Lateral Orbitofrontal Research Articles

Shift work effects on incident neuropsychiatric disorders and shift work tolerance

BackgroundShift work is associated with susceptibility to several neuropsychiatric disorders. This study aims to investigate the effect of shift work on the incidence of neuropsychiatric disorders, and highlighting how individual variability may influence the association. MethodsUK Biobank participants with employment information were included. Cox survival was conducted in main and subgroup analyses. Correlation analyses explored the impact of shift work on brain structures, and mediation analyses were performed to elucidate the shared underlying mechanisms. Shift work tolerance was evaluated through survival analyses contrasting the risks associated with five neuropsychiatric disorders in shift versus non-shift workers across different demographic or occupational strata. ResultsThe analysis encompassed 254,646 participants. Shift work was associated with higher risk of dementia (HR 1.29, 95 % CI 1.10–1.52), anxiety (1.08, 1.01–1.15), depression (1.29, 1.22–1.36), and sleep disorders (1.18, 1.09–1.28), but not stroke (p = 0.20). Shift work was correlated with decreasing volume of various brain regions, particularly in thalamus, lateral orbitofrontal, and middle temporal. Mediation analysis revealed that increased immune response and glucose levels are common pathways linking shift work to these disorders. We observed diversity in shift work tolerance across different individual characteristics, among which socioeconomic status and length of working hours were the most essential. LimitationsSelf-reported employment information may cause misclassification and recall bias. And since we focused on the middle-aged population, the conclusions may not be representative of younger or older populations. ConclusionsOur findings indicated the need to monitor shift worker health and provide personalized management to help adapt to shift work.

1-11C]-Butanol Positron Emission Tomography reveals an impaired brain to nasal turbinates pathway in aging amyloid positive subjects

BackgroundReduced clearance of cerebrospinal fluid (CSF) has been suggested as a pathological feature of Alzheimer’s disease (AD). With extensive documentation in non-human mammals and contradictory human neuroimaging data it remains unknown whether the nasal mucosa is a CSF drainage site in humans. Here, we used dynamic PET with [1-11C]-Butanol, a highly permeable radiotracer with no appreciable brain binding, to test the hypothesis that tracer drainage from the nasal pathway reflects CSF drainage from brain. As a test of the hypothesis, we examined whether brain and nasal fluid drainage times were correlated and affected by brain amyloid.Methods24 cognitively normal subjects (≥ 65 years) were dynamically PET imaged for 60 min. using [1-11C]-Butanol. Imaging with either [11C]-PiB or [18F]-FBB identified 8 amyloid PET positive (Aβ+) and 16 Aβ- subjects. MRI-determined regions of interest (ROI) included: the carotid artery, the lateral orbitofrontal (LOF) brain, the cribriform plate, and an All-turbinate region comprised of the superior, middle, and inferior turbinates. The bilateral temporalis muscle and jugular veins served as control regions. Regional time-activity were used to model tracer influx, egress, and AUC.ResultsLOF and All-turbinate 60 min AUC were positively associated, thus suggesting a connection between the brain and the nose. Further, the Aβ+ subgroup demonstrated impaired tracer kinetics, marked by reduced tracer influx and slower egress.ConclusionThe data show that tracer kinetics for brain and nasal turbinates are related to each other and both reflect the amyloid status of the brain. As such, these data add to evidence that the nasal pathway is a potential CSF drainage site in humans. These data warrant further investigation of brain and nasal contributions to protein clearance in neurodegenerative disease.

Evidence based on Mendelian randomization and colocalization analysis strengthens causal relationships between structural changes in specific brain regions and risk of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the degeneration of motor neurons in the brain and spinal cord with a poor prognosis. Previous studies have observed cognitive decline and changes in brain morphometry in ALS patients. However, it remains unclear whether the brain structural alterations contribute to the risk of ALS. In this study, we conducted a bidirectional two-sample Mendelian randomization (MR) and colocalization analysis to investigate this causal relationship. Summary data of genome-wide association study were obtained for ALS and the brain structures, including surface area (SA), thickness and volume of subcortical structures. Inverse-variance weighted (IVW) method was used as the main estimate approach. Sensitivity analysis was conducted detect heterogeneity and pleiotropy. Colocalization analysis was performed to calculate the posterior probability of causal variation and identify the common genes. In the forward MR analysis, we found positive associations between the SA in four cortical regions (lingual, parahippocampal, pericalcarine, and middle temporal) and the risk of ALS. Additionally, decreased thickness in nine cortical regions (caudal anterior cingulate, frontal pole, fusiform, inferior temporal, lateral occipital, lateral orbitofrontal, pars orbitalis, pars triangularis, and pericalcarine) was significantly associated with a higher risk of ALS. In the reverse MR analysis, genetically predicted ALS was associated with reduced thickness in the bankssts and increased thickness in the caudal middle frontal, inferior parietal, medial orbitofrontal, and superior temporal regions. Colocalization analysis revealed the presence of shared causal variants between the two traits. Our results suggest that altered brain morphometry in individuals with high ALS risk may be genetically mediated. The causal associations of widespread multifocal extra-motor atrophy in frontal and temporal lobes with ALS risk support the notion of a continuum between ALS and frontotemporal dementia. These findings enhance our understanding of the cortical structural patterns in ALS and shed light on potentially viable therapeutic targets.

Relationship of Neural Correlates of Gait Characteristics and Cognitive Dysfunction in Patients with Mild Cognitive Impairment.

Background: Some patients with mild cognitive impairment (MCI) experience gait disturbances. However, there are few reports on the relationship between gait disturbance and cognitive function in patients with MCI. Therefore, we investigated the neural correlates of gait characteristics related to cognitive dysfunction. Methods: Eighty patients diagnosed with MCI from three dementia centers in Gangwon-do, Korea, were recruited for this study. We defined MCI as a Clinical Dementia Rating global score of 0.5 or higher, with a memory domain score of 0.5 or greater. The patients were classified as having either higher or lower MMSE and the groups were based on their Mini Mental Status Examination z-scores. Multiple logistic regression analysis was performed to examine the association between the gait characteristics and cognitive impairment. Analyses included variables such as age, sex, years of education, number of comorbidities, body mass index, and height. Results: Gait velocity, step count, step length, heel-to-heel base support, swing and stance phase duration, and support time were associated with cognitive function. A decrease in gray matter volume in the right pericalcarine area was associated with gait characteristics related to cognitive dysfunction. An increase in the curvature of gray matter in the right entorhinal, right lateral orbitofrontal, right cuneus, and right and left pars opercularis areas was also associated with gait characteristics related to cognitive dysfunction. Conclusion: Since gait impairment is an important factor in determining activities of daily living in patients with mild cognitive impairment, the evaluation of gait and cognitive functions in patients with mild cognitive impairment is important.

Reduced neurite density index in the prefrontal cortex of adults with autism assessed using neurite orientation dispersion and density imaging.

Core symptoms of autism-spectrum disorder (ASD) have been associated with prefrontal cortex abnormalities. However, the mechanisms behind the observation remain incomplete, partially due to the challenges of modeling complex gray matter (GM) structures. This study aimed to identify GM microstructural alterations in adults with ASD using neurite orientation dispersion and density imaging (NODDI) and voxel-wise GM-based spatial statistics (GBSS) to reduce the partial volume effects from the white matter and cerebrospinal fluid. A total of 48 right-handed participants were included, of which 22 had ASD (17 men; mean age, 34.42 ± 8.27 years) and 26 were typically developing (TD) individuals (14 men; mean age, 32.57 ± 9.62 years). The metrics of NODDI (neurite density index [NDI], orientation dispersion index [ODI], and isotropic volume fraction [ISOVF]) were compared between groups using GBSS. Diffusion tensor imaging (DTI) metrics and surface-based cortical thickness were also compared. The associations between magnetic resonance imaging-based measures and ASD-related scores, including ASD-spectrum quotient, empathizing quotient, and systemizing quotient were also assessed in the region of interest (ROI) analysis. After controlling for age, sex, and intracranial volume, GBSS demonstrated significantly lower NDI in the ASD group than in the TD group in the left prefrontal cortex (caudal middle frontal, lateral orbitofrontal, pars orbitalis, pars triangularis, rostral middle frontal, and superior frontal region). In the ROI analysis of individuals with ASD, a significantly positive correlation was observed between the NDI in the left rostral middle frontal, superior frontal, and left frontal pole and empathizing quotient score. No significant between-group differences were observed in all DTI metrics, other NODDI (i.e., ODI and ISOVF) metrics, and cortical thickness. GBSS analysis was used to demonstrate the ability of NODDI metrics to detect GM microstructural alterations in adults with ASD, while no changes were detected using DTI and cortical thickness evaluation. Specifically, we observed a reduced neurite density index in the left prefrontal cortices associated with reduced empathic abilities.

Predicting long-term outcome in anorexia nervosa: a machine learning analysis of brain structure at different stages of weight recovery.

Anorexia nervosa (AN) is characterized by sizable, widespread gray matter (GM) reductions in the acutely underweight state. However, evidence for persistent alterations after weight-restoration has been surprisingly scarce despite high relapse rates, frequent transitions to other psychiatric disorders, and generally unfavorable outcome. While most studies investigated brain regions separately (univariate analysis), psychiatric disorders can be conceptualized as brain network disorders characterized by multivariate alterations with only subtle local effects. We tested for persistent multivariate structural brain alterations in weight-restored individuals with a history of AN, investigated their putative biological substrate and relation with 1-year treatment outcome. We trained machine learning models on regional GM measures to classify healthy controls (HC) (N = 289) from individuals at three stages of AN: underweight patients starting intensive treatment (N = 165, used as baseline), patients after partial weight-restoration (N = 115), and former patients after stable and full weight-restoration (N = 89). Alterations after weight-restoration were related to treatment outcome and characterized both anatomically and functionally. Patients could be classified from HC when underweight (ROC-AUC = 0.90) but also after partial weight-restoration (ROC-AUC = 0.64). Alterations after partial weight-restoration were more pronounced in patients with worse outcome and were not detected in long-term weight-recovered individuals, i.e. those with favorable outcome. These alterations were more pronounced in regions with greater functional connectivity, not merely explained by body mass index, and even increases in cortical thickness were observed (insula, lateral orbitofrontal, temporal pole). Analyzing persistent multivariate brain structural alterations after weight-restoration might help to develop personalized interventions after discharge from inpatient treatment.

The impact of prenatal alcohol and/or tobacco exposure on brain structure in a large sample of children from a South African birth cohort.

Neuroimaging studies have emphasized the impact of prenatal alcohol exposure (PAE) on brain development, traditionally in heavily exposed participants. However, less is known about how naturally occurring community patterns of PAE (including light to moderate exposure) affect brain development, particularly in consideration of commonly occurring concurrent impacts of prenatal tobacco exposure (PTE). Three hundred thirty-two children (ages 8 to 12) living in South Africa's Cape Flats townships underwent structural magnetic resonance imaging. During pregnancy, their mothers reported alcohol and tobacco use, which was used to evaluate PAE and PTE effects on their children's brain structure. Analyses involved the main effects of PAE and PTE (and their interaction) and the effects of PAE and PTE quantity on cortical thickness, surface area, and volume. After false-discovery rate (FDR) correction, PAE was associated with thinner left parahippocampal cortices, while PTE was associated with smaller cortical surface area in the bilateral pericalcarine, left lateral orbitofrontal, right posterior cingulate, right rostral anterior cingulate, left caudal middle frontal, and right caudal anterior cingulate gyri. There were no PAE × PTE interactions nor any associations of PAE and PTE exposure on volumetrics that survived FDR correction. PAE was associated with reduction in the structure of the medial temporal lobe, a brain region critical for learning and memory. PTE had stronger and broader associations, including with regions associated with executive function, reward processing, and emotional regulation, potentially reflecting continued postnatal exposure to tobacco (i.e., second-hand smoke exposure). These differential effects are discussed with respect to reduced PAE quantity in our exposed group versus prior studies within this geographical location, the deep poverty in which participants live, and the consequences of apartheid and racially and economically driven payment practices that contributed to heavy drinking in the region. Longer-term follow-up is needed to determine potential environmental and other moderators of the brain findings here and assess the extent to which they endure over time.

Superior pitch identification ability revealed by cortical complexity measures in nonmusicians

Previous research has investigated the brain structure of musicians with absolute pitch (AP); however, pitch identification (PI) ability also exists in nonmusicians. The current study examined the relationship between PI ability and cortical complexity in nonmusicians using fractal dimensionality, a relatively novel way to analyze morphological patterns of cortical organization. Results showed that compared to nonmusicians with average PI ability, those with superior PI exhibited more fractal dimensionality of the left middle and transverse temporal gyrus, right paracentral lobule, superior frontal and precentral gyri, bilateral lateral orbitofrontal, medial orbitofrontal, superior temporal and postcentral gyri as well as less fractal dimensionality of the left precuneus, right superior parietal lobule and insula gyrus, and bilateral supramarginal gyrus. Moreover, the PI score for the superior PI group was positively correlated with fractal dimensionality of the left medial orbitofrontal, superior temporal, and supramarginal gyri; for the average PI group, their PI score was negatively correlated with fractal dimensionality of the left middle temporal, right superior frontal, and right insula gyri. Although the research about fractal dimensionality in young adults has been scant so far, the present study extends our understanding of the neuroanatomical correlates of AP musicians to encompass those with superior PI ability in nonmusicians.

Altered Prefrontal Blood Flow Related With Mild Cognitive Impairment in Parkinson's Disease: A Longitudinal Study.

Cognitive impairment is a common non-motor symptom in Parkinson's disease (PD), with executive dysfunction being an initial manifestation. We aimed to investigate whether and how longitudinal changes in the prefrontal perfusion correlate with mild cognitive impairment (MCI) in patients with PD. We recruited 49 patients with PD with normal cognition and 37 matched healthy control subjects (HCs). Patients with PD completed arterial spin labeling MRI (ASL–MRI) scans and a comprehensive battery of neuropsychological assessments at baseline (V0) and 2-year follow-up (V1). HCs completed similar ASL–MRI scans and neuropsychological assessments at baseline. At V1, 10 patients with PD progressed to MCI (converters) and 39 patients remained cognitively normal (non-converters). We examined differences in the cerebral blood flow (CBF) derived from ASL–MRI and neuropsychological measures (a) between patients with PD and HCs at V0 (effect of the disease), (b) between V1 and V0 in patients with PD (effect of the disease progression), and (c) between converters and non-converters (effect of the MCI progression) using t-tests or ANOVAs with false discovery rate correction. We further analyzed the relationship between longitudinal CBF and neuropsychological changes using multivariate regression models with false discovery rate correction, focusing on executive functions. At V0, no group difference was found in prefrontal CBF between patients with PD and HCs, although patients with PD showed worse performances on executive function. At V1, patients with PD showed significantly reduced CBF in multiple prefrontal regions, including the bilateral lateral orbitofrontal, medial orbitofrontal, middle frontal, inferior frontal, superior frontal, caudal anterior cingulate, and rostral anterior cingulate. More importantly, converters showed a more significant CBF reduction in the left lateral orbitofrontal cortex than non-converters. From V0 to V1, the prolonged completion time of Trail Making Test-B (TMT-B) negatively correlated with longitudinal CBF reduction in the right caudal anterior cingulate cortex. The decreased accuracy of the Stroop Color-Word Test positively correlated with longitudinal CBF reduction in the left medial orbitofrontal cortex. In addition, at V1, the completion time of TMT-B negatively correlated with CBF in the left caudal anterior cingulate cortex. Our findings suggest that longitudinal CBF reduction in the prefrontal cortex might impact cognitive functions (especially executive functions) at the early stages of PD.

Ultra-high field 7 T MRI localizes regional brain volume recovery following corticotroph adenoma resection and hormonal remission in Cushing's disease: A case series.

Background: Cushing’s disease (CD) is defined by glucocorticoid excess secondary to the increased section of corticotropin by a pituitary adenoma. Magnetic resonance imaging (MRI) studies performed at 1.5 or 3 Tesla (T) have demonstrated correlations between regional changes in brain structure and the progression of CD. In this report, we examine the changes in brain volume following corticotroph pituitary adenoma resection using ultra-high field 7 T MRI to increase the accuracy of our volumetric analyses.Methods: Thirteen patients were referred to the endocrinology clinic at our institution from 2017 to 2020 with symptoms of cortisol excess and were diagnosed with ACTH-dependent endogenous Cushing syndrome. Five patients had follow-up 7 T imaging at varying time points after a transsphenoidal resection.Results: Symmetrized percent change in regional volumes demonstrated a postoperative increase in cortical volume that was relatively larger than that of cerebral white matter or subcortical gray matter (percent changes = 0.0172%, 0.0052%, and 0.0120%, respectively). In the left cerebral hemisphere, the medial orbitofrontal, lateral orbitofrontal, and pars opercularis cortical regions experienced the most robust postoperative percent increases (percent changes = 0.0166%, 0.0122%, and 0.0068%, respectively). In the right cerebral hemisphere, the largest percent increases were observed in the pars triangularis, rostral portion of the middle frontal gyrus, and superior frontal gyrus (percent changes = 0.0156%, 0.0120%, and 0.0158%).Conclusion: Cerebral volume recovery following pituitary adenoma resection is driven by changes in cortical thickness predominantly in the frontal lobe, while subcortical white and gray matter volumes increase more modestly.

Correspondence between cortical tau and atrophy in aged non‐demented adults with Down syndrome

AbstractBackgroundIndividuals with Down syndrome (DS) have a higher likelihood of developing early‐onset Alzheimer’s disease which has been associated with abnormal tau proteins and atrophy in the brain [1]. Prior research has shown a spatial relationship between tau and atrophy in neurotypicals with dementia [2]. Although tau and atrophy certainly contribute independently to dementia, the synergistic relationship in a non‐demented population with DS is not well understood. This study aims to identify cortical regions with high tau and atrophy in aged, non‐demented participants with DS.MethodAnalysis included 28 non‐demented participants (49.8 +/‐ 6.4 years; 17 males) with DS from the Alzheimer’s Disease in Down Syndrome (ADDS) study. Tau PET (18F‐AV1451) and MRI scans were acquired within the same timeframe (1.8 months +/‐1.5). Gray‐matter cortical ribbons were extracted from T1 MRI segmentations with Freesurfer (RRID: SCR_001847). The cortical ribbons were used to mask the coregistered PET scan data and converted to standard uptake value ratio (SUVR) units using the cerebellar cortex reference region. The tau and gray‐matter images were converted to z‐score images using the group mean and standard deviation. We defined high tau as voxels with z‐scores >=2.0 and high atrophy as voxels with gray matter z‐scores <= ‐2.0. The z‐score images were spatially normalized into MNI space with ANTs (RRID: SCR_004757) and a voxel‐based correspondence analysis was performed. Voxels surviving the high tau and high atrophy thresholds were evaluated to determine anatomical localization using the Desikan/Killiany atlas [3].ResultWe found high correspondence between tau and atrophy in the following regions (figure 1): entorhinal cortex, insula, fusiform, pars orbitalis, paracentral, precentral, superior temporal, medial orbitofrontal, lateral orbitofrontal, temporal pole, rostral middle frontal, superior frontal, pars triangularis, lingual, and the amygdala.ConclusionOur study demonstrated a correspondence between atrophy and tau in deep cortical structures, as well as frontotemporal regions in aged, non‐demented adults with DS. Many of these regions are consistent with findings in neurotypical populations and shown in our prior work to be regions associated with increased amyloid (18F‐AV‐45) as a function of disease severity in DS [4].

Cortical remodeling across the lifespan in healthy brain reveals structural network vulnerability to neurodegeneration

AbstractBackgroundAging is the main risk factor for most of the neurodegenerative diseases. The aim of this study was to investigate typical cortical thinning changes across lifespan in the healthy brain revealing structural network vulnerability to neurodegeneration.MethodThe cohort included 128 healthy individuals aged 20‐85 years that underwent an MRI scan. Structural T1‐weighted images were used to estimate vertex‐wise cortical thickness maps, then grouped into 83 regions. For each region, cortical thickness trajectory with advancing age was estimated, including sex as covariate. Additionally, all regions were ranked based on their relative thickness at the end of the observed lifetime, assessing regional changes over time. Finally, regional mean thickness was correlated with relative change over time.ResultThe highest cortical thinning was observed in the temporal lobe (parahippocampal, entorhinal, superior and middle temporal and fusiform), in the frontal lobe (lateral orbitofrontal, superior and inferior frontal and rostral anterior cingulate), in the parietal lobe (the isthmus of cingulate, precuneus, supramarginal and inferior parietal) and in the insular cortex. Interestingly, occipital regions (cuneus, lateral occipital, lingual, pericalcarine), and motor and premotor areas (precentral, postcentral and paracentral regions) showed the least cortical thickness change relative to the whole brain. Finally, positive correlation was found between mean regional thickness and its relative change over time.ConclusionThis study highlights structural vulnerability of brain regions to aging. Furthermore, results provide information concerning trajectories of normal brain aging, identifying those areas that might be more vulnerable to the attack of neurodegeneration. Supported by: European Research Council (StG‐2016_714388_NeuroTRACK).

Alcohol use is associated with mental health problems and brain structural alterations in adolescents with perinatally acquired HIV infection on ART.

Alcohol use, presents unique challenges for HIV-1 treatment in adolescents with perinatally acquired infection. The effects of alcohol on host-virus interaction in the brain and the immune system remains understudied in this population. Adolescents with perinatally acquired HIV infection (PHIV) well established on ART, from the Cape Town Adolescent Antiretroviral Cohort who self-reported alcohol use (PHIV+alcohol) (n=26) were compared to age matched 26 PHIV (PHIV-alcohol) and 26 healthy controls (HC) who reported no use of alcohol. Participants completed clinical investigations including highly-sensitive CRP (hs-CRP), a comprehensive neurocognitive test battery and mental health measures. In addition, we investigated the relationship between alcohol use in PHIV and diffusion tensor imaging (DTI) and structural brain magnetic resonance imaging (MRI) to determine fractional anisotropy (FA), mean diffusivity (MD), grey and white matter volumes and cortical thickness. PHIV (mean age 12,5 years; mean age of ART initiation 3.15 years) reported an occasional weekend drinking pattern of alcohol use. hs-CRP was significantly different between groups, with PHIV+alcohol higher than PHIV-alcohol and HC. General intelligence, attention, working memory, processing speed and executive function were more impaired in the PHIV+alcohol than PHIV alone, with HC having the highest scores. In addition, self-concept was significantly lower in PHIV+alcohol. The Child Behavior Checklist (CBCL) Externalizing behaviour, internalising behaviour and CBCL Total problems were significantly higher in PHIV+alcohol. FA of the superior corona radiata, superior fronto-occipital fasciculus and corpus callosum was significantly lower in PHIV+alcohol compared to PHIV-alcohol and MD of the corona radiata was significantly increased in PHIV+alcohol. The cortical thickness of the lateral orbitofrontal, middle frontal and precentral gyri were significantly lower in PHIV+alcohol compared to PHIV-alcohol and HC. In conclusion PHIV associated impairments in systemic inflammation, cognitive function, mental health and changes in brain structure may be exacerbated by alcohol use, even if only occasional use. However, the study is cross-sectional, which is not able to distinguish between cause and effect.

Effects of Meditation on Structural Changes of the Brain in Patients With Mild Cognitive Impairment or Alzheimer's Disease Dementia.

Previous cross-sectional studies reported positive effects of meditation on the brain areas related to attention and executive function in the healthy elderly population. Effects of long-term regular meditation in persons with mild cognitive impairment (MCI) and Alzheimer’s disease dementia (AD) have rarely been studied. In this study, we explored changes in cortical thickness and gray matter volume in meditation-naïve persons with MCI or mild AD after long-term meditation intervention. MCI or mild AD patients underwent detailed clinical and neuropsychological assessment and were assigned into meditation or non-meditation groups. High resolution T1-weighted magnetic resonance images (MRI) were acquired at baseline and after 6 months. Longitudinal symmetrized percentage changes (SPC) in cortical thickness and gray matter volume were estimated. Left caudal middle frontal, left rostral middle frontal, left superior parietal, right lateral orbitofrontal, and right superior frontal cortices showed changes in both cortical thickness and gray matter volume; the left paracentral cortex showed changes in cortical thickness; the left lateral occipital, left superior frontal, left banks of the superior temporal sulcus (bankssts), and left medial orbitofrontal cortices showed changes in gray matter volume. All these areas exhibited significantly higher SPC values in meditators as compared to non-meditators. Conversely, the left lateral occipital, and right posterior cingulate cortices showed significantly lower SPC values for cortical thickness in the meditators. In hippocampal subfields analysis, we observed significantly higher SPC in gray matter volume of the left CA1, molecular layer HP, and CA3 with a trend for increased gray matter volume in most other areas. No significant changes were found for the hippocampal subfields in the right hemisphere. Analysis of the subcortical structures revealed significantly increased volume in the right thalamus in the meditation group. The results of the study point out that long-term meditation practice in persons with MCI or mild AD leads to salutary changes in cortical thickness and gray matter volumes. Most of these changes were observed in the brain areas related to executive control and memory that are prominently at risk in neurodegenerative diseases.

Cortical Correlates of Impulsive Aggressive Behavior in Pediatric Bipolar Disorder.

Background: Impulsive aggression represents a frequent characteristic of pediatric bipolar disorder (PBD). Cortical alterations associated with impulsive aggression and its multiple facets have not been investigated yet in youth with bipolar disorder.Aim: To investigate the relationship between cortical thickness and facets of impulsive aggression in youth with PBD.Materials and Methods: Twenty-three youth with PBD and 23 healthy controls (HC) were administered the aggression questionnaire (AQ) and underwent 3T magnetic resonance imaging scan. Cortical thickness was assessed with FreeSurfer. Canonical correlation analyses were used to investigate the relationship between AQ total and subscale scores and cortical thickness in youth with PBD.Results: Youth with PBD had increased scores in the subscales of AQ-anger and AQ-hostility and cortical thinning in in areas belonging to the affective network (AN), frontoparietal network (FPN) and cingulo-opercular network (CON), i.e., right rostral anterior cingulate, right caudal anterior cingulate, right lateral orbitofrontal, right medial orbitofrontal, left and right inferior parietal, left posterior cingulate, left and right supramarginal left lingual cortices. Greater thickness in these networks positively correlated with the AQ-hostility subscale and negatively correlated with AQ-anger subscale.Conclusions: The opposite patterns observed between areas belonging to AN, FPN, CON, and the two facets of IA, namely anger and hostility, corroborate clinical findings supporting the different nature of these two constructs.

Associations Between Amyloid and Tau Pathology, and Connectome Alterations, in Alzheimer's Disease and Mild Cognitive Impairment.

The roles of amyloid-β and tau in the degenerative process of Alzheimer's disease (AD) remain uncertain. [18F]AV-45 and [18F]AV-1451 PET quantify amyloid-β and tau pathology, respectively, while diffusion tractography enables detection of their microstructural consequences. Examine the impact of amyloid-β and tau pathology on the structural connectome and cognition, in mild cognitive impairment (MCI) and AD. Combined [18F]AV-45 and [18F]AV-1451 PET, diffusion tractography, and cognitive assessment in 28 controls, 32 MCI, and 26 AD patients. Hippocampal connectivity was reduced to the thalami, right lateral orbitofrontal, and right amygdala in MCI; alongside the insula, posterior cingulate, right entorhinal, and numerous cortical regions in AD (all p < 0.05). Hippocampal strength inversely correlated with [18F]AV-1451 SUVr in MCI (r = -0.55, p = 0.049) and AD (r = -0.57, p = 0.046), while reductions in hippocampal connectivity to ipsilateral brain regions correlated with increased [18F]AV-45 SUVr in those same regions in MCI (r = -0.33, p = 0.003) and AD (r = -0.31, p = 0.006). Cognitive scores correlated with connectivity of the right temporal pole in MCI (r = -0.60, p = 0.035) and left hippocampus in AD (r = 0.69, p = 0.024). Clinical Dementia Rating Scale scores correlated with [18F]AV-1451 SUVr in multiple areas reflecting Braak stages I-IV, including the right (r = 0.65, p = 0.004) entorhinal cortex in MCI; and Braak stages III-VI, including the right (r = 0.062, p = 0.009) parahippocampal gyrus in AD. Reductions in hippocampal connectivity predominate in the AD connectome, correlating with hippocampal tau in MCI and AD, and with amyloid-β in the target regions of those connections. Cognitive scores correlate with microstructural changes and reflect the accumulation of tau pathology.

Regional amyloid accumulation predicts memory decline in initially cognitively unimpaired individuals.

IntroductionThe value of quantitative longitudinal and regional amyloid beta (Aβ) measurements in predicting cognitive decline in initially cognitively unimpaired (CU) individuals remains to be determined.MethodsWe selected 133 CU individuals with two or more [11C]Pittsburgh compound B ([11C]PiB) scans and neuropsychological data from Open Access Series of Imaging Studies (OASIS‐3). Baseline and annualized distribution volume ratios were computed for a global composite and four regional clusters. The predictive value of Aβ measurements (baseline, slope, and interaction) on longitudinal cognitive performance was examined.ResultsGlobal performance could only be predicted by Aβ burden in an early cluster (precuneus, lateral orbitofrontal, and insula) and the precuneus region of interest (ROI) by itself significantly improved the model. Precuneal Aβ burden was also predictive of immediate and delayed episodic memory performance. In Aβ subjects at baseline (N = 93), lateral orbitofrontal Aβ burden predicted working and semantic memory performance.DiscussionQuantifying longitudinal and regional changes in Aβ can improve the prediction of cognitive functioning in initially CU individuals.

Why do we need an Asian brain template in clinical trials of Alzheimer's disease? A comparative study of brain structures between Asian vs Caucasian brains

AbstractBackgroundThere is a recognized need for the creation of ethnic‐specific brain templates of cognitively normal older adults for the purpose of evaluating structural and functional brain imaging data in the normal aging process and neurodegenerative disease including Alzheimer’s disease. However, previous studies of racial difference in cortical thickness of cognitively normal older adults have been restricted to small sample size and have not adequately controlled biases. We aimed to compare cerebral cortical thickness between cognitively normal older adults of East Asians and of Caucasians adjusting for age, gender, education.MethodWe evaluated the brain cortical thickness by using FreeSurfer on standard T1‐weighted images of cognitively normal older adults in East Asians [n= 321 (60’s = 166, 70’s = 155)] and Caucasians [n= 282 (60’s = 111, 70’s = 171)], and examined the difference in cortical thickness between two races by whole brain analysis (ANCOVA adjusting age, education, MMSE scores, corrected p &lt; 0.05, FDR correction).ResultEast Asians were shown to have a higher cortical thickness in bilateral superior frontal, lateral and medial orbitofrontal, middle temporal, left superior parietal, right inferior parietal, and inferior temporal cortex and lower cortical thickness in bilateral parahippocampus, postcentral, lateral occipital, left transverse temporal, lingual, precuneus, right superior temporal, fusiform cortex than Caucasians. Additionally, interactions between age and race had an impact on cortical thickness in right superior frontal cortex.ConclusionThe findings indicated that there was a significant difference in cortical thickness between cognitively healthy elderly in East Asians and in Caucasians according to the brain regions. The findings could contribute to a better understanding of the race‐specific structural change in the normal aging and provide an importance of an ethnic‐specific template for evaluating the structural and functional brain imaging in the healthy aging and neurodegenerative disease including Alzheimer’s disease.

Individual pain sensitivity is associated with resting-state cortical activities in healthy individuals but not in patients with migraine: a magnetoencephalography study

BackgroundPain sensitivity may determine the risk, severity, prognosis, and efficacy of treatment of clinical pain. Magnetic resonance imaging studies have linked thermal pain sensitivity to changes in brain structure. However, the neural correlates of mechanical pain sensitivity remain to be clarified through investigation of direct neural activities on the resting-state cortical oscillation and synchrony.MethodsWe recorded the resting-state magnetoencephalographic (MEG) activities of 27 healthy individuals and 30 patients with episodic migraine (EM) and analyzed the source-based oscillatory powers and functional connectivity at 2 to 59 Hz in pain-related cortical regions, which are the bilateral anterior cingulate cortex (ACC), medial orbitofrontal (MOF) cortex, lateral orbitofrontal (LOF) cortex, insula cortex, primary somatosensory cortex (SI), primary motor cortex (MI), and posterior cingulate cortex (PCC). The mechanical punctate pain threshold (MPPT) was obtained at the supraorbital area (the first branch of the trigeminal nerve dermatome, V1) and the forearm (the first thoracic nerve dermatome, T1) and further correlated with MEG measures.ResultsThe MPPT is inversely correlated with the resting-state relative powers of gamma oscillation in healthy individuals (all corrected P < 0.05). Specifically, inverse correlation was noted between the MPPT at V1 and gamma powers in the bilateral insula (r = − 0.592 [left] and − 0.529 [right]), PCC (r = − 0.619 and − 0.541) and MI (r = − 0.497 and − 0.549) and between the MPPT at T1 and powers in the left PCC (r = − 0.561) and bilateral MI (r = − 0.509 and − 0.520). Furthermore, resting-state functional connectivity at the delta to beta bands, especially between frontal (MOF, ACC, LOF, and MI), parietal (PCC), and sensorimotor (bilateral SI and MI) regions, showed a positive correlation with the MPPT at V1 and T1 (all corrected P < 0.05). By contrast, in patients with EM, the MPPT was not associated with resting-state cortical activities.ConclusionsPain sensitivity in healthy individuals is associated with the resting-state gamma oscillation and functional connectivity in pain-related cortical regions. Further studies must be conducted in a large population to confirm whether resting-state cortical activities can be an objective measurement of pain sensitivity in individuals without clinical pain.

Gray matter volumetric correlates of behavioral activation and inhibition system traits in children: An exploratory voxel-based morphometry study of the ABCD project data

Approach and avoidance represent two fundamental behavioral traits that develop early in life. Previous studies have examined the neural correlates of approach and avoidance traits in adults and adolescents. Here, using the data set of the Adolescent Brain Cognition Development project, we investigated the structural cerebral bases of behavioral activation system (BAS) and behavioral inhibition system (BIS) in children. We employed voxel-based morphometry to examine how gray matter volumes (GMV) related specifically to BAS and BIS traits in 11,542 children (5491 girls, age 9–10 years) with 648 and 2697 identified as monozygotic twins (MZ) and dizygotic twins/siblings (DZ), respectively. After accounting for the BIS score, higher BAS scores (residuals) were positively correlated with the GMV of the ventral striatum (VS), and the correlation was stronger in MZ than in DZ and unrelated children, with a heritability (h2) of 0.8463. Higher BAS scores were negatively correlated with the GMV of bilateral visual, lateral orbitofrontal, temporal, and inferior frontal cortex, as well as the precuneus. Higher BIS (after accounting for BAS) scores were negatively correlated with the GMVs of the ventral caudate and bilateral putamen/pallidum, hypothalamus, and right anterior insula, and the correlation was stronger in MZ than in DZ and unrelated children, with a heritability of 0.8848. A cluster in the VS showed positive and negative correlation with the BAS and BIS scores, respectively. These findings suggest shared and distinct cerebral volumetric bases of the BAS and BIS traits in children. Whereas both traits have a strong genetic basis, the BAS relative to BIS appears to be more amenable to environmental influences. These findings add to the literature of developmental neuroscience and may help identify genetic risk factors of externalizing and internalizing psychopathology.