Probing myelin and axon abnormalities separately in psychiatric disorders using MRI techniques

In this manuscript we present novel MRI approaches to dissecting axon vs. myelin abnormalities in psychiatric disorders. Existing DTI approaches are not able to provide specific information on these subcellular elements but novel approaches are beginning to do so. We review two approaches (magnetization transfer ratio—MTR; and diffusion tensor spectroscopy—DTS) and the theoretical framework for interpreting data derived from these approaches. Work is ongoing to collect data that will answer some relevant questions using these techniques in schizophrenia and related conditions

Deficient biological motion perception in schizophrenia: results from a motion noise paradigm

Background:: Schizophrenia patients exhibit deficient processing of perceptual and cognitive information. However, it is not well-understood how basic perceptual deficits contribute to higher level cognitive problems in this mental disorder. Perception of biological motion, a motion-based cognitive recognition task, relies on both basic visual motion processing and social cognitive processing, thus providing a useful paradigm to evaluate the potentially hierarchical relationship between these two levels of information processing. Methods: In this study, we designed a biological motion paradigm in which basic visual motion signals were manipulated systematically by incorporating different levels of motion noise. We measured the performances of schizophrenia patients (n = 21) and healthy controls (n = 22) in this biological motion perception task, as well as in coherent motion detection, theory of mind, and a widely used biological motion recognition task. Results: Schizophrenia patients performed the biological motion perception task with significantly lower accuracy than healthy controls when perceptual signals were moderately degraded by noise. A more substantial degradation of perceptual signals, through using additional noise, impaired biological motion perception in both groups. Performance levels on biological motion recognition, coherent motion detection and theory of mind tasks were also reduced in patients. Conclusion: The results from the motion-noise biological motion paradigm indicate that in the presence of visual motion noise, the processing of biological motion information in schizophrenia is deficient. Combined with the results of poor basic visual motion perception (coherent motion task) and biological motion recognition, the association between basic motion signals and biological motion perception suggests a need to incorporate the improvement of visual motion perception in social cognitive remediation

Temporal isolation of neural processes underlying face preference decisions

Decisions about whether we like someone are often made so rapidly from first impressions that it is difficult to examine the engagement of neural structures at specific points in time. Here, we used a temporally extended decision-making paradigm to examine brain activation with functional MRI (fMRI) at sequential stages of the decision-making process. Activity in reward-related brain structures—the nucleus accumbens (NAC) and orbitofrontal cortex (OFC)—was found to occur at temporally dissociable phases while subjects decided which of two unfamiliar faces they preferred. Increases in activation in the OFC occurred late in the trial, consistent with a role for this area in computing the decision of which face to choose. Signal increases in the NAC occurred early in the trial, consistent with a role for this area in initial preference formation. Moreover, early signal increases in the NAC also occurred while subjects performed a control task (judging face roundness) when these data were analyzed on the basis of which of those faces were subsequently chosen as preferred in a later task. The findings support a model in which rapid, automatic engagement of the NAC conveys a preference signal to the OFC, which in turn is used to guide choice

Altered Functional Connectivity of Striatum Based on the Integrated Connectivity Model in First-Episode Schizophrenia

Background: The human striatum is a heterogeneous structure involved in diverse functional domains that related to distinct striatum subregions. Striatal dysfunction was thought to be a fundamental element in schizophrenia. However, the connectivity pattern of striatum solely based on functional or structural characteristics leads to inconsistent findings in healthy adult and also schizophrenia. This study aims to develop an integrated striatal model and reveal the altered functional connectivity pattern of the striatum in schizophrenia. Methods: Two data-driven approaches, task-dependent meta-analytic connectivity modeling (MACM) and task-independent resting-state functional connectivity (RSFC), were used for seven anatomical connectivity-based striatum subregions to provide an integrated striatal model. Then, RSFC analyses of seven striatal subregions were applied to 45 first-episode schizophrenia (FES) and 27 healthy controls to examine the difference, based on the integrated model, of functional connectivity pattern of striatal subregions. Results: MACM and RSFC results showed that striatum subregions were associated with discrete cortical regions and involved in distinct cognitive processes. Besides, RSFC results overlapped with MACM findings but showed broader distributions. Importantly, significantly reduced functional connectivity was identified between limbic subregion and thalamus, medial prefrontal cortex, anterior cingulate cortex, and insula and also between executive subregions and thalamus, supplementary motor area, and insula in FES. Conclusions: Combing functional and structural connectivity information, this study provides the integrated model of corticostriatal subcircuits and confirms the abnormal functional connectivity of limbic and executive striatum subregions with different networks and thalamus, supporting the important role of the corticostriatal-thalamic loop in the pathophysiology of schizophrenia

Prevalence and Associated Features of Anxiety Disorder Comorbidity in Bipolar Disorder: A Meta-Analysis and Meta-Regression Study

Objective: Bipolar disorder is highly comorbid with anxiety disorders, however current and lifetime comorbidity patterns of each anxiety disorder and their associated features are not well studied. Here, we aimed to conduct a meta-analysis and meta-regression study of current evidence.Method: We searched PubMed to access relevant articles published until September 2015, using the keywords “Bipolar disorder” or “Affective Psychosis” or “manic depressive” separately with “generalized anxiety,” “panic disorder,” “social phobia,” “obsessive compulsive,” and “anxiety.” Variables for associated features and prevalence of anxiety disorders were carefully extracted.Results: Lifetime any anxiety disorder comorbidity in BD was 40.5%; panic disorder (PD) 18.1%, generalized anxiety disorder (GAD) 13.3%, social anxiety disorder (SAD) 13.5% and obsessive compulsive disorder (OCD) 9.7%. Current any anxiety disorder comorbidity in BD is 38.2%; GAD is 15.2%, PD 13.3%, SAD 11.7%, and OCD 9.9%. When studies reporting data about comorbidities in BDI or BDII were analyzed separately, lifetime any anxiety disorder comorbidity in BDI and BDII were 38% and 34%, PD was 15% and 15%, GAD was 14% and 16.6%, SAD was 8% and 13%, OCD was 8% and 10%, respectively. Current any DSM anxiety disorder comorbidity in BDI or BDII were 31% and 37%, PD was 9% and 13%, GAD was 8% and 12%, SAD was 7% and 11%, and OCD was 8% and 7%, respectively. The percentage of manic patients and age of onset of BD tended to have a significant impact on anxiety disorders. Percentage of BD I patients significantly decreased the prevalence of panic disorder and social anxiety disorder. A higher rate of substance use disorder was associated with greater BD–SAD comorbidity. History of psychotic features significantly affected current PD and GAD.Conclusions: Anxiety disorder comorbidity is high in BD with somewhat lower rates in BDI vs BDII. Age of onset, substance use disorders, and percentage of patients in a manic episode or with psychotic features influences anxiety disorder comorbidity

Reduced gray matter volume in ventral prefrontal cortex but not amygdala in bipolar disorder:significant effects of gender and trait anxiety

Neuroimaging studies in bipolar disorder report gray matter volume (GMV) abnormalities in neural regions implicated in emotion regulation. This includes a reduction in ventral/orbital medial prefrontal cortex (OMPFC) GMV and, inconsistently, increases in amygdala GMV. We aimed to examine OMPFC and amygdala GMV in bipolar disorder type 1 patients (BPI) versus healthy control participants (HC), and the potential confounding effects of gender, clinical and illness history variables and psychotropic medication upon any group differences that were demonstrated in OMPFC and amygdala GMV. Images were acquired from 27 BPI (17 euthymic, 10 depressed) and 28 age- and gender-matched HC in a 3T Siemens scanner. Data were analyzed with SPM5 using voxel-based morphometry (VBM) to assess main effects of diagnostic group and gender upon whole brain (WB) GMV. Post-hoc analyses were subsequently performed using SPSS to examine the extent to which clinical and illness history variables and psychotropic medication contributed to GMV abnormalities in BPI in a priori and non-a priori regions has demonstrated by the above VBM analyses. BPI showed reduced GMV in bilateral posteromedial rectal gyrus (PMRG), but no abnormalities in amygdala GMV. BPI also showed reduced GMV in two non-a priori regions: left parahippocampal gyrus and left putamen. For left PMRG GMV, there was a significant group by gender by trait anxiety interaction. GMV was significantly reduced in male low-trait anxiety BPI versus male low-trait anxiety HC, and in high- versus low-trait anxiety male BPI. Our results show that in BPI there were significant effects of gender and trait-anxiety, with male BPI and those high in trait-anxiety showing reduced left PMRG GMV. PMRG is part of medial prefrontal network implicated in visceromotor and emotion regulation

Damage to the prefrontal cortex increases utilitarian moral judgements

The psychological and neurobiological processes underlying moral judgement have been the focus of many recent empirical studies1–11. Of central interest is whether emotions play a causal role in moral judgement, and, in parallel, how emotion-related areas of the brain contribute to moral judgement. Here we show that six patients with focal bilateral damage to the ventromedial prefrontal cortex (VMPC), a brain region necessary for the normal generation of emotions and, in particular, social emotions12–14, produce an abnor- mally ‘utilitarian’ pattern of judgements on moral dilemmas that pit compelling considerations of aggregate welfare against highly emotionally aversive behaviours (for example, having to sacrifice one person’s life to save a number of other lives)7,8. In contrast, the VMPC patients’ judgements were normal in other classes of moral dilemmas. These findings indicate that, for a selective set of moral dilemmas, the VMPC is critical for normal judgements of right and wrong. The findings support a necessary role for emotion in the generation of those judgements

Can obsessions drive you mad? Longitudinal evidence that obsessive-compulsive symptoms worsen the outcome of early psychotic experiences

Although there is substantial comorbidity between psychotic disorder and obsessive-compulsive disorder (OCD), little is known about how these clinical phenotypes, and their subclinical extended phenotypes, covary and impact on each other over time. This study examined cross-sectional and longitudinal associations between both (extended) phenotypes in the general population.status: publishe

Increased cerebral blood flow in the right anterior cingulate cortex and fronto-orbital cortex during go/no-go task in children with ADHD

Objective Arterial spin labeling (ASL) is a relatively new imaging modality in the field of the cognitive neuroscience. In the present study, we aimed to compare the dynamic regional cerebral blood flow alterations of children with ADHD and healthy controls during a neurocognitive task by using event-related ASL scanning. Methods The study comprised of 17 healthy controls and 20 children with ADHD. The study subjects were scanned on 3 Tesla MRI scanner to obtain ASL imaging data. Subjects performed go/no-go task during the ASL image acquisition. The image analyses were performed by FEAT (fMRI Expert Analysis Tool) Version 6. Results The mean age was 10.88 +/- 1.45 and 11 +/- 1.91 for the control and ADHD group, respectively (p = .112). The go/no-go task was utilized during the ASL scanning. The right anterior cingulate cortex (BA32) extending into the frontopolar and orbitofrontal cortices (BA10 and 11) displayed greater activation in ADHD children relative to the control counterparts (p < .001). With a lenient significance threshold, greater activation was revealed in the right-sided frontoparietal regions during the go session, and in the left precuneus during the no-go session. Conclusion These results indicate that children with ADHD needed to over-activate frontopolar cortex, anterior cingulate as well as the dorsal and ventral attention networks to compensate for the attention demanded in a given cognitive task

Dysregulated protocadherin-pathway activity as an intrinsic defect in induced pluripotent stem cell-derived cortical interneurons from subjects with schizophrenia.

We generated cortical interneurons (cINs) from induced pluripotent stem cells derived from 14 healthy controls and 14 subjects with schizophrenia. Both healthy control cINs and schizophrenia cINs were authentic, fired spontaneously, received functional excitatory inputs from host neurons, and induced GABA-mediated inhibition in host neurons in vivo. However, schizophrenia cINs had dysregulated expression of protocadherin genes, which lie within documented schizophrenia loci. Mice lacking protocadherin-α showed defective arborization and synaptic density of prefrontal cortex cINs and behavioral abnormalities. Schizophrenia cINs similarly showed defects in synaptic density and arborization that were reversed by inhibitors of protein kinase C, a downstream kinase in the protocadherin pathway. These findings reveal an intrinsic abnormality in schizophrenia cINs in the absence of any circuit-driven pathology. They also demonstrate the utility of homogenous and functional populations of a relevant neuronal subtype for probing pathogenesis mechanisms during development