Brain Volumetric Correlates of Right Unilateral Versus Bitemporal Electroconvulsive Therapy for Treatment-Resistant Depression.

OBJECTIVE: The selection of a bitemporal (BT) or right unilateral (RUL) electrode placement affects the efficacy and side effects of ECT. Previous studies have not entirely described the neurobiological underpinnings of such differential effects. Recent neuroimaging research on gray matter volumes is contributing to our understanding of the mechanism of action of ECT and could clarify the differential mechanisms of BT and RUL ECT. METHODS: To assess the whole-brain gray matter volumetric changes observed after treating patients with treatment-resistant depression with BT or RUL ECT, the authors used MRI to assess 24 study subjects with treatment-resistant depression (bifrontotemporal ECT, N=12; RUL ECT, N=12) at two time points (before the first ECT session and after ECT completion). RESULTS: Study subjects receiving BT ECT showed gray matter volume increases in the bilateral limbic system, but subjects treated with RUL ECT showed gray matter volume increases limited to the right hemisphere. The authors observed significant differences between the two groups in midtemporal and subcortical limbic structures in the left hemisphere. CONCLUSIONS: These findings highlight that ECT-induced gray matter volume increases may be specifically observed in the stimulated hemispheres. The authors suggest that electrode placement may relevantly contribute to the development of personalized ECT protocols.

Dynamic functional connectivity reveals altered variability in functional connectivity among patients with major depressive disorder.

Resting-state fMRI (RS-fMRI) has become a useful tool to investigate the connectivity structure of mental health disorders. In the case of major depressive disorder (MDD), recent studies regarding the RS-fMRI have found abnormal connectivity in several regions of the brain, particularly in the default mode network (DMN). Thus, the relevance of the DMN to self-referential thoughts and ruminations has made the use of the resting-state approach particularly important for MDD. The majority of such research has relied on the grand averaged functional connectivity measures based on the temporal correlations between the BOLD time series of various brain regions. We, in our study, investigated the variations in the functional connectivity over time at global and local level using RS-fMRI BOLD time series of 27 MDD patients and 27 healthy control subjects. We found that global synchronization and temporal stability were significantly increased in the MDD patients. Furthermore, the participants with MDD showed significantly increased overall average (static) functional connectivity (sFC) but decreased variability of functional connectivity (vFC) within specific networks. Static FC increased to predominance among the regions pertaining to the default mode network (DMN), while the decreased variability of FC was observed in the connections between the DMN and the frontoparietal network. Hum Brain Mapp 37:2918-2930, 2016. © 2016 Wiley Periodicals, Inc.

Val66Met BDNF genotypes in melancholic depression: effects on brain structure and treatment outcome.

BACKGROUND: A brain-derived neurotrophic factor (BDNF) prodomain single-nucleotide polymorphism resulting in a valine to methionine substitution (Val66Met) has been associated with depression-related phenotypes and brain alterations involving regions consistently associated with major depressive disorder (MDD). The aim of our study was to evaluate the association of regional gray matter (GM) volume within the hippocampus and other unpredicted regions at the whole-brain level with the BDNF Val66Met polymorphism in MDD patients with melancholic features and their impact on treatment outcome. METHODS: A sample of 37 MDD inpatients was assessed with three-dimensional magnetic resonance imaging (1.5-T scanner). GM volume was analyzed with voxel-based morphometry (VBM) using Statistical Parametric Mapping (SPM5). The BDNF Val66Met variant was genotyped using SNPlex technology. MDD patients were classified according to genotype distribution under a dominant model of inheritance and thus comparing Val66 homozygotes (n = 22) versus Met66 carriers (n = 15). RESULTS: A significant GM volume reduction in the left hippocampus was observed in Met66 carriers. Conversely, in the same group, a volume increase in the right orbitofrontal cortex was detected. Moreover, a significant negative correlation between left hippocampal volume and days to remission was found in Val66 homozygotes, whereas right orbitofrontal volume was inversely correlated to days to remission in Met66 carriers. CONCLUSIONS: Our results suggest that the Val66Met BDNF variant may have a differential impact on the brain structure of melancholic patients with possible treatment outcome implications.

ICOnnecta't: Development and Initial Results of a Stepped Psychosocial eHealth Ecosystem to Facilitate Risk Assessment and Prevention of Early Emotional Distress in Breast Cancer Survivors' Journey.

Psychosocial interventions prevent emotional distress and facilitate adaptation in breast cancer (BC). However, conventional care presents accessibility barriers that eHealth has the potential to overcome. ICOnnecta't is a stepped digital ecosystem designed to build wellbeing and reduce psychosocial risks during the cancer journey through a European-funded project. Women recently diagnosed with BC in a comprehensive cancer center were offered the ecosystem. ICOnnecta't consists of four care levels, provided according to users' distress: screening and monitoring, psychoeducation campus, peer-support community, and online-group psychotherapy. Descriptive analyses were conducted to assess the platform's implementation, while multilevel linear models were used to study users' psychosocial course after diagnosis. ICOnnecta't showed acceptance, use and attrition rates of 57.62, 74.60, and 29.66%, respectively. Up to 76.19% of users reported being satisfied with the platform and 75.95% informed that it was easy to use. A total of 443 patients' needs were detected and responsively managed, leading 94.33% of users to remain in the preventive steps. In general, strong social support led to a better psychosocial course. ICOnnecta't has been successfully implemented. The results showed that it supported the development of a digital relation with healthcare services and opened new early support pathways.

Acceptability and participation predictors for a pragmatic randomized controlled trial to test a smoking cessation intervention after discharge from mental health wards.

BACKGROUND AND AIM: Hospitalization is an ideal time to promote smoking cessation, but interventions are limited for supporting cessation maintenance after discharge. This study aimed to evaluate the acceptability of participating in a trial that tested the efficacy of an intensive telephone-based intervention for smokers after discharge. METHODS: Adult smokers admitted to mental health wards of six hospitals were invited to participate in the trial. We studied the study acceptance/decline rates by analyzing the characteristics of participants (e.g., sex, age, psychiatric disorder, smoking pattern) and hospitals (e.g., size, tobacco control implementation). We calculated adjusted odds ratios (aOR) to assess predictors of non-participation. RESULTS: Of 530 smokers that met the study inclusion criteria, 55.5% (n = 294) agreed to participate. Participant and non-participants were not different in sex, age, or psychiatric diagnosis. Compared to non-participants, participants had made more attempts to quit in the past year (66.1% vs 33.9%; p < 0.001) and reported higher abstinence rates during the hospital stay (66.7% vs. 33.3%; p = 0.05). Participation rates by hospital varied from 30.9% to 82.0% (p < 0.001). Predictors of non-participation were not having attempted to quit in the last year (aOR=2.42; 95%CI: 1.66-3.53) and low level of tobacco control in the hospital (aOR range: 1.79-6.39, p < 0.05). CONCLUSIONS: A telephone-based intervention to promote smoking cessation after discharge was accepted by half of the smokers with mental health disorders. Smokers that had attempted to quit previously and those that stayed in hospitals with a strong tobacco control policy were more likely to participate in the trial.

Consistency and functional specialization in the default mode brain network.

The notion of a "default mode of brain function" has taken on certain relevance in human neuroimaging studies and in relation to a network of lateral parietal and midline cortical regions that show prominent activity fluctuations during passive imaging states, such as rest. In this study, we perform three fMRI experiments that demonstrate consistency and specialization in the default mode network. Correlated activity fluctuations of default mode network regions are identified during (i) eyes-closed spontaneous rest, (ii) activation by moral dilemma, and (iii) deactivation by Stroop task performance. Across these imaging states, striking uniformity is shown in the basic anatomy of the default mode network, but with both tasks clearly and differentially modulating this activity compared with spontaneous fluctuations of the network at rest. Against rest, moral dilemma is further shown to evoke regionally specific activity increases of hypothesized functional relevance. Mapping spontaneous and task-related brain activity will help to constrain the meaning of the default mode network. These findings are discussed in relation to recent debate on the topic of default modes of brain function.

Dynamic assessment of the right lateral frontal cortex response to painful stimulation.

The lateral surface of the right frontal lobe has a relevant role in modulating behavioral responses to aversive stimuli and may significantly influence pain experience. Imaging studies suggest that this modulatory role is multifaceted, but no studies have assessed the regional specialization of this cortex on the basis of its response dynamics during pain processing. We aimed to investigate functional specialization within the right lateral frontal cortex using a dynamic fMRI approach. Brain responses to a mechanical painful stimulus and a preceding anticipatory cue (auditory tone) were assessed in 25 healthy subjects. Functional data were decomposed into 15 sequential activation maps covering the full anticipation-painful stimulation cycle using a finite impulse response (FIR) analysis approach. Movie sequences showing the temporal evolution of brain activation illustrate the findings. A region involving premotor-prefrontal cortices was activated soon after the anticipatory cue and showed a significant correlation with both anterior cingulate cortex activation and subjective pain ratings. The frontal operculum also showed a significant anticipatory response, but the most robust activation followed painful stimulation onset and was strongly correlated with insula activation. The anterior prefrontal cortex showed full activation during late painful stimulation and was negatively correlated with pain unpleasantness. In conclusion, different elements within the right lateral frontal cortex showed distinct activation dynamics in response to painful stimulation, which would suggest relevant regional specialization during pain processing. These findings are congruent with the broad functional role of the right frontal cortex and its influence on crucial aspects of human behavior.

Effectiveness of a telephone-based intervention for smoking cessation in patients with severe mental disorders: study protocol for a randomized controlled trial.

BACKGROUND: Up to 75% of inpatients with mental disorders smoke, and their life expectancy is decreased by up to 25 years compared to the general population. Hospitalized patients without monitoring after discharge quickly return to prehospitalization levels of tobacco use. The aim of the 061 QuitMental study is to assess the effectiveness of a multicomponent and motivational telephone-based intervention to stop smoking through a quitline addressed to smokers discharged from mental health hospital wards. METHODS: A pragmatic randomized controlled trial, single blinded, will include 2:1 allocation to the intervention group (IG) and the control group (CG). The IG will receive telephone assistance to quit smoking (including psychological and psychoeducational support, and pharmacological treatment advice if required) proactively for 12 months, and the CG will receive only brief advice after discharge. The sample size, calculated with an expected difference of 15 points on smoking abstinence between groups (IG, 20% and CG, 5%), α = 0.05, ß = 0.10, and 20% loss, will be 334 participants (IG) and 176 participants (CG). Participants are adult smokers discharged from psychiatric units of five acute hospitals. Measurements include dependent variables (self-reported 7-day point prevalence smoking abstinence (carbon monoxide verified), duration of abstinence, number of quit attempts, motivation, and self-efficacy to quit) and independent variables (age, sex, and psychiatric diagnoses). In data analysis, IG and CG data will be compared at 48 h and 1, 6, and 12 months post discharge. Multivariate logistic regression (odds ratio; 95% confidence interval) of dependent variables adjusted for potential confounding variables will be performed. The number needed to treat to achieve one abstinence outcome will be calculated. We will compare the abstinence rate of enrolled patients between groups. DISCUSSION: This trial evaluates an innovative format of a quitline for smokers with severe mental disorders regardless of their motivation to quit. If effective, the pragmatic nature of the study will permit transfer to routine clinical practice in the National Health System. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03230955 . Registered on 24 July 2017.

Modulatory effects of psychopathy on Wisconsin Card Sorting Test performance in male offenders with Antisocial Personality Disorder.

Neuropsychological deficits in executive functions (EF) have been linked to antisocial behavior and considered to be cardinal to the onset and persistence of severe antisocial and aggressive behavior. However, when psychopathy is present, prior evidence suggests that the dorsolateral prefrontal cortex is unaffected leading to intact EF. Ninety-one male offenders with Antisocial Personality Disorder (ASPD) and 24 controls completed the Wisconsin Card Sorting Test (WCST). ASPD individuals were grouped in three categories according to Psychopathy Checklist-Revised (PCL-R) scores (low, medium and high). We hypothesized that ASPD offenders with high PCL-R scores will not differ from healthy controls in EF and will show better EF performance in comparison with subjects with low PCL-R scores. Results showed that ASPD offenders with low PCL-R scores committed more perseverative errors and responses than controls and offenders with high PCL-R scores, which did not differ from healthy controls. Moreover, scores on Factor 1 and the interpersonal facet of the PCL-R were predictors of better WCST performance. Our results suggest a modulatory role of psychopathy in the cognitive performance of ASPD offenders, and provide further evidence supporting that offenders with ASPD and psychopathy are characterized by a cognitive profile different from those with ASPD without psychopathy.

Modulation of Limbic and Prefrontal Connectivity by Electroconvulsive Therapy in Treatment-resistant Depression: A Preliminary Study.

BACKGROUND: Although current models of depression suggest that a sequential modulation of limbic and prefrontal connectivity is needed for illness recovery, neuroimaging studies of electroconvulsive therapy (ECT) have focused on assessing functional connectivity (FC) before and after an ECT course, without characterizing functional changes occurring at early treatment phases. OBJECTIVE: To assess sequential changes in limbic and prefrontal FC during the course of ECT and their impact on clinical response. METHODS: Longitudinal intralimbic and limbic-prefrontal networks connectivity study. We assessed 15 patients with treatment-resistant depression at four different time-points throughout the entire course of an ECT protocol and 10 healthy participants at two functional neuroimaging examinations. Furthermore, a path analysis to test direct and indirect predictive effects of limbic and prefrontal FC changes on clinical response measured with the Hamilton Rating Scale for Depression was also performed. RESULTS: An early significant intralimbic FC decrease significantly predicted a later increase in limbic-prefrontal FC, which in turn significantly predicted clinical improvement at the end of an ECT course. CONCLUSIONS: Our data support that treatment response involves sequential changes in FC within regions of the intralimbic and limbic-prefrontal networks. This approach may help in identifying potential early biomarkers of treatment response.

Functional Connectivity Bias in the Prefrontal Cortex of Psychopaths.

BACKGROUND: Psychopathy is characterized by a distinctive interpersonal style that combines callous-unemotional traits with inflexible and antisocial behavior. Traditional emotion-based perspectives link emotional impairment mostly to alterations in amygdala-ventromedial frontal circuits. However, these models alone cannot explain why individuals with psychopathy can regularly benefit from emotional information when placed on their focus of attention and why they are more resistant to interference from nonaffective contextual cues. The present study aimed to identify abnormal or distinctive functional links between and within emotional and cognitive brain systems in the psychopathic brain to characterize further the neural bases of psychopathy. METHODS: High-resolution anatomic magnetic resonance imaging with a functional sequence acquired in the resting state was used to assess 22 subjects with psychopathy and 22 control subjects. Anatomic and functional connectivity alterations were investigated first using a whole-brain analysis. Brain regions showing overlapping anatomic and functional changes were examined further using seed-based functional connectivity mapping. RESULTS: Subjects with psychopathy showed gray matter reduction involving prefrontal cortex, paralimbic, and limbic structures. Anatomic changes overlapped with areas showing increased degree of functional connectivity at the medial-dorsal frontal cortex. Subsequent functional seed-based connectivity mapping revealed a pattern of reduced functional connectivity of prefrontal areas with limbic-paralimbic structures and enhanced connectivity within the dorsal frontal lobe in subjects with psychopathy. CONCLUSIONS: Our results suggest that a weakened link between emotional and cognitive domains in the psychopathic brain may combine with enhanced functional connections within frontal executive areas. The identified functional alterations are discussed in the context of potential contributors to the inflexible behavior displayed by individuals with psychopathy.

Disrupted neural processing of emotional faces in psychopathy.

Psychopaths show a reduced ability to recognize emotion facial expressions, which may disturb the interpersonal relationship development and successful social adaptation. Behavioral hypotheses point toward an association between emotion recognition deficits in psychopathy and amygdala dysfunction. Our prediction was that amygdala dysfunction would combine deficient activation with disturbances in functional connectivity with cortical regions of the face-processing network. Twenty-two psychopaths and 22 control subjects were assessed and functional magnetic resonance maps were generated to identify both brain activation and task-induced functional connectivity using psychophysiological interaction analysis during an emotional face-matching task. Results showed significant amygdala activation in control subjects only, but differences between study groups did not reach statistical significance. In contrast, psychopaths showed significantly increased activation in visual and prefrontal areas, with this latest activation being associated with psychopaths' affective-interpersonal disturbances. Psychophysiological interaction analyses revealed a reciprocal reduction in functional connectivity between the left amygdala and visual and prefrontal cortices. Our results suggest that emotional stimulation may evoke a relevant cortical response in psychopaths, but a disruption in the processing of emotional faces exists involving the reciprocal functional interaction between the amygdala and neocortex, consistent with the notion of a failure to integrate emotion into cognition in psychopathic individuals.

Identifying brain imaging correlates of clinical response to repetitive transcranial magnetic stimulation (rTMS) in major depression.

BACKGROUND: Partial response and non-response to treatments are common problems in major depression. The identification of biological markers of clinical response may be of special interest for some adjunctive treatments, such as repetitive transcranial magnetic stimulation (rTMS), as it may ultimately improve their cost-effectiveness. OBJECTIVE: To identify pre-treatment functional imaging correlates of clinical response to rTMS in major depression. METHODS: We evaluated 21 depressed patients. They were randomized to receive 15 sessions of active or sham rTMS on the left dorsolateral prefrontal cortex. Functional magnetic resonance imaging (fMRI) was used to assess pre-treatment regional brain activity evoked by a word generation task. These regional activations were correlated (voxel-wise) with the Hamilton Rating Scale for Depression (HAM-D) reduction between baseline and end of treatment. A group of 13 healthy controls was also assessed using the same fMRI protocol to obtain reference imaging measurements. RESULTS: At the end of treatment, the percentage of patients with a HAM-D reduction greater than 50% was larger in the active than in the sham rTMS group (70% vs. 27.3%). In the active rTMS group, larger HAM-D reductions were significantly correlated with smaller deactivations during pre-treatment fMRI assessment in the anterior cingulate, the left medial orbitofrontal and the right middle frontal cortices, in addition to larger activations in the left ventral-caudal putamen. CONCLUSIONS: These results suggest that brain activity in regions arguably relevant for major depression may predict clinical response to rTMS. This approach may help in identifying the most suitable candidates to undergo rTMS treatment.

Cerebrospinal fluid space alterations in melancholic depression.

Melancholic depression is a biologically homogeneous clinical entity in which structural brain alterations have been described. Interestingly, reports of structural alterations in melancholia include volume increases in Cerebro-Spinal Fluid (CSF) spaces. However, there are no previous reports of CSF volume alterations using automated whole-brain voxel-wise approaches, as tissue classification algorithms have been traditionally regarded as less reliable for CSF segmentation. Here we aimed to assess CSF volumetric alterations in melancholic depression and their clinical correlates by means of a novel segmentation algorithm ('new segment', as implemented in the software Statistical Parametric Mapping-SPM8), incorporating specific features that may improve CSF segmentation. A three-dimensional Magnetic Resonance Image (MRI) was obtained from seventy patients with melancholic depression and forty healthy control subjects. Although imaging data were pre-processed with the 'new segment' algorithm, in order to obtain a comparison with previous segmentation approaches, tissue segmentation was also performed with the 'unified segmentation' approach. Melancholic patients showed a CSF volume increase in the region of the left Sylvian fissure, and a CSF volume decrease in the subarachnoid spaces surrounding medial and lateral parietal cortices. Furthermore, CSF increases in the left Sylvian fissure were negatively correlated with the reduction percentage of depressive symptoms at discharge. None of these results were replicated with the 'unified segmentation' approach. By contrast, between-group differences in the left Sylvian fissure were replicated with a non-automated quantification of the CSF content of this region. Left Sylvian fissure alterations reported here are in agreement with previous findings from non-automated CSF assessments, and also with other reports of gray and white matter insular alterations in depressive samples using automated approaches. The reliable characterization of CSF alterations may help in the comprehensive characterization of brain structural abnormalities in psychiatric samples and in the development of etiopathogenic hypotheses relating to the disorders.

Breakdown in the brain network subserving moral judgment in criminal psychopathy.

Neuroimaging research has demonstrated the involvement of a well-defined brain network in the mediation of moral judgment in normal population, and has suggested the inappropriate network use in criminal psychopathy. We used functional magnetic resonance imaging (fMRI) to prove that alterations in the brain network subserving moral judgment in criminal psychopaths are not limited to the inadequate network use during moral judgment, but that a primary network breakdown would exist with dysfunctional alterations outside moral dilemma situations. A total of 22 criminal psychopathic men and 22 control subjects were assessed and fMRI maps were generated to identify (i) brain response to moral dilemmas, (ii) task-induced deactivation of the network during a conventional cognitive task and (iii) the strength of functional connectivity within the network during resting-state. The obtained functional brain maps indeed confirmed that the network subserving moral judgment is underactive in psychopathic individuals during moral dilemma situations, but the data also provided evidence of a baseline network alteration outside moral contexts with a functional disconnection between emotional and cognitive elements that jointly construct moral judgment. The finding may have significant social implications if considering psychopathic behavior to be a result of a primary breakdown in basic brain systems.

Neural correlates of moral sensitivity in obsessive-compulsive disorder.

CONTEXT: Heightened moral sensitivity seems to characterize patients with obsessive-compulsive disorder (OCD). Recent advances in social cognitive neuroscience suggest that a compelling relationship may exist between this disorder-relevant processing bias and the functional activity of brain regions implicated in OCD. OBJECTIVE: To test the hypothesis that patients with OCD demonstrate an increased response of relevant ventromedial prefrontal and orbitofrontal cortex regions in a functional magnetic resonance imaging study of difficult moral decision making. DESIGN: Case-control cross-sectional study. SETTING: Hospital referral OCD unit and magnetic resonance imaging facility. PARTICIPANTS: Seventy-three patients with OCD (42 men and 31 women) and 73 control participants matched for age, sex, and education level. MAIN OUTCOME MEASURES: Functional magnetic resonance imaging activation maps representing significant changes in blood oxygenation level-dependent signal in response to 24 hypothetical moral dilemma vs nondilemma task vignettes and additional activation maps representing significant linear associations between patients' brain responses and symptom severity ratings. RESULTS: In both groups, moral dilemma led to robust activation of frontal and temporoparietal brain regions. Supporting predictions, patients with OCD demonstrated significantly increased activation of the ventral frontal cortex, particularly of the medial orbitofrontal cortex. In addition, the left dorsolateral prefrontal cortex and left middle temporal gyrus were more robustly activated in patients with OCD. These results were unexplained by group differences in comorbid affective symptoms. Patients' global illness severity predicted the relative magnitude of orbitofrontal-striatal activation. The severity of "harm/checking" symptoms and "sexual/religious" obsessions predicted the magnitude of posterior temporal and amygdala-paralimbic activation, respectively. CONCLUSIONS: The neural correlates of moral sensitivity in patients with OCD partly coincide with brain regions that are of general interest to pathophysiologic models of this disorder. In particular, these findings suggest that the orbitofrontal cortex together with the left dorsolateral prefrontal cortex may be relevant for understanding the link between neurobiological processes and certain maladaptive cognitions in OCD.

Cross-sectional and longitudinal assessment of structural brain alterations in melancholic depression.

BACKGROUND: Whole-brain imaging approaches may contribute to the characterization of neuroanatomic alterations in major depression, especially in clinically homogenous patient groups such as those with melancholic features. We assessed brain anatomic alterations, both cross-sectionally and longitudinally, in patients with melancholic depression using a whole-brain voxel-wise approach. METHODS: Whole-brain magnetic resonance images were collected from a relatively aged sample of 70 consecutively recruited major depressive disorder inpatients with melancholic features and from a group of 40 healthy control subjects. All patients were clinically followed for at least 2 years, and a subset of 30 depressive patients and 20 control subjects were rescanned after a 7-year period. Imaging data were analyzed with voxel- and tensor-based morphometry techniques. RESULTS: Melancholic patients showed gray matter reductions in the left insula and white matter increases in the upper brainstem tegmentum. Male patients showed gray matter decreases in the right thalamus, and periventricular white matter reductions were specifically observed in older patients. Volume decreases in the left insula, hippocampus, and lateral parietal cortex predicted a slower recovery after treatment initiation. In longitudinal assessment, white matter of the upper brainstem tegmentum showed a different temporal evolution between groups. Additionally, bilateral gray matter reductions in the insulae were associated with the number of relapses during follow-up. CONCLUSIONS: Structural alterations were identified in regions potentially related to relevant aspects of melancholia pathophysiology. Longitudinal analyses indicated region-specific interactions of baseline alterations with age as well as a significant association of clinical severity with focal changes occurring over time.

Enhanced brain responsiveness during active emotional face processing in obsessive compulsive disorder.

OBJECTIVES. The abnormal processing of emotional stimuli is common to a variety of psychiatric disorders. Specifically, patients with prominent anxiety symptoms generally overreact to emotional cues, which has been linked to increased amygdala activation. However, in OCD, enhanced responses are predominantly obtained using disease-specific stimuli and preferentially involve frontostriatal systems. METHODS. We assessed 21 OCD patients and 21 healthy controls with fMRI during an emotional face-processing paradigm involving active response generation to test for alterations in both brain activation and task-induced functional connectivity of the frontal cortex, the amygdala and the fusiform face area. RESULTS. OCD patients showed significantly greater activation of "face-processing" regions including the amygdala, fusiform gyrus and dorsolateral prefrontal cortex. The reciprocal connectivity between face-processing regions was enhanced in OCD. Importantly, we detected significant correlations between patients' clinical symptom severity and both task-related region activation and network functional connectivity. CONCLUSIONS. The results suggest that OCD patients may show enhanced brain responsiveness during emotional face-processing when tasks involve active response generation. Our findings diverge from previously described alterations in anxiety disorders, as patients showed enhanced amygdala-prefrontal connectivity as opposed to negative reciprocal interaction. This pattern would appear to be disorder-specific and was significantly related to obsessive-compulsive symptom severity.

Task-induced deactivation from rest extends beyond the default mode brain network.

Activity decreases, or deactivations, of midline and parietal cortical brain regions are routinely observed in human functional neuroimaging studies that compare periods of task-based cognitive performance with passive states, such as rest. It is now widely held that such task-induced deactivations index a highly organized 'default-mode network' (DMN): a large-scale brain system whose discovery has had broad implications in the study of human brain function and behavior. In this work, we show that common task-induced deactivations from rest also occur outside of the DMN as a function of increased task demand. Fifty healthy adult subjects performed two distinct functional magnetic resonance imaging tasks that were designed to reliably map deactivations from a resting baseline. As primary findings, increases in task demand consistently modulated the regional anatomy of DMN deactivation. At high levels of task demand, robust deactivation was observed in non-DMN regions, most notably, the posterior insular cortex. Deactivation of this region was directly implicated in a performance-based analysis of experienced task difficulty. Together, these findings suggest that task-induced deactivations from rest are not limited to the DMN and extend to brain regions typically associated with integrative sensory and interoceptive processes.

Effects of duloxetine treatment on brain response to painful stimulation in major depressive disorder.

Major depressive disorder (MDD) is characterized by a constellation of affective, cognitive, and somatic symptoms associated with functional abnormalities in relevant brain systems. Painful stimuli are primarily stressful and can trigger consistent responses in brain regions highly overlapping with the regions altered in MDD patients. Duloxetine has proven to be effective in treating both core emotional symptoms and somatic complaints in depression. This study aimed to assess the effects of duloxetine treatment on brain response to painful stimulation in MDD patients. A total of 13 patients and a reference group of 20 healthy subjects were assessed on three occasions (baseline, treatment week 1, and week 8) with functional magnetic resonance imaging (fMRI) during local application of painful heat stimulation. Treatment with duloxetine was associated with a significant reduction in brain responses to painful stimulation in MDD patients in regions generally showing abnormally enhanced activation at baseline. Clinical improvement was associated with pain-related activation reductions in the pregenual anterior cingulate cortex, right prefrontal cortex, and pons. Pontine changes were specifically related to clinical remission. Increased baseline activations in the right prefrontal cortex and reduced deactivations in the subgenual anterior cingulate cortex predicted treatment responders at week 8. This is the first fMRI study addressed to assess the effect of duloxetine in MDD. As a novel approach, the application of painful stimulation as a basic neural stressor proved to be effective in mapping brain response changes associated with antidepressant treatment and brain correlates of symptom improvement in regions of special relevance to MDD pathophysiology.