Cortical Alterations Research Articles

Morphometric Similarity Patterning of Amyloid-β and Tau Proteins Correlates with Transcriptomics in the Alzheimer’s Disease Continuum

Bridging the gap between cortical morphometric remodeling and gene expression can help to clarify the effects of the selective brain accumulation of Amyloid-β (Aβ) and tau proteins occurring in the Alzheimer’s disease (AD). To this aim, we derived morphometric similarity (MS) networks from 126 Aβ- and tau-positive (Aβ+/tau+) and 172 Aβ−/tau− subjects, and we investigated the association between group-wise regional MS differences and transcriptional correlates thanks to an imaging transcriptomics approach grounded in the Allen Human Brain Atlas (AHBA). The expressed gene with the highest correlation with MS alterations was BCHE, a gene related to Aβ homeostasis. In addition, notably, among the most promising results derived from the enrichment analysis, we found the immune response to be a biological process and astrocytes, microglia, and oligodendrocyte precursors for the cell types. In summary, by relating cortical MS and AHBA-derived transcriptomics, we were able to retrieve findings suggesting the biological mechanisms underlying the Aβ- and tau- induced cortical MS alterations in the AD continuum.

NIMG-13. CHANGES IN CORTICAL ARCHITECTURE ASSOCIATED WITH GLIOBLASTOMA ASSOCIATED EPILEPSY

Abstract BACKGROUND Emerging evidence suggests both local hyper-excitability promoting epilepsy, and synaptic and paracrine mediated integration of Glioblastoma into brain-wide neural networks. In this study we sought clinical evidence of disease progression, and concurrent radiological evidence of differences in remote cortical architecture, in Glioblastoma patients with and without epilepsy. METHODS 55 patients with biopsy-confirmed Glioblastoma, mean-age 59.4yrs±10.9yrs, were studied. 23 patients had a diagnosis of Glioblastoma-related epilepsy on presentation. We compared clinical markers of disease progression in individuals with and without epilepsy. Further, we explored differences in cortical architecture between both groups. Utilising pre-operative T1-weighted, contrast-enhanced MRI scans (n=45), we performed vertex-wise measurements of cortical thickness (CT) and cortical surface area (CSA) using the Virtual Brain Grafting Toolbox and FreeSurfer v.7.0. Radiologically-identifiable tumour and oedema was masked and excluded from analysis. Scans with right-hemispheric tumours were flipped to the left. Linear mixed-effects models were applied to pre-processed imaging-data. RESULTS Individuals with epilepsy had shorter progression-free survival (median 4.2 months) than those without seizures (9.3 months, p<0.05) with gold-standard treatment. No significant difference between lesion volumes (tumour and oedema) existed between the two groups (unpaired t-test, p>0.05). Controlling for age and tumour location, significant increases (p<0.01) in CT and CSA were observed in patients with Glioblastoma-related epilepsy in lesion-ipsilateral supramarginal gyrus, superior parietal lobule, precuneus/cuneus and temporal lobe compared to those without epilepsy. Interestingly, significant (p<0.05) increases in CT in lesion-contralateral supramarginal gyrus were additionally observed in those with epilepsy compared to those without. CONCLUSIONS Glioblastoma-related epilepsy was associated with poorer survival outcomes and changes in remote cortical architecture. Implicated regions form part of the default mode network, which has previously been identified as a crucial hub for epilepsy. Biological underpinnings of cortical network alterations, and their possible role in promoting not only hyper-excitability but also Glioblastoma progression, require correlation with histopathological characteristics and validation in larger study cohorts.

Cortical Alterations Associated with Executive Function Deficits in Youth with a Congenital Heart Defect

Abstract Adolescents and young adults born with a complex congenital heart defect (CHD) are at risk for executive function (ExF) impairments, which contribute to the psychological and everyday burden of CHD. Cortical dysmaturation has been well described in fetuses and neonates with CHD and early evidence suggests that cortical alterations in thickness, surface area, and gyrification index are non-transient and can be observed in adolescents with CHD. However, cortical alterations have yet to be correlated with ExF deficits in youth with CHD. This study aims to use a data-driven approach to identify the most important cortical features associated with ExF deficits in adolescents and young adults with CHD. To do so, we combined two comparable datasets acquired at the Research Institute of the McGill University Health Centre and the University Children’s Hospital Zurich each including both youth with CHD and healthy controls. For each participant, a high-resolution T1-weighted magnetic resonance image, a self-reported ExF assessment (the Behaviour Rating Inventory of Executive Function— Adult Scale), and their clinical and demographic characteristics were available. Corticometric Iterative Vertex-Based Estimation of Thickness (CIVET) was used to extract cortical thickness, cortical surface area, and local gyrification index measures. Using orthogonal projective non-negative matrix factorization (OPNMF), we identified non-overlapping spatial components that integrate cortical thickness, cortical surface area, and local gyrification index and capture structural covariance across these features. Behavioural partial least squares correlation (bPLS) analysis was then used to compute correlations between the individual variability in the OPNMF covariance patterns and ExF outcomes for each subject. A total of 56 youth with CHD who underwent cardiopulmonary bypass surgery before three years of age and 56 age- and sex-matched healthy controls were included in our analyses. Cortical grey matter volume, cortical thickness, and cortical surface area were found to be significantly reduced in CHD patients compared to controls. OPNMF identified 12 stable cortex-wide components summarizing the inter-subject variability in cortical thickness, cortical surface area, and local gyrification index. bPLS revealed two significant latent variables (LV) accounting for a total of 82.8% of the variance in the sample, each describing distinct patterns between the brain and cognitive data. LV1 summarized a pattern of belonging to the CHD group, worse scores on most BRIEF-A scales, younger age at MRI, and female sex. This pattern was associated with increased cortical thickness, local gyrification index, and decreased cortical surface area in several OPNMF components. Finally, we identified a positive relationship between the LV1 brain-behaviour pattern and total aortic cross-clamp time in the CHD group, indicating that longer aortic cross-clamp time was associated with worse neurodevelopmental outcomes. In this study, we uncover novel multivariate relationships between ExF and alterations in cortical thickness, surface area, and local gyrification index in adolescents and young adults with CHD using a data-driven approach. Although our findings highlight the important role played by the cortex in higher order cognitive processes, future studies are needed to elucidate the individual contribution of individual and clinical attributes into the deficits observed in this population.

Causal relationships between cortical brain structural alterations and migraine subtypes: a bidirectional Mendelian randomization study of 2,347 neuroimaging phenotypes

BackgroundPrevious studies have shown that migraines are associated with brain structural changes. However, the causal relationships between these changes and migraine, as well as its subtypes, migraine with aura (MA) and migraine without aura (MO), remain largely unclear.MethodsWe utilized genome-wide association study (GWAS) summary statistics from European cohorts for 2,347 cortical structural magnetic resonance imaging (MRI) phenotypes, derived from both T1-weighted and diffusion tensor imaging scans (n = 36,663), with migraine and its subtypes (n = 147,970–375,752). Cortical phenotypes included both macrostructural (e.g., cortical thickness, surface area) and microstructural (e.g., fractional anisotropy, mean diffusivity) features. Genetic correlations were first assessed to identify significant associations, followed by bidirectional Mendelian randomization (MR) analyses to determine causal relationships between these brain phenotypes and migraine, as well as its subtypes (MA and MO). Sensitivity analyses were applied to ensure the robustness of the results.ResultsGenetic correlation analysis identified 510 significant associations between cortical structural phenotypes and migraine across 401 distinct traits. Forward MR analysis revealed nine significant causal effects of cortical structural changes on migraine risk. Specifically, increased cortical thickness and local gyrification index in specific cortical regions were associated with a decreased risk of overall migraine, MA, and MO, while intracellular volume fraction and orientation diffusion index in specific regions increased the risk of MA and MO. Reverse MR analysis demonstrated that MA causally increased mean diffusivity in the insular and frontal opercular cortex. Sensitivity analyses confirmed the robustness of these findings, with no evidence of horizontal pleiotropy or heterogeneity.ConclusionThis study identifies causal relationships between cortical neuroimaging phenotypes and migraine, highlighting potential biomarkers for migraine diagnosis, treatment, and prevention.

Renal medullary perfusion differs from that in renal cortex in patients with sepsis associated acute kidney injury and correlates with renal function prognosis: A prospective cohort study.

Renal perfusion status remains poorly studied at the bedside during sepsis associated acute kidney injury (AKI). The aim of the study is to examine renal cortical and medullary perfusion using renal contrast enhanced ultrasound (CEUS) in septic patients. In this single-center, prospective longitudinal study, septic patients were enrolled. Renal ultrasonography was performed within 24 hours of ICU admission (D1), then repeated at D3, D5 and D7. Each measurement consisted of three destruction replenishment sequences that were recorded for delayed analysis with dedicated software (Vuebox). Renal cortex and medulla perfusion were quantified by measuring time to peak (TTP). Receiver operating characteristic (ROC) analysis was used to evaluate 28-day renal prognosis. The study included 149 septic patients, including 70 non-AKI patients and 79 AKI patients. Both renal cortical and medullary TTP was longer in the AKI group than in the non-AKI group. The difference of TTP between renal cortex and medulla in AKI group was higher than that in the non-AKI group (p = 0.000). Medullary TTP on day 3 had the best performance in predicting the prognosis of 28-day renal function (AUC 0.673, 95% confidence interval 0.528-0.818, p = 0.024), and its cut-off value was 45 s with a sensitivity 52.2% and a specificity of 82.1%. Cortical TTP on day 3 also had the performance in predicting the prognosis of 28-day renal function (AUC 0.657, 95% confidence interval 0.514-0.800, p = 0.039), and its cut-off value was 33 s with a sensitivity 78.3% and a specificity of 55.0%. Renal medullary perfusion alterations differ from those in cortex, with the medulla is worse. Simultaneous and dynamic assessment of cortical and medullary microcirculatory flow alterations necessary. TTP on day 3, especially medullary TTP, seems to be a relatively stable and useful indicator, which correlates with 28-day renal function prognosis in septic patients. Early correction of renal cortical and medullary perfusion alterations reduces the incidence of adverse renal events.

Corticostriatal Maldevelopment in the R6/2 Mouse Model of Juvenile Huntington's Disease.

There is a growing consensus that brain development in Huntington's disease (HD) is abnormal, leading to the idea that HD is not only a neurodegenerative but also a neurodevelopmental disorder. Indeed, structural and functional abnormalities have been observed during brain development in both humans and animal models of HD. However, a concurrent study of cortical and striatal development in a genetic model of HD is still lacking. Here we report significant alterations of corticostriatal development in the R6/2 mouse model of juvenile HD. We examined wildtype (WT) and R6/2 mice at postnatal (P) days 7, 14, and 21. Morphological examination demonstrated early structural and cellular alterations reminiscent of malformations of cortical development, and ex vivo electrophysiological recordings of cortical pyramidal neurons (CPNs) demonstrated significant age- and genotype-dependent changes of intrinsic membrane and synaptic properties. In general, R6/2 CPNs had reduced cell membrane capacitance and increased input resistance (P7 and P14), along with reduced frequency of spontaneous excitatory and inhibitory synaptic events during early development (P7), suggesting delayed cortical maturation. This was confirmed by increased occurrence of GABA A receptor-mediated giant depolarizing potentials at P7. At P14, the rheobase of CPNs was significantly reduced, along with increased excitability. Altered membrane and synaptic properties of R6/2 CPNs recovered progressively, and by P21 they were similar to WT CPNs. In striatal medium-sized spiny neurons (MSNs), a different picture emerged. Intrinsic membrane properties were relatively normal throughout development, except for a transient increase in membrane capacitance at P14. The first alterations in MSNs synaptic activity were observed at P14 and consisted of significant deficits in GABAergic inputs, however, these also were normalized by P21. In contrast, excitatory inputs began to decrease at this age. We conclude that the developing HD brain is capable of compensating for early developmental abnormalities and that cortical alterations precede and are a main contributor of striatal changes. Addressing cortical maldevelopment could help prevent or delay disease manifestations.

Behavioral Changes and Long-Term Cortical Thickness Alterations in Women with Fibromyalgia

ObjectivesThe purpose of this study was to examine long-term brain and behavioral changes in patients with fibromyalgia (FM) compared to healthy individuals. MethodsData from 33 female volunteers with FM and 33 healthy controls women paired by age and school degree were used to analyze the cortical thickness from high-resolution T1-weighted magnetic resonance imaging (MRI) obtained through a 3T-MRI scanner. Additionally, the Toronto Alexithymia Scale, the Positive and Negative Affect Scale, the emotion regulation questionnaire (ERQ), and the Hamilton Depression and Anxiety rating scales were used to evaluate the behavioral changes. ResultsThe findings indicate significant cortical structure differences in the right cerebral hemisphere between groups in the insular anterior cortex precentral and postcentral gyrus (P < .001). The FM group scored higher for alexithymia (P < .01), negative affect (P < .01), anxiety (P < .01), and depression (P < .01) symptoms, on the other hand, scored lower for positive affect (P < .01). No differences were found on the left cerebral hemisphere. Furthermore, there was a negative correlation between the right insular anterior cortex and Toronto Alexithymia Scale (P < .001). ConclusionThis study showed long-term brain and behavioral changes in patients with FM, suggesting notable neurophysiological alterations associated with this chronic pain condition. It provides new insights into how FM may affect brain health and potential biomarkers for the condition.

Association of bacterial overgrowth in the small intestine with cortical thickness and functional connectivity in Parkinson's disease involving mild cognitive impairment.

This study explored potential associations of bacterial overgrowth in the small intestine, as detected based on levels of hydrogen and methane in breath after lactulose consumption, with cortical thickness and resting-state functional connectivity in different brain regions. Prospective comparison of 35 patients with Parkinson's disease (PD) involving mild cognitive impairment, 35 patients with PD with normal cognitive function and 17 healthy controls showed the largest level of hydrogen alone and the largest combined level of hydrogen and methane in patients with mild cognitive impairment. The comparison also revealed a significant negative correlation between those levels and thickness of the right insular cortex. Mild cognitive patients showed different functional connectivity between the right insula and cognition-related brain networks from normal cognitive patients. Our results suggest that bacterial overgrowth in the small intestine may contribute to cortical thinning and alterations in resting-state functional connectivity in PD involving mild cognitive impairment. These insights support and deepen previous observations implicating the gut-brain axis in the neurological disorder.

Cortical microstructural alterations in different stages of Parkinson's disease.

To explore the cortical microstructural alterations in Parkinson's disease (PD) at different stages.149 PD patients and 76 healthy controls were included. PD patients were divided into early stage PD (EPD) (Hoehn-Yahr stage ≤ 2) and moderate-to-late stage PD (MLPD) (Hoehn-Yahr stage ≥ 2.5) according to their Hoehn-Yahr stages. All participants underwent two-shell diffusion MRI and the images were fitted to Neurite Orientation Dispersion and Density Imaging (NODDI) model to obtain the neurite density index (NDI) and orientation dispersion index (ODI) to reflect the cortical microstructure. We used gray matter-based spatial statistics method to compare the voxel-wise cortical NODDI metrics between groups. Partial correlation was used to correlate the NODDI metrics and global composite outcome in PD patients.Compared with healthy controls, EPD patients showed lower ODI in widespread regions, covering bilateral frontal, temporal, parietal and occipital cortices, as well as regional lower NDI in bilateral cingulate and frontal lobes. Compared with healthy controls, MLPD patients showed lower ODI and NDI in more widespread regions. Compared with EPD patients, MLPD patients showed lower ODI in bilateral temporal, parietal and occipital cortices, where the ODI values were negatively correlated with global composite outcome in PD patients.PD patients showed widespread cortical microstructural degeneration, characterized by reduced neurite density and orientation dispersion, and the cortical neuritic microstructure exhibit progressive degeneration during the progression of PD.

Towards a neurodevelopmental model of bipolar disorder: a critical review of trait- and state-related functional neuroimaging in adolescents and young adults.

Neurodevelopmental mechanisms are increasingly implicated in bipolar disorder (BD), highlighting the importance of their study in young persons. Neuroimaging studies have demonstrated a central role for frontotemporal corticolimbic brain systems that subserve processing and regulation of emotions, and processing of reward in adults with BD. As adolescence and young adulthood (AYA) is a time when fully syndromal BD often emerges, and when these brain systems undergo dynamic maturational changes, the AYA epoch is implicated as a critical period in the neurodevelopment of BD. Functional magnetic resonance imaging (fMRI) studies can be especially informative in identifying the functional neuroanatomy in adolescents and young adults with BD (BDAYA) and at high risk for BD (HR-BDAYA) that is related to acute mood states and trait vulnerability to the disorder. The identification of early emerging brain differences, trait- and state-based, can contribute to the elucidation of the developmental neuropathophysiology of BD, and to the generation of treatment and prevention targets. In this critical review, fMRI studies of BDAYA and HR-BDAYA are discussed, and a preliminary neurodevelopmental model is presented based on a convergence of literature that suggests early emerging dysfunction in subcortical (e.g., amygdalar, striatal, thalamic) and caudal and ventral cortical regions, especially ventral prefrontal cortex (vPFC) and insula, and connections among them, persisting as trait-related features. More rostral and dorsal cortical alterations, and bilaterality progress later, with lateralization, and direction of functional imaging findings differing by mood state. Altered functioning of these brain regions, and regions they are strongly connected to, are implicated in the range of symptoms seen in BD, such as the insula in interoception, precentral gyrus in motor changes, and prefrontal cortex in cognition. Current limitations, and outlook on the future use of neuroimaging evidence to inform interventions and prevent the onset of mood episodes in BDAYA, are outlined.

A polarized FGF8 source specifies frontotemporal signatures in spatially oriented cell populations of cortical assembloids

Organoids generating major cortical cell types in distinct compartments are used to study cortical development, evolution and disorders. However, the lack of morphogen gradients imparting cortical positional information and topography in current systems hinders the investigation of complex phenotypes. Here, we engineer human cortical assembloids by fusing an organizer-like structure expressing fibroblast growth factor 8 (FGF8) with an elongated organoid to enable the controlled modulation of FGF8 signaling along the longitudinal organoid axis. These polarized cortical assembloids mount a position-dependent transcriptional program that in part matches the in vivo rostrocaudal gene expression patterns and that is lost upon mutation in the FGFR3 gene associated with temporal lobe malformations and intellectual disability. By producing spatially oriented cell populations with signatures related to frontal and temporal area identity within individual assembloids, this model recapitulates in part the early transcriptional divergence embedded in the protomap and enables the study of cortical area-relevant alterations underlying human disorders.

Subtyping drug-free first-episode major depressive disorder based on cortical surface area alterations

BackgroundMajor depressive disorder (MDD) is recognized as a complex and heterogeneous metal illness, characterized by diverse clinical symptoms and variable treatment outcomes. Previous studies have repeatedly reported alterations in brain morphology in MDD, but findings vary across sample characteristics. Whether this neurobiological substrate could stratify MDD into more homogeneous clinical subgroups thus improving personalized medicine remains unknown. MethodsWe included 65 drug-free patients with first-episode MDD and 66 healthy controls (HCs) and collected their structural MRI data. We performed the surface reconstruction and calculated cortical surface area using Freesurfer. The surface area of 34 Gy matter regions in each hemisphere based on the Desikan-Killiany atlas were extracted for each participant and subtyping results were obtained with the Louvain community detection algorithm. The demographic and clinical characteristics were then compared between MDD subgroups. ResultsTwo subgroups defined by distinct patterns of cortical surface area were identified in first-episode MDD. Subgroup 1 exhibited a significant reduction in surface area across nearly the entire cortex compared to subgroup 2 and HCs, whereas subgroup 2 demonstrated increased surface area than HCs. Further, subgroup 1 exhibited a higher proportion of females, and higher severity of anxiety symptoms compared to subgroup 2. LimitationsThe relatively small sample size. ConclusionsThis study identified two neurobiologically subgroups with distinct alterations in cortical surface area among drug-free patients with first-episode MDD. Our results highlight the promise of in delineating morphological heterogeneity within MDD, particularly in relation to the severity of anxiety symptoms.

Causal association among glaucoma, cerebral cortical structures, and Alzheimer's disease: insights from genetic correlation and Mendelian randomization.

Glaucoma and Alzheimer's disease are critical degenerative neuropathies with global impact. Previous studies have indicated that glaucomatous damage could extend beyond ocular structures, leading to brain alterations potentially associated with Alzheimer's disease risk. This study aimed to explore the causal associations among glaucoma, brain alterations, and Alzheimer's disease. We conducted a comprehensive investigation into the genetic correlation and causality between glaucoma, glaucoma endophenotypes, cerebral cortical surficial area and thickness, and Alzheimer's disease (including late-onset Alzheimer's disease, cognitive performance, and reaction time) using linkage disequilibrium score regression and Mendelian randomization. This study showed suggestive genetic correlations between glaucoma, cortical structures, and Alzheimer's disease. The genetically predicted all-caused glaucoma was nominally associated with a decreased risk of Alzheimer's disease (OR = 0.96, 95% CI: 0.93-0.99, P = 0.013). We found evidence for suggestive causality between glaucoma (endophenotypes) and 20 cortical regions and between 29 cortical regions and Alzheimer's disease (endophenotypes). Four cortical regions were causally associated with cognitive performance or reaction time at a significant threshold (P < 6.2E-04). Thirteen shared cortical regions between glaucoma (endophenotypes) and Alzheimer's disease (endophenotypes) were identified. Our findings complex causal relationships among glaucoma, cerebral cortical structures, and Alzheimer's disease. More studies are required to clarify the mediation effect of cortical alterations in the relationship between glaucoma and Alzheimer's disease.

Changes in cortical thickness: yet another indication of supraspinal adaptations in degenerative cervical myelopathy.

This scientific commentary refers to 'Patterns of cortical thickness alterations in degenerative cervical myelopathy: associations with dexterity and gait dysfunctions', by Muhammad et al. (https://doi.org/10.1093/braincomms/fcae279).

Patterns of cortical thickness alterations in degenerative cervical myelopathy: associations with dexterity and gait dysfunctions.

Degenerative cervical myelopathy (DCM) can lead to significant brain structural reorganization. The association between the cortical changes and specific motor symptoms in DCM has yet to be fully elucidated. We investigated the associations between cortical thickness changes with neurological symptoms, such as dexterity and gait abnormalities, in patients with DCM in a case-control study. A 3 Tesla MRI scanner was used to acquire high-resolution T1-weighted structural scans from 30 right-handed patients with DCM and 22 age-matched healthy controls. Pronounced cortical thinning was observed in DCM patients relative to healthy controls, particularly in the bilateral precentral and prefrontal gyri, left pars triangularis, left postcentral gyrus, right transverse temporal and visual cortices (P ≤ 0.04). Notably, cortical thickness in these regions showed strong correlations with objective motor deficits (P < 0.0001). Specifically, the prefrontal cortex, premotor area and supplementary motor area exhibited significant thickness reductions correlating with diminished dexterity (R2 = 0.33, P < 0.0007; R2 = 0.34, P = 0.005, respectively). Similarly, declines in gait function were associated with reduced cortical thickness in the visual motor and frontal eye field cortices (R2 = 0.39, P = 0.029, R2 = 0.33, P = 0.04, respectively). Interestingly, only the contralateral precuneus thickness was associated with the overall modified Japanese Orthopaedic Association (mJOA) scores (R2 = 0.29, P = 0.003). However, the upper extremity subscore of mJOA indicated an association with the visual cortex and the anterior prefrontal (R2 = 0.48, P = 0.002, R2 = 0.33, P = 0.0034, respectively). In conclusion, our findings reveal patterns of cortical changes correlating with motor deficits, highlighting the significance of combining objective clinical and brain imaging assessments for understanding motor network dysfunction in DCM.

Shared and distinct cortical morphometric alterations in five neuropsychiatric symptoms of Parkinson’s disease

Neuropsychiatric symptoms (including anxiety, depression, apathy, impulse–compulsive behaviors and hallucinations) are among the most common non-motor features of Parkinson’s disease. Whether these symptoms should be considered as a direct consequence of the pathophysiologic mechanisms of Parkinson’s disease is controversial. Morphometric similarity network analysis and epicenter mapping approach were performed on T1-weighted images of 505 patients with Parkinson’s disease and 167 age- and sex-matched healthy participants from Parkinson’s Progression Markers Initiative database to reveal the commonalities and specificities of distinct neuropsychiatric symptoms. Abnormal cortical co-alteration pattern in patients with neuropsychiatric symptoms was in somatomotor, vision and frontoparietal regions, with epicenters in somatomotor regions. Apathy, impulse–compulsive behaviors and hallucinations shares structural abnormalities in somatomotor and vision regions, with epicenters in somatomotor regions. In contrast, the cortical abnormalities and epicenters of anxiety and depression were prominent in the default mode network regions. By embedding each symptom within their co-alteration space, we observed a cluster composed of apathy, impulse–compulsive behaviors and hallucinations, while anxiety and depression remained separate. Our findings indicate different structural mechanisms underlie the occurrence and progression of different neuropsychiatric symptoms. Based upon these results, we propose that apathy, impulse-compulsive behaviors and hallucinations are directly related to damage of motor circuit, while anxiety and depression may be the combination effects of primary pathophysiology of Parkinson’s disease and psychosocial causes.

Unveiling the link between glymphatic function and cortical microstructures in post-traumatic stress disorder

PurposeThe discovery of the glymphatic system, crucial for cerebrospinal and interstitial fluid exchange, has enhanced our grasp of brain protein balance and its potential role in neurodegenerative disease prevention and therapy. Detecting early neurodegenerative shifts via noninvasive biomarkers could be key in identifying at-risk individuals for Alzheimer's disease (AD). Our research explores a diffusion tensor imaging (DTI) method that measures cortical mean diffusivity (cMD), potentially a more sensitive indicator of neurodegeneration than traditional macrostructural methods. Materials and methodsWe analyzed 67 post-traumatic stress disorder (PTSD)-diagnosed veterans from the Alzheimer's Disease Neuroimaging Initiative database. Participants underwent structural MRI, DTI, Aβ PET imaging, and cognitive testing. We focused on the DTI-ALPS technique to assess glymphatic function and its relation to cMD, cortical Aβ accumulation, and thickness, accounting for age and APOE ε4 allele variations. ResultsThe cohort, all male with an average age of 68.1 (SD 3.4), showed a strong inverse correlation between DTI-ALPS and cMD in AD-affected regions, especially in the entorhinal, parahippocampal, and fusiform areas. Higher DTI-ALPS readings were consistently linked with greater cortical thickness, independent of Aβ deposits and genetic risk factors. Age and cMD emerged as inversely proportional predictors of DTI-ALPS, indicating a complex interaction with age. ConclusionThe study confirms a meaningful association between glymphatic efficiency and cMD in AD-sensitive zones, accentuating cortical microstructural alterations in PTSD. It positions DTI-ALPS as a viable biomarker for assessing glymphatic function in PTSD, implicating changes in DTI-ALPS as indicative of glymphatic impairment.

Shared genetic architecture of cortical thickness alterations in major depressive disorder and schizophrenia

BackgroundMajor depressive disorder (MDD) and schizophrenia (SCZ) are heritable brain disorders characterized by alterations in cortical thickness. However, the shared genetic basis for cortical thickness changes in these disorders remains unclear. MethodsWe conducted a systematic literature search on cortical thickness in MDD and SCZ through PubMed and Web of Science. A coordinate-based meta-analysis was performed to identify cortical thickness changes. Additionally, utilizing summary statistics from the largest genome-wide association studies for depression (Ncase = 268,615, Ncontrol = 667,123) and SCZ (Ncase = 53,386, Ncontrol = 77,258), we explored shared genomic loci using conjunctional false discovery rate (conjFDR) analysis. Transcriptome-neuroimaging association analysis was then employed to identify shared genes associated with cortical thickness alterations, and enrichment analysis was finally carried out to elucidate the biological significance of these genes. ResultsOur search yielded 34 MDD (Ncase = 1621, Ncontrol = 1507) and 19 SCZ (Ncase = 1170, Ncontrol = 1043) neuroimaging studies for cortical thickness meta-analysis. Specific alterations in the left supplementary motor area were observed in MDD, while SCZ exhibited widespread reductions in various brain regions, particularly in the frontal and temporal areas. The conjFDR approach identified 357 genomic loci jointly associated with MDD and SCZ. Within these loci, 55 genes were found to be associated with cortical thickness alterations in both disorders. Enrichment analysis revealed their involvement in nervous system development, apoptosis, and cell communication. ConclusionThis study revealed the shared genetic architecture underlying cortical thickness alterations in MDD and SCZ, providing insights into common neurobiological pathways. The identified genes and pathways may serve as potential transdiagnostic markers, informing precision medicine approaches in psychiatric care.

Cortical morphological alterations in cognitively normal Parkinson’s disease with severe hyposmia

Olfactory dysfunction is a common non-motor symptom of Parkinson’s disease(PD) and may hold valuable insights into the disease’s underlying pathophysiology. This study aimed to investigate cortical morphometry alterations in PD patients with severe hyposmia(PD-SH) and mild hyposmia(PD-MH) using surface-based morphometry(SBM) methods. Participants included 36 PD-SH patients, 38 PD-MH patients, and 40 healthy controls(HCs). SBM analysis revealed distinct patterns of cortical alterations in PD-SH and PD-MH patients. PD-MH patients exhibited reduced cortical thickness in the right supramarginal gyrus, while PD-SH patients showed widespread cortical thinning in regions including the bilateral pericalcarine cortex, bilateral lingual gyrus, left inferior parietal cortex, left lateral occipital cortex, right pars triangularis, right cuneus, and right superior parietal cortex. Moreover, PD-SH patients displayed reduced cortical thickness in the right precuneus compared to PD-MH patients. Fractal dimension analysis indicated increased cortical complexity in PD-MH patients’ right superior temporal cortex and right supramarginal gyrus, as well as decreased complexity in the bilateral postcentral cortex, left superior parietal cortex, and right precentral cortex. Similarly, cortical gyrification index and cortical sulcal depth exhibited heterogeneous patterns of changes in PD-SH and PD-MH patients compared to HCs. These findings underscore the multifaceted nature of olfactory impairment in PD, with distinct patterns of cortical morphometry alterations associated with different degrees of hyposmia. The observed discrepancies in brain regions showing alterations reflect the complexity of PD’s pathophysiology. These insights contribute to a deeper understanding of olfactory dysfunction in PD and provide potential avenues for early diagnosis and targeted interventions.

Associations of polygenic risk scores differentiating attention-deficit hyperactivity disorder from autism spectrum disorder with cognitive and cortical alterations in Schizophrenia patients.

Schizophrenia (SCZ) is a clinically and genetically heterogeneous disorder that shares genetic factors with autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). A genome-wide association study (GWAS) differentiating ADHD from ASD was performed recently. In this study, we investigated whether polygenic risk scores (PRSs) differentiating ASD from ADHD are associated with cognitive impairments and alterations in cortical structures in SCZ patients. Based on the GWAS data (9,315 ASD and 11,964 ADHD patients), PRSs differentiating ADHD from ASD (indicating a greater risk of ADHD and a lower risk of ASD) were calculated for SCZ patients (n = 168). Cognitive performance, including verbal comprehension (VC), perceptual organization (PO), working memory (WM), and processing speed (PS), was assessed using the WAIS-III (n = 145). The surface areas and cortical thicknesses of 34 bilateral brain regions were extracted using FreeSurfer (n = 126). We examined the associations of these PRSs with cognitive performance and cortical structures in SCZ patients. Among the four cognitive domains, a higher PRS, indicating a greater risk of ADHD, was associated with impaired WM in SCZ patients (beta=-0.21, p = 0.012). A lower PRS, indicating a greater risk of ASD, was associated with decreased surface areas of the left medial orbitofrontal (beta = 0.21, p = 8.29 × 10- 4), left entorhinal (beta = 0.21, p = 0.025), left postcentral (beta = 0.18, p = 7.52 × 10- 3), right fusiform (beta = 0.17, p = 6.64 × 10- 3), and left fusiform cortices (beta = 0.17, p = 7.77 × 10- 3) in SCZ patients. A higher PRS, indicating a greater risk of ADHD, was associated with decreased cortical thickness in the bilateral transverse temporal regions (left, beta=-0.17, p = 0.039; right, beta=-0.17, p = 0.045). Our study revealed a relationship between genetic factors that differentiate ADHD patients from ASD patients and both cortical structure and cognitive performance in SCZ patients. These findings suggest that the heterogeneity of SCZ might be partly derived from genetic factors related to neurodevelopmental and psychiatric disorders other than SCZ.