Caudal Anterior Cingulate Cortex Research Articles

Functional Connectivity, Physical Activity, and Neurocognitive Performances in Patients with Vascular Cognitive Impairment, No Dementia.

Vascular Cognitive Impairment, No Dementia (VCIND) is a key stage at which early intervention will delay or prevent dementia. The pathophysiology of VCIND posits that a lesion in a single location in the brain has the ability to disrupt brain networks, and the subsequent abnormal Functional Connectivity (FC) of brain networks leads to deficits in corresponding neurobehavioral domains. In this study, we tested the hypothesis that disrupted anterior cingulate cortex and striatal networks mediated the effects of Physical Activity (PA) on neurobehavioral function. In 27 patients with VCIND, FC within the brain networks and neurobehavioral dysfunction were assessed. The relationship between the cognitive scores, FC, and PA was studied. The Fitbit Charge 2 was used to measure step counts, distance, and calories burned. In patients with VCIND, a cross-sectional Spearman's correlation to analyze the relationship among patient-level measures of PA, cognitive function scores, and FC strength within the brain networks. Average step counts and average distance were associated with Trail Making Test B (TMB) time to completion (seconds) and Instrumental Activities of Daily Living (IADL) score (P < 0.05). The average calories burned were associated with IADL score (P = 0.009). The FC within the brain networks anchored by left caudal Anterior Cingulate Cortex (ACC) seeds (x= -5, y= 0, z= 36) and (x= -5, y= -10, z= 47) were positively correlated with average step counts and average distance, were negatively correlated with TMB time to completion (seconds), and were positively correlated with IADL score (P < 0.05). The FC within the brain networks anchored by left subgenual ACC seed (x= -5, y= 25, z= -10) were negatively correlated with average step counts and average distance were positively correlated with TMB time to completion (seconds), and were negatively correlated with IADL score (P < 0.05). The FC within the striatal networks was positively correlated with average calories burned and IADL score (P < 0.05). FC within the brain networks anchored by caudal ACC seeds was positively correlated with more average step counts/average distance and better IADL score; negatively correlated with longer TMB time to completion (seconds), whereas FC of subgenual ACC seed was negatively correlated with the same parameters. FC within the brain networks anchored by putamen rather than caudate or pallidum was positively correlated with average calories burned and IADL score.

Cerebral Blood Flow in the Salience Network of Individuals with Alcohol Use Disorder.

Magnetic resonance imaging (MRI) studies have identified structural and functional differences in salience network nodes of individuals with alcohol use disorders (AUDs) after chronic exposure to alcohol. However, no studies have investigated cerebral blood flow (CBF) in nontreatment-seeking (NTS) individuals with AUD. In this work, we sought to quantify putative CBF deficits in NTS individuals relative to social drinking (SD) controls and determine if CBF in the salience network is associated with AUD severity. Fifteen NTS (36.5 ± 11.2years old, 30.0 ± 22.7 drinks/week) and 22 SD (35.6 ± 11.9 years old, 9.1 ± 5.7 drinks/week) underwent pseudocontinuous arterial spin labeling MRI. Compared with social drinkers, NTS individuals had significantly lower CBF in the right and left dorsal anterior insula, and the left ventral anterior and posterior insula. The Alcohol Use Disorder Identification Test (AUDIT) score showed a significant negative relationship with CBF in the bilateral caudal anterior cingulate cortex. In addition, a significant negative correlation was present between number of standard drinks consumed per week and the left frontal opercular CBF. These results provide evidence that insular CBF is negatively associated with heavy drinking, and that severity of alcohol use is related to CBF deficits in key nodes of the salience network. Longitudinal data are needed to understand if disruptions of CBF in the insula and the salience network are a predisposition for or a consequence of chronic AUD.

Association between Visceral Adiposity Index, Binge Eating Behavior, and Grey Matter Density in Caudal Anterior Cingulate Cortex in Severe Obesity.

Visceral adipose tissue accumulation is an important determinant of metabolic risk and can be estimated by the visceral adiposity index (VAI). Visceral adiposity may impact brain regions involved in eating behavior. We aimed to examine the association between adiposity measurements, binge eating behavior, and grey matter density. In 20 men and 59 women with severe obesity, Grey matter density was measured by voxel-based morphometry for six regions of interest associated with reward, emotion, or self-regulation: insula, orbitofrontal cortex, caudal and rostral anterior cingulate cortex (ACC), ventromedial prefrontal cortex (vmPFC), and dorsolateral prefrontal cortex (DLPFC). Binge eating behavior, depression and impulsivity was assessed by the Binge Eating Scale, Beck Depression Inventory and UPPS Impulsive Behavior Scale, respectively. Men and women were distinctively divided into two subgroups (low-VAI and high-VAI) based on the mean VAI score. Women with high-VAI were characterized by metabolic alterations, higher binge eating score and lower grey matter density in the caudal ACC compared to women with low-VAI. Men with high-VAI were characterized by a higher score for the sensation-seeking subscale of the UPPS–Impulsive Behavior Scale compared to men with low-VAI. Using a moderation–mediation analysis, we found that grey matter density in the caudal ACC mediates the association between VAI and binge eating score. In conclusion, visceral adiposity is associated with higher binge eating severity in women. Decreased grey matter density in the caudal ACC, a region involved in cognition and emotion regulation, may influence this relationship.

Small Nucleus Accumbens and Large Cerebral Ventricles in Infants and Toddlers Prior to Receiving Diagnoses of Autism Spectrum Disorder.

Early interventions for autism spectrum disorder (ASD) are increasingly available, while only 42-50% of ASD children are diagnosed before 3 years old (YO). To identify neuroimaging biomarkers for early ASD diagnosis, we evaluated surface- and voxel-based brain morphometry in participants under 3YO who were later diagnosed with ASD. Magnetic resonance imaging data were retrospectively obtained from patients later diagnosed with ASD at Boston Children's Hospital. The ASD participants with comorbidities such as congenital disorder, epilepsy, and global developmental delay/intellectual disability were excluded from statistical analyses. Eighty-five structural brain magnetic resonance imaging images were collected from 81 participants under 3YO and compared with 45 images from 45 gender- and age-matched nonautistic controls (non-ASD). Using an Infant FreeSurfer pipeline, 236 regionally distributed measurements were extracted from each scan. By t-tests and linear mixed models, the smaller nucleus accumbens and larger bilateral lateral, third, and fourth ventricles were identified in the ASD group. Vertex-wise t-statistical maps showed decreased thickness in the caudal anterior cingulate cortex and increased thickness in the right medial orbitofrontal cortex in ASD. The smaller bilateral accumbens nuclei and larger cerebral ventricles were independent of age, gender, or gestational age at birth, suggesting that there are MRI-based biomarkers in prospective ASD patients before they receive the diagnosis and that the volume of the nucleus accumbens and cerebral ventricles can be key MRI-based early biomarkers to predict the emergence of ASD.

Antioxidative Defense Genes and Brain Structure in Youth Bipolar Disorder.

BackgroundOxidative stress is implicated in the neuropathology of bipolar disorder (BD). We investigated the association of single-nucleotide polymorphisms (SNPs) in the antioxidative genes superoxide dismutase 2 (SOD2) and glutathione peroxidase 3 (GPX3) with structural neuroimaging phenotypes in youth BD.Methods SOD2 rs4880 and GPX3 rs3792797 SNP genotypes, along with structural magnetic resonance imaging, were obtained from 147 youth (BD = 75; healthy controls = 72). Images were processed using FreeSurfer, yielding surface area, volume, and thickness values for regions of interest (prefrontal cortex [PFC], caudal anterior cingulate cortex, hippocampus) and for vertex-wise whole-brain analysis. Analyses controlled for age, sex, race, and intracranial volume for volume, area, and thickness analyses.ResultRegions of interest analyses revealed diagnosis-by-SOD2 rs4880 interaction effects for caudal anterior cingulate cortex volume and surface area as well as PFC volume; in each case, there was lower volume/area in the BD GG genotype group vs the healthy controls GG genotype group. There was a significant BD diagnosis × GPX3 rs3793797 interaction effect for PFC surface area, where area was lower in the BD A-allele carrier group vs the other genotype groups. Vertex-wise analyses revealed significant interaction effects in frontal, temporal, and parietal regions related to smaller brain structure in the BD SOD2 rs4880 GG group and BD GPX3 rs3793797 A-allele carrier group.ConclusionWe found preliminary evidence that SOD2 rs4880 and GPX3 rs3792797 are differentially associated with brain structures in youth with BD in regions that are relevant to BD. Further studies incorporating additional neuroimaging phenotypes and blood levels of oxidative stress markers are warranted.

Orbitofrontal and Cingulate Thickness Asymmetry Associated with Depressive Symptom Dimensions.

Both clinical depression and subthreshold depressive symptoms have been associated with alterations in cortical thickness. Studies have yielded conflicting results regarding whether cortical thinning or cortical thickening best characterize the depressive state. Also unclear is whether cortical thickness differences are lateralized. This study examined the relationship between depressive symptom dimensions and cortical thickness asymmetry in cingulate and orbitofrontal regions. Fifty-four community-dwelling adults between the ages of 18 and 81 years received a 3-Tesla magnetic resonance imaging scan and completed the Center for Epidemiologic Studies Depression Scale (CES-D). Cortical thickness values were extracted for the rostral anterior cingulate, caudal anterior cingulate, posterior cingulate, isthmus cingulate, and orbitofrontal cortex. An asymmetry index was calculated for each region. Data were analyzed using separate general linear models for each region, in which the CES-D somatic symptoms, negative affect, and anhedonia subscale scores predicted the asymmetry indices, controlling for age and sex. Higher scores on the anhedonia subscale were associated with right-sided asymmetry in orbitofrontal thickness, whereas higher somatic symptom subscale scores predicted greater left-sided asymmetry in posterior cingulate thickness. Follow-up analyses showed the orbitofrontal effect was specific to the medial, not the lateral, orbitofrontal cortex. These results suggest asymmetries in cortical thickness are apparent at even subthreshold levels of depressive symptoms, as all but five participants were below the CES-D cutoff for clinical depression, and that the relationship varies for different symptom dimensions of depression. Understanding brain asymmetries across the range of depressive symptom severity is important for informing targeted depression treatment.

Altered gray matter structural covariance networks in postpartum depression: a graph theoretical analysis

BackgroundPostpartum depression (PPD) is a serious postpartum mental health problem worldwide. To date, minimal is known about the alteration of topographical organization in the brain structural covariance network of patients with PPD. This study investigates the brain structural covariance networks of patients with PPD by using graph theoretical analysis. MethodsHigh-resolution 3D T1 structural images were acquired from 21 drug-naive patients with PPD and 18 healthy postpartum women. Cortical thickness was extracted from 64 brain regions to construct the whole-brain structural covariance networks by calculating the Pearson correlation coefficients, and their topological properties (e.g., small-worldness, efficiency, and nodal centrality) were analyzed by using graph theory. Nonparametric permutation tests were further used for group comparisons of topological metrics. A node was set as a hub if its betweenness centrality (BC) was at least two standard deviations higher than the mean nodal centrality. Network-based statistic (NBS) was used to determine the connected subnetwork. ResultsThe PPD and control groups showed small-worldness of group networks, but the small-world network was more evidently in the PPD group. Moreover, the PPD group showed increased network local efficiency and almost similar network global efficiency. However, the difference of the network metrics was not significant across the range of network densities. The hub nodes of the patients with PPD were right inferior parietal lobule (BC = 13.69) and right supramarginal gyrus (BC = 13.15), whereas those for the HCs were left cuneus (BC = 14.96), right caudal anterior-cingulate cortex (BC = 15.51), and right precuneus gyrus (BC = 15.74). NBS demonstrated two disrupted subnetworks that are present in PPD: the first subnetwork with decreased internodal connections is mainly involved in the cognitive-control network and visual network, and the second subnetwork with increased internodal connections is mainly involved in the default mode network, cognitive-control network and visual network. ConclusionsThis study demonstrates the alteration of topographical organization in the brain structural covariance network of patients with PPD, providing in sight on the notion that PPD could be characterized as a systems-level disorder.

Differential roles of prelimbic and anterior cingulate cortical region in the modulation of histaminergic and non-histaminergic itch

Itch is an unpleasant sensation that evokes a desire to scratch. Itch processing in the peripheral and spinal cord has been studied extensively, but the mechanism of itch in the central nervous system is still unclear. Anterior cingulate cortex (ACC) and prelimbic cortex (Prl), two subregions of the prefrontal cortex closely related to emotion and motivation, have been reported to be activated during itching in a series of functional imaging studies. However, the exact role of Prl and the differences between ACC and Prl in itch modulation remains unknown. To directly test the differential roles of ACC and Prl in itch processing, we chemogeneticlly inhibited the caudal ACC and Prl, respectively. We found that inhibition of caudal ACC reduced histaminergic but not non-histaminergic itch-induced scratching behaviors. In contrast, inhibition of Prl reduced both histaminergic and non-histaminergic itch-induced scratching behaviors. Our study provided direct evidence of Prl involvement in itch modulation and revealed the differential roles of caudal ACC and Prl in regulating histaminergic and non-histaminergic itch.

Pain differences in sympathetic nervous system reactivity during simple and complex walking tasks: potential cerebral mechanisms

Autonomic dysregulation may lead to blunted sympathetic reactivity in chronic pain states and autonomic responses are controlled by the central autonomic network (CAN). Little research has examined sympathetic reactivity and associations with brain CAN structures in the presence of chronic pain; thus, the present study aims to investigate chronic pain differences in sympathetic reactivity and associations with CAN brain region volumes. Sympathetic reactivity was measured as change in skin conductance level (ΔSCL) between a resting preparation and walking phases of typical and complex walking tasks (obstacle and dual-task) in 31 participants with (n=19) and without (n=12) chronic musculoskeletal pain using a repeated measures-ANCOVA with Bonferroni corrections. Structural 3T MRI was used to determine gray matter volume associations with ΔSCL in regions of the CAN (i.e., brainstem, amygdala, insula, and anterior cingulate cortex, using partial correlations (FDR-corrected) adjusting for important covariates. ΔSCL varied across all walking tasks (main effect p=0.036), with lower ΔSCL in chronic pain participants (21.0±5.4µS) compared to controls (43.4±7.5µS). ΔSCL during typical walking was associated with multiple CAN gray matter volumes, including brainstem, bilateral insula, amygdala, right caudal anterior cingulate cortex (FDRp's<0.05). ΔSCL from typical-to-obstacle walking were associated with volumes of the midbrain segment of the brainstem and anterior segment of the circular sulcus of the insula (FDRp's<0.05), with no other significant associations. ΔSCL from typical-to-dual task walking was associated with the bilateral caudal anterior cingulate cortex, and left rostral cingulate cortex (FDRp's<0.05). Sympathetic reactivity is blunted during typical and complex walking tasks in persons with chronic pain. Additionally, blunted sympathetic reactivity is associated with CAN brain structure, in a brain region-dependent manner. These results support the idea that chronic pain may negatively impact typical autonomic responses needed for walking performance via its potential impact on the brain. R01AR071431, K01AG048259, and 1 F31 AR077996-01. Autonomic dysregulation may lead to blunted sympathetic reactivity in chronic pain states and autonomic responses are controlled by the central autonomic network (CAN). Little research has examined sympathetic reactivity and associations with brain CAN structures in the presence of chronic pain; thus, the present study aims to investigate chronic pain differences in sympathetic reactivity and associations with CAN brain region volumes. Sympathetic reactivity was measured as change in skin conductance level (ΔSCL) between a resting preparation and walking phases of typical and complex walking tasks (obstacle and dual-task) in 31 participants with (n=19) and without (n=12) chronic musculoskeletal pain using a repeated measures-ANCOVA with Bonferroni corrections. Structural 3T MRI was used to determine gray matter volume associations with ΔSCL in regions of the CAN (i.e., brainstem, amygdala, insula, and anterior cingulate cortex, using partial correlations (FDR-corrected) adjusting for important covariates. ΔSCL varied across all walking tasks (main effect p=0.036), with lower ΔSCL in chronic pain participants (21.0±5.4µS) compared to controls (43.4±7.5µS). ΔSCL during typical walking was associated with multiple CAN gray matter volumes, including brainstem, bilateral insula, amygdala, right caudal anterior cingulate cortex (FDRp's<0.05). ΔSCL from typical-to-obstacle walking were associated with volumes of the midbrain segment of the brainstem and anterior segment of the circular sulcus of the insula (FDRp's<0.05), with no other significant associations. ΔSCL from typical-to-dual task walking was associated with the bilateral caudal anterior cingulate cortex, and left rostral cingulate cortex (FDRp's<0.05). Sympathetic reactivity is blunted during typical and complex walking tasks in persons with chronic pain. Additionally, blunted sympathetic reactivity is associated with CAN brain structure, in a brain region-dependent manner. These results support the idea that chronic pain may negatively impact typical autonomic responses needed for walking performance via its potential impact on the brain. R01AR071431, K01AG048259, and 1 F31 AR077996-01.

Pain modulatory network is influenced by sex and age in a healthy state and during osteoarthritis progression in rats.

Old age and female sex are risk factors for the development of osteoarthritis (OA) and chronic pain. We investigated the effects of sex and age on pain modulatory networks in a healthy state and during OA progression. We used functional MRI to determine the effects of sex and age on periaqueductal gray functional connectivity (PAG FC) in a healthy state (pre-OA) and during the early and late phases of monosodium iodoacetate (MIA)-induced OA in male and female Fischer 344 rats (young, 3-6 mo / old, 20-24 mo). For functional MRI, rats were scanned using a Bruker 7T MRI (TR = 1500 ms, in plane resolution = 400 μm, slice thickness 1 mm, acquisition time: 15 minutes) and under isoflurane anesthesia ≤ 1.5%. We then examined how sex and age affect longitudinal changes in PAG FC in OA. In a healthy state, females exhibited more widespread PAG FC than males, and this effect was exaggerated with aging. Young males had moderate PAG FC changes during the early phase but recruited additional brain regions, including the rostral anterior cingulate cortex (ACC), during the late phase. Young females exhibited widespread PAG FC in the early phase, which includes connections to insula, caudal ACC, and nucleus accumbens (NAc). Older groups had strong PAG FC with fewer regions in the early phase, but they recruited additional brain regions, including NAc, in the late phase. Overall, our findings show that PAG FC is modulated by sex and age in a healthy state. A widespread PAG network in the early phase of OA pain may contribute to the transition from acute to chronic OA pain and the increased risk of developing chronic pain for females. Enhanced PAG FC with the reward system may represent a potential mechanism underlying chronic OA pain in elderly patients. NIH-NIA grant AG053783 (JYR) and NIH-NIDCR grant DE0027808 (JYR).

Altered cortical morphology in major depression disorder patients with suicidality.

Major depressive disorder (MDD) is associated with high risk of suicide, but the biological underpinnings of suicidality in MDD patients are far from conclusive. Previous neuroimaging studies using voxel-based morphometry (VBM) demonstrated that depressed individuals with suicidal thoughts or behaviors exhibit specific cortical structure alterations. To complement VBM findings, surface-based morphometry (SBM) can provide more details into gray matter structure, including the cortical complexity, cortical thickness and sulcal depth for brain images. This study aims to use SBM to investigate cortical morphology alterations to obtain evidence for neuroanatomical alterations in depressed patients with suicidality. Here, 3D T1-weighted MR images of brain from 39 healthy controls, 40 depressed patients without suicidality (patient controls), and 39 with suicidality (suicidal groups) were analyzed based on SBM to estimate the fractal dimension, gyrification index, sulcal depth, and cortical thickness using the Computational Anatomy Toolbox. Correlation analyses were performed between clinical data and cortical surface measurements from patients. Surface-based morphometry showed decreased sulcal depth in the parietal, frontal, limbic, occipital and temporal regions and decreased fractal dimension in the frontal regions in depressed patients with suicidality compared to both healthy and patient controls. Additionally, in patients with depression, the sulcal depth of the left caudal anterior cingulate cortex was negatively correlated with Hamilton Depression Rating Scale scores. Depressed patients with suicidality had abnormal cortical morphology in some brain regions within the default mode network, frontolimbic circuitry and temporal regions. These structural deficits may be associated with the dysfunction of emotional processing and impulsivity control. This study provides insights into the underlying neurobiology of the suicidal brain.

Pain modulatory network is influenced by sex and age in a healthy state and during osteoarthritis progression in rats.

Old age and female sex are risk factors for the development of osteoarthritis (OA) and chronic pain. We investigated the effects of sex and age on pain modulatory networks in a healthy state and during OA progression. We used functional MRI to determine the effects of sex and age on periaqueductal gray functional connectivity (PAG FC) in a healthy state (pre‐OA) and during the early and late phases of monosodium iodoacetate‐induced OA in rats. We then examined how sex and age affect longitudinal changes in PAG FC in OA. In a healthy state, females exhibited more widespread PAG FC than males, and this effect was exaggerated with aging. Young males had moderate PAG FC changes during the early phase but recruited additional brain regions, including the rostral anterior cingulate cortex (ACC), during the late phase. Young females exhibited widespread PAG FC in the early phase, which includes connections to insula, caudal ACC, and nucleus accumbens (NAc). Older groups had strong PAG FC with fewer regions in the early phase, but they recruited additional brain regions, including NAc, in the late phase. Overall, our findings show that PAG FC is modulated by sex and age in a healthy state. A widespread PAG network in the early phase of OA pain may contribute to the transition from acute to chronic OA pain and the increased risk of developing chronic pain for females. Enhanced PAG FC with the reward system may represent a potential mechanism underlying chronic OA pain in elderly patients.

Chronic Pain is Associated With Reduced Sympathetic Nervous System Reactivity During Simple and Complex Walking Tasks: Potential Cerebral Mechanisms

Background Autonomic dysregulation may lead to blunted sympathetic reactivity in chronic pain states. Autonomic responses are controlled by the central autonomic network (CAN). Little research has examined sympathetic reactivity and associations with brain CAN structures in the presence of chronic pain; thus, the present study aims to investigate how chronic pain influences sympathetic reactivity and associations with CAN brain region volumes. Methods Sympathetic reactivity was measured as change in skin conductance level (ΔSCL) between a resting reference period and walking periods for typical and complex walking tasks (obstacle and dual-task). Participants included 31 people with (n = 19) and without (n = 12) chronic musculoskeletal pain. Structural 3 T MRI was used to determine gray matter volume associations with ΔSCL in regions of the CAN (i.e., brainstem, amygdala, insula, and anterior cingulate cortex). Results ΔSCL varied across walking tasks (main effect p = 0.036), with lower ΔSCL in chronic pain participants compared to controls across trials 2 and 3 under the obstacle walking condition. ΔSCL during typical walking was associated with multiple CAN gray matter volumes, including brainstem, bilateral insula, amygdala, and right caudal anterior cingulate cortex (p’s < 0.05). The difference in ΔSCL from typical-to-obstacle walking were associated with volumes of the midbrain segment of the brainstem and anterior segment of the circular sulcus of the insula (p’s < 0.05), with no other significant associations. The difference in ΔSCL from typical-to-dual task walking was associated with the bilateral caudal anterior cingulate cortex, and left rostral cingulate cortex (p’s < 0.05). Conclusions Sympathetic reactivity is blunted during typical and complex walking tasks in persons with chronic pain. Additionally, blunted sympathetic reactivity is associated with CAN brain structure, with direction of association dependent on brain region. These results support the idea that chronic pain may negatively impact typical autonomic responses needed for walking performance via its potential impact on the brain.

Roles of 5,10-Methylenetetrahydrofolate Reductase C677T Polymorphisms in First-Episode, Drug-Naive Adult Patients With Depression.

5,10-Methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism is considered as a predisposition and promising genetic candidate to major depressive disorder (MDD), as it is associated with impaired one-carbon cycles, which may be involved in the pathogenesis of depression. Cortical thickness (CT) and subcortical structure volumes have been extensively studied in MDD and have been proposed as one of the phenotypes for MDD. We intend to discuss the association between CT, subcortical structure volume, and MTHFR C677T polymorphism in first-episode, treatment-naive patients with MDD. In this study, 127 adult patients with MDD and 101 age- and gender-matched healthy controls (HCs) were included. All subjects underwent T1-weighted MRI, MTHFR C677T genotyping, and FreeSurfer software-based morphological analysis. MDD patients have been detected to have significantly decreased volumes in the left nucleus accumbens (P < 0.001). The MTHFR 677 T allele carriers manifested with thinner CT in the left caudal anterior cingulate cortex (cACC, P = 0.009) compared with CC genotype. There were significant genotype-by-diagnosis interactions for the CT in the left cACC (P = 0.009), isthmus cingulate (P = 0.002), medial orbitofrontal lobe (P = 0.012), posterior cingulate (P = 0.030), and the right lateral orbitofrontal lobe (P = 0.012). We also found a trend in the interaction effect on the volume of the left putamen (P = 0.050). Our results revealed that MTHFR C677T polymorphism may be involved in the dysfunction of limbic–cortical–striatal–pallidal–thalamic (LCSPT) circuits mediating emotion processing, which may contribute to pathogenesis of MDD.

Cingulate Cortex Structural Alterations in Substance Use Disorder Psychiatric Inpatients.

Substance use disorder (SUD) includes maladaptive patterns of substance use despite negative consequences. Previous structural neuroimaging studies showed some structural alterations in SUD, but it remains unknown whether these alterations are specifically associated with SUD or common comorbidities. This study attempts to validate the findings of structural differences between SUD, healthy controls (HC), and psychiatric controls (PC). We used HC (N = 86) matched for demographics, and PC (N = 86) matched for demographics and psychiatric diagnoses to a group of SUD patients (N = 86). We assessed the group differences of subcortical volumes, cortical volumes, thickness, and surface areas between SUD and HC. We then analyzed the group differences between SUD and PC within regions showing differences between SUD and HC. SUD had smaller left nucleus accumbens, right thalamus, right hippocampus, left caudal anterior cingulate cortex (ACC) volume, and larger right caudal ACC volume, and right caudal ACC, right caudal middle frontal gyrus (MFG), and right posterior cingulate cortex (PCC) surface than HC. Increased right caudal ACC volume and right PCC surface in SUD were the only findings when compared with PC. Several areas showed thickness alterations between SUD and HC, but none survived multiple comparisons vs PC. Our findings suggest that cingulate structures may be altered in SUD compared with both HC and PC. These results are among the first to indicate that some structural alterations may be SUD-specific, and highlight a cautionary note about using HC in psychiatric biomarker research. (Am J Addict 2021;30:72-79).

Fusiform gyrus volume reduction associated with impaired facial expressed emotion recognition and emotional intensity recognition in patients with schizophrenia spectrum psychosis

Impaired social cue perception such as emotional recognition is a prominent feature in patients with schizophrenia, adversely affecting psychosocial outcomes and worsening clinical manifestations of the disease. However, few structural neuroimaging studies have investigated both facial emotion recognition and emotion intensity recognition in schizophrenia. Ninety patients with schizophrenia spectrum psychosis and fifty healthy controls underwent structural magnetic resonance imaging. The gray matter volumes of emotion recognition areas such as the bilateral caudal anterior cingulate cortex, rostral anterior cingulate cortex, fusiform gyrus, insula, amygdala, and hippocampus, were compared between patients and controls. Emotional recognition levels and symptom severities were examined. Group analysis showed that the gray matter volumes of the patients were significantly smaller in left hippocampus and fusiform gyrus compared with healthy controls. A correlation analysis revealed that larger left fusiform gyrus volume was associated with better facial emotion recognition and emotional intensity recognition in patients with schizophrenia spectrum psychosis. Additionally, left fusiform gyrus volumes showed a significant negative correlation with the negative symptom scores at baseline. These findings suggest that gray matter abnormalities in the left fusiform gyrus are associated with impaired social emotion recognition and severity of negative symptoms at baseline in patients with schizophrenia spectrum psychosis.

Smaller Regional Brain Volumes Predict Posttraumatic Stress Disorder at 3 Months After Mild Traumatic Brain Injury

BackgroundBrain volumes in regions such as the hippocampus and amygdala have been associated with risk for the development of posttraumatic stress disorder (PTSD). The objective of this study was to determine whether a set of regional brain volumes, measured by magnetic resonance imaging at 2 weeks following mild traumatic brain injury, were predictive of PTSD at 3 and 6 months after injury. MethodsUsing data from TRACK-TBI (Transforming Research and Clinical Knowledge in TBI), we included patients (N = 421) with Glasgow Coma Scale scores 13–15 assessed after evaluation in the emergency department and at 2 weeks, 3 months, and 6 months after injury. Probable PTSD diagnosis (PTSD Checklist for DSM-5 score, ≥33) was the outcome. FreeSurfer 6.0 was used to perform volumetric analysis of three-dimensional T1-weighted magnetic resonance images at 3T obtained 2 weeks post injury. Brain regions selected a priori for volumetric analyses were insula, hippocampus, amygdala, superior frontal cortex, rostral and caudal anterior cingulate, and lateral and medial orbitofrontal cortices. ResultsOverall, 77 (18.3%) and 70 (16.6%) patients had probable PTSD at 3 and 6 months. A composite volume derived as the first principal component incorporating 73.8% of the variance in insula, superior frontal cortex, and rostral and caudal cingulate contributed to the prediction of 3-month (but not 6-month) PTSD in multivariable models incorporating other established risk factors. ConclusionsResults, while needing replication, provide support for a brain reserve hypothesis of PTSD and proof of principle for how prediction of at-risk individuals might be accomplished to enhance prognostic accuracy and enrich clinical prevention trials for individuals at the highest risk of PTSD following mild traumatic brain injury.

Individual resting-state frontocingular functional connectivity predicts the intermittent theta burst stimulation response to stress in healthy female volunteers.

Intermittent theta burst stimulation (iTBS) delivered to the dorsolateral prefrontal cortex (DLPFC) has been investigated as a promising treatment for stress and stress‐related mental disorders such as major depression, yet large individual differences in responsiveness demand further exploration and optimization of its effectiveness. Clinical research suggests that resting‐state functional connectivity (rsFC) between the DLPFC and the anterior cingulate cortex (ACC) can predict iTBS treatment response in depression. The present study aimed to investigate whether rsFC between the left DLPFC and ACC subregions could predict the degree to which the stress system is affected by iTBS. After assessment of baseline resting‐state fMRI data, 34 healthy female participants performed the Trier Social Stress Test on two separate days, each followed by active or sham iTBS over the left DLPFC. To evaluate iTBS effects on the stress‐system, salivary cortisol was measured throughout the procedure. Our results showed that a stronger negative correlation between the left DLPFC and the caudal ACC was linked to a larger attenuation of stress‐system sensitivity during active, but not during sham iTBS. In conclusion, based on individual rsFC between left DLPFC and caudal ACC, iTBS could be optimized to more effectively attenuate deregulation of the stress system.

Effect of Ketamine on Limbic GABA and Glutamate: A Human In Vivo Multivoxel Magnetic Resonance Spectroscopy Study.

IntroductionConverging evidence suggests that ketamine elicits antidepressant effects via enhanced neuroplasticity precipitated by a surge of glutamate and modulation of GABA. Magnetic resonance spectroscopic imaging (MRSI) illustrates changes to cerebral glutamate and GABA immediately following ketamine administration during dissociation. However, few studies assess subacute changes in the first hours following application, when ketamine’s antidepressant effects emerge. Moreover, ketamine metabolites implicated in its antidepressant effects develop during this timeframe. Thus, this study aimed to investigate subacute changes in cerebral Glx (glutamate + glutamine), GABA and their ratio in seven brain regions central to depressive pathophysiology and treatment.MethodsTwenty-five healthy subjects underwent two multivoxel MRS scans using a spiral encoded, MEGA-edited LASER-localized 3D-MRSI sequence, at baseline and 2 h following intravenous administration of racemic ketamine (0.8 mg/kg bodyweight over 50 min). Ketamine, norketamine and dehydronorketamine plasma levels were determined at routine intervals during and after infusion. Automated region-of-interest (ROI)–based quantification of mean metabolite concentration was used to assess changes in GABA+/total creatine (tCr), Glx/tCr, and GABA+/Glx ratios in the thalamus, hippocampus, insula, putamen, rostral anterior cingulate cortex (ACC), caudal ACC, and posterior cingulate cortex. Effects of ketamine on neurotransmitter levels and association with ketamine- and metabolite plasma levels were tested with repeated measures analyses of variance (rmANOVA) and correlation analyses, respectively.ResultsFor GABA+/tCr rmANOVA revealed a measurement by region interaction effect (puncorr < 0.001) and post hoc pairwise comparisons showed a reduction in hippocampal GABA+/tCr after ketamine (pcorr = 0.02). For Glx/tCr and GABA+/Glx neither main effects of measurement nor measurement by region interactions were observed (all puncorr > 0.05). Furthermore, no statistically significant associations between changes in any of the neurotransmitter ratios and plasma levels of ketamine, norketamine, or dehydronorketamine were observed (pcorr > 0.05).ConclusionThis study provides evidence for decreased hippocampal GABA+/tCr ratio 2 h following ketamine administration. As MRS methodology measures total levels of intra- and extracellular GABA, results might indicate drug induced alterations in GABA turnover. Our study in healthy humans suggests that changes in GABA levels, particularly in the hippocampus, should be further assessed for their relevance to ketamine´s antidepressant effects.

Accelerated cortical thinning and volume reduction over time in young people at high genetic risk for bipolar disorder.

Bipolar disorder (BD) is a familial psychiatric disorder associated with frontotemporal and subcortical brain abnormalities. It is unclear whether such abnormalities are present in relatives without BD, and little is known about structural brain trajectories in those at risk. Neuroimaging was conducted at baseline and at 2-year follow-up interval in 90 high-risk individuals with a first-degree BD relative (HR), and 56 participants with no family history of mental illness who could have non-BD diagnoses. All 146 subjects were aged 12-30 years at baseline. We examined longitudinal change in gray and white matter volume, cortical thickness, and surface area in the frontotemporal cortex and subcortical regions. Compared to controls, HR participants showed accelerated cortical thinning and volume reduction in right lateralised frontal regions, including the inferior frontal gyrus, lateral orbitofrontal cortex, frontal pole and rostral middle frontal gyrus. Independent of time, the HR group had greater cortical thickness in the left caudal anterior cingulate cortex, larger volume in the right medial orbitofrontal cortex and greater area of right accumbens, compared to controls. This pattern was evident even in those without the new onset of psychopathology during the inter-scan interval. This study suggests that differences previously observed in BD are developing prior to the onset of the disorder. The pattern of pathological acceleration of cortical thinning is likely consistent with a disturbance of molecular mechanisms responsible for normal cortical thinning. We also demonstrate that neuroanatomical differences in HR individuals may be progressive in some regions and stable in others.