Cingulate Thickness Research Articles

Exploring cortical predictors of clinical response to electroconvulsive therapy in major depression.

Electroconvulsive therapy (ECT) is a rapid and highly effective treatment option for treatment-resistant major depressive disorder (TRD). The neural mechanisms underlying such beneficial effects are poorly understood. Exploring associations between changes of brain structure and clinical response is crucial for understanding ECT mechanisms of action and relevant for the validation of potential biomarkers that can facilitate the prediction of ECT efficacy. The aim of this explorative study was to identify cortical predictors of clinical response in TRD patients treated with ECT. We longitudinally investigated 12 TRD patients before and after ECT. Twelve matched healthy controls were studied cross sectionally. Demographical, clinical, and structural magnetic resonance imaging data at 3T and multiple cortical markers derived from surface-based morphometry (SBM) analyses were considered. Multiple regression models were computed to identify predictors of clinical response to ECT, as reflected by Hamilton Depression Rating Scale (HAMD) score changes. Symptom severity differences pre-post-ECT were predicted by models including demographic data, clinical data and SBM of frontal, cingulate, and entorhinal structures. Using all-subsets regression, a model comprising HAMD score at baseline and cortical thickness of the left rostral anterior cingulate gyrus explained most variance in the data (multiple R2 = 0.82). The data suggest that SBM provides powerful measures for identifying biomarkers for ECT response in TRD. Rostral anterior cingulate thickness and HAMD score at baseline showed the greatest predictive power of clinical response, in contrast to cortical complexity, cortical gyrification, or demographical data.

DGCR2 influences cortical thickness through a mechanism independent of schizophrenia pathogenesis

We investigated the role of DGCR2, a corticogenesis-related gene, on schizophrenia (SZ) and its subphenotypes, including brain morphology. A total of 221 SZ patients, 263 controls and 70 antipsychotic-naïve first episode of psychosis (FEP) were genotyped for 17 DGCR2 polymorphisms. While no association between DGCR2 polymorphisms and SZ was found, the missense variant rs2072123 was associated to left rostral anterior cingulate thickness, showing that DGCR2 seems not to be associated directly with the SZ but might be influencing the brain morphology. We also showed a DGCR2 downregulation in SZ patients when compared to controls and FEP.

BASELINE DIFFERENCES IN BRAIN MORPHOMETRY AND IMAGE GRADING OF INDIVIDUALS ON THE CONTINUUM FROM SUBJECTIVE COGNITIVE DECLINE TO AD: RESULTS FROM THE CIMA-Q STUDY

Individuals expressing subjective complaints of cognitive decline (SCD) without objective cognitive impairment may represent a group at risk of developing mild cognitive impairment (MCI), and hence AD. To validate this concept using biomarkers, we compared participants with normal cognitive functioning (CON, n=30), SCD (n=67), early MCI (eMCI, n=22), late MCI (lMCI, n=8), and AD (n=16) from the CIMA-Q study on measures derived from T1w MRIs: 1) Anatomical morphometry (volumes, surfaces, and thicknesses) from 90 brain regions, computed using FreeSurfer and normalized for age, sex, intracranial volume, scanner strength and type; 2) Tissue grading, according to a nonlocal image patch estimator (provided by TPMD) in the hippocampi (HPC) and entorhinal cortices (EC). The patented TPMD technique (see NeuroImage:Clinical 1(1):141-152,2012) grades images by matching patches of voxels within a region to similar neighbourhoods in a pre-labeled set of training images. Each patch is tagged with information known a priori from the selected training images, achieving a grading score expressing the similarity to images of tissue from individuals with probable AD. We hypothesized that there would be gradients of increasing biomarker severity from CON to AD, with SCD showing a small, but significant difference from CON in the EC and HPC. Qualitatively, morphometry results showed a gradient of changes from CON to AD in the EC and HPC (Figure 1), especially for the left EC and right HPC, but with SCD not significantly different from CON. Furthermore, compared to CON, SCD had significant lower right lingual surface (p=.021), left posterior cingulate thickness (p=.026), right rostral anterior cingulate thickness (p=.012), left supramarginal surface (p=.019) and volume (p=.039), however none of those differences resisted FDR correction. Grading results (Figure 2) were similar to morphometry, with a gradient of changes from CON to AD, especially for the left EC and right HPC, but no significant difference between SCD and CON.

Effects of Sedentary Behavior and Physical Activity on Cognitive Function are Conferred by Cortical Thickness

Physical activity and aerobic fitness may have positive impacts on brain structure and function in older adults. Conversely, sedentary behavior may have negative effects. PURPOSE: To determine associations of sedentary behavior with cerebral cortical thickness and neurocognitive function in older adults in cognitively normal older adults (NC) and patients with mild cognitive impairment (MCI). METHODS: We tested 28 NC and 50 MCI participants matched for age, sex, and education. Participants wore a 3D accelerometer for 1 week to measure daily physical activity levels. Minutes spent in sedentary behavior (<4.0METs) and moderate-to-vigorous physical activity (MVPA) (>5.0METs) were recorded. RESULTS: Sedentary behavior and MVPA were associated with cortical thickness in multiple brain regions within the default mode network. The effects of sedentary behavior on Trails B performance were mediated through left middle temporal gyrus (B=0.0017, SE=0.0010, 0.0002 to 0.0046 95% CI) and right frontal pole (B=0.0027, SE=0.0013, 0.0006 to 0.0058 95%CI) cortical thickness. MVPA (B=-0.011, SE=0.0070, -0.0304 to -0.0006 95%CI) positively impacted Trails B through left middle temporal gyrus thickness. California Verbal Learning Test cued recall was negatively affected by sedentary behavior (B=-0.00026, SE=0.0013, 0.0006 to 0.0058 95%CI), but positively affected by MVPA (B=0.0012, SE=0.0008, 0.0001 to 0.0033 95%CI) through right superior parietal cortical thickness. Cognitive status moderated the association of sedentary behavior with left posterior cingulate thickness (interaction, p=0.02) and MVPA to right supramarginal gyrus thickness (interaction, p=0.04) with greater effects occurring in NC. CONCLUSION: Sedentary behavior is associated with reductions in cerebral cortical thickness which lead to impairment in memory and executive function in older adults. Sedentary behavior may be more detrimental to individuals with normal cognitive function. Supported by the NIH (R01AG033106)

Marijuana effects on changes in brain structure and cognitive function among HIV+ and HIV− adults

BackgroundThe current study examined the independent and interactive effects of HIV and marijuana (MJ) use on brain structure and cognitive function among a sample of HIV-positive (HIV+) and HIV-negative (HIV–) individuals. MethodsParticipants (HIV+, n=48; HIV–, n=29) individuals underwent cognitive testing, questionnaires about substance use, and brain MRI. The HIV+ group was clinically stable based upon current plasma CD4 count, 50% had undetectable viral load (i.e.,<20 copies/mL), and all were on a stable regimen of cART. ResultsFor HIV+ and HIV- participants, higher levels of MJ use were associated with smaller volumes in the entorhinal cortex and fusiform gyrus. HIV status (but not MJ use) was associated with cingulate thickness, such that HIV+ participants evidenced smaller thickness of the cingulate, as compared to HIV- controls. Regarding neurocognitive functioning, there was a HIV*MJ interactive effect on global cognition, such that when the amount of MJ use was less than 1.43g per week, the HIV- group displayed significantly better neurocognitive performance than the HIV+ group (t=3.14, p=0.002). However, when MJ use reached 1.43g per week, there were no significant HIV group differences in global cognitive performance (t=1.39, p=0.168). ConclusionsOur results show independent and interactive effects of HIV and MJ on brain structure and cognition. However, our results do not support that HIV+ MJ users are at greater risk for adverse brain or cognitive outcomes compared to HIV- MJ users.

Symptom attribution and frontal cortical thickness in first-episode schizophrenia.

Misattribution of symptoms is a common feature of schizophrenia, and likely involves impairment of metacognitive function that may be mediated by the frontal cortex. We aimed to compare frontal cortical thickness in first-episode schizophrenia (FES) patients with matched controls, and investigate its relationship with the symptom attribution dimension of insight in FES patients. We examined frontal cortical thickness in 92 minimally treated FES patients at baseline presentation and 93 healthy controls aged 16-45 years. We examined for correlations between symptom attribution as determined by the Birchwood Insight Scale (BIS) symptom relabeling subscale score and cortical thickness of frontal regions of interest (ROIs). We then examined for an association between symptom attribution and cortical thickness using multiple regression analysis. FES patients exhibited significantly reduced cortical thicknesses for a number of frontal regions, namely the left medial orbitofrontal, left superior frontal, left frontal pole, right rostral middle frontal, right lateral orbitofrontal and right superior frontal regions. Reduced cortical thickness in FES patients was associated with symptom misattribution for the left and right rostral middle frontal, left caudal anterior cingulate, right superior frontal, and left and right pars triangularis regions. Reduced left rostral middle frontal thickness and left anterior cingulate thickness remained significant on regression analysis. Our findings suggest that frontal neuroanatomical deficits that are present early in the disease process may be critical to the pathogenesis of symptom attribution in schizophrenia.

A comparison of FreeSurfer-generated data with and without manual intervention

This paper examined whether FreeSurfer—generated data differed between a fully—automated, unedited pipeline and an edited pipeline that included the application of control points to correct errors in white matter segmentation. In a sample of 30 individuals, we compared the summary statistics of surface area, white matter volumes, and cortical thickness derived from edited and unedited datasets for the 34 regions of interest (ROIs) that FreeSurfer (FS) generates. To determine whether applying control points would alter the detection of significant differences between patient and typical groups, effect sizes between edited and unedited conditions in individuals with the genetic disorder, 22q11.2 deletion syndrome (22q11DS) were compared to neurotypical controls. Analyses were conducted with data that were generated from both a 1.5 tesla and a 3 tesla scanner. For 1.5 tesla data, mean area, volume, and thickness measures did not differ significantly between edited and unedited regions, with the exception of rostral anterior cingulate thickness, lateral orbitofrontal white matter, superior parietal white matter, and precentral gyral thickness. Results were similar for surface area and white matter volumes generated from the 3 tesla scanner. For cortical thickness measures however, seven edited ROI measures, primarily in frontal and temporal regions, differed significantly from their unedited counterparts, and three additional ROI measures approached significance. Mean effect sizes for edited ROIs did not differ from most unedited ROIs for either 1.5 or 3 tesla data. Taken together, these results suggest that although the application of control points may increase the validity of intensity normalization and, ultimately, segmentation, it may not affect the final, extracted metrics that FS generates. Potential exceptions to and limitations of these conclusions are discussed.

Dorsal Anterior Cingulate Thickness Is Related to Alexithymia in Childhood Trauma-Related PTSD.

Alexithymia, or “no words for feelings”, is highly prevalent in samples with childhood maltreatment and posttraumatic stress disorder (PTSD). The dorsal anterior cingulate cortex (dACC) has been identified as a key region involved in alexithymia, early life trauma, and PTSD. Functional alterations in the dACC also have been associated with alexithymia in PTSD. This study examined whether dACC morphology is a neural correlate of alexithymia in child maltreatment-related PTSD. Sixteen adults with PTSD and a history of childhood sexual abuse, physical abuse, or exposure to domestic violence, and 24 healthy controls (HC) completed the Toronto Alexithymia Scale 20 (TAS–20) and underwent magnetic resonance imaging. Cortical thickness of the dACC was measured using FreeSurfer, and values were correlated with TAS–20 scores, controlling for sex and age, in both groups. Average TAS–20 score was significantly higher in the PTSD than the HC group. TAS–20 scores were significantly positively associated with dACC thickness only in the PTSD group. This association was strongest in the left hemisphere and for TAS–20 subscales that assess difficulty identifying and describing feelings. We found that increasing dACC gray matter thickness is a neural correlate of greater alexithymia in the context of PTSD with childhood maltreatment. While findings are correlational, they motivate further inquiry into the relationships between childhood adversity, emotional awareness and expression, and dACC morphologic development in trauma-related psychopathology.

Comparison of Brain Structural Variables, Neuropsychological Factors, and Treatment Outcome in Early-Onset Versus Late-Onset Late-Life Depression

To compare differences in gray matter volumes, white matter and subcortical gray matter hyperintensities, neuropsychological factors, and treatment outcome between early- and late-onset late-life depressed (LLD) subjects. We conducted a prospective, nonrandomized, controlled trial at the outpatient clinics at Washington University and Duke University on 126 subjects, aged 60 years or older, who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depression, scored 20 or more on the Montgomery-Asberg Depression Rating Scale (MADRS), and received neuropsychological testing and magnetic resonance imaging. Subjects were excluded for cognitive impairment or severe medical disorders. After 12 weeks of sertraline treatment, subjects' MADRS scores over time and neuropsychological factors were studied. Left anterior cingulate thickness was significantly smaller in the late-onset depressed group than in the early-onset LLD subjects. The late-onset group also had more hyperintensities than the early-onset LLD subjects. No differences were found in neuropsychological factor scores or treatment outcome between early-onset and late-onset LLD subjects. Age at onset of depressive symptoms in LLD subjects are associated with differences in cortical thickness and white matter and subcortical gray matter hyperintensities, but age at onset did not affect neuropsychological factors or treatment outcome.

Cingulate and premotor cortical thickness changes may reflect post-stroke plasticity

Cingulate and premotor cortical thickness changes may reflect post-stroke plasticity

Level of Executive Function Influences Verbal Memory in Amnestic Mild Cognitive Impairment and Predicts Prefrontal and Posterior Cingulate Thickness

This study aims to investigate the relationship between executive function and verbal memory and to explore the underlying neuroanatomical correlates in 358 individuals with amnestic mild cognitive impairment (MCI) and 222 healthy controls (HCs). The MCI participants were divided into 2 groups (high vs. low) based on executive function task performance. Results demonstrated that although both MCI groups were impaired on all memory measures relative to HCs, MCI individuals with higher executive function (HEF) demonstrated better verbal memory performance than those with lower executive function (LEF), particularly on measures of learning. The 2 MCI groups did not differ in mesial temporal morphometric measures, but the MCI LEF group showed significant thinning in dorsolateral prefrontal and posterior cingulate cortices bilaterally compared with the MCI HEF and HCs. Further, thickness in numerous regions of frontal cortex, and bilateral posterior cingulate, was significantly associated with memory performance in all MCI participants above and beyond the contribution of the mesial temporal regions known to be associated with episodic memory. Overall, these results demonstrate the importance of evaluating executive function in individuals with MCI to predict involvement of brain areas beyond the mesial temporal lobe.

Regionally Specific Cortical Thinning and Gray Matter Abnormalities in the Healthy Relatives of Schizophrenia Patients

Accumulated evidence suggests that schizophrenia is associated with subtle gray matter deficits throughout the cerebral cortex and regional cortical thinning. Although findings are not entirely consistent, healthy relatives of schizophrenia patients also show abnormalities in cortical gray matter volume, suggesting that this may be one aspect of an unexpressed genetic liability to the disorder. Cortical thickness and surface area are additional indicators of cortical cytoarchitectural integrity. To investigate the nature of cortical abnormalities in the healthy relatives of patients, this study used magnetic resonance imaging to evaluate gray matter volume, surface area, and thickness of 13 regions using an automated parcellation methodology. Compared with controls (n = 22), relatives (n = 19) had decreased volume and surface area in the right cingulate gyrus, a bilateral decrease in cingulate thickness, and decreased surface area in the superior temporal lobe. In addition, relatives had a subtle increase in gray matter volume and surface area in the left hemisphere, bilaterally in the parahippocampal gyri, and in the left middle temporal lobe. The results of this study suggest that the cortical regions most affected by the unexpressed genetic liability to schizophrenia may be the cingulate and temporal regions--regions associated with higher level cognitive, affective, and memory functions.