Gray Matter Volume In Orbitofrontal Cortex Research Articles

Relationships between serotonin 1A receptor DNA methylation, self-reported history of childhood abuse and gray matter volume in major depression

BackgroundEarly life adversity is a risk factor for psychopathology and is associated with epigenetic alterations in the 5-HT1A receptor gene promoter. The 5-HT1A receptor mediates neurotrophic effects, which could affect brain structure and function. We examined relationships between self-reported early childhood abuse, 5-HT1A receptor promoter DNA methylation, and gray matter volume (GMV) in Major Depressive Disorder (MDD). MethodsPeripheral DNA methylation of 5-HT1A receptor promoter CpG sites −681 and −1007 was assayed in 50 individuals with MDD, including 18 with a history of childhood abuse. T1-weighted structural magnetic resonance imaging (MRI) was performed. Voxel-based morphometry (VBM) was quantified in amygdala, hippocampus, insula, occipital lobe, orbitofrontal cortex, temporal lobe, parietal lobe, and at the voxel level. ResultsNo relationship was observed between DNA methylation and history of childhood abuse. We observed regional heterogeneity comparing −681 CpG site methylation and GMV (p = 0.014), with a positive relationship to GMV in orbitofrontal cortex (p = 0.035). Childhood abuse history was associated with higher GMV considering all ROIs simultaneously (p < 0.01). In whole-brain analyses, childhood abuse history was positively correlated with GMV in multiple clusters, including insula and orbitofrontal cortex (pFWE = 0.005), and negatively in intracalcarine cortex (pFWE = 0.001). LimitationsSmall sample size, childhood trauma assessment instrument used, and assay of peripheral, rather than CNS, methylation. ConclusionsThese cross-sectional findings support hypotheses of 5-HT1A receptor-related neurotrophic effects, and of increased regional GMV as a potential regulatory mechanism in the setting of childhood abuse. Orbitofrontal cortex was uniquely associated with both childhood abuse history and 5-HT1A receptor methylation.

Interaction of recent stressful life events and childhood abuse on orbitofrontal grey matter volume in adults with depression

BackgroundThe diathesis-stress model of major depressive disorder (MDD) predicts interactions of recent stressful life events (SLEs) in adulthood and early developmental risk factors. We tested, for the first time, the diathesis stress model on brain structure in a large group of MDD patients. MethodsStructural magnetic resonance imaging data of 1465 participants (656 with lifetime diagnosis MDD; 809 healthy controls) were analyzed using voxel-based morphometry to identify clusters associated with recent SLEs (Life Events Questionnaire). Those clusters were then examined for group (healthy/MDD) × early developmental risk (operationalized as childhood abuse [Childhood Trauma Questionnaire] and a major psychiatric disorder [i.e., MDD, bipolar disorder, schizophrenia, and schizoaffective disorder] in a first-degree relative) × recent SLEs three-way interactions on grey matter volume. ResultsThere was a group × childhood abuse × recent SLEs interaction on left medial orbitofrontal cortex grey matter volume. This three-way interaction arose because childhood abuse and recent SLEs interacted in MDD subjects but not in healthy subjects. LimitationsWe are not able to draw conclusions about the cause and effect relationship due to our cross-sectional study design. ConclusionsOur data provides evidence for an interplay between orbitofrontal cortex structure, childhood abuse and recent SLEs. These factors have previously been linked to MDD and their complex interaction contributes to the pathogenesis of MDD.

Reduced Gray Matter Volume in Orbitofrontal Cortex Across Schizophrenia, Major Depressive Disorder, and Bipolar Disorder: A Comparative Imaging Study.

Schizophrenia (SZ), major depressive disorder (MDD), and bipolar disorder (BD) are severe psychiatric disorders and share common characteristics not only in clinical symptoms but also in neuroimaging. The purpose of this study was to examine common and specific neuroanatomical features in individuals with these three psychiatric conditions. In this study, 70 patients with SZ, 85 patients with MDD, 42 patients with BD, and 95 healthy controls (HCs) were recruited. Voxel-based morphometry (VBM) analysis was used to explore brain imaging characteristics. Psychopathology was assessed using the Beck Depression Inventory (BDI), the Beck Anxiety Inventory (BAI), the Young Mania Rating Scale (YMRS), and the Positive and Negative Syndrome Scale (PANSS). Cognition was assessed using the digit symbol substitution test (DSST), forward-digital span (DS), backward-DS, and semantic fluency. Common reduced gray matter volume (GMV) in the orbitofrontal cortex (OFC) region was found across the SZ, MDD, and BD. Specific reduced GMV of brain regions was also found. For patients with SZ, we found reduced GMV in the frontal lobe, temporal pole, occipital lobe, thalamus, hippocampus, and cerebellum. For patients with MDD, we found reduced GMV in the frontal and temporal lobes, insular cortex, and occipital regions. Patients with BD had reduced GMV in the medial OFC, inferior temporal and fusiform regions, insular cortex, hippocampus, and cerebellum. Furthermore, the OFC GMV was correlated with processing speed as assessed with the DSST across four groups (r = 0.17, p = 0.004) and correlated with the PANSS positive symptoms sub-score in patients with SZ (r = − 0.27, p = 0.026). In conclusion, common OFC alterations in SZ, MDD, and BD provided evidence that this region dysregulation may play a critical role in the pathophysiology of these three psychiatric disorders.

Gray Matter Abnormalities of Orbitofrontal Cortex and Striatum in Drug-Naïve Adult Patients With Obsessive-Compulsive Disorder.

Objective: This study examined whether obsessive-compulsive disorder (OCD) patients have gray matter abnormalities in regions related to executive function, and whether such abnormalities are associated with impaired executive function.Methods: Multiple scales were administered to 27 first-episode drug-naïve OCD patients and 29 healthy controls. Comprehensive brain morphometric indicators of orbitofrontal cortex (OFC) and three striatum areas (caudate, putamen, and pallidum) were determined. Hemisphere lateralization index was calculated for each region of interest. Correlations between lateralization index and psychological variables were examined in OCD group.Results: The OCD group had greater local gyrification index for the right OFC and greater gray matter volumes of the bilateral putamen and left pallidum than healthy controls. They also had weaker left hemisphere superiority for local gyrification index of the OFC and gray matter volume of the putamen, but stronger left hemisphere superiority for gray matter volume of the pallidum. Patients' lateralization index for local gyrification index of the OFC correlated negatively with Yale-Brown Obsessive Compulsive Scale and Dysexecutive Questionnaire scores, respectively.Conclusion: Structural abnormalities of the bilateral putamen, left pallidum, and right OFC may underlie OCD pathology. Abnormal lateralization in OCD may contribute to the onset of obsessive-compulsive symptoms and impaired executive function.

Novelty seeking is associated with increased body weight and orbitofrontal grey matter volume reduction

Novelty seeking (NS) has previously been identified as a personality trait that is associated with elevated body mass index (BMI) and obesity. Of note, both obesity and reduced impulse control – a core feature of NS – have previously been associated with grey matter volume (GMV) reductions in the orbitofrontal cortex (OFC). Yet, it remains unknown, if body weight-related grey matter decline in the OFC might be explained by higher levels of NS.To address this question, we studied associations between NS, BMI and brain structure in 355 healthy subjects. Brain images were pre-processed using voxel-based morphometry (VBM). BMI was calculated from self-reported height and weight. The Tridimensional Personality Questionnaire (TPQ) was used to assess NS.NS and BMI were associated positively (r = .137, p = .01) with NS being a significant predictor of BMI (B = 0.172; SE B = 0.05; ß = 0.184; p = 0.001). Significant associations between BMI and GMV specifically in the OFC (x = −44, y = 56, z = −2, t(350) = 4.34, k = 5, pFWE = 0.011) did not uphold when correcting for NS in the model. In turn, a significant negative association between NS and OFC GMV was found independent of BMI (x = −2, y = 48, z = −10, t(349) = 4.42, k = 88, pFWE = 0.008). Body mass-related grey matter decrease outside the OFC could not be attributed to NS.Our results suggest that body-weight-related orbitofrontal grey matter reduction can at least partly be linked to higher levels of NS. Given the pivotal role of the OFC in overweight as well as cognitive domains such as impulse inhibition, executive control and reward processing, its association with NS seems to provide a tenable neurobiological correlate for future research.

Subjective response to alcohol: Associated alcohol use and orbitofrontal gray matter volume in bipolar disorder

BackgroundAlcohol use disorders (AUDs) are highly prevalent in bipolar disorder, however the developmental etiology of this comorbidity remains unknown. Structural differences in the orbitofrontal cortex (OFC) have been linked to problematic drinking in bipolar disorder and typically developing youth, with evidence implicating variations in OFC in differential subjective response to alcohol in typical development. MethodsSubjective response to alcohol, recent alcohol use, impulsivity, and variation in OFC gray matter volume were investigated in 48 emerging adults (24 with bipolar disorder, 24 typically developing). On average 1.5 years later, drinking patterns were reassessed and relations between subjective response and changes in alcohol use were explored. ResultsGroups did not differ in baseline alcohol use or subjective response. At baseline, decreased subjective response to alcohol was associated with increased alcohol use in both groups. Lower gray matter volume in medial OFC in bipolar disorder was associated with increased subjective response to alcohol, whereas lower gray matter volume in OFC in typically developing participants was associated with decreased subjective response to alcohol. Increase in alcohol use (baseline to follow-up) was associated with increased baseline subjective response to alcohol in bipolar disorder, and decreased baseline subjective response in the typically developing group. LimitationsPreliminary study with a small sample size. ConclusionUnderlying OFC biology may contribute to differences in alcohol sensitivity in bipolar disorder which may also relate to prospective changes in alcohol use patterns. Future studies are needed to examine how these factors prospectively relate to development of AUDs in bipolar disorder.

Genetic and environmental influences on corticostriatal circuits in twins with autism

Corticostriatal circuits (CSC) have been implicated in the presentation of some restricted and repetitive behaviours (RRBs) in children with autism-spectrum disorder (ASD), and preliminary evidence suggests that disruptions in these pathways may be associated with differences in genetic and environmental influences on brain development. The objective of this investigation was to examine the impact of genetic and environmental factors on CSC regions in twins with and without ASD and to evaluate their relationship with the severity of RRBs. We obtained T1-weighted MRIs from same-sex monozygotic and dizygotic twin pairs, aged 6–15 years. Good-quality data were available from 48 ASD pairs (n = 96 twins; 30 pairs concordant for ASD, 15 monozygotic and 15 dizygotic; 18 pairs discordant for ASD, 4 monozygotic and 14 dizygotic) and 34 typically developing control pairs (n = 68 twins; 20 monozygotic and 14 dizygotic pairs). We generated structural measures of the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), caudate, putamen, pallidum and thalamus using FreeSurfer. Twin pair comparisons included intraclass correlation analyses and ACE modelling (a2 = additive genetics; c2 = common or shared environment; e2 = unique or nonshared environment). We also assessed correlations with RRB severity. Structural variation in CSC regions was predominantly genetically mediated in typically developing twins (a2 = 0.56 to 0.87), except for ACC white matter volume (a2 = 0.42, 95% confidence interval [CI] 0.08 to 0.77). We also observed similar magnitudes of genetic influence in twins with ASD (a2 = 0.65 to 0.97), but the cortical thickness of the ACC (c2 = 0.44, 95% CI 0.22 to 0.66) and OFC (c2 = 0.60, 95% CI 0.25 to 0.95) was primarily associated with environmental factors in only twins with ASD. Twin pair differences in OFC grey matter volume were also correlated with RRB severity and were predominantly environmentally mediated. We obtained MRIs on 2 scanners, and analytical approaches could not identify specific genetic and environmental factors. Genetic factors primarily contribute to structural variation in subcortical CSC regions, regardless of ASD, but environmental factors may exert a greater influence on the development of grey matter thickness in the OFC and ACC in children with ASD. The increased vulnerability of OFC grey matter to environmental influences may also mediate some heterogeneity in RRB severity in children with ASD.

Obesity is associated with reduced orbitofrontal cortex volume: A coordinate-based meta-analysis

Neural models of obesity vary in their focus upon prefrontal and striatal differences. Animal and human studies suggest that differential functioning of the orbitofrontal cortex is associated with obesity. However, meta-analyses of functional neuroimaging studies have not found a clear relationship between the orbitofrontal cortex and obesity. Meta-analyses of structural imaging studies of obesity have shown mixed findings with regards to an association with reduced orbitofrontal cortex gray matter volume. To clarify these findings, we conducted a meta-analysis of 25 voxel-based morphometry studies, and found that greater body mass index is associated with decreased gray matter volume in the right orbitofrontal cortex (Brodmanns’ areas 10 and 11), where family-wise corrected p < .05, N = 7,612. Use of the right orbitofrontal cortex as a seed in a Neurosynth Network Coactivation analysis showed that this region is associated with activity in the left frontal medial cortex, left temporal lobe, right precuneus cortex, posterior division of the left middle temporal gyrus, and right frontal pole. When Neurosynth Network Coactivation results were submitted as regions of interest in the Human Connectome Project data, we found that greater body mass index was associated with greater activity in left frontal medial cortex response to the Gambling Task, where p < .05, although this did not survive Bonferroni-correction. Our findings highlight the importance of the orbitofrontal cortex structure and functioning in neural models of obesity. Exploratory analyses suggest more studies are needed that examine the functional significance of reduced orbitofrontal cortex gray matter volume in obesity, and the effect of age and weight changes on this relationship using longitudinal designs.

Orbitofrontal cortex grey matter volume is related to children’s depressive symptoms

Adults with a history of depression show distinct patterns of grey matter volume (GMV) in frontal cortical (e.g., prefrontal cortex, orbitofrontal cortex) and limbic (e.g., anterior cingulate, amygdala, hippocampus, dorsal striatum) structures, regions relevant to the processing and regulation of reward, which is impaired in the context of depression. However, it is unclear whether these GMV associations with depression precede depressive disorder onset or whether GMV is related to early emerging symptoms or familial depression. To address these questions, we used voxel-based morphometry (VBM) to examine GMV in 85 community-dwelling children (M = 11.12 years, SD = 0.63 years) screened for current and lifetime depression. Associations between children’s depressive symptoms (self- and mother-report of children’s symptoms), children’s maternal depression history, and GMV were examined. Although maternal depression history was unrelated to children’s GMV, child GMV in the orbitofrontal cortex (OFC) was negatively related to children’s self-reported depressive symptoms, using both a priori ROI and whole-brain analyses. Moderated regression analyses indicated that girls’ GMV was negatively related to girls’ depressive symptoms (as indexed by both self- and mother-report of girls’ symptoms), whereas boys’ symptoms were positively related to GMV. Our findings suggest that brain morphology in the OFC, a region with functional roles in processes relevant to depressive symptoms (i.e., reward-based learning and reward processing), is associated with early depressive symptoms prior to the development of clinically significant depression.

Inconsistency between cortical reorganization and functional connectivity alteration in the sensorimotor cortex following incomplete cervical spinal cord injury.

The aim of this study was to explore whether there will be any alterations in sensorimotor-related cortex and the possible causes of sensorimotor dysfunction after incomplete cervical spinal cord injury (ICSCI). Structural and resting-state functional magnetic resonance imaging (rs-fMRI) of nineteen ICSCI patients and nineteen healthy controls (HCs) was acquired. Voxel based morphometry (VBM) and tract-based spatial statistics were performed to assess differences in gray matter volume (GMV) and white matter integrity between ICSCI patients and HCs. Whole brain functional connectivity (FC) was analyzed using the results of VBM as seeds. Associations between the clinical variables and the brain changes were studied. Compared with HCs, ICSCI patients demonstrated reduced GMV in the right fusiform gyrus (FG) and left orbitofrontal cortex (OFC) but no changes in areas directly related to sensorimotor function. There were no significant differences in brain white matter. Additionally, the FC in the left primary sensorimotor cortex and cerebellum decreased when the FG and OFC, respectively, were used as seeds. Subsequent relevance analysis suggests a weak positive correlation between the left OFC's GMV and visual analog scale (VAS) scores. In conclusion, brain structural changes following ICSCI occur mainly in certain higher cognitive regions, such as the FG and OFC, rather than in the brain areas directly related to sensation or motor control. The functional areas of the brain that are related to cognitive processing may play an important role in sensorimotor dysfunction through the decreased FC with sensorimotor areas after ICSCI. Therefore, cognition-related functional training may play an important role in rehabilitation of sensorimotor function after ICSCI.

Orbitofrontal structural markers of negative affect in alcohol dependence and their associations with heavy relapse-risk at 6 months post-treatment

BackgroundAlcohol relapse is often occurring to regulate negative affect during withdrawal. On the neurobiological level, alcoholism is associated with gray matter (GM) abnormalities in regions that regulate emotional experience such as the orbitofrontal cortex (OFC). However, no study to our knowledge has investigated the neurobiological unpinning of affect in alcoholism at early withdrawal and the associations of OFC volume with long-term relapse risk. MethodsOne hundred and eighty-two participants were included, 95 recently detoxified alcohol dependent patients (ADP) and 87 healthy controls (HC). We measured affective states using the positive and negative affect schedule (PANAS). We collected T1-weighted brain structural images and performed Voxel-based morphometry (VBM). ResultsFindings revealed GM volume decrease in alcoholics in the prefrontal cortex (including medial OFC), anterior cingulate gyrus, and insula. GM volume in the medial OFC was positively associated with NA in the ADP group. Cox regression analysis predicted that risk to heavy relapse at 6 months increases with decreased GM volume in the medial OFC. ConclusionsNegative affect during alcohol withdrawal was positively associated with OFC volume. What is more, increased GM volume in the OFC also moderated risk to heavy relapse at 6 months. Reduced GM in the OFC poses as risk to recovery from alcohol dependence and provides valuable insights into transient negative affect states during withdrawal that can trigger relapse. Implications exist for therapeutic interventions signifying the OFC as a neurobiological marker to relapse and could explain the inability of ADP to regulate internal negative affective states.

Sex differences in socioemotional functioning, attentional bias, and gray matter volume in maltreated children: A multilevel investigation.

While maltreatment is known to impact social and emotional functioning, threat processing, and neural structure, the potentially dimorphic influence of sex on these outcomes remains relatively understudied. We investigated sex differences across these domains in a large community sample of children aged 10 to 14 years (n = 122) comprising 62 children with verified maltreatment experience and 60 well-matched nonmaltreated peers. The maltreated group relative to the nonmaltreated comparison group exhibited poorer social and emotional functioning (more peer problems and heightened emotional reactivity). Cognitively, they displayed a pattern of attentional avoidance of threat in a visual dot-probe task. Similar patterns were observed in males and females in these domains. Reduced gray matter volume was found to characterize the maltreated group in the medial orbitofrontal cortex, bilateral middle temporal lobes, and bilateral supramarginal gyrus; sex differences were observed only in the supramarginal gyrus. In addition, a disordinal interaction between maltreatment exposure and sex was found in the postcentral gyrus. Finally, attentional avoidance to threat mediated the relationship between maltreatment and emotional reactivity, and medial orbitofrontal cortex gray matter volume mediated the relationship between maltreatment and peer functioning. Similar mediation patterns were observed across sexes. This study highlights the utility of combining multiple levels of analysis when studying the "latent vulnerability" engendered by childhood maltreatment and yields tentative findings regarding a neural basis of sex differences in long-term outcomes for maltreated children.

Optimism and the brain: trait optimism mediates the protective role of the orbitofrontal cortex gray matter volume against anxiety.

Converging evidence identifies trait optimism and the orbitofrontal cortex (OFC) as personality and brain factors influencing anxiety, but the nature of their relationships remains unclear. Here, the mechanisms underlying the protective role of trait optimism and of increased OFC volume against symptoms of anxiety were investigated in 61 healthy subjects, who completed measures of trait optimism and anxiety, and underwent structural scanning using magnetic resonance imaging. First, the OFC gray matter volume (GMV) was associated with increased optimism, which in turn was associated with reduced anxiety. Second, trait optimism mediated the relation between the left OFC volume and anxiety, thus demonstrating that increased GMV in this brain region protects against symptoms of anxiety through increased optimism. These results provide novel evidence about the brain-personality mechanisms protecting against anxiety symptoms in healthy functioning, and identify potential targets for preventive and therapeutic interventions aimed at reducing susceptibility and increasing resilience against emotional disturbances.

Burning odor-elicited anxiety in OEF/OIF combat veterans: Inverse relationship to gray matter volume in olfactory cortex

Despite the anatomical overlap between the brain's fear/threat and olfactory systems, a very limited number of investigations have considered the role of odors and the central olfactory system in the pathophysiology of PTSD. The goal of the present study was to assess structural differences in primary and secondary olfactory cortex between combat veterans with and without PTSD (CV + PTSD, CV-PTSD, respectively). An additional goal was to determine the relationship between gray matter volume (GMV) in olfactory cortex and the distressing properties of burning-related odors. A region of interest voxel-based morphometric (VBM) approach was used to measure GMV in olfactory cortex in a well-characterized group of CV + PTSD (n = 20) and CV-PTSD (n = 25). Prior to the MRI exam, combat-related (i.e., burning rubber) and control odors were systematically sampled and rated according to their potential for eliciting PTSD symptoms. Results showed that CV + PTSD exhibited significantly reduced GMV in anterior piriform (primary olfactory) and orbitofrontal (secondary olfactory) cortices compared to CV-PTSD (both p < .01). For the entire group, GMV in bilateral anterior piriform cortex was inversely related to burning rubber odor-elicited memories of trauma (p < .05). GMV in orbitofrontal cortex was inversely related to both clinical and laboratory measures of PTSD symptoms (all p < .05). In addition to replicating an established inverse relationship between GMV in anxiety-associated brain structures and PTSD symptomatology, the present study extends those findings by being the first report of volumetric decreases in olfactory cortex that are inversely related to odor-elicited PTSD symptoms. Potential mechanisms underlying these findings are discussed.

Orbitofrontal cortex, emotional decision-making and response to cognitive behavioural therapy for psychosis

Grey matter volume (GMV) in the orbitofrontal cortex (OFC) may relate to better response to cognitive behavioural therapy for psychosis (CBTp) because of the region׳s role in emotional decision-making and cognitive flexibility. This study aimed to determine the relation between pre-therapy OFC GMV or asymmetry, emotional decision-making and CBTp responsiveness. Emotional decision-making was measured by the Iowa Gambling task (IGT). Thirty patients received CBTp+standard care (CBTp+SC; 25 completers) for 6–8 months. All patients (before receiving CBTp) and 25 healthy participants underwent structural magnetic resonance imaging. Patients׳ symptoms were assessed before and after therapy. Pre-therapy OFC GMV was measured using a region-of-interest approach, and IGT performance was measured as overall learning, attention to reward, memory for past outcomes and choice consistency. Both these measures, were comparable between patient and healthy groups. In the CBTp+SC group, greater OFC GMV correlated with positive symptom improvement, specifically hallucinations and persecution. Greater rightward OFC asymmetry correlated with improvement in several negative and general psychopathology symptoms. Greater left OFC GMV was associated with lower IGT attention to reward. The findings suggest that greater OFC volume and rightward asymmetry, which maintain the OFC׳s function in emotional decision-making and cognitive flexibility, are beneficial for CBTp responsiveness.

1897 – Overlapping orbitofrontal volume loss involved in stimulant dependence and weight gain

Introduction Stimulant dependence is commonly associated with decreases in cortical volume in inhibitory control regions, such as the orbitofrontal cortex (OFC). Obese individuals similarly show abnormalities in frontal gray matter, with volume reductions correlating with BMI. These structural deficits may contribute to underlying problems with impulsivity or self-control present in both groups. Objectives Shared structural abnormalities relating to over-consumption of food or drugs of abuse could shed light on similar neurocognitive impairments associated with these behaviors (loss of control, poor decision-making), and could provide evidence for the classification of over-eating as an addictive disorder. Aims To identify overlapping regions of gray matter volume loss associated with both stimulant dependence and increased BMI, specifically in the OFC. Methods Structural MRI scans of stimulant dependent and healthy control individuals were compared using voxel based morphometry analysis. OFC volume was correlated with BMI in all participants, as well as years of drug use in stimulant dependent individuals. Results Both stimulant use and BMI negatively correlated with bilateral OFC gray matter volume. Additionally, select OFC regions showed decreases relating to both variables, indicating an overlap between volume loss associated with years of use and BMI in both stimulant dependent and control individuals. Conclusions Overlapping decreases in OFC gray matter volume that correspond to both overeating and drug use severity indicate underlying commonalities between these two behaviors. This suggests there may be shared cognitive deficits maintained in the OFC, such as poor inhibitory control or decision-making abilities, that preclude these types of behaviors.

Neuroanatomical correlates of impaired decision‐making and facial emotion recognition in early Parkinson’s disease

Decision-making and recognition of emotions are often impaired in patients with Parkinson's disease (PD). The orbitofrontal cortex (OFC) and the amygdala are critical structures subserving these functions. This study was designed to test whether there are any structural changes in these areas that might explain the impairment of decision-making and recognition of facial emotions in early PD. We used the Iowa Gambling Task (IGT) and the Ekman 60 faces test which are sensitive to the integrity of OFC and amygdala dysfunctions in 24 early PD patients and 24 controls. High-resolution structural magnetic resonance images (MRI) were also obtained. Group analysis using voxel-based morphometry (VBM) showed significant and corrected (P < 0.05 FEW-small volume correction) gray matter (GM) loss in the right amygdala and bilaterally in the OFC in PD patients. Volumetric analyses were also performed but did not yield significant differences between groups. Left lateral GM volume in OFC showed a slight correlation with the IGT, and bilateral OFC GM was strongly correlated with Ekman test performance in PD patients. We conclude that: (i) impairment in decision-making and recognition of facial emotions occurs at the early stages of PD, (ii) these neuropsychological deficits are accompanied by degeneration of OFC and amygdala, and (iii) bilateral OFC reductions are associated with impaired recognition of emotions, and GM volume loss in left lateral OFC is related to decision-making impairment in PD.

Orbitofrontal cortex gray matter volumes in bipolar disorder patients: a region‐of‐interest MRI study

Functional and postmortem studies suggest that the orbitofrontal cortex (OFC) is involved in the pathophysiology of bipolar disorder (BD). This anatomical magnetic resonance imaging (MRI) study examined whether BD patients have smaller OFC gray matter volumes compared to healthy comparison subjects (HC). Twenty-eight BD patients were compared to 28 age- and gender-matched HC. Subjects underwent a 1.5T MRI with 3D spoiled gradient recalled acquisition. Total OFC and medial and lateral subdivisions were manually traced by a blinded examiner. Images were segmented and gray matter volumes were calculated using an automated method. Analysis of covariance, with intracranial volume as covariate, showed that BD patients and HC did not differ in gray matter volumes of total OFC or its subdivisions. However, total OFC gray matter volume was significantly smaller in depressed patients (n = 10) compared to euthymic patients (n = 18). Moreover, total OFC gray matter volumes were inversely correlated with depressive symptom intensity, as assessed by the Hamilton Depression Rating Scale. OFC gray matter volumes were not related to lithium treatment, age at disease onset, number of episodes, or family history of mood disorders. Our results suggest that abnormal OFC gray matter volumes are not a pervasive characteristic of BD, but may be associated with specific clinical features of the disorder.

Medial Orbitofrontal Cortex Gray Matter Is Reduced in Abstinent Substance-Dependent Individuals

Chronic exposure to drugs of addiction induces cellular adaptations in orbitofrontal cortex (OFC) and associated limbic-prefrontal pathways that might underlie abuse-related behavior. A propensity to make risky decisions in spite of substantial negative consequences might be mediated by medial OFC dysfunction in substance-dependent individuals (SDI). We tested the hypothesis that medial OFC gray matter (GM) volume would be lower in SDI compared with control subjects. Nineteen SDI and 20 control subjects participated. The SDI were dependent on two or more substances, most often cocaine, amphetamine, and alcohol, with mean duration of abstinence 4.7, 2.4, and 3.2 years, respectively. High-resolution T1-weighted images were acquired on a 3-T magnetic resonance system. Image processing and analyses were conducted with voxel-based morphometry (VBM) implemented in Statistical Parametric Mapping (SPM) 5. Differences in regional GM volume were tested with an analysis of covariance model, co-varying for global GM and age. Statistical maps were set at p < .05, corrected for multiple comparisons. Medial OFC GM volume was correlated with behavioral performance on a modified gambling task. There was lower GM volume specifically in bilateral medial OFC in SDI compared with control subjects. There was a small but significant correlation between medial OFC GM and persistence of playing high-risk decks on a modified gambling task. This is the first study to use VBM with whole brain correction for multiple comparisons in SDI after prolonged abstinence. Reduced medial OFC GM might reflect long-term adaptations within the reward-learning circuit underlying pathological decision-making in substance dependence.

Orbitofrontal, amygdala and hippocampal volumes in teenagers with first-presentation borderline personality disorder

It is not known whether the fronto-limbic volume reductions found in adults with established borderline personality disorder (BPD) are present early in the disorder. The aim of the study was to investigate orbitofrontal cortex (OFC), hippocampal and amygdala volumes in a first-presentation teenage BPD sample with minimal exposure to treatment. Groups of 20 BPD patients and 20 healthy control participants underwent magnetic resonance imaging. Hippocampal, amygdala, OFC and whole brain volumes were estimated and compared between the two groups. Analysis of variance revealed reversal of the normal (right > left) asymmetry of OFC grey matter volume in the BPD group, reflecting right-sided OFC grey matter loss in the BPD group compared with control participants. No significant differences were found for amygdala or hippocampal volumes comparing BPD with control participants. We identified OFC but not hippocampal or amygdala volumetric differences early in the course of BPD. Hippocampal and amygdala volume reductions observed in adult BPD samples might develop during the course of the disorder, although longitudinal studies are needed to examine this.