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1.  Report on the Inaugural Meeting of the International Consortium on Hallucination Research: A Clinical and Research Update and 16 Consensus-Set Goals for Future Research 
Schizophrenia Bulletin  2012;38(2):258-262.
This article presents a report on the first meeting of the International Consortium on Hallucination Research, which took place on September 13–14, 2011 at the Institute of Psychiatry, London. The first day of the meeting served to reflect on the current state of knowledge regarding auditory hallucinations in different diagnostic groups, based on the presentations from the phenomenology, cognition, emotion, electrophysiology, neurochemical, neuroimaging, genetics, treatment, and computational modeling working groups. The second day comprised a discussion forum where the most important and urgent questions for future research were identified. The meeting recognized that a lot has been achieved in auditory hallucination research but that much still remains to be done. Here, we outline the top 16 goals for research on auditory hallucinations, which cover topics of conceptual importance, academic and treatment issues, scientific rigor, and cross-disciplinary collaboration. Concerted and coordinated actions will be required to make substantial research progress.
doi:10.1093/schbul/sbr181
PMCID: PMC3283162  PMID: 22223735
auditory hallucinations; meeting; phenomenology; cognition; electrophysiology; neuroimaging; treatment
2.  Comparing Cognitive and Somatic Symptoms of Depression in Myocardial Infarction Patients and Depressed Patients in Primary and Mental Health Care 
PLoS ONE  2013;8(1):e53859.
Depression in myocardial infarction patients is often a first episode with a late age of onset. Two studies that compared depressed myocardial infarction patients to psychiatric patients found similar levels of somatic symptoms, and one study reported lower levels of cognitive/affective symptoms in myocardial infarction patients. We hypothesized that myocardial infarction patients with first depression onset at a late age would experience fewer cognitive/affective symptoms than depressed patients without cardiovascular disease. Combined data from two large multicenter depression studies resulted in a sample of 734 depressed individuals (194 myocardial infarction, 214 primary care, and 326 mental health care patients). A structured clinical interview provided information about depression diagnosis. Summed cognitive/affective and somatic symptom levels were compared between groups using analysis of covariance, with and without adjusting for the effects of recurrence and age of onset. Depressed myocardial infarction and primary care patients reported significantly lower cognitive/affective symptom levels than mental health care patients (F (2,682) = 6.043, p = 0.003). Additional analyses showed that the difference between myocardial infarction and mental health care patients disappeared after adjusting for age of onset but not recurrence of depression. These group differences were also supported by data-driven latent class analyses. There were no significant group differences in somatic symptom levels. Depression after myocardial infarction appears to have a different phenomenology than depression observed in mental health care. Future studies should investigate the etiological factors predictive of symptom dimensions in myocardial infarction and late-onset depression patients.
doi:10.1371/journal.pone.0053859
PMCID: PMC3544747  PMID: 23342019
3.  Hemispheric Asymmetry for Affective Stimulus Processing in Healthy Subjects–A fMRI Study 
PLoS ONE  2012;7(10):e46931.
Background
While hemispheric specialization of language processing is well established, lateralization of emotion processing is still under debate. Several conflicting hypotheses have been proposed, including right hemisphere hypothesis, valence asymmetry hypothesis and region-specific lateralization hypothesis. However, experimental evidence for these hypotheses remains inconclusive, partly because direct comparisons between hemispheres are scarce.
Methods
The present fMRI study systematically investigated functional lateralization during affective stimulus processing in 36 healthy participants. We normalized our functional data on a symmetrical template to avoid confounding effects of anatomical asymmetries. Direct comparison of BOLD responses between hemispheres was accomplished taking two approaches: a hypothesis-driven region of interest analysis focusing on brain areas most frequently reported in earlier neuroimaging studies of emotion; and an exploratory whole volume analysis contrasting non-flipped with flipped functional data using paired t-test.
Results
The region of interest analysis revealed lateralization towards the left in the medial prefrontal cortex (BA 10) during positive stimulus processing; while negative stimulus processing was lateralized towards the right in the dorsolateral prefrontal cortex (BA 9 & 46) and towards the left in the amygdala and uncus. The whole brain analysis yielded similar results and, in addition, revealed lateralization towards the right in the premotor cortex (BA 6) and the temporo-occipital junction (BA 19 & 37) during positive stimulus processing; while negative stimulus processing showed lateralization towards the right in the temporo-parietal junction (BA 37,39,42) and towards the left in the middle temporal gyrus (BA 21).
Conclusion
Our data suggests region-specific functional lateralization of emotion processing. Findings show valence asymmetry for prefrontal cortical areas and left-lateralized negative stimulus processing in subcortical areas, in particular, amygdala and uncus.
doi:10.1371/journal.pone.0046931
PMCID: PMC3466188  PMID: 23056533
4.  Subjective Loudness and Reality of Auditory Verbal Hallucinations and Activation of the Inner Speech Processing Network 
Schizophrenia Bulletin  2010;37(5):1009-1016.
Background: One of the most influential cognitive models of auditory verbal hallucinations (AVH) suggests that a failure to adequately monitor the production of one’s own inner speech leads to verbal thought being misidentified as an alien voice. However, it is unclear whether this theory can explain the phenomenological complexity of AVH. We aimed to assess whether subjective perceptual and experiential characteristics may be linked to neural activation in the inner speech processing network. Methods: Twenty-two patients with schizophrenia and AVH underwent a 3-T functional magnetic resonance imaging scan, while performing a metrical stress evaluation task, which has been shown to activate both inner speech production and perception regions. Regions of interest (ROIs) comprising the putative inner speech network were defined using the Anatomical Automatic Labeling system. Correlations were calculated between scores on the “loudness” and “reality” subscales of the Auditory Hallucination Rating Scale (AHRS) and activation in these ROIs. Second, the AHRS subscales, and general AVH severity, indexed by the Positive and Negative Syndrome Scale, were correlated with a language lateralization index. Results: Louder AVH were associated with reduced task-related activity in bilateral angular gyrus, anterior cingulate gyrus, left inferior frontal gyrus, left insula, and left temporal cortex. This could potentially be due to a competition for shared neural resources. Reality on the other hand was found to be associated with reduced language lateralization. Conclusion: Strong activation of the inner speech processing network may contribute to the subjective loudness of AVH. However, a relatively increased contribution from right hemisphere language areas may be responsible for the more complex experiential characteristics, such as the nonself source or how real AVH are.
doi:10.1093/schbul/sbq007
PMCID: PMC3160225  PMID: 20164122
fMRI; schizophrenia; language; cognition
5.  Reduced Connectivity in the Self-Processing Network of Schizophrenia Patients with Poor Insight 
PLoS ONE  2012;7(8):e42707.
Lack of insight (unawareness of illness) is a common and clinically relevant feature of schizophrenia. Reduced levels of self-referential processing have been proposed as a mechanism underlying poor insight. The default mode network (DMN) has been implicated as a key node in the circuit for self-referential processing. We hypothesized that during resting state the DMN network would show decreased connectivity in schizophrenia patients with poor insight compared to patients with good insight. Patients with schizophrenia were recruited from mental health care centers in the north of the Netherlands and categorized in groups having good insight (n = 25) or poor insight (n = 19). All subjects underwent a resting state fMRI scan. A healthy control group (n = 30) was used as a reference. Functional connectivity of the anterior and posterior part of the DMN, identified using Independent Component Analysis, was compared between groups. Patients with poor insight showed lower connectivity of the ACC within the anterior DMN component and precuneus within the posterior DMN component compared to patients with good insight. Connectivity between the anterior and posterior part of the DMN was lower in patients than controls, and qualitatively different between the good and poor insight patient groups. As predicted, subjects with poor insight in psychosis showed decreased connectivity in DMN regions implicated in self-referential processing, although this concerned only part of the network. This finding is compatible with theories implying a role of reduced self-referential processing as a mechanism contributing to poor insight.
doi:10.1371/journal.pone.0042707
PMCID: PMC3415395  PMID: 22912723
6.  Social-Skills and Parental Training plus Standard Treatment versus Standard Treatment for Children with ADHD – The Randomised SOSTRA Trial 
PLoS ONE  2012;7(6):e37280.
Objective
To investigate the effects of social-skills training and parental training programme for children with attention deficit hyperactivity disorder (ADHD).
Methods
We conducted a randomized two-armed, parallel group, assessor-blinded superiority trial consisting of social-skills training plus parental training and standard treatment versus standard treatment alone. A sample size calculation showed at least 52 children should be included for the trial with follow up three and six months after randomization. The primary outcome measure was ADHD symptoms and secondary outcomes were social skills and emotional competences.
Results 56
children (39 boys, 17 girls, mean age 10.4 years, SD 1.31) with ADHD were randomized, 28 to the experimental group and 27 to the control group. Mixed-model analyses with repeated measures showed that the time course (y  =  a + bt + ct2) of ADHD symptoms (p = 0.40), social skills (p = 0.80), and emotional competences (p = 0.14) were not significantly influenced by the intervention.
Conclusions
Social skills training plus parental training did not show any significant benefit for children with attention deficit hyperactivity disorder when compared with standard treatment. More and larger randomized trials are needed.
Trial Registration
ClinicalTrials.gov NCT00937469
doi:10.1371/journal.pone.0037280
PMCID: PMC3380035  PMID: 22745657
7.  Brain Circuitries Involved in Semantic Interference by Demands of Emotional and Non-Emotional Distractors 
PLoS ONE  2012;7(5):e38155.
Background
Previous studies have indicated that the processes leading to the resolution of emotional and non-emotional interference conflicts are unrelated, involving separate networks. It is also known that conflict resolution itself suggests a considerable overlap of the networks. Our study is an attempt to examine how these findings may be related.
Methodology/Principal Findings
We used functional magnetic resonance imaging (fMRI) to study neural responses of 24 healthy subjects to emotional and non-emotional conflict paradigms involving the presentation of congruent and incongruent word-face pairs based on semantic incompatibility between targets and distractors. In the emotional task, the behavioral interference conflict was greater (compared to the non-emotional task) and was paralleled by involvement of the extrastriate visual and posterodorsal medial frontal cortices. In both tasks, we also observed a common network including the dorsal anterior cingulate, the supplemental motor area, the anterior insula and the inferior prefrontal cortex, indicating that these brain structures are markers of experienced conflict. However, the emotional task involved conflict-triggered networks to a considerably higher degree.
Conclusions/Significance
Our findings indicate that responses to emotional and non-emotional distractors involve the same systems, which are capable of flexible adjustments based on conflict demands. The function of systems related to conflict resolution is likely to be adjusted on the basis of an evaluation process that primarily involves the extrastriate visual cortex, with target playing a significant role.
doi:10.1371/journal.pone.0038155
PMCID: PMC3362560  PMID: 22666470
8.  The Sound of Feelings: Electrophysiological Responses to Emotional Speech in Alexithymia 
PLoS ONE  2012;7(5):e36951.
Background
Alexithymia is a personality trait characterized by difficulties in the cognitive processing of emotions (cognitive dimension) and in the experience of emotions (affective dimension). Previous research focused mainly on visual emotional processing in the cognitive alexithymia dimension. We investigated the impact of both alexithymia dimensions on electrophysiological responses to emotional speech in 60 female subjects.
Methodology
During unattended processing, subjects watched a movie while an emotional prosody oddball paradigm was presented in the background. During attended processing, subjects detected deviants in emotional prosody. The cognitive alexithymia dimension was associated with a left-hemisphere bias during early stages of unattended emotional speech processing, and with generally reduced amplitudes of the late P3 component during attended processing. In contrast, the affective dimension did not modulate unattended emotional prosody perception, but was associated with reduced P3 amplitudes during attended processing particularly to emotional prosody spoken in high intensity.
Conclusions
Our results provide evidence for a dissociable impact of the two alexithymia dimensions on electrophysiological responses during the attended and unattended processing of emotional prosody. The observed electrophysiological modulations are indicative of a reduced sensitivity to the emotional qualities of speech, which may be a contributing factor to problems in interpersonal communication associated with alexithymia.
doi:10.1371/journal.pone.0036951
PMCID: PMC3352858  PMID: 22615853
9.  Can Variation in Hypothalamic-Pituitary-Adrenal (HPA)-Axis Activity Explain the Relationship between Depression and Cognition in Bipolar Patients? 
PLoS ONE  2012;7(5):e37119.
Background
Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is thought to be associated with more mood symptoms and worse cognitive functioning. This study examined whether variation in HPA axis activity underlies the association between mood symptoms and cognitive functioning.
Methodology/Principal Findings
In 65 bipolar patients cognitive functioning was measured in domains of psychomotor speed, speed of information processing, attentional switching, verbal memory, visual memory, executive functioning and an overall mean score. Severity of depression was assessed by the Inventory of Depressive Symptomatology-self rating version. Saliva cortisol measurements were performed to calculate HPA axis indicators: cortisol awakening response, diurnal slope, the evening cortisol level and the cortisol suppression on the dexamethasone suppression test. Regression analyses of depressive symptoms and cognitive functioning on each HPA axis indicator were performed. In addition we calculated percentages explanation of the association between depressive symptoms and cognition by HPA axis indicators. Depressive symptoms were associated with dysfunction in psychomotor speed, attentional switching and the mean score, as well as with attenuation in diurnal slope value. No association was found between HPA axis activity and cognitive functioning and HPA axis activity did not explain the associations between depressive symptoms and cognition.
Conclusions/Significance
As our study is the first one in this field specific for bipolar patients and changes in HPA-axis activity did not seem to explain the association between severity of depressive symptoms and cognitive functioning in bipolar patients, future studies are needed to evaluate other factors that might explain this relationship.
doi:10.1371/journal.pone.0037119
PMCID: PMC3351438  PMID: 22606339
10.  Neuroimaging Evidence for Processes Underlying Repetition of Ignored Stimuli 
PLoS ONE  2012;7(5):e36089.
Prolonged response times are observed with targets having been presented as distractors immediately before, called negative priming effect. Among others, inhibitory and retrieval processes have been suggested underlying this behavioral effect. As those processes would involve different neural activation patterns, a functional magnetic resonance imaging (fMRI) study including 28 subjects was conducted. Two tasks were used to investigate stimulus repetition effects. One task focused on target location, the other on target identity. Both tasks are known to elicit the expected response time effects. However, there is less agreement about the relationship of those tasks with the explanatory accounts under consideration. Based on within-subject comparisons we found clear differences between the experimental repetition conditions and the neutral control condition on neural level for both tasks. Hemodynamic fronto-striatal activation patterns occurred for the location-based task favoring the selective inhibition account. Hippocampal activation found for the identity-based task suggests an assignment to the retrieval account; however, this task lacked a behavioral effect.
doi:10.1371/journal.pone.0036089
PMCID: PMC3341391  PMID: 22563478
11.  Adolescent Binge Drinking Leads to Changes in Alcohol Drinking, Anxiety, and Amygdalar Corticotropin Releasing Factor Cells in Adulthood in Male Rats 
PLoS ONE  2012;7(2):e31466.
Heavy episodic drinking early in adolescence is associated with increased risk of addiction and other stress-related disorders later in life. This suggests that adolescent alcohol abuse is an early marker of innate vulnerability and/or binge exposure impacts the developing brain to increase vulnerability to these disorders in adulthood. Animal models are ideal for clarifying the relationship between adolescent and adult alcohol abuse, but we show that methods of involuntary alcohol exposure are not effective. We describe an operant model that uses multiple bouts of intermittent access to sweetened alcohol to elicit voluntary binge alcohol drinking early in adolescence (∼postnatal days 28–42) in genetically heterogeneous male Wistar rats. We next examined the effects of adolescent binge drinking on alcohol drinking and anxiety-like behavior in dependent and non-dependent adult rats, and counted corticotropin-releasing factor (CRF) cell in the lateral portion of the central amygdala (CeA), a region that contributes to regulation of anxiety- and alcohol-related behaviors. Adolescent binge drinking did not alter alcohol drinking under baseline drinking conditions in adulthood. However, alcohol-dependent and non-dependent adult rats with a history of adolescent alcohol binge drinking did exhibit increased alcohol drinking when access to alcohol was intermittent. Adult rats that binged alcohol during adolescence exhibited increased exploration on the open arms of the elevated plus maze (possibly indicating either decreased anxiety or increased impulsivity), an effect that was reversed by a history of alcohol dependence during adulthood. Finally, CRF cell counts were reduced in the lateral CeA of rats with adolescent alcohol binge history, suggesting semi-permanent changes in the limbic stress peptide system with this treatment. These data suggest that voluntary binge drinking during early adolescence produces long-lasting neural and behavioral effects with implications for anxiety and alcohol use disorders.
doi:10.1371/journal.pone.0031466
PMCID: PMC3275622  PMID: 22347484
12.  Brain Training Game Improves Executive Functions and Processing Speed in the Elderly: A Randomized Controlled Trial 
PLoS ONE  2012;7(1):e29676.
Background
The beneficial effects of brain training games are expected to transfer to other cognitive functions, but these beneficial effects are poorly understood. Here we investigate the impact of the brain training game (Brain Age) on cognitive functions in the elderly.
Methods and Results
Thirty-two elderly volunteers were recruited through an advertisement in the local newspaper and randomly assigned to either of two game groups (Brain Age, Tetris). This study was completed by 14 of the 16 members in the Brain Age group and 14 of the 16 members in the Tetris group. To maximize the benefit of the interventions, all participants were non-gamers who reported playing less than one hour of video games per week over the past 2 years. Participants in both the Brain Age and the Tetris groups played their game for about 15 minutes per day, at least 5 days per week, for 4 weeks. Each group played for a total of about 20 days. Measures of the cognitive functions were conducted before and after training. Measures of the cognitive functions fell into four categories (global cognitive status, executive functions, attention, and processing speed). Results showed that the effects of the brain training game were transferred to executive functions and to processing speed. However, the brain training game showed no transfer effect on any global cognitive status nor attention.
Conclusions
Our results showed that playing Brain Age for 4 weeks could lead to improve cognitive functions (executive functions and processing speed) in the elderly. This result indicated that there is a possibility which the elderly could improve executive functions and processing speed in short term training. The results need replication in large samples. Long-term effects and relevance for every-day functioning remain uncertain as yet.
Trial Registration
UMIN Clinical Trial Registry 000002825
doi:10.1371/journal.pone.0029676
PMCID: PMC3256163  PMID: 22253758
13.  Mood Induction in Depressive Patients: A Comparative Multidimensional Approach 
PLoS ONE  2012;7(1):e30016.
Anhedonia, reduced positive affect and enhanced negative affect are integral characteristics of major depressive disorder (MDD). Emotion dysregulation, e.g. in terms of different emotion processing deficits, has consistently been reported. The aim of the present study was to investigate mood changes in depressive patients using a multidimensional approach for the measurement of emotional reactivity to mood induction procedures. Experimentally, mood states can be altered using various mood induction procedures. The present study aimed at validating two different positive mood induction procedures in patients with MDD and investigating which procedure is more effective and applicable in detecting dysfunctions in MDD. The first procedure relied on the presentation of happy vs. neutral faces, while the second used funny vs. neutral cartoons. Emotional reactivity was assessed in 16 depressed and 16 healthy subjects using self-report measures, measurements of electrodermal activity and standardized analyses of facial responses. Positive mood induction was successful in both procedures according to subjective ratings in patients and controls. In the cartoon condition, however, a discrepancy between reduced facial activity and concurrently enhanced autonomous reactivity was found in patients. Relying on a multidimensional assessment technique, a more comprehensive estimate of dysfunctions in emotional reactivity in MDD was available than by self-report measures alone and this was unsheathed especially by the mood induction procedure relying on cartoons. The divergent facial and autonomic responses in the presence of unaffected subjective reactivity suggest an underlying deficit in the patients' ability to express the felt arousal to funny cartoons. Our results encourage the application of both procedures in functional imaging studies for investigating the neural substrates of emotion dysregulation in MDD patients. Mood induction via cartoons appears to be superior to mood induction via faces and autobiographical material in uncovering specific emotional dysfunctions in MDD.
doi:10.1371/journal.pone.0030016
PMCID: PMC3253810  PMID: 22253861
14.  Insight in Psychosis: Relationship With Neurocognition, Social Cognition and Clinical Symptoms Depends on Phase of Illness 
Schizophrenia Bulletin  2010;37(1):29-37.
Reduced insight has been reported in a majority of patients with a psychotic disorder. Most studies have focused on associations with neurocognition, neglecting relations with social cognition. Two hundred seventy patients with nonaffective psychosis participated in this study, which was part of the GROUP (Genetic Risk and OUtcome of Psychosis)-project. Linear regression analyses were performed to investigate the predictive value of composite measures of neurocognition, social cognition, and clinical symptoms. The moderating effect of phase of illness was also investigated. Insight was measured with a composite measure, based on the insight item on the Positive And Negative Syndrome Scale (PANSS) and the Birchwood Insight Scale (BIS). Insight on the BIS and the PANSS correlated significantly (r = .406). All independent variables correlated with the insight composite measure. The additional effect of social cognition and clinical symptoms were both significant. Phase of illness was a moderating variable: In patients with recent-onset psychosis (ROP), none of the independent variables explained variance. In patients with multiple episode or chronic psychosis, both social cognition and clinical symptoms had additional effects and explained insight, along with neurocognition, together explaining 20% of the variance. These findings indicate that multiple factors are associated with insight in psychosis. Specifically, associations of insight with social cognitive and clinical symptom measures were observed, over and above a contribution of neurocognition. This supports theories that imply a role for deficient emotion recognition and mentalizing in reduced insight. Further studies need to investigate insight in ROP into more detail.
doi:10.1093/schbul/sbq133
PMCID: PMC3004183  PMID: 21097989
insight; awareness; schizophrenia; neuropsychology; GROUP
15.  How Doctors Generate Diagnostic Hypotheses: A Study of Radiological Diagnosis with Functional Magnetic Resonance Imaging 
PLoS ONE  2011;6(12):e28752.
Background
In medical practice, diagnostic hypotheses are often made by physicians in the first moments of contact with patients; sometimes even before they report their symptoms. We propose that generation of diagnostic hypotheses in this context is the result of cognitive processes subserved by brain mechanisms that are similar to those involved in naming objects or concepts in everyday life.
Methodology and Principal Findings
To test this proposal we developed an experimental paradigm with functional magnetic resonance imaging (fMRI) using radiological diagnosis as a model. Twenty-five radiologists diagnosed lesions in chest X-ray images and named non-medical targets (animals) embedded in chest X-ray images while being scanned in a fMRI session. Images were presented for 1.5 seconds; response times (RTs) and the ensuing cortical activations were assessed. The mean response time for diagnosing lesions was 1.33 (SD ±0.14) seconds and 1.23 (SD ±0.13) seconds for naming animals. 72% of the radiologists reported cogitating differential diagnoses during trials (3.5 seconds). The overall pattern of cortical activations was remarkably similar for both types of targets. However, within the neural systems shared by both stimuli, activation was significantly greater in left inferior frontal sulcus and posterior cingulate cortex for lesions relative to animals.
Conclusions
Generation of diagnostic hypotheses and differential diagnoses made through the immediate visual recognition of clinical signs can be a fast and automatic process. The co-localization of significant brain activation for lesions and animals suggests that generating diagnostic hypotheses for lesions and naming animals are served by the same neuronal systems. Nevertheless, diagnosing lesions was cognitively more demanding and associated with more activation in higher order cortical areas. These results support the hypothesis that medical diagnoses based on prompt visual recognition of clinical signs and naming in everyday life are supported by similar brain systems.
doi:10.1371/journal.pone.0028752
PMCID: PMC3237491  PMID: 22194902
16.  Individual differences in dispositional mindfulness and brain activity involved in reappraisal of emotion 
The regulation of negative emotion through reappraisal has been shown to induce increased prefrontal activity and decreased amygdala activity. Individual differences in dispositional mindfulness reflect differences in typical recognition, detachment and regulation of current experience, thought to also operate as top–down control mechanism. We sought to investigate whether such individual differences would be associated with brain activity elicited during reappraisal of negative emotion. Eighteen healthy participants completed a functional magnetic resonance imaging task that involved attending to or reappraising negative stimuli, and provided emotion experience ratings after each trial. Dispositional mindfulness was assessed with a self-report questionnaire. Reappraisal induced activity in a brain network involving predominantly dorsal portions of the prefrontal cortex, replicating previous studies. A voxelwise regression analysis showed that individual differences in the tendency to be mindful predicted activity in neural regions underlying reappraisal, with dorsomedial prefrontal cortex activation increasing with more mindfulness traits. Notably, this prefrontal activation was inversely correlated with the amygdala response to negative scenes, further supporting its role in down-regulating emotion-generation regions. These findings suggest that individual differences in dispositional mindfulness, which reflect the tendency to recognize and regulate current states, may modulate activity in neural systems involved in the effective cognitive control of negative emotion.
doi:10.1093/scan/nsq006
PMCID: PMC2999757  PMID: 20147457
emotion regulation; fMRI; individual differences; mindfulness; prefrontal cortex
17.  Capacity-Speed Relationships in Prefrontal Cortex 
PLoS ONE  2011;6(11):e27504.
Working memory (WM) capacity and WM processing speed are simple cognitive measures that underlie human performance in complex processes such as reasoning and language comprehension. These cognitive measures have shown to be interrelated in behavioral studies, yet the neural mechanism behind this interdependence has not been elucidated. We have carried out two functional MRI studies to separately identify brain regions involved in capacity and speed. Experiment 1, using a block-design WM verbal task, identified increased WM capacity with increased activity in right prefrontal regions, and Experiment 2, using a single-trial WM verbal task, identified increased WM processing speed with increased activity in similar regions. Our results suggest that right prefrontal areas may be a common region interlinking these two cognitive measures. Moreover, an overlap analysis with regions associated with binding or chunking suggest that this strategic memory consolidation process may be the mechanism interlinking WM capacity and WM speed.
doi:10.1371/journal.pone.0027504
PMCID: PMC3223164  PMID: 22132105
18.  Inner Speech during Silent Reading Reflects the Reader's Regional Accent 
PLoS ONE  2011;6(10):e25782.
While reading silently, we often have the subjective experience of inner speech. However, there is currently little evidence regarding whether this inner voice resembles our own voice while we are speaking out loud. To investigate this issue, we compared reading behaviour of Northern and Southern English participants who have differing pronunciations for words like ‘glass’, in which the vowel duration is short in a Northern accent and long in a Southern accent. Participants' eye movements were monitored while they silently read limericks in which the end words of the first two lines (e.g., glass/class) would be pronounced differently by Northern and Southern participants. The final word of the limerick (e.g., mass/sparse) then either did or did not rhyme, depending on the reader's accent. Results showed disruption to eye movement behaviour when the final word did not rhyme, determined by the reader's accent, suggesting that inner speech resembles our own voice.
doi:10.1371/journal.pone.0025782
PMCID: PMC3198452  PMID: 22039423
19.  REFLEX, a social-cognitive group treatment to improve insight in schizophrenia: study protocol of a multi-center RCT 
BMC Psychiatry  2011;11:161.
Background
Insight is impaired in a majority of people with schizophrenia. Impaired insight is associated with poorer outcomes of the disorder. Based on existing literature, we developed a model that explains which processes may possibly play a role in impaired insight. This model was the starting point of the development of REFLEX: a brief psychosocial intervention to improve insight in schizophrenia. REFLEX is a 12-sessions group training, consisting of three modules of four sessions each. Modules in this intervention are: "coping with stigma", "you and your personal narrative", and "you in the present".
Methods/Design
REFLEX is currently evaluated in a multicenter randomized controlled trial. Eight mental health institutions in the Netherlands participate in this evaluation. Patients are randomly assigned to either REFLEX or an active control condition, existing of cognitive remediation exercises in a group. In a subgroup of patients, fMRI scans are made before and after training in order to assess potential haemodynamic changes associated with the effects of the training.
Discussion
REFLEX is one of the few interventions aiming specifically to improving insight in schizophrenia and has potential value for improving insight. Targeting insight in schizophrenia is a complex task, that comes with several methodological issues. These issues are addressed in the discussion of this paper.
Trial registration
Current Controlled Trials: ISRCTN50247539
doi:10.1186/1471-244X-11-161
PMCID: PMC3222612  PMID: 21975132
schizophrenia; insight; treatment; self-reflection; self-stigma; perspective-taking
20.  Down-Regulation of Negative Emotional Processing by Transcranial Direct Current Stimulation: Effects of Personality Characteristics 
PLoS ONE  2011;6(7):e22812.
Evidence from neuroimaging and electrophysiological studies indicates that the left dorsolateral prefrontal cortex (DLPFC) is a core region in emotional processing, particularly during down-regulation of negative emotional conditions. However, emotional regulation is a process subject to major inter-individual differences, some of which may be explained by personality traits. In the present study we used transcranial direct current stimulation (tDCS) over the left DLPFC to investigate whether transiently increasing the activity of this region resulted in changes in the ratings of positive, neutral and negative emotional pictures. Results revealed that anodal, but not cathodal, tDCS reduced the perceived degree of emotional valence for negative stimuli, possibly due to an enhancement of cognitive control of emotional expression. We also aimed to determine whether personality traits (extraversion and neuroticism) might condition the impact of tDCS. We found that individuals with higher scores on the introversion personality dimension were more permeable than extraverts to the modulatory effects of the stimulation. The present study underlines the role of the left DLPFC in emotional regulation, and stresses the importance of considering individual personality characteristics as a relevant variable, although replication is needed given the limited sample size of our study.
doi:10.1371/journal.pone.0022812
PMCID: PMC3146508  PMID: 21829522
21.  Dyskinesia and Parkinsonism in Antipsychotic-Naive Patients With Schizophrenia, First-Degree Relatives and Healthy Controls: A Meta-analysis 
Schizophrenia Bulletin  2008;36(4):723-731.
Background: Several studies have reported the presence of dyskinesia and parkinsonism in antipsychotic-naive patients with schizophrenia as well as in their first-degree relatives. These movement disorders may therefore form an integral part of the illness and its (genetic) liability. Method: A systematic search was conducted in the Medline, EMBASE, and PsychINFO databases to identify studies reporting on dyskinesia and parkinsonism assessed in antipsychotic-naive patients with schizophrenia (n = 213) and controls (n = 242) and separately in nonill first-degree relatives (n = 395) and controls (n = 379). Effect sizes were pooled using random-effect models to calculate odds ratios (ORs) to compare the risk of these movement disorders among patients and healthy relatives each with matched controls. Results: Antipsychotic-naive schizophrenia was found to be strongly associated with dyskinesia (OR: 3.59, 95% confidence interval [CI]: 1.53–8.41) and parkinsonism (OR: 5.32, 95% CI: 1.75–16.23) compared with controls. Dyskinesia and parkinsonism were also significantly more prevalent in healthy first-degree relatives of patients with schizophrenia as compared with healthy controls (OR: 1.38, 95% CI: 1.06–1.81, and OR: 1.37, 95% CI: 1.05–1.79, respectively).Conclusion: The results suggest that movement disorders, and by inference abnormalities in the nigrostriatal pathway, are not only associated with schizophrenia itself but may also be related to the (genetic) risk of developing the disease.
doi:10.1093/schbul/sbn146
PMCID: PMC2894597  PMID: 18990712
spontaneous; movement disorders; vulnerability; family; nonaffective psychosis
22.  Hearing Feelings: Affective Categorization of Music and Speech in Alexithymia, an ERP Study 
PLoS ONE  2011;6(5):e19501.
Background
Alexithymia, a condition characterized by deficits in interpreting and regulating feelings, is a risk factor for a variety of psychiatric conditions. Little is known about how alexithymia influences the processing of emotions in music and speech. Appreciation of such emotional qualities in auditory material is fundamental to human experience and has profound consequences for functioning in daily life. We investigated the neural signature of such emotional processing in alexithymia by means of event-related potentials.
Methodology
Affective music and speech prosody were presented as targets following affectively congruent or incongruent visual word primes in two conditions. In two further conditions, affective music and speech prosody served as primes and visually presented words with affective connotations were presented as targets. Thirty-two participants (16 male) judged the affective valence of the targets. We tested the influence of alexithymia on cross-modal affective priming and on N400 amplitudes, indicative of individual sensitivity to an affective mismatch between words, prosody, and music. Our results indicate that the affective priming effect for prosody targets tended to be reduced with increasing scores on alexithymia, while no behavioral differences were observed for music and word targets. At the electrophysiological level, alexithymia was associated with significantly smaller N400 amplitudes in response to affectively incongruent music and speech targets, but not to incongruent word targets.
Conclusions
Our results suggest a reduced sensitivity for the emotional qualities of speech and music in alexithymia during affective categorization. This deficit becomes evident primarily in situations in which a verbalization of emotional information is required.
doi:10.1371/journal.pone.0019501
PMCID: PMC3090419  PMID: 21573026
23.  Apathy, but Not Depression, Reflects Inefficient Cognitive Strategies in Parkinson's Disease 
PLoS ONE  2011;6(3):e17846.
Background
The relationship between apathy, depression and cognitive impairment in Parkinson's disease (PD) is still controversial. The objective of this study is to investigate whether apathy and depression are associated with inefficient cognitive strategies in PD.
Methods
In this prospective clinical cohort study conducted in a university-based clinical and research movement disorders center we studied 48 PD patients. Based on clinical evaluation, they were classified in two groups: PD with apathy (PD-A group, n = 23) and PD without apathy (PD-NA group, n = 25). Patients received clinical and neuropsychological evaluations. The clinical evaluation included: Apathy Evaluation Scale-patient version, Hamilton Depression Rating Scale-17 items, the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr staging system; the neuropsychological evaluation explored speed information processing, attention, working memory, executive function, learning abilities and memory, which included several measures of recall (immediate free, short delay free, long delay free and cued, and total recall).
Findings
PD-A and PD-NA groups did not differ in age, disease duration, treatment, and motor condition, but differed in recall (p<0.001) and executive tasks (p<0.001). Immediate free recall had the highest predictive value for apathy (F =  10.94; p = 0.002). Depression and apathy had a weak correlation (Pearson index  = 0.3; p<0.07), with three items of the depression scale correlating with apathy (Pearson index between .3 and.4; p<0.04). The depressed and non-depressed PD patients within the non-apathetic group did not differ.
Conclusion
Apathy, but not depression, is associated with deficit in implementing efficient cognitive strategies. As the implementation of efficient strategies relies on the fronto-striatal circuit, we conclude that apathy, unlike depression, is an early expression of executive impairment in PD.
doi:10.1371/journal.pone.0017846
PMCID: PMC3060914  PMID: 21437255
24.  Stress Strengthens Memory of First Impressions of Others' Positive Personality Traits 
PLoS ONE  2011;6(1):e16389.
Encounters with strangers bear potential for social conflict and stress, but also allow the formation of alliances. First impressions of other people play a critical role in the formation of alliances, since they provide a learned base to infer the other's future social attitude. Stress can facilitate emotional memories but it is unknown whether stress strengthens our memory for newly acquired impressions of other people's personality traits. To answer this question, we subjected 60 students (37 females, 23 males) to an impression-formation task, viewing portraits together with brief positive vs. negative behavior descriptions, followed by a 3-min cold pressor stress test or a non-stressful control procedure. The next day, novel and old portraits were paired with single trait adjectives, the old portraits with a trait adjective matching the previous day's behavior description. After a filler task, portraits were presented again and subjects were asked to recall the trait adjective. Cued recall was higher for old (previously implied) than the novel portraits' trait adjectives, indicating validity of the applied test procedures. Overall, recall rate of implied trait adjectives did not differ between the stress and the control group. However, while the control group showed a better memory performance for others' implied negative personality traits, the stress group showed enhanced recall for others' implied positive personality traits. This result indicates that post-learning stress affects consolidation of first impressions in a valence-specific manner. We propose that the stress-induced strengthening of memory of others' positive traits forms an important cue for the formation of alliances in stressful conditions.
doi:10.1371/journal.pone.0016389
PMCID: PMC3027645  PMID: 21298099
25.  “Keep Calm and Carry On”: Structural Correlates of Expressive Suppression of Emotions 
PLoS ONE  2011;6(1):e16569.
There is a growing appreciation that individuals differ systematically in their use of particular emotion regulation strategies. Our aim was to examine the structural correlates of the habitual use of expressive suppression of emotions. Based on our previous research on the voluntary suppression of actions we expected this response-focused emotion regulation strategy to be associated with increased grey matter volume in the dorsomedial prefrontal cortex (dmPFC). On high-resolution MRI scans of 42 college-aged healthy adults we computed optimized voxel-based-morphometry (VBM) to explore the correlation between grey matter volume and inter-individual differences in the tendency to suppress the expression of emotions assessed by means of the Emotion Regulation Questionnaire (Gross & John, 2003). We found a positive correlation between the habitual use of expressive suppression as an emotion regulation strategy and grey matter volume in the dmPFC. No other brain area showed a significant positive or negative correlation with the Emotion Regulation Questionnaire scores. The association between the suppression of expression of emotions and volume in the dmPFC supports the behavioural stability and biological foundation of the concept of this particular emotion regulation strategy within an age-homogenous sample of adults.
doi:10.1371/journal.pone.0016569
PMCID: PMC3027672  PMID: 21298057

Results 1-25 (61)