Association between air pollution exposure and brain cortical thickness throughout the lifespan: A systematic review.

Increasing research has focused on the impact of air pollution on brain health. As the prevalence of air pollution is increasing alongside other environmental harms, the importance of studying the effects of these changes on human health has become more significant. Additionally, gaining insight into how air pollution exposure, measured at different points in the lifespan, can affect brain structure is critical, as this could be a precursor to cognitive decline later in life. The purpose of this review was to synthesize the literature on the association between air pollutant exposure and cortical thickness, a structural change with known associations with later cognition and neurodegenerative disease. After screening, twelve studies were included in this systematic review. Across a majority of studies, results suggest significant associations between increasing air pollution exposure and decreases in cortical thickness, primarily in areas such as prefrontal cortex, precuneus, and temporal regions of the brain. These results did differ somewhat between age groups and different air pollutants, with the most prominent results being found with exposure to PM2.5, the smallest particulate matter size included in the review. In the future, it is important to continue studying cortical thickness as it is essential to brain functioning and can be influential in disease progression. Furthermore, conducting more longitudinal studies in which air pollution is measured as a cumulation throughout the lifespan would help elucidate when exposure is most impactful and when brain structural changes become observable.

Association of Compensatory Mechanisms in Prefrontal Cortex and Impaired Anatomical Correlates in Semantic Verbal Fluency: A Functional Near-Infrared Spectroscopy Study.

OBJECTIVE: Semantic verbal fluency (SVF) engages cognitive functions such as executive function, mental flexibility, and semantic memory. Left frontal and temporal lobes, particularly the left inferior frontal gyrus (IFG), are crucial for SVF. This study investigates SVF and associated neural processing in older adults with mild SVF impairment and the relationship between structural abnormalities in the left IFG and functional activation during SVF in those individuals. METHODS: Fifty-four elderly individuals with modest level of mild cognitive impairment whose global cognition were preserved to normal but exhibited mild SVF impairment were participated. Prefrontal oxyhemoglobin (HbO2) activation and frontal cortical thickness were collected from the participants using functional near-infrared spectroscopy (fNIRS) and brain MRI, respectively. We calculated the ß coefficient of HbO2 activation induced by tasks, and performed correlation analysis between SVF induced HbO2 activation and cortical thickness in frontal areas. RESULTS: We observed increased prefrontal activation during SVF task compared to the resting and control task. The activation distinct to SVF was identified in the midline superior and left superior prefrontal regions (p<0.05). Correlation analysis revealed an inverse relationship between SVF-specific activation and cortical thickness in the left IFG, particularly in pars triangularis (r(54)=-0.304, p=0.025). CONCLUSION: The study contributes to understanding the relationship between reduced cortical thickness in left IFG and increased functional activity in cognitively normal individuals with mild SVF impairment, providing implications on potential compensatory mechanisms for cognitive preservation.

Structural brain characteristics of epilepsy patients with comorbid migraine without aura.

Migraine is a common bi-directional comorbidity of epilepsy, indicating potential complex interactions between the two conditions. However, no previous studies have used brain morphology analysis to assess possible interactions between epilepsy and migraine. Voxel-based morphometry (VBM), surface-based morphometry (SBM), and structural covariance networks (SCNs) can be used to detect morphological changes with high accuracy. We recruited 30 individuals with epilepsy and comorbid migraine without aura (EM), along with 20 healthy controls (HC) and 30 epilepsy controls (EC) without migraine. We used VBM, SBM, and SCN analysis to compare differences in gray matter volume, cortical thickness, and global level and local level graph theory indexes between the EM, EC, and HC groups to investigate structural brain changes in the EM patients. VBM analysis showed that the EM group had gray matter atrophy in the right temporal pole compared with the HC group (p < 0.001, false discovery rate correction [FDR]). Furthermore, the headache duration in the EM group was negatively correlated with the gray matter volume of the right temporal pole (p < 0.05). SBM analysis showed cortical atrophy in the left insula, left posterior cingulate gyrus, left postcentral gyrus, left middle temporal gyrus, and left fusiform gyrus in the EM compared with the HC group (p < 0.001, family wise error correction). We found a positive correlation between headache frequency and the cortical thickness of the left middle temporal gyrus (p < 0.05). SCN analysis revealed no differences in global parameters between the three groups. The area under the curve (AUC) of the nodal betweenness centrality in the right postcentral gyrus was lower in the EM group compared with the HC group (p < 0.001, FDR correction), and the AUC of the nodal degree in the right fusiform gyrus was lower in the EM group compared with the EC group (p < 0.001, FDR correction). We found clear differences in brain structure in the EM patients compared with the HC group. Accordingly, migraine episodes may influence brain structure in epilepsy patients. Conversely, abnormal brain structure may be an important factor in the development of epilepsy with comorbid migraine without aura. Further studies are needed to investigate the role of brain structure in individuals with epilepsy and comorbid migraine without aura.

The relationship between structural properties of frontal cortical regions and response inhibition in 6-14-year-old children.

Development of attentional skills and inhibitory control rely on maturational changes in the brain across childhood and youth. However, both brain anatomy and different components of attention and inhibition show notable individual variation. Research on ADHD and inhibitory training and control have shown that variations in the thickness and surface area of particularly inferior cortical structures are associated with attentional control. However, the intricacies of how the development of inhibitory control is associated with the anatomical variations beyond the general age- and gender-dependent differences have not been resolved. Here, we sought to address these questions by quantifying the cortical thickness and surface area in frontal cortical regions and inhibitory control using the stop signal task performance in 6-14-year-old children. Our results showed that the thickness of the left medial orbitofrontal cortex and the surface area of the left caudal anterior cingulate were associated with the inhibitory performance, beyond the variance that could be explained by the subjects' age and gender. The results highlight the importance of factoring in anatomical variations when following attentional development and the importance of evaluating multiple anatomical measures when aiming to link the properties of cortical structures with variations in cognitive performance.

Interactive roles of preterm-birth and socioeconomic status in cortical thickness of language-related brain structures: Findings from the Adolescent Brain Cognitive Development (ABCD) study.

Preterm-born (PTB) children are at an elevated risk for neurocognitive difficulties in general and language difficulties more specifically. Environmental factors such as socio-economic status (SES) play a key role for Term children's language development. SES has been shown to predict PTB children's behavioral developmental trajectories, sometimes surpassing its role for Term children. However, the role of SES in the neurocognitive basis of PTB children's language development remains uncharted. Here, we aimed to evaluate the role of SES in the neural basis of PTB children's language performance. Leveraging the Adolescent Brain Cognitive Development (ABCD) Study, the largest longitudinal study of adolescent brain development and behavior to date, we showed that prematurity status (PTB versus Term) and multiple aspects of SES additively predict variability in cortical thickness, which is in turn related to children's receptive vocabulary performance. We did not find evidence to support the differential role of environmental factors for PTB versus Term children, underscoring that environmental factors are significant contributors to development of both Term and PTB children. Taken together, our results suggest that the environmental factors influencing language development might exhibit similarities across the full spectrum of gestational age.

Anatomical measurements and field modeling to assess transcranial magnetic stimulation motor and non-motor effects.

OBJECTIVE: Explore how anatomical measurements and field modeling can be leveraged to improve investigations of transcranial magnetic stimulation (TMS) effects on both motor and non-motor TMS targets. METHODS: TMS motor effects (targeting the primary motor cortex [M1]) were evaluated using the resting motor threshold (rMT), while TMS non-motor effects (targeting the superior temporal gyrus [STG]) were assessed using a pain memory task. Anatomical measurements included scalp-cortex distance (SCD) and cortical thickness (CT), whereas field modeling encompassed the magnitude of the electric field (E) induced by TMS. RESULTS: Anatomical measurements and field modeling values differed significantly between M1 and STG. For TMS motor effects, rMT was correlated with SCD, CT, and E values at M1 (p < 0.05). No correlations were found between these metrics for the STG and TMS non-motor effects (pain memory; all p-values > 0.05). CONCLUSION: Although anatomical measurements and field modeling are closely related to TMS motor effects, their relationship to non-motor effects - such as pain memory - appear to be much more tenuous and complex, highlighting the need for further advancement in our use of TMS and virtual lesion paradigms.

Starting the pill during adolescence: Age of onset and duration of use influence morphology of the hippocampus and ventromedial prefrontal cortex.

From adolescence, women become more likely to experience fear dysregulation. Oral contraceptives (OCs) can modulate the brain regions involved in fear processes. OCs are generally used for years and often initiated during adolescence, a sensitive period where certain brain regions involved in the fear circuitry are still undergoing important reorganization. It remains unknown whether OC use during adolescence may induce long-lasting changes in the fear circuitry. This study aimed to examine whether age of onset moderated the relationship between duration of use and fear-related brain structures. We collected structural MRI data in 98 healthy adult women (61 current users, 37 past users) and extracted grey matter volumes (GMV) and cortical thickness (CT) of key regions of the fear circuitry. Non-linear multiple regressions revealed interaction effects between age of onset and quadratic duration of use on GMV of the right hippocampus and right ventromedial prefrontal cortex (vmPFC). Among women who initiated OCs earlier in adolescence, a short duration of use was associated with smaller hippocampal GMV and thicker vmPFC compared to a longer duration of use. For both GMV and CT of the right vmPFC, women with an early OC onset had more grey matter at a short duration of use than those with a later onset. Our results suggest that OC use earlier in adolescence may induce lasting effects on structural correlates of fear learning and its regulation. These findings support further investigation into the timing of OC use to better comprehend how OCs could disrupt normal brain development processes.

Impact of excessive abdominal obesity on brain microstructural abnormality in schizophrenia.

Significant evidence links obesity and schizophrenia (SZ), but the brain associations are still largely unclear. 48 people with SZ were divided into two subgroups: patients with lower waist circumference (SZ-LWC: n = 24) and patients with higher waist circumference (SZ-HWC: n = 24). Healthy controls (HC) were included for comparison (HC: n = 27). Using tract-based spatial statistics, we compared fractional anisotropy (FA) of the whole-brain white matter skeleton between these three groups (SZ-LWC, SZ-HWC, HC). Using Free Surfer, we compared whole-brain cortical thickness and the selected subcortical volumes between the three groups. FA of widespread white matter and the mean cortical thickness in the right temporal lobe and insular cortex were significantly lower in the SZ-HWC group than in the HC group. The FA of regional white matter was significantly lower in the SZ-LWC group than in the HC group. There were no significant differences in mean subcortical volumes between the groups. Additionally, the cognitive performances were worse in the SZ-HWC group, who had more severe triglycerides elevation. This study provides evidence for microstructural abnormalities of white matter, cortical thickness and neurocognitive deficits in SZ patients with excessive abdominal obesity.

Poor sleep and decreased cortical thickness in veterans with mild traumatic brain injury and post-traumatic stress disorder.

BACKGROUND: Poor sleep quality has been associated with changes in brain volume among veterans, particularly those who have experienced mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD). This study sought to investigate (1) whether poor sleep quality is associated with decreased cortical thickness in Iraq and Afghanistan war veterans, and (2) whether these associations differ topographically depending on the presence or absence of mTBI and PTSD. METHODS: A sample of 440 post-9/11 era U.S. veterans enrolled in the Translational Research Center for Traumatic Brain Injury and Stress Disorders study at VA Boston, MA from 2010 to 2022 was included in the study. We examined the relationship between sleep quality, as measured by the Pittsburgh Sleep Quality Index (PSQI), and cortical thickness in veterans with mTBI (n = 57), PTSD (n = 110), comorbid mTBI and PTSD (n = 129), and neither PTSD nor mTBI (n = 144). To determine the topographical relationship between subjective sleep quality and cortical thickness in each diagnostic group, we employed a General Linear Model (GLM) at each vertex on the cortical mantle. The extent of topographical overlap between the resulting statistical maps was assessed using Dice coefficients. RESULTS: There were no significant associations between PSQI and cortical thickness in the group without PTSD or mTBI (n = 144) or in the PTSD-only group (n = 110). In the mTBI-only group (n = 57), lower sleep quality was significantly associated with reduced thickness bilaterally in frontal, cingulate, and precuneus regions, as well as in the right parietal and temporal regions (ß = -0.0137, P < 0.0005). In the comorbid mTBI and PTSD group (n = 129), significant associations were observed bilaterally in frontal, precentral, and precuneus regions, in the left cingulate and the right parietal regions (ß = -0.0094, P < 0.0005). Interaction analysis revealed that there was a stronger relationship between poor sleep quality and decreased cortical thickness in individuals with mTBI (n = 186) compared to those without mTBI (n = 254) specifically in the frontal and cingulate regions (ß = -0.0077, P < 0.0005). CONCLUSIONS: This study demonstrates a significant relationship between poor sleep quality and lower cortical thickness primarily within frontal regions among individuals with both isolated mTBI or comorbid diagnoses of mTBI and PTSD. Thus, if directionality is established in longitudinal and interventional studies, it may be crucial to consider addressing sleep in the treatment of veterans who have sustained mTBI.

Multivariate brain-cognition associations in euthymic bipolar disorder.

BACKGROUND: People with bipolar disorder (BD) tend to show widespread cognitive impairment compared to healthy controls. Impairments in processing speed (PS), attention and executive function (EF) may represent 'core' impairments that have a role in wider cognitive dysfunction. Cognitive impairments appear to relate to structural brain abnormalities in BD, but whether core deficits are related to particular brain regions is unclear and much of the research on brain-cognition associations is limited by univariate analysis and small samples. METHODS: Euthymic BD patients (n = 56) and matched healthy controls (n = 26) underwent T1-weighted MRI scans and completed neuropsychological tests of PS, attention and EF. We utilised public datasets to develop normative models of cortical thickness (n = 5977) to generate robust estimations of cortical abnormalities in patients. Canonical correlation analysis was used to assess multivariate brain-cognition associations in BD, controlling for age, sex and premorbid IQ. RESULTS: BD showed impairments on tests of PS, attention and EF, and abnormal cortical thickness in several brain regions compared to healthy controls. Impairments in tests of PS and EF were most strongly associated with cortical thickness in the left inferior temporal, right entorhinal and right temporal pole areas. CONCLUSION: Impairments in PS, attention and EF can be observed in euthymic BD and may be related to abnormal cortical thickness in temporal regions. Future research should continue to leverage normative modelling and multivariate methods to examine complex brain-cognition associations in BD. Future research may benefit from exploring covariance between traditional brain structural morphological metrics such as cortical thickness, cortical volume and surface area.

Executive function and cortical thickness in biomarker aMCI.

INTRODUCTION: Memory deficits are the primary symptom in amnestic Mild Cognitive Impairment (aMCI); however, executive function (EF) deficits are common. The current study examined EF in aMCI based upon amyloid status (A+/A-) and regional atrophy in signature areas of Alzheimer's disease (AD). METHOD: Participants included 110 individuals with aMCI (A+ = 66; A- = 44) and 33 cognitively healthy participants (HP). EF was assessed using four neuropsychological assessment measures. The cortical thickness of the AD signature areas was calculated using structural MRI data. RESULTS: A + had greater EF deficits and cortical atrophy relative to A - in the supramarginal gyrus and superior parietal lobule. A - had greater EF deficits relative to HP, but no difference in signature area cortical thickness. DISCUSSION: The current study found that the degree of EF deficits in aMCI are a function of amyloid status and cortical thinning in the parietal cortex.

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

BACKGROUND: Major 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. METHODS: We 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. RESULTS: Our 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. CONCLUSION: This 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.

Baseline brain volume predicts home-based transcranial direct current stimulation effects on inattention in adults with attention-deficit/hyperactivity disorder.

BACKGROUND: Home-based transcranial direct current stimulation (Hb-tDCS) is a non-invasive brain stimulation technique that utilizes low-intensity electric currents delivered via scalp electrodes to modulate brain activity. It holds significant promise for addressing inattention in adults with attention-deficit/hyperactivity disorder (ADHD). However, its effectiveness varies among individuals, and predicting outcomes remains uncertain, partially due to the influence of individual differences in ADHD-related brain anatomy. METHODS: We analyzed data from a subsample, composed by twenty-nine adult patients with ADHD, of the Treatment of Inattention Symptoms in Adult Patients with ADHD (TUNED) trial. Fourteen patients underwent active anodal right cathodal left dorsolateral prefrontal cortex (DLPFC) Hb-tDCS for 4 weeks and fifteen received sham-related tDCS intervention. Inattention outcome was evaluated at both baseline and endpoint (4th week). Baseline structural measures of the DLPFC, anterior cingulate cortex (ACC) and subcortical structures, previously associated with ADHD, were quantified. Several linear mixed models, with a three-way interaction between the fixed predictors brain volume or thickness, time, and treatment were calculated. Multiple comparison corrections were applied using the Benjamini-Hochberg method. RESULTS: Baseline volume of the left DLPFC regions middle frontal gyrus (t (25) = 3.33, p-adjusted = 0.045, Cohen's d = 1.33, 95% CI = [0.45, 2.19]), inferior frontal gyrus (orbital part) (t (25) = 3.10, p-adjusted = 0.045, Cohen's d = 1.24, 95% CI = [0.37, 2.08]), and of the left ACC supragenual (t (25) = 3.15, p-adjusted = 0.045, Cohen's d = 1.26, 95% CI = [0.39, 2.11]) presented significant association with the inattentive score improvement only in the active tDCS group. More specifically, the smaller these regions were, the more the symptoms improved following anodal right cathodal left DLPFC Hb-tDCS. CONCLUSION: Hb-tDCS was associated with greater improvement in brain areas related to attention regulation. Brain MRI can be potentially used to predict clinical response to tDCS in ADHD adults.

Retinal Microvasculature Causally Affects the Brain Cortical Structure: A Mendelian Randomization Study.

Purpose: To reveal the causality between retinal vascular density (VD), fractal dimension (FD), and brain cortex structure using Mendelian randomization (MR). Design: Cross-sectional study. Participants: Genome-wide association studies of VD and FD involving 54 813 participants from the United Kingdom Biobank were used. The brain cortical features, including the cortical thickness (TH) and surface area (SA), were extracted from 51 665 patients across 60 cohorts. Surface area and TH were measured globally and in 34 functional regions using magnetic resonance imaging. Methods: Bidirectional univariable MR (UVMR) was used to detect the causality between FD, VD, and brain cortex structure. Multivariable MR (MVMR) was used to adjust for confounding factors, including body mass index and blood pressure. Main Outcome Measures: The global and regional measurements of brain cortical SA and TH. Results: At the global level, higher VD is related to decreased TH (ß = -0.0140 mm, 95% confidence interval: -0.0269 mm to -0.0011 mm, P = 0.0339). At the functional level, retinal FD is related to the TH of banks of the superior temporal sulcus and transverse temporal region without global weighted, as well as the SA of the posterior cingulate after adjustment. Vascular density is correlated with the SA of subregions of the frontal lobe and temporal lobe, in addition to the TH of the inferior temporal, entorhinal, and pars opercularis regions in both UVMR and MVMR. Bidirectional MR studies showed a causation between the SA of the parahippocampal and cauda middle frontal gyrus and retinal VD. No pleiotropy was detected. Conclusions: Fractal dimension and VD causally influence the cortical structure and vice versa, indicating that the retinal microvasculature may serve as a biomarker for cortex structural changes. Our study provides insights into utilizing noninvasive fundus images to predict cortical structural deteriorations and neuropsychiatric disorders. Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Blind individuals' enhanced ability to sense their own heartbeat is related to the thickness of their occipital cortex.

Blindness is associated with heightened sensory abilities, such as improved hearing and tactile acuity. Moreover, recent evidence suggests that blind individuals are better than sighted individuals at perceiving their own heartbeat, suggesting enhanced interoceptive accuracy. Structural changes in the occipital cortex have been hypothesized as the basis of these behavioral enhancements. Indeed, several studies have shown that congenitally blind individuals have increased cortical thickness within occipital areas compared to sighted individuals, but how these structural differences relate to behavioral enhancements is unclear. This study investigated the relationship between cardiac interoceptive accuracy and cortical thickness in 23 congenitally blind individuals and 23 matched sighted controls. Our results show a significant positive correlation between performance in a heartbeat counting task and cortical thickness only in the blind group, indicating a connection between structural changes in occipital areas and blind individuals' enhanced ability to perceive heartbeats.

CAT: a computational anatomy toolbox for the analysis of structural MRI data.

A large range of sophisticated brain image analysis tools have been developed by the neuroscience community, greatly advancing the field of human brain mapping. Here we introduce the Computational Anatomy Toolbox (CAT)-a powerful suite of tools for brain morphometric analyses with an intuitive graphical user interface but also usable as a shell script. CAT is suitable for beginners, casual users, experts, and developers alike, providing a comprehensive set of analysis options, workflows, and integrated pipelines. The available analysis streams-illustrated on an example dataset-allow for voxel-based, surface-based, and region-based morphometric analyses. Notably, CAT incorporates multiple quality control options and covers the entire analysis workflow, including the preprocessing of cross-sectional and longitudinal data, statistical analysis, and the visualization of results. The overarching aim of this article is to provide a complete description and evaluation of CAT while offering a citable standard for the neuroscience community.

Distinct Patterns of Brain Atrophy in Amnestic Mild Cognitive Impairment and Motoric Cognitive Risk Syndromes.

INTRODUCTION: Motoric cognitive risk (MCR) and amnestic mild cognitive impairment (aMCI) syndromes are each reliable predictors of incident Alzheimer's disease (AD), but MCR may be a stronger predictor of vascular dementia than AD. This study contrasted cortical and hippocampal atrophy patterns in MCR and aMCI. METHODS: Cross-sectional data from 733 older adults without dementia or disability (M age = 73.6; 45% women) in the multicountry MCR consortium were examined. MCR was defined as presence of slow gait and cognitive concerns. Amnestic MCI was defined as poor episodic memory performance and cognitive concerns. Cortical thickness and hippocampal volumes were quantified from structural MRIs. Multivariate and univariate general linear models were used to examine associations between cortical thickness and hippocampal volume in MCR and aMCI, adjusting for age, sex, education, total intracranial volume, white matter lesions, and study site. RESULTS: The prevalence of MCR and aMCI was 7.64% and 12.96%, respectively. MCR was associated with widespread cortical atrophy, including prefrontal, insular, cingulate, motor, parietal, and temporal atrophy. aMCI was associated with hippocampal atrophy. CONCLUSION: Distinct patterns of atrophy were associated with MCR and aMCI. A distributed pattern of cortical atrophy - that is more consistent with VaD or mixed dementia- was observed in MCR. A more restricted pattern of atrophy - that is more consistent with AD - was observed in aMCI. The biological underpinnings of MCR and aMCI likely differ and may require tailored interventions.

Neural correlates of anhedonia in young adults with subthreshold depression: A graph theory approach for cortical-subcortical structural covariance.

BACKGROUND: Anhedonia is an enduring symptom of subthreshold depression (StD) and predict later onset of major depressive disorder (MDD). Brain structural covariance describes the inter-regional distribution of morphological changes compared to healthy controls (HC) and reflects brain maturation and disease progression. We investigated neural correlates of anhedonia from the structural covariance. METHODS: T1-weighted brain magnetic resonance images were acquired from 79 young adults (26 StD, 30 MDD, and 23 HC). Intra-individual structural covariance networks of 68 cortical surface area (CSAs), 68 cortical thicknesses (CTs), and 14 subcortical volumes were constructed. Group-level hubs and principal edges were defined using the global and regional graph metrics, compared between groups, and examined for the association with anhedonia severity. RESULTS: Global network metrics were comparable among the StD, MDD, and HC. StD exhibited lower centralities of left pallidal volume than HC. StD showed higher centralities than HC in the CSAs of right rostral anterior cingulate cortex (ACC) and pars triangularis, and in the CT of left pars orbitalis. Less anhedonia was associated with higher centralities of left pallidum and right amygdala, higher edge betweenness centralities in the structural covariance (EBSC) of left postcentral gyrus-parahippocampal gyrus and LIPL-right amygdala. More anhedonia was associated with higher centralities of left inferior parietal lobule (LIPL), left postcentral gyrus, left caudal ACC, and higher EBSC of LIPL-left postcentral gyrus, LIPL-right lateral occipital gyrus, and left caudal ACC-parahippocampal gyrus. LIMITATIONS: This study has a cross-sectional design. CONCLUSIONS: Structural covariance of brain morphologies within the salience and limbic networks, and among the salience-limbic-default mode-somatomotor-visual networks, are possible neural correlates of anhedonia in depression.

Blood-derived microRNAs are related to cognitive domains in the general population.

INTRODUCTION: Blood-derived microRNAs (miRNAs) are potential candidates for detecting and preventing subclinical cognitive dysfunction. However, replication of previous findings and identification of novel miRNAs associated with cognitive domains, including their relation to brain structure and the pathways they regulate, are still lacking. METHODS: We examined blood-derived miRNAs and miRNA co-expression clusters in relation to cognitive domains, structural magnetic resonance imaging measures, target gene expression, and genetic variants in 2869 participants of a population-based cohort. RESULTS: Five previously identified and 14 novel miRNAs were associated with cognitive domains. Eleven of these were also associated with cortical thickness and two with hippocampal volume. Multi-omics analysis showed that certain identified miRNAs were genetically influenced and regulated genes in pathways like neurogenesis and synapse assembly. DISCUSSION: We identified miRNAs associated with cognitive domains, brain regions, and neuronal processes affected by aging and neurodegeneration, making them promising candidate blood-based biomarkers or therapeutic targets of subclinical cognitive dysfunction. HIGHLIGHTS: We investigated the association of blood-derived microRNAs with cognitive domains. Five previously identified and 14 novel microRNAs were associated with cognition. Eleven cognition-related microRNAs were also associated with cortical thickness. Identified microRNAs were linked to genes associated with neuronal functions. Results provide putative biomarkers or therapeutic targets of cognitive aging.

Mapping brain morphology to cognitive deficits: a study on PD-CRS scores in Parkinson's disease with mild cognitive impairment.

Background: The Parkinson's Disease-Cognitive Rating Scale (PD-CRS) is a widely used tool for detecting mild cognitive impairment (MCI) in Parkinson's Disease (PD) patients, however, the neuroanatomical underpinnings of this test's outcomes require clarification. This study aims to: (a) investigate cortical volume (CVol) and cortical thickness (CTh) disparities between PD patients exhibiting mild cognitive impairment (PD-MCI) and those with preserved cognitive abilities (PD-IC); and (b) identify the structural correlates in magnetic resonance imaging (MRI) of overall PD-CRS performance, including its subtest scores, within a non-demented PD cohort. Materials and methods: This study involved 51 PD patients with Hoehn & Yahr stages I-II, categorized into two groups: PD-IC (n = 36) and PD-MCI (n = 15). Cognitive screening evaluations utilized the PD-CRS and the Montreal Cognitive Assessment (MoCA). PD-MCI classification adhered to the Movement Disorder Society Task Force criteria, incorporating extensive neuropsychological assessments. The interrelation between brain morphology and cognitive performance was determined using FreeSurfer. Results: Vertex-wise analysis of the entire brain demonstrated a notable reduction in CVol within a 2,934 mm2 cluster, encompassing parietal and temporal regions, in the PD-MCI group relative to the PD-IC group. Lower PD-CRS total scores correlated with decreased CVol in the middle frontal, superior temporal, inferior parietal, and cingulate cortices. The PD-CRS subtests for Sustained Attention and Clock Drawing were associated with cortical thinning in distinct regions: the Clock Drawing subtest correlated with changes in the parietal lobe, insula, and superior temporal cortex morphology; while the PD-CRS frontal-subcortical scores presented positive correlations with CTh in the transverse temporal, medial orbitofrontal, superior temporal, precuneus, fusiform, and supramarginal regions. Additionally, PD-CRS subtests for Semantic and Alternating verbal fluency were linked to CTh changes in orbitofrontal, temporal, fusiform, insula, and precentral regions. Conclusion: PD-CRS performance mirrors neuroanatomical changes across extensive fronto-temporo-parietal areas, covering both lateral and medial cortical surfaces, in PD patients without dementia. The observed changes in CVol and CTh associated with this cognitive screening tool suggest their potential as surrogate markers for cognitive decline in PD. These findings warrant further exploration and validation in multicenter studies involving independent patient cohorts.