Dorsolateral Prefrontal Cortex Volume Research Articles

Linking the evolution of two prefrontal brain regions to social and foraging challenges in primates.

The diversity of cognitive skills across primates remains both a fascinating and a controversial issue. Recent comparative studies provided conflicting results regarding the contribution of social vs ecological constraints to the evolution of cognition. Here, we used an interdisciplinary approach combining comparative cognitive neurosciences and behavioral ecology. Using brain imaging data from 16 primate species, we measured the size of two prefrontal brain regions, the frontal pole (FP) and the dorso-lateral prefrontal cortex (DLPFC), respectively, involved in metacognition and working memory, and examined their relation to a combination of socio-ecological variables. The size of these prefrontal regions, as well as the whole brain, was best explained by three variables: body mass, daily traveled distance (an index of ecological constraints), and population density (an index of social constraints). The strong influence of ecological constraints on FP and DLPFC volumes suggests that both metacognition and working memory are critical for foraging in primates. Interestingly, FP volume was much more sensitive to social constraints than DLPFC volume, in line with laboratory studies showing an implication of FP in complex social interactions. Thus, our data highlights the relative weight of social vs ecological constraints on the evolution of specific prefrontal brain regions and their associated cognitive operations in primates.

Linking the evolution of two prefrontal brain regions to social and foraging challenges in primates

The diversity of cognitive skills across primates remains both a fascinating and a controversial issue. Recent comparative studies provided conflicting results regarding the contribution of social vs ecological constraints to the evolution of cognition. Here, we used an interdisciplinary approach combining comparative cognitive neurosciences and behavioral ecology. Using brain imaging data from 16 primate species, we measured the size of two prefrontal brain regions, the frontal pole (FP) and the dorso-lateral prefrontal cortex (DLPFC), respectively, involved in metacognition and working memory, and examined their relation to a combination of socio-ecological variables. The size of these prefrontal regions, as well as the whole brain, was best explained by three variables: body mass, daily traveled distance (an index of ecological constraints), and population density (an index of social constraints). The strong influence of ecological constraints on FP and DLPFC volumes suggests that both metacognition and working memory are critical for foraging in primates. Interestingly, FP volume was much more sensitive to social constraints than DLPFC volume, in line with laboratory studies showing an implication of FP in complex social interactions. Thus, our data highlights the relative weight of social vs ecological constraints on the evolution of specific prefrontal brain regions and their associated cognitive operations in primates.

Predicting the Outcome of First Episode Psychosis Subjects by Assessing Dorsolateral Prefrontal Cortex Volume

Aim: Dorsolateral prefrontal cortex (DLPFC), Neurological Soft Signs (NSS) and Cognitive impairment have been described as predictors of outcome of First Episode Psychosis (FEP), therefore we aimed to find the predictors of clinical, social and functional outcome variables in a cohort of first episode non affective psychotic subjects. Subjects and Methods: A prospective follow up study was conducted from August 2018 to August 2020 in a tertiary care hospital of South India. A semi-structured questionnaire was given to all subjects for socio-demographic details. All subjects were assessed with Heidelberg scale, Bender Gestalt Test (BGT) and underwent MRI Brain 3D volumetric scan to examine NSS, cognitive impairment, and DLPFC volume at baseline respectively. Brief Psychiatric Rating Scale (BPRS) and Social and Occupational Functioning Assessment Scale scales (SOFAS) were administered at baseline, 1 month and at three month follow up. At 3 months, clinical and socio-functional outcome was defined by BPRS scores and SOFAS scores. Pearson’s correlation was found between DLPFC volume of all subjects, BPRS, BGT scores at baseline with BPRS and SOFAS at 3 months. To test the statistical significance of the comparison of mean values of all continuous clinical and demographic parameters between two groups of BPRS and SOFAS, Mann Whitney U test was used. Results: Smaller DLPFC volume predicted clinical, socio-functional outcome significantly. A significant moderate correlation was found between NSS and BPRS scores at baseline. Conclusion: Baseline right DLPFC volume can be an important predictor of clinical and socio-functional outcome in FEP.

Association between internet addiction, brain structure, and social capital in adolescents

ABSTRACTOf late, internet addiction among adolescents has become a serious problem, with increased internet use. Previous research suggests that the more people become addicted to the internet, the more they isolate themselves from society. Conversely, it has been suggested that abundant social capital (the networks of relationships among people who live and work in a particular society) protects people from becoming addicted to the internet. This study focused on the brain structure of typical adolescents (10–18 years of age) and hypothesized that the size of the left dorsolateral prefrontal cortex (DLPFC), which is thought to be associated with self-control ability, is associated with both internet addiction and social capital. Voxel-based morphometry analysis indicated that left DLPFC volume was negatively correlated with the severity of internet addiction and positively correlated with social capital. Furthermore, correlation analysis demonstrated that the severity of internet addiction and social capital were negatively correlated. The statistical association between them was no longer significant when left DLPFC volume was used as a control variable. These results suggest that the left DLPFC may mediate the relationship between social capital and internet addiction in adolescents.

Measures of Connectivity and Dorsolateral Prefrontal Cortex Volumes and Depressive Symptoms Following Treatment With Selective Serotonin Reuptake Inhibitors in Adolescents

Selective serotonin reuptake inhibitors (SSRIs) are considered a first-line pharmacological treatment for adolescent depression with moderate or higher levels of symptom severity. Thus, it is important to understand neurobiological changes related to SSRIs during the course of treatment for adolescents with depression. To examine neurobiological changes associated with SSRI treatment in adolescents with major depressive disorder (MDD) by measuring longitudinal changes in volume and resting-state functional connectivity (rsFC) in the dorsolateral prefrontal cortex (DLPFC), a core region of cognitive control. This cohort study was conducted with an open-label design. Adolescents with MDD and healthy controls were recruited at the Seoul National University Hospital (Seoul, South Korea). Adolescents with MDD were treated with escitalopram for 8 weeks. Data analysis was conducted between April 2021 and February 2022. Depressive symptoms were assessed using the Children's Depression Rating Scale-Revised. The outcome measure was defined as the change in Children's Depression Rating Scale-Revised scores from week 0 (before treatment) to week 8 (after treatment) or upon termination. Participants completed structural and resting-state functional magnetic resonance imaging (rsfMRI) assessments before (week 0) and after (week 8) SSRI treatment. Repeated measures analysis of variance and liner mixed model analyses were used to examine the longitudinal associations of SSRI treatment with DLPFC volume and rsFC between responders who showed at least a 40% decrease in depressive symptoms and nonresponders who did not. Ninety-five adolescents with MDD and 57 healthy controls were initially recruited. The final analyses of volume included 36 responders (mean [SD] age, 15.0 [1.6] years; 25 girls [69.4%]) and 26 nonresponders (mean [SD] age, 15.3 [1.5] years; 19 girls [73.1%]). Analyses of rsFC included 33 responders (mean [SD] age, 15.2 [1.5] years; 21 girls [63.6%]) and 26 nonresponders (mean [SD] age, 15.3 [1.5] years; 19 girls [73.1%]). The longitudinal associations of SSRI treatment were more evident in responders than in nonresponders. Responders showed significantly increased right DLPFC volume, decreased bilateral DLPFC rsFC with the superior frontal gyri, and decreased left DLPFC rsFC with the ventromedial PFC after treatment compared with before treatment. Furthermore, increased right DLPFC volume was correlated with decreased rsFC between the right DLPFC and superior frontal gyri after SSRI treatment. The preliminary results of this cohort study suggest that the DLPFC volumetric and rsFC changes may serve as potential neurobiological treatment markers that are associated with symptom improvement in adolescents with MDD.

Evaluation of volumetric asymmetry of the dorsolateral prefrontal cortex and medial temporal lobe in Alzheimer's disease using the atlas-based method.

Brain areas affected during neurodegenerative disease progression are considered anatomically connected to the first affected areas. The dorsolateral prefrontal cortex (DLPFC) has connections with the medial temporal lobe (MTL), which includes regions that become atrophic in Alzheimer's disease. In this study, we aimed to investigate the degree of volumetric asymmetry of DLPFC and MTL structures. This is a cross-sectional volumetric study involving 25 Alzheimer's disease patients and 25 healthy adults who underwent MRI with a 3D turbo spin echo sequence at 1.5 Tesla. The atlas-based method incorporated MRIStudio software to automatically measure the volume of brain structures. We compared the asymmetry index and volumetric changes across study groups and correlated them with Mini-Mental State Examination scores. We observed significant volumetric rightward lateralization in the DLPFC and superior frontal gyrus in Alzheimer's disease patients compared to the healthy controls. There was a significant volume loss in the MTL structures of Alzheimer's disease patients. Atrophy of MTL structures was positively correlated with right DLPFC volume changes in Alzheimer's disease patients. Volumetric asymmetry of the DLPFC may be a characteristic for determining disease progression in Alzheimer's disease patients. Future studies are recommended to evaluate whether these volumetric asymmetrical changes are specific to Alzheimer's disease and whether asymmetry measurements can serve as diagnostic markers.

Right dorsolateral prefrontal cortex volumetric reduction is associated with antidepressant effect of low-dose ketamine infusion: A randomized, double-blind, midazolam-controlled PET-MRI clinical trial

BackgroundEvidence has shown a rapid antidepressant and antisuicidal effects of low-dose ketamine infusion among patients with treatment-resistant depression (TRD) and prominent suicidal ideation (SI). The dorsolateral prefrontal cortex (DLPFC) plays a crucial role in the TRD pathomechanisms. ObjectiveWhether the structural and functional changes of the DLPFC, particularly Brodmann area 46, are associated with the antidepressant and antisuicidal effects of ketamine infusion among such patients is unknown. MethodsWe randomized 48 patients with TRD and SI into groups receiving a single infusion of 0.5 mg/kg ketamine or 0.045 mg/kg midazolam. The Hamilton Depression Rating Scale and the Montgomery–Asberg Depression Rating Scale were used to assess symptoms. Positron emission tomography (PET)–magnetic resonance imaging was conducted prior to infusion and on Day 3 postinfusion. We performed longitudinal voxel-based morphometry (VBM) analysis to evaluate the gray matter (GM) volume changes of the DLPFC. The standardized uptake value ratio (SUVr) of 18F-fluorodeoxyglucose PET images was calculated using the SUV of the cerebellum as a reference region. ResultsThe VBM analysis revealed a small but significant volumetric reduction in the right DLPFC in the ketamine group compared with that in the midazolam group. A greater reduction in depressive symptoms was associated with a smaller decrease in right DLPFC volumes (p = 0.025). However, we found no SUVr changes of the DLPFC between baseline and post-Day 3 ketamine infusion. DiscussionThe optimal modulation of the right DLPFC GM volumes may play an essential role in the antidepressant neuromechanisms of low-dose ketamine.

Association of disease course and brain structural alterations in major depressive disorder.

The investigation of disease course-associated brain structural alterations in Major Depressive Disorder (MDD) have resulted in heterogeneous findings, possibly due to low reliability of single clinical variables used for defining disease course. The present study employed a principal component analysis (PCA) on multiple clinical variables to investigate effects of cumulative lifetime illness burden on brain structure in a large and heterogeneous sample of MDD patients. Gray matter volumes (GMV) was estimated in n = 681 MDD patients (mean age: 35.87 years; SD = 12.89; 66.6% female) using voxel-based-morphometry. Five clinical variables were included in a PCA to obtain components reflecting disease course to associate resulting components with GMVs. The PCA yielded two main components: Hospitalization reflected by patients' frequency and duration of inpatient treatment and Duration of Illness reflected by the frequency and duration of depressive episodes. Hospitalization revealed negative associations with bilateral dorsolateral prefrontal cortex (DLPFC) and left insula volumes. Duration of Illness showed significant negative associations with left hippocampus and right DLPFC volumes. Results in the DLPFC and hippocampus remained significant after additional control for depressive symptom severity, psychopharmacotherapy, psychiatric comorbidities, and remission status. This study shows that a more severe and chronic lifetime disease course in MDD is associated with reduced volume in brain regions relevant for executive and cognitive functions and emotion regulation in a large sample of patients representing the broad heterogeneity of MDD disease course. These findings were only partly influenced by other clinical characteristics (e.g., remission status, psychopharmacological treatment).

DLPFC volume is a neural correlate of resilience in healthy high-risk individuals with both childhood maltreatment and familial risk for depression.

Two prominent risk factors for major depressive disorder (MDD) are childhood maltreatment (CM) and familial risk for MDD. Despite having these risk factors, there are individuals who maintain mental health, i.e. are resilient, whereas others develop MDD. It is unclear which brain morphological alterations are associated with this kind of resilience. Interaction analyses of risk and diagnosis status are needed that can account for complex adaptation processes, to identify neural correlates of resilience. We analyzed brain structural data (3T magnetic resonance imaging) by means of voxel-based morphometry (CAT12 toolbox), using a 2 × 2 design, comparing four groups (N = 804) that differed in diagnosis (healthy v. MDD) and risk profiles (low-risk, i.e. absence of CM and familial risk v. high-risk, i.e. presence of both CM and familial risk). Using regions of interest (ROIs) from the literature, we conducted an interaction analysis of risk and diagnosis status. Volume in the left middle frontal gyrus (MFG), part of the dorsolateral prefrontal cortex (DLPFC), was significantly higher in healthy high-risk individuals. There were no significant results for the bilateral superior frontal gyri, frontal poles, pars orbitalis of the inferior frontal gyri, and the right MFG. The healthy high-risk group had significantly higher volumes in the left DLPFC compared to all other groups. The DLPFC is implicated in cognitive and emotional processes, and higher volume in this area might aid high-risk individuals in adaptive coping in order to maintain mental health. This increased volume might therefore constitute a neural correlate of resilience to MDD in high risk.

Exercise and Fitness Neuroprotective Effects: Molecular, Brain Volume and Psychological Correlates and Their Mediating Role in Healthy Late-Middle-Aged Women and Men.

Background: Although exercise is known to have a neuroprotective effect in aging, the mediators underlying the exercise-cognition association remain poorly understood. In this paper we aimed to study the molecular, brain, and behavioral changes related to physical activity and their potential role as mediators.Methods: We obtained demographic, physical activity outcomes [sportive physical activity and cardiorespiratory fitness (CRF)], plasma biomarkers (TNF-α, ICAM-1, HGF, SDF1-α, and BDNF), structural-MRI (brain volume areas), psychological and sleep health (mood, depressive and distress symptoms, and sleep quality), and multi-domain cognitive data from 115 adults aged 50–70 years. We conducted linear regression models and mediation analyses stratifying results by sex in a final sample of 104 individuals [65 women (age = 56.75 ± 4.96) and 39 men (age = 58.59 ± 5.86)].Results: Women engaging in greater amounts of exercising showed lower TNF-α levels and greater dorsolateral prefrontal cortex and temporal lobe volumes. Men engaging in greater amounts of exercise showed greater temporal lobe volumes. CRF levels were not related to any of the analyzed outcomes in women but in men higher CRF was associated with lower TNF-α, HGF and ventricle volumes, greater volume of temporal and parietal lobes and fewer depressive symptoms and better mood. In men, reduced TNF-α and HGF levels mediated brain and cognitive CRF-related benefits.Conclusion: Our results show that exercise is a promising approach for influencing inflammation and brain volume and also contributes to ongoing discussions about the physiological mediators for the association between CRF and cognition in men.

Exploring brain insulin resistance in adults with bipolar depression using extracellular vesicles of neuronal origin

Accumulating evidence suggests that disrupted insulin signaling is involved in bipolar disorder (BD) pathogenesis. Herein, we aimed to directly explore the potential role of neuronal insulin signaling using an innovative technique based on biomarkers derived from plasma extracellular vesicles enriched for neuronal origin (NEVs). We leveraged plasma samples from a randomized, double-blind, placebo-controlled, 12-week clinical trial evaluating infliximab as a treatment of bipolar depression. We isolated NEVs using immunoprecipitation against neuronal marker L1CAM from samples collected at baseline and weeks 2, 6 and 12 (endpoint) and measured NEV biomarkers using immunoassays. We assessed neuronal insulin signaling at its first node (IRS-1) and along the canonical (Akt, GSK-3β, p70S6K) and alternative (ERK1/2, JNK and p38-MAPK) pathways. A subset of participants (n = 27) also underwent whole-brain magnetic resonance imaging (MRI) at baseline and endpoint. Pre-treatment, NEV biomarkers of insulin signaling were independently associated with cognitive function and MRI measures (i.e. hippocampal and ventromedial prefrontal cortex [vmPFC] volumes). In fact, the association between IRS-1 phosphorylation at serine site 312 (pS312-IRS-1), an indicator of insulin resistance, and cognitive dysfunction was mediated by vmPFC volume. In the longitudinal analysis, patients treated with infliximab, a tumor necrosis factor-alpha antagonist with known insulin sensitizing properties, compared to those treated with placebo, had augmented phosphorylation of proteins from the alternative pathway. Infliximab responders had significant increases in phosphorylated JNK levels, relative to infliximab non-responders and placebo responders. In addition, treatment with infliximab resulted in increase in MRI measures of brain volume; treatment-related changes in the dorsolateral prefrontal cortex volume were mediated by changes in biomarkers from the insulin alternative pathway. In conclusion, our findings support the idea that brain insulin signaling is a target for further mechanistic and therapeutic investigations.

Medial temporal contributions to learning, retrieval, and accuracy monitoring in verbal memory

AbstractBackgroundVerbal memory profiles are commonly characterized as reflective of frontal or medial temporal dysfunction in clinical practice. Frontal‐subcortical patterns are marked by intrusion errors and impoverished recall that improves with cueing and recognition. However, retrieval deficits, intrusion errors, and impoverished learning are also seen in disorders affecting the medial temporal lobes (MTL), such as Alzheimer’s disease. The aim of the current study was to determine the relative contribution of prefrontal and MTL structural integrity to verbal memory patterns typically attributed to frontal or MTL dysfunction in a mixed neurodegenerative sample.Method1148 participants at the UCSF Memory and Aging Center completed the CVLT‐III‐Short Form, and an MRI (T1‐weighted) scan. Participants varied in neurodegenerative syndrome. 55 functionally intact older adults were included for comparison. MRI analyses focused on a priori regions of interest including dorsolateral prefrontal cortex (DLPFC) and MTL regions (Hippocampus, Parahippocampal Gyrus, and Entorhinal Cortex). Linear regression models assessed the relative contribution of DLPFC and MTL volumes to six CVLT metrics of interest: 1. Benefit from multiple learning trials 2. Learning Slope 3. Cued Recall Gains 4. Total Intrusions 5. Recognition Gains 6. Response Bias.ResultsAlthough participants with smaller DLPFC volumes exhibited a greater benefit from recognition, as would be expected based on commonly characterized frontally‐mediated retrieval deficits, DLPFC volume was not associated with benefit from cueing, intrusions, or response bias. In contrast, patients with smaller MTL volumes benefited less from cued recall and recognition, and the relative contribution of MTL volume was 1.5‐2 times larger than DLPFC. Furthermore, only MTL volume was associated with intrusion errors and benefit from multiple learning trials. Performance was not associated with either region of interest in the control group.ConclusionWhile the current findings support the association between retrieval deficits and prefrontal integrity, they highlight the prominent contribution of MTL to commonly characterized frontal memory deficits, including improvements with repetition, cueing, and recognition. When interpreting verbal memory patterns in neurodegenerative samples, consideration of both PFC and MTL integrity is warranted.

Preservation of white matter integrity on DTI 3 years after early menopausal hormone therapies

AbstractBackgroundThe critical‐period theory of menopausal hormone therapy (mHT) suggests that if menopausal hormone therapy begins shortly after menopause, it may have beneficial effects on brain structure and cognitive health. We investigated white matter integrity with diffusion tensor MRI (DTI) 3 years after the end of mHT trial in recently menopausal women who were randomized shortly after menopause.MethodParticipants of this study were enrolled in the Kronos Early Estrogen Prevention Study (aged 42–56 years; 5–36 months past menopause). Participants received the following treatments: 0.45 mg/d oral conjugated equine estrogen (oCEE, n=19); 50 μg/d transdermal 17β‐estradiol (tE2, n=22); or placebo (n=33) for 4 years. Oral progesterone (200 mg/d) was given to hormone therapy groups for 12 days each month. DTI was performed 3 years after the end of 4 years of hormone therapy (n=75), which corresponded to 7 years after randomization. Voxel‐based analysis was performed on DTI to evaluate fractional anisotropy (FA) and mean diffusivity (MD) differences between treatment groups (uncorrected p<0.001).ResultVoxel based analysis showed higher FA, a measure of white matter integrity, in the superior corona radiata, anterior limb of the internal capsule and splenium of the corpus callosum of participants treated with oCEE compared to placebo (p <0.001, Figure 1A). Furthermore, higher FA was observed in the superior corona radiata, anterior limb of internal capsule and thalamus in participants treated with tE2 compared to placebo (p <0.001, Figure 1B). There were no differences in FA findings between oCEE and tE2 groups, and no MD differences between treatments groups.ConclusionA relatively higher FA in a variety of white matter regions in the oCEE and tE2 groups compared to placebo suggest that mHT may have long‐term protective effects on white matter integrity. Previously, we had shown that women in the tE2 group preserved their dorsolateral prefrontal cortex volumes better than the placebo group over 7 years. Our findings suggest that the tracts that connect the dorsolateral prefrontal cortex and the thalamus such as the superior corona radiata and the anterior limb of internal capsule may particularly benefit from mHT.

Cortisol-dehydroepiandrosterone ratios are inversely associated with hippocampal and prefrontal brain volume in schizophrenia

While high levels of glucocorticoids are generally neuro-damaging, a related adrenal steroid, dehydroepiandrosterone (DHEA), has anti-glucocorticoid and neuroprotective properties. Previous work has shown increased circulating levels of DHEA and abnormal cortisol/DHEA ratios in people with schizophrenia, however reports are limited and their relationship to neuropathology is unclear. We performed the largest study to date to compare levels of serum DHEA and cortisol/DHEA ratios in people with schizophrenia and healthy controls, and investigated the extent to which cortisol/DHEA ratios predict brain volume. Serum cortisol and DHEA were assayed in 94 people with schizophrenia and 81 healthy controls. T1-weighted high-resolution anatomical scans were obtained using a 3 T Achieva scanner on a subset of 59 people with schizophrenia and 60 healthy controls. Imaging data were preprocessed and analyzed using SPM12. People with schizophrenia had significantly increased serum DHEA levels (p = 0.002), decreased cortisol/DHEA ratios (p = 0.02) and no difference in cortisol levels compared to healthy controls. Cortisol/DHEA ratios were inversely correlated with hippocampal (r = -0.33 p = 0.01) and dorsolateral prefrontal cortex (r = -0.30, p = 0.02) volumes in patients. Our findings suggest that the cortisol/DHEA ratio may be a molecular blood signature of hippocampal and cortical damage. These results further implicate the role of DHEA and hypothalamic-pituitary-adrenal axis dysfunction in the pathophysiology of schizophrenia.

Objectively measured physical activity is associated with dorsolateral prefrontal cortex volume in older adults

BackgroundEpidemiological studies suggest physical activity (PA) can slow or prevent both cognitive decline and age-related atrophy in frontal and hippocampal gray matter volumes. However, much of this evidence is based on self-reported measures of PA. MethodsPA was measured objectively with a SenseWear™ Armband to examine the cross-sectional associations between the duration of light, moderate and vigorous intensity PA with gray matter volume in the dorsolateral prefrontal cortex (DLPFC) and hippocampus in 167 (female: 43%) cognitively healthy older adults aged 73 to 78. ResultsThe duration of objective moderate to vigorous intensity physical activity (MVPA) was associated with a greater volume of the right DLPFC (β ​= ​0.16; p ​= ​0.04). In addition, objective moderate-intensity PA alone was also associated with greater volume of the left (β ​= ​0.17; p ​= ​0.03) and right (β ​= ​0.19; p ​= ​0.01) DLPFC after controlling for covariates and adjustment for multiple comparisons. In contrast, there were no significant associations between light- or vigorous-intensity PA and gray matter volumes (all p ​> ​0.05). No associations between PA and cognitive performance were detected, and self-reported PA was not associated with any of the outcomes investigated. ConclusionsThese findings suggest that an intensity-dependent relationship may exist, whereby a greater duration of MVPA, perhaps driven by moderate-intensity PA, is associated with preserved gray matter volume in frontal regions of the brain. Future research should investigate the mechanisms of this dose-effect and determine whether greater brain volumes associated with objective PA convey protective effects against cognitive decline.

Preliminary study of structural magnetic resonance imaging phenotypes related to genetic variation in Interleukin-1β rs16944 in adolescents with Bipolar Disorder

BackgroundBipolar disorder (BD), among the most heritable psychiatric conditions, is associated with increased pro-inflammatory blood markers and pro-inflammatory gene expression in post-mortem brain. We therefore examined the effects of pro-inflammatory single nucleotide polymorphism interleukin-1β (IL-1β) rs16944 on brain structure in adolescents with BD and healthy control (HC) adolescents. MethodsT1-weighted 3-T magnetic resonance imaging data were acquired for 38 adolescents with BD and 32 HC adolescents (14–20 years). Using FreeSurfer, a priori regions of interest analyses, examining hippocampus, amygdala, dorsolateral prefrontal cortex (DLPFC), and caudal anterior cingulate cortex, were complemented by exploratory whole-brain vertex-wise analyses. General linear models assessed the association between IL-1β rs16944 and the ROIs, controlling for sex, age, and intracranial volume. ResultsThere was an IL-1β rs16944 polymorphism-by-diagnosis interaction effect on the DLPFC; T-carriers with BD had greater surface area compared to non-carriers with BD. Whereas, HC T-carriers had smaller DLPFC volume compared to HC non-carriers. In vertex-wise analyses, similar interactions were evident in a pars triangularis surface area cluster and a lateral occipital cortex volume cluster. Whole-brain analyses also yielded a main effect of IL-1β rs16944 polymorphism, whereby T-carriers had greater lateral occipital cortex surface area and volume. ConclusionsThe IL-1β rs16944 polymorphism is associated with neurostructural phenotypes in cognitive and visual regions that subserve functions, including facial recognition and response inhibition, which are known to be aberrant in BD. Future studies are warranted to evaluate whether the observed rs16944-related structural differences are relevant to neurocognitive function, functional neuroimaging phenotypes and IL-1β protein levels.

Are primary and secondary types of brain anomalies exclusive factors affecting the attention networks in individuals with spina bifida?

Individuals with spina bifida myelomeningocele (SBM) frequently exhibit cognitive impairments on tasks mediated by brain regions involved in the posterior attention network. Although such deficits have been historically assumed to result from primary and secondary brain insults, there is a dearth of literature regarding whether sequential versus simultaneous surgical closure of neural folds and surgical shunt placement affect neuropsychological function and brain structure of attention networks that have been widely studied in individuals with SBM. The current study addressed these gaps in a large cohort of children and adults with SBM. White matter pathways and regional brain volumes of anterior and posterior attention networks were quantified through probabilistic tractography and automated segmentation, respectively. The Child Attention Network Test measured behavioral components of posterior and anterior attention networks. Sequential operations were associated with reduced orienting accuracy and smaller left superior parietal and dorsolateral prefrontal cortex volumes compared to simultaneous operations, controlling for a number of shunt revisions and age. Greater number of shunt revisions was associated with higher radial diffusivity values in the parietal tectocortical pathway. Older participants had greater accuracy and faster conflict resolution performance compared to younger participants, across operation type and number of shunt revisions. Shunt treatment and revision history related to brain structure and functions associated with the posterior attention network. Neurosurgical history also differentiated the harmful effects of early hydrocephalus on brain structure of the posterior from the anterior attention networks in SBM. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Sex-Specific Relationship Between Long-Term Maintenance of Physical Activity and Cognition in the Health ABC Study: Potential Role of Hippocampal and Dorsolateral Prefrontal Cortex Volume.

Physical activity (PA) is a promising strategy for the promotion of brain health, although substantial variation exists in the effects of PA at the individual level. Given the greater prevalence and faster progression of Alzheimer's disease in women compared to men, and known sex differences in brain architecture, analysis of sex differences in the relationship between PA, cognition, and brain region volumes is warranted. To address this, we conducted secondary analyses of data from the Health, Aging, and Body Composition study. To determine whether longitudinal changes in PA over 10 years predicted declines in global cognitive functioning and executive functions and processing speed differently in males and females, latent growth curve modeling was utilized. Magnetic resonance imaging was performed at year 10, and the hippocampus and dorsolateral prefrontal cortex were identified as regions of interest. Maintaining PA over 10 years predicted less declines in executive functions and processing speed in females but not males. Maintaining PA over 10 years was significantly associated with greater volume of the left dorsolateral prefrontal cortex, a brain region involved in executive functions, in year 10 in females only. Maintaining physical activity was associated with better global cognitive function in both males and females, and also predicted volume of the left hippocampus, albeit in different directions with females showing a negative relationship and males showing a positive relationship. These findings suggest that the relationship of PA with cognition and its neurobiological correlates differ by sex, with females apparently benefiting from PA to a greater extent than males. Development of personalized, tailored exercise recommendations to promote healthy brain aging should account for sex differences.

Dysregulation of kynurenine metabolism is related to proinflammatory cytokines, attention, and prefrontal cortex volume in schizophrenia

The kynurenine pathway (KP) of tryptophan (TRP) catabolism links immune system activation with neurotransmitter signaling. The KP metabolite kynurenic acid (KYNA) is increased in the brains of people with schizophrenia. We tested the extent to which: (1) brain KP enzyme mRNAs, (2) brain KP metabolites, and (3) plasma KP metabolites differed on the basis of elevated cytokines in schizophrenia vs. control groups and the extent to which plasma KP metabolites were associated with cognition and brain volume in patients displaying elevated peripheral cytokines. KP enzyme mRNAs and metabolites were assayed in two independent postmortem brain samples from a total of 71 patients with schizophrenia and 72 controls. Plasma KP metabolites, cognition, and brain volumes were measured in an independent cohort of 96 patients with schizophrenia and 81 healthy controls. Groups were stratified based on elevated vs. normal proinflammatory cytokine mRNA levels. In the prefrontal cortex (PFC), kynurenine (KYN)/TRP ratio, KYNA levels, and mRNA for enzymes, tryptophan dioxygenase (TDO) and kynurenine aminotransferases (KATI/II), were significantly increased in the high cytokine schizophrenia subgroup. KAT mRNAs significantly correlated with mRNA for glial fibrillary acidic protein in patients. In plasma, the high cytokine schizophrenia subgroup displayed an elevated KYN/TRP ratio, which correlated inversely with attention and dorsolateral prefrontal cortex (DLPFC) volume. This study provides further evidence for the role of inflammation in a subgroup of patients with schizophrenia and suggests a molecular mechanism through which inflammation could lead to schizophrenia. Proinflammatory cytokines may elicit conversion of TRP to KYN in the periphery and increase the N-methyl-d-aspartate receptor antagonist KYNA via increased KAT mRNA and possibly more enzyme synthesis activity in brain astrocytes, leading to DLPFC volume loss, and attention impairment in schizophrenia.

The left dorsolateral prefrontal cortex volume is reduced in adults reporting childhood trauma independent of depression diagnosis

Both major depressive disorder (MDD) and childhood trauma have been linked with brain structural changes. As childhood trauma is more highly prevalent in MDD patients, previous morphometric findings in MDD therefore might have been confounded by childhood trauma. This study aimed to differentiate the impact of childhood trauma from the influence of MDD diagnosis on gray matter volume (GMV). Seventy-eight subjects were recruited into four study groups (n = 16, MDD patients with childhood trauma exposures, CTE/MDD; n = 14, MDD patients without CTE, non-CTE/MDD; n = 24, healthy controls with CTE, CTE/HC; and n = 24, HCs without CTE, non-CTE/HC). All participants underwent high-resolution structural magnetic resonance scans. Voxel-based morphometry was used to investigate GM alterations, and a 2 × 2 analysis of variance was performed to identify the main effects of diagnosis, childhood trauma, and their interactions. The main effects of diagnosis displayed abnormal GMV located in the left superior parietal lobule (MDD < HC) and right middle occipital gyrus (MDD > HC). While the left dorsolateral prefrontal cortex (DLPFC) volume revealed a significant main effect of childhood trauma, as shown by decreased GMV of the left DLPFC in subjects with CTE, regardless of diagnosis. A negative correlation was also found between the left DLPFC volume and emotional neglect in individuals reporting CTE. The present findings suggest that decreased GMV of the left DLPFC is a function of childhood trauma rather than MDD, which may represent the biological risk for developing MDD.