Thickness In Prefrontal Cortex Research Articles

Dual-task performance and brain morphologic characteristics in Parkinson's disease.

Introduction Parkinson's disease (PD) reduces an individual's capacity for automaticity which limits their ability to perform two tasks simultaneously, negatively impacting daily function. Understanding the neural correlates of dual-tasks (DT) may pave the way for targeted therapies. To better understand automaticity in PD, we aimed to explore whether individuals with differing DT performances possessed differences in brain morphologic characteristics. Methods Data were obtained from 34 individuals with PD and 47 healthy older adults including: 1) demographics (age, sex), 2) disease severity (Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Hoehn & Yahr, levodopa equivalent daily dose (LEDD)), 3) cognition (Montreal Cognitive Assessment), 4) Levodopa Equivalent Daily Dose, 5) single task- and DT- performance during a DT-Timed-Up-and-Go test utilizing a serial-subtraction task, and 6) Cortical thicknesses and subcortical volumes obtained from volumetric MRI. Participants were categorized as low or high DT performers if their combined DT-effect was greater than the previously determined mean value for healthy older adults (μ=74.2). Nonparametric testing using Quade's ANCOVA was conducted to compare cortical thicknesses and brain volumes between the highDT and lowDT groups while controlling for covariates: age, sex, MDS-UPDRS part III, LEDD, and intracranial volume. Secondarily, similar comparisons were made between the healthy older adult group the highDT and lowDT groups. Lastly, a hierarchical linear regression model was conducted regressing combined DT-effect on covariates (block one) and cortical thicknesses (block 2) in stepwise fashion. Results The highDT group had thicker cortices than the lowDT group in the right primary somatosensory (p=0.001), bilateral primary motor (p=<0.001, left; p=0.002, right), bilateral supplementary motor area (p=0.001, left; p<0.001, right), and mean of the bilateral hemispheres (p=0.001, left; p<0.001, right). Of note, left primary cortex thickness (p=0.002), left prefrontal cortex thickness (p<0.001), and right supplementary motor area thickness (p=0.003) differed when adding a healthy comparison group. Additionally, the regression analysis found that the left paracentral lobule thickness explained 20.8% of the variability in combined DT-effect (p=0.011) beyond the influence of covariates. Conclusions These results suggest regions underlying dual-task performance; specifically, a convergence of neural control relying sensorimotor integration, motor planning, and motor activation to achieve higher levels of DT performance for individuals with PD.

Study on the correlation between prefrontal cortex thickness and alcohol addiction using magnetic resonance imaging in alcohol-dependent patients

Objective: To investigate the correlation between alcohol addiction and prefrontal cortex thickness using magnetic resonance imaging (MRI). Subject and method: Conducted at the Thai Nguyen National Hospital from 2020 to 2022, the cross-sectional study involved 70 alcohol-dependent individuals and 70 healthy counterparts. Participants, right-handed males, were categorized based on DSM-5 criteria diagnosed with alcoholism or no by a psychiatrist. MRI imaging, employing a Siemens 1.5 Tesla scanner, captured brain structural data. Statistical analysis included Student's t-test and multivariate linear regression models. Result: While age and intracranial volume showed no significant differences between healthy and addicted groups, BMI differed significantly. Dorsolateral prefrontal cortex thickness reductions were observed in various regions for the alcoholic group, with significant correlations (p<0.001). Age and intracranial volume emerged as predictors for specific regions. Conclusion: Alcohol addiction is associated with decreased gray matter thickness in the prefrontal cortex, emphasizing the role of age and intracranial volume in predicting these structural changes. The study underscores the need for further research to comprehensively understand the complexities of alcohol-induced brain damage.

Lateral prefrontal cortex thickness is associated with stress but not cognitive fatigue in exhaustion disorder.

Impaired executive functioning, including cognitive fatigue, is a core feature of the long-term stress-related condition exhaustion disorder (ED). Recent research suggests that a key area for executive control, the lateral prefrontal cortex (LPFC), may be mechanistically linked to cognitive fatigue due to stress. Here, we therefore asked if and how stress, the LPFC and cognitive fatigue may be related in ED. We used a multimodal cross-sectional study design with high-resolution structural magnetic resonance imaging (MRI), self-reported measures, and path analysis modeling in 300 participants with ED. We found positive associations between stress and cognitive fatigue, and stress and LPFC thickness,but no association between LPFC thickness and cognitive fatigue. Furthermore, LPFC thickness did not mediate or moderate the association between stress and cognitive fatigue. These findings suggest that LPFC brain morphology is related to perceived stress levels but not cognitive fatigue, expanding previous research on the role of the LPFC in executive functioning. Moreover, the results support the notion that the LPFC may be mechanistically involved in stress-related executive function impairment but prompt further research into if and how this may be related to cognitive symptoms in ED.

Assessing sleep architecture and cognition in older adults with depressive symptoms attending a memory clinic

BackgroundWhile depression is intrinsically and bidirectionally linked with both sleep disturbance and cognition, the inter-relationships between sleep, cognition, and brain integrity in older people with depression, especially those with late-onset depression are undefined. MethodsOne hundred and seventy-two older adults (mean age 64.3 ± 6.9 years, Depression: n = 66, Control: n = 106) attending a memory clinic underwent a neuropsychological battery of declarative memory, executive function tasks, cerebral magnetic resonance imaging and overnight polysomnography with quantitative electroencephalography. ResultsThe time spent in slow-wave sleep (SWS) and rapid eye movement (REM) sleep, slow-wave activity, sleep spindles, hippocampal volume and prefrontal cortex thickness did not differ between depression and control and depression onset groups. However, sleep onset latency (p = 0.005) and REM onset latency (p = 0.02) were later in the Depression group compared to controls. Less SWS was associated with poorer memory (r = 0.31, p = 0.023) in the depression group, and less SWS was related to better memory in the control group (r = −0.20, p = 0.043; Fishers r-to-z = −3.19). LimitationsLongitudinal studies are needed to determine if changes in sleep in those with depressive symptoms predict cognitive decline and illness trajectory. ConclusionOlder participants with depressive symptoms had delayed sleep initiation, suggestive of delayed sleep phase. The association between SWS and memory suggests SWS may be a useful target for cognitive intervention in older adults with depression symptoms. Reduced hippocampal volumes did not mediate this relationship, indicating a broader distributed neural network may underpin these associations.

Advances in Mind/Body Therapies: Concept, Data and Delivery

Mind/body therapies, such as yoga, mindfulness, and guided imagery, are often touted in media reports as ways to slow cognitive decline, improve brain health, and ameliorate negative psychological symptoms such as stress and depression. However, the clinical and neurobiological evidence base for these uses in older adults is limited. Moreover, many older adults, particularly during the COVID-19 pandemic, have difficulty accessing these therapies due to the in-person, group formats in which they are often delivered. A major difficulty in understanding the objective benefits of mind/body therapies for subjective cognitive and psychological symptoms is infrequent measurement during clinical trials using retrospective questionnaires. Thus, increased clinical efficacy research, neurobiological research, and methodological research to identify new ways to deliver and measure the effects of mind/body therapies is urgently needed.In this general session, three presenters will discuss recent advances in mind/body therapies, including new evidence from large-scale trials, and methodological innovations enabling remote therapy delivery and the assessment of behavioral outcomes.First, Dr. Felipe Jain will discuss smartphone delivery of mind/body therapies and new technologies that use passive smartphone sensors to enable continuous measurement of behavior. The development of digital phenotypes of psychological symptoms from these fine-grained behavioral assessments will be discussed. Dr. Jain's presentation will describe a smartphone application which delivers mind/body tools, mentalizing imagery therapy (MIT), and caregiver skills, to older adult family caregivers of persons living with dementia. His talk will elucidate simultaneous capture of usage data and passive smartphone sensor data in a subset of participants in a clinical trial using the application. Statistical methods to derive individual behavioral phenotypes for symptom tracking of psychological stress and sleep will be presented.Second, Dr. Eric Lenze will share clinical and neuroimaging results of a large trial of mindfulness-based stress reduction (MBSR) with and without exercise aimed at improving cognitive function and brain health in older adults. His talk will include clinical effects of intervention on episodic memory and executive function, and structural brain markers including hippocampal volume and dorsolateral prefrontal cortex thickness and surface area. Finally, he will focus on sensitive analyses of functional brain connectivity from before to after treatment.Finally, Dr. Helen Lavretsky will discuss the recent trends in the methodology of conducting mind-body efficacy and effectiveness trials. She will also discuss the results of a recently completed trial of Kundalini yoga for prevention of cognitive decline in women with subjective memory complaints and at risk for AD. This will also cover clinical outcomes and the role of neural and peripheral biomarkers of response.The panel discussion will outline future research directions in mind-body therapies for treatment and prevention in older adults, with a focus on diversity and inclusion of underrepresented populations.

Right Prefrontal Cortical Thickness Is Associated With Response to Cognitive-Behavioral Therapy in Children With Obsessive-Compulsive Disorder

Cognitive-behavioral therapy (CBT) is considered a first-line treatment for obsessive-compulsive disorder (OCD) in pediatric and adult populations. Nevertheless, some patients show partial or null response. The identification of predictors of CBT response may improve clinical management of patients with OCD. Here, we aimed to identify structural magnetic resonance imaging (MRI) predictors of CBT response in 2 large series of children and adults with OCD from the worldwide ENIGMA-OCD consortium. Data from 16 datasets from 13 international sites were included in the study. We assessed which variations in baseline cortical thickness, cortical surface area, and subcortical volume predicted response to CBT (percentage of baseline to post-treatment symptom reduction) in 2 samples totaling 168 children and adolescents (age range 5-17.5 years) and 318 adult patients (age range 18-63 years) with OCD. Mixed linear models with random intercept were used to account for potential cross-site differences in imaging values. Significant results were observed exclusively in the pediatric sample. Right prefrontal cortex thickness was positively associated with the percentage of CBT response. In a post hoc analysis, we observed that the specific changes accounting for this relationship were a higher thickness of the frontal pole and the rostral middle frontal gyrus. We observed no significant effects of age, sex, or medication on our findings. Higher cortical thickness in specific right prefrontal cortex regions may be important for CBT response in children with OCD. Our findings suggest that the right prefrontal cortex plays a relevant role in the mechanisms of action of CBT in children.

Effects of Mindfulness Training and Exercise on Cognitive Function in Older Adults

Episodic memory and executive function are essential aspects of cognitive functioning that decline with aging. This decline may be ameliorable with lifestyle interventions. To determine whether mindfulness-based stress reduction (MBSR), exercise, or a combination of both improve cognitive function in older adults. This 2 × 2 factorial randomized clinical trial was conducted at 2 US sites (Washington University in St Louis and University of California, San Diego). A total of 585 older adults (aged 65-84 y) with subjective cognitive concerns, but not dementia, were randomized (enrollment from November 19, 2015, to January 23, 2019; final follow-up on March 16, 2020). Participants were randomized to undergo the following interventions: MBSR with a target of 60 minutes daily of meditation (n = 150); exercise with aerobic, strength, and functional components with a target of at least 300 minutes weekly (n = 138); combined MBSR and exercise (n = 144); or a health education control group (n = 153). Interventions lasted 18 months and consisted of group-based classes and home practice. The 2 primary outcomes were composites of episodic memory and executive function (standardized to a mean [SD] of 0 [1]; higher composite scores indicate better cognitive performance) from neuropsychological testing; the primary end point was 6 months and the secondary end point was 18 months. There were 5 reported secondary outcomes: hippocampal volume and dorsolateral prefrontal cortex thickness and surface area from structural magnetic resonance imaging and functional cognitive capacity and self-reported cognitive concerns. Among 585 randomized participants (mean age, 71.5 years; 424 [72.5%] women), 568 (97.1%) completed 6 months in the trial and 475 (81.2%) completed 18 months. At 6 months, there was no significant effect of mindfulness training or exercise on episodic memory (MBSR vs no MBSR: 0.44 vs 0.48; mean difference, -0.04 points [95% CI, -0.15 to 0.07]; P = .50; exercise vs no exercise: 0.49 vs 0.42; difference, 0.07 [95% CI, -0.04 to 0.17]; P = .23) or executive function (MBSR vs no MBSR: 0.39 vs 0.31; mean difference, 0.08 points [95% CI, -0.02 to 0.19]; P = .12; exercise vs no exercise: 0.39 vs 0.32; difference, 0.07 [95% CI, -0.03 to 0.18]; P = .17) and there were no intervention effects at the secondary end point of 18 months. There was no significant interaction between mindfulness training and exercise (P = .93 for memory and P = .29 for executive function) at 6 months. Of the 5 prespecified secondary outcomes, none showed a significant improvement with either intervention compared with those not receiving the intervention. Among older adults with subjective cognitive concerns, mindfulness training, exercise, or both did not result in significant differences in improvement in episodic memory or executive function at 6 months. The findings do not support the use of these interventions for improving cognition in older adults with subjective cognitive concerns. ClinicalTrials.gov Identifier: NCT02665481.

The β2V287L nicotinic subunit linked to sleep-related epilepsy differently affects fast-spiking and regular spiking somatostatin-expressing neurons in murine prefrontal cortex.

Mutant subunits of the neuronal nicotinic ACh receptor (nAChR) can cause Autosomal Dominant Sleep-related Hypermotor Epilepsy (ADSHE), characterized by frontal seizures during non-rapid eye movement (NREM) sleep. We studied the cellular bases of the pathogenesis in brain slices from mice conditionally expressing the ADSHE-linked β2V287L nAChR subunit. β2V287L mice displayed minor structural alterations, except for a ~10% decrease of prefrontal cortex thickness. However, they showed a substantial decrease of the excitatory input to layer V fast-spiking (FS) interneurons, despite a concomitant increase in the number of glutamatergic terminals around the cell soma. Hence, prefrontal hyperexcitability may depend on a permanent impairment of surround inhibition. The effect disappeared when β2V287L was silenced until postnatal day 15th, suggesting that the transgene selectively affects the maturation of glutamatergic synapses on FS neurons. The other main population of interneurons in layer V was constituted by somatostatin-expressing regular spiking cells. When tested with 10µM nicotine, these displayed larger somatic nicotinic currents in transgenic mice. Thus, during wakefulness, activation of β2V287L-containing nAChRs by the high cholinergic tone may counteract hyperexcitability by promoting local inhibition by somatostatin-expressing cells and decreasing the effect of glutamatergic deficit in FS neurons. This interpretation was tested in networks disinhibited by 2μM bicuculline. Slices expressing β2V287L were more susceptible to develop synchronized activity in the absence of nicotine. Addition of the drug boosted excitability in the controls, but had little effect in β2V287L. Our findings suggest why NREM sleep favors ADSHE seizures and nicotine can be palliative in patients.

Association of cognitive impairment and reduced cortical thickness in prefrontal cortex and anterior cingulate cortex with treatment-resistant depression.

Accumulating evidence suggests the critical role of cortical thinning in the pathophysiology of major depressive disorder. However, the association of cortical thickness and cognitive impairment with treatment-resistant depression (TRD) has rarely been investigated. In total, 48 adult patients with TRD and 48 healthy controls were recruited and administered a series of neurocognitive and neuroimaging examinations, including 1-back and 2-back working memory tasks and brain magnetic resonance imaging (MRI). Whole-brain cortical thickness analysis was performed to investigate the differences in the cortical thickness between patients with TRD and controls. The patients had reduced cortical thickness in the frontal cortex, particularly at the left frontal pole, left inferior frontal cortex, and left anterior cingulate cortex, and left middle temporal cortex compared with the healthy controls. Moreover, in the 2-back working memory task, the cortical thickness in the left frontal pole and left anterior cingulate cortex was positively associated with mean error in the patients, but not in the controls. Reduced cortical thickness in the frontal pole and anterior cingulate cortex is associated with TRD and related cognitive impairment. Our study indicated the crucial effects of the frontal and temporal cortical thickness on the pathophysiology of TRD and cognitive impairment in patients with TRD.

APOEɛ4 Allele Moderates the Association Between Basal Forebrain Nuclei Volumes and Allocentric Navigation in Older Adults Without Dementia.

Cholinergic deficit and medial temporal lobe (MTL) atrophy are hallmarks of Alzheimer's disease (AD) leading to early allocentric spatial navigation (aSN) impairment. APOEɛ4 allele (E4) is a major genetic risk factor for late-onset AD and contributes to cholinergic dysfunction. Basal forebrain (BF) nuclei, the major source of acetylcholine, project into multiple brain regions and, along with MTL and prefrontal cortex (PFC), are involved in aSN processing. We aimed to determine different contributions of individual BF nuclei atrophy to aSN in E4 positive and E4 negative older adults without dementia and assess whether they operate on aSN through MTL and PFC or independently from these structures. 120 participants (60 E4 positive, 60 E4 negative) from the Czech Brain Aging Study underwent structural MRI and aSN testing in real-space arena setting. Hippocampal and BF nuclei volumes and entorhinal cortex and PFC thickness were obtained. Associations between brain regions involved in aSN were assessed using MANOVA and complex model of mutual relationships was built using structural equation modelling (SEM). Path analysis based on SEM modeling revealed that BF Ch1-2, Ch4p, and Ch4ai nuclei volumes were indirectly associated with aSN performance through MTL (pch1-2 = 0.039; pch4p = 0.042) and PFC (pch4ai = 0.044). In the E4 negative group, aSN was indirectly associated with Ch1-2 nuclei volumes (p = 0.015), while in the E4 positive group, there was indirect effect of Ch4p nucleus (p = 0.035). Our findings suggest that in older adults without dementia, BF nuclei affect aSN processing indirectly, through MTL and PFC, and that APOE E4 moderates these associations.

Neuroanatomical Correlates of Perceived Stress Controllability in Adolescents and Emerging Adults.

Stressful life events predict changes in brain structure and increases in psychopathology, but not everyone is equally affected by life stress. The learned helplessness theory posits that perceiving life stressors as uncontrollable leads to depression. Evidence supports this theory for youth, but the impact of perceived control diverges based on stressor type: perceived lack of control over dependent (self-generated) stressors is associated with greater depression symptoms when controlling for the frequency of stress exposure, but perceived control over independent (non-self-generated) stressors is not. However, it is unknown how perceived control over these stressor types is associated with brain structure. We tested whether perceived lack of control over dependent and independent life stressors, controlling for stressor exposure, is associated with gray matter (GM) in a priori regions of interest (ROIs; mPFC, hippocampus, amygdala) and across the cortex in a sample of 108 adolescents and emerging adults ages 14-22. There were no associations across the full sample between perceived control over either stressor type and GM in the ROIs. However, less perceived control over dependent stressors was associated with greater amygdala gray matter volume in female youth and greater medial prefrontal cortex thickness in male youth. Furthermore, whole-cortex analyses revealed less perceived control over dependent stressors was associated with greater GM thickness in cortical regions involved in cognitive and emotional regulation. Thus, appraisals of control have distinct associations with brain morphology while controlling for stressor frequency, highlighting the importance of differentiating between these aspects of the stress experience in future research.

Prefrontal cortical thickness mediates the association between cortisol reactivity and executive function in childhood

The impact of stress hormones, such as cortisol, on the brain is proposed to contribute to differences in executive function of school-age children from impoverished backgrounds. However, the association between cortisol reactivity, prefrontal cortex, and executive function is relatively unexplored in young children. The current longitudinal study examined whether 63 children's early preschool-age (3–5 years, Time 1) and concurrent school-age (5–9 years, Time 2) salivary cortisol reactivity were associated with executive function and prefrontal cortical thickness at school-age. Two measures of cortisol reactivity were calculated: area under the curve with respect to ground (AUCg; total cortisol release) and with respect to increase (AUCi; total change in cortisol). Results demonstrated that Time 2 total cortisol release was negatively associated with executive function, Time 1 total cortisol release positively related to right middle frontal cortical thickness, and Time 2 total cortisol change was negatively associated with right inferior frontal cortical thickness. Moreover, greater right middle frontal cortical thickness mediated the association between greater Time 1 total cortisol release and lower executive function. This study provides support for an early adversity framework in which individual differences in executive function in childhood are directly related to the variations of cortisol-release and the effects on the prefrontal cortex thickness.

CACNB2 rs11013860 polymorphism correlates of prefrontal cortex thickness in bipolar patients with first-episode mania

BackgroundThe β2 subunit of the voltage-gated l-type calcium channel gene(CACNB2) rs11013860 polymorphism is a putative genetic susceptibility marker for bipolar disorder (BD). However, the neural effects of CACNB2 rs11013860 in BD are largely unknown. MethodsForty-six bipolar patients with first-episode mania and eighty-three healthy controls (HC) were genotyped for CACNB2 rs11013860 and were scanned with a 3.0 Tesla structural magnetic resonance imaging system to measure cortical thickness of prefrontal cortex (PFC) components (superior frontal cortex, orbitofrontal cortex, middle and inferior frontal gyri). ResultsCortical thickness was thinner in patients on all PFC measurements compared to HC (p < 0.050). Moreover, we found a significant interaction between CACNB2 genotype and diagnosis for the right superior frontal cortical thickness (F = 8.190, p = 0.040). Bonferroni corrected post-hoc tests revealed that, in CACNB2 A-allele carriers, patients displayed thinner superior frontal thickness compared to HC (p < 0.001). In patients, CACNB2 A-allele carriers also exhibited reduced superior frontal thickness compared to CACNB2 CC-allele carriers (p = 0.016). LimitationsLithium treatment may influence our results, and the sample size in our study is relatively small. ConclusionsOur results suggest that the CACNB2 rs11013860 might impact PFC thickness in patients with first-episode mania. These findings provide evidence to support CACNB2 rs11013860 involvement in the emotion-processing neural circuitry abnormality in the early stage of BD, which will ultimately contribute to revealing the link between the variation in calcium channel genes and the neuropathological mechanism of BD.

Associations Among Body Mass Index, Cortical Thickness, and Executive Function in Children

A total of 25.7 million children in the United States are classified as overweight or obese. Obesity is associated with deficits in executive function, which may contribute to poor dietary decision-making. Less is known about the associations between being overweight or obese and brain development. To examine whether body mass index (BMI) is associated with thickness of the cerebral cortex and whether cortical thickness mediates the association between BMI and executive function in children. In this cross-sectional study, cortical thickness maps were derived from T1-weighted structural magnetic resonance images of a large, diverse sample of 9 and 10-year-old children from 21 US sites. List sorting, flanker, matrix reasoning, and Wisconsin card sorting tasks were used to assess executive function. A 10-fold nested cross-validation general linear model was used to assess mean cortical thickness from BMI across cortical brain regions. Associations between BMI and executive function were explored with Pearson partial correlations. Mediation analysis examined whether mean prefrontal cortex thickness mediated the association between BMI and executive function. Among 3190 individuals (mean [SD] age, 10.0 [0.61] years; 1627 [51.0%] male), those with higher BMI exhibited lower cortical thickness. Eighteen cortical regions were significantly inversely associated with BMI. The greatest correlations were observed in the prefrontal cortex. The BMI was inversely correlated with dimensional card sorting (r = -0.088, P < .001), list sorting (r = -0.061, P < .003), and matrix reasoning (r = -0.095, P < .001) but not the flanker task. Mean prefrontal cortex thickness mediated the association between BMI and list sorting (mean [SE] indirect effect, 0.014 [0.008]; 95% CI, 0.001-0.031) but not the matrix reasoning or card sorting task. These results suggest that BMI is associated with prefrontal cortex development and diminished executive functions, such as working memory.

Clinical, cortical thickness and neural activity predictors of future affective lability in youth at risk for bipolar disorder: initial discovery and independent sample replication.

We aimed to identify markers of future affective lability in youth at bipolar disorder risk from the Pittsburgh Bipolar Offspring Study (BIOS) (n=41, age=14, SD=2.30), and validate these predictors in an independent sample from the Longitudinal Assessment of Manic Symptoms study (LAMS) (n=55, age=13.7, SD=1.9). We included factors of mixed/mania, irritability, and anxiety/depression (29 months post MRI scan) in regularized regression models. Clinical and demographic variables, along with neural activity during reward and emotion processing and gray matter structure in all cortical regions at baseline, were used to predict future affective lability factor scores, using regularized regression. Future affective lability factor scores were predicted in both samples by unique combinations of baseline neural structure, function, and clinical characteristics. Lower bilateral parietal cortical thickness, greater left ventrolateral prefrontal cortex thickness, lower right transverse temporal cortex thickness, greater self-reported depression, mania severity, and age at scan predicted greater future mixed/mania factor score. Lower bilateral parietal cortical thickness, greater right entorhinal cortical thickness, greater right fusiform gyral activity during emotional face processing, diagnosis of Major Depressive Disorder, and greater self-reported depression severity predicted greater irritability factor score. Greater self-reported depression severity predicted greater anxiety/depression factor score. Elucidating unique clinical and neural predictors of future specific affective lability factors is a step toward identifying objective markers of bipolar disorder risk, to provide neural targets to better guide and monitor early interventions in bipolar disorder at-risk youth.

Investigating the separate and interactive associations of trauma and depression on brain structure: implications for cognition and aging.

Trauma and depression are associated with brain structural alterations; their combined effects on these outcomes are unclear. We previously reported a negative effect of trauma, independent of depression, on verbal learning and memory; less is known about underlying structural associates. We investigated separate and interactive associations of trauma and depression on brain structure. Adults aged 30-89 (N=203) evaluated for depression (D+) and trauma history (T+) using structured clinical interviews were divided into 53 D+T+, 42 D+T-, 50 D-T+, and 58 D-T-. Multivariable linear regressions examined the separate and interactive associations of depression and trauma with prefrontal and temporal lobe cortical thickness composites and hippocampal volumes adjusting for age, sex, predicted verbal IQ, comorbid anxiety, and vascular risk. Significant results informed analyses of tract-based structural connectomic measures of efficiency and centrality. Trauma, independent of depression, was associated with greater left prefrontal cortex (PFC) thickness, in particular the medial orbitofrontal cortex and pars orbitalis. A trauma×depression interaction was observed for the right PFC in age-stratified analyses: Older D+T+ had reduced PFC thickness compared with older D-T+ individuals. Regardless of age, trauma was associated with more left medial orbitofrontal cortex efficiency and less pars orbitalis centrality. In the T+ group, left pars orbitalis cortical thickness and centrality negatively correlated with verbal learning. Trauma, independent of depression, associated with altered PFC characteristics, morphologically and in terms of structural network communication and influence. Additionally, findings suggest that there may be a combined effect of trauma and depression in older adults. Copyright © 2017 John Wiley & Sons, Ltd.

SKA2 methylation predicts reduced cortical thickness in prefrontal cortex.

SKA2 methylation predicts reduced cortical thickness in prefrontal cortex.

A novel locus in the oxidative stress-related gene ALOX12 moderates the association between PTSD and thickness of the prefrontal cortex

Oxidative stress has been implicated in many common age-related diseases and is hypothesized to play a role in posttraumatic stress disorder (PTSD)-related neurodegeneration (Miller and Sadeh, 2014). This study examined the influence of the oxidative stress-related genes ALOX 12 and ALOX 15 on the association between PTSD and cortical thickness. Factor analyses were used to identify and compare alternative models of the structure of cortical thickness in a sample of 218 veterans. The best-fitting model was then used for a genetic association analysis in White non-Hispanic participants (n=146) that examined relationships between 33 single nucleotide polymorphisms (SNPs) spanning the two genes, 8 cortical thickness factors, and each SNP×PTSD interaction. Results identified a novel ALOX12 locus (indicated by two SNPs in perfect linkage disequilibrium: rs1042357 and rs10852889) that moderated the association between PTSD and reduced thickness of the right prefrontal cortex. A whole-cortex vertex-wise analysis showed this effect to be localized to clusters spanning the rostral middle frontal gyrus, superior frontal gyrus, rostral anterior cingulate cortex, and medial orbitofrontal cortex. These findings illustrate a novel factor-analytic approach to neuroimaging-genetic analyses and provide new evidence for the possible involvement of oxidative stress in PTSD-related neurodegeneration.

Cortical thickness differences in the prefrontal cortex in children and adolescents with ADHD in relation to dopamine transporter (DAT1) genotype

Several lines of evidence suggest that the dopamine transporter gene (DAT1) plays a crucial role in attention deficit hyperactivity disorder (ADHD). Concretely, recent data indicate that the 10-repeat (10R) DAT1 allele may mediate neuropsychological functioning, response to methylphenidate, and even brain function and structure in children with ADHD. This study aimed to investigate the influence of 10R DAT1 on thickness of the prefrontal cortex in children and adolescents with ADHD. To this end, brain magnetic resonance images were acquired from 33 patients with homozygosity for the 10R allele and 30 patients with a single copy or no copy of the allele. The prefrontal cortex of each MRI scan was automatically parceled into regions of interest (ROIs) based on Brodmann areas (BA). The two groups were matched for age, gender, IQ, ADHD subtype, symptom severity, comorbidity and medication status. However, patients with two copies of the 10R allele exhibited significantly decreased cortical thickness in right BA 46 relative to patients with one or fewer copies of the allele. No other prefrontal ROI differed significantly between the two groups. Present findings suggest that cortical thickness of right lateral prefrontal cortex (BA 46) is influenced by the presence of the DAT1 10 repeat allele in children and adolescents with ADHD.

Brain Alterations and Neurocognitive Dysfunction in Patients With Complex Regional Pain Syndrome

Few studies have examined the involvement of specific subregions of the prefrontal cortex in complex regional pain syndrome (CRPS). We analyzed cortical thickness to identify morphologic differences in local brain structures between patients with CRPS and healthy control subjects (HCs). Furthermore, we evaluated the correlation between cortical thickness and neurocognitive function. Cortical thickness was measured in 25 patients with CRPS and 25 HCs using the FreeSurfer method. Pain severity and psychiatric symptoms were assessed using the Short Form McGill Pain Questionnaire and the Beck Depression and Anxiety Inventories, respectively. Neurocognitive function was assessed via the Wisconsin Card Sorting Test and the stop-signal task. The right dorsolateral prefrontal cortex and left ventromedial prefrontal cortex were significantly thinner in CRPS patients than in HCs. CRPS patients made more perseveration errors on the Wisconsin Card Sorting Test and had longer stop-signal task reaction times than HCs. Although the Beck Depression Inventory and the Beck Anxiety Inventory differ significantly between the groups, they were not correlated with cortical thickness. Our study suggests that the pathophysiology of CRPS may be related to reduced cortical thickness in the dorsolateral prefrontal cortex and the ventromedial prefrontal cortex. The structural alterations in dorsolateral prefrontal cortex may explain executive dysfunction and disinhibited pain perception in CRPS. PerspectiveThe present study reports decreased cortical thickness in the prefrontal cortex and neurocognitive dysfunctions in patients with CRPS. These findings may contribute to the understanding of pain-related impairments in cognitive function and could help explain the symptoms or progression of CRPS.