PMID 42092705 · Publisher ↗
BACKGROUND: The hypothalamus serves as a critical neuroendocrine center, yet its specific topographical and microarchitectural vulnerabilities during the preclinical stages of Alzheimer's disease remain poorly elucidated...
BACKGROUND: The hypothalamus serves as a critical neuroendocrine center, yet its specific topographical and microarchitectural vulnerabilities during the preclinical stages of Alzheimer's disease remain poorly elucidated. This study aimed to comprehensively investigate the macroscopic volumetric and microstructural alterations within hypothalamic subregions in patients with mild cognitive impairment (MCI) and their associations with cognitive and functional decline. METHODS: In this cross-sectional study, a total of 92 participants, comprising 47 MCI patients and 45 healthy controls (HC), underwent 3 T multimodal magnetic resonance imaging. The hypothalamus was automatically segmented into five bilateral subregions. Macroscopic volumetry (adjusted for estimated total intracranial volume) and diffusion tensor imaging (DTI) metrics-including fractional anisotropy (FA) and mean diffusivity (MD)-were extracted. Multiple regression models and sex-stratified correlation analyses were utilized to map structural trajectories against age, education, and clinical assessments. RESULTS: Hypothalamic alterations in MCI showed marked spatial heterogeneity and sexual dimorphism. Age-related volume loss was observed in HCs, whereas MCI patients exhibited sex-specific atrophic trajectories. MCI patients showed significantly reduced FA in the left anterior-inferior subregion compared with HCs. Microstructural disruption in the left tubular-superior subregion was significantly associated with lower MMSE scores and higher ADL scores. Higher educational attainment was independently associated with preserved microstructure in the posterior hypothalamus, supporting the cognitive reserve hypothesis. CONCLUSION: Hypothalamic degeneration in MCI is a spatially heterogeneous and sex-specific process. Localized microstructural disruption, especially in the left tubular-superior subregion, represents a sensitive imaging biomarker for early cognitive and functional impairment.
"Locked in my body, caught up in my mind": Neural signatures of body image rumination in anorexia nervosa.
Di Giuliano M, Schumann A, Geisler M … +3 more , Rieger K, Bär KJ, de la Cruz F
Brain Res Bull · 2026 Jun · PMID 42092704 · Publisher ↗
OBJECTIVES: Body image is a multidimensional construct crucial to the development and maintenance of anorexia nervosa (AN). Cognitive-emotional mechanisms shaping body image, particularly AN patients' tendency to ruminat...
OBJECTIVES: Body image is a multidimensional construct crucial to the development and maintenance of anorexia nervosa (AN). Cognitive-emotional mechanisms shaping body image, particularly AN patients' tendency to ruminate, remain insufficiently understood. This study investigated body-focused rumination using a novel functional magnetic resonance imaging (fMRI) Rumination Induction task. METHODS: Patients (n = 18) and healthy controls (n = 19) completed baseline assessments of rumination, body appreciation, and clinical measures. During fMRI, participants engaged in a task with self- and body-focused prompts contrasted with a neutral condition. Emotional valence and intensity were assessed pre- and post-task, alongside task-specific self-report ratings of affective valence and rumination experience. Whole-brain activations were examined for the main contrast (rumination vs. neutral) and, exploratorily, for early versus late rumination phases. RESULTS: Compared to controls, patients showed reduced activation in default mode network (DMN) overlapping regions, encompassing perigenual cingulate cortex, lateral parietal and temporal regions, praecuneus, temporoparietal junction, and cerebellum. A decreased engagement of the ventrolateral prefrontal cortex-key frontoparietal network node-in AN during early versus late rumination phases is outlined. CONCLUSIONS: Reduced DMN hubs activation may reflect disrupted cognitive-affective, autobiographical, and social mentalization processes in AN, as elicited by self-centred cognitions. At the same time, decreased ventrolateral prefrontal activity may suggest diminished ability to initiate affective reappraisal of self-focused cognitions, limiting voluntary suppression of repetitive thoughts in early versus later rumination stages. Overall, these findings support a model in which body image distortions are sustained by maladaptive cognitive-emotional mechanisms, whose neuronal markers may be highlighted through rumination predisposition.
Differential regulation of the central medial thalamic nucleus-basolateral amygdala pathway in acute itch and acute pain.
Liu J, Ji P, Liu Y … +3 more , Zhang T, Wang L, Liang S
Brain Res Bull · 2026 Jun · PMID 42092703 · Publisher ↗
As core aversive somatosensory sensations, itch and pain rely on precise central modulation, in which the central medial thalamic nucleus (CM) and basolateral amygdala (BLA) are critically involved. However, the involved...
As core aversive somatosensory sensations, itch and pain rely on precise central modulation, in which the central medial thalamic nucleus (CM) and basolateral amygdala (BLA) are critically involved. However, the involved regulatory circuits remain unclear. c-Fos staining showed that CM and BLA neurons were activated by Chloroquine (CQ)-, and Histamine (His)-induced acute itch and Formalin-induced acute pain. Subsequently, morphological tracing results confirmed the CM-BLA pathway, with CM neurons simultaneously projecting to both the BLA and BLA neurons. Furthermore, behavioral data revealed that CM-BLA pathway exerts differential regulation with anti-pruritic effects on acute itch and pronociceptive effects on acute pain. Accordingly, selective activation of either CM-BLA pathway or CM-BLA pathway also showed similar behaviors. In addition, results from fiber photometry also confirmed that the BLA‑projecting CM neurons exhibited significantly enhanced activity under both acute itch and nociceptive stimuli. Notably, postsynaptic BLA neurons in the CM-BLA pathway displayed differential functional predominance upon co-activation: VGAT1-positive neurons responded more robustly to acute itch than CaMKIIα-positive neurons, whereas CaMKIIα-positive neurons exhibited greater activation by acute pain stimuli than VGAT1-positive neurons. We therefore infer that during acute itch, CM neurons may suppress itch by activating BLA GABAergic interneurons to indirectly modulate local excitatory glutamatergic circuits, whereas in acute pain, CM neurons may facilitate pain via BLA glutamatergic principal neurons, while co‑activating GABAergic interneurons to synergistically enhance pain facilitation in the CM‑BLA pathway. These findings delineate a critical supraspinal circuit that differentially modulates acute itch and pain, providing novel mechanistic insights into somatosensory integration.
Rapid sequential activation from A1 to V1 in congenitally blind and sighted subjects.
Paré S, Baillet S, Ptito M … +1 more , Kupers R
Brain Res Bull · 2026 Jul · PMID 42070638 · Publisher ↗
Tactile information in congenitally blind (CB) individuals is funneled to the visual cortex through both via a fast thalamo-cortical and a strengthened polysynaptic cortico-cortical pathway. Auditory inputs can also acti...
Tactile information in congenitally blind (CB) individuals is funneled to the visual cortex through both via a fast thalamo-cortical and a strengthened polysynaptic cortico-cortical pathway. Auditory inputs can also activate the visual cortex in CB individuals, but whether these signals rely on the same dual route remains unclear. We used magnetoencephalography (MEG) to map the spatiotemporal dynamics and measure directed functional connectivity between regional brain responses to monaural auditory cues in eight CB and eight sex and age-matched sighted control (SC) participants. In both groups, a distinct sequential activation pattern was observed, initiating in the thalamus 10-20 ms after stimulus onset, followed by auditory cortex (A1) at approximately 35 ms, and visual cortex (V1) at 45-50 ms post-cue. Because monosynaptic cortico-cortical transmission typically occurs within about 10-15 ms, this temporal sequence suggests that auditory inputs reach the visual cortex through a direct, likely monosynaptic pathway between A1 and V1 in both CB and SC participants. Effective connectivity in the alpha band (8-12 Hz) was stronger in CB, birectionally between the thalamus and V1 and unidirectionally from A1 to V1, indicating functional strengthening of these pathways in congenital blindness. These findings suggest that, in CB, auditory signals are relayed to the occipital cortex primarily through an enhanced monosynaptic A1-to-V1 pathway that is also present, though weaker, in sighted individuals. This organization contrasts with tactile information processing in CB, which additionally engages a novel thalamo-cortical route to V1. Our results provide MEG-based evidence for a rapid, likely monosynaptic, A1-to-V1 pathway that is strengthened in congenital blindness.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe