Anterior Cingulate Cortex Volume Research Articles

Shared and distinct alterations in brain morphology in children with ADHD and obesity: Reduced cortical surface area in ADHD and thickness in overweight/obesity

ObjectiveTo investigate shared versus distinct differences in brain structure among children with ADHD and obesity, we examined the morphology of regions implicated in cognitive control and reward function in a single cross-sectional cohort of children with and without ADHD and overweight/obesity (OV/OB). MethodParticipants included 471 children ages 8–12 years with ADHD (n = 244; 58 OV/OB) and neurotypical (NT) controls (n = 227; 81 OV/OB) classified as healthy-weight (HW; BMI %ile 5th to <85th) vs. having OV/OB (BMI %ile≥85th). Structural MRI was performed to obtain measures of cortical and subcortical morphology and compared across ADHD × BMI groups. ResultsSurface area was generally lower in ADHD vs. NT including in anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (dlPFC), medial (m)PFC, and primary motor (M1) cortex. In contrast, cortical thickness was generally lower in OV/OB vs. HW for ACC, dlPFC, orbitofrontal cortex (OFC), mPFC, and supplementary motor cortex (SMC). Furthermore, ADHD × OV/OB interactions were observed for the ACC and OFC, with the lowest ACC volume in the ADHD + OV/OB group and the highest OFC surface area in the NT + OV/OB group. Subcortical volumes did not differ between groups. ConclusionsOur findings reveal distinct alterations in cortical morphology in association with ADHD and overweight, with cortical surface area reduced in ADHD vs. thickness reduced in OV/OB. Additionally, the findings provide evidence of combined effects of ADHD × OV/OB in brain regions integral to cognition and motivation. Our results support further investigation of causes and correlates of shared and distinct ADHD- and OV/OB-associated differences in developing frontocingulate morphology.

Structural and functional correlates of olfactory reward processing in behavioral variant frontotemporal dementia

The behavioral variant of frontotemporal dementia (bvFTD) includes symptoms that reflect altered pursuit of rewards, including food, alcohol, and money. Little is known, however, about how these reward changes relate to atrophy and functional connectivity within reward-related regions. The goal of this study was to examine the structural and functional correlates of valence perception for olfactory rewards in 24 patients with bvFTD. Regression analysis of resting-state brain functional connectivity indicated that more positive valence ratings of olfactory stimuli were predicted by ventral pallidum connectivity to other reward circuit regions, particularly functional connectivity between ventral pallidum and bilateral anterior cingulate cortex/ventromedial prefrontal cortex. Structural analysis showed that atrophy of the anterior cingulate cortex was also significantly associated with perceiving stimuli as more rewarding. Finally, there was a significant interaction between ventral pallidum connectivity and atrophy of the anterior cingulate cortex. More specifically, the ventral pallidum connectivity had a greater effect on the positive perception of olfactory stimuli in the setting of low anterior cingulate cortex volume. These findings indicate that atrophy and functional connectivity within reward-relevant regions exert independent and interacting effects on the perception of pleasantness in bvFTD, potentially due to changes in hedonic “liking” signals.

Posthospitalization COVID-19 cognitive deficits at 1 year are global and associated with elevated brain injury markers and gray matter volume reduction.

The spectrum, pathophysiology and recovery trajectory of persistent post-COVID-19 cognitive deficits are unknown, limiting our ability to develop prevention and treatment strategies. We report the 1-year cognitive, serum biomarker and neuroimaging findings from a prospective, national study of cognition in 351 COVID-19 patients who required hospitalization, compared with 2,927 normative matched controls. Cognitive deficits were global, associated with elevated brain injury markers and reduced anterior cingulate cortex volume 1 year after COVID-19. Severity of the initial infective insult, postacute psychiatric symptoms and a history of encephalopathy were associated with the greatest deficits. There was strong concordance between subjective and objective cognitive deficits. Longitudinal follow-up in 106 patients demonstrated a trend toward recovery. Together, these findings support the hypothesis that brain injury in moderate to severe COVID-19 may be immune-mediated, and should guide the development of therapeutic strategies.

Understanding Depression in Autism: The Role of Subjective Perception and Anterior Cingulate Cortex Volume.

The prevalence of depression is elevated in individuals with autism spectrum disorder (ASD) compared to the general population, yet the reasons for this disparity remain unclear. While social deficits central to ASD may contribute to depression, it is uncertain whether social interaction behavior themselves or individuals' introspection about their social behaviors are more impactful. Although the anterior cingulate cortex (ACC) and amygdala are frequently implicated in ASD, depression, and social functioning, it is unknown if these regions explain differences between ASD adults with and without co-occurring depression. The present study contrasted observed vs. subjective perception of autism symptoms and social performances assessed with both standardized measures and a lab task, in 65 sex-balanced (52.24% male) autistic young adults. We also quantified ACC and amygdala volume with 7-Tesla structural neuroimaging to examine correlations with depression and social functioning. We found that ASD individuals with depression exhibited differences in subjective evaluations including heightened self-awareness of ASD symptoms, lower subjective satisfaction with social relations, and less perceived affiliation during the social interaction task, yet no differences in corresponding observed measures, compared to those without depression. Larger ACC volume was related to depression, greater self-awareness of ASD symptoms, and worse subjective satisfaction with social interactions. In contrast, amygdala volume, despite its association with clinician-rated ASD symptoms, was not related to depression. Due to the cross-sectional nature of our study, we cannot determine the directionality of the observed relationships. Additionally, we included only individuals with an IQ over 60 to ensure participants could complete the social task, which excluded many on the autism spectrum. We also utilized self-reported depression indices instead of clinically diagnosed depression, which may limit the comprehensiveness of the findings. Our approach highlights the unique role of subjective perception of autism symptoms and social interactions, beyond the observable manifestation of social interaction in ASD, in contributing to depression, with the ACC playing a crucial role. These findings imply possible heterogeneity of ASD concerning co-occurring depression. Using neuroimaging, we were able to demarcate depressive phenotypes co-occurring alongside autistic phenotypes.

Atlas-based structural analysis of prefrontal cortex atrophy in major depressive disorder: Correlations with severity and episode frequency

BackgroundCurrent models of major depressive disorder (MDD) primarily focus on the structural and functional changes in key prefrontal areas responsible for emotional regulation. Among these regions some sections such as the dorsal prefrontal area, has received limited attention regarding its structural abnormalities in MDD. This study aims to evaluate volumetric abnormalities in brain regions associated with markers of depression severity and episode frequency. MethodsThe study included 33 MDD patients and 33 healthy subjects. Using an atlas-based method, we measured the volumes of several key brain regions based on MRI data. The regions of interest included prefrontal and posterior sections of the middle frontal gyrus (MFG) and superior frontal gyrus (SFG). Additionally, we evaluated the volumes of the dorsal anterior cingulate cortex (dACC), perigenual (rostral) anterior cingulate cortex (pgACC), subgenual cingulate cortex (sgACC), posterior cingulate cortex (PCC), hippocampus (HPC), and parahippocampus (paraHPC). Hamilton Depression Scale (HAM-D) scores and count of the depressive episodes of patients were also obtained. A regression analysis with sex as the confounding factor has been made. ResultsAnalysis of covariances, controlling for sex, showed significant atrophy in the sgACC in the depression group: F(1, 63) = 4.013, p = 0.049 (left) and F(1, 63) = 8.786, p < 0.004 (right). Poisson regression, also controlling for sex, found that each additional depressive episode was associated with a significant reduction in left posterior MFG volume (0.952 times, 95 % CI, 0.906 to 1.000; p = 0.049). ConclusionsFindings in this study highlight the structural abnormalities in MDD patients in correlation to either current depression severity or chronicity of the disease.

Baseline Frontoparietal Gray Matter Volume Predicts Executive Function Performance in Aging and Mild Cognitive Impairment at 24-Month Follow-Up.

Executive dysfunction in mild cognitive impairment (MCI) has been associated with gray matter atrophy. Prior studies have yielded limited insight into associations between gray matter volume and executive function in early and late amnestic MCI (aMCI). To examine the relative importance of predictors of executive function at 24 months and relationships between baseline regional gray matter volume and executive function performance at 24-month follow-up in non-demented older adults. 147 participants from the Alzheimer's Disease Neuroimaging Initiative (mean age = 70.6 years) completed brain magnetic resonance imaging and neuropsychological testing and were classified as cognitively normal (n = 49), early aMCI (n = 60), or late aMCI (n = 38). Analyses explored the importance of demographic, APOEɛ4, biomarker (p-tau/Aβ42, t-tau/Aβ42), and gray matter regions-of-interest (ROI) variables to 24-month executive function, whether ROIs predicted executive function, and whether relationships varied by baseline diagnostic status. Across all participants, baseline anterior cingulate cortex and superior parietal lobule volumes were the strongest predictors of 24-month executive function performance. In early aMCI, anterior cingulate cortex volume was the strongest predictor and demonstrated a significant interaction such that lower volume related to worse 24-month executive function in early aMCI. Educational attainment and inferior frontal gyrus volume were the strongest predictors of 24-month executive function performance for cognitively normal and late aMCI groups, respectively. Baseline frontoparietal gray matter regions were significant predictors of executive function performance in the context of aMCI and may identify those at risk of Alzheimer's disease. Anterior cingulate cortex volume may predict executive function performance in early aMCI.

New insights into the effects of type and timing of childhood maltreatment on brain morphometry.

Childhood maltreatment (CM) is known to influence brain development. To obtain a better understanding of related brain alterations, recent research has focused on the influence of the type and timing of CM. We aimed to investigate the association between type and timing of CM and local brain volume. Anatomical magnetic resonance images were collected from 93 participants (79 female/14 male) with a history of CM. CM history was assessed with the German Interview Version of the "Maltreatment and Abuse Chronology of Exposure" scale, "KERF-40 + ". Random forest regressions were performed to assess the impact of CM characteristics on the volume of amygdala, hippocampus and anterior cingulate cortex (ACC). The volume of the left ACC was predicted by neglect at age 3 and 4 and abuse at age 16 in a model including both type and timing of CM. For the right ACC, overall CM severity and duration had the greatest impact on volumetric alterations. Our data point to an influence of CM timing on left ACC volume, which was most pronounced in early childhood and in adolescence. We were not able to replicate previously reported effects of maltreatment type and timing on amygdala and hippocampal volume.

The Brain Structure of Patients with Borderline Personality Disorder: A Review of Positron Emission Tomography and Structural Magnetic Resonance Imaging

Borderline personality disorder (BPD) is a severe mental disorder characterized by a consistent pattern of emotional inconsistency, poor impulse management, unstable personal relationships, and a constantly fluctuating self-image. Researchers have lately made significant progress in grasping the potential neurobiological underpinnings of BPD, and neuroimaging has emerged as a pivotal instrument in examining differences between BPD patients and healthy controls. This article will explore past studies on neuroimaging of patients with bipolar disorder, including PET and sMRI. BPD patients are likely to display hypometabolism in prefrontal regions and metabolic changes in temporal and parietal lobes. There are also studies pointing to the significance of anterior cingulate cortex (ACC) and structural volume. However, the results are mainly inconsistent. The limiting sample sizes may be one of the reasons for such a high level of variance. Therefore, studies with larger and more inclusive sample sizes are needed to reach firm conclusions. Moreover, the relationship between medication/therapy and the changes in BPD patients brain activities also needed to be explored.

Associations between low-moderate prenatal alcohol exposure and brain development in childhood

BackgroundThe effects of low-moderate prenatal alcohol exposure (PAE) on brain development have been infrequently studied. AimTo compare cortical and white matter structure between children aged 6 to 8 years with low-moderate PAE in trimester 1 only, low-moderate PAE throughout gestation, or no PAE. MethodsWomen reported quantity and frequency of alcohol consumption before and during pregnancy. Magnetic resonance imaging was undertaken for 143 children aged 6 to 8 years with PAE during trimester 1 only (n = 44), PAE throughout gestation (n = 58), and no PAE (n = 41). T1-weighted images were processed using FreeSurfer, obtaining brain volume, area, and thickness of 34 cortical regions per hemisphere. Fibre density (FD), fibre cross-section (FC) and fibre density and cross-section (FDC) metrics were computed for diffusion images. Brain measures were compared between PAE groups adjusted for age and sex, then additionally for intracranial volume. ResultsAfter adjustments, the right caudal anterior cingulate cortex volume (pFDR = 0.045) and area (pFDR = 0.008), and right cingulum tract cross-sectional area (pFWE < 0.05) were smaller in children exposed to alcohol throughout gestation compared with no PAE. ConclusionThis study reports a relationship between low-moderate PAE throughout gestation and cingulate cortex and cingulum tract alterations, suggesting a teratogenic vulnerability. Further investigation is warranted.

Relevance of the anterior cingulate cortex volume and personality in motivated physical activity behaviors

Some recent theories about the origins and maintenance of regular physical activity focus on the rewards of the properties of practicing this activity. Animal and human studies have demonstrated that mesolimbic dopamine plays a crucial role in the involvement in voluntary physical activity. Here, we test this possible role in a sample of 66 right-handed healthy young adults by studying the influence of personality and the volume of reward-related brain areas on individual differences in voluntary physical activity, objectively measured by accelerometer and subjectively self-reported by questionnaire. Our results show that a smaller volume of the right anterior cingulate cortex and lower scores on reward sensitivity contributed to explaining low levels of daily physical activity. Moreover, the volume of the right anterior cingulate cortex correlates positively with self-reported total physical activity. Results are discussed by highlighting the need to use objective measures of daily physical activity, as well as the important role of the anterior cingulate cortex and personality in promoting effortful and invigorating actions to obtain rewards.

Preliminary investigation of the interactive role of physiological arousal and insomnia complaints in gray matter volume alterations in chronic widespread pain.

Brain regions involved in insomnia and chronic pain are overlapping and diffuse. The interactive role of physiological arousal in associations between insomnia symptoms and neural regions is unknown. This preliminary study examined whether arousal interacted with sleep in associations with gray matter volume of frontal (dorsolateral prefrontal cortex, anterior cingulate cortex) and temporal (right/left hippocampus) regions in adults with chronic widespread pain and insomnia complaints. Forty-seven adults with chronic widespread pain and insomnia (mean age = 46.00, standard deviation = 13.88, 89% women) completed 14 daily diaries measuring sleep onset latency (SOL), wake time after sleep onset, and total sleep time (TST), as well as Holter monitor assessments of heart rate variability (measuring physiological arousal), and magnetic resonance imaging. Multiple regressions examined whether average SOL, wake time after sleep onset, or TST were independently or interactively (with arousal/heart rate variability) associated with dorsolateral prefrontal cortex, anterior cingulate cortex, and left/right hippocampus gray matter volumes. Shorter TST was associated with lower right hippocampus volume. TST also interacted with arousal in its association with right hippocampal volume, Specifically, shorter TST was associated with lower volume at highest and average arousal levels. SOL interacted with arousal in its association with anterior cingulate cortex volume, such that, among individuals with lowest arousal, longer SOL was associated with lower volume. Preliminary findings highlight the interactive roles of physiological arousal and insomnia symptoms in associations with neural structure in chronic widespread pain and insomnia. Individuals with the highest physiological arousal may be particularly vulnerable to the impact of shorter TST on hippocampal volume loss. Reducing SOL may only impact anterior cingulate cortex volume in those with lower physiological arousal. Curtis AF, Nair N, Hayse B, etal. Preliminary investigation of the interactive role of physiological arousal and insomnia complaints in gray matter volume alterations in chronic widespread pain. J Clin Sleep Med. 2024;20(2):293-302.

Effects of inhaled corticosteroids on brain volumetry, depression and anxiety-like behaviors in a rat model of asthma

Brain functional deficits have been reported in asthma patients which can result in behavioral disorders like depression and anxiety. These deficits may be associated with factors like resistance to treatment, incorrect self-evaluation, and inadequate self-control. However, changes in the brain volume in allergic asthma and the effects of inhaled corticosteroids, the most common anti-inflammatory agents for asthma treatment, on these alterations remain largely unclear. Here, we evaluated depression and anxiety-like behavior as well as volume changes in different brain area, using magnetic resonance imaging in an animal model of allergic asthma with pretreatment of inhaled fluticasone propionate. Asthma-induced behavioral changes were partially, but not completely, prevented by pretreatment with inhaled fluticasone propionate. Volumetry findings showed that the allergen decreased volumes of the corpus callosum and subcortical white matter, as well as the septal region and hippocampus (especially CA1 and fimbria). However, volumes of neocortex, insular, and anterior cingulate cortex increased in asthmatic rats compared to controls. Namely, pretreatment with inhaled fluticasone propionate partially prevented asthma-induced brain volume changes, but not completely. These findings suggest that asthma is associated with structural alterations in the brain, which may contribute to the induction of psychological disorders. Thus, considering brain changes in the clinical assessments could have important implications for asthma treatment.

Hormonal contraceptive exposure relates to changes in resting state functional connectivity of anterior cingulate cortex and amygdala.

Hormonal contraceptives (HCs), nowadays one of the most used contraceptive methods, downregulate endogenous ovarian hormones, which have multiple plastic effects in the adult brain. HCs usually contain a synthetic estrogen, ethinyl-estradiol, and a synthetic progestin, which can be classified as androgenic or anti-androgenic, depending on their interaction with androgen receptors. Both the anterior cingulate cortex (ACC) and the amygdala express steroid receptors and have shown differential functionality depending on the hormonal status of the participant and the use of HC. In this work, we investigated for the first time the relationship between ACC and amygdala resting state functional connectivity (rs-FC) and HC use duration, while controlling for progestin androgenicity. A total of 231 healthy young women participated in five different magnetic resonance imaging studies and were included in the final analysis. The relation between HC use duration and (i) gray matter volume, (ii) fractional amplitude of low-frequency fluctuations, and (iii) seed-based connectivity during resting state in the amygdalae and ACC was investigated in this large sample of women. In general, rs-FC of the amygdalae with frontal areas, and between the ACC and temporoparietal areas, decreased the longer the HC exposure and independently of the progestin's androgenicity. The type of HC's progestin did show a differential effect in the gray matter volume of left ACC and the connectivity between bilateral ACC and the right inferior frontal gyrus.

Chronic Cough-Related Differences in Brain Morphometry in Adults: A Population-Based Study

Individuals with cough hypersensitivity have increased central neural responses to tussive stimuli, which may result in maladaptive morphometric changes in the central cough processing systems. Are the volumes of the brain regions implicated in cough hypersensitivity different in adults with chronic cough compared with adults without chronic cough? Between 2009 and 2014, participants in the Rotterdam Study, a population-based cohort, underwent brain MRI and were interviewed for chronic cough, which was defined as daily coughing for at least 3months. Regional brain volumes were quantified with the use of parcellation software. Based on literature review, we identified and studied seven brain regions that previously had been associated with altered functional brain activity in chronic cough. The relationship between chronic cough and regional brain volumes was investigated with the use of multivariable regression models. Chronic cough was prevalent in 9.6%(No.= 349) of the 3,620 study participants (mean age, 68.5 ± 9.0 years; 54.6%female). Participants with chronic cough had significantly smaller anterior cingulate cortex volume than participants without chronic cough (mean difference, -126.16mm3; 95%CI, -245.67 to -6.66; P= .039). Except for anterior cingulate cortex, there were no significant difference in the volume of other brain regions based on chronic cough status. The volume difference in the anterior cingulate cortex was more pronounced in the left hemisphere (mean difference, -88.11mm3; 95%CI, -165.16 to -11.06; P= .025) and in male participants (mean difference, -242.58mm3; 95%CI, -428.60 to -56.55; P= .011). Individuals with chronic cough have a smaller volume of the anterior cingulate cortex, which is a brain region involved in cough suppression. The Netherlands National Trial Registry (NTR; www.trialregister.nl) and the World Health Organization's International Clinical Trials Registry Platform (ICTRP; www.who.int/ictrp/network/primary/en/) under the joint catalogue number NTR6831.

Physical Activity Level Moderates the Association Between Response Inhibition and Anterior Cingulate Cortex Volume in Older Adults

AbstractBackgroundAging is generally associated with a decline in executive function, a cognitive domain that is critical to functional independence. Response inhibition is an executive process that contributes to anticipation, planning, and goal setting. The anterior cingulate cortex (ACC) is a key brain structure that supports response inhibition and shows gray matter loss with age. Evidence suggests that both response inhibition performance and the Anterior Cingulate Cortex (ACC) are responsive to exercise training. Whether physical activity moderates the relationship between response inhibition and the ACC in older adults is unknown.MethodA cross‐sectional analysis of a subset of community‐dwelling older adults enrolled in a 3‐arm, 8‐week proof of concept randomized control trial of computerized cognitive training, with or without exercise, who completed T1 magnetic resonance imaging (MRI) at baseline. Of the 68 MRI participants, 11 were removed from this analysis due to poor scan quality. Response inhibition was measured using the Flanker Task from the NIH Toolbox Cognitive Battery. Participants were split into either a high or low physical activity groups determined by their median Physical Activity Scale for the Elderly (PASE) score. Caudal and rostral ACC volumes were segmented and quantified using FreeSurfer. To assess for moderation, we performed linear regressions with age‐adjusted Flanker Task score as the dependent variable, and ACC volume, high/low PASE, and the interaction of ACC volume * high/low PASE as independent variables.ResultPhysical activity level significantly moderated the association between left caudal anterior cingulate cortex (LCACC) volume and age‐adjusted Flanker Task score, (β = –6.428, t(53) = ‐2.075, p &lt; .05). Among those with low physical activity levels (n = 30), greater LCACC volume was associated with better response inhibition (r = 0.44, p = .01) while there was no association among those with high physical activity levels (n = 27; r = ‐0.13; p = .52).ConclusionHigher physical activity may mitigate the negative effects of age‐related gray matter loss in the ACC on response inhibition performance in community‐dwelling older adults.

The Effects of Stressful Life Events on Alzheimer’s Disease Biomarkers, Neuroinflammation and Brain Integrity in Later Life: A Life Course Perspective

AbstractBackgroundStress is associated with adverse health outcomes, but the pathways through which stressful life events affect brain health, and the age periods most vulnerable to these effects, are unknown. We investigated these questions in relation to Alzheimer’s disease (AD) pathophysiology and brain integrity in cognitively unimpaired participants at risk for AD.MethodIn this cross‐sectional cohort study, 1168 participants completed the 18‐item Elder’s Life Stress Inventory measuring the occurrence (and age at occurrence) of stressful life events. Of these, 393 participants had data available on AD biomarkers (cerebrospinal fluid [CSF] phosphorylated‐tau and amyloid‐beta1−42/amyloid‐beta1−40 ratio measured with Elecsys® assays and NeuroToolKit panel of robust prototype assays [Roche Diagnostics International Ltd, Rotkreuz, Switzerland], respectively) and neuroinflammation markers (CSF interleukin 6 [IL‐6], soluble TREM‐2 and glial fibrillary acidic protein measured with NeuroToolKit). In total, 830 had structural magnetic resonance imaging data available for amygdala and hippocampal volume, and grey matter volume/thickness for areas of the prefrontal cortex. The association of stressful events with AD biomarkers, neuroinflammation and brain integrity (adjusting for total intracranial volume) was examined using multiple regression analyses adjusting for sex, age and education. Associations of stressful events during early life (ages 0−25), early adulthood (26−40), middle adulthood (41−55) and late adulthood (≥56) were also examined. Analyses were stratified by sex and Apolipoprotein ε4 (APOE ε4)‐status.ResultParticipants’ age ranged between 47−76 and 62.5% were women. A higher number of stressful events during life‐course was associated with an increase in IL‐6 levels among APOE ε4‐carriers; with a decreased amyloid‐beta ratio among APOE ε4‐noncarriers; and with a reduction in caudal anterior cingulate cortex volume among women. A higher number of events during early adulthood was associated with higher phosphorylated‐tau levels and prefrontal brain integrity, and during middle adulthood was associated with decreased prefrontal brain integrity (Table 1. &amp; 2.).ConclusionStress may affect later‐life brain health through multiple pathways, including neuroinflammation, amyloid‐beta and brain integrity, depending on APOE ε4‐carrier status and sex. Stressful events during early adulthood may promote phosphorylated‐tau in later‐life, while events during early/middle adulthood may have differential effects on brain integrity, suggesting potential windows for stress‐prevention strategies.

Sex-specific association between prenatal androgenization (second-to-fourth digit length ratio) and frontal brain volumes in adolescents

Prenatal androgenization associates sex-dependently with behavior and mental health in adolescence and adulthood, including risk-taking, emotionality, substance use, and depression. However, still little is known on how it affects underlying neural correlates, like frontal brain control regions. Thus, we tested whether prenatal androgen load is sex-dependently related to frontal cortex volumes in a sex-balanced adolescent sample. In a cross-sectional magnetic resonance imaging study, we examined 61 adolescents (28 males, 33 females; aged 14 or 16 years) and analyzed associations of frontal brain region volumes with the second-to-fourth digit length ratio (2D:4D), an established marker for prenatal androgenization, using voxel-based morphometry in a region-of-interest approach. Lower 2D:4D (indicative of higher prenatal androgen load) correlated significantly with smaller volumes of the right anterior cingulate cortex (r-ACC; β = 0.45) in male adolescents and with larger volumes of the left inferior frontal gyrus orbital part (l-IFGorb; β = – 0.38) in female adolescents. The regression slopes of 2D:4D on the r-ACC also differed significantly between males and females. The study provides novel evidence that prenatal androgenization may influence the development of the frontal brain in a sex- and frontal brain region-specific manner. These effects might contribute to the well-known sex differences in risk-taking, emotionality, substance use, and depression. Future research is needed to elucidate the role of prenatal androgenization within the biopsychosocial model.

Effect of an 18-Month Meditation Training on Regional Brain Volume and Perfusion in Older Adults

No lifestyle-based randomized clinical trial directly targets psychoaffective risk factors of dementia. Meditation practices recently emerged as a promising mental training exercise to foster brain health and reduce dementia risk. To investigate the effects of meditation training on brain integrity in older adults. Age-Well was a randomized, controlled superiority trial with blinded end point assessment. Community-dwelling cognitively unimpaired adults 65 years and older were enrolled between November 24, 2016, and March 5, 2018, in France. Participants were randomly assigned (1:1:1) to (1) an 18-month meditation-based training, (2) a structurally matched non-native language (English) training, or (3) no intervention arm. Analysis took place between December 2020 and October 2021. Meditation and non-native language training included 2-hour weekly group sessions, practice of 20 minutes or longer daily at home, and 1-day intensive practices. Primary outcomes included volume and perfusion of anterior cingulate cortex (ACC) and insula. Main secondary outcomes included a global composite score capturing metacognitive, prosocial, and self-regulatory capacities and constituent subscores. Among 137 participants (mean [SD] age, 69.4 [3.8] years; 83 [60.6%] female; 54 [39.4%] male) assigned to the meditation (n = 45), non-native language training (n = 46), or no intervention (n = 46) groups, all but 1 completed the trial. There were no differences in volume changes of ACC (0.01 [98.75% CI, -0.02 to 0.05]; P = .36) or insula (0.01 [98.75% CI, -0.02 to 0.03]; P = .58) between meditation and no intervention or non-native language training groups, respectively. Differences in perfusion changes did not reach statistical significance for meditation compared with no intervention in ACC (0.02 [98.75% CI, -0.01 to 0.05]; P = .06) or compared with non-native language training in insula (0.02 [98.75% CI, -0.01 to 0.05]; P = .09). Meditation was superior to non-native language training on 18-month changes in a global composite score capturing attention regulation, socioemotional, and self-knowledge capacities (Cohen d, 0.52 [95% CI, 0.19-0.85]; P = .002). The study findings confirm the feasibility of meditation and non-native language training in elderly individuals, with high adherence and very low attrition. Findings also show positive behavioral effects of meditation that were not reflected on volume, and not significantly on perfusion, of target brain areas. ClinicalTrials.gov Identifier: NCT02977819.

Possible Role of Endocannabinoids in Olfactory and Taste Dysfunctions in COVID-19 Patients and Volumetric Changes in the Brain.

IntroductionCOVID-19 infection develops neurologic symptoms such as smell and taste loss. We aimed to determine the volumetric changes in the brain and correlation of possible related biochemical parameters and endocannabinoid levels after COVID-19 recovery.MethodsBrain magnetic resonance images of recovered COVID-19 patients and healthy volunteers, whose olfactory and gustatory scores were obtained through a questionnaire, were taken, and the volumes of the brain regions associated with taste and smell were measured by automatic and semiautomatic methods. Endocannabinoids (EC), which are critical in the olfactory system, and vitamin B12, zinc, iron, ferritin, thyroid-stimulating hormone (TSH), and thyroxine (T4) levels, which are reported to have possible roles in olfactory disorders, were measured in peripheral blood.ResultsTaste and smell disorder scores and EC levels were found to be higher in recovered COVID-19 patients compared to controls. EC levels were negatively correlated with bilateral entorhinal cortex (ENT) volumes in the COVID-19 group. Subgenual anterior cingulate cortex volumes showed correlations with gustatory complaints and ferritin in recovered COVID-19 patients.ConclusionsThe critical finding of our study is the high EC levels and negative correlation between EC levels and left ENT volumes in recovered COVID-19 patients.ImplicationsIt is possible that ECs are potential neuromodulators in many conditions leading to olfactory disorders, including COVID-19.

The Relationships between Dopaminergic, Glutamatergic, and Cognitive Functioning in 22q11.2 Deletion Syndrome: A Cross-Sectional, Multimodal 1H-MRS and 18F-Fallypride PET Study.

Background: Individuals with 22q11.2 deletion syndrome (22q11DS) are at increased risk of developing psychosis and cognitive impairments, which may be related to dopaminergic and glutamatergic abnormalities. Therefore, in this exploratory study, we examined the association between dopaminergic and glutamatergic functioning in 22q11DS. Additionally, the associations between glutamatergic functioning and brain volumes in 22q11DS and healthy controls (HC), as well as those between dopaminergic and cognitive functioning in 22q11DS, were also examined. Methods: In this cross-sectional, multimodal imaging study, glutamate, glutamine, and their combined concentration (Glx) were assessed in the anterior cingulate cortex (ACC) and striatum in 17 22q11DS patients and 20 HC using 7T proton magnetic resonance spectroscopy. Ten 22q11DS patients also underwent 18F-fallypride positron emission tomography to measure dopamine D2/3 receptor (D2/3R) availability in the ACC and striatum. Cognitive performance was assessed with the Cambridge Neuropsychological Test Automated Battery. Results: No significant associations were found between ACC or striatal (1) glutamate, glutamine, or Glx concentrations and (2) D2/3R availability. In HC but not in 22q11DS patients, we found a significant relationship between ACC volume and ACC glutamate, glutamine, and Glx concentration. In addition, some aspects of cognitive functioning were significantly associated with D2/3R availability in 22q11DS. However, none of the associations remained significant after Bonferroni correction. Conclusions: Although our results did not reach statistical significance, our findings suggest an association between glutamatergic functioning and brain volume in HC but not in 22q11DS. Additionally, D2/3R availability seems to be related to cognitive functioning in 22q11DS. Studies in larger samples are needed to further elucidate our findings.