Fronto-limbic Structures Research Articles

Differential Developmental Associations of Material Hardship Exposure and Adolescent Amygdala-Prefrontal Cortex White Matter Connectivity.

Accumulating literature has linked poverty to brain structure and function, particularly in affective neural regions; however, few studies have examined associations with structural connections or the importance of developmental timing of exposure. Moreover, prior neuroimaging studies have not used a proximal measure of poverty (i.e., material hardship, which assesses food, housing, and medical insecurity) to capture the lived experience of growing up in harsh economic conditions. The present investigation addressed these gaps collectively by examining the associations between material hardship (ages 1, 3, 5, 9, and 15 years) and white matter connectivity of frontolimbic structures (age 15 years) in a low-income sample. We applied probabilistic tractography to diffusion imaging data collected from 194 adolescents. Results showed that material hardship related to amygdala-prefrontal, but not hippocampus-prefrontal or hippocampus-amygdala, white matter connectivity. Specifically, hardship during middle childhood (ages 5 and 9 years) was associated with greater connectivity between the amygdala and dorsomedial pFC, whereas hardship during adolescence (age 15 years) was related to reduced amygdala-orbitofrontal (OFC) and greater amygdala-subgenual ACC connectivity. Growth curve analyses showed that greater increases of hardship across time were associated with both greater (amygdala-subgenual ACC) and reduced (amygdala-OFC) white matter connectivity. Furthermore, these effects remained above and beyond other types of adversity, and greater hardship and decreased amygdala-OFC connectivity were related to increased anxiety and depressive symptoms. Results demonstrate that the associations between material hardship and white matter connections differ across key prefrontal regions and developmental periods, providing support for potential windows of plasticity for structural circuits that support emotion processing.

Correlations between peripheral levels of inflammatory mediators and frontolimbic structures in bipolar disorder: an exploratory analysis.

Altered peripheral immune/inflammatory system and brain volumetric changes have been implicated in the pathophysiology of bipolar disorder (BD). This study aimed to evaluate how peripheral levels of cytokines are related to volumetric brain changes in euthymic patients with BD. Euthymic patients with BD (n=21) and healthy controls (n=22) were enrolled in this exploratory study. Blood samples were collected on the same day of clinical assessment and neuroimaging. Cytokines were measured through cytometric bead array method. Neuroimaging data were acquired using a sagittal three-dimensional magnetic resonance imaging T1-weighted fast field echo sequence and was processed using FreeSurfer. Compared to controls, BD patients had significantly lower volumes in the cingulate, medial-orbitofrontal (MOF) and parahippocampal regions. We found a negative correlation between right MOF volume and interferon-gamma levels (β=-0.431, P=.049) and a positive correlation between interleukin-10 levels and left posterior cingulate volume (β=0.457, P=.048). Our results support the involvement of inflammatory pathways in structural brain changes in BD.

Increased amygdala and decreased hippocampus volume after schedule-induced polydipsia in high drinker compulsive rats

Fronto-limbic structures and serotonin 2A receptors (5-HT2A) have been implicated in the pathophysiology and treatment of compulsive spectrum disorders. Schedule-Induced Polydipsia (SIP), characterized by the development of excessive drinking under intermittent food reinforcement schedules, is a valid preclinical model for studying the compulsive phenotype. In the present study, we explored the individual differences and effect of SIP in brain volume and 5-HT2A receptor binding in fronto-limbic structures in rats selected according to their compulsive drinking behavior. Rats were divided into high (HD) and low drinkers (LD) by SIP (20 sessions); later, we analyzed the brains of HD and LD selected rats, in two different conditions: non-re-exposure (NRE) or re-exposure to SIP (RE), with four groups: LD-NRE, LD-RE, HD-NRE and HD-RE. Histological analyses were carried out for volumetric (stereology) and receptor binding (autoradiography) in the prelimbic and infralimbic cortex, dorsal hippocampus and basolateral amygdala. After SIP re-exposure, HD-RE showed an increased basolateral amygdala and a reduced hippocampus volume compared to HD-NRE rats, and also compared to LD-RE rats. No differences were found between HD and LD in NRE condition. Moreover, HD rats exhibit a lower 5-HT2A receptor binding in the basolateral amygdala, independently of SIP re-exposure, compared to LD rats. However, LD-RE showed a decreased 5-HT2A receptor binding in basolateral amygdala compared to LD-NRE. No differences were found in the remaining structures. These findings suggest that SIP might be differentially impacting HD and LD brains, pointing towards a possible explanation of how the latent vulnerability to compulsivity is triggered.

Major Depressive Disorder in Neuroimaging: What is Beyond Fronto-limbic Model?

Background: The major depressive disorder (MDD) is a chronic illness with major manifestations in cognitive, social and occupational functions. The pathophysiological model is an intrigue issue for scientists to understand the origin of MDD. Objective: In the beginning, the cortico-limbic-striato-pallidal-thalamic model has been proposed to link the clinical symptoms with the abnormalities in brain structure and function. However, the model is still evolving due to recent advances in the neuroimaging techniques, especially for functional magnetic resonance imaging (fMRI). The recent findings in the fMRI studies in MDD showed the importance of fronto-limbic model for the modulations between cognitive function and primitive and negative emotions. Method: This review will focus on the literature of fMRI studies in MDD with findings not in the fronto-limbic structures. Results: Additional regions beyond the fronto-limbic model have been observed in some literature of MDD. Some regions in the parietal, temporal and occipital lobes have been shown with the alterations in gray matter, white matter and brain function. The importance of sensory detection, visuospatial function, language reception, motor response and emotional memories in these regions might provide the clues to understand the cognitive misinterpretations related to altered reception of outside information, behavioral responses related to biased cognition and emotional memories and clinical symptoms related to the significant alterations of interactions between different brain regions. Conclusion: Future studies to establish a more comprehensive model for MDD will be warranted, especially for the model beyond the fronto-limbic structures.

Associations between subclinical depressive symptoms and reduced brain volume in middle-aged to older adults

ABSTRACTObjectives: The associations between subclinical depressive symptoms, as well specific symptom subscales, on brain structure in aging are not completely elucidated. This study investigated the extent to which depressive symptoms were related to brain volumes in fronto-limbic structures in a sample of middle-aged to older adults.Method: Eighty participants underwent structural neuroimaging and completed the Beck Depression Inventory, 2nd Edition (BDI-II), which comprises separate affective, cognitive, and somatic subscales. Gray matter volumes were extracted from the caudal and rostral anterior cingulate, posterior cingulate, hippocampus, and amygdala. Hierarchical regression models examined the relationship between brain volumes and (i) total depressive symptoms and (ii) BDI-II subscales were conducted.Results: After adjusting for total intracranial volume, race, and age, higher total depressive symptoms were associated with smaller hippocampal volume (p = 0.005). For the symptom subscales, after controlling for the abovementioned covariates and the influence of the other symptom subscales, more somatic symptoms were related to smaller posterior cingulate (p = 0.025) and hippocampal (p < 0.001) volumes. In contrast, the affective and cognitive subscales were not associated with brain volumes in any regions of interest.Conclusion: Our data showed that greater symptomatology was associated with smaller volume in limbic brain regions. These findings provide evidence for preclinical biological markers of major depression and specifically advance knowledge of the relationship between subclinical depressive symptoms and brain volume. Importantly, we observed variations by specific depressive symptom subscales, suggesting a symptom-differential relationship between subclinical depression and brain volume alterations in middle-aged and older individuals.

S170 REM – Dreaming – Emotions: The neurophysiology of nightmare disorder

Objectives Nightmares are intense and highly unpleasant mental experiences that occur usually – but not exclusively – during late-night Rapid Eye Movement (REM) sleep and often provoke abrupt awakenings.The underlying mechanism of nightmare disorder was only scarcely investigated and remains poorly understood. The most influential model of nightmare disorder that provided a common framework fortrauma-related and non-traumatic (idiopathic) nightmares was introduced by Levin and Nielsen (2007). One of the main assumptions of the model is that nightmares reflect unsuccessful fear-extinction processes during (REM) sleep due to a dysfunctional brain network comprising fronto-limbic structures. Consequently, amygdalar over-activation and inefficient (prefrontal) inhibition lead to the emotional intensification of dreaming and hyperarousal during sleep. Nevertheless, sleep quality and emotional regulation in nightmare sufferers was mainly examined by questionnaire-based studies. Methods We have performed a series of quantitative EEG analyses based on the polysomnographic data of young (non-ptsd) nightmare sufferers and matched controls. Moreover, in a subsequent study we investigated emotional habituation to arousing images after a night of polysomnographically monitored sleep in a group of nightmare sufferers and matched controls. Emotional reactivity was quantified by subjective evaluations and psychophysiological measures (HRV, SCR). Results In line with questionnaire-based findings, we found that nightmare sufferers are characterized by fragmented sleep, reduced Slow Wave Sleep (SWS), enhanced microarousals during NREM sleep and heightened wake-like oscillations during REM sleep. Furthermore, arousal-related cortical activity coupled with attenuated parasympathetic regulation were evidenced in nightmare sufferers specifically during NREM to REM transitions. Discussion Given that the neural network underlying emotional memory processing is highly active during REM periods, and REM sleep seems to be intimately related to fear memory processing, our findings might indirectly support Levin and Nielsen’s assumption of disrupted REM-dependent fear-extinction in nightmare disorder. Nevertheless, the association between impaired emotional regulation and altered sleep physiology remains to be investigated. Conclusions In our experiments we aimed to directly test Levin and Nielsen’s fear-extintion model of nightmare disorder and to relate impaired emotional regulation to specific sleep EEG features. We conclude that examining nightmare disorder by such integrative approach would shed more light on the enigma of REM sleep and emotional memory processing. Significance Our research could shed more light on the mechanism of nightmare formation, propagate the professional knowledge of nightmare disorder, and facilitate the development of effective, evidence-based treatment procedures.

Frontolimbic Morphometric Abnormalities in Intermittent Explosive Disorder and Aggression

BackgroundConverging evidence from neuroimaging studies suggests that impulsive aggression, the core behavior in the DSM-5 diagnosis intermittent explosive disorder (IED), is regulated by frontolimbic brain structures, particularly orbitofrontal cortex, ventral medial prefrontal cortex, anterior cingulate cortex, amygdala, insula, and uncus. Despite this evidence, no brain volumetric studies of IED have been reported as yet. This study was conducted to test the hypothesis that gray matter volume in frontolimbic brain structures of subjects with IED is lower than in healthy subjects and subjects with other psychiatric conditions. MethodsHigh-resolution magnetic resonance imaging scans using a three-dimensional magnetization-prepared rapid acquisition gradient-echo sequence were performed in 168 subjects (n = 53 healthy control subjects, n = 58 psychiatric controls, n = 57 subjects with IED). Imaging data were analyzed by voxel-based morphometry methods employing Statistical Parametric Mapping (SPM8) software. ResultsGray matter volume was found to be significantly lower in subjects with IED compared with healthy control subjects and psychiatric controls in orbitofrontal cortex, ventral medial prefrontal cortex, anterior cingulate cortex, amygdala, insula, and uncus. These differences were not due to various confounding factors or to comorbidity with other disorders previously reported to have reduced gray matter volume. Gray matter volume in these areas was significantly and inversely correlated with measures of aggression. ConclusionsReductions in the gray matter volume of frontolimbic structures may be a neuronal characteristic of impulsively aggressive individuals with DSM-5 IED. These data suggest an anatomic correlate accounting for functional deficits in social-emotional information processing in these individuals.

1078 – Is there evidence for a link between stress and addiction?

Stress and reward processing are two of the principal mechanisms involved in the modulation of homeostasis in the body. According to neurobiological research, these two mechanisms overlap in the cortico-striatal-limbic circuit, which can be disrupted due to chronic stress and substance abuse. Stress is primarily modulated by the hypothalamic-pituitary-adrenal (HPA) axis, from which cortisol is an end-product. The aim of the study was to investigate the effects of chronic stimulant abuse on the cortico-striatal limbic circuit. This was examined by relating cortisol levels with grey matter volume in brain structures associated with addiction and stress. We hypothesised that stimulant-dependent individuals show increased cortisol levels and abnormalities in the corticostriatal- limbic circuit. We further hypothesised relationships between altered grey matter volume and increased cortisol levels in the patients. Twenty-two stimulant-dependent individuals and 21 healthy volunteers (matched for age and gender) underwent an assessment session and structural MRI brain scan. Cortisol was assessed in saliva and blood plasma. Mood, impulsivity and compulsivity were measured by clinical instruments. Stimulant-dependent individuals showed higher levels of cortisol in both saliva and blood, which were associated with distinct alterations in grey matter volume in fronto-limbic structures. Plasma cortisol was positively correlated with the duration of cocaine use. No relationships were found with current mood, trait-impulsivity and drug-related compulsivity. The relationships observed between cortisol and fronto-limbic structures may, in part, be explained by HPA axis dysfunction and its downstream effects on brain structures involved in stress modulation in stimulant-dependent individuals.

Functional alteration in frontolimbic systems relevant to moral judgment in cocaine‐dependent subjects

Cocaine addiction is characterized by persistent decision-making deficits, which are linked to structural and functional abnormalities in frontolimbic systems. Moral judgment is as a special instance of decision making, in which both cognitive and emotional signals must be adequately integrated to decide how to resolve moral dilemmas. Here, we employed a moral dilemmas functional magnetic resonance imaging (fMRI) task to explore possible alterations of frontolimbic systems in cocaine-dependent subjects. We also explored if these alterations relate to more basic deficits in functional connectivity within these systems during spontaneous resting-state activation. Ten cocaine-dependent subjects and 14 non-drug-using controls participated in the study. Cocaine-dependent subjects were carefully selected to discard potentially confounding co-morbidities, and they underwent a uniform supervised abstinence period of 10 days. Both groups were scanned, and fMRI maps were generated to identify (1) brain response to moral dilemmas; and (2) the strength of functional connectivity within frontolimbic systems during resting-state. During the moral dilemmas task, cocaine-dependent subjects showed reduced activation involving frontolimbic structures as the anterior cingulate cortex (ACC), left insula and brain stem. Connectivity analyses showed that cocaine users had less resting-state functional connectivity between ACC, thalamus, insula and brain stem. These results demonstrate that cocaine-dependent subjects have functional alterations in the frontolimbic systems that support moral judgment and social decision making.

Fronto-limbic volumetric changes in major depressive disorder

Fronto-limbic dysregulation in major depressive disorder (MDD) may be influenced by early life stress and antidepressant treatment. The present structural MRI study aimed to determine the relationship between amygdala, cingulate and subgenual prefrontal cortex volumes in MDD and their associations with child abuse and antidepressants. Right-handed subjects (21-50 years), meeting DSM-IV criteria for MDD, either with (n=19) or without (n=20) childhood sexual or physical abuse. Healthy controls (n=34) were matched for age, sex, education and smoking. 3D-MPRAGE images with a spatial resolution of 1.5 mm×1.0 mm×1.0 mm were acquired with a Siemens Sonata 1.5 T system. Volumes of subgenual prefrontal cortex, amygdala and affective, cognitive, superior and posterior divisions of cingulate cortex were analyzed using DISPLAY software using reliable volumetric protocols. Groups were compared using ANCOVA, with intracranial volume as a covariate. MDD subjects had low cingulate (cognitive division) and high amygdala volumes. Low cingulate volume was related to abuse and treatment history. Amygdala volume was predicted by subgenual prefrontal and cingulate (cognitive division) volumes and the presence of paracingulate cortex. This study was cross sectional and the sample size was limited for subgroup and correlational analyses. Our data suggest that MDD may be associated with alterations in anterior cingulate cortex and amygdala. Morphological variation, early stress and stress-protective factors may contribute to differences in fronto-limbic structures in MDD.

A longitudinal study of fronto-limbic brain structures in bipolar I patients during lithium treatment

Salih Selek1, 2, Mark Nicoletti 1, Giovana B. Zunta-Soares 1, John P. Hatch3, Fabiano G. Nery1, Koji Matsuo4, Jair C. Soares1 1UT Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, Texas, 2Psychiatry Department, Harran University Faculty of Medicine, Sanliurfa, Turkey, 3 Departments of Developmental Dentistry and Psychiatry, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, 4Division of Neuropsychiatry, Department of Neuroscience, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan

The interacting role of media violence exposure and aggressive–disruptive behavior in adolescent brain activation during an emotional Stroop task

Only recently have investigations of the relationship between media violence exposure (MVE) and aggressive behavior focused on brain functioning. In this study, we examined the relationship between brain activation and history of media violence exposure in adolescents, using functional magnetic resonance imaging (fMRI). Samples of adolescents with no psychiatric diagnosis or with disruptive behavior disorder (DBD) with aggression were compared to investigate whether the association of MVE history and brain activation is moderated by aggressive behavior/personality. Twenty-two adolescents with a history of aggressive behavior and diagnosis of either conduct disorder or oppositional-defiant disorder (DBD sample) and 22 controls completed an emotional Stroop task during fMRI. Primary imaging results indicated that controls with a history of low MVE demonstrated greater activity in the right inferior frontal gyrus and rostral anterior cingulate during the violent word condition. In contrast, in adolescents with DBD, those with high MVE exhibited decreased activation in the right amygdala, compared with those with low MVE. These findings are consistent with research demonstrating the importance of fronto-limbic structures for processing emotional stimuli, and with research suggesting that media violence may affect individuals in different ways depending on the presence of aggressive traits.

Change in Regional Cerebral Function in L'Aquila Earthquake Survivors with Post-Traumatic Stress Disorder: Preliminary Findings

Subjects with post-traumatic stress disorder (PTSD) present a diminished or blunted emotional response, sometimes called "emotional numbing" (EN), that constitutes one of the central symptoms in PTSD. Symptoms of EN include diminished interest in activities, feeling detached or estranged from others, and restricted range of affect (American Psychiatric Association, 2000). The present work studied the emotional components in individuals with PTSD with the principal aim of investigating subjects' functional alteration in the limbic regions, insula and frontal cortex during an emotional task compared with healthy subjects. Ten subjects with PTSD (survivors of the 6.3 magnitude earthquake of April 6, 2009 in L'Aquila) and ten healthy controls underwent fMRI. PTSD was diagnosed according to DSM-IV-R (APA 2000). All subjects underwent fMRI while viewing content-neutral and emotional stimuli. Data analysis revealed that PTSD subjects had significantly greater cerebral activation in particular in the right anterior insula and in bilateral inferior frontal gyrus. Our data suggest that there is a change in the activation of brain areas responsible for emotional processing in patients with PTSD and are consistent with previous findings demonstrating hyperactivation in frontolimbic structures during emotional tasks. Our study suggests that close personal experience may be critical in engaging the neural mechanisms underlying the emotional modulation of memory. Our findings provide evidence that significant alterations in brain function, similar in many ways to those observed in PTSD, can be seen shortly after major traumatic experiences, highlighting the need for early evaluation and intervention for trauma survivors.

P.1.e.011 Fronto-limbic interaction of working memory and emotion in the medial prefrontal cortex

Fronto-limbic dysregulation in major depressive disorder (MDD) may be influenced by early life stress and antidepressant treatment. The present structural MRI study aimed to determine the relationship between amygdala, cingulate and subgenual prefrontal cortex volumes in MDD and their associations with child abuse and antidepressants.Right-handed subjects (21–50 years), meeting DSM-IV criteria for MDD, either with (n = 19) or without (n = 20) childhood sexual or physical abuse. Healthy controls (n = 34) were matched for age, sex, education and smoking. 3D-MPRAGE images with a spatial resolution of 1.5 mm × 1.0 mm × 1.0 mm were acquired with a Siemens Sonata 1.5T system. Volumes of subgenual prefrontal cortex, amygdala and affective, cognitive, superior and posterior divisions of cingulate cortex were analyzed using DISPLAY software using reliable volumetric protocols. Groups were compared using ANCOVA, with intracranial volume as a covariate.MDD subjects had low cingulate (cognitive division) and high amygdala volumes. Low cingulate volume was related to abuse and treatment history. Amygdala volume was predicted by subgenual prefrontal and cingulate (cognitive division) volumes and the presence of paracingulate cortex. Limitations: This study was cross sectional and the sample size was limited for subgroup and correlational analyses.Our data suggest that MDD may be associated with alterations in anterior cingulate cortex and amygdala. Morphological variation, early stress and stress-protective factors may contribute to differences in fronto-limbic structures in MDD.

Gender differences in α-[ 11C]MTrp brain trapping, an index of serotonin synthesis, in medication-free individuals with major depressive disorder: A positron emission tomography study

Women are at higher risk than men for developing major depressive disorder (MDD), but the mechanisms underlying this higher risk are unknown. Here, we report proportionally normalized α-[ 11C]methyl- L-tryptophan brain trapping constant (α-[ 11C]MTrp K* N), an index of serotonin synthesis, in 25 medication-free individuals with MDD and in 25 gender- and age-matched healthy subjects who were studied using positron emission tomography (PET). Comparisons of α-[ 11C]MTrp K* N values between the men and women were conducted at the voxel and cluster levels using Statistical Parametric Mapping 2 (SPM2) analysis. In addition, the α-[ 11C]MTrp K* N values on both sides of the brain were extracted and compared to identify the left to right differences, as well as the gender differences. Women with MDD displayed higher α-[ 11C]MTrp K* N than men in the inferior frontal gyrus, anterior cingulate cortex (ACC), parahippocampal gyrus, precuneus, superior parietal lobule, and occipital lingual gyrus. In a matched group of normal subjects the gender differences were opposite from those found in MDD patients. Significant hemispheric differences in fronto-limbic structures between men and women with MDD were also observed. The K* N extracted from the volumes identified in MDD patients and in male and female normal subjects suggested no significant differences between males and females. In conclusion, depressed women have higher serotonin synthesis in multiple regions of the prefrontal cortex and limbic system involved with mood regulation, as compared with depressed men. Gender differences in brain serotonin synthesis may be related to higher risk for MDD in women.

Frontolimbic function and cortisol reactivity in response to emotional stimuli

Frontolimbic structures involved in fear conditioning have also been associated with hypothalamic-pituitary-adrenal (HPA)-axis modulation, including amygdaloid, hippocampal, and ventromedial prefrontal cortex regions. Although HPA-axis function and endocrine changes have been investigated in the context of stress provocation, much research has not been conducted using functional neuroimaging in the study of the HPA axis and frontolimbic function in response to emotional stimuli. Using functional magnetic resonance imaging, the association of blood-oxygen-level dependent signal with salivary cortisol in response to an emotional visual scene paradigm was investigated, with prescan and postscan salivary cortisol analyzed as a covariate of interest during specific conditions. Cortisol reactivity to the paradigm was positively associated with amygdalar and hippocampal activity and negatively associated with ventromedial prefrontal cortex activity in conditions involving emotional imagery.

Increased fronto-temporal perfusion in bipolar disorder

Objectives Previous imaging reports showed over-activation of fronto-limbic structures in bipolar patients, particularly in response to emotional stimuli. In this study, for the first time, we used perfusion weighted imaging (PWI) to analyze lobar cerebral blood volume (CBV) in bipolar disorder to further explore the vascular component to its pathophysiology. Methods Fourteen patients with DSM-IV bipolar disorder (mean age ± SD = 49.00 ± 12.30 years; 6 males, 8 females) and 29 normal controls (mean age ± SD = 45.07 ± 10.30 years; 13 males, 16 females) were studied. PWI images were obtained following intravenous injection of paramagnetic contrast agent (Gadolinium-DTPA), with a 1.5 T Siemens magnet using an echo-planar sequence. The contrast of enhancement (CE), was calculated pixel by pixel as the ratio of the maximum signal intensity drop during the passage of contrast agent (Sm) by the baseline pre-bolus signal intensity (So) (CE = Sm/So ⁎100) for frontal, temporal, parietal, and occipital lobes, bilaterally, on two axial images. Higher CE values correspond to lower CBV and viceversa. Results Bipolar patients had significantly lower CE values in left frontal and temporal lobes ( p = 0.01 and p = 0.03, respectively) and significantly inverse laterality index for frontal lobe ( p = 0.017) compared to normal controls. No significant correlations between CE measure and age or clinical variables were found ( p > 0.05). Conclusion This study found increased left frontal and temporal CBV in bipolar disorder. Fronto-temporal hyper-perfusion may sustain over-activation of these structures during emotion modulation, which have been observed in patients with bipolar illness.

Structural and functional MRI‐ findings in children and adolescents with antisocial behavior

The developmental course of children with conduct disorder (CD) is heterogeneous. Especially children who exhibit symptoms early in their lifetimes are characterized by a negative outcome. Neurobiological aspects of CD have been investigated in these children but little is known about structural and functional brain aberrations. We describe the developmental taxonomy of children with CD and focus on those with the early onset subtype. Structural MRI data of these children and antisocial adults are recapitulated. The impact of investigating neurobiological underpinnings of antisocial behavior and how this might contribute to future forensic and psychiatric assessments is discussed. RESULTS/ CONCLUSION: Children display similar structural aberrations of fronto-limbic structures to adults with antisocial behavior, and amygdala dysfunction might be closely related to dysregulated emotions. Though the investigation of biological factors in antisocial subjects has made great progress in recent years, today MRI is still a rather complex, expensive and indistinct method for forensic assessment.

Gastric fundic distension activates fronto-limbic structures but not primary somatosensory cortex: A functional magnetic resonance imaging study

Introduction: The brain representation of visceral stimulation bears important similarities to that of somatic stimulation. However, the role of the primary (S1) and secondary (S2) somatosensory cortices in mediating gastric sensation is uncertain. Materials and methods: Eighteen healthy, right-handed volunteers (age 32 years ± 6.5 years; 14 men) underwent dynamic assessment of the relationship between sensation and fundic barostat distending pressure and volume, and then brain functional magnetic resonance imaging (fMRI) during noxious fundic distension. Cytoarchitectonic probability maps were used to examine in detail the null hypothesis that fundic distension did not produce significant activation of S1 or S2. Results: Distending volume explained 74% of the variance in gastric sensation, compared to 64% with distending pressure. Incorporating distending volume into the regressor function for our fMRI analyses, we found that noxious fundic distension activated a widespread network of brain regions, including the pontine brainstem, thalami, cerebellum, insular cortex bilaterally, anterior and posterior cingulate cortex, right frontal lobe, and inferior parietal lobules. In detailed analyses, we found no evidence of activation of S1, but did find activation in one region of S2. Discussion: Our findings suggest that an extensive, predominantly fronto-limbic network of brain regions, including the insular cortex, mediates perception of noxious gastric fundic distension in healthy humans, without significant participation by the primary somatosensory cortex. This and other recent studies lay the groundwork for investigations comparing brain processing of visceral stimuli between healthy volunteers and patients with functional dyspepsia.

Fronto-Limbic Brain Abnormalities in Juvenile Onset Bipolar Disorder

Advances in brain imaging techniques and cognitive neuropsychology have brought new possibilities for the in vivo study of the pathophysiology of neuropsychiatric disorders, including bipolar disorder (BD). Recently, such studies have been extended to the pediatric age range. Here we review the neuroimaging and neuropsychological studies conducted in BD children and adolescents. A review of the peer-reviewed published literature was conducted in Medline for the period of 1966 to April 2005. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) studies suggest abnormalities in fronto-limbic structures in pediatric BD patients, similar to those found in adults. A notable exception in pediatric BD patients is smaller amygdala volumes compared to healthy controls, contrary to what has been reported in most adult studies. Further research evaluating children and adolescents is needed to study the normal neurodevelopmental process and to answer how and when the illness processes that result in bipolar disorder exert their effects on the developing brain.