Thalamic Volume Research Articles

The volume of the thalamus and hippocampus in a right-handed female episodic migraine group

Background/aimMigraine is a disabling headache with clinical and radiological complications. The aim of this study was to investigate the volume of the thalamus and hippocampus in migraineurs, the role of white matter lesions (WMLs), and the migraine characteristics in volume changes.MethodsBrain MRIs of 161 right-handed female episodic migraine patients and 40 right-handed, age-related, healthy women were performed. Left and right thalamus segmentation was performed on the 3D MPRAGE images using the Freesurfer 5.3 image analysis suite. Hippocampal subfield segmentation was based on a novel statistical atlas built primarily upon ultra-high-resolution ex vivo MRI data.ResultsThe left hippocampus had a smaller and the left thalamus had a larger total volume than the right one in both the control (p < 0.001) and migraine groups (p <0.001). Patients with white matter lesions (L+) showed smaller right thalamus and right hippocampal tail volumes than patients without lesions (L–) (p = 0.002 and p = 0.015, respectively) and controls (p = 0.039 and p = 0.025, respectively). For the right hippocampal body, we found significantly smaller volume in L+ patients when compared to L– patients (p = 0.018) and a similar trend when compared to the control group (p = 0.064). Patients without aura (A–) showed a larger right hippocampus (p = 0.029), right hippocampal body (p = 0.012), and tail volumes (p = 0.011) than patients with aura (A+). Inverse correlations were found between attack frequency and the volumes of the left and right hippocampal tails (p = 0.018 and p = 0.008, respectively).ConclusionThese findings indicate that WMLs may influence the volume of the right thalamus and hippocampus, while migraine aura and attack frequency may lead to volume changes in different parts of the hippocampi in migraine patients. These data support the necessity of effective migraine management to limit subcortical volume loss in migraineurs.

Structural and Functional Alterations of Motor-Thalamus in Different Motor Subtype of Parkinson’s Disease: An Individual Study

This study aimed to investigate the structural and functional alterations occurring within bilateral premotor thalamus (mPMtha) in motor subtypes of Parkinson's disease (PD). Sixty-one individuals with instability and gait difficulty (PIGD) subtype, 60individuals with tremor-dominant (TD) subtype and 66healthy controls (HCs) participated in the study. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) and 3D T1-weighted (3DT1) scans. Functional connectivity (FC) analysis and Voxel-based morphometry (VBM) analysis were performed to evaluate the function and volume of mPMtha. Additionally, correlations between motor performance and FC values, volumes were examined separately. Support vector machine (SVM) model based on FC values and thalamic volumes was conducted to assist in the clinical diagnosis of PD motor subtype. Compared toHCs and PIGD, TD subtype showed increased FC between the bilateral mPMtha and left middle occipital gyrus, left inferior parietal lobule (IPL). While PIGD subtype demonstrated decreased FC between right mPMtha and precentral gyrus (PreCG), supramarginal, IPL and superior parietal lobule. FC of bilateral mPMtha with the identified regions were significantly correlated with motor performance scores in PD patients. The SVM classification based on FC values demonstrated a high level of efficiency (AUC=0.874). The volumes of the bilateral mPMtha were indifferent among three groups. We noted distinct FC alterations of mPMtha in TD and PIGD subtypes, and these changes were correlated with motor performance. Furthermore, the machine learning based on statistically significant FC might be served as an alternative approach for automatically classifying PD motor subtypes individually.

Effects of brain atrophy and altered functional connectivity on poststroke cognitive impairment

Background and PurposeBrain atrophy and disrupted functional connectivity are often present in patients with poststroke cognitive impairment (PSCI). This study aimed to explore the relationship between remote brain atrophy, connectional diaschisis and cognitive impairment in ischemic stroke patients to provide valuable information about the mechanisms underlying cognitive function recovery. MethodsForty first-time stroke patients with basal ganglia infarcts and twenty-nine age-matched healthy people were enrolled. All participants underwent T1-weighted and functional MRI scans, comprehensive cognitive function assessments at baseline, and 3-month follow-up. Brain volumes were calculated, and the atrophic regions were regarded as regions of interest in seed-based functional connectivity analyses. Pearson correlation analysis was used to explore the relationships among cognitive performance, brain atrophy, and functional connectivity alterations. ResultsCompared with healthy participants, stroke patients had worse cognitive performance at baseline and the 3-month follow-up. Worse cognitive performance was associated with smaller bilateral thalamus, left hippocampus, and left amygdala volumes, as well as lower functional connectivity between the left thalamus and the left medial superior frontal gyrus, between the right thalamus and the left median cingulate and paracingulate gyri, between the right hippocampus and the left medial superior frontal gyrus, and between the left amygdala and the right dorsolateral superior frontal gyrus. ConclusionsIn patients with basal ganglia infarction, connectional diaschisis between remote brain atrophy and the prefrontal lobe plays a significant role in PSCI. This finding provides new scientific evidence for understanding the mechanisms of PSCI and indicates that the prefrontal lobe may be a target to improve cognitive function after stroke.

A neuroimaging study of altered cortical and subcortical volume in adolescent methamphetamine users

Purpose: The aim of this study was is to compare brain structure volume, including cortical and subcortical regions of adolescents- methamphetamine users versus non-users.
 Materials and Methods: The study was designed to be cross-sectional, and structural magnetic resonance imaging scans were obtained from the participants, including ten methamphetamine users and nine non-users. volBrain program was used to evaluate the images. 
 Results: The results showed that methamphetamine users altered brain structures- temporal, parietal lobes, nucleus accumbens, amygdala, hippocampus, and thalamus volume. Also, the statistically significant difference in the volume between methamphetamine users and non-users was found in subcortical regions except putamen by age. Volumetric analysis of methamphetamine use in adolescents confirms a reduction in temporal lobes (methamphetamine users M±SD=3.43±0.18 non-users M±SD=3.48±0.22) and parietal lobes (methamphetamine users M±SD=2.23±0.24, non-users M±SD=2.37±0.33) in cortical regions in the brain as tissue volume. However, methamphetamine uses caused an increase in volume in the subcortical regions.
 Conclusion: Methamphetamine use appears to show decreased volume in the brain regions with age, which has adverse effects on cognitive, emotional, memory, and social abilities.

Striatal and thalamic automatic segmentation, morphology, and clinical correlates in Parkinsonism: Parkinson's disease, multiple system atrophy and progressive supranuclear palsy

Parkinson's disease (PD), multisystem atrophy (MSA), and progressive supranuclear palsy (PSP) present similarly with bradykinesia, tremor, rigidity, and cognitive impairments. Neuroimaging studies have found differential changes in the nigrostriatal pathway in these disorders, however whether the volume and shape of specific regions within this pathway can distinguish between atypical Parkinsonian disorders remains to be determined. This paper investigates striatal and thalamic volume and morphology as distinguishing biomarkers, and their relationship to neuropsychiatric symptoms. Automatic segmentation to calculate volume and shape analysis of the caudate nucleus, putamen, and thalamus were performed in 18 PD patients, 12 MSA, 15 PSP, and 20 healthy controls, then correlated with clinical measures. PSP bilateral thalami and right putamen were significantly smaller than controls, but not MSA or PD. The left caudate and putamen significantly correlated with the Neuropsychiatric Inventory total score. Bilateral thalamus, caudate, and left putamen had significantly different morphology between groups, driven by differences between PSP and healthy controls. This study demonstrated that PSP patient striatal and thalamic volume and shape are significantly different when compared with controls. Parkinsonian disorders could not be differentiated on volumetry or morphology, however there are trends for volumetric and morphological changes associated with PD, MSA, and PSP.

Associations Between Cognitive Impairment and Neuroimaging in Patients with Multiple Sclerosis.

Multiple sclerosis (MS) is a debilitating inflammatory and neurodegenerative disease which commonly involves cognitive dysfunction. Magnetic resonance imaging (MRI) studies have shown that patients with MS (pwMS) have diffuse patterns of brain atrophy, however, the relationship between the presentation of cognitive dysfunction and brain tissue loss remains understudied. Given the integral function of thalamus as a central nervous system relay center and its involvement in various brain circuits, thalamic atrophy may play a key role in the development and progression of cognitive dysfunction. The purpose of this study is to examine the relationship between cognitive impairment in pwMS and thalamic atrophy. A total of 121 pwMS who had neuropsychological testing and quantitative MRI within 1 year of each were retrospectively identified. Grouped LASSO linear regression with 10-fold cross validation was used to estimate each neuropsychological test score with thalamic volume as the focal predictor and all other demographic and MRI metrics as covariates. Rates of impairment ranged from 19% to 44%. Results showed notable associations between thalamic volume and Symbol Digit Modalities Test (β= 0.11), Brief Visuospatial Memory Test, delayed (β = 0.12), California Verbal Learning Test, delayed and total (β = 0.24 and β = 0.15 respectively), and Trail Making Test Part A (β = -0.01), after adjusting for covariates. These findings demonstrate an independent association between thalamic volumes and processing speed and memory performance, after accounting for demographic, clinical, and other MRI variables, among pwMS.

Thalamic asymmetry in Multiple Sclerosis.

Multiple Sclerosis (MS) is a chronic neuroinflammatory disease that affects the central nervous system. Asymmetry is one of the finding in brain MRI of these patients, which is related to the debilitating symptoms of the disease. This study aimed to investigate and compare the thalamic asymmetry in MS patients and its relationship with other MRI and clinical findings of these patients. This cross-sectional study conducted on 83 patients with relapse-remitting MS (RRMS), 43 patients with secondary progressive MS (SPMS), and 89 healthy controls. The volumes of total intracranial, total gray matter, total white matter, lesions, thalamus, and also the thalamicasymmetry indices were calculated. The 9-hole peg test (9-HPT) and Expanded Disability Status Scale (EDSS) were assessed as clinical findings. We showed that the normalized whole thalamic volume in healthy subjects was higher than MS patients (both RRMS and SPMS). Thalamic asymmetry index (TAI) was significantly different between RRMS patients and SPMS patients (p=0.011). The absolute value of TAI was significantly lower in healthy subjects than in RRMS (p < 0.001) and SPMS patients (p < 0.001), and SPMS patients had a higher absolute TAI compared to RRMS patients (p=0.037). In this cross-sectional study we showed a relationship between normalized whole thalamic volume and MS subtype. Also, we showed that the asymmetric indices of the thalamus can be related to the progression of the disease. Eventually, we showed that thalamic asymmetry can be related to the disease progression and subtype changes in MS.

The impact of cumulative obstetric complications and childhood trauma on brain volume in young people with psychotic experiences

Psychotic experiences (PEs) occur in 5–10% of the general population and are associated with exposure to childhood trauma and obstetric complications. However, the neurobiological mechanisms underlying these associations are unclear. Using the Avon Longitudinal Study of Parents and Children (ALSPAC), we studied 138 young people aged 20 with PEs (n = 49 suspected, n = 53 definite, n = 36 psychotic disorder) and 275 controls. Voxel-based morphometry assessed whether MRI measures of grey matter volume were associated with (i) PEs, (ii) cumulative childhood psychological trauma (weighted summary score of 6 trauma types), (iii) cumulative pre/peri-natal risk factors for psychosis (weighted summary score of 16 risk factors), and (iv) the interaction between PEs and cumulative trauma or pre/peri-natal risk. PEs were associated with smaller left posterior cingulate (pFWE < 0.001, Z = 4.19) and thalamus volumes (pFWE = 0.006, Z = 3.91). Cumulative pre/perinatal risk was associated with smaller left subgenual cingulate volume (pFWE < 0.001, Z = 4.54). A significant interaction between PEs and cumulative pre/perinatal risk found larger striatum (pFWE = 0.04, Z = 3.89) and smaller right insula volume extending into the supramarginal gyrus and superior temporal gyrus (pFWE = 0.002, Z = 4.79), specifically in those with definite PEs and psychotic disorder. Cumulative childhood trauma was associated with larger left dorsal striatum (pFWE = 0.002, Z = 3.65), right prefrontal cortex (pFWE < 0.001, Z = 4.63) and smaller left insula volume in all participants (pFWE = 0.03, Z = 3.60), and there was no interaction with PEs group. In summary, pre/peri-natal risk factors and childhood psychological trauma impact similar brain pathways, namely smaller insula and larger striatum volumes. The effect of pre/perinatal risk was greatest in those with more severe PEs, whereas effects of trauma were seen in all participants. In conclusion, environmental risk factors affect brain networks implicated in schizophrenia, which may increase an individual’s propensity to develop later psychotic disorders.

Cortical thickness and cognition in older people with multiple sclerosis.

The structural changes associated with cognitive performance in older people with multiple sclerosis (PwMS; age ≥ 50years old) remain unknown. To determine the relationship between whole-brain (WBV), thalamus as the largest deep gray matter nuclei, and cortex-specific volume measurements with both cognitive impairment and numerical performance in older PwMS. The main hypothesis is that cognitive impairment (CI) in older PwMS is explained by cortical thinning in addition to global and thalamic neurodegenerative changes. A total of 101 older PwMS underwent cognitive and neuroimaging assessment. Cognitive assessment included tests established as sensitive in MS samples (Minimal Assessment of Cognitive Function in MS; MACFIMS), as well as those tests often utilized in Alzheimer's dementia studies (Wechsler's Memory Scale, Boston Naming Test, Visual Motor Integration and language). Cognitive impairment (CI) was based on -1.5 standard deviations in at least 2 cognitive domains (executive function, learning and memory, spatial processing, processing speed and working memory and language) when compared to healthy controls. WBV and thalamic volume were calculated using SIENAX/FIRST and cortical thickness using FreeSurfer. Differences in cortical thickness between CI and cognitively preserved (CP) were determined using age, sex, education, depression and WBV-adjusted analysis of covariance (ANCOVA). The relationship between domain-specific cognitive performance and cortical thickness was analyzed by linear regression models adjusted for age, sex, education, depression, WBV and thalamic volume. Benjamini-Hochberg-adjusted p-values lower than 0.05 were considered significant. The average age of the study population was 62.6 (5.9) years old. After adjustment, CI PwMS had significantly thinner left fusiform (p = 0.0003), left inferior (p = 0.0032), left transverse (p = 0.0013), and bilateral superior temporal gyri (p = 0.002 and p = 0.0011) when compared to CP PwMS. After adjusting for age, sex, education, depression WBV, and thalamic volume, CI status was additionally predicted by the thickness of the left fusiform (p = 0.001) and left cuneus gyri (p = 0.004). After the adjustment, SDMT scores were additionally associated with left fusiform gyrus (p < 0.001) whereas letter-based verbal fluency performance with left pars opercularis gyrus (p < 0.001). In addition to global and thalamic neurodegenerative changes, the presence of CI in older PwMS is additionally explained by the thickness of multiple cortical regions.

A voxel- and source-based morphometry analysis of grey matter volume differences in very-late-onset schizophrenia-like psychosis.

Very-late-onset schizophrenia-like psychosis (VLOSLP) is associated with significant burden. Its clinical importance is increasing as the global population of older adults rises, yet owing to limited research in this population, the neurobiological underpinnings of VLOSP remain insufficiently clarified. Here we address this knowledge gap using novel morphometry techniques to investigate grey matter volume (GMV) differences between VLOSLP and healthy older adults, and their correlations with neuropsychological scores. In this cross-sectional study, we investigated whole-brain GMV differences between 35 individuals with VLOSLP (mean age 76.7, 26 female) and 36 healthy controls (mean age 75.7, 27 female) using whole-brain voxel-based morphometry (VBM) and supplementary source-based morphometry (SBM) on high resolution 3D T1-weighted MRI images. Additionally, we investigated relationships between GMV differences and cognitive function assessed with an extensive neuropsychological battery. VBM showed lower GMV in the thalamus, left inferior frontal gyrus and left insula in patients with VLOSLP compared to healthy controls. SBM revealed lower thalamo-temporal GMV in patients with VLOSLP. Processing speed, selective attention, mental flexibility, working memory, verbal memory, semantic fluency and confrontation naming were impaired in patients with VLOSLP. Correlations between thalamic volumes and memory function were significant within the group of individuals with VLOSLP, whereas no significant associations remained in the healthy controls. Lower GMV in the thalamus and fronto-temporal regions may be part of the underlying neurobiology of VLOSLP, with lower thalamic GMV contributing to memory impairment in the disorder.

Differences in resting-state brain networks and gray matter between APOE ε2 and APOE ε4 carriers in non-dementia elderly.

Apolipoprotein E (APOE) ε2 and APOE ε4 are the most distinct alleles among the three APOE alleles, both structurally and functionally. However, differences in cognition, brain function, and brain structure between the two alleles have not been comprehensively reported in the literature, especially in non-demented elderly individuals. A neuropsychological test battery was used to evaluate the differences in cognitive performance in five cognitive domains. Independent component analysis (ICA) and voxel-based morphometry (VBM) were used separately to analyze resting-state functional magnetic resonance imaging (rs-fMRI) data and the structure MRI data between the two groups. Finally, correlations between differential brain regions and neuropsychological tests were calculated. APOE ε2 carriers had better cognitive performance in general cognitive, memory, attention, and executive function than APOE ε4 carriers (all p < 0.05). In ICA analyses of rs-fMRI data, the difference in the resting-state functional connectivity (rsFC) between two groups is shown in 7 brain networks. In addition, VBM analyses of the T1-weighted image revealed that APOE ε2 carriers had a larger thalamus and right postcentral gyrus volume and a smaller bilateral putamen volume than APOE ε4 carriers. Finally, differences in brain function and structure may be might be the reason that APOE ε2 carriers are better than APOE ε4 carriers in cognitive performance. These findings suggest that there are significant differences in brain function and structure between APOE ε2 carriers and APOE ε4 carriers, and these significant differences are closely related to their cognitive performance.

Subcortical volumetric alterations in four major psychiatric disorders: a mega-analysis study of 5604 subjects and a volumetric data-driven approach for classification.

Differential diagnosis is sometimes difficult in practical psychiatric settings, in terms of using the current diagnostic system based on presenting symptoms and signs. The creation of a novel diagnostic system using objective biomarkers is expected to take place. Neuroimaging studies and others reported that subcortical brain structures are the hubs for various psycho-behavioral functions, while there are so far no neuroimaging data-driven clinical criteria overcoming limitations of the current diagnostic system, which would reflect cognitive/social functioning. Prior to the main analysis, we conducted a large-scale multisite study of subcortical volumetric and lateralization alterations in schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorder using T1-weighted images of 5604 subjects (3078 controls and 2526 patients). We demonstrated larger lateral ventricles volume in schizophrenia, bipolar disorder, and major depressive disorder, smaller hippocampus volume in schizophrenia and bipolar disorder, and schizophrenia-specific smaller amygdala, thalamus, and accumbens volumes and larger caudate, putamen, and pallidum volumes. In addition, we observed a leftward alteration of lateralization for pallidum volume specifically in schizophrenia. Moreover, as our main objective, we clustered the 5,604 subjects based on subcortical volumes, and explored whether data-driven clustering results can explain cognitive/social functioning in the subcohorts. We showed a four-biotype classification, namely extremely (Brain Biotype [BB] 1) and moderately smaller limbic regions (BB2), larger basal ganglia (BB3), and normal volumes (BB4), being associated with cognitive/social functioning. Specifically, BB1 and BB2-3 were associated with severe and mild cognitive/social impairment, respectively, while BB4 was characterized by normal cognitive/social functioning. Our results may lead to the future creation of novel biological data-driven psychiatric diagnostic criteria, which may be expected to be useful for prediction or therapeutic selection.

Serum glial fibrillary acidic protein in natalizumab-treated relapsing-remitting multiple sclerosis: An alternative to neurofilament light.

There is a need in Relapsing-Remitting Multiple Sclerosis (RRMS) treatment for biomarkers that monitor neuroinflammation, neurodegeneration, treatment response, and disease progression despite treatment. To assess the value of serum glial fibrillary acidic protein (sGFAP) as a biomarker for clinical disease progression and brain volume measurements in natalizumab-treated RRMS patients. sGFAP and neurofilament light (sNfL) were measured in an observational cohort of natalizumab-treated RRMS patients at baseline, +3, +12, and +24 months and at the last sample follow-up (median 5.17 years). sGFAP was compared between significant clinical progressors and non-progressors and related to magnetic resonance imaging (MRI)-derived volumes of the whole brain, ventricle, thalamus, and lesion. The relationship between sGFAP and sNfL was assessed. A total of 88 patients were included, and 47.7% progressed. sGFAP levels at baseline were higher in patients with gadolinium enhancement (1.3-fold difference, p = 0.04) and decreased in 3 months of treatment (adj. p < 0.001). No association was found between longitudinal sGFAP levels and progressor status. sGFAP at baseline and 12 months was significantly associated with normalized ventricular (positively), thalamic (negatively), and lesion volumes (positively). Baseline and 12-month sGFAP predicted annualized ventricle volume change rate after 1 year of treatment. sGFAP correlated with sNfL at baseline (p < 0.001) and last sample follow-up (p < 0.001) but stabilized earlier. sGFAP levels related to MRI markers of neuroinflammation and neurodegeneration.

Leucocyte telomere length, brain volume and risk of dementia: a prospective cohort study

BackgroundThe evidence regarding the association between leucocyte telomere length (LTL) and brain health is sparse and inconclusive.AimsTo investigate the associations of LTL with brain structure and the risk of dementia...

Preoperative thalamus volume is not associated with preoperative cognitive impairment (preCI) or postoperative cognitive dysfunction (POCD)

A growing body of literature suggests the important role of the thalamus in cognition and neurodegenerative diseases. This study aims to elucidate whether the preoperative thalamic volume is associated with preoperative cognitive impairment (preCI) and whether it is predictive for postoperative cognitive dysfunction at 3 months (POCD). We enrolled 301 patients aged 65 or older and without signs of dementia who were undergoing elective surgery. Magnetic resonance imaging was conducted prior to surgery. Freesurfer (version 5.3.) was used to automatically segment the thalamus volume. A neuropsychological test battery was administered before surgery and at a 3 month follow-up. It included the computerized tests Paired Associate Learning (PAL), Verbal Recognition Memory (VRM), Spatial Span Length (SSP), Simple Reaction Time (SRT), the pen-and-paper Trail-Making-Test (TMT) and the manual Grooved Pegboard Test (GPT). Using a reliable change index, preCI and POCD were defined as total Z-score > 1.96 (sum score over all tests) and/or Z-scores > 1.96 in ≥ 2 individual cognitive test parameters. For statistical analyses, multivariable logistic regression models were applied. Age, sex and intracranial volume were covariates in the models. Of 301 patients who received a presurgical neuropsychological testing and MRI, 34 (11.3%) had preCI. 89 patients (29.5%) were lost to follow-up. The remaining 212 patients received a follow-up cognitive test after 3 months, of whom 25 (8.3%) presented with POCD. Independently of age, sex and intracranial volume, neither preCI (OR per cm3 increment 0.81 [95% CI 0.60–1.07] p = 0.14) nor POCD (OR 1.02 per cm3 increment [95% CI 0.75–1.40] p = 0.87) were statistically significantly associated with patients’ preoperative thalamus volume. In this cohort we could not show an association of presurgical thalamus volume with preCI or POCD.Clinical Trial Number: NCT02265263 (https://clinicaltrials.gov/ct2/show/results/NCT02265263).

Influence of cardiorespiratory fitness and MRI measures of neuroinflammation on hippocampal volume in multiple sclerosis

BackgroundThe hippocampus is a clinically relevant region where neurogenesis and neuroplasticity occur throughout the whole lifespan. Neuroinflammation and cardiorespiratory fitness (CRF) may influence hippocampal integrity by modulating the processes promoting...

Association between intracranial vessel calcifications, structural brain damage, and cognitive impairment after minor strokes: a prospective study.

Vascular calcifications are a hallmark of atherosclerosis, and in the coronary arteries are routinely used as a prognostic marker. Calcifications of intracranial vessels (ICC) are frequently observed on non-contrast CT (NCCT) and their effect on post-stroke cognitive impairment (PSCI) remains unclear. Our aim was to explore the association of ICC with prospective long-term cognitive function and advanced MRI-measures in a large prospective cohort of cognitively intact mild stroke survivors. Data from the Tel-Aviv brain acute stroke cohort (TABASCO) study [ClinicalTrials.gov #NCT01926691] were analyzed. This prospective cohort study (n = 575) aimed to identify predictors of PSCI, in cognitively intact mild stroke survivors. A quantitative assessment of the intracranial calcium content - The ICC score (ICCS) was calculated semi-automatically on NCCT using a validated calcium quantification application. Participants underwent a 3 T-MRI and prospective comprehensive cognitive clinical and laboratory assessments at enrollment, 6, 12, and 24-months. Data were available for 531 participants (67.4 years, 59.5% males). The incidence of PSCI at two-years doubled in the high ICCS group (26% vs. 13.7%, p < 0.001). The high ICCS group had significantly greater small-vessel-disease (SVD) tissue changes and reduced microstructural-integrity assessed by Diffusion-Tensor-Imaging (DTI) maps (p < 0.05 for all). In multivariate analysis, a higher ICCS was independently associated with brain atrophy manifested by lower normalized white and gray matter, hippocampal and thalamic volumes (β = -0.178, β = -0.2, β = -0.137, β = -0.157; p < 0.05) and independently predicted PSCI (OR 1.83, 95%CI 1.01-3.35). Our findings suggest that the ICCS, which is a simple and readily available imaging marker on NCCT, is associated with brain atrophy, microstructural damage, the extent of SVD, and may predict PSCI. This finding has implications for identifying individuals at risk for PSCI and implementing targeted interventions to mitigate this risk.

Prenatal tobacco exposure on brain morphometry partially mediated poor cognitive performance in preadolescent children.

To evaluate whether prenatal tobacco exposure (PTE) is related to poorer cognitive performance, abnormal brain morphometry, and whether poor cognitive performance is mediated by PTE-related structural brain differences. The Adolescent Brain Cognitive Development study dataset was used to compare structural MRI data and neurocognitive (NIH Toolbox®) scores in 9-to-10-year-old children with (n=620) and without PTE (n=10,989). We also evaluated whether PTE effects on brain morphometry mediated PTE effects on neurocognitive scores. Group effects were evaluated using Linear Mixed Models, covaried for socio-demographics and prenatal exposures to alcohol and/or marijuana, and corrected for multiple comparisons using the false-discovery rate (FDR). Compared to unexposed children, those with PTE had poorer performance (all p-values <0.05) on executive function, working memory, episodic memory, reading decoding, crystallized intelligence, fluid intelligence and overall cognition. Exposed children also had thinner parahippocampal gyri, smaller surface areas in the posterior-cingulate and pericalcarine cortices; the lingual and inferior parietal gyri, and smaller thalamic volumes (all p-values <0.001). Furthermore, among children with PTE, girls had smaller surface areas in the superior-frontal (interaction-FDR-p=0.01), precuneus (interaction-FDR-p=0.03) and postcentral gyri (interaction-FDR-p=0.02), while boys had smaller putamen volumes (interaction-FDR-p=0.02). Smaller surface areas across regions of the frontal and parietal lobes, and lower thalamic volumes, partially mediated the associations between PTE and poorer neurocognitive scores (p-values <0.001). Our findings suggest PTE may lead to poorer cognitive performance and abnormal brain morphometry, with sex-specific effects in some brain regions, in pre-adolescent children. The poor cognition in children with PTE may result from the smaller areas and subcortical brain volumes.

Brain networks and epilepsy development in patients with Alzheimer disease.

This study aimed to investigate the association between brain networks and epilepsy development in patients with Alzheimer disease (AD). We enrolled patients newly diagnosed with AD at our hospital who underwent three-dimensional T1-weighted magnetic resonance imaging at the time of AD diagnosis and included healthy controls. We obtained the cortical, subcortical, and thalamic nuclei structural volumes using FreeSurfer and applied graph theory to obtain the global brain network and intrinsic thalamic network based on the structural volumes using BRAPH. We enrolled 25 and 56 patients with AD with and without epilepsy development, respectively. We also included 45 healthy controls. The global brain network differed between the patients with AD and healthy controls. The local efficiency (2.026 vs. 3.185, p=.048) and mean clustering coefficient (0.449 vs. 1.321, p=.024) were lower, whereas the characteristic path length (0.449 vs. 1.321, p=.048) was higher in patients with AD than in healthy controls. Both global and intrinsic thalamic networks were significantly different between AD patients with and without epilepsy development. In the global brain network, local efficiency (1.340 vs. 2.401, p=.045), mean clustering coefficient (0.314 vs. 0.491, p=.045), average degree (27.442 vs. 41.173, p=.045), and assortative coefficient (-0.041 vs. -0.011, p=.045) were lower, whereas the characteristic path length (2.930 vs. 2.118, p=.045) was higher in patients with AD with epilepsy development than in those without. In the intrinsic thalamic network, the mean clustering coefficient (0.646 vs. 0.460, p=.048) was higher, whereas the characteristic path length (1.645 vs. 2.232, p=.048) was lower in patients with AD with epilepsy development than in those without. We found that the global brain network differs between patients with AD and healthy controls. In addition, we demonstrated significant associations between brain networks (both global brain and intrinsic thalamic networks) and epilepsy development in patients with AD.

Reduced alpha2 power is associated with slowed information processing speed in multiple sclerosis.

Cognitive impairment is common in multiple sclerosis (MS), significantly impacts daily functioning, is time-consuming to assess, and is prone to practice effects. We examined whether the alpha band power measured with magnetoencephalography (MEG) is associated with the different cognitive domains affected by MS. Sixty-eight MS patients and 47 healthy controls underwent MEG, T1- and FLAIR-weighted magnetic resonance imaging (MRI), and neuropsychological testing. Alpha power in the occipital cortex was quantified in the alpha1 (8-10 Hz) and alpha2 (10-12 Hz) bands. Next, we performed best subset regression to assess the added value of neurophysiological measures to commonly available MRI measures. Alpha2 power significantly correlated with information processing speed (p < 0.001) and was always retained in all multilinear models, whereas thalamic volume was retained in 80% of all models. Alpha1 power was correlated with visual memory (p < 0.001) but only retained in 38% of all models. Alpha2 (10-12 Hz) power in rest is associated with IPS, independent of standard MRI parameters. This study stresses that a multimodal assessment, including structural and functional biomarkers, is likely required to characterize cognitive impairment in MS. Resting-state neurophysiology is thus a promising tool to understand and follow up changes in IPS.