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[Display omitted] • Surface brain morphometry was explored in type 1 diabetes and neuropathic phenotypes. • Cortical thickness was reduced in diabetes and neuropathic pain. • Reduced postcentral gyrus sulcus depth associated with neuropathic pain. • Brain morphometry may offer deeper insights into diabetes and neuropathic pain. This study explored surface brain morphometry in type 1 diabetes including focus on painful diabetic peripheral neuropathy (DPN). Brain MRI was obtained from 56 individuals with diabetes (18 without DPN, 19 with painless DPN, 19 with painful DPN) and 20 healthy controls. Cortical thickness, sulcus depth, and gyrification were analysed globally and regionally in each group and in the combined diabetes group. Associations with clinical characteristics and pain were assessed. Globally, cortical thickness was reduced in the combined diabetes group and in painful DPN compared to healthy controls. No differences in sulcus depth and gyrification were found. Several regions, including the middle frontal gyrus showed reduced cortical thickness in the combined diabetes- and painful DPN group. The postcentral gyrus exhibited reduced cortical thickness in painful DPN compared to healthy controls, and reduced sulcus depth compared to painless DPN correlating with higher pain intensity. Cortical thinning manifested across the brain cortex in diabetes, especially for painful DPN. Altered postcentral gyrus morphometry may be associated with neuropathic pain. Assessing cortical morphometry may be critical for comprehending central neuropathy and the manifestation of painful DPN in diabetes. [ABSTRACT FROM AUTHOR]

Background: Memory decline is common in multiple sclerosis (MS), although pathophysiological mechanisms are not fully understood. Objective: The objective was to investigate the relationship of changes in structural and functional neuroimaging markers to memory decline over 3-year follow-up. Methods: Participants with MS underwent cognitive evaluation and structural, diffusion, and functional 3T magnetic resonance imaging (MRI) scans at baseline and 3-year follow-up. Changes in neuroimaging metrics from baseline to follow-up were compared between memory stable and memory decline groups. Our hypothesis that structural and functional connectivity changes mediate the association of atrophy to memory decline was tested. Results: A total of 249 MS patients completed baseline visit; 169 (67.8%) returned at 3-year follow-up. Based on ⩾10% decline, memory decline was observed in 44.4% (n = 75). Those with memory decline showed marginally greater whole-brain volume loss over time compared with those with stable memory performance (p = 0.08). In those with memory decline, changes in white matter tract integrity were related to regional cortical thinning (p < 0.01). Exploratory mediation analysis revealed structural and functional connectivity to mediate the relationship of atrophy to verbal and visual memory decline. Conclusion: Further work is needed to characterize complex interrelationships of atrophy and structural/functional connectivity changes to memory decline in MS. [ABSTRACT FROM AUTHOR]

Osteoporosis in postmenopausal women is one of the causes of femoral fractures and is prevented by the administration of bisphosphonates. Individual morphologies are considered to increase the risk of atypical fractures associated with long‐term administration. To evaluate cortical bone morphology quantitatively, we established a method to measure the distance from the center point of a cross‐section to the external and internal borders based on CT images. Using this method, 44 sides of a female femoral skeleton specimen were examined and areas of protrusion and thickening in the medial anterior and lateral posterior regions just below the lesser trochanter were identified. These positions strongly correlated with the anteversion angle, suggesting the involvement of the distribution of the load received from body weight defined by the angle. The finite element method was used to examine the relationships between the positions of these areas with compressive and tensile stress distribution areas in the one‐legged standing condition. The medial anterior region and lateral posterior region protruded and thickened in response to compressive and tensile stress, respectively. In addition, a hierarchical relationship was observed between the anteversion angle, tensile stress distribution, protrusion, and thickening in femurs with thinning of cortical bone, indicating that morphogenesis occurs adaptively to loading. The present results demonstrate the usefulness of this method in considering the formation mechanism and function of the femoral diaphysis and suggest that bone remodeling is necessary to maintain adaptability. [ABSTRACT FROM AUTHOR]

Dopamine (DA) signaling is critical for optimal cognitive aging, especially in prefrontal-parietal and fronto-striatal networks. Single nucleotide polymorphisms associated with dopamine regulation, COMT Val158Met and DRD2 C957T , stand to exert influence on executive function performance via neural properties. The current study investigated whether longitudinal thinning of mesocortical regions is related to COMT and DRD2 genetic predisposition and associated with decline in executive function over four-years. N =235 healthy adults aged 20–94 years were recruited, with n =124 returning 4-years later. Latent mixed effects modeling revealed dopamine-related thinning in several frontal, parietal, and cingulate regions as well as decline in verbal fluency category switching across 4-years. Mesocortical thinning was also related to switching performance. Greater cortical thinning interacted with DA-genotype risk for lower DA-availability to predict poorer switching performance in parietal and posterior cingulate cortex. These findings lend support to the notion that early-life factors, such as genetic influence on neurotransmitter function, play a role in cognitive and brain aging and their linked association. • Dopamine signaling decreases significantly with aging and predicts poorer cognition. • Genetic polymorphisms regulating dopamine availability predict cognitive performance. • Greater cortical thinning seen in genotypes at risk for lower synaptic availability. • Dopamine-related thinning was associated with poorer executive function performance. • Genetic predisposition to lower dopamine availability impacts neurocognitive aging. [ABSTRACT FROM AUTHOR]

Cherubism is a rare autosomal dominant skeletal dysplasia, affecting the maxilla and/or mandible. The condition typically has childhood onset, followed by progression until puberty, with subsequent regression. Cherubism lesions share histological features with giant cell tumor of bone, where high-dose monthly denosumab is an effective medical treatment. Therefore, high-dose denosumab has also been trialed in children with cherubism with positive outcomes. However, the role of denosumab in adult cherubism, particularly a lower dose and frequency, has not been established. We present the case of a 60-year-old man with cherubism, reviewed for a new 39 × 21 mm left mandibular lesion. The patient had multiple surgeries up to the age of 30 for tumors in the right maxilla and mandible. Given the impact of further surgery on his appearance and quality of life, the patient was referred to Endocrinology for consideration of medical therapy. His bone turnover markers were slightly elevated with normal calcium, phosphate, 25-OH vitamin D, and parathyroid hormone levels. A bone density scan showed lumbar spine osteopenia. He was commenced on 60 mg denosumab 6-monthly with excellent clinical and radiological responses over the next 30 months. The most recent CT mandible showed a sustained reduction in the lesion size, measuring 36 × 18 mm, with osteoid formation and improvement in cortical thinning. Surgery is no longer indicated. No adverse effects from denosumab were reported in the patient. This is the first study to report the efficacy and safety of a low-dose denosumab regimen in the management of cherubism. This treatment approach was able to prevent major surgery and minimize denosumab-related adverse effects. While the optimal treatment duration remains unclear, the patient will continue with 60 mg denosumab 6-monthly in the short-term given the favorable response. In summary, a low-dose denosumab regimen should be considered for patients with cherubism, particularly those with contraindications or preferences to avoid surgery. [ABSTRACT FROM AUTHOR]

Introduction: Amyotrophic lateral sclerosis (ALS) is a rare, devastating neurodegenerative disease that affects upper and lower motor neurons, resulting in muscle atrophy, spasticity, hyperreflexia, and paralysis. Inflammation plays an important role in the development of ALS, and associated with rapid disease progression. Current observational studies indicate the thinning of cortical thickness in patients with ALS is associated with rapid disease progression and cognitive changes. However, the effects of inflammatory cytokines on cortical thickness in patients with ALS are unclear. Here, we investigated the relationship between inflammatory cytokines and cortical thickness in patients with ALS. Methods: We evaluated 51 patients with ALS for inflammatory cytokines including interleukin (IL)-4, interferon (IFN)-α, IL-1β, IL-2, IL-5, IL-12, tumor necrosis factor (TNF)-α, IL-6, IL-10, IL-8, IL-17, and IFN-γ and analyzed the correlation between these indicators and the ALS functional rating scale-revised (ALSFRS-R) score or disease progression rate (ΔFS score). Twenty-six patients with ALS and 26 controls were studied using whole-cortex analysis, and post-hoc analyses were performed to examine the correlation between brain cortical thickness and ALSFRS-R or ΔFS scores. Results: IL-4, IFN-α, IL-1β, and IL-2 levels were significantly correlated with ALSFRS-R scores, and the IL-2 level was significantly correlated with ΔFS scores. After controlling for age and sex, the ALS group had thinner cortexes in multiple clusters across the brain than the control group. Further analyses revealed that cortical thickness in the right superior temporal and lingual gyrus regions was inversely correlated with ΔFS scores. There was a significant positive correlation between the clusters in the right lingual cortex and IL-2 level. Conclusion: These results suggest cortical thickness was reduced in patients with ALS in motor and non-motor cortical areas. Inflammatory factors (especially IL-2) were correlated with cortical thickness, and both were related to the disease progression rate, suggesting IL-2 plays an important role in ALS. [ABSTRACT FROM AUTHOR]

Background: Accumulation of β-amyloid (Aβ) in the brain is a hallmark of Alzheimer's Disease (AD). Cerebral deposition of Aβ initiates deteriorating pathways which eventually can lead to AD. However, the exact mechanisms are not known. A possible pathway could be that Aβ affects the cerebral vessels, causing inadequate cerebrovascular function. In the present study, we examined if Aβ accumulation is associated with a reduced cerebral blood flow response (CBF) to neuronal activation by visual stimulation (ΔCBFVis.Act.) in cognitively normal subjects from the Metropolit Danish Male Birth Cohort. Methods: 64 subjects participated in the present study. ΔCBFVis.Act. was measured using arterial spin labelling (ASL) combined with blood-oxygen-level-dependent (BOLD) MRI. Neuronal activation was obtained by visual stimulation by a flickering checkerboard presented on a screen in the MRI-scanner. Brain Aβ accumulation and cerebral glucose metabolism were assessed by PET imaging using the radiotracers [11C]Pittsburgh Compound-B (PiB) and [18F]Fluorodeoxyglucose (FDG), respectively. Cortical thickness was measured from structural MRI. Results: ΔCBFVis.Act. correlated negatively (β = -32.1 [95% confidence interval (CI): -60.2; -4.1], r = -0.30, p = 0.025) with PiB standardized uptake value ratio (SUVr) in the brain regions activated by visual stimulation. ΔCBFVis.Act. did not correlate with FDG SUVr (β = 1.9 [CI: -23.8; 27.6], r = 0.02, p = 0.88) or cortical thickness (β = 10.3 [CI: -8.4; 29.0], r = 0.15, p = 0.27) in the activated brain regions. Resting CBF did not correlate with PiB SUVr neither in the regions activated by visual stimulation (β = -17.8 [CI:-71.9; 36.2], r =- 0.09, p = 0.51) nor in the remaining cortex (β = 5.2 [CI:-3.9; 14.2], r = 0.15, p = 0.26). Conclusion: We found a correlation between high PiB SUVr and reduced CBF response to neuronal activation, indicating a link between Aβ accumulation and impaired cerebrovascular function. The impairment was not associated with cortical thinning or hypometabolism, suggesting that Aβ accumulation affecting brain vessel function could be a very early pathology leading to neurodegenerative disease. [ABSTRACT FROM AUTHOR]

Objective Methods Results Interpretation To assess the interrelationship between cortical lesions and cortical thinning and volume loss in people with multiple sclerosis within cortical networks, and how this relates to future cognition.In this longitudinal study, 230 people with multiple sclerosis and 60 healthy controls underwent 3 Tesla MRI at baseline and neuropsychological assessment at baseline and 5‐year follow‐up. Cortical regions (N = 212) were divided into seven functional networks. Regions were defined as either lesional or normal‐appearing cortex based on presence of a cortical lesion on artificial intelligence‐generated double inversion‐recovery scans. Cortical volume and thickness were determined within lesional or normal‐appearing cortex.Prevalence of at least one cortical lesion was highest in the limbic (73%) followed by the default mode network (70.9%). Multiple sclerosis‐related cortical thinning was more pronounced in lesional (mean Z‐score = 0.70 ± 0.84) compared to normal‐appearing cortex (−0.45 ± 0.60; P < 0.001) in all, except sensorimotor, networks. Cognitive dysfunction, particularly of verbal memory, visuospatial memory, and inhibition, at follow‐up was best predicted by baseline network volume of normal‐appearing cortex of the default mode network [B (95% CI) = 0.31 (0.18; 0.43), P < 0.001]. Mediation analysis showed that the effect of cortical lesions on future cognition was mediated by volume loss of the normal‐appearing instead of lesional cortex, independent of white matter lesion volume.Multiple sclerosis‐related cortical thinning was worse in lesional compared to normal‐appearing cortex, while volume loss of normal‐appearing cortex was most predictive of subsequent cognitive decline, particularly in the default mode network. Mediation analyses indicate that cortical lesions impact cognitive decline plausibly by inducing atrophy, rather than through a direct effect. [ABSTRACT FROM AUTHOR]

Studies with genetically modified mice have implicated the transcriptional regulator STAT3 as a key modulator of bone development. STAT3-OKO knockout mouse lines were generated in two genetic backgrounds, pure C57BL/6 (STAT3-OKO-BL) and mixed C57BL/6, CD1 (STAT3-OKO-M). Both lines exhibited defective postnatal bone development resulting in reduced body weight and shortened femurs that displayed low bone mineral density as well as cortical widening and thinning in the diaphyseal region. Remarkably, each of these defects displayed sexual dimorphism that was dependent on genetic background: the phenotype was entirely male-specific in STAT3-OKO-M but not in STAT3-OKO-BL, in which defects were similar in both sexes. However, both lines exhibited a male-specific bone defect in mineralization, and also in bone mechanical properties related to bone quality, such as yield stress and ultimate stress. On the other hand, bone mechanical properties such as ultimate force, that may reflect density and macrostructure rather than bone quality, showed male-specific defects only in STAT3-OKO-M. These findings suggest that STAT3 may regulate multiple sex-dependent mechanisms in bone development that control either mineralization or bone accrual, and that the sex-dependence of at least some of these mechanisms is affected by genetic background. Finally, we used CRISPR/Cas9 to generate STAT3-deficient preosteoblastic cells from immortalized wild-type bone marrow stem cells and showed that the defective osteoblastic differentiation of STAT3-ablated cells was associated with reduced gene expression of Wnt3a and Wnt5a, consistent with other studies that identify Wnt signaling pathways as potential effector mechanisms for STAT3-mediated regulation of bone development. [ABSTRACT FROM AUTHOR]

Neurodegeneration is a seminal feature of many neurological disorders. Chronic traumatic encephalopathy (CTE) is caused by repetitive head impacts (RHI) and is characterized by sulcal tau pathology. However, quantitative assessments of regional neurodegeneration in CTE have not been described. In this study, we quantified three key neurodegenerative measures, including cortical thickness, neuronal density, and synaptic proteins, in contact sport athletes (n = 185) and non-athlete controls (n = 52) within the sulcal depth, middle, and gyral crest of the dorsolateral frontal cortex. Cortical thickness and neuronal density were decreased within the sulcus in CTE compared to controls (p's < 0.05). Measurements of synaptic proteins within the gyral crest showed a reduction of α-synuclein with CTE stage (p = 0.002) and variable changes in PSD-95 density. After adjusting for age, multiple linear regression models demonstrated a strong association between the duration of contact sports play and cortical thinning (p = 0.001) and neuronal loss (p = 0.032) within the sulcus. Additional regression models, adjusted for tau pathology, suggest that within the sulcus, the duration of play was associated with neuronal loss predominantly through tau pathology. In contrast, the association of duration of play with cortical thinning was minimally impacted by tau pathology. Overall, CTE is associated with cortical atrophy and a predominant sulcal neurodegeneration. Furthermore, the duration of contact sports play is associated with measures of neurodegeneration that are more severe in the cortical sulcus and may occur through tau-dependent and independent mechanisms. [ABSTRACT FROM AUTHOR]

Previous studies on age-related changes in cortical and hippocampal morphology were not designed or able to reveal the complex spatial patterns of changes across the lifespan. To this end, the current study examined these changes in a decade-by-decade manner by comparing consecutive age decades at the vertex-wise level. Additionally, the lifespan trajectories of cortical/hippocampal mean thickness and total surface area were modeled and plotted out to provide an overview of their age-related changes. Using two lifespan datasets (Ntotal = 1378; 18 ≤ age ≤ 100), vertex-wise thickness and surface area measurements were extracted from the cortical and unfolded hippocampal surfaces and analyzed using whole-brain/hippocampus vertex-wise analyses. Lifespan trajectories of cortical/hippocampal mean thickness and total surface area were modeled with generalized additive models for location, scale, and shape. These models revealed fairly linear declines in both cortical measures and inverted U-shaped trajectories for both hippocampal measures. Across the different age decades, the sizes and locations of cortical thinning clusters were highly variable across the age decades. No significant clusters of cortical surface area changes were observed across the age decades. Significant clusters of hippocampal surface area and thickness reduction were not observed until the 70s. Generally, the agreement between datasets on the hippocampal findings was much higher than those of the cortical surface. These findings revealed important nuances in the age-related changes of cortical and hippocampal morphology and cautioned against using lifespan trajectories to infer decade-by-decade changes in the cortical surface and the hippocampus. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is one of the foremost causes of disability and mortality globally. While the scientific and medical emphasis is to save lives and avoid disability during acute period of injury, a severe health problem can manifest years after injury. For instance, TBI increases the risk of cognitive impairment in the elderly. Remote TBI history was reported to be a cause of the accelerated clinical trajectory of Alzheimer's disease-related dementia (ADRD) resulting in earlier onset of cognitive impairment and increased AD-associated pathological markers like greater amyloid deposition and cortical thinning. It is not well understood whether a single TBI event may increase the risk of dementia. Moreover, the cellular signaling pathways remain elusive for the chronic effects of TBI on cognition. We have hypothesized that a single TBI induces sustained neuroinflammation and disrupts cellular communication in a way that results later in ADRD pathology. To test this, we induced TBI in young adult CD1 mice and assessed the behavioral outcomes after 11 months followed by pathological, histological, transcriptomic, and MRI assessment. On MRI scans, these mice showed significant loss of tissue, reduced CBF, and higher white matter injury compared to sham mice. We found these brains showed progressive atrophy, markers of ADRD, sustained astrogliosis, loss of neuronal plasticity, and growth factors even after 1-year post-TBI. Because of progressive neurodegeneration, these mice had motor deficits, showed cognitive impairments, and wandered randomly in open field. We, therefore, conclude that progressive pathology after adulthood TBI leads to neurodegenerative conditions such as ADRD and impairs neuronal functions. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Tau pathology is recognized as a primary contributor to neurodegeneration and clinical symptoms in Alzheimers disease (AD). This study aims to localize the early tau pathology in cognitively normal older people that is predictive of subsequent neurodegeneration and memory decline, and delineate factors underlying tau-related memory decline in individuals with and without β-amyloid (Aβ). METHODS: A total of 138 cognitively normal older individuals from the Berkeley Aging Cohort Study underwent 11 C-Pittsburgh Compound-B (PiB) positron emission tomography (PET) to determine Aβ positivity and 18 F-Flortaucipir (FTP) PET to measure tau deposition, with prospective cognitive assessments and structural magnetic resonance imaging. Voxel-wise FTP analyses examined associations between baseline tau deposition and longitudinal memory decline, longitudinal hippocampal atrophy, and longitudinal cortical thinning in AD signature regions. We also examined whether hippocampal atrophy and cortical thinning mediate tau effects on future memory decline. RESULTS: We found Aβ-dependent tau associations with memory decline in the entorhinal and temporoparietal regions, Aβ-independent tau associations with hippocampal atrophy within the medial temporal lobe (MTL), and that widespread tau was associated with mean cortical thinning in AD signature regions. Tau-related memory decline was mediated by hippocampal atrophy in Aβ- individuals and by mean cortical thinning in Aβ+ individuals. INTERPRETATION: Our results suggest that tau may affect memory through different mechanisms in normal aging and AD. Early tau deposition independent of Aβ predicts subsequent hippocampal atrophy that may lead to memory deficits in normal older individuals, whereas elevated cortical tau deposition is associated with cortical thinning that may lead to more severe memory decline in AD. ANN NEUROL 2024;95:249-259.

The document delves into multiple studies on Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Degeneration, focusing on topics such as disease diagnosis, patient stratification, and understanding disease mechanisms. It discusses the importance of biomarkers, autonomic nervous function, and astrocyte pathology in ALS research and clinical trials. Additionally, the research explores genetic risk factors, respiratory impairments, and the impact of genetic polymorphisms on survival in ALS and FTD patients, aiming to improve prognosis and management of these neurodegenerative diseases. [Extracted from the article]

The brain undergoes extensive development during late childhood and early adolescence. Cortical thinning is a prominent feature of this development, and some researchers have suggested that differences in cortical thickness may be related to internalizing symptoms, which typically increase during the same period. However, research has yielded inconclusive results. We utilized a new method that estimates the combined effect of individual differences in vertex‐wise cortical thickness on internalizing symptoms. This approach allows for many small effects to be distributed across the cortex and avoids the necessity of correcting for multiple tests. Using a sample of 8763 children aged 8.9 to 11.1 from the ABCD study, we decomposed the total variation in caregiver‐reported internalizing symptoms into differences in cortical thickness, additive genetics, and shared family environmental factors and unique environmental factors. Our results indicated that individual differences in cortical thickness accounted for less than 0.5% of the variation in internalizing symptoms. In contrast, the analysis revealed a substantial effect of additive genetics and family environmental factors on the different components of internalizing symptoms, ranging from 06% to 48% and from 0% to 34%, respectively. Overall, while this study found a minimal association between cortical thickness and internalizing symptoms, additive genetics, and familial environmental factors appear to be of importance for describing differences in internalizing symptoms in late childhood. Research Highlights: We utilized a new method for modelling the total contribution of vertex‐wise individual differences in cortical thickness to internalizing symptoms in late childhood.The total contribution of individual differences in cortical thickness accounted for <0.5% of the variance in internalizing symptoms.Additive genetics and shared family environmental variation accounted for 17% and 34% of the variance in internalizing symptoms, respectively.Our results suggest that cortical thickness is not an important indicator for internalizing symptoms in childhood, whereas genetic and environmental differences have a substantial impact. [ABSTRACT FROM AUTHOR]

Bone drilling mechanism study is the basis for the optimization of cortical bone drilling process and drill geometry. In this paper, a drilling force model for modified drills with thinned chisel edge is established considering the heterogeneous structure of cortical bone. The bone mineral density is embedded into the established model, the model can predict the axial thrust force change along the drilling depth direction, and the model is verified through cortical bone drilling experiments. The thrust force and torque predicted by the model are in good agreement with the drilling experimental results of cortical bone drilling. Then, the drilling performance of the modified drill and the common drill is compared through cortical bone drilling experiments. Compared with common drill bits, the maximum reduction in average thrust force of the modified drill bit during stable drilling is 21.21 % (n = 2500 rpm, V f =60 mm/min). The maximum reduction in average roughness of the hole wall is 21.87 % (n = 500 rpm, V f =10 mm/min). The drill chisel edge thinning design reduces the negative impact of the negative normal rake angle on the cutting lip of common drill on drilling force and stability. Therefore, the drill bit chisel edge thinning design can effectively improve the drilling performance. • Considering the heterogeneous structure of cortical bone, a drilling force model is established.. • The model can predict the variation of axial thrust force and torque along the drilling depth. • Thinning the chisel edge of the drill can effectively improve the drilling performance. [ABSTRACT FROM AUTHOR]

Introduction: Cortical thinning is well-documented in individuals with amyotrophic lateral sclerosis (ALS), yet its association with speech deterioration remains understudied. This study characterizes anatomical changes in the brain within the context of speech impairment patterns in individuals with ALS, providing insight into the disease's multiregional spread and biology. Methods: To evaluate patterns of cortical thickness in speakers with ALS with and without functional speech changes compared to healthy controls (HCs) using whole-brain and region of interest (ROI) analyses. Forty individuals with ALS and 22 HCs underwent a T1-weighted 3-Tesla magnetic resonance imaging (MRI). Individuals with ALS were divided into two groups based on the preserved speech [ps-ALS] (n = 18) or deteriorated speech [ds-ALS] (n = 22) as measured by the ALSFRSF-R speech subscore (=4 or <4 points, respectively). Sixteen a priori-defined and automatically segmented cortical and subcortical brain ROIs were selected based on their previously documented roles in speech production. Two cortical thickness analyses were performed: (1) group-level whole-brain surface-based analyses and (2) group-level ROI analyses. A case study of 6 ALS individuals examined the cortical thickness, and their speech was characterized using quantitative and qualitative measures. Results: Based on the group-level whole-brain surface-based analyses, the ds-ALS group demonstrated significant cortical thinning compared to HCs in the left primary motor and somatosensory cortices and the right inferior parietal lobe with its adjacent lateral occipital cortical regions. The ps-ALS group demonstrated no significant cortical thinning compared to HCs. Based on the group-level ROI analyses, the ds-ALS group demonstrated significant cortical thinning compared to HCs in bilateral middle motor cortices, right posterior dorsal premotor cortex, and left anterior cingulate cortex. The case study analysis revealed that ALS speakers with speech features characteristic of spastic dysarthria exhibited cortical thinning, while those with speech features characteristic of flaccid dysarthria did not. Discussion: Individuals with ALS have anatomical changes involving multiregional neocortical areas beyond the primary motor cortex that may manifest as subjective (i.e., clinical judgment) and objective (i.e., speaking rate) changes in speech production. Further longitudinal work in ALS is needed to better understand the link between MRI cortical thickness changes and bulbar dysfunction. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment (CI) is common in Parkinson’s disease (PD). Multiple brain regions and their interactions are involved in PD associated CI. Magnetic resonance imaging (MRI) technology is a non-invasive method in investigating brain structure and interregional connections. In this study, by comparing cortical thickness, subcortical volume, and brain network topology properties in PD patients with and without CI, we aimed to understand the changes of brain structure and structural covariance network properties in PD associated CI. Methods: A total of 18 PD patients with CI and 33 PD patients without CI were recruited. Movement Disorder Society Unified Parkinson’s Disease Rating Scale, Hoehn and Yahr stage, Mini Mental State Examination Scale, Non-motor Symptom Rating Scale, Hamilton Anxiety Scale, and Hamilton Depression Scale were assessed. All participants underwent structural 3T MRI. Cortical thickness, subcortical volume, global and nodal network topology properties were measured. Results: Compared with PD patients without CI, the volumes of white matter, thalamus and hippocampus were lower in PD patients with CI. And decreased whole-brain local efficiency is associated with CI in PD patients. While the cortical thickness and nodal network topology properties were comparable between PD patients with and without CI. Conclusion: Our findings support the alterations of brain structure and disruption of structural covariance network are involved in PD associated CI, providing a new insight into the association between graph properties and PD associated CI. [ABSTRACT FROM AUTHOR]

Background: For over three decades, the concomitance of cortical neurodegeneration and white matter hyperintensities (WMH) has sparked discussions about their coupled temporal dynamics. Longitudinal studies supporting this hypothesis nonetheless remain scarce. Methods: We applied global and regional bivariate latent growth curve modelling to determine the extent to which WMH and cortical thickness were interrelated over a four-year period. For this purpose, we leveraged longitudinal MRI data from 451 cognitively unimpaired participants (DELCODE; median age 69.71 [IQR 65.51, 75.50] years; 52.32% female). Participants underwent MRI sessions annually over a four-year period (1815 sessions in total, with roughly four MRI sessions per participant). We adjusted all models for demographics and cardiovascular risk. Results: Our findings were three-fold. First, larger WMH volumes were linked to lower cortical thickness (σ = -0.165, SE = 0.047, Z = -3.515, P < 0.001). Second, individuals with higher WMH volumes experienced more rapid cortical thinning (σ = -0.226, SE = 0.093, Z = -2.443, P = 0.007), particularly in temporal, cingulate, and insular regions. Similarly, those with lower initial cortical thickness had faster WMH progression (σ = -0.141, SE = 0.060, Z = -2.336, P = 0.009), with this effect being most pronounced in temporal, cingulate, and insular cortices. Third, faster WMH progression was associated with accelerated cortical thinning (σ = -0.239, SE = 0.139, Z = -1.710, P = 0.044), particularly in frontal, occipital, and insular cortical regions. Conclusions: Our study suggests that cortical thinning and WMH progression could be mutually reinforcing rather than parallel, unrelated processes, which become entangled before cognitive deficits are detectable. Trial registration: German Clinical Trials Register (DRKS00007966, 04/05/2015). [ABSTRACT FROM AUTHOR]

Background: CSF1R-related leukoencephalopathy is a type of autosomal dominant leukodystrophy caused by mutations in the colony stimulating factor 1 receptor (CSF1R) gene. Subcortical ischemic vascular dementia (SIVaD), which is caused by cerebral small vessel disease, is similar to CSF1R-related leukoencephalopathy in that it mainly affects subcortical white matter. In this study, we compared the patterns of white matter hyperintensity (WMH) and cortical thickness in CSF1R-related leukoencephalopathy with those in SIVaD. Methods: Fourteen patients with CSF1R-related leukoencephalopathy and 129 with SIVaD were retrospectively recruited from three tertiary medical centers. We extracted and visualized WMH data using voxel-based morphometry to compare the WMH distributions between the two groups. Cortical thickness was measured using a surface-based method. Statistical maps of differences in cortical thickness between the two groups were generated using a surface model, with age, sex, education, and intracranial volume as covariates. Results: Predominant distribution of WMH in the CSF1R-related leukoencephalopathy group was in the bilateral frontal and parietal areas, whereas the SIVaD group showed diffuse WMH involvement in the bilateral frontal, parietal, and temporal areas. Compared with the SIVaD group, the CSF1R-related leukoencephalopathy group showed more severe corpus callosum atrophy (CCA) and widespread cortical thinning. Conclusions: To our knowledge, this is the first study using the automated MR measurement to capture WMH, cortical thinning, and CCA with signal changes in CSF1R-related leukoencephalopathy. It provides new evidence regarding differences in the patterns of WMH distribution and cortical thinning between CSF1R-related leukoencephalopathy and SIVaD. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study is to examine the alterations in subcortical brain volume and cortical thickness among individuals diagnosed with Type 2 diabetes mellitus (T2DM) through the application of morphometry techniques and, additionally, to investigate the potential association between these modifications and insulin resistance (IR). Materials and methods: The present cross‐sectional study comprised a total of 121 participants (n = 48 with healthy controls [HCs] and n = 73 with T2DM) who were recruited and underwent a battery of cognitive testing and structural magnetic resonance imaging (MRI). FreeSurfer was used to process the MRI data. Analysis of covariance compared discrepancies in cortical thickness and subcortical brain volume between T2DM and HCs, adjusting for the potential confounding effects of gender, age, education, and body mass index (BMI). Exploratory partial correlations investigated links between IR and brain structure in T2DM participants. Results: Compared with HCs, individuals with T2DM demonstrated a cortical thickness decrease in the right caudal middle frontal gyrus, right pars opercularis, left precentral gyrus, and bilateral superior frontal gyrus. Furthermore, this study for T2DM found that the severity of IR was inversely related to the volume of the left putamen and left hippocampus, as well as the thickness of the left pars orbitalis, left pericalcarine, right entorhinal area, and right rostral anterior cingulate gyrus. Conclusion: The evidence for structural brain changes in T2DM was observed, and alterations in cortical thickness were concentrated in the frontal lobes. Correlations between IR and frontal cortical thinning may serve as a potential neuroimaging marker of T2DM and lead to various diabetes‐related brain complications. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease is a progressive neurodegenerative disease characterized by structural changes in the brain, including hippocampal atrophy, cortical thinning, amyloid plaques, and tau tangles. Due to the aging of the global population, the burden of Alzheimer's disease is expected to increase, making the exploration of non-pharmacological interventions, such as physical exercise, an urgent priority. Results: There is emerging evidence that regular physical exercise may mitigate the structural and functional declines associated with Alzheimer's disease. The underlying mechanisms, however, remain poorly understood. Gut–brain axis research is a promising area for further investigation. This system involves bidirectional communication between the gut microbiome and the brain. According to recent studies, the gut microbiome may influence brain health through modulating neuroinflammation, producing neuroactive compounds, and altering metabolic processes. Exercise has been shown to alter the composition of the gut microbiome, potentially impacting brain structure and function. In this review, we aim to synthesize current research on the relationship between physical exercise, structural brain changes in Alzheimer's disease, and the gut–brain axis. Conclusions: In this study, we will investigate whether changes in the gut microbiome induced by physical exercise can mediate its neuroprotective effects, offering new insights into the prevention and treatment of Alzheimer's disease. By integrating findings from neuroimaging studies, clinical trials, and microbiome research, this review will highlight potential mechanisms. It will also identify key gaps in the literature. This will pave the way for future research directions. [ABSTRACT FROM AUTHOR]

Adolescence is a period of substantial social-emotional development, accompanied by dramatic changes to brain structure and function. Social isolation due to lockdowns that were imposed because of the COVID-19 pandemic had a detrimental impact on adolescent mental health, with the mental health of females more affected than males. We assessed the impact of the COVID-19 pandemic lockdowns on adolescent brain structure with a focus on sex differences. We collected MRI structural data longitudinally from adolescents prior to and after the pandemic lockdowns. The pre-COVID data were used to create a normative model of cortical thickness change with age during typical adolescent development. Cortical thickness values in the post-COVID data were compared to this normative model. The analysis revealed accelerated cortical thinning in the post-COVID brain, which was more widespread throughout the brain and greater in magnitude in females than in males. When measured in terms of equivalent years of development, the mean acceleration was found to be 4.2 y in females and 1.4 y in males. Accelerated brain maturation as a result of chronic stress or adversity during development has been well documented. These findings suggest that the lifestyle disruptions associated with the COVID-19 pandemic lockdowns caused changes in brain biology and had a more severe impact on the female than the male brain. [ABSTRACT FROM AUTHOR]

White matter hyperintensities (WMH) are associated with cortical thinning. Although they are primarily detected in older participants, these lesions can appear in younger and midlife individuals. Here, we tested whether WMH are associated with cortical thinning in relatively younger (26–50 years) and relatively older (58–84) participants who were free of dementia, and how these associations are moderated by WMH localization. WMH were automatically quantified and categorized according to the localization of three classes of white matter tracts: association, commissural and projection fibers. Mediation analyses were used to infer whether differences in cortical thickness between younger and older participants were explained by WMH. Our results revealed that total WMH explained between 20.6 % and 65.5 % of the effect of age on cortical thickness in AD-signature regions including the lateral temporal lobes and supramarginal gyrus, among others. This mediation was slightly stronger for projection WMH, although it was still significant for association and commissural WMH. These results suggest that there is an interplay between vascular and AD causes of cognitive impairment that starts at younger ages. • White matter hyperintensities (WMH) are apparent in middle-age. • WMH correlate with cortical thickness, especially in younger adults. • WMH explain up to 65.6 % of age-related cortical thickness differences. • The effect of WMH on atrophy starts during the mid-life. [ABSTRACT FROM AUTHOR]

Schizophrenia is a highly heritable disorder characterized by increased cortical thinning throughout the life span. Studies have reported a shared genetic basis between schizophrenia and cortical thickness. However, no genes whose expression is related to abnormal cortical thinning in schizophrenia have been identified. We conducted linear mixed models to estimate the rates of accelerated cortical thinning across 68 regions from the Desikan-Killiany atlas in individuals with schizophrenia compared with healthy control participants from a large longitudinal sample (n cases = 169 and n controls = 298, ages 16–70 years). We studied the correlation between gene expression data from the Allen Human Brain Atlas and accelerated thinning estimates across cortical regions. Finally, we explored the functional and genetic underpinnings of the genes that contribute most to accelerated thinning. We found a global pattern of accelerated cortical thinning in individuals with schizophrenia compared with healthy control participants. Genes underexpressed in cortical regions that exhibit this accelerated thinning were downregulated in several psychiatric disorders and were enriched for both common and rare disrupting variation for schizophrenia and neurodevelopmental disorders. In contrast, none of these enrichments were observed for baseline cross-sectional cortical thickness differences. Our findings suggest that accelerated cortical thinning, rather than cortical thickness alone, serves as an informative phenotype for neurodevelopmental disruptions in schizophrenia. We highlight the genetic and transcriptomic correlates of this accelerated cortical thinning, emphasizing the need for future longitudinal studies to elucidate the role of genetic variation and the temporal-spatial dynamics of gene expression in brain development and aging in schizophrenia. [ABSTRACT FROM AUTHOR]

Mechanisms of resilience against tau pathology in individuals across the Alzheimer's disease spectrum are insufficiently understood. Longitudinal data are necessary to reveal which factors relate to preserved cognition (i.e. cognitive resilience) and brain structure (i.e. brain resilience) despite abundant tau pathology, and to clarify whether these associations are cross-sectional or longitudinal. We used a longitudinal study design to investigate the role of several demographic, biological and brain structural factors in yielding cognitive and brain resilience to tau pathology as measured with PET. In this multicentre study, we included 366 amyloid-β-positive individuals with mild cognitive impairment or Alzheimer's disease dementia with baseline 18F-flortaucipir-PET and longitudinal cognitive assessments. A subset (n = 200) additionally underwent longitudinal structural MRI. We used linear mixed-effects models with global cognition and cortical thickness as dependent variables to investigate determinants of cognitive resilience and brain resilience, respectively. Models assessed whether age, sex, years of education, APOE-ε4 status, intracranial volume (and cortical thickness for cognitive resilience models) modified the association of tau pathology with cognitive decline or cortical thinning. We found that the association between higher baseline tau-PET levels (quantified in a temporal meta-region of interest) and rate of cognitive decline (measured with repeated Mini-Mental State Examination) was adversely modified by older age (Stβinteraction = -0.062, P = 0.032), higher education level (Stβinteraction = -0.072, P = 0.011) and higher intracranial volume (Stβinteraction = -0.07, P = 0.016). Younger age, higher education and greater cortical thickness were associated with better cognitive performance at baseline. Greater cortical thickness was furthermore associated with slower cognitive decline independent of tau burden. Higher education also modified the negative impact of tau-PET on cortical thinning, while older age was associated with higher baseline cortical thickness and slower rate of cortical thinning independent of tau. Our analyses revealed no (cross-sectional or longitudinal) associations for sex and APOE-ε4 status on cognition and cortical thickness. In this longitudinal study of clinically impaired individuals with underlying Alzheimer's disease neuropathological changes, we identified education as the most robust determinant of both cognitive and brain resilience against tau pathology. The observed interaction with tau burden on cognitive decline suggests that education may be protective against cognitive decline and brain atrophy at lower levels of tau pathology, with a potential depletion of resilience resources with advancing pathology. Finally, we did not find major contributions of sex to brain nor cognitive resilience, suggesting that previous links between sex and resilience might be mainly driven by cross-sectional differences.

Progressive grey matter loss has been demonstrated among clinical high-risk (CHR) individuals who convert to psychosis, but it is unknown whether these changes occur prior to psychosis onset. Identifying illness-related neurobiological mechanisms that occur prior to conversion is essential for targeted early intervention. Among participants in the third wave of the North American Prodrome Longitudinal Study (NAPLS3), this report investigated if steeper cortical thinning was observable prior to psychosis onset among CHR individuals who ultimately converted (CHR-C) and assessed the shortest possible time interval in which rates of cortical thinning differ between CHR-C, CHR non-converters (CHR-NC), and health controls (HC). 338 CHR-NC, 42 CHR-C, and 62 HC participants (age 19.3±4.2, 44.8% female, 52.5% racial/ethnic minority) completed up to 5 MRI scans across 8 months. Accelerated thinning among CHR-C compared to CHR-NC and HC was observed in multiple prefrontal, temporal, and parietal cortical regions. CHR-NC also exhibited accelerated cortical thinning compared to HC in several of these areas. Greater percent decrease in cortical thickness was observed among CHR-C compared to other groups across 2.9±1.8 months, on average, in several cortical areas. ROC analyses discriminating CHR-C from CHR-NC by percent thickness change in a left hemisphere region of interest, scanner, age, age2, and sex had an AUC of 0.74, with model predictive power driven primarily by percent thickness change. Findings indicate that accelerated cortical thinning precedes psychosis onset and differentiates CHR-C from CHR-NC and HC across short time intervals. Mechanisms underlying cortical thinning may provide novel treatment targets prior to psychosis onset.

Adolescent development of human brain structural and functional networks is increasingly recognized as fundamental to emergence of typical and atypical adult cognitive and emotional processes. We analysed multimodal magnetic resonance imaging (MRI) data collected from N ~ 300 healthy adolescents (51%; female; 14 to 26 y) each scanned repeatedly in an accelerated longitudinal design, to provide an analyzable dataset of 469 structural scans and 448 functional MRI scans. We estimated the morphometric similarity between each possible pair of 358 cortical areas on a feature vector comprising six macro- and microstructural MRI metrics, resulting in a morphometric similarity network (MSN) for each scan. Over the course of adolescence, we found that morphometric similarity increased in paralimbic cortical areas, e.g., insula and cingulate cortex, but generally decreased in neocortical areas, and these results were replicated in an independent developmental MRI cohort (N~304). Increasing hubness of paralimbic nodes in MSNs was associated with increased strength of coupling between their morphometric similarity and functional connectivity. Decreasing hubness of neocortical nodes in MSNs was associated with reduced strength of structure-function coupling and increasingly diverse functional connections in the corresponding fMRI networks. Neocortical areas became more structurally differentiated and more functionally integrative in a metabolically expensive process linked to cortical thinning and myelination, whereas paralimbic areas specialized for affective and interoceptive functions became less differentiated, as hypothetically predicted by a developmental transition from periallocortical to proisocortical organization of the cortex. Cytoarchitectonically distinct zones of the human cortex undergo distinct neurodevelopmental programs during typical adolescence. [ABSTRACT FROM AUTHOR]

Spinocerebellar ataxias (SCAs) are inherited neurodegenerative diseases characterized by loss of balance, coordination, and slurred speech. Recently, a digenic mode of inheritance of TBP/STUB1 contributing to SCA was demonstrated. The clinical manifestations of SCATBP/STUB1 include not only ataxia but also obvious cognitive and behavioral impairment. Here, we describe a Chinese family with SCATBP/STUB1 and performed a literature search for similar cases. We identified a Chinese family with SCATBP/STUB1 and compare our clinical findings with other cases described in the literature so far. Four individuals in this family have been found to carry SCATBP/STUB1, of which three have clinical manifestations. A heterozygous deletion mutation in the STIP1-homologous and U-box containing protein 1 (STUB1) gene, NM_005861.4:c433_435del(p.K145del), was identified. The proband is a 34-year-old female with progressive dementia and dysarthria. The mother and uncle of the proband first presented with motor abnormalities and gradually developed cognitive impairment. The proband and her uncle showed cerebellar atrophy on MRI. The proband's brother carried digenic variants but was asymptomatic. SCATBP/STUB1 is a novel SCA subtype. The main clinical manifestations are motor, cognitive, and behavioral abnormalities. Brain MRI shows significant cerebellar atrophy and cortical thinning. The independent segregation of TBP and STUB1 alleles should be considered when evaluating patients with cognitive impairment and ataxia. [ABSTRACT FROM AUTHOR]

Background: Computer-aided machine learning models are being actively developed with clinically available biomarkers to diagnose Alzheimer's disease (AD) in living persons. Despite considerable work with cross-sectional in vivo data, many models lack validation against postmortem AD neuropathological data. Objective: Train machine learning models to classify the presence or absence of autopsy-confirmed severe AD neuropathology using clinically available features. Methods: AD neuropathological status are assessed at postmortem for participants from the National Alzheimer's Coordinating Center (NACC). Clinically available features are utilized, including demographics, Apolipoprotein E(APOE) genotype, and cortical thicknesses derived from ante-mortem MRI scans encompassing AD meta regions of interest (meta-ROI). Both logistic regression and random forest models are trained to identify linearly and nonlinearly separable features between participants with the presence (N = 91, age-at-MRI = 73.6±9.24, 38 women) or absence (N = 53, age-at-MRI = 68.93±19.69, 24 women) of severe AD neuropathology. The trained models are further validated in an external data set against in vivo amyloid biomarkers derived from PET imaging (amyloid-positive: N = 71, age-at-MRI = 74.17±6.37, 26 women; amyloid-negative: N = 73, age-at-MRI = 71.59±6.80, 41 women). Results: Our models achieve a cross-validation accuracy of 84.03% in classifying the presence or absence of severe AD neuropathology, and an external-validation accuracy of 70.14% in classifying in vivo amyloid positivity status. Conclusions: Our models show that clinically accessible features, including APOE genotype and cortical thinning encompassing AD meta-ROIs, are able to classify both postmortem confirmed AD neuropathological status and in vivo amyloid status with reasonable accuracies. These results suggest the potential utility of AD meta-ROIs in determining AD neuropathological status in living persons. [ABSTRACT FROM AUTHOR]

Brain atrophy and cortical thinning are typically observed in people with Alzheimer's disease (AD) and, to a lesser extent, in those with mild cognitive impairment. In asymptomatic middle‐aged apolipoprotein ε4 (ΑPOE4) carriers, who are at higher risk of future AD, study reports are discordant with limited evidence of brain structural differences between carriers and non‐carriers of the ε4 allele. Alternative imaging markers with higher sensitivity at the presymptomatic stage, ideally quantified using typically acquired structural MRI scans, would thus be of great benefit for the detection of early disease, disease monitoring and subject stratification. In the present cross‐sectional study, we investigated textural properties of T1‐weighted 3T MRI scans in relation to APOE4 genotype, age and sex. We pooled together data from the PREVENT‐Dementia and ALFA studies focused on midlife healthy populations with dementia risk factors (analysable cohort: 1585 participants; mean age 56.2 ± 7.4 years). Voxel‐based and texture (examined features: contrast, entropy, energy, homogeneity) based morphometry was used to identify areas of volumetric and textural differences between APOE4 carriers and non‐carriers. Textural maps were generated and were subsequently harmonised using voxel‐wise COMBAT. For all analyses, APOE4, sex, age and years of education were used as model predictors. Interactions between APOE4 and age were further examined. There were no group differences in regional brain volume or texture based on APOE4 carriership or when age × APOE4 interactions were examined. Older people tended to have a less homogeneous textural profile in grey and white matter and a more homogeneous profile in the ventricles. A more heterogeneous textural profile was observed for females in areas such as the ventricles, frontal and parietal lobes and for males in the brainstem, cerebellum, precuneus and cingulate. Overall, we have shown the absence of volumetric and textural differences between APOE4 carriers and non‐carriers at midlife and have established associations of textural features with ageing and sex. [ABSTRACT FROM AUTHOR]

Background: Myotonic dystrophy is a multisystem disorder characterized by widespread organic involvement including central nervous system symptoms. Although myotonic dystrophy disease types 1 (DM1) and 2 (DM2) cover a similar spectrum of symptoms, more pronounced clinical and brain alterations have been described in DM1. Here, we investigated brain volumetric and white matter alterations in both disease types and compared to healthy controls (HC). Methods: MRI scans were obtained from 29 DM1, 27 DM2, and 56 HC. We assessed macro- and microstructural brain changes by surface-based analysis of cortical thickness of anatomical images and tract-based spatial statistics of fractional anisotropy (FA) obtained by diffusion-weighted imaging, respectively. Global MRI measures were related to clinical and neuropsychological scores to evaluate their clinical relevance. Results: Cortical thickness was reduced in both patient groups compared to HC, showing similar patterns of regional distribution in DM1 and DM2 (occipital, temporal, frontal) but more pronounced cortical thinning for DM1. Similarly, FA values showed a widespread decrease in DM1 and DM2 compared to HC. Interestingly, FA was significantly lower in DM1 compared to DM2 within most parts of the brain. Conclusion: Comparisons between DM1 and DM2 indicate a more pronounced cortical thinning of grey matter and a widespread reduction in microstructural integrity of white matter in DM1. Future studies are required to unravel the underlying and separating mechanisms for the disease courses of the two types and their neuropsychological symptoms. [ABSTRACT FROM AUTHOR]

An 11-month-old female Saanen goat, weighing 12.7 kg, was taken to the Veterinary Hospital of the Federal University of Minas Gerais because of sternal recumbency. On clinical examination, the animal was much smaller than expected and had hair similar to that of puppies and areas of hyperpigmentation on the head and dorsocervical and dorsothoracic cranial regions. Radiographic examination revealed fractures in both femurs and severe generalized osteoporosis. Given the unfavourable prognosis, the animal was euthanized. Necropsy revealed generalized pallor, muscular atrophy of the pelvic limbs and little reserve of subcutaneous adipose tissue. Both femurs had complete and closed diaphyseal fractures. The second lumbar vertebra was severely reduced in length as a result of a fracture, with dorsal displacement of the vertebral body towards the vertebral canal and compression of the spinal cord. Long bones and vertebrae had severe cortical thinning, enlargement of the medullary canal and reduced resistance. The thyroid gland was not in its normal anatomical location. A pale red nodule (1.0 × 0.4 cm) in the serosa of the middle third of the trachea, close to the thoracic entrance, was confirmed as ectopic thyroid tissue. Microscopically, the bones had evidence of growth arrest and severe osteoporosis. The ectopic thyroid nodule was hyperplastic with severe hypertrophy of follicular cells. The spinal cord was compressed by vertebral fractures and had focally extensive and severe myelomalacia. Based on the pathological features, the case was diagnosed as thyroid dysgenesis characterized by eutopic thyroid agenesis and ectopic thyroid tissue, associated with interruption of bone growth with dwarfism, osteoporosis and spontaneous secondary fractures with compression of the lumbar spinal cord. [ABSTRACT FROM AUTHOR]

Alterations in grey matter (GM) and white matter (WM) are associated with memory impairment across the neurocognitive aging spectrum and theorised to spread throughout brain networks. Functional and structural connectivity (FC,SC) may explain widespread atrophy. We tested the effect of SC and FC to the hippocampus on cortical thickness (CT) of connected areas. In 419 (223 F) participants (age mean =73 ± 8) from the Alzheimer's Disease Neuroimaging Initiative, cortical regions associated with memory (Rey Auditory Verbal Learning Test) were identified using Lasso regression. Two structural equation models (SEM), for SC and resting-state FC, were fitted including CT areas, and SC and FC to the left and right hippocampus (LHIP,RHIP). LHIP (β =-0.150, p =<.001) and RHIP (β =-0.139, p =<.001) SC predicted left temporopolar/rhinal CT; RHIP SC predicted right temporopolar/rhinal CT (β =-0.191, p =<.001). LHIP SC predicted right fusiform/parahippocampal (β =-0.104, p =.011) and intraparietal sulcus/superior parietal CT (β =0.101, p =.028). Increased RHIP FC predicted higher left inferior parietal CT (β =0.132, p =.042) while increased LHIP FC predicted lower right fusiform/parahippocampal CT (β =-0.97; p =.023). The hippocampi may be epicentres for cortical thinning through disrupted connectivity. • Connectivity to the hippocampi is associated with grey matter alterations. • Both structural and functional connectivity can predict grey matter thickness. • The study supports the idea that the hippocampi are an epicentre for atrophy. [ABSTRACT FROM AUTHOR]

The intricate dynamics of brain aging, especially the neurodegenerative mechanisms driving accelerated (ABA) and resilient brain aging (RBA), are pivotal in neuroscience. Understanding the temporal dynamics of these phenotypes is crucial for identifying vulnerabilities to cognitive decline and neurodegenerative diseases. Currently, there is a lack of comprehensive understanding of the temporal dynamics and neuroimaging biomarkers linked to ABA and RBA. This study addressed this gap by utilizing a large-scale UK Biobank (UKB) cohort, with the aim to elucidate brain aging heterogeneity and establish the foundation for targeted interventions. Employing Lasso regression on multimodal neuroimaging data, structural MRI (sMRI), diffusion MRI (dMRI), and resting-state functional MRI (rsfMRI), we predicted the brain age and classified individuals into ABA and RBA cohorts. Our findings identified 1949 subjects (6.2%) as representative of the ABA subpopulation and 3203 subjects (10.1%) as representative of the RBA subpopulation. Additionally, the Discriminative Event-Based Model (DEBM) was applied to estimate the sequence of biomarker changes across aging trajectories. Our analysis unveiled distinct central ordering patterns between the ABA and RBA cohorts, with profound implications for understanding cognitive decline and vulnerability to neurodegenerative disorders. Specifically, the ABA cohort exhibited early degeneration in four functional networks and two cognitive domains, with cortical thinning initially observed in the right hemisphere, followed by the temporal lobe. In contrast, the RBA cohort demonstrated initial degeneration in the three functional networks, with cortical thinning predominantly in the left hemisphere and white matter microstructural degeneration occurring at more advanced stages. The detailed aging progression timeline constructed through our DEBM analysis positioned subjects according to their estimated stage of aging, offering a nuanced view of the aging brain's alterations. This study holds promise for the development of targeted interventions aimed at mitigating age-related cognitive decline. [ABSTRACT FROM AUTHOR]

Objectives: Comparisons between Indigenous peoples over time and within a particular geographic region can shed light on the impact of environmental transitions on the skeleton, including relative bone strength, sexual dimorphism, and age‐related changes. Here we compare long bone structural properties of the inhabitants of the late prehistoric‐early historic Pecos Pueblo with those of present‐day Indigenous individuals from New Mexico. Materials and Methods: Femora and tibiae of 126 adults from Pecos Pueblo and 226 present‐day adults were included in the study. Cross‐sectional diaphyseal properties—areas and second moments of area—were obtained from past studies of the Pecos Pueblo skeletal sample, and from computed tomography scans of recently deceased individuals in the present‐day sample. Results: Femora and tibiae from Pecos individuals are stronger relative to body size than those of present‐day Indigenous individuals. Present‐day individuals are taller but not wider, and this body shape difference affects cross‐sectional shape, more strongly proximally. The tibia shows anteroposterior strengthening among Pecos individuals, especially among males. Sexual dimorphism in midshaft bone shape is stronger within the Pecos Pueblo sample. With aging, Pecos individuals show more medullary expansion but also more subperiosteal expansion than present‐day individuals, maintaining bone strength despite cortical thinning. Discussion: Higher activity levels, carried out over rough terrain and throughout adult life, likely explain the relatively stronger lower limb bones of the Pecos individuals, as well as their greater subperiosteal expansion with aging. Greater sexual dimorphism in bone structure among Pecos individuals potentially reflects greater gender‐based differences in behavioral patterns. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Sleep is crucial for memory consolidation and the clearance of toxic proteins associated with Alzheimer's disease (AD). We examined the association between sleep characteristics and imaging biomarkers of early amyloid beta (Aβ) and tau pathology as well as neurodegeneration in brain regions known to be affected in the incipient stages of AD. METHODS: Thirty‐nine cognitively unimpaired (CU) participants of the Harvard Aging Brain Study underwent at‐home polysomnography as well as tau positron emission tomography (flortaucipir‐PET), amyloid PET (Pittsburgh compound B [PiB]‐PET), and magnetic resonance imaging–derived assessment of cortical thickness (CT). RESULTS: Increased N1 sleep was associated with a higher tau PET signal (β = 0.009, p = 0.001) and lower CT in the temporal composite region of interest (β = –0.017, p = 0.007). Decreased slow‐wave sleep (SWS) was associated with higher tau burden in the temporal composite (β = –0.008, p = 0.005) and lower CT (β = 0.008, p = 0.002), even after controlling for global PiB‐PET. DISCUSSION: In CU older adults, lower SWS and higher N1 sleep were associated with higher tau burden and lower CT in brain regions associated with early tau deposition and vulnerable to AD‐related neurodegeneration through mechanisms dissociable from amyloid deposition. Highlights: We report the results of an observational study, which leveraged ‐a well‐characterized cohort of healthy aging (Harvard Aging Brain Study) by adding in‐home full polysomnograms.By adding at‐home polysomnograms to this unique and deeply phenotyped cohort, we examined variations in sleep architecture that are associated with Alzheimer's disease (AD) pathologic changes.Our results confirmed the association of sleep changes with early tau and cortical neurodegenerative changes that were independent of amyloid.The results will be of importance in monitoring sleep‐related variations in relation to the natural history of AD pathology and in designing sleep‐focused clinical trials. [ABSTRACT FROM AUTHOR]

Abstract: Aim: We propose a modified Lekholm and Zarb classification that considers all possible combinations of cortical and cancellous bone to provide parameters that favor greater repeatability and reproducibility. Materials and Methods: This observational and analytical study consisted of a sample of 50 cone beam computed tomography (CBCT) scans. Two new types (V and VI), three subtypes to type II (II-A, II-B, and II-C), and two subtypes to type III (III-A and III-B) were added to the original bone quality classification. The new types refer to regenerated bone (type V) and bone with some pathology (type VI). The subtypes are described as type II-A: thick cortical surrounding the abundant cancellous bone with sharp trabeculae throughout the image and presence of small and visible medullary spaces; type II-B: thick cortical surrounding the abundant cancellous bone with predominance of diffuse trabeculae in the basal bone and predominant presence of wide and visible medullary spaces; type II-C: thick cortical surrounding the abundant cancellous bone with predominance of very thick and sharp trabeculae in the basal third as well as presence of small and visible medullary spaces; type III-A: thin cortical surrounding the abundant cancellous bone with sharp trabeculae throughout the image and presence of small and visible medullary spaces; type III-B: thin cortical surrounding the abundant cancellous bone with predominance of diffuse trabeculae and presence of diffuse medullary spaces. Five dental specialists were trained in the use of the modified classification and were provided with CBCT-sectioned images of edentulous jaws for classification. Each specialist classified the images twice at a 7-day interval. The strength of intra-examiner and inter-examiner agreement was measured with Cohen's and Fleiss' kappa index, respectively. In addition, the agreement between both classifications was analyzed. All data were analyzed at a 95% confidence level, considering a P -value <0.05. Results: According to the modified Lekholm and Zarb classification, an almost perfect intra-examiner agreement was significant (P < 0.05) in all five specialists, with the kappa index [ k ] ranging from 0.91 [95% confidence interval (CI): 0.82–0.99) to 0.95 (95% CI: 0.89–1.00). Furthermore, substantial inter-examiner concordance (k =0.76; 95% CI: 0.73–0.79) was significant (P < 0.05). Conclusion: The high repeatability and reproducibility of the modified Lekholm and Zarb classification on CBCT suggest its applicability to distinguish between the various combinations of cortical and cancellous bone and help to define treatment appropriately to optimize results. [ABSTRACT FROM AUTHOR]

A fundamental puzzle about brain development is why the volume of gray matter (GM) apparently declines as white matter (WM) grows when children enter adolescence. Since pruned synapses are too small to affect GM volume, a prevailing theory posits that an expanded distribution of myelin causes the inner edge of the GM to "whiten" while total brain volume remains steady, shifting the MRI‐measured WM:GM boundary closer to the brain's outer surface. This theory inherently predicts that GM volume loss is concurrent with WM volume growth across regions, within sexes and over time, although these predictions have yet to be explicitly tested. In this study, we test these predictions by mapping regional GM and WM volumetric changes in 2333 participants of the Adolescent Brain Cognitive Development study aged 9–14 years who each received three MRI scans 2 years apart. We show that average GM and WM volume changes follow distinct spatial, temporal, and sex‐specific patterns, indicating that GM volume loss is not balanced by WM volume growth, although cortical GM thinning is weakly correlated with WM growth in some regions. We conclude that myelin is not the main source of measured GM volume loss, and we propose alternative candidates. [ABSTRACT FROM AUTHOR]

Progression to psychosis has been associated with increased cortical thinning in the frontal, temporal and parietal lobes in individuals at clinical high risk for the disorder (CHR-P). The timing and spatial extent of these changes are thought to be influenced by age. However, most evidence so far stems from adult samples. Longitudinal studies are essential to understanding the neuroanatomical changes associated to transition to psychosis during adolescence, and their relationship with age. We conducted a longitudinal, multisite study including adolescents at CHR-P and healthy controls (HC), aged 10–17 years. Structural images were acquired at baseline and at 18-month follow-up. Images were processed with the longitudinal pipeline in FreeSurfer. We used a longitudinal two-stage model to compute the regional cortical thickness (CT) change, and analyze between-group differences controlling for age, sex and scan, and corrected for multiple comparisons. Linear regression was used to study the effect of age at baseline. A total of 103 individuals (49 CHR-P and 54 HC) were included in the analysis. During follow-up, the 13 CHR-P participants who transitioned to psychosis exhibited greater CT decrease over time in the right parietal cortex compared to those who did not transition to psychosis and to HC. Age at baseline correlated with longitudinal changes in CT, with younger individuals showing greater cortical thinning in this region. The emergence of psychosis during early adolescence may have an impact on typical neuromaturational processes. This study provides new insights on the cortical changes taking place prior to illness onset. [ABSTRACT FROM AUTHOR]

Cortical thickness changes dramatically during development and is associated with adolescent drinking. However, previous findings have been inconsistent and limited by region-of-interest approaches that are underpowered because they do not conform to the underlying spatially heterogeneous effects of alcohol. In this study, adolescents (n = 657; 12-22 years at baseline) from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) study who endorsed little to no alcohol use at baseline were assessed with structural magnetic resonance imaging and followed longitudinally at four yearly intervals. Seven unique spatial patterns of covarying cortical thickness were obtained from the baseline scans by applying an unsupervised machine learning method called non-negative matrix factorization (NMF). The cortical thickness maps of all participants' longitudinal scans were projected onto vertex-level cortical patterns to obtain participant-specific coefficients for each pattern. Linear mixed-effects models were fit to each pattern to investigate longitudinal effects of alcohol consumption on cortical thickness. We found in six NMF-derived cortical thickness patterns, the longitudinal rate of decline in no/low drinkers was similar for all age cohorts. Among moderate drinkers the decline was faster in the younger adolescent cohort and slower in the older cohort. Among heavy drinkers the decline was fastest in the younger cohort and slowest in the older cohort. The findings suggested that unsupervised machine learning successfully delineated spatially coordinated patterns of vertex-level cortical thickness variation that are unconstrained by neuroanatomical features. Age-appropriate cortical thinning is more rapid in younger adolescent drinkers and slower in older adolescent drinkers, an effect that is strongest among heavy drinkers.

BACKGROUND: A carbohydrate-restricted diet aimed at lowering insulin levels has the potential to slow Alzheimers disease (AD). Restricting carbohydrate consumption reduces insulin resistance, which could improve glucose uptake and neural health. A hallmark feature of AD is widespread cortical thinning; however, no study has demonstrated that lower net carbohydrate (nCHO) intake is linked to attenuated cortical atrophy in patients with AD and confirmed amyloidosis. OBJECTIVE: We tested the hypothesis that individuals with AD and confirmed amyloid burden eating a carbohydrate-restricted diet have thicker cortex than those eating a moderate-to-high carbohydrate diet. METHODS: A total of 31 patients (mean age 71.4±7.0 years) with AD and confirmed amyloid burden were divided into two groups based on a 130 g/day nCHO cutoff. Cortical thickness was estimated from T1-weighted MRI using FreeSurfer. Cortical surface analyses were corrected for multiple comparisons using cluster-wise probability. We assessed group differences using a two-tailed two-independent sample t-test. Linear regression analyses using nCHO as a continuous variable, accounting for confounders, were also conducted. RESULTS: The lower nCHO group had significantly thicker cortex within somatomotor and visual networks. Linear regression analysis revealed that lower nCHO intake levels had a significant association with cortical thickness within the frontoparietal, cingulo-opercular, and visual networks. CONCLUSIONS: Restricting carbohydrates may be associated with reduced atrophy in patients with AD. Lowering nCHO to under 130 g/day would allow patients to follow the well-validated MIND diet while benefiting from lower insulin levels.

Introduction: The cause of Developmental Coordination Disorder (DCD) is unknown, but neuroimaging evidence suggests that DCD may be related to altered brain development. Children with DCD show less structural and functional connectivity compared to typically developing (TD) children, but few studies have examined cortical volume in children with DCD. The purpose of this study was to investigate cortical grey matter volume using voxel-based morphometry (VBM) in children with DCD compared to TD children. Methods: This cross-sectional study was part of a larger randomized-controlled trial (ClinicalTrials.gov ID: NCT02597751) that involved various MRI scans of children with/without DCD. This paper focuses on the anatomical scans, performing VBM of cortical grey matter volume in 30 children with DCD and 12 TD children. Preprocessing and VBM data analysis were conducted using the Computational Anatomy Tool Box-12 and a study-specific brain template. Differences between DCD and TD groups were assessed using a one-way ANOVA, controlling for total intracranial volume. Regression analyses examined if motor and/or attentional difficulties predicted grey matter volume. We used threshold-free cluster enhancement (5,000 permutations) and set an alpha level of 0.05. Due to the small sample size, we did not correct for multiple comparisons. Results: Compared to the TD group, children with DCD had significantly greater grey matter in the left superior frontal gyrus. Lower motor scores (meaning greater impairment) were related to greater grey matter volume in left superior frontal gyrus, frontal pole, and right middle frontal gyrus. Greater grey matter volume was also significantly correlated with higher scores on the Conners 3 ADHD Index in the left superior frontal gyrus, superior parietal lobe, and precuneus. These results indicate that greater grey matter volume in these regions is associated with poorer motor and attentional skills. Discussion: Greater grey matter volume in the left superior frontal gyrus in children with DCD may be a result of delayed or absent healthy cortical thinning, potentially due to altered synaptic pruning as seen in other neurodevelopmental disorders. These findings provide further support for the hypothesis that DCD is related to altered brain development. [ABSTRACT FROM AUTHOR]

Objective/background: To assess whether cerebral structural alterations in isolated rapid eye movement sleep behavior disorder (iRBD) are progressive and differ from those of normal aging and whether they are related to clinical symptoms. Patients/methods: In a longitudinal study of 18 patients with iRBD (age, 66.1 ± 5.7 years; 13 males; follow-up, 1.6 ± 0.6 years) and 24 age-matched healthy controls (age, 67.0 ± 4.9 years; 12 males; follow-up, 2.0 ± 0.9 years), all participants underwent multiple extensive clinical examinations, neuropsychological tests, and magnetic resonance imaging at baseline and follow-up. Surface-based cortical reconstruction and automated subcortical structural segmentation were performed on T1-weighted images. We used mixed-effects models to examine the differences between the groups and the differences in anatomical changes over time. Results: None of the patients with iRBD demonstrated phenoconversion during the follow-up. Patients with iRBD had thinner cortices in the frontal, occipital, and temporal regions, and more caudate atrophy, compared to that in controls. In similar regions, group-by-age interaction analysis revealed that patients with iRBD demonstrated significantly slower decreases in cortical thickness and caudate volume with aging than that observed in controls. Patients with iRBD had lower scores on the Korean version of the Mini-Mental Status Examination (p = 0.037) and frontal and executive functions (p = 0.049) at baseline than those in controls; however, no significant group-by-age interaction was identified. Conclusion: Patients with iRBD show brain atrophy in the regions that are overlapped with the areas that have been documented to be affected in early stages of Parkinson's disease. Such atrophy in iRBD may not be progressive but may be slower than that in normal aging. Cognitive impairment in iRBD is not progressive. [ABSTRACT FROM AUTHOR]

Background: Early life adversity impairs hippocampal development and function across diverse species. While initial evidence indicated potential variations between males and females, further research is required to validate these observations and better understand the underlying mechanisms contributing to these sex differences. Furthermore, most of the preclinical work in rodents was performed in adult males, with only few studies examining sex differences during adolescence when such differences appear more pronounced. To address these concerns, we investigated the impact of limited bedding (LB), a mouse model of early adversity, on hippocampal development in prepubescent and adolescent male and female mice. Methods: RNA sequencing, confocal microscopy, and electron microscopy were used to evaluate the impact of LB and sex on hippocampal development in prepubescent postnatal day 17 (P17) mice. Additional studies were conducted on adolescent mice aged P29-36, which included contextual fear conditioning, retrograde tracing, and ex vivo diffusion magnetic resonance imaging (dMRI). Results: More severe deficits in axonal innervation and myelination were found in the perforant pathway of prepubescent and adolescent LB males compared to LB female littermates. These sex differences were due to a failure of reelin-positive neurons located in the lateral entorhinal cortex (LEC) to innervate the dorsal hippocampus via the perforant pathway in males, but not LB females, and were strongly correlated with deficits in contextual fear conditioning. Conclusions: LB impairs the capacity of reelin-positive cells located in the LEC to project and innervate the dorsal hippocampus in LB males but not female LB littermates. Given the critical role that these projections play in supporting normal hippocampal function, a failure to establish proper connectivity between the LEC and the dorsal hippocampus provides a compelling and novel mechanism to explain the more severe deficits in myelination and contextual freezing found in adolescent LB males. Plain Language Summary: Childhood adversity, such as severe deprivation and neglect, leads to structural changes in human brain development that are associated with learning deficits and behavioral difficulties. Some of the most consistent findings in individuals exposed to childhood adversity are reduced hippocampal volume and abnormal hippocampal function. This is important because the hippocampus is necessary for learning and memory, and it plays a crucial role in depression and anxiety. Although initial studies suggested more pronounced hippocampal deficits in men, additional research is needed to confirm these findings and to elucidate the mechanisms responsible for these sex differences. We found that male and female mice exposed to early impoverishment and deprivation exhibit similar structural changes to those observed in deprived children. Interestingly, adolescent male mice, but not females, display severe deficits in their ability to freeze when placed back in a box where they were previously shocked. The ability to associate "shock/danger" with a "box/place" is referred to as contextual fear conditioning and requires normal connections between the entorhinal cortex and the hippocampus. We found that these connections did not form properly in male mice exposed to impoverished conditions, but they were only minimally affected in females. These findings appear to explain why exposure to impoverished conditions impairs contextual fear conditioning in male mice but not in female mice. Additional work is needed to determine whether similar sex-specific changes in these connections are also observed in adolescents exposed to neglect and deprivation. Highlights: The number of reelin-positive cells projecting from the lateral entorhinal cortex via the perforant pathway to the dorsal hippocampus is four times lower in adolescent male mice exposed to limited bedding (LB) compared to LB female littermates or control mice. Given the critical role that these projections play in hippocampal function, these findings provide a novel mechanism to explain the sex-specific deficits in contextual fear conditioning observed in adolescent LB male mice. Sparse axonal innervation in perforant pathway terminals also explains the reduced myelination observed in the stratum lacunosum moleculare, which is one of the most highly myelinated regions in the developing hippocampus. Adolescent LB male and female mice are hyperactive and exhibit significant cortical thinning, which mirrors findings in humans exposed to severe early deprivation. [ABSTRACT FROM AUTHOR]

Introduction: The findings of epidemiological studies suggest that a relationship exists between the risk of schizophrenia and winter births in the Northern Hemisphere, which may affect the process of fetal neurodevelopment. However, it remains unclear whether birth seasons are associated with the brain morphological characteristics of patients within the schizophrenia spectrum. Methods: The present magnetic resonance imaging study using FreeSurfer software examined the effects of birth seasons (i.e., summer-born vs. winterborn) on the comprehensive brain surface characteristics of 101 patients with schizophrenia (48 summer- and 53 winter-born), 46 with schizotypal disorder (20 summer- and 26 winter-born), and 76 healthy control subjects (28 summerand 48 winter-born). Results: In comparisons with summer-born patients, winter-born patients, particularly those with schizophrenia, showed significantly increased gyrification mainly in the left lateral occipital and inferior temporal regions and right fronto-parietal region as well as cortical thinning in the right superior frontal region. Birth seasons did not significantly affect the local gyrification index or cortical thickness in healthy controls. Discussion: The present whole-brain surface-based analysis demonstrated that brain morphological characteristics reported in the schizophrenia spectrum were more pronounced in winter-born patients than in summer-born patients, suggesting the contribution of early neurodevelopmental factors associated with birth seasons to the pathophysiology of the schizophrenia spectrum. [ABSTRACT FROM AUTHOR]

Adverse experiences throughout development confer risk for a multitude of negative long-term outcomes, but the processes via which these experiences are neurobiologically embedded are still unclear. Adolescence provides an opportunity to understand how these experiences impact the brain's rapidly changing structure. Two models are central to current adversity conceptualizations: a cumulative risk model, where all types of experiences are combined to represent accumulating stress, and a dimensional model, where certain features of experience (e.g., threat or deprivation) exert unique neurophysiological influence. In this registered report, we extended upon previous research by using a form of representational similarity analysis to examine whether the dimensional and cumulative risk models of adversity predict cortical thinning in frontoparietal and frontotemporal networks and volumetric changes in subcortical regions throughout adolescence. Drawing from a longitudinal sample of 179 adolescent girls (ages 10–13 years at the first wave) from Lane County, Oregon, United States, and up to four waves of follow-up data, we found that operationalizing adversity by similarity in threat and deprivation provided better prediction of brain development than similarity in overall adversity. However, these dimensions do not exhibit unique associations with developmental changes in the hypothesized brain changes. These results underscore the significance of carefully defining adversity and considering its impact on the entire brain. Public Significance Statement: Difficult experiences adolescents face while growing up can shape pathways of brain development over many years. The more one adolescent's experiences differ from another adolescent's experiences, especially in cases of threat or neglect, the more their rates of brain development diverge. [ABSTRACT FROM AUTHOR]

To evaluate automated digital speech measures, derived from spontaneous speech (picture descriptions), in assessing bulbar motor impairments in patients with ALS-FTD spectrum disorders (ALS-FTSD). Automated vowel algorithms were employed to extract two vowel acoustic measures: vowel space area (VSA), and mean second formant slope (F2 slope). Vowel measures were compared between ALS with and without clinical bulbar symptoms (ALS + bulbar (n = 49, ALSFRS-r bulbar subscore: x¯ = 9.8 (SD = 1.7)) vs. ALS-nonbulbar (n = 23), behavioral variant frontotemporal dementia (bvFTD, n = 25) without a motor syndrome, and healthy controls (HC, n = 32). Correlations with bulbar motor clinical scales, perceived listener effort, and MRI cortical thickness of the orobuccal primary motor cortex (oral PMC) were examined. We compared vowel measures to speaking rate, a conventional metric for assessing bulbar dysfunction. ALS + bulbar had significantly reduced VSA and F2 slope than ALS-nonbulbar (|d|=0.94 and |d|=1.04, respectively), bvFTD (|d|=0.89 and |d|=1.47), and HC (|d|=0.73 and |d|=0.99). These reductions correlated with worse bulbar clinical scores (VSA: R = 0.33, p = 0.043; F2 slope: R = 0.38, p = 0.011), greater listener effort (VSA: R=-0.43, p = 0.041; F2 slope: p > 0.05), and cortical thinning in oral PMC (F2 slope: β = 0.0026, p = 0.017). Vowel measures demonstrated greater sensitivity and specificity for bulbar impairment than speaking rate, while showing independence from cognitive and respiratory impairments. Automatic vowel measures are easily derived from a brief spontaneous speech sample, are sensitive to mild-moderate stage of bulbar disease in ALS-FTSD, and may present better sensitivity to bulbar impairment compared to traditional assessments such as speaking rate. [ABSTRACT FROM AUTHOR]

Introduction: Ocrelizumab (OCR) and Fingolimod (FGL) are two high-efficacy treatments in multiple sclerosis which, besides their strong anti-inflammatory activity, may limit neurodegeneration. Aim: To compare the effect of OCR and FGL on clinical and MRI endpoints. Methods: 95 relapsing–remitting patients (57 OCR, 38 FGL) clinically followed for 36 months underwent a 3-Tesla MRI at baseline and after 24 months. The annualized relapse rate, EDSS, new cortical/white matter lesions and regional cortical and deep grey matter volume loss were evaluated. Results: OCR reduced the relapse rate from 0.48 to 0.04, FGL from 0.32 to 0.05 (both p < 0.001). Compared to FGL, OCR-group experienced fewer new white matter lesions (12% vs 32%, p = 0.005), no differences in new cortical lesions, lower deep grey matter volume loss (− 0.12% vs − 0.66%; p = 0.002, Cohen's d = 0.54), lower global cortical thickness change (− 0.45% vs − 0.70%; p = 0.036; d = 0.42) and reduced cortical thinning/volume loss in several regions of interests, including those of parietal gyrus (d-range = 0.65–0.71), frontal gyrus (d-range = 0.47–0.60), cingulate (d-range = 0.41–0.72), insula (d = 0.36), cerebellum (cortex d = 0.72, white matter d = 0.44), putamen (d = 0.35) and thalamus (d = 0.31). The effect on some regional thickness changes was confirmed in patients without focal lesions. Conclusions: When compared with FGL, patients receiving OCR showed greater suppression of focal MRI lesions accumulation and lower cortical and deep grey matter volume loss. [ABSTRACT FROM AUTHOR]