Cortical Morphology Research Articles

Association between hearing ability and cortical morphology in the elderly: multiparametric mapping, cognitive relevance, and neurobiological underpinnings

Hearing impairment is a common condition in the elderly. However, a comprehensive understanding of its neural correlates is still lacking. We recruited 284 elderly adults who underwent structural MRI, magnetic resonance spectroscopy, audiometry, and cognitive assessments. Individual hearing abilities indexed by pure tone average (PTA) were correlated with multiple structural MRI-derived cortical morphological indices. For regions showing significant correlations, mediation analyses were performed to examine their role in the relationship between hearing ability and cognitive function. Finally, the correlation maps between hearing ability and cortical morphology were linked with publicly available connectomic gradient, transcriptomic, and neurotransmitter maps. Poorer hearing was related to cortical thickness (CT) reductions in widespread regions and gyrification index (GI) reductions in the right Area 52 and Insular Granular Complex. The GI in the right Area 52 mediated the relationship between hearing ability and executive function. This mediating effect was further modulated by glutamate and N-acetylaspartate levels in the right auditory region. The PTA-CT correlation map followed microstructural connectomic hierarchy, were related to genes involved in certain biological processes (e.g., glutamate metabolic process), cell types (e.g., excitatory neurons and astrocytes), and developmental stages (i.e., childhood to young adulthood), and covaried with dopamine receptor 1, dopamine transporter, and fluorodopa. The PTA-GI correlation map was related to 5-hydroxytryptamine receptor 2a. Poorer hearing is associated with cortical thinning and folding reductions, which may be engaged in the relationship between hearing impairment and cognitive decline in the elderly and have different neurobiological substrates. See the Acknowledgements section.

Correction to: White matter tract microstructure, macrostructure, and associated cortical gray matter morphology across the lifespan

Correction to: White matter tract microstructure, macrostructure, and associated cortical gray matter morphology across the lifespan

Human-specific insights into candidate genes and boosted discoveries of novel loci illuminate roles of neuroglia in reading disorders.

Reading disorders (RD) are human-specific neuropsychological conditions associated with decoding printed words and/or reading comprehension. So far only a handful of candidate genes segregated in families and 42 loci from genome-wide association study (GWAS) have been identified that jointly provided little clues of pathophysiology. Leveraging human-specific genomic information, we critically assessed the RD candidates for the first time and found substantial human-specific features within. The GWAS candidates (i.e., population signals) were distinct from the familial counterparts and were more likely pleiotropic in neuropsychiatric traits and to harbor human-specific regulatory elements (HSREs). Candidate genes associated with human cortical morphology indeed showed human-specific expression in adult brain cortices, particularly in neuroglia likely regulated by HSREs. Expression levels of candidate genes across human brain developmental stages showed a clear pattern of uplifted expression in early brain development crucial to RD development. Following the new insights and loci pleiotropic in cognitive traits, we identified four novel genes from the GWAS sub-significant associations (i.e., FOXO3, MAPT, KMT2E and HTT) and the Semaphorin gene family with functional priors (i.e., SEMA3A, SEMA3E and SEMA5B). These novel genes were related to neuronal plasticity and disorders, mostly conserved the pattern of uplifted expression in early brain development and had evident expression in cortical neuroglial cells. Our findings jointly illuminated the association of RD with neuroglia regulation-an emerging hotspot in studying neurodevelopmental disorders, and highlighted the need of improving RD phenotyping to avoid jeopardizing future genetic studies of RD.

Corpus callosum morphology and relationships to illness phenotypes in individuals with anorexia nervosa

Anorexia nervosa is an often-severe psychiatric illness characterized by significantly low body weight, fear of gaining weight, and distorted body image. Multiple neuroimaging studies have shown abnormalities in cortical morphology, mostly associated with the starvation state. Investigations of white matter, while more limited in number, have suggested global and regional volume reductions, as well as abnormal diffusivity in multiple regions including the corpus callosum. Yet, no study has specifically examined thickness of the corpus callosum, a large white matter tract instrumental in the inter-hemispheric integration of sensory, motor, and cognitive information. We analyzed MRI data from 48 adolescents and adults with anorexia nervosa and 50 healthy controls, all girls/women, to compare corpus callosum thickness and examined relationships with body mass index (BMI), illness duration, and eating disorder symptoms (controlling for BMI). There were no significant group differences in corpus callosum thickness. In the anorexia nervosa group, severity of body shape concerns was significantly, positively correlated with callosal thickness in the rostrum, genu, rostral body, isthmus, and splenium. In addition, there were significant positive correlations between eating disorder-related obsessions and compulsions and thickness of the anterior midbody, rostral body, and splenium. There were no significant associations between callosal thickness and BMI or illness duration. In sum, those with AN with worse concerns about bodily appearance and worse eating disorder-related obsessive thought patterns and compulsive behaviours have regionally thicker corpus callosum, independent of current weight status. These findings provide important neurobiological links to key, specific eating disorder behavioural phenotypes.

Osteomodulin deficiency in mice causes a specific reduction of transversal cortical bone size.

Skeletal growth, modeling, and remodeling are regulated by various molecules, one of them being the recently identified osteoanabolic factor WNT1. We have previously reported that WNT1 transcriptionally activates the expression of Omd, encoding Osteomodulin (OMD), in a murine mesenchymal cell line, which potentially explained the skeletal fragility of mice with mutational WNT1 inactivation, since OMD has been shown to regulate type I collagen fibril formation in vitro. In this study we confirmed the strong induction of Omd expression in a genome-wide expression analysis of transfected cells, and we obtained further evidence for Omd being a direct target gene of WNT1. To assess the in vivo relevance of this regulation, we crossed Omd-deficient mice with a mouse line harboring an inducible, osteoblast-specific Wnt1 transgene. After induction of Wnt1 expression for 1 or 3weeks, the osteoanabolic potency of WNT1 was not impaired despite the Omd deficiency. Since current knowledge regarding the in vivo physiological function of OMD is limited, we next focused on skeletal phenotyping of wild-type and Omd-deficient littermates, in the absence of a Wnt1 transgene. Here we did not observe an impact of Omd deficiency on trabecular bone parameters by histomorphometry and μCT either. Importantly, however, male and female Omd-deficient mice at the ages of 12 and 24weeks displayed a slender bone phenotype with significantly smaller long bones in the transversal dimension, while the longitudinal bone growth remained unaffected. Although mechanical testing revealed no significant changes explained by impaired bone material properties, atomic force microscopy of the femoral bone surface of Omd-deficient mice revealed moderate changes at the nanostructural level, indicating altered regulation of collagen fibril formation and aggregation. Taken together, our data demonstrate that, although OMD is dispensable for the osteoanabolic effect of WNT1, its deficiency in mice specifically modulates transversal cortical bone morphology.

Aberrant cortical morphology patterns are associated with cognitive impairment in patients with chronic heart failure.

A mounting body of evidences suggests that patients with chronic heart failure (HF) frequently experience cognitive impairments, but the neuroanatomical mechanism underlying these impairments remains elusive. In this retrospective study, 49 chronic HF patients and 49 healthy controls (HCs) underwent brain structural MRI scans and cognitive assessments. Cortical morphology index (cortical thickness, complexity, sulcal depth and gyrification) were evaluated. Correlations between cortical morphology and cognitive scores and clinical variables were explored. Logistic regression analysis was employed to identify risk factors for predicting 3-year major adverse cardiovascular events. Compared with HCs, patients with chronic HF exhibited decreased cognitive scores (p < .001) and decreased cortical thickness, sulcal depth and gyrification in brain regions involved cognition, sensorimotor, autonomic nervous system (family-wise error correction, all p values <.05). Notably, HF duration and New York Heart Association (NYHA) demonstrated negative correlations with abnormal cortex morphology, particularly HF duration and thickness in left precentral gyrus (r = -.387, p = .006). Cortical morphology characteristics exhibited positive associations with global cognition, particularly cortical thickness in left pars opercularis (r= .476, p< .001). NYHA class is an independent risk factor for adverse outcome (p = .001). The observed correlation between abnormal cortical morphology and global cognition suggested that cortical morphology may serve as a promising imaging biomarker and provide insights into neuroanatomical underpinnings of cognitive impairment in patients with chronic HF.

Altered Cortical Gyrification Morphology in Nonsucidal Self-injury

IntroductionNonsuicidal self-injury (NSSI) is defined as deliberate and direct damage to one’s body tissues without any suicidal intent. NSSI is now recognized as a major risk factor for suicide and is prevalent among adolescents, with prevalence rates ranging from 7.5% to 46.5%, leading to increased interest in the pathophysiology of NSSI. This study aimed to examine cortical gyrification morphology, a neurobiological index of cortical folding and patterning, among unmedicated individuals with NSSI, which is prevalent in adolescents and young adults.Objectives The main objective of this study is to compare cortical morphological abnormalities between individuals with NSSI and controls in terms of the local gyrification index (LGI), the ratio of the smooth cortical surface area at each vertex to the corresponding sulcal folds. In addition, we hypothesized that the LGI, a stable neurodevelopmental marker of cortical and subcortical circuit intergrity, would correlate with clinical measures in youth with NSSI.Methods A total of 101 individuals with NSSI and 100 age-, gender-, and handedness-matched controls completed self-report questionnaires and structural magnetic resonance imaging (MRI) data were acquired on a 3T Siemens scanner. A surface-based analysis was conducted using the Computational Anatomy Toolbox (CAT12) in Statistical Parametric Mapping (SPM12). Partial correlation analysis was also performed using R software to investigate the association between the LGI values extracted from the region of interest (ROI) and clinical symptoms, including depression, anxiety, emotion dysregulation, and anhedonia in individuals with NSSI.ResultsIndividuals with NSSI showed significantly increased LGI in the right insula sulcus and left superior temporal sulcus (STS), along with decreased LGI in the right calcarine and left superior parietal sulcus (SPS), compared to controls (5000 permutation correction, threshold-free cluster enhancement with a threshold of p &lt; .05). In addition, higher LGI in left STS was correlated with greater scores of the Beck Anxiety Inventory (r = 0.22, p &lt; .05) and of the Impulse Control Difficulties subscale of the Difficulties in Emotion Regulation Scale (r = 0.34, p &lt; .001). Conversely, reduced LGI of the right calcarine was associated with a higher score on the Anhedonia subscale of the Beck Depression Inventory (r = -0.23, p &lt; .05) within individuals with NSSI.ConclusionsThis study identified hypergyria in the right insular and left STS and hypogyria in the right calcarine and left SPS in individuals with NSSI. The former pattern was associated with anxiety and impulse control difficulties, and the latter was with anhedonia. This study is the first to alter distinct neurodevelopmental patterns of local gyrification and their correlations with clinical manifestations in individuals with NSSI.Disclosure of InterestNone Declared

Cortical morphology variations during the menstrual cycle in individuals with and without premenstrual dysphoric disorder

BackgroundPremenstrual dysphoric disorder (PMDD) is hypothesized to stem from maladaptive neural sensitivity to ovarian steroid hormone fluctuations. Recently, we found thinner cortices in individuals with PMDD, compared to healthy controls, during the symptomatic phase. Here, we aimed at investigating whether such differences illustrate state-like characteristics specific to the symptomatic phase, or trait-like features defining PMDD. MethodsPatients and controls were scanned using structural magnetic resonance imaging during the mid-follicular and late-luteal phase of the menstrual cycle. Group-by-phase interaction effects on cortical architecture metrics (cortical thickness, gyrification index, cortical complexity, and sulcal depth) were assessed using surface-based morphometry. ResultsIndependently of menstrual cycle phase, a main effect of diagnostic group on surface metrics was found, primarily illustrating thinner cortices (0.3 < Cohen's d > 1.1) and lower gyrification indices (0.4 < Cohen's d > 1.0) in patients compared to controls. Furthermore, menstrual cycle-specific effects were detected across all participants, depicting a decrease in cortical thickness (0.4 < Cohen's d > 1.7) and region-dependent changes in cortical folding metrics (0.4 < Cohen's d > 2.2) from the mid-follicular to the late luteal phase. LimitationsSmall effects (d = 0.3) require a larger sample size to be accurately characterized. ConclusionsThese findings provide initial evidence of trait-like cortical characteristics of the brain of individuals with premenstrual dysphoric disorder, together with indications of menstrual cycle-related variations in cortical architecture in patients and controls. Further investigations exploring whether these differences constitute stable vulnerability markers or develop over the years may help understand PMDD etiology.

A multimodal submillimeter MRI atlas of the human cerebellum

The human cerebellum is engaged in a broad array of tasks related to motor coordination, cognition, language, attention, memory, and emotional regulation. A detailed cerebellar atlas can facilitate the investigation of the structural and functional organization of the cerebellum. However, existing cerebellar atlases are typically limited to a single imaging modality with insufficient characterization of tissue properties. Here, we introduce a multifaceted cerebellar atlas based on high-resolution multimodal MRI, facilitating the understanding of the neurodevelopment and neurodegeneration of the cerebellum based on cortical morphology, tissue microstructure, and intra-cerebellar and cerebello-cerebral connectivity.

Morphometric similarity differences in drug-naive Parkinson's disease correlate with transcriptomic signatures.

Differences in cortical morphology have been reported in individuals with Parkinson's disease (PD). However, the pathophysiological mechanism of transcriptomic vulnerability in local brain regions remains unclear. This study aimed to characterize the morphometric changes of brain regions in early drug-naive PD patients and uncover the brain-wide gene expression correlates. The morphometric similarity (MS) network analysis was used to quantify the interregional structural similarity from multiple magnetic resonance imaging anatomical indices measured in each brain region of 170 early drug-naive PD patients and 123 controls. Then, we applied partial least squares regression to determine the relationship between regional changes in MS and spatial transcriptional signatures from the Allen Human Brain Atlas dataset, and identified the specific genes related to MS differences in PD. We further investigated the biological processes by which the PD-related genes were enriched and the cellular characterization of these genes. Our results showed that MS was mainly decreased in cingulate, frontal, and temporal cortical areas and increased in parietal and occipital cortical areas in early drug-naive PD patients. In addition, genes whose expression patterns were associated with regional MS changes in PD were involved in astrocytes, excitatory, and inhibitory neurons and were functionally enriched in neuron-specific biological processes related to trans-synaptic signaling and nervous system development. These findings advance our understanding of the microscale genetic and cellular mechanisms driving macroscale morphological abnormalities in early drug-naive PD patients and provide potential targets for future therapeutic trials.

Cortical bone architecture of hominid intermediate phalanges reveals functional signals of locomotion and manipulation.

Reconstruction of fossil hominin manual behaviors often relies on comparative analyses of extant hominid hands to understand the relationship between hand use and skeletal morphology. In this context, the intermediate phalanges remain understudied. Thus, here we investigate cortical bone morphology of the intermediate phalanges of extant hominids and compare it to the cortical structure of the proximal phalanges, to investigate the relationship between cortical bone structure and inferred loading during manual behaviors. Using micro-CT data, we analyze cortical bone structure of the intermediate phalangeal shaft of digits 2-5 in Pongo pygmaeus (n = 6 individuals), Gorilla gorilla (n = 22), Pan spp. (n = 23), and Homo sapiens (n = 23). The R package morphomap is used to study cortical bone distribution, cortical thickness and cross-sectional properties within and across taxa. Non-human great apes generally have thick cortical bone on the palmar shaft, with Pongo only having thick cortex on the peaks of the flexor sheath ridges, while African apes have thick cortex along the entire flexor sheath ridge and proximal to the trochlea. Humans are distinct in having thicker dorsal shaft cortex as well as thick cortex at the disto-palmar region of the shaft. Variation in cortical bone distribution and properties of the intermediate phalanges is consistent with differences in locomotor and manipulative behaviors in extant great apes. Comparisons between the intermediate and proximal phalanges reveals similar patterns of cortical bone distribution within each taxon but with potentially greater load experienced by the proximal phalanges, even in knuckle-walking African apes. This study provides a comparative context for the reconstruction of habitual hand use in fossil hominins and hominids.

Microtubule-binding protein MAP1B regulates interstitial axon branching of cortical neurons via the tubulin tyrosination cycle

Regulation of directed axon guidance and branching during development is essential for the generation of neuronal networks. However, the molecular mechanisms that underlie interstitial (or collateral) axon branching in the mammalian brain remain unresolved. Here, we investigate interstitial axon branching in vivo using an approach for precise labeling of layer 2/3 callosal projection neurons (CPNs). This method allows for quantitative analysis of axonal morphology at high acuity and also manipulation of gene expression in well-defined temporal windows. We find that the GSK3β serine/threonine kinase promotes interstitial axon branching in layer 2/3 CPNs by releasing MAP1B-mediated inhibition of axon branching. Further, we find that the tubulin tyrosination cycle is a key downstream component of GSK3β/MAP1B signaling. These data suggest a cell-autonomous molecular regulation of cortical neuron axon morphology, in which GSK3β can release a MAP1B-mediated brake on interstitial axon branching upstream of the posttranslational tubulin code.

Gender Incongruence and Autistic Traits: Cerebral and Behavioral Underpinnings

Gender dysphoria and autism spectrum disorder (ASD) co-occur at high rates. Yet, it is unknown whether gender dysphoria and ASD are associated with common or distinct neurobiological correlates or how they relate to experiences of gender-related body incongruence. Using the Social Responsiveness Scale, we assessed autistic traits in 99 transgender and 99 cisgender individuals and investigated their associations with gender-related body incongruence, measured via a visually based “Body Morph” test, and with cortical thickness in the brain. Autistic traits were significantly higher among transgender individuals, and those with higher autistic traits had higher body incongruence scoring. Among transgender individuals, higher autistic traits were linked with a thinner cortex bilaterally in the temporal pole and the superior and inferior temporal gyri. Autistic traits were only partly associated with cortical morphology patterns previously reported in transgender individuals; instead, they were primarily linked to temporal lobe areas mediating social cognition. While replicating the previous literature on the increased prevalence of autistic traits among transgender individuals, this study reports specific regions in the brains of transgender individuals where cortical thickness is associated with autistic traits.

Cortical Sulcal Abnormalities Revealed by Sulcal Morphometry in Patients with Chronic and Episodic Migraine.

Previous studies have reported mixed results regarding the importance of cortical abnormalities in patients with migraines. However, cortical sulci, as a component of the cerebral cortex, have not been specifically investigated in migraine patients. Therefore, we aim to evaluate alterations in cortical sulcal morphology among patients with chronic migraine (CM), episodic migraine (EM), and healthy controls (HCs). In this cross-sectional study, structural magnetic resonance images were acquired from 35 patients with CM, 35 with EM, and 35 HCs. Cortical sulci were identified and reconstructed using the BrainVisa 5.0.4 software. We focused on regions involved in pain processing in which abnormal cortical structure were identified in previous neuroimaging studies. Morphometric analysis was performed to calculate sulcal parameters including mean depth, cortical thickness, and opening width. Partial correlation analyses of clinical characteristics and sulcal parameters were performed for CM, EM and the combined migraine (CM + EM) groups. In comparison with HCs, both CM and EM groups showed increased opening width in bilateral insula. In comparison with HC and EM groups, CM patients showed increased cortical thickness in bilateral superior postcentral sulcus, bilateral median frontal sulcus and left superior parietal sulcus, as well as increased mean depth in the left anterior callosomarginal fissure and decreased mean depth in bilateral superior frontal sulcus and left median frontal sulcus. Migraine frequency and disease duration were both correlated with cortical thickness in bilateral superior postcentral sulcus. Abnormal sulcal morphometry primarily affected areas associated with pain processing in patients with migraine, with CM exhibiting more extensive abnormalities in areas related to sensory and affective processing. These changes may contribute to understanding the pathology of EM and CM.

Age-related decrease in inter-subject similarity of cortical morphology and task and resting-state functional connectivity.

"All old people are the same" is an unfortunate characterization of the perceived homogeneity in the older age group. This study attempts to debunk this myth in the context of the structural and functional brain. Within older relative to younger age groups, individuals are hypothesized to be more dissimilar to their similar-aged peers-thus demonstrating an age-related divergence. This study analyzed functional connectivity (FC) during multiple fMRI paradigms (2 rest + 5 tasks) and cortical thickness (CT) data from two lifespan datasets (Ntotal = 1161). On average, between-subject FC/CT correlations became weaker in the older age groups. Further analyses ruled out the possibility that more rapid age-related changes in older brains have increased the dissimilarity in these older age groups. Brain-wide analyses revealed significant effects of age-related divergence across most of the brain. Finally, CT similarity between a dyad significantly predicted their FC similarity across multiple fMRI task paradigms-demonstrating a close relationship between brain structure and function even at the between-dyad level. Contrary to the myth that "all old people are the same," these findings suggest young people are more similar to each other. This study presents major implications in the study of neural fingerprinting and brain-behavior associations.

Cortical Bone Thickness and Morphology at the Infrazygomatic Crest Area in Growing Thai Patients with UCLP: A CBCT Study.

To determine and compare buccal cortical bone thickness and morphology (in terms of shape and height) at the infrazygomatic (IZ) crest in growing Thai patients with unilateral cleft lip and palate (UCLP) using cone-beam computed tomography (CBCT) with the ultimate goal of identifying potential sites that are suitable for the placement of miniplates. Prospective study. Institutional research. Twenty-four Thai patients with non-syndromic complete UCLP with Class III skeletal discrepancy aged 10-14 years. A total of 48 CBCT images captured the IZ crest. Five horizontal and six vertical reference planes were established in the IZ crest area. The mean buccal cortical bone thickness of the cleft and non-cleft sides were 1.13 ± 0.45 mm and 1.15 ± 0.46 mm, respectively. The most frequently observed shape for the IZ crest was the external concave contour. There were no statistically significant differences in cortical bone thickness and shape distribution between the cleft and non-cleft sides. (P > .05). The thickness of the buccal cortical bone increased anteriorly and superiorly from V + 0 and H + 0. The average height of IZ crest on the cleft side was 16.20 ± 1.59 mm and 16.78 ± 1.84 mm on the non-cleft side. Notably, significant differences were detected in terms of height between the cleft and non-cleft side and cortical bone thickness by gender (P < .05). The IZ crest was found to provide sufficient support for the insertion of a miniplate, particularly in the superior and anterior regions, ensuring primary stability in growing Thai patients with UCLP.

Cortical changes in the brain of patients with hemifacial spasm.

Hemifacial spasm (HFS) is a movement disorder characterized by involuntary muscle contractions on one side of the face. It is associated with disturbances in the brain's functional architecture. Despite this, the structural alterations in the brain related to HFS remain poorly understood. In this study, we investigated the cortical morphology changes in patients with HFS compared to healthy controls (HCs). We analyzed 3D T1-weighted MRI images from 33 patients with left-sided primary HFS and 33 age- and sex-matched HCs. Measurements of cortical thickness (CTh), sulcal depth, local gyrification index (lGI), and fractal dimension were taken using a computational anatomy toolbox. A general linear model, accounting for age, gender, and total brain volume, was applied for statistical analyses. Significant clusters were then assessed for correlations with clinical parameters. The HFS patients displayed several cortical abnormalities when compared to HCs, including reduced CTh in the contralateral precentral gyrus and left orbitofrontal cortex, decreased sulcal depth in the left orbitofrontal cortex, and increased lGI in the right insula and superior temporal cortex. However, fractal dimension did not differ significantly between the groups. Additionally, in HFS patients, a notable negative correlation was found between the sulcal depth in the left orbitofrontal cortex and the Beck Depression Inventory-II scores. Our findings reveal that HFS is associated with specific surface-based morphological changes in the brain. These alterations contribute to a deeper understanding of the neurophysiological mechanisms involved in HFS and may have implications for future research and treatment strategies.

Structural connectome architecture shapes the maturation of cortical morphology from childhood to adolescence

Cortical thinning is an important hallmark of the maturation of brain morphology during childhood and adolescence. However, the connectome-based wiring mechanism that underlies cortical maturation remains unclear. Here, we show cortical thinning patterns primarily located in the lateral frontal and parietal heteromodal nodes during childhood and adolescence, which are structurally constrained by white matter network architecture and are particularly represented using a network-based diffusion model. Furthermore, connectome-based constraints are regionally heterogeneous, with the largest constraints residing in frontoparietal nodes, and are associated with gene expression signatures of microstructural neurodevelopmental events. These results are highly reproducible in another independent dataset. These findings advance our understanding of network-level mechanisms and the associated genetic basis that underlies the maturational process of cortical morphology during childhood and adolescence.

Pten knockout in mouse preosteoblasts leads to changes in bone turnover and strength.

Bone development and remodeling are controlled by the phosphoinositide-3-kinase (Pi3k) signaling pathway. We investigated the effects of downregulation of phosphatase and tensin homolog (Pten), a negative regulator of Pi3k signaling, in a mouse model of Pten deficiency in preosteoblasts. We aimed to identify mechanisms that are involved in the regulation of bone turnover and are linked to bone disorders. Femora, tibiae, and bone marrow stromal cells (BMSCs) isolated from mice with a conditional deletion of Pten (Pten cKO) in Osterix/Sp7-expressing osteoprogenitor cells were compared to Cre-negative controls. Bone phenotyping was performed by μCT measurements, bone histomorphometry, quantification of bone turnover markers CTX and procollagen type 1N propeptide (P1NP), and three-point bending test. Proliferation of BMSCs was measured by counting nuclei and Ki-67-stained cells. In vitro, osteogenic differentiation capacity was determined by ALP staining, as well as by detecting gene expression of osteogenic markers. BMSCs from Pten cKO mice were functionally different from control BMSCs. Osteogenic markers were increased in BMSCs derived from Pten cKO mice, while Pten protein expression was lower and Akt phosphorylation was increased. We detected a higher trabecular bone volume and an altered cortical bone morphology in Pten cKO bones with a progressive decrease in bone and tissue mineral density. Pten cKO bones displayed fewer osteoclasts and more osteoblasts (P = .00095) per trabecular bone surface and a higher trabecular bone formation rate. Biomechanical analysis revealed a significantly higher bone strength (P = .00012 for males) and elasticity of Pten cKO femora. On the cellular level, both proliferation and osteogenic differentiation capacity of Pten cKO BMSCs were significantly increased compared to controls. Our findings suggest that Pten knockout in osteoprogenitor cells increases bone stability and elasticity by increasing trabecular bone mass and leads to increased proliferation and osteogenic differentiation of BMSCs.

Effects and central mechanism of electroacupuncture and MRI-navigated rTMS for PSD: study protocol for an fMRI-based single-center, randomized, controlled, open-label trial.

Post-stroke depression (PSD) is the most common mental complication after stroke and has a serious impact on functional outcomes and quality of life for stroke patients. Antidepressants are the first-line treatment for PSD; however, many reported side effects remain. Clinical research and practice guidelines have shown that electro-acupuncture (EA) or rTMS have a positive effect on PSD. However, there are few clinical studies on EA and MRI-navigated rTMS for PSD that explore the fMRI-based central mechanism in depression. In this randomized, controlled, open-label trial, 64 patients with PSD will be randomly allocated into the experiment group (n = 32) or control group (n = 32). The experiment group will receive EA and MRI-navigated rTMS and the control group will receive MRI-navigated rTMS treatment, in 12-20 sessions over 4 weeks. In addition, 10 healthy people for fMRI scanning will be recruited as a healthy control group without any intervention. The primary outcome will be the change from baseline in the Hamilton Depression Scale-24 item (HAMD-24) scores at week 4. The primary analysis of the central mechanism will mainly involve cortical morphology, local spontaneous brain activity, and the default mode network (DMN) functional connectivity based on fMRI at 0 and 4 weeks. Secondary outcomes will include the neuro-patho-physiological and quality of life changes in cortical excitability, determined using the motor evoked potential test (MEP), National Institutes of Health Stroke Scale (NIHSS), EuroQol Five Dimensions Questionnaire (EQ-5D) Scale, Modified Barthel Index (MBI) Scale, and Health Scale of Traditional Chinese Medicine (HSTCM). Additional indicators will include the Acceptability Questionnaire and Health Economics Evaluation (cost-effectiveness analysis) to assess the acceptability and economic practicality of the treatment under study. Outcomes will be assessed at baseline and post intervention. EA and MRI-navigated rTMS therapy could become an alternative treatment for PSD, and it is expected that this trial will provide reliable clinical evidence and a potential central mechanism for the future use of EA and MRI-navigated rTMS for PSD. NCT05516680, ClinicalTrials.gov (registered in August 2022).