Abnormalities In Neural Systems Research Articles

Regional cerebral activity abnormality in pregnant women with antenatal depression

BackgroundAntenatal depression (ATDP) is one of the most common mental disorders that occur during the antenatal period. As a serious problem in households around the world, ATDP has adverse consequences for both mothers and offspring and heavily burdens their families and society. However, until recently, the neurobiological mechanisms underlying ATDP remained unclear, which impeded early detection and intervention for this disorder. MethodsTo explore the intrinsic cerebral activity alternations in ATDP, we investigated fractional amplitude of low-frequency fluctuation (fALFF) differences in 20 treatment-naïve ATDP patients and 22 healthy pregnant women (HPW) using voxel-based whole-brain analysis by resting-state functional magnetic resonance imaging. The correlation between the regional functional abnormalities and clinical variables in ATDP patients was also examined. ResultsCompared with HPW, ATDP patients showed increased fALFF in the left medial prefrontal cortex, dorsolateral prefrontal cortex and anterior cingulate cortex, as well as decreased fALFF in the bilateral orbitofrontal cortex, the right insula, the cluster covering the right ventral temporal cortex (VTC) and the parahippocampus (PHP). The Edinburgh Postnatal Depression Scale scores of ATDP patients were negatively correlated with fALFF values in the right VTC and PHP. LimitationsThe study is limited by a small sample size and the fact that only antenatal maternal women in the second and third trimesters were assessed. ConclusionThe aberrant regional functional activities of ATDP patients were mainly located within the prefrontal-limbic circuit related to multiple neural system abnormalities. This finding provides insight into the potential psychopathology of ATDP.

Large-Scale Hypoconnectivity Between Resting-State Functional Networks in Unmedicated Adolescent Major Depressive Disorder.

Major depressive disorder (MDD) often emerges during adolescence, a critical period of brain development. Recent resting-state fMRI studies of adults suggest that MDD is associated with abnormalities within and between resting-state networks (RSNs). Here we tested whether adolescent MDD is characterized by abnormalities in interactions among RSNs. Participants were 55 unmedicated adolescents diagnosed with MDD and 56 matched healthy controls. Functional connectivity was mapped using resting-state fMRI. We used the network-based statistic (NBS) to compare large-scale connectivity between groups and also compared the groups on graph metrics. We further assessed whether group differences identified using nodes defined from functionally defined RSNs were also evident when using anatomically defined nodes. In addition, we examined relations between network abnormalities and depression severity and duration. Finally, we compared intranetwork connectivity between groups and assessed the replication of previously reported MDD-related abnormalities in connectivity. The NBS indicated that, compared with controls, depressed adolescents exhibited reduced connectivity (p<0.024, corrected) between a specific set of RSNs, including components of the attention, central executive, salience, and default mode networks. The NBS did not identify group differences in network connectivity when using anatomically defined nodes. Longer duration of depression was significantly correlated with reduced connectivity in this set of network interactions (p=0.020, corrected), specifically with reduced connectivity between components of the dorsal attention network. The dorsal attention network was also characterized by reduced intranetwork connectivity in the MDD group. Finally, we replicated previously reported abnormal connectivity in individuals with MDD. In summary, adolescents with MDD show hypoconnectivity between large-scale brain networks compared with healthy controls. Given that connectivity among these networks typically increases during adolescent neurodevelopment, these results suggest that adolescent depression is associated with abnormalities in neural systems that are still developing during this critical period.

Adolescents with current major depressive disorder show dissimilar patterns of age-related differences in ACC and thalamus.

ObjectiveThere is little understanding of the neural system abnormalities subserving adolescent major depressive disorder (MDD). In a cross-sectional study we compare currently unipolar depressed with healthy adolescents to determine if group differences in grey matter volume (GMV) were influenced by age and illness severity.MethodStructural neuroimaging was performed on 109 adolescents with current MDD and 36 healthy controls, matched for age, gender, and handedness. GMV differences were examined within the anterior cingulate cortex (ACC) and across the whole-brain. The effects of age and self-reported depressive symptoms were also examined in regions showing significant main or interaction effects.ResultsWhole-brain voxel based morphometry revealed no significant group differences. At the whole-brain level, both groups showed a main effect of age on GMV, although this effect was more pronounced in controls. Significant group-by-age interactions were noted: A significant regional group-by-age interaction was observed in the ACC. GMV in the ACC showed patterns of age-related differences that were dissimilar between adolescents with MDD and healthy controls. GMV in the thalamus showed an opposite pattern of age-related differences in adolescent patients compared to healthy controls. In patients, GMV in the thalamus, but not the ACC, was inversely related with self-reported depressive symptoms.ConclusionsThe depressed adolescent brain shows dissimilar age-related and symptom-sensitive patterns of GMV differences compared with controls. The thalamus and ACC may comprise neural markers for detecting these effects in youth. Further investigations therefore need to take both age and level of current symptoms into account when disaggregating antecedent neural vulnerabilities for MDD from the effects of MDD on the developing brain.

Differentiating Patterns of Amygdala-Frontal Functional Connectivity in Schizophrenia and Bipolar Disorder

Background:Insight into the neural mechanisms underlying the shared and disparate features of schizophrenia (SZ) and bipolar disorder (BD) is limited. The amygdala and prefrontal cortex (PFC) appear to have crucial roles in SZ and BD, yet abnormalities appear to manifest differently in the 2 disorders.Methods:Eighteen participants with SZ, 18 participants with BD, and 18 healthy controls (HC) underwent resting-state functional magnetic resonance imaging. Resting-state functional connectivity (rsFC) between the PFC and the amygdala divided into 3 subregions (the laterobasal, centromedial, and superficial amygdala) was examined using probabilistic anatomic maps. For each participant, rsFC maps of the 3 amygdala subregions were computed and compared across the 3 groups.Results:Compared with the HC group, we found significant differences in rsFC between the amygdala and PFC in the SZ and BD groups. In direct comparison between the SZ and BD groups, distinct patterns of rsFC between the amygdala and PFC were observed, particularly in the superficial amygdala. RsFC between the amygdala and the dorsal lateral PFC was significantly decreased in the SZ group, whereas rsFC between the amygdyala and the ventral PFC was significantly decreased in the BD group.Conclusions:These results strongly suggest dorsal vs ventral PFC differentiation in amygdala-PFC neural system abnormalities between SZ and BD. These regional differences in SZ and BD may give rise to the differences in clinical characteristics observed in SZ and BD, and may implicate potential avenues for differentiating the 2 disorders during early stages of illness.

A ventral prefrontal-amygdala neural system in bipolar disorder: a view from neuroimaging research.

In the past decade, neuroimaging research has identified key components in the neural system that underlies bipolar disorder (BD). The ventral prefrontal cortex (VPFC) and amygdala are highly interconnected structures that jointly play a central role in emotional regulation. Numerous research groups have reported prominent structural and functional abnormalities within the VPFC and amygdala supporting their essential role in a neural system underlying the emotional dysregulation that is a core feature of BD. Findings in BD also include those in brain regions interconnected with the VPFC and amygdala, including the ventral striatum, hippocampus and the cerebellum. Abnormalities in these regions may contribute to symptoms that reflect disruption in functions sub-served by these structures, including motivational, mnemonic and psychomotor functions. This article will first review leads from behavioural neurology that implicated these neural system abnormalities in BD. It will then review findings from structural and functional imaging studies to support the presence of abnormalities within these neural system components in BD. It will also review new findings from studies using diffusion tensor imaging (DTI) that provide increasing evidence of abnormalities in the connections between these neural system components in BD. Emerging data supporting differences in this neural system during adolescence, as well as potential beneficial effects of treatment on structure and function will also be presented. Finally, the article will discuss the implications for future investigations, including those for early identification and treatment of BD.

Prefrontal cortical and striatal activity to happy and fear faces in bipolar disorder is associated with comorbid substance abuse and eating disorder

Background: The spectrum approach was used to examine contributions of comorbid symptom dimensions of substance abuse and eating disorder to abnormal prefrontal-cortical and subcortical-striatal activity to happy and fear faces previously demonstrated in bipolar disorder (BD). Method: Fourteen remitted BD-type I and sixteen healthy individuals viewed neutral, mild and intense happy and fear faces in two event-related fMRI experiments. All individuals completed Substance-Use and Eating-Disorder Spectrum measures. Region-of-Interest analyses for bilateral prefrontal and subcortical-striatal regions were performed. Results: BD individuals scored significantly higher on these spectrum measures than healthy individuals ( p < 0.05), and were distinguished by activity in prefrontal and subcortical-striatal regions. BD relative to healthy individuals showed reduced dorsal prefrontal-cortical activity to all faces. Only BD individuals showed greater subcortical-striatal activity to happy and neutral faces. In BD individuals, negative correlations were shown between substance use severity and right PFC activity to intense happy faces ( p < 0.04), and between substance use severity and right caudate nucleus activity to neutral faces ( p < 0.03). Positive correlations were shown between eating disorder and right ventral putamen activity to intense happy ( p < 0.02) and neutral faces ( p < 0.03). Exploratory analyses revealed few significant relationships between illness variables and medication upon neural activity in BD individuals. Limitations: Small sample size of predominantly medicated BD individuals. Conclusion: This study is the first to report relationships between comorbid symptom dimensions of substance abuse and eating disorder and prefrontal-cortical and subcortical-striatal activity to facial expressions in BD. Our findings suggest that these comorbid features may contribute to observed patterns of functional abnormalities in neural systems underlying mood regulation in BD.

Functional neuroimaging studies of bipolar disorder: Examining the wide clinical spectrum in the search for disease endophenotypes

Bipolar disorder (BP) is among the top ten most disabling illnesses worldwide. This review includes findings from recent studies employing functional neuroimaging to examine functional abnormalities in neural systems underlying core domains of the psychopathology in BP: emotion processing, emotion regulation and executive control, and common comorbid features of BP, that are relevant to the wide spectrum of BP rather than focused on the more traditional BPI subtype, and that may facilitate future identification of diagnostically-relevant biomarkers of the disorder. In addition, an emerging number of studies are reviewed that demonstrate the use of neuroimaging to elucidate biomarkers whose identification may help to (1) identify at-risk individuals who will subsequently develop the illness to facilitate early intervention, (2) identify targets for treatment and markers of treatment response. The use of newer neuroimaging techniques and potential confounds of psychotropic medication upon neuroimaging findings in BP are also examined. These approaches will help to improve diagnosis and the mental well-being of all individuals with BP.

Metabolic networks for assessment of therapy and diagnosis in Parkinson's disease

Neuroimaging and modern computational techniques like spatial covariance analysis have contributed greatly to the understanding of neural system abnormalities in neurodegenerative disorders such as Parkinson's disease (PD). The application of network analysis to metabolic PET data obtained from patients with PD has led to the identification and validation of two distinct spatial covariance patterns associated with the motor and cognitive manifestations of the disease. Quantifying the activity of these patterns in individual subjects has provided an objective tool for the assessment of treatment efficacy and differential diagnosis. We have found that activity of the PD motor-related network is modulated by antiparkinsonian treatments such as dopaminergic therapy, deep brain stimulation (DBS), and subthalamic nucleus (STN) gene therapy. By contrast, the cognitive-related network is not altered by these interventions for PD motor symptoms. This pattern may however change in response to therapies targeting the cognitive symptoms of this disorder. Recent work has focused on the identification of specific network biomarkers for atypical parkinsonian conditions such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). These disease-related patterns can potentially be used in an automated imaging-based algorithm to classify patients with these disorders.

Identifying Functional Neuroimaging Biomarkers of Bipolar Disorder: Toward DSM-V

Bipolar disorder is one of the most debilitating and common illnesses worldwide. Individuals with bipolar disorder frequently present to clinical services when depressed but are often misdiagnosed with unipolar depression, leading to inadequate treatment and poor outcome. Increased accuracy in diagnosing bipolar disorder, especially during depression, is therefore a key long-term goal to improve the mental health of individuals with the disorder. The attainment of this goal can be facilitated by identifying biomarkers reflecting pathophysiologic processes in bipolar disorder, namely impaired emotion regulation, impaired attention, and distractibility, which persist during depression and remission and are not common to unipolar depression. In this critical review, we examine the feasibility of identifying biomarker of bipolar disorder by discussing existing findings regarding functional abnormalities in neural systems underlying emotion processing (amygdala centered), working memory, and attention (dorsolateral prefrontal cortex centered) that persist through bipolar depression and remission and are bipolar specific rather than common to unipolar depression. We then focus on future research goals relating to major clinical problems in bipolar disorder, including, the identification of biomarkers allowing detection of individuals at risk of subsequent development of the disorder. Bipolar disorder is a common, debilitating, and potentially fatal disorder. Current and future research in bipolar disorder should focus on identification of disorder biomarkers to improve diagnostic accuracy and the mental heath of those with the disorder.

Facilitation of Extinction of Conditioned Fear by D-Cycloserine

Excessive fear and anxiety are characteristic of disorders such as post-traumatic stress disorder (PTSD) and phobias and are believed to reflect abnormalities in neural systems governing the development and reduction of conditioned fear. Conditioned fear can be suppressed through a process known as extinction, in which repeated exposure to a feared stimulus in the absence of an aversive event leads to a gradual reduction in the fear response to that stimulus. Like conditioned fear learning, extinction is dependent on a particular protein (the N-methyl-D-aspartate or NMDA receptor) in a part of the brain called the amygdala. Blockade of this receptor blocks extinction and improving the activity of this receptor with a drug called D-cycloserine speeds up extinction in rats. Because exposure-based psychotherapy for fear disorders in humans resembles extinction in several respects, we investigated whether D-cycloserine might facilitate the loss of fear in human patients. Consistent with findings from the animal laboratory, patients receiving D-cycloserine benefited more from exposure-based psychotherapy than did placebo-treated controls. Although very preliminary, these data provide initial support for the use of cognitive enhancers in psychotherapy and demonstrate that preclinical studies in rodents can have direct benefits to humans.

Patterns of neural response to emotive stimuli distinguish the different symptom dimensions of obsessive-compulsive disorder.

Despite its heterogeneous symptomatology, obsessive-compulsive disorder (OCD) is currently conceptualized as a unitary diagnostic entity. Recent factor-analytic studies have identified several OCD symptom dimensions that are associated with different demographic variables, comorbidity, patterns of genetic transmission, and treatment response. Functional abnormalities in neural systems important for emotion perception, including the orbitofrontal cortex, lateral prefrontal cortex, anterior cingulate gyrus, and limbic regions, have been reported in OCD. In this review, we discuss the extent to which neurobiological markers may distinguish these different symptom dimensions and whether specific symptom dimensions, such as contamination/washing, are associated with abnormalities in emotion and, in particular, disgust, perception in OCD. Also discussed are findings that indicate that anxiety can be induced in healthy volunteers in response to OCD symptom-related material, and that associated increases in activity within neural systems important for emotion perception occur to washing- and hoarding-related material in particular in these subjects. Further examination of neural responses during provocation of different symptom dimensions in OCD patients will help determine the extent to which specific abnormalities in neural systems underlying emotion perception are associated with different symptom dimensions and predict treatment response in OCD.

Frontotemporal neural systems in bipolar disorder.

Relatively less research has been performed in the delineation of the neural system abnormalities underlying bipolar disorder (BD) than in their correlates in unipolar depression. However, neuroimaging research has recently provided in vivo evidence to support the involvement of regional brain abnormalities in BD implicated by the localization of lesions associated with secondary mood symptoms. This article reviews (1) neural systems implicated in BD by brain lesions associated with secondary mood changes and impaired neuropsychologic paradigm performance; (2) structural and functional neuroimaging evidence to support the involvement of these neural systems in BD; and (3) potential functional neuroanatomic models of BD symptoms. Because depression is covered in detail elsewhere in this issue, this article focuses primarily on abnormalities associated with the manic state, as well as ones associated with euthymia, and may thus represent trait abnormalities in BD. We suggest that ventral and medial prefrontal and amygdalar abnormalities may play important roles in a subset of BD symptoms and are potential targets for treatments.