Explore the vast range of titles available.

Neurofibrillary tau tangles are a hallmark pathology of Alzheimer's disease (AD) and are more closely associated with AD-related cortical atrophy and symptom severity than amyloid-beta (Aβ). However, studies regarding the effect of tau on longitudinal cortical thinning, particularly in healthy aging and preclinical AD, have been limited in number due to the relatively recent introduction of in vivo PET tracers for imaging tau pathology. Here, we investigate [18F]-flortaucipir (FTP, a marker of paired helical filament tau) PET as a predictor of atrophy in healthy aging and preclinical AD. We examine longitudinal structural MRI brain imaging data, retrospectively and prospectively relative to FTP imaging, using piecewise linear mixed-effect models with time centered at each participant's FTP-PET session. Participants include 111 individuals from the Harvard Aging Brain Study who underwent at least three MRI sessions over an average of 4.46 years and one FTP-PET at the approximate midpoint of the observation period. Our primary analyses focus on inferior temporal (IT) FTP standardized uptake value ratios and longitudinal FreeSurfer defined cortical regions of interest. Relationships were also explored using other regional FTP measures (entorhinal, composite, and local), within high and low Pittsburgh compound-B (PiB) PET groups, and with longitudinal subcortical volume. Strong associations between IT FTP and cortical thinning were found, most notably in temporal, midline, and prefrontal regions, with stronger effects generally observed in the prospective as compared to retrospective time frame. Significant differences between prospective and retrospective rates of thinning were found in the inferior and middle temporal gyri, cingulate areas, as well as pars orbitalis such that higher IT FTP was associated with greater prospective rates of thinning. Within the high PiB group, significant differences between prospective and retrospective rates of thinning were similarly observed. However, no consistent pattern of tau-related change in cortical thickness within the low PiB group was discerned. These results provide support for the hypothesis that tau pathology is a driver of future atrophy as well as provide additional evidence for tau-PET as an effective AD biomarker for interventional clinical trials. •Tau positron emission tomography images were acquired for 111 individuals.•Magnetic resonance data were longitudinally collected (nscans = 386).•Prospective structural changes were observed with higher inferior temporal tau.•Lateral temporal regions may represent an inflection point in preclinical AD.•Findings are consistent with the hypothesis that tau is a driver of atrophy.

Cortical thinning occurs throughout the entire life and extends to late-life neurodegeneration, yet the neurobiological substrates are poorly understood. Here, we used a virtual-histology technique and gene expression data from the Allen Human Brain Atlas to compare the regional profiles of longitudinal cortical thinning through life (4004 magnetic resonance images [MRIs]) with those of gene expression for several neuronal and non-neuronal cell types. The results were replicated in three independent datasets. We found that inter-regional profiles of cortical thinning related to expression profiles for marker genes of CA1 pyramidal cells, astrocytes and, microglia during development and in aging. During the two stages of life, the relationships went in opposite directions: greater gene expression related to less thinning in development and vice versa in aging. The association between cortical thinning and cell-specific gene expression was also present in mild cognitive impairment and Alzheimer’s Disease. These findings suggest a role of astrocytes and microglia in promoting and supporting neuronal growth and dendritic structures through life that affects cortical thickness during development, aging, and neurodegeneration. Overall, the findings contribute to our understanding of the neurobiology underlying variations in MRI-derived estimates of cortical thinning through life and late-life disease.

Positive symptoms are a useful predictor of aggression in schizophrenia. Although a similar pattern of abnormal brain structures related to both positive symptoms and aggression has been reported, this observation has not yet been confirmed in a single sample. To study the association between positive symptoms and aggression in schizophrenia on a neurobiological level, a prospective meta-analytic approach was employed to analyze harmonized structural neuroimaging data from 10 research centers worldwide. We analyzed brain MRI scans from 902 individuals with a primary diagnosis of schizophrenia and 952 healthy controls. The result identified a widespread cortical thickness reduction in schizophrenia compared to their controls. Two separate meta-regression analyses revealed that a common pattern of reduced cortical gray matter thickness within the left lateral temporal lobe and right midcingulate cortex was significantly associated with both positive symptoms and aggression. These findings suggested that positive symptoms such as formal thought disorder and auditory misperception, combined with cognitive impairments reflecting difficulties in deploying an adaptive control toward perceived threats, could escalate the likelihood of aggression in schizophrenia.

Speech‐motor and cognitive impairments are commonly observed in age‐related neurodegenerative diseases, including mild cognitive impairment (MCI) and Alzheimer's Disease (AD). Although there is a strong interaction between motor and cognitive functions, intact speech motor control is a crucial yet often‐overlooked component of cognitive functioning. Additionally, motor decline can occur independently and may precede the onset of cognitive impairment in neurodegenerative conditions. These impairments can confound measures of higher‐order cognition, typically assessed through behavioral performance. Notably, the associations between cognitive performance and biological indices of speech motor production have been largely unexplored. This study is the first to examine cognitive associations of cortical thickness in brain regions implicated in speech motor performance across the adult lifespan, and to investigate whether age‐related structural changes in speech motor regions precede those seen in the hippocampus. Our sample included 699 cognitively healthy adults (56% female) spanning 35–90 years from the Human Connectome Project (HCP)‐Aging dataset. Cognition was estimated using standard neuropsychological assessments including: the Trail Making Task A/B (TMT), the Rey Auditory Verbal Learning Test (RAVLT), and a cognitive composite score (summating cognitive performance across multiple tasks). Whole‐brain T1‐ and T2‐weighted MRI images were acquired using 3‐Tesla scanners across multiple study sites. Structural images were preprocessed using the HCP minimal preprocessed pipelines to reconstruct cortical surfaces. Volume‐based estimates including hippocampal volume and total gray matter volume were adjusted for head size using an adjusted measure of estimated Total Intracranial Volume (eTIV). Speech motor regions were investigated relative to well‐characterized relationships with hippocampal volume (a hallmark region for memory and cognition and AD‐related atrophy). Estimates of cortical thickness were extracted from 14 bilateral speech motor control regions spanning premotor, motor, somatosensory, insular, and prefrontal cortices. Performance across all cognitive tasks and estimates of brain structure were all highly correlated with age. After controlling for the effects of age, greater hippocampal volume remained correlated with better cognitive performance across all cognitive tasks. However, only cognitive associations with greater total gray matter volume survived correction for multiple comparisons. As expected, age associations with hippocampal volume differed between early (−0.191%/year) and late adulthood (−0.714%/year) (T = 6.179, p = 0.0002). Age associations with speech motor control regions significantly differed from the associations seen in GMV, mCT, and/or hippocampal volume across the lifespan (Pcor < 0.0001) and during late adulthood when compared separately. Half the speech motor control regions explored showed decelerated estimated percent difference per year from early and late adulthood. Our results suggest that neurocognitive relationships are highly impacted and often confounded by age. The thickness of several speech motor regions was not associated with cognitive performance and can therefore provide a more intrinsic measure of aging. Additionally, speech motor control regions decline earlier in adulthood than hippocampal volume and may therefore serve as a target and early indicator of AD‐related neurodegeneration. This nuanced understanding is critical for refining early diagnostic criteria for neurodegenerative diseases, including AD, and sheds light on the complex interplay between age‐related changes, disease pathology, and cognitive decline. Speech motor control thickness measures were generally not correlated with cognitive performance and showed stronger age associations than hippocampal volume during early adulthood. Thinning of specific speech motor regions precedes reduction in hippocampal volume during early adulthood, and may serve as a target and early indicator of AD‐related neurodegeneration.

INTRODUCTION The emergence, stability, and contributing factors of Alzheimer's disease (AD) gray matter subtypes remain unclear. METHODS We analyzed data from 1323 individuals without a diagnosis of dementia (CDR < 1) with T1w‐MRI and amyloid‐PET, including 622 with longitudinal data (3.66 ± 1.78 years). Cortical thickness subtypes were identified using a non‐negative matrix factorization (NMF) clustering algorithm. We examined clinical and demographic differences, subtype stability, and longitudinal thinning patterns using brain network models and imaging‐transcriptomic analysis. Replication was performed with an alternative clustering approach and a validation cohort. RESULTS Two stable subtypes emerged: limbic‐predominant and hippocampal‐sparing. Limbic‐predominant participants were older, had higher amyloid burden, and faster memory decline, while hippocampal‐sparing individuals showed greater attention and executive function decline. Distinct thinning patterns were linked to specific network properties and gene expression profiles. DISCUSSION These MRI‐based subtypes reflect underlying pathophysiological mechanisms and may aid in prognostication and clinical trial stratification. Highlights Two gray matter thickness subtypes can already be identified in preclinical stages, exhibiting distinct clinical characteristics and progression patterns. Individual subtype assignment remains stable over time. Longitudinal cortical thinning patterns follow distinct network‐ and transcriptomic‐based mechanisms within each subtype.

BackgroundJuvenile myoclonic epilepsy (JME) is associated with cortical thinning of the motor areas. The relative contribution of antiseizure medication to cortical thickness is unknown. We aimed to investigate how valproate influences the cortical morphology of JME.MethodsIn this cross-sectional study, individuals with JME with and without valproate, with temporal lobe epilepsy (TLE) with valproate and controls were selected through propensity score matching. Participants underwent T1-weighted brain imaging and vertex-wise calculation of cortical thickness.ResultsWe matched 36 individuals with JME on valproate with 36 individuals with JME without valproate, 36 controls and 19 individuals with TLE on valproate. JME on valproate showed thinning of the precentral gyri (left and right, p<0.001) compared with controls and thinning of the left precentral gyrus when compared with JME not on valproate (p<0.01) or to TLE on valproate (p<0.001). Valproate dose correlated negatively with the thickness of the precentral gyri, postcentral gyri and superior frontal gyrus in JME (left and right p<0.0001), but not in TLE.ConclusionsValproate was associated with JME-specific and dose-dependent thinning of the cortical motor regions. This suggests that valproate is a key modulator of cortical morphology in JME, an effect that may underlie its high efficacy in this syndrome.

The cognitive and behavioral development of children and adolescents is closely related to the maturation of brain morphology. Although the trajectory of brain development has been depicted in detail, the underlying biological mechanism of normal cortical morphological development in childhood and adolescence remains unclear. By combining the Allen Human Brain Atlas dataset with two single‐site magnetic resonance imaging data including 427 and 733 subjects from China and the United States, respectively, we performed partial least squares regression and enrichment analysis to explore the relationship between the gene transcriptional expression and the development of cortical thickness in childhood and adolescence. We found that the spatial model of normal cortical thinning during childhood and adolescence is associated with genes expressed predominantly in astrocytes, microglia, excitatory and inhibitory neurons. Top cortical development‐related genes are enriched for energy‐related and DNA‐related terms and are associated with psychological and cognitive disorders. Interestingly, there is a great deal of similarity between the findings derived from the two single‐site datasets. This fills the gap between early cortical development and transcriptomes, which promotes an integrative understanding of the potential biological neural mechanisms. The underlying biological mechanism of early cortical morphological development remains unclear. We found linear development pattern of cortical thickness during childhood and adolescence is associated with spatially varying gene transcription, which expresses predominantly in astrocytes, microglia, excitatory and inhibitory neurons, and ontologically enriches for energy‐related and DNA‐related terms. Cortical development‐related genes are also associated with psychological and cognitive disorders.

Clinical implementation of risk calculator models in the clinical high-risk for psychosis (CHR-P) population has been hindered by heterogeneous risk distributions across study cohorts which could be attributed to pre-ascertainment illness progression. To examine this, we tested whether the duration of attenuated psychotic symptom (APS) worsening prior to baseline moderated performance of the North American prodrome longitudinal study 2 (NAPLS2) risk calculator. We also examined whether rates of cortical thinning, another marker of illness progression, bolstered clinical prediction models. Participants from both the NAPLS2 and NAPLS3 samples were classified as either 'long' or 'short' symptom duration based on time since APS increase prior to baseline. The NAPLS2 risk calculator model was applied to each of these groups. In a subset of NAPLS3 participants who completed follow-up magnetic resonance imaging scans, change in cortical thickness was combined with the individual risk score to predict conversion to psychosis. The risk calculator models achieved similar performance across the combined NAPLS2/NAPLS3 sample [area under the curve (AUC) = 0.69], the long duration group (AUC = 0.71), and the short duration group (AUC = 0.71). The shorter duration group was younger and had higher baseline APS than the longer duration group. The addition of cortical thinning improved the prediction of conversion significantly for the short duration group (AUC = 0.84), with a moderate improvement in prediction for the longer duration group (AUC = 0.78). These results suggest that early illness progression differs among CHR-P patients, is detectable with both clinical and neuroimaging measures, and could play an essential role in the prediction of clinical outcomes.

Cortical thickness reductions associated with chronic methamphetamine use exhibit a non-uniform spatial distribution across brain regions. A potential neurobiological mechanism underlying for this heterogeneous pattern may involve the structural and functional organization of cortical connectivity networks, which could mediate the propagation of neuroanatomical alterations. Here, we aimed to explore how brain network architecture constrains cortical thickness alterations and their clinical relevance. The 3D-T1 images were acquired from 139 patients with methamphetamine use disorder (MUD) and 119 sex- and age-matched healthy controls. We first characterized distributed cortical thinning patterns in patients with MUD, then evaluated the relationships between regional atrophy and (1) multimodal nodal centrality measures (structural, morphological, and functional) and (2) atrophy profiles of structural connected neighbors. Individual network-weighted cortical abnormality maps were used to identify distinct MUD biotypes and related to clinical features through k-means clustering and partial least squares regression. Cortical thinning patterns demonstrated significant associations with nodal centrality across all modalities, as well as cortical thinning of connected neighbors revealing a network-dependent atrophy architecture. Fronto-temporal regions emerged as critical epicenters, showing both high nodal centrality and strong correlations with connected neighbors' thinning severity. We found that the individual differences in network-weighted cortical abnormality corresponded to clinical symptom variability, and distinguished two MUD biotypes associated with drug use. Our findings suggest that cortical thinning in MUD is influenced by the brain connectome architecture, providing a mechanistic framework for understanding individual variability in addiction progression.

INTRODUCTION We investigated the association between white matter hyperintensities (WMH) and regional cortical thickness, amyloid and tau deposition, and synaptic density in the WMH‐connected cortex using multimodal images. METHODS We included 107 participants (59 with Alzheimer's disease [AD]; 27 with mild cognitive impairment; 21 cognitively normal controls) with amyloid beta (Aβ) positivity on amyloid positron emission tomography (PET). The cortex connected to WMH was identified using probabilistic tractography. RESULTS We found that WMH connected to the cortex with more severe regional degeneration as measured by cortical thickness, Aβ and tau deposition, and synaptic vesicle glycoprotein 2 A (SV2A) density using 18F‐SynVesT‐1 PET. In addition, higher ratios of Aβ in the deep WMH‐connected versus WMH‐unconnected cortex were significantly related to lower cognitive scores. Last, the cortical thickness of WMH‐connected cortex reduced more than WMH‐unconnected cortex over 12 months. DISCUSSION Our results suggest that WMH may be associated with AD‐intrinsic processes of degeneration, in addition to vascular mechanisms. Highlights We studied white matter hyperintensities (WMHs) and WMH‐connected cortical changes. WMHs are associated with more severe regional cortical degeneration. Findings suggest WMHs may be associated with Alzheimer's disease–intrinsic processes of degeneration.