Disentangling the effect of sex from brain size on brain organization and cognitive functioning.

Neuroanatomical sex differences estimated in neuroimaging studies are confounded by total intracranial volume (TIV) as a major biological factor. Employing a matching approach widely used for causal modeling, we disentangled the effect of TIV from sex to study sex-differentiated brain aging trajectories, their relation to functional networks and cytoarchitectonic classes, brain allometry, and cognition. Using data from the UK Biobank, we created subsamples that removed, maintained, or exaggerated the TIV differences in the original sample.

Differential effects of prolonged post-fixation on immunohistochemical and histochemical staining for postmortem human brains.

Purpose: Immunohistochemical (IHC) and histochemical (HC) staining techniques are widely used on human brains that are post-fixed in formalin and stored in brain banks worldwide for varying durations, from months to decades. Understanding the effects of prolonged post-fixation, postmortem interval (PMI), and age on these staining procedures is important for accurately interpreting their outcomes, thereby improving the diagnosis and research of brain disorders afflicting millions of people worldwide.

Methods: In this study, we conducted both IHC and HC staining on the prefrontal cortex of postmortem human brains post-fixed for 1, 5, 10, 15, and 20 years.

Sustained improvements in brain health and metabolic markers 24 months following bariatric surgery.

Obesity and its metabolic complications are associated with lower grey matter and white matter densities, whereas weight loss after bariatric surgery leads to an increase in both measures. These increases in grey and white matter density are significantly associated with post-operative weight loss and improvement of the metabolic/inflammatory profiles. While our recent studies demonstrated widespread increases in white matter density 4 and 12 months after bariatric surgery, it is not clear if these changes persist over time.

Distinctive whole-brain cell types predict tissue damage patterns in thirteen neurodegenerative conditions.

For over a century, brain research narrative has mainly centered on neuron cells. Accordingly, most neurodegenerative studies focus on neuronal dysfunction and their selective vulnerability, while we lack comprehensive analyses of other major cell types' contribution. By unifying spatial gene expression, structural MRI, and cell deconvolution, here we describe how the human brain distribution of canonical cell types extensively predicts tissue damage in 13 neurodegenerative conditions, including early- and late-onset Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, amyotrophic lateral sclerosis, mutations in presenilin-1, and 3 clinical variants of frontotemporal lobar degeneration (behavioral variant, semantic and non-fluent primary progressive aphasia) along with associated three-repeat and four-repeat tauopathies and TDP43 proteinopathies types A and C.

Patient-specific models link neurotransmitter receptor mechanisms with motor and visuospatial axes of Parkinson's disease.

Parkinson's disease involves multiple neurotransmitter systems beyond the classical dopaminergic circuit, but their influence on structural and functional alterations is not well understood. Here, we use patient-specific causal brain modeling to identify latent neurotransmitter receptor-mediated mechanisms contributing to Parkinson's disease progression. Combining the spatial distribution of 15 receptors from post-mortem autoradiography with 6 neuroimaging-derived pathological factors, we detect a diverse set of receptors influencing gray matter atrophy, functional activity dysregulation, microstructural degeneration, and dendrite and dopaminergic transporter loss.

White Matter Hyperintensity Trajectories in Patients With Progressive and Stable Mild Cognitive Impairment.

Background And Objectives: White matter hyperintensities (WMH) are pathologic brain changes that are associated with increased age and cognitive decline. However, the association of WMH burden with amyloid positivity and conversion to dementia in people with mild cognitive impairment (MCI) is unclear. The aim of this study was to expand on this research by examining whether change in WMH burden over time differs in amyloid-negative (Aβ-) and amyloid-positive (Aβ+) people with MCI who either remain stable or convert to dementia.

A comparison of anatomic and cellular transcriptome structures across 40 human brain diseases.

Genes associated with risk for brain disease exhibit characteristic expression patterns that reflect both anatomical and cell type relationships. Brain-wide transcriptomic patterns of disease risk genes provide a molecular-based signature, based on differential co-expression, that is often unique to that disease. Brain diseases can be compared and aggregated based on the similarity of their signatures which often associates diseases from diverse phenotypic classes.

Reproducibility of cerebellar involvement as quantified by consensus structural MRI biomarkers in advanced essential tremor.

Essential tremor (ET) is the most prevalent movement disorder with poorly understood etiology. Some neuroimaging studies report cerebellar involvement whereas others do not. This discrepancy may stem from underpowered studies, differences in statistical modeling or variation in magnetic resonance imaging (MRI) acquisition and processing.

Obesity-Associated Neurodegeneration Pattern Mimics Alzheimer's Disease in an Observational Cohort Study.

Background: Excess weight in adulthood leads to health complications such as diabetes, hypertension, or dyslipidemia. Recently, excess weight has also been related to brain atrophy and cognitive decline. Reports show that obesity is linked with Alzheimer's disease (AD)-related changes, such as cerebrovascular damage or amyloid-β accumulation.

Topographical differences in white matter hyperintensity burden and cognition in aging, MCI, and AD.

White matter hyperintensities (WMHs) are pathological changes that occur with increased age and are associated with cognitive decline. Most WMH research has not examined regional differences and focuses on a whole-brain approach. This study examined regional WMHs between normal controls (NCs), people with mild cognitive impairment (MCI), and Alzheimer's disease (AD).

Impact of weight loss on brain age: Improved brain health following bariatric surgery.

Individuals living with obesity tend to have increased brain age, reflecting poorer brain health likely due to grey and white matter atrophy related to obesity. However, it is unclear if older brain age associated with obesity can be reversed following weight loss and cardiometabolic health improvement. The aim of this study was to assess the impact of weight loss and cardiometabolic improvement following bariatric surgery on brain health, as measured by change in brain age estimated based on voxel-based morphometry (VBM) measurements.

Multivariate genomic and transcriptomic determinants of imaging-derived personalized therapeutic needs in Parkinson's disease.

Due to the marked interpersonal neuropathologic and clinical heterogeneity of Parkinson's disease (PD), current interventions are not personalized and fail to benefit all patients. Furthermore, we continue to lack well-established methods and clinical tests to tailor interventions at the individual level in PD. Here, we identify the genetic determinants of individual-tailored treatment needs derived from longitudinal multimodal neuroimaging data in 294 PD patients (PPMI data).

The PaleoArchiNeo (PAN) human brain atlas: A dataset on a standard neuroanatomical MRI template following a phylogenetic approach.

Cortical atlases provide consistent divisions of the human cortex into areas that have common structural as well as meaningful and distinctive functional characteristics. They constitute a fundamental tool to study and quantify changes in healthy and pathological states. Historically, the most widely used atlases follow the cytoarchitecture described by Brodmann and/or the myeloarchitectonic characteristics described by Vogt-Vogt.

Relationship between impulsivity, uncontrolled eating and body mass index: a hierarchical model.

Background: Impulsivity increases the risk for obesity and weight gain. However, the precise role of impulsivity in the aetiology of overeating behavior and obesity is currently unknown. Here we examined the relationships between personality-related measures of impulsivity, Uncontrolled Eating, body mass index (BMI), and longitudinal weight changes.

Spontaneous neural activity changes after bariatric surgery: A resting-state fMRI study.

Background: Metabolic disorders associated with obesity could lead to alterations in brain structure and function. Whether these changes can be reversed after weight loss is unclear. Bariatric surgery provides a unique opportunity to address these questions because it induces marked weight loss and metabolic improvements which in turn may impact the brain in a longitudinal fashion.

White matter integrity differences in obesity: A meta-analysis of diffusion tensor imaging studies.

Some Diffusion Tensor Imaging studies have shown a loss of white matter (WM) integrity linked to impaired cognitive function in obese individuals. However, inconsistent WM integrity changes have been reported. We aimed to identify which WM tracts show consistent changes with obesity.

Association vs. Prediction: The Impact of Cortical Surface Smoothing and Parcellation on Brain Age.

Association and prediction studies of the brain target the biological consequences of aging and their impact on brain function. Such studies are conducted using different smoothing levels and parcellations at the preprocessing stage, on which their results are dependent. However, the impact of these parameters on the relationship between association values and prediction accuracy is not established.

Orbitofrontal-Striatal Structural Alterations Linked to Negative Symptoms at Different Stages of the Schizophrenia Spectrum.

Negative symptoms such as anhedonia and apathy are among the most debilitating manifestations of schizophrenia (SZ). Imaging studies have linked these symptoms to morphometric abnormalities in 2 brain regions implicated in reward and motivation: the orbitofrontal cortex (OFC) and striatum. Higher negative symptoms are generally associated with reduced OFC thickness, while higher apathy specifically maps to reduced striatal volume.

Sex effects on brain structure in de novo Parkinson's disease: a multimodal neuroimaging study.

Parkinson's disease varies in severity and age of onset. One source of this variability is sex. Males are twice as likely as females to develop Parkinson's disease, and tend to have more severe symptoms and greater speed of progression.

Neural correlates of polygenic risk score for autism spectrum disorders in general population.

Autism spectrum disorder is a highly prevalent and highly heritable neurodevelopmental condition, but studies have mostly taken traditional categorical diagnosis approach (yes/no for autism spectrum disorder). In contrast, an emerging notion suggests a continuum model of autism spectrum disorder with a normal distribution of autistic tendencies in the general population, where a full diagnosis is at the severe tail of the distribution. We set out to investigate such a viewpoint by investigating the interaction of polygenic risk scores for autism spectrum disorder and Age on neuroimaging measures (cortical thickness and white matter connectivity) in a general population (=391, with age ranging from 3 to 21 years from the Pediatric Imaging, Neurocognition and Genetics study).

Origins of atrophy in Parkinson linked to early onset and local transcription patterns.

There is enormous clinical value in inferring the brain regions initially atrophied in Parkinson disease for individual patients and understanding its relationship with clinical and genetic risk factors. The aim of this study is to leverage a new seed-inference algorithm demonstrated for Alzheimer's disease to the Parkinsonian context and to cluster patients in meaningful subgroups based on these incipient atrophy patterns. Instead of testing brain regions separately as the likely initiation site for each patient, we solve an L1-penalized optimization problem that can return a more predictive heterogeneous, multi-locus seed patterns.

White Matter Hyperintensities Mediate Impact of Dysautonomia on Cognition in Parkinson's Disease.

Background: Patients with Parkinson's disease (PD) present with a broad spectrum of nonmotor features including autonomic disorders. More severe autonomic dysfunction in PD is associated with increased cognitive deficits. The presence of cerebral small-vessel disease, measured by T2-weighted magnetic resonance imaging white matter hyperintensity (WMH) burden, is also observed in patients with PD with faster cognitive decline.

Neural Correlates of Evidence and Urgency During Human Perceptual Decision-Making in Dynamically Changing Conditions.

Current models of decision-making assume that the brain gradually accumulates evidence and drifts toward a threshold that, once crossed, results in a choice selection. These models have been especially successful in primate research; however, transposing them to human fMRI paradigms has proved it to be challenging. Here, we exploit the face-selective visual system and test whether decoded emotional facial features from multivariate fMRI signals during a dynamic perceptual decision-making task are related to the parameters of computational models of decision-making.