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Markers of HPA axis function, including diurnal cortisol rhythm and cortisol responses to stress or pharmacological manipulation, are increasingly reported as disrupted in schizophrenia (SZ) and bipolar disorder (BD). However, there has been no direct comparison of cortisol responses to stress in SZ and BD in the same study, and associations between cortisol dysfunction and illness characteristics remain unclear. In this study we used spline embedded linear mixed models to examine cortisol levels of SZ and BD participants at waking, during the first 45min after waking (representing the cortisol awakening response; CAR), during the period of rapid cortisol decline post the awakening response, and in reaction to a stressor (MRI scan), relative to healthy controls (HC). Contrary to expectations, neither SZ nor BD showed differences in waking cortisol levels, CAR, or immediate post-CAR decline compared to HC; however, waking cortisol levels were greater in BD relative to SZ. In response to the MRI stressor, the SZ group showed a significant absence of the expected increase in cortisol responsivity to stress, which was seen in both the BD and HC groups. Clinical factors affecting the CAR differed between SZ and BD. In SZ, higher antipsychotic medication dosage was associated with a steeper incline of the CAR, while greater positive symptom severity was associated with a more blunted CAR, and greater levels of anxiety were associated with the blunted cortisol response to stress. In BD, longer illness duration was associated with a steeper incline in CAR and lower levels of waking cortisol. These results suggest that cortisol responses may normalize with medication (in SZ) and longer illness duration (in BD), in line with findings of aberrant cortisol levels in the early stages of psychotic disorders., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Vocal expressions of emotions consistently activate regions in the superior temporal cortex (STC), including regions in the primary and secondary auditory cortex (AC). Studies usually report broadly extended functional activations in response to vocal expressions, with considerable variation in peak locations across several auditory subregions. This might suggest different and distributed functional roles across these subregions instead of a uniform role for the decoding of vocal emotions. We reviewed recent studies and conducted an activation likelihood estimation meta-analysis summarizing recent fMRI and PET studies dealing with the processing of vocal expressions in the STC and AC. We included two stimulus-specific factors (paraverbal/nonverbal expression, stimulus valence) and one task-specific factor (attentional focus) in the analysis. These factors considerably influenced whether functional activity was located in the AC or STC (influence of valence and attentional focus), the laterality of activations (influence of paraverbal/nonverbal expressions), and the anterior-posterior location of STC activity (influence of valence). These data suggest distributed functional roles and a differentiated network of auditory subregions in response to vocal expressions., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The popular go/no-go paradigm is supposed to ensure a reliable probing of response inhibition mechanisms. Functional magnetic resonance imaging (fMRI) studies have repeatedly found a large number of structures, usually including a right lateralized parieto-frontal network and the pre-supplementary motor area (pre-SMA). However, it is unlikely that all these regions are directly related to the mechanism that actively suppresses the motor command. Since most go/no-go designs involve complex stimulus identification/detection processes, these activations may rather reflect the engagement of different cognitive processes that are intrinsically related and quite difficult to disentangle. The current critical review is based on repeated meta-analyses of 30 go/no-go fMRI experiments using the Activation Likelihood Estimate method to contrast studies using simple vs. complex stimuli. The results show that most of the activity typically elicited by no-go signals, including pre-SMA hemodynamic response, is actually driven by the engagement of high attentional or working memory resources, not by inhibitory processes per se. Implications for current methods and theories of inhibitory control are discussed, and new lines of inquiry are proposed., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

This review examines the neural correlates of Gray's model (Gray and McNaughton, 2000; McNaughton and Corr, 2004), supplemented by a fourth dimension: constraint (Carver, 2005). The purpose of this review is to summarize findings from fMRI studies that tap on neural correlates of personality aspects in healthy subjects, in order to provide insight into the neural activity underlying human temperament. BAS-related personality traits were consistently reported to correlate positively to activity of the ventral and dorsal striatum and ventral PFC in response to positive stimuli. FFFS and BIS-related personality traits are positively correlated to activity in the amygdala in response to negative stimuli. There is limited evidence that constraint is associated with PFC and ACC activity. In conclusion, functional MRI research sheds some light on the specific neural networks underlying personality. It is clear that more sophisticated task paradigms are required, as well as personality questionnaires that effectively differentiate between BAS, FFFS, BIS, and constraint. Further research is proposed to potentially reveal new insight in the neural subsystems governing basic human behavior., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: The previous resting perfusion or task-based studies have provided evidence of functional changes in the brains of patients with late-life depression (LLD). Little is known, so far, about the changes in the spontaneous brain activity in LLD during the resting state. The aim of this study was to investigate the spontaneous neural activity in first-episode, treatment-naive patients with LLD by using resting-state functional magnetic resonance imaging (fMRI)., Methods: A novel analytical method, coherence-based regional homogeneity (Cohe-ReHo), was used to assess regional spontaneous neural activity during the resting state in 15 first-episode, treatment-naive patients with LLD and 15 age- and gender-matched healthy controls., Results: Compared to the healthy controls, the LLD group showed significantly decreased Cohe-ReHo in left caudate nucleus, right anterior cingulate gyrus, left dorsolateral prefrontal cortex, right angular gyrus, bilateral medial prefrontal cortex, and right precuneus, while significantly increased Cohe-ReHo in left cerebellum posterior lobe, left superior temporal gyrus, bilateral supplementary motor area, and right postcentral gyrus (p<0.005, corrected for multiple comparisons)., Conclusions: These findings indicated abnormal spontaneous neural activity was distributed extensively in first-episode, treatment-naive patients with LLD during the resting state. Our results might supply a novel way to look into the underlying pathophysiology mechanisms of patients with LLD., (Copyright © 2012 Elsevier Inc. All rights reserved.)

While adolescent internet addicts are immersed in cyberspace, they are easily able to experience 'disembodied state'. The purposes of this study were to investigate the difference of brain activity between adolescent internet addicts and normal adolescents in a state of disembodiment, and to find the correlation between the activities of disembodiment-related areas and the behavioral characteristics related to internet addiction. The fMRI images were taken while the addiction group (N=17) and the control group (N=17) were asked to perform the task composed with ball-throwing animations. The task reflected on either self-agency about ball-throwing or location of a ball. And each block was shown with either different (Changing View) or same animations (Fixed View). The disembodiment-related condition was the interaction between Agency Task and Changing View. Within-group analyses revealed that the addiction group exhibited higher activation in the thalamus, bilateral precentral area, bilateral middle frontal area, and the area around the right temporo-parietal junction. And between-group analyses showed that the addiction group exhibited higher activation in the area near the left temporo-parieto-occipital junction, right parahippocampal area, and other areas than the control group. Finally, the duration of internet use was significantly correlated with the activity of posterior area of left middle temporal gyrus in the addiction group. These results show that the disembodiment-related activation of the brain is easily manifested in adolescent internet addicts. Internet addiction of adolescents could be significantly unfavorable for their brain development related with identity formation., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The neural mechanisms supporting social bonds between adult men remain uncertain. In this double-blind, placebo-controlled study, we investigate the impact of intranasally administered oxytocin (OT) and vasopressin (AVP) on behavior and brain activity among men in the context of an iterated Prisoner's Dilemma game, which models a real-life social situation. fMRI results show that, relative to both AVP and placebo, OT increases the caudate nucleus response to reciprocated cooperation, which may augment the reward of reciprocated cooperation and/or facilitate learning that another person can be trusted. OT also enhances left amygdala activation in response to reciprocated cooperation. Behaviorally, OT was associated with increased rates of cooperation following unreciprocated cooperation in the previous round compared with AVP. AVP strongly increased cooperation in response to a cooperative gesture by the partner compared with both placebo and OT. In response to reciprocated cooperation, AVP increased activation in a region spanning known vasopressin circuitry implicated in affiliative behaviors in other species. Finally, both OT and AVP increase amygdala functional connectivity with the anterior insula relative to placebo, which may increase the amygdala's ability to elicit visceral somatic markers that guide decision making. These findings extend our knowledge of the neural and behavioral effects of OT and AVP to the context of genuine social interactions., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objectives: Structural abnormality of both gray and white matter has been detected in patients with bipolar disorder (BD). But results were greatly inconsistent across studies which were most likely attributed to heterogeneous populations as well as processing techniques. The present study aimed to investigate brain structural and microstructural alterations in a relative homogenous sample of bipolar mania., Methods: 3D T1-weighted magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) were conducted in 18 patients with BD and 27 healthy volunteers. Gray matter (GM) and white matter (WM) differences were evaluated using voxel-based morphometry (VBM) and voxel-based analysis of fractional anisotropy (FA) maps derived from DTI, respectively., Results: Patients with BD had a larger volume of GM in the left thalamus and bilateral basal ganglia, including the bilateral putamen and extending to the left claustrum, as well as reduced FA values in the left posterior corona radiata., Conclusions: By combined analysis, alterations in subcortical GM areas and part of the corresponding association fiber area were detected. Compared with observations in homogeneous samples, our findings indicate that disruption of the limbic network may be intrinsic to BD., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: In major depression, the neural mechanisms underlying suicide related thoughts and behaviors as well as the expression of other depressive symptoms are incompletely characterized. Evidence indicates that both the striatum and cortical midline structures (CMS) may be involved with both suicide and emotional dysregulation in unipolar illness. The aim of this study was to identify striatal-CMS circuits associated with current depression severity and suicidal ideation (SI) as well as a history of self-harm., Methods: Twenty-two male subjects with recurrent unipolar depression were studied using functional MRI. All subjects were unmedicated and without current psychiatric comorbidity. Correlational analyses were used to determine whether striatal-CMS functional connectivity was associated with any of the three clinical variables., Results: A network involving the bilateral striatum and anterior CMS was found to be associated with depressive symptom severity. Current SI was associated with a similar but less extensive circuit in the left hemisphere. A distinct striatal motor/sensory network was associated with self-harm behaviors, but not current SI or depression severity., Conclusions: The striatal-anterior CMS circuit likely plays a significant role in the expression of depressive symptoms and SI. In contrast, a striatum-motor/sensory cortex network may be a trait marker of suicide-related behaviors. If replicated, this result might eventually lead to the development of a biomarker that would be useful for studies of pharmacologic and/or psychotherapeutic suicide prevention interventions., (Published by Elsevier Inc.)

While cognitive changes and mood instability are frequent symptoms reported by menopausal women, the degree to which the decline in estrogen production is responsible is not yet clear. Several lines of evidence suggest that estrogen may produce its effects on cognition and mood through modulation of serotonergic function. To test this hypothesis, we used the tryptophan depletion (TD) paradigm to lower central serotonin levels and pharmacologically manipulated estrogen levels in healthy menopausal women. We examined the individual and combined effects of estradiol and serotonin on working memory, emotion processing and task-related brain activation. Eight healthy predominantly early postmenopausal women underwent TD or sham depletion followed by functional magnetic resonance imaging (fMRI) both before and after short-term transdermal estradiol 75-150 μg/d administration. There was an estradiol treatment by TD interaction for brain activation during performance on both the N-back Task (working memory) and Emotion Identification Task (affective processing). During the 2-back condition, TD attenuated activation prior to, but not after, estradiol treatment in the right and left dorsal lateral prefrontal and middle frontal/cingulate gyrus. During emotion identification, TD heightened activation in the orbital frontal cortex and bilateral amygdala, and this effect was attenuated by estradiol treatment. These results provide preliminary evidence that serotonergic effects directly mediate the impact of estrogen on brain activation during working memory and affective processing., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Magnetic resonance imaging (MRI) scans are a novel environment for most participants. The hypothalamic-pituitary-adrenal (HPA) axis modulates neurohormonal responses to novel and stressful experiences. We sought to examine the neurohormonal responses to MRI scans with the measurement of salivary cortisol. We examined: (1) acute effects of MRI scans by acquiring cortisol measurements immediately preceding and following the scan in comparison with basal cortisol levels, and (2) effects of novelty by measuring cortisol during repeated MRI scans in the same subjects. We examined these effects in two groups of subjects: healthy individuals (n=27, mean age 41.6 years) and patients with depression (n=24, mean age 40.0 years). Both groups showed elevated cortisol levels immediately preceding the MRI scan, particularly for the initial MRI scan, which normalised after the follow up MRI scans as compared with mean basal cortisol levels. There were no significant differences in the acute or mean basal cortisol levels between the groups. In summary, the MRI experience is stressful, particularly for the initial scan, but the stress response is reduced with subsequent scans., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

The present study sought to identify abnormalities in activation in several brain regions in response to an auditory attention task in patients with schizophrenia. Ten patients and twenty healthy control participants were examined using Functional Magnetic Resonance Imaging (FMRI) measures acquired during an auditory attention task. Region of interest analyses of activation of targeted regions implicated in attention included: anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), hippocampus, parahippocampal gyrus (PHG), and superior temporal gyrus (STG). The results indicated over-activation in patients with schizophrenia. While the control group showed notable coherence in activation within and across hemispheres the schizophrenia group showed relatively less coherence overall that was only present in the right hemisphere. These findings suggest that patients with schizophrenia show both an over-engagement of brain regions during attention task as well as a lack of communication among neural regions involved.

Success in functional neuroimaging has brought the promise of quantitative data in the form of brain images to the diagnosis of disorders of the central nervous system for which only qualitative clinical criteria have previously existed. Even though the translation of research to clinical neuroimaging for conditions such as major depression may not be available yet, rapid innovation along this trajectory of discovery to implementation compels exploration of how such information will eventually affect providers and patients. Clinical neuroethics is devoted to elucidating ethical challenges prior to and during the transfer of new research capabilities to the bedside. Through a model of proactive ethics, clinical neuroethics promotes the development of responsible social and public policies in response to new diagnostic and prognostic capabilities for the benefit of patients and their families, and for providers within the health care systems in which they practice. To examine views about the potential interaction of clinical neuroimaging and depression, we surveyed both mental health providers and outpatients and inpatients diagnosed with major depressive disorder. From responses of 52 providers and 72 patients, we found high receptivity to brain scans for treatment tailoring and choice, for improving understanding of and coping with disease, and for mitigating the effects of stigma and self-blame. Our results suggest that, once ready, roll out of the fully validated technology has significant potential to reduce social burden associated with highly stigmatized illnesses like depression.