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Original Research ARTICLE
Reduction in ventral striatal activity when anticipating a reward in depression and schizophrenia: a replicated cross-diagnostic finding
- 1Department of Psychiatry, University of Cambridge, Cambridge, UK
- 2Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, UK
- 3Cambridgeshire and Peterborough NHS Foundation Trust, UK
- 4Psychiatric Liaison Service, Ipswich Hospital, Norfolk and Suffolk NHS Foundation Trust, UK
- 5Department of Psychology, University of Cambridge, Cambridge, UK
- 6Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK
In the research domain framework (RDoC), dysfunctional reward expectation has been proposed to be a cross-diagnostic domain in psychiatry, which may contribute to symptoms common to various neuropsychiatric conditions, such as anhedonia or apathy/avolition. We used a modified version of the Monetary Incentive Delay (MID) paradigm to obtain functional MRI images from 22 patients with schizophrenia, 24 with depression and 21 controls. Anhedonia and other symptoms of depression, and overall positive and negative symptomatology were also measured. We hypothesized that the two clinical groups would have a reduced activity in the ventral striatum when anticipating reward (compared to anticipation of a neutral outcome) and that striatal activation would correlate with clinical measures of motivational problems and anhedonia. Results were consistent with the first hypothesis: two clusters in both the left and right ventral striatum were found to differ between the groups in reward anticipation. Post-hoc analysis showed that this was due to higher activation in the controls compared to the schizophrenia and the depression groups in the right ventral striatum, with activation differences between depression and controls also seen in the left ventral striatum. No differences were found between the two patient groups, and there were no areas of abnormal cortical activation in either group that survived correction for multiple comparisons. Reduced ventral striatal activity was related to greater anhedonia and overall depressive symptoms in the schizophrenia group, but not in the participants with depression. Findings are discussed in relation to previous literature but overall are supporting evidence of reward system dysfunction across the neuropsychiatric continuum, even if the specific clinical relevance is still not fully understood. We also discuss how the RDoC approach may help to solve some of the replication problems in psychiatric fMRI research.
Current psychiatric diagnostic manuals divide psychopathology into separate diagnostic categories based in the co-occurrence of signs and symptoms rather than on the basis of underlying physiology. However, within each of these categories there is great heterogeneity in the type and severity of symptoms and, similarly, it is common to have overlap in symptoms between the different diagnoses (Lilienfeld, 2014). Recently the Research Domain Criteria (RDoC) framework has been proposed as an alternative framework in order to advance the understanding of mental disorders (Insel et al., 2010). The specific aim of the RDoC project is to increase research that validates new cross-diagnostic dimensions and biological and behavioral measures to carry out better classifications of mental problems. To achieve this improved classification, the RDoC group has proposed a set of five domains or functional systems that are typically affected in psychopathology, and seven units of analysis at which these five constructs can be studied, thus creating a 2-dimensional matrix that can guide research. Additionally, this matrix also includes a further column of “paradigms,” that is, tools that can be used to measure abnormalities in the domains (Cuthbert, 2014a).
Schizophrenia patients, as defined in current diagnostic manuals, typically suffer from symptoms of psychosis (delusions, hallucinations, and disordered behavior, thought, and speech), whereas depression patients are diagnosed on the basis of low mood, anhedonia, and accompanying physical symptoms such as reduced energy. However, psychotic symptoms can appear in the course of a major depressive episode and low mood, blunted affect, alogia, or anhedonia are also characteristic of schizophrenia (Bedwell et al., 2014). Moreover, the boundary between depression and schizophrenia is frequently unclear, and the diagnosis of schizoaffective disorder is often used in cases in which a patient has features of mood disorder and schizophrenia. Additionally, the existence of mild symptoms of psychosis in young people, previously thought to be confer a high risk for schizophrenia, has been shown to be a more general risk factor for different psychiatric disorders including depression (Murray and Jones, 2012; Hui et al., 2013).
At the cognitive-behavioral construct level, disrupted reward processing has been implicated in both schizophrenia and depression. Moreover, it has been suggested that whereas reward receipt may only be subtly affected in both disorders (Cohen and Minor, 2010; Arrondo et al., 2015), the anticipation of reward (Juckel et al., 2006b; Sherdell et al., 2012) and its motivational aspects (e.g., the effort that a subject is willing to make to get it) (Treadway et al., 2012; Barch et al., 2014; Gard et al., 2014) may be markedly dysfunctional in schizophrenia and in depression (for in-depth reviews of the issue see Barch and Dowd, 2010; Kring and Caponigro, 2010; Treadway and Zald, 2011; Der-Avakian and Markou, 2012; Argyropoulos and Nutt, 2013; Kring and Barch, 2014; Whitton et al., 2015). Abnormalities in reward prediction error signaling in the striatum in schizophrenia are also a well-known finding that could be involved in the pathogenesis of psychotic symptoms (Fletcher and Frith, 2009; Ziauddeen and Murray, 2010). Similar changes have also been found in depression (Kumar et al., 2008), and indeed when participants in both patient groups were studied within the same prediction error learning paradigm researchers found brain activation differences between controls and the two groups of patients (Gradin et al., 2011).
Hence, consistent with the RDoC proposal, there appears to be dimensional continuity between schizophrenia and depression with respect to at least some aspects of reward processing. According to the RDoC matrix some of the stated similarities would fit in the Positive Valence systems domain, which is defined as involving “Systems primarily responsible for responses to positive motivational situations or contexts, such as reward seeking, consummatory behavior, and reward/habit learning,” and specifically the Expectancy/Reward Prediction Error component within the Approach Motivation subsystem. The ventral striatum/nucleus accumbens is considered a key area involved in the processing of reward anticipation, and the main neurotransmitter thought to be involved in predicting rewards and learning from them is dopamine. The Monetary Incentive Delay task (MID) is a paradigm that it is well-known to elicit strong striatal activations related to the expectation and salience of rewards (Knutson et al., 2001). It has been widely used both in the healthy population and in patients with neuropsychiatric symptoms, with several results pointing toward both schizophrenia and depression patients having a decreased activity in the striatum when anticipating rewards (Juckel et al., 2006a,b; Nielsen et al., 2012; Stoy et al., 2012). Moreover, reanalyzing data from a set of studies, Hägele and colleagues showed that depression, schizophrenia and alcohol disorders were all associated with reduced activity in the right ventral striatum with this effect correlated with depressive symptoms as measured by the Beck Depression Inventory (Hägele et al., 2015). However, given that patient groups were not matched to each other or to controls in age and gender in the study by Hägele and colleagues we sought to replicate and extend it using a specifically-designed study with matched groups; we also wished to relate neural responses to additional key symptoms, as previous work has indicated that ventral striatum (de)activation could also relate to other symptoms such as anhedonia (Simon et al., 2010; Stoy et al., 2012) and more generally, to positive (Nielsen et al., 2012), and negative (Juckel et al., 2006a; Waltz et al., 2009) symptoms.
In brief, we compared patients with depression and schizophrenia to healthy controls in a Monetary Incentive Delay task. The aim was to further understand how perturbation of the anticipation of reward relates to anhedonia, depression, and overall positive and negative symptoms. Consistent with the results of Hägele and colleagues, we hypothesized that the two clinical groups would have a reduced activity in the ventral striatum when anticipating reward and that the striatal activation would correlate with clinical measures (in a direction such that patients with the least activation would have the more pronounced psychopathology).
Materials and Methods
Sixty seven participants were recruited for the study, of whom 22 had a diagnosis of schizophrenia, 24 a diagnosis of major depressive disorder and 21 were healthy volunteers. DSM-IV criteria were used for group classification. Inclusion criteria were to be aged between 18 and 65 and speak English proficiently. Exclusion criteria were any contraindication for entering a MRI scan and history of neurological disorder, physical illness, and alcohol or drug dependence. Participants from both clinical groups had subjective symptoms of anhedonia. Demographic and clinical details of participants are provided in Table 1. Patients with schizophrenia were recruited through psychiatric community services of the Cambridgeshire and Peterborough NHS Foundation Trust. Patients with depression were recruited through psychiatric and psychological community services of the Cambridgeshire and Peterborough NHS Foundation Trust, and through public advertisement. Diagnoses for patients from psychiatric services of the Cambridgeshire and Peterborough NHS Foundation Trust and suitability for the study were confirmed by the review of all available clinical and anamnestic information by each individual's psychiatrist (an experienced psychiatrist with several years of postgraduate experience who had passed the membership examination of the Royal College of Psychiatrists). Diagnoses for patients recruited from psychology services or advertisement were confirmed by a psychiatric interview including PANSS (Kay et al., 1987) and assessment with the Mini-International Psychiatric Inventory (Sheehan et al., 1998) the interview was conducted either by an experienced research psychiatrist with several years of postgraduate experience who had passed the membership examination of the Royal College of Psychiatrists or by a registered clinical psychologist with several years postgraduate experience.
Thirteen of the depressed participants were taking antidepressant medication: citalopram 30–60 mg daily, mirtazapine 30–45 mg, and venlafaxine 75–225 mg. All patients with schizophrenia were taking atypical antipsychotic medication (specifically clozapine, aripiprazole, risperidone, quetiapine, or olanzapine); two patients were taking a combination of typical and atypical medication. The mean chlorpromazine equivalent dose was 401.24 (sd 91.43) mg/day (Kroken et al., 2009). Eight patients with schizophrenia were additionally taking antidepressant medication: citalopram 20–40 mg, fluoxetine 20 mg, mirtazapine 45 mg, venlafaxine 150–225 mg.
The study was conducted at University of Cambridge (Wolfson Brain Imaging Centre and Department of Psychiatry). All participants were evaluated using the following clinical scales: Brief Psychiatric Rating Scale (BPRS, Overall and Gorham, 1962); Positive and Negative Syndrome Scale (PANSS, Kay et al., 1987); Scale for the Assessment of Negative Symptoms Beck Depression Inventory, (SANS, BDI, Beck et al., 1996); Snaith–Hamilton Pleasure Scale (SHAPS, Snaith et al., 1995); and the Temporal Experience of Pleasure scale–TEPS, (Gard et al., 2006). Scales were selected to measure constructs with a possible striatal neural substrate and also according to previous findings of significant correlations with ventral striatum activity during the MID. The Cattell Culture Fair Intelligence Test (CFIT) was used to measure IQ (Cattell et al., 1973).
The study was approved by the Cambridgeshire 3 National Health Service research ethics committee. Written informed consent was obtained from all participants prior to participation.
The fMRI paradigm was a variation of the Monetary Incentive Delay (MID) task (Figure 1). It used an event-related design in which stimuli served as cues signaling the subsequent outcome. Overall, there were 60 trials in the experiment, which was conducted in a single scanning session. There were two types of cues (after Kirsch et al., 2003): reward cue (an arrow pointing upwards; 30 events) or neutral (a horizontal bar with arrows in both extremes; 30 events), and the participants were instructed to press a button in a rapid manner when requested, after the cues disappeared but before the outcome was known. After a 1–4 s random interval showing a fixation cross, the image of a coin indicated the amount of reward (£1 in 70% of the events and 1 penny in 30%; 21 and 9 events) in the case of the win cue, whereas a yellow or orange circle (70 and 30% of events, respectively; 21 and 9 events) were shown after the neutral cue. Hence, despite our instruction to the participants (which was designed to help engagement with the task), rewards did not depend on the subject's performance while pressing the button. This alteration from the original MID task was intended to reduce the confounds of motor preparation and task-induced anxiety which have been proposed as possible reasons for the previously inconsistent results in depression using the MID (Treadway and Zald, 2011). The inter-trial interval, in which a black screen was shown, lasted between 2 and 6 s. Reward and neutral cues, as well as ensuing outcomes were pseudo-randomly presented. Thus, the design was optimized to detect differences between the two anticipation conditions. Behavioral information obtained from the task included reaction time and responses. Data on response times was lost for 8 participants due to programming problems that did not affect acquisition of other data.
Figure 1. Design of the paradigm. There were two conditions, reward (top) and neutral (bottom) that were signaled by an unambiguous cue and were followed by the subject pressing a button and then by two possible outcomes with different frequencies (0.7 or 0.3 probability of occurrence).
MRI Acquisition and Preprocessing
A Siemens Trio Tim 3 T scanner with a 12 channel head coil was used for image acquisition. Functional images were obtained using a Gradient-echo T2*-weighted echo planar sequence and consisted in 32 non-contiguous oblique axial planes (in order to minimize signal drop-out in ventral regions, which was especially important according to our hypothesis). Other parameters included relaxation time = 2000 ms; echo time = 30 ms; flip angle = 78; voxel size = 3.14 × 3.14 × 3.75 mm3, matrix size 64 × 64; bandwidth 2232 HZ/Px. The structural image was obtained using a high-resolution T1-weighted three-dimensional MP-RAGE sequence.
Imaging preprocessing and analysis was carried out using the FEAT v5.98 (FMRI Expert Analysis Tool) routine within the FSL program (FMRIB's Software Library, www.fmrib.ox.ac.uk/fsl). Functional time-series were sequentially realigned, coregistered to a whole brain echo-planar image and finally to the structural high resolution T1 image, and non-brain components were removed. Functional images were also spatially smoothed using a 6 mm at full width half-maximum (FWHM) Gaussian kernel and frequency filtered (130 s cut off). Images were normalized to the Montreal Neurological Institute (MNI) standard template and the first six volumes were discarded to allow for T1 equilibration effects.
Non-imaging comparisons were carried out in SPSS 21 (IBM, Armonk, NW, US). Results were considered significant if p < 0.05. Normality of all variables was initially evaluated through visual inspection of histograms, whisker plots, and Q-Q plots in the 3 groups.
Results from clinical scales did not follow a normal distribution in at least one of the groups. Hence, differences between groups were tested using Kruskal-Wallis ANOVA. To investigate differences in proportions (gender, handedness, and ethnicity) Chi-square comparisons were carried out. Finally, variables which a-priori were considered to be more likely to meet ANOVA assumptions, and for which the results of the initial inspection was less clear (age, intelligence, and education), were taken to a One-Way ANOVA, residuals saved, and explored through inspection of histograms, whisker plots, and Q-Q plots. In the case of these three variables there was some evidence for a non-fully normal distribution of the residuals. However, since ANOVA is considered to be robust to deviations from normality, parametric results are reported in the main article. Additionally, results from Kruskal-Wallis ANOVAs for these variables can be found in Supplementary Material.
Whenever an ANOVA was significant, we conducted post-hoc tests consisting of pair-wise comparisons corrected for multiple testing. In the case of Kruskal-Wallis ANOVA, adjusted significance levels were calculated by multiplying the unadjusted significance values by the number of comparisons with a maximum p-value of 1 (SPSS standard method). Gabriel (due to the slightly unequal sample sizes) or Games-Howell procedures were used for One-Way ANOVAs depending on the result of Levene's test on the inequality of variances; the latter was used if the test was significant.
In the case of response times, whisker plots representing data in the reward and neutral condition showed that a participant with depression had a much higher response time in both conditions. However, the difference between the RT in both conditions was within normal parameters (as confirmed by the evaluation of the residuals of the RT differences between conditions), and therefore not likely to influence the results. Nevertheless, we carried out a repeated-measures ANOVA (within subjects effect: Two levels of condition, between subjects effect: group) with and without this participant.
We used a single statistical linear regression model with 6 explanatory variables (reward cue, neutral cue; high reward outcome, low reward outcome, and the two neutral outcomes) and their temporal derivatives. Movement parameters from the realignment step were also included in the first-level model.
The a-priori contrast of interest was the anticipation of reward and consisted of the comparison of the BOLD levels during the reward cue and the neutral cue. The reward anticipation contrast uses all cue events in the experiment, with 30 neutral cues and 30 reward cues. Other possible contrasts included the comparison between outcomes, but it was decided not to investigate them at the group level due the reduced number of events that they involved, and because well-predicted rewards often evoke limited brain activity at the time of reward delivery (Berns et al., 2001).
The reward anticipation contrast (reward cue vs. neutral cue) from the first level was taken to the group-level analysis, where it was included in a one sample analysis (control group only, to illustrate this contrast in the healthy population), and One-Way between groups ANOVA (to investigate group differences). Differences were evaluated at the whole brain level and within an a-priori volume of interest mask of the ventral striatum previously used by our group (Bernacer et al., 2013). This region of interest (ROI) included the nucleus accumbens and ventral aspects of the caudate nucleus and putamen (blue regions in Figure 4). Comparisons at the whole brain level and within the ROI were cluster-thresholded using a family-wise error (FWE) correction of p < 0.05 after a strict initial cluster threshold of Z>3 (Woo et al., 2014). Uncorrected results are also displayed in Supplementary Material as part of exploratory analyses that may be of use in future hypothesis generation and meta-analyses, using the same Z>3 threshold and a minimum cluster size of 10 across the whole brain.
We extracted the mean parameter estimates for all clusters of differential activation between groups in the imaging ANOVA analysis (using the FSL tool Featquery in the normalized individual images). Then, post-hoc pairwise comparisons (two-tailed t-tests, equality of variances was not assumed if Levene's test was statistically significant), aimed at exploring the group differences that were driving the significant ANOVA results, were carried out in SPSS. The same post-hoc analysis procedure was used for the significant clusters within the ROI comparison of the ventral striatum region.
Activation tables were created using Autoaq (Automatic atlas queries for fsl: http://brainder.org/2012/07/30/automatic-atlas-queries-in-fsl). Number of voxels, maximum voxel Z-value (Z max), MNI coordinates of the maximum peak (MAX X,Y,Z), anatomical label of the max peak and significant pairwise post-hoc t-test comparisons are reported within tables. Anatomical labels were the most probable location of the highest peak according to the Harvard-Oxford cortical and subcortical structural atlases included in FSL (Desikan et al., 2006). Images were created using MRIcroN (C. Rorden; http://www.mccauslandcenter.sc.edu/mricro/mricron/index.html) and presented in neurological form (right in the image corresponds to the right hemisphere).
A secondary analysis consisted of carrying out Spearman correlations between the mean parameter estimates in the right ventral striatum and clinical symptoms in each of the groups separately. The right ventral striatum was selected as it was the region with reduced activation in schizophrenia and in depression.
There were no group differences in age, gender, handedness, years of education, or ethnicity. As expected, participants with schizophrenia had a lower IQ and patients had greater psychiatric symptomatology than healthy controls (Table 1, Table S1).
Response times were shorter in the reward condition (F = 36.71, p≤0.001) but did not differ between groups (F = 0.384, p = 0.683). Figure 2 shows whisker plots for the three groups and the two conditions and Table 2 summarizes means and standard deviations. This difference in response time between conditions is characteristic of the paradigm hence indicating that the experimental manipulation was effective in the whole group of participants (Hägele et al., 2015). Results did not change when a subject with slow RTs was taken out (within subject factor F = 40.348, p≤0.001; between subject factor F = 0.624 p = 0.540).
Figure 2. Reaction time. Repeated measures ANOVA (within subject factor: condition, between subject factor: group): reaction times in reward trials were shorter (F = 36.71, p = 0.001) but did not differ between groups (F = 0.384, p = 0.683). For graphical purposes a subject from the depression group was eliminated from the image due to a much greater mean RT (around 800 ms) in both conditions, but included in the statistical analysis (However, its elimination from the ANOVA did not change significant results). Central line represents the median value (second quartile, Q2) and the box borders indicate the 1st (Q1) and 3rd quartile (Q3). Hence, the total length of the box is the interquartile range (IQR). Whiskers mark last value in the sample located between the 1.5 × IQR below Q1 and 1.5 × IQR above Q3. Circles represent data between the 1.5 and 3 × IQR below Q1 or above Q3.
Reward anticipation (contrast of reward cue vs. neutral cue) in the control group activated areas in the frontal lobe (medial frontal cortex, anterior cingulate cortex), striatum, and thalamus, and cerebellum (FWE cluster corrected across the whole brain p < 0.05; see Figure 3 and Table S2). When the three groups were compared using ANOVA, no clusters survived the multiple comparison correction at the whole brain level. However, the ROI analysis in the ventral striatum led to the appearance of two clusters (significant when corrected for multiple comparison) bilaterally in the accumbens nuclei (Figure 4, Table 3). As ANOVA does not indicate the direction of group difference effects, we employed post-hoc tests. Post-hoc analysis showed activation was significantly greater in the controls than the depressed patients in the right and left accumbens; controls' activation was significantly higher in the right, but not left, accumbens when compared to schizophrenia patients; the two patient groups did not differ from each other (Figure 5 and Table 3).
Figure 3. Increased activation during the anticipation of a reward (reward cue vs. neutral cue) in the healthy controls (1-sample t-test of the first level contrast between reward and neutral cues). Yellow color indicates voxels within significant clusters corrected at the whole brain level (cluster family wise error corrected p < 0.05 after a cluster-inducing primary threshold of Z>3). Numbers under slices indicate mm in the MNI coordinate system. The left side of the image represents the left side of the brain.
Figure 4. Differences between groups in reward anticipation (One-Way ANOVA of the first level contrast between reward and neutral cues). Yellow color indicates voxels within significant clusters: cluster family wise error corrected p < 0.05 within the ventral striatum after a cluster-inducing primary threshold of Z > 3. The region of interest is shown in blue on the left of the image. For improved visualization cluster limits are not circumscribed to our ROI. Differences were driven by greater activations in the healthy controls group compared to both groups of patients (right ventral striatum) or only the depression group (left ventral striatum). Numbers under slices indicate mm in the MNI coordinate system. The left side of the image represents the left side of the brain.
Table 3. Differences between groups in reward anticipation compared to the anticipation of a neutral outcome (ANOVA F test).
Figure 5. Reward anticipation mean parameter estimates in the accumbens nucleus: Obtained from the right and left significant clusters (p < 0.05 FWE cluster corrected after a cluster-inducing threshold of Z > 3 within a ventral striatum ROI) in the between groups One-Way ANOVA of the first level contrast comparing reward and neutral cues. Parameter estimates are arbitrarily scaled values. Central line represents the median value (second quartile, Q2) and the box borders indicate the 1st (Q1), and 3rd quartile (Q3). Hence, the total length of the box is the interquartile range (IQR). Whiskers mark last value in the sample located between the 1.5 × IQR below Q1 and 1.5 × IQR above Q3. Circles represent data between the 1.5 and 3 × IQR below Q1 or above Q3, whereas asterisks are data further apart from the median.
There were two clusters with Z-values above 3 and a cluster size greater than 10 in the uncorrected whole-brain analysis (Table S3). One was located in the right accumbens, the other in the frontal pole. A cluster of eight voxels in the left accumbens was the next biggest cluster. The frontal pole result was derived from a reduced activation in the depression group compared to the other two groups.
An analysis of correlations between anhedonia (SHAPS and TEPS scales), depression (BDI), psychiatric symptoms (BPRS), and positive and negative symptoms (PANSS and SANS scales) and the parameter estimates in the right ventral striatal cluster of significant differences in the ANOVA was carried out (Table 4 and Figures S1–S9 in Supplementary Material). A negative correlation between severity of depression and anhedonia symptoms and ventral striatum activity was found in the schizophrenia group. Regarding anhedonia, SHAPS and the total TEPS score were statistically significant, whereas TEPS' subscales showed a trend toward significance (marginal significance). The correlation with SANS was also close to significance. Significant results found in schizophrenia patients did not hold in the other groups and the direction of other correlations, such as the BPRS and PANSS negative symptoms within the depression group, was opposed to that expected.
We used a Monetary Incentive Delay (MID) paradigm in a single experiment designed to examine activation during reward anticipation in controls, schizophrenia, and depression. Both clinical groups had a reduction in right ventral striatal activity when anticipating rewards as predicted; results in the left ventral striatum were reduced in depression but not definitively reduced in schizophrenia. We were not able to find a clear correlation between striatal activation and clinical symptoms of depression or anhedonia in the depression group, but such a correlation was present in the schizophrenia group. The design of the study is consistent with the Research Domain Criteria (RDoC) project: one of the designs that the RDoC framework has proposed is to include participants with disorders from different sections of the DSM/ICD diagnostic manuals with the aim of exploring an abnormal neurobehavioral construct to further understand its pathological mechanisms (Cuthbert, 2014a). The rationale underlying the study was the fact that neurocognitive domains of motivation and reward processing have been proposed to be abnormal in both disorders, and such abnormalities may be at the root of the some of the common features between schizophrenia and depression.
Our results of reduced right ventral striatal activity during reward anticipation in both depression and schizophrenia can be considered a replication of the work of Hägele et al. which was recently published (2015). The combined evidence of both studies suggests that reduced BOLD signaling in the right nucleus accumbens is indeed a hallmark of pathological reward anticipation. The results in the left accumbens are more equivocal; unlike Hägele and colleagues, we demonstrated reduced left accumbens activation in depression, but similar to Hägele and colleagues we failed to demonstrate a conclusive abnormality here in schizophrenia. Further study will be required to investigate whether there is any fundamental pathological importance in this small laterality effect or whether it relates to more trivial issues such as the precise sensitivity of the paradigm.
In the case of schizophrenia, our findings are not new, as previous studies had also found decreased activity in the basal ganglia and specifically in the ventral striatum (Nielsen et al., 2012), although other smaller studies did not find such differences (Walter et al., 2009; Waltz et al., 2010). On the other hand, results in the MID paradigm with depression patients have been surprisingly inconclusive. For example, the first study using the MID in depression (n = 14 patients and 12 controls) showed no evidence of abnormality in the basal ganglia (Knutson et al., 2008). Our study and the work by Hägele et al. are among the ones with the biggest sample sizes and when taken into account in a combined way strongly suggest that abnormalities in the reward circuit are not limited to patients with a diagnosis of schizophrenia, but also relate to patients with depression symptoms. Other data such as a meta-analysis on reward and depression (Zhang et al., 2013) and a study by Pizzagalli et al. (2009), indicate that reduced basal ganglia activations may not only (or even primarily) be located in the ventral striatum, but could also involve other subcortical regions such as the caudate head or the posterior putamen. We were not able to confirm the results of the meta-analysis by Zhang and colleagues suggesting frontal and anterior cingulate over-activation in depression during reward anticipation.
One reason that has been put forward to account for the discrepancies between MID depression studies has been that reward is usually contingent on a speeded performance on the MID, which might be influencing some patients through a stress related, possibly dopaminergic, response (Treadway and Zald, 2011); these authors argue that the necessity to respond rapidly may enhance activation particularly in anxious patients, whose motivation may relate to hypersensitivity to perceived failure. To deal with this potential confound we modified the original task so reward did not depend on the speed of the response. This change may be related to the finding of reduced accumbens activation, which has also been shown in other experiments in which a speeded motor response was not involved (Smoski et al., 2009). It must be noted however that the paradigm used in the studies reported by Hägele et al. (2015) was closer to the original design of the MID and included the necessity of a fast response to obtain the reward. Similarly, we did not include a loss condition in our design, as it has been proposed that the strongest activations in healthy controls and when comparing them to patients come from contrasting the gain and neutral cues (Hägele et al., 2015) Hence, our design may be suitable and sensitive for psychiatric research when the main objective is to study reward processing. Although reward was delivered irrespective of the speed of button pressing, response time in the reward condition was shorter. Valence effects on response time can occur irrespective of a direct consequence of speeded responses (O'doherty et al., 2004; Pessiglione et al., 2006; Murray et al., 2008b). The phenomenon has been termed “reinforcement related speeding” (Cools et al., 2005; Murray et al., 2008a), and it is thought that a potential reward leads to enhanced motivation and hence faster responding (Crespi, 1942).
Whilst the right accumbens was a site of common underactivation in both patient groups compared to controls, no differences between the two patient groups were found. This result indicates that the two groups of psychiatric participants may be more similar to each other than when compared to healthy controls, which would be in accordance with the RDoC perspective of a common abnormal domain. Comparisons between patient groups were not reported in Hägele et al., but a qualitative analysis of their plotted results show them to be in line with ours; the two patient groups had a similar activity reduction in the striatum. Regarding the effects of the medications for psychosis, it is a limitation that all of the schizophrenia patients were taking antipsychotic medication. Thus, we cannot exclude the possibility that the results may in part be secondary to medication effects. However, we note that as a previous study from the Berlin group found that the striatal deactivation normalized when changing from typical to atypical antipsychotics (Schlagenhauf et al., 2008), and as all of our schizophrenia patients were taking atypical antipsychotic medication, it is unlikely that the results are solely due to medication. Nevertheless, it will be important, albeit challenging, to study medication free samples in future research.
The second hypothesis was that the BOLD signal in the striatum would negatively correlate with clinical symptoms of depression and anhedonia. Previous studies have only reported one or two clinical measures per study, but clinical constructs that correlated with the activity of the ventral striatum have included depression (Hägele et al., 2015) anhedonia and apathy (Simon et al., 2010; Stoy et al., 2012), positive symptoms (Nielsen et al., 2012) or negative (Juckel et al., 2006a; Waltz et al., 2009) symptoms, and severity of overall psychiatric symptoms measured by the BPRS (Waltz et al., 2009). In accordance with our cross-diagnostic approach and the aim of further investigating the mechanisms of abnormal reward processing, we decided to include a broad range of clinical measures that encompassed most of the constructs previously reported to correlate with striatal activity in the MID. Results in this regard were mixed. On the one hand we were able to replicate Hägele's et al. results of reduced activity in the right accumbens nucleus of those schizophrenia participants with more depressive symptoms. We also extend the results of Hägele and colleagues to relationships between less activity and more anhedonia in schizophrenia, as measured by the TEPS and SHAPS scales. A limitation of our work is that we did not correct our correlation analyses for multiple comparisons, and considering the modest effect sizes observed, those significant correlations we do find may be vulnerable to Type I error. In contrast to results from Hägele et al., neither the BDI nor any of the other measures were associated with ventral striatal activation in both patient groups. However, the lack of brain-symptom associations demonstrated in the depression group, and the control group (as some of the scales were designed to assess patients only), cannot be considered as evidence of absence of brain-symptom relations. Some correlations such as the significant positive relationship between activation and the BPRS and PANSS (negative symptoms subscale) scales in the depression group were counterintuitive (and not maintained across groups). This may reflect a chance finding, or, as Treadway and Zald (2011) have speculated, the activation elicited by the MID task may be a composite of activation associated with reward anticipation and anticipatory anxiety about potential failure. We attempted to address this possibility by our modification of the task to dissociate reinforcement from performance but it remains possible that, especially in depression, some symptoms may relate to striatal overactivity (leading to greater activation when more psychopathology) and other symptoms may relate to underactivity. The relationship between psychopathology and striatal reward processing activation may be complex, and it is possible that striatal (dys)function may contribute to symptom expression only through interactions with other regional dysfunction and other psychological processes. The concept of dysfunction of one psychological process in one brain area leading to expression of one symptom has the attraction of being a testable hypothesis but is necessarily an oversimplification.
An important challenge in assessing brain-symptom relationships is accurate symptom measurement. This is especially challenging when experts disagree about what constitutes a particular symptom. Anhedonia is defined in the DSM-IV-TR as a loss of interest or pleasure (American Psychiatric Association, 2000), which arguably reflects the consensus use of the term over the past 100 or so years (e.g., Myerson, 1922; see also Berrios, 1996). However, the DSM-5 contains a new definition within the schizophrenia (not depression) chapter, “the decreased ability to experience pleasure from positive stimuli or a degradation in the recollection of pleasure previously experienced,” and arguments continue as to whether a broad or narrow use of the term is more helpful (recently discussed by Treadway and Zald, 2011; Der-Avakian and Markou, 2012; Romer Thomsen et al., 2015). Consensus appears to be building that in depression and schizophrenia, anticipatory, and motivational aspects of reward are more compromised than consummatory (reward receipt) aspects, possibly related to dopaminergic abnormalities in both conditions (Argyropoulos and Nutt, 2013; Kring and Barch, 2014; Whitton et al., 2015); though see a recent study (Gard et al., 2014) documenting enhanced anticipation of pleasure in schizophrenia). However, it remains possible that this relative consensus may in part reflect the methods that have been recently used to investigate the issue. Variants of the monetary incentive delay task as we used here may be more sensitive to reward anticipation effects than reward delivery effects, as well-predicted rewards tend to evoke less strong brain responses than surprising rewards (e.g., Berns et al., 2001). In addition, given the limited temporal resolution of fMRI it can be hard to dissociate anticipatory and consummatory aspects of reward. Furthermore, most fMRI patient studies have, as we did, used monetary rewards, but processing of primary and secondary rewards may differ in important respects (Sescousse et al., 2013).
Strengths and Limitations
As noted, our work is similar to existing research, such as that of Hägele and colleagues. However, there are differences between the two studies. Our study was at higher field strength (we used a 3 Tesla magnet vs. a 1.5 Tesla of Hägele and all). Our study uses a matched control group whereas Hägele and colleagues, because theirs is a retrospective synthesis and re-analysis of previously published separate works, use a control group that is not matched to their patients in the basic features of age and gender. Our study uses different (slightly simpler) stimuli to Hägele and colleagues and, while both studies require a button press, in ours, the reinforcement is not actually contingent on the button press reaction time (as discussed above, this was suggested by Treadway and Zald (2011) as being advantageous in reducing anticipatory anxiety). Our study includes a more detailed assessment of psychopathology (with the limitations that, as previously mentioned, when utilizing the psychopathology for correlation analyses we did not correct for multiple correlations, and that our sample size is modest for correlation analysis).
In summary, while a reduced activation in the ventral striatum when anticipating rewards is a common endophenotype in psychopathology, the mechanisms underpinning this finding and related symptoms are not completely clear. It will be crucial to further pinpoint the clinical relevance of this finding but it will require further studies and replications. Although some evidence from both the previous literature and our work points toward negative or depressive symptoms being more related to the reported finding, they require further confirmation. The future of this line of research fits nicely within the specifications laid out by the RDoC project, although it also faces similar challenges, such as the measurement error, and the biological and psychometric limitations of proposed endophenotypes and their relationship to behavior (Cuthbert, 2014b; Lilienfeld, 2014; Weinberger and Goldberg, 2014). Upcoming studies on reward and psychopathology will have to use bigger sample sizes and a broader range of clinical measurements in order to be able to obtain a compelling evidence of the relationship between brain activation and everyday behavior. As shown in our work, future studies could benefit from including participants with a range of diagnoses. This aim can be best achieved by a large-scale collaboration across different research groups. Moreover, the wide use of the MID task makes it a good candidate measure for such collaboration, although a common “official” version would be important. Our results indicate that a paradigm that does not base reward on performance might be better fitted for research with stress-prone participants.
Our overall findings are further evidence of reward system dysfunction across the neuropsychiatric continuum, even if the specific clinical relevance is still not fully understood. Studies on this line of fruitful research could provide new insights on the cross-diagnostic mechanisms of psychopathological symptoms, especially if conducted in a way that minimizes the challenges posed to the Research Domain Criteria approach.
Conflict of Interest Statement
Trevor W. Robbins has received research support from or served as a consultant to Cambridge Cognition, Eli Lilly, GlaxoSmithKline, and Lundbeck. Hisham Ziauddeen has been jointly funded by the Wellcome Trust and GlaxoSmithKline on the Translational Medicine and Therapeutics programme. Paul C. Fletcher has received funds from GlaxoSmithKline for consultation services and from Astra Zeneca for a lecture. Gonzalo Arrondo, Nuria Segarra, Antonio Metastasio, Jennifer Spencer, Robert B. Dudas, and Graham K. Murray and Niels R. Reinders have no financial interests.
Supported by the Wellcome Trust Institutional Strategic Support Fund [097814/Z/11], a MRC Clinician Scientist [G0701911], a Brain and Behavior Research Foundation Young Investigator, and an Isaac Newton Trust award to GM; an award to NS from the Secretary for Universities and Research of the Ministry of Economy and Knowledge of the Government of Catalonia and the European Union; by the University of Cambridge Behavioural and Clinical Neuroscience Institute, funded by a joint award from the Medical Research Council [G1000183]and Wellcome Trust [093875/Z/10/Z]; by awards from the Wellcome Trust  and the Bernard Wolfe Health Neuroscience Fund to PF, and by the Cambridge NIHR Biomedical Research Centre. The authors are grateful for the help of clinical staff in CAMEO, in the Cambridge Rehabilitation and Recovery service and Pathways, and in the Cambridge IAPT service, for help with participant recruitment.
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/article/10.3389/fpsyg.2015.01280
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Keywords: reward system, ventral striatum, monetary incentive delay, depressive symptoms, research domain framework
Citation: Arrondo G, Segarra N, Metastasio A, Ziauddeen H, Spencer J, Reinders NR, Dudas RB, Robbins TW, Fletcher PC and Murray GK (2015) Reduction in ventral striatal activity when anticipating a reward in depression and schizophrenia: a replicated cross-diagnostic finding. Front. Psychol. 6:1280. doi: 10.3389/fpsyg.2015.01280
Received: 04 March 2015; Accepted: 11 August 2015;
Published: 26 August 2015.
Edited by:Eduardo A. Garza-Villarreal, National Institute of Psychiatry, Mexico
Reviewed by:Sharna Jamadar, Monash University, Australia
Kristine Rømer Thomsen, Aarhus University, Denmark
Tracy Barbour, Massachusetts General Hospital, USA
Copyright © 2015 Arrondo, Segarra, Metastasio, Ziauddeen, Spencer, Reinders, Dudas, Robbins, Fletcher and Murray. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Graham K. Murray, Department of Psychiatry, University of Cambridge, Box 189 Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK, email@example.com

domain: literature


text:
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CANCELLED - Voyages by Road and Sea
Now through Sun, August 30, 2020 8:00 A.M.
First Floor Gallery West
Parkway Central Library
Voyages by Road and Sea explores the legacies of Walt Whitman and Herman Melville through contemporary voices and art in Parkway Central Library's West Gallery. Marking the bicentennial years for both Whitman and Melville, Voyages examines the personal and literary journeys of these two American authors, both born in 1819. Archival images and documents are showcased alongside artwork from contemporary Philadelphia-area artists. Including comics, sculpture, painting, and poetry, among other mediums, the art enters into dialogue with the legacies of Whitman and Melville on critical present-day issues like immigration, sexuality, and conservation. Visitors are invited to consider how Whitman and Melville have inspired subsequent generations of artists and writers, and how their writings speak to us and challenge us today.
Voyages by Road and Sea runs from November 13, 2019 to August 31, 2020.


text:
The burning sun sank into the barren landscape as I rode into my very last Melbourne sunset. Vulkey, my trusty Kawasaki Vulcan S powering me across the stretched deserted roads of Melbourne’s sparse outer north west suburbs. My belongings strapped to my back in a 13 kilo, 55 litre backpack. Continue Reading
Why Central Asia you ask? I could go somewhere easy like South America. I could go somewhere chill like Southeast Asia. But when am I ever going to get the chance to visit some of the most remote landscapes in the world? Countries some people don’t even know exist?

domain: geography


text:
We do not mark merchandise values below value or mark items as “gifts” – US and International government regulations prohibit such behavior. The item “USED CHOGOKIN Disney KING ROBO MICKEY & FRIENDS BANDAI TAMASHII NATIONS” is in sale since Saturday, March 23, 2019. This item is in the category “Toys & Hobbies\Action Figures & Accessories\Action Figures”. The seller is “bhjapan” and is located in Kyoto. This item can be shipped worldwide.
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text:
My mom, Harriett Beach has offered to do some book reveiws on her food related reads. Here is the first with more to come.
The Reach of A Chef ( Beyond the Kitchen), Michael Ruhlman, 2006, Viking Press,
Penguin Group, 338 pages.
Ruhlman gives the reader an "in-the-trenches" look at professional Chefs whose life work is to feed others in order to feed themselves. This is a chronicle of the current business of food preparation as it goes from just preparing food "ordinaire"to the shift in American culture that has raised restaurant cooking to the level of performance art and the status of the celebrity Chef to being a CEO of his food empire. Ruhlman over the years has developed the skills and contacts with the Chef stars in the food world to hold his own in a commercial kitchen and thus writes from personal experience.
The narrative leads the reader through some of the most illustrious and ingenious kitchens in America while exploring how and why a successful kitchen or style of food preparation has evolved. The state of professional cooking has been elevated and shaped by the likes of industry giants such as, Thomas Keller, Masa Takayama, Grant Achatz, Melissa Kelly.and Emerial Lagassee. The description of the food
preparation in the various kitchens illustrates how much the art of food preparation has gone beyond that of Julia Child and The Food Network. In some kitchens even the equipment is no longer just stoves, coolers, and sinks but equipment usually found in industrial settings or the chemistry lab. This is no longer " your Mama's
kitchen" as food preparation and food tastes are changing.
Ruhlman's writing is an exciting review of the current cooking world that is a "don't skip a word" page turner that leaves the reader wanting more as they finish the last page. The writing captures the ritual and routine of creative food
preparation that centers the soul of the professional or "at-home" chef.

domain: food


Pedro Caixinha couldn’t have asked for a better start as Rangers boss after cruising to a win over Hamilton.
But his post-match comments have been given the Hotline treatment and it was anything but child’s play.
Ian Muir, Cromarty, said: “I’ve just read Caixinha's comments following a very impressive performance against Hamilton. That's great that it worked, but when Mark Warburton asked them to play like kids they were running around like headless chickens.”
Craig Walker, Glasgow, said: “ Rangers shouldn’t be getting carried away with a win over a poor Hamilton side.
“Caixinha said he asked his players to play like kids but he must be aware it’s been boys against men for most of the season at Ibrox.”
Graeme Egan, Saltcoats, said: “I’m encouraged by what I’ve seen and heard from Caixinha so far and long may it continue. He’s obviously brought a bit of belief into the team and it’s the most optimistic I've felt as a Rangers fan in a long time.”
Walter Robertson, Springburn, said: “The performance against Accies was much more like it and Caixinha has a bit of fire in his belly which is rubbing off on the team. It’s a refreshing change to hear someone speak from the heart after all the rubbish spouted by Warburton.
Carl McArdle, Lanarkshire, said: “Pedro has made a rod for his own back with his recent statements. He has dodged bulls in the past but he will be dodging angry bears in the future and that will start following his team’s Scottish Cup exit next month.”
Eddie Paterson, Wishaw, said: “Rangers win one game against Hamilton and suddenly they are world beaters but it won’t be long before Caixinha discovers why they are a country mile behind Celtic. He may believe he has the best squad in Scotland but the Scottish Cup semi-final next month will bring him to his senses.”
John Scott, e-mailed: “ Celtic assistant boss Chris Davies says they will be stronger next season, but ironically they won't be anywhere near as far ahead and Rangers will also be stronger.
Rab Picken, e-mailed: “Who is this EPL failure Moussa Dembele, seriously. Big Clint Hill is now the man in form and he doesn't need penalties to score, the big man scores from open play. If Dembele is worth £30million then Clint must be worth £10million.”
Hearts boss Ian Cathro’s next in the line of fire with many believing director of football Craig Levein is running the show.
Pat Mulvery, Edinburgh, said: “Cathro’s like a little boy in the wrong movie. The defeat against Aberdeen showed just why changes need to be made now. It’s obvious Levein is in charge and Cathro is just carrying out his instruction. We all saw Jon Daly running down to the Pittodrie dugout with messages and I’d urge Ann Budge to get rid of all the coaches and start with Levein who is using the club for his own ends.”
Ian McDonald, Innerleithen, said: “Saturday’s shambles on and off the park showed just how much trouble we are in. Levein is killing Hearts and no manager worth his salt would touch the club as long as he is there interfering continues. Cathro is way out his depth, but the most worrying thing for me is the fact that Mrs budge is doing nothing about the situation, these are worrying times in Gorgie.”
Gareth Oliver, Edinburgh , said: “All of the good work which has been done at Hearts in recent times is now in danger of being wasted by continuing with this horrible coaching experiment. Cathro needs to go and so does Levein, let’s bring in a manager who can take us forward and stop complicating everything.”
And finally some rugby.
Joe Wilson, Spean Bridge, said: “What a pleasure watching the rugby in recent weeks. The players accept the referee’s decisions without mumping and walking away after a rough tackle as well as clapping the winning team off the park at full time. Fans have also been enjoying a civilised pint. What a change from the con artists in football. It’s a man's game played by gentlemen.”


The Decisive Moment …
The moment our desired image becomes reality and presents itself. We then shoot to capture our vision. For me in the case of animals it’s when they look at me. It could be the pole-vaulter clears the bar or the light strikes our subject or the baseball player gets the pie in the face or possibly the special moment of my child’s first steps.
Sometimes we must pause, breath withheld, as in a dream that has stopped for our vision to materialize.
The decisive moment can be the final step in the classis photo visualization process or be the part of the critical spontaneous talent of the classic street photographer like David S. Johnson. Either way it’s our prize, our summit, and our success as photographers.
Let's Talk Photography!What kind of pictures do you take? What kind of pictures do you WANT to take?
I can help you get where you want to be, whether you take pictures as a hobby or professionally!


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NVHS Choir Tours
Every 3 years, all current students and families of the curricular choirs in the NVHS Choral Department are eligible to pursue a once-in-a-lifetime opportunity to travel and perform internationally. Show below are the countries in which the choirs have previously visited and performed, and we look forward to the next tour to incredible desinations, likely occuring the summer of 2022! Music is a cultural universal, and NVHS feels it is an powerful and almost essential component of a comprehensive music education to provide opportunities for students to experience the music of other cultures first-hand and in return, benevolently share our music with others around the world. These trips not only provide opportunites for students to experience iconic destinations and landmarks around the world, but quite possibly even more powerful, to sing at those destinations and make a memorable, joy-filled impact on others with our music, cutting through language and cultural barriers and creating a connection that will never be forgotten. These trips are often one of the most significant, unforgettable memories of students' high school experience!

domain: artistic


12th Annual R&B/Soul Album Nominee
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Record Label: Self-Released
Home Base: New York, NY
Categories Entered: R&B/Soul Album
Work Submitted: Distraction
Artists Featured: ORLY (vocals + additional keys & percussion) – Ben Altman (Guitar) – Mark Palmer (Keyboards + Background vocals on “Temporary” & “This Time”) – Kevin Farrell (Bass) – Adam Jackson (Drums + Percussion) – Dani Elliott (Background vocals on “Beautiful Disguise”) – Aaron Nevezie (additional guitar + percussion)
Who are your influences?: I feel like there are too many to list! I have a huge range of influences from Jazz artists such as Ella Fitzgerald and Dianne Reeves to Old-School Soul singers like, Stevie Wonder and Donny Hathaway. More recently I’ve drawn inspiration from the most amazing singers around, like Erykah Badu and Nikka Costa.
I also draw a lot of inspiration from my peers and co-writers. I’m constantly surrounded by talented people, and learn a lot from all of them.
Describe your nominated work: The alluring and ardent sounds of soul are on display and evident throughout Distraction, the debut full-length album from Australian singer-songwriter, “ORLY.” This powerful and soulful record is a showcase of an up-and-coming star with the determination and hunger necessary to propel this singer into the leagues of Adele and Amy Winehouse. Each track, different to the previous, highlights the versatility and eclectic ability of this talented artist and showcases her many musical influences. From old school soul, to beautiful ballads, to pop, this record is uplifting, sexy and exquisite.
Did you use any unusual effects or instruments in this recording?: Well, my keyboard player thought it would be funny to play a toy piano during one of the sessions, but we kind of loved it and kept it in.
Were there any happy accidents while in the studio, or did everything go as planned?: There are always happy accidents in the studio. As much as we went in with a plan, there are always things that come to you in the moment, or wrong notes played, that will make it into the final mix.
How did you raise the funds for this project? How long do you expect it will take to recoup your out-of-pocket recording expenses?: I am so grateful to have managed to make the record through a Pledge Music campaign. My family, friends and fans were an incredible support throughout the whole process.
I go into these projects knowing I might not ever recoup my out-of-pocket expenses. It would be nice if I could, but that’s not why I make these records.
Why did you choose to submit this work to The 12th IMAs?: I think it’s amazing that there are awards that recognize the efforts of independent artists. We work so hard, just as hard as signed artists do, but very rarely get recognized for our efforts as much. I appreciate the IMAs for being there to draw attention to so many talented people in so many different genres.
What’s your definition of success and how will you know when you’ve achieved it?: I think once we follow our passions, and let go of needing the approval of others, we have achieved success. I feel that as long as I am able to express myself creatively, as long as I get to sing, I am successful.
Are there any songs you wish you wrote and why?: There are 3 full albums I wish that I had written. Who is Jill Scott? by Jill Scott, Grace by Jeff Buckley and Pebble to a Pearl by Nikka Costa. All 3 records are simply fantastic! Each of those records changed me as a musician when I heard them.
How do you discover new music? Do you buy music or are you content with streaming?: I usually ask others who they are listening to. I am not against streaming. I think it’s a good way to discover new music. And I appreciate that my music has been discovered by others through Pandora and Spotify. But once I have discovered a musician and like their music, I prefer to purchase it. I love owning music I love.
Finish this sentence: The music industry is…constantly changing.
What do you have in the works for the upcoming year?: My first ever music video will be released on May 15! I’ve also started a YouTube series called, “ORLY SINGS with…” where every Thursday I get to sing with some of my favourite musicians! http://www.youtube.com/ORLYSINGS (or check them out on the facebook page!)


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With the advent of spring and the approach of one of the greatest Easter holidays, many housewives are preparing to bake the most delicious Easter cake. The “Lace Woman” deserves special attention: since this Easter recipe has its own subtleties of preparation, and the baking is unusually airy. Everyone who loves the light and delicate structure of the dough will appreciate this recipe. It’s not for nothing that the “Lace Woman” received such an original name: after all, a papillon in a section very much resembles light lace. Let's cook this airy “Lace Woman” together!
- wheat flour (premium) - 300 - 350 grams;
- dry yeast (Saf moment) - 4 grams;
- cow's milk - 150 milliliters;
- chicken egg yolks - 7 pieces;
- butter (fat content not less than 82%) - 75 grams;
- sugar sand - 50 grams;
- salt - a quarter of a teaspoon;
- vanilla essence.
Delicious Easter cake "Lace woman". Step by step recipe
- We slightly heat the milk and dissolve 4 grams of dry yeast in it.
- Important! In no case should milk be hotter: since the yeast in it will die and all our efforts will go down the drain.
- Pour half a portion of wheat flour (approximately 150 grams) into a deep bowl, pour the milk-yeast mixture into it and mix well with a spoon. It turns out the so-called dough.
- We cover the bowl with the dish with a kitchen towel or cling film. We put in a warm place and let rise several times.
- In the meantime, do the rest of the ingredients.
- In a deep bowl or bowl of the mixer we send seven egg yolks, pour salt, 50 grams of sugar and beat well with a mixer until the mass brightens.
- In a separate bowl, beat the butter.
- Now combine the remaining flour, dough and whipped yolks together. Add a couple of drops of vanilla essence and knead thoroughly to make a soft and uniform dough.
- We lay the resulting dough on an absolutely dry work surface (for such purposes I use a silicone mat) and knead until the dough starts to stick off from the hands and the table.
- In small portions, add whipped butter to the dough and knead it well again. The dough should not stick to the hands and work surface. This process will take you at least 5 to 10 minutes.
- We give the resulting test a rounded shape and send for proofing in a bowl greased with vegetable oil. Cover with a towel, put in a warm place and allow to double in size.
- When the dough has come, we thoroughly crush it. If you like raisins in Easter baking, now is the time to add it. I do not use raisins for baking this lace woman.
- We divide the dough into the number of baking dishes. This Easter recipe is designed for two forms for Easter cakes (diameter 12 centimeters).
- Divide the dough into two equal parts. We give them a rounded shape.
- Forms for baking Easter cakes generously grease with butter. In order to make Easter cakes easily come out of forms, I advise putting circles of baking paper on the bottom of the form (the diameter of the circle corresponds to the diameter of the form). Thanks to this technique, our air cakes will never stick to the bottom.
- We send our dough into forms. Since the dough will rise strongly during baking, you should not fill the form with more than half its volume. The optimal filling of the form is one third of its volume.
- We leave the cakes to rise to a double increase.
- When the Easter cakes have risen well, grease the tops with a beaten egg.
- We heat the oven to a temperature of 180 - 190 degrees and send our air cakes to bake.
- The baking time depends, first of all, on the weight of the cakes and on the technical characteristics of your oven. Therefore, I check the readiness of my cakes with a dry wand. If you pierce the pastry with a stick and there are no traces of dough on it, then the cake is ready. So, on average, a cake weighing 500 grams will be baked for about 40 minutes.
- After baking, we carefully take out the cakes from the mold, put it on a clean towel and let it cool completely. You can periodically turn them from side to side so that they do not deform due to their delicate structure.
- A fully cooled Easter cake for Easter, if desired, can be decorated with sugar fudge, protein glaze or dried fruits.
That's all! The magnificent "Lace Woman" is ready. A delicious Easter cake, no doubt, will take first place in the Easter basket. The “I love to cook" team wishes you a pleasant appetite and happy holidays in the circle of close people!


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From John Wilkes Booth to Lee Harvey Oswald, nine would-be and successful presidential assassins inspire each other to pull the trigger and change their worlds in a perverse, wry and thrillingly entertaining vaudeville.
Directed by Artistic Director Eric Schaeffer, a cast of Signature favorites including Nova Y. Payton, Tracy Lynn Olivera, Evan Casey, Bobby Smith and others explore Sondheim’s stunning music and sardonic lyrics in a fascinating examination of the twisted American Dream.
1hr 50min (No Intermission)
August 11th, 2019
September 30th, 2019
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domain: entertainment


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Happy 4th of July
Not censored yet:
Our National Anthem.
Happy Independence Day! May we the People reclaim the good and righteous aspects that we want to be represented in our country, and be able to celebrate that into the future. Guiding the Fourth Turning with a Righteous Reset. Aloha, Steve.
We celebrated Independence Day with full swing but at home due to pandemic. Had to work for sometimes at resume edit service for a while, but overall it went really well.

domain: sociology


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- Traditional Kecak Fire Dance Show at Uluwatu.
- Go Scuba Diving.
- Bike Ride Adventure through Ubud!.
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- Discover the World Heritage Site of Borobudur.
- Enjoy beautiful trekking in the forests of East Java.
- Journey to lush tea plantations with mountainous backdrops.
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domain: travel


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No charges against officers who fatally shot Thurman Blevins
Charges will not be filed against the two Minneapolis Police Officers who fatally shot Thurman Blevins, Hennepin County Attorney Mike Freeman announced at a news conference Monday.
Witness testimony, body camera video and forensic testing all proved that Blevins had a nine millimeter semi-automatic handgun in his hand and refused multiple commands to drop the gun during the foot chase that ended in his death on June 23, Freeman said.
The two officers, Ryan Kelly and Justin Schmidt, were responding to a 911 call by a resident who said he had seen an apparently drunk man walking down the street firing a semi-automatic handgun into the air and into the ground. The caller was concerned about the safety of himself and his neighbors. The caller also gave a very detailed description of the shooter.
Kelly and Schmidt responded to the call and eventually saw Blevins sitting at the corner of 48th and Camden Avenues North with a bottle in his hand and a woman and a baby in a stroller nearby. Blevins matched the description and as they were stopping the car, Officer Schmidt yelled, “he’s got a gun,” which he could see protruding from Blevins’ pants pocket, Freeman said.
Blevins refused the officers orders to drop his gun and put his hands up, and instead, led the two officers on a foot chase that ended in an alley between Aldrich and Bryant and 48th and 47th Avenues. Blevins took the gun from his pants pocket and began to turn towards the officers. Officer Schmidt immediately fired and Kelly, who was a short distance behind, also fired, Freeman stated. The officers fired 14 shots from their weapons, four of which struck Blevins.
“When Mr. Blevins fled from the officers with a loaded handgun, refused to follow their commands for him to stop and show his hands and then took the gun out of his pocket and turned toward the officers, Mr. Blevins represented a danger to the lives of Officer Schmidt and Officer Kelly, “ Freeman said. “Their decision to use deadly force against Mr. Blevins under those circumstances was authorized by Minn. Stat. § 609.066 and as such there is no basis to issue criminal charges against either officer.”
Thurman Blevins charging decision speech from Michael O. Freeman (PDF)
Report on the shooting death of Thurman Blevins (PDF)
Justin Schmidt RAW BWC video (YouTube)
Ryan Kelly RAW BWC video (YouTube)
NCAVF analyzed body worn camera video (YouTube)
BCA link to the entire redacted case file
Video of Mike Freeman's speech (YouTube)

domain: news


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Singapore Grand Prix – With Romain Grosjean refinding his form in Formula 1 after a dreadful start to the 2018 season, the French driver says he had to take time to reflect on what he was doing wrong to rectify the situation.
Grosjean’s early season form was very poor, with the Haas driver failing to score points in the first eight rounds. While these weren’t all necessarily his fault, high profile mistakes such as his triggering of the first lap crash in Spain as well as sliding off under Safety Car conditions in Baku meant that accusatory fingers were being pointed in his direction, particularly as teammate Kevin Magnussen was more consistently bringing home strong points finishes.
However, in the six races from Austria through to Italy, Grosjean seems to have figured it all out. Outscoring Magnussen 27 points to the Danish driver’s 22, this doesn’t even take into account Grosjean’s disqualification from Italy for an illegal floor – the result remains under appeal from Haas. Had Grosjean been allowed keep his P6 finish from Monza, he’d be on 35 points.
“I’ve worked on myself to understand why things were not going right before.” said Grosjean. “The car is giving me a better feeling, as well. I’m enjoying my time, and I’m hoping there will be more and it keeps going.”
Grosjean is well known on the grid for having sought the help of sports psychologists before. In 2012, he was involved in a series of incidents and accidents that led to him being the only contemporary race driver to have been barred from a race, after being found to be the catalyst for the violent crash on the opening lap of that year’s Belgian Grand Prix.
Grosjean is well liked at Haas, and his willingness to concede his shortcomings may yet grant him a stay of execution. He is without contract at the team for next year and, while team boss Guenther Steiner has admitted to frustration with Grosjean, he says that his form has turned around. Steiner says the change is down to whatever Grosjean is doing differently, but doesn’t know what that is: “If I would’ve known that, I would’ve made it happen earlier. I think he’s focusing really hard on it. He knows our expectations of him. Just by focusing and concentrating on what to do, I think that has helped him.”


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When Erin Budde was asked to become executive director of stl250—the nonprofit created to celebrate St. Louis’ 250th birthday in 2014—the native St. Louisan knew it was an offer she couldn’t refuse. “The next time an opportunity like this will come up in St. Louis, I’ll be in my 90s, so I won’t be doing it then!” she says. “I love St. Louis and I have no intent of finding a home somewhere else. If I want to contribute to this amazing initiative—this region-wide, very positive-oriented effort that is a look at where we’ve been, the momentum we have going on today and how to sustain that momentum into the future—this is the time to do it.”
Having previously headed the nationwide community affairs team for Wells Fargo Advisors and served as president of Gateway Center for Giving, Budde is definitely up to the task. Her main goal for the celebration year is that it be inclusive. “We want it to be informed by folks throughout the region and have a big tent. We are, from neighborhood to neighborhood and from community to community, extremely diverse. Everyone will have a different way they want to approach the celebration.” She hopes this inclusive approach will help people discover new organizations and learn more about the region, as well as connect to their identity as St. Louisans.
Given this approach, Budde says the celebration will be twofold: First, through four signature events, including Fair St. Louis, a Birthday Bash on Valentine’s Day weekend, and bookended by First Night celebrations in Grand Center; and secondly, through events done in conjunction with celebration partners. “We want everybody to help figure out how to celebrate within their groups and share it with us,” she says. “This will make it so creative because you’re not going to have just one group thinking of things—you’ll have thousands of people throughout the region thinking about it.”
One way they’re getting the wider community involved is though the Cake Walk project, which will see 250 giant cakes decorated by artists and placed at important institutions and historical points of interest throughout the St. Louis region, Budde says. The locations will be unveiled at a City Hall event on Feb. 15, as part of the Birthday Bash weekend celebration. Each cake will reflect the location it represents, which will be chosen by stl250’s history committee with input from the public, as well. People can explore the sites through a smart phone application, which will provide information about each cake they find, and allow them to take part in a sweepstakes. “What I love the most about this is it gives us the opportunity to program and build activities around those locations,” Budde says, adding that maps will be created for school groups, family outings and more in different parts of town.
More than just a celebration, Budde hopes stl250 will help St. Louisans appreciate the region’s past and start a conversation about where it’s going. “We want them to feel like it’s theirs, that they belong here and they have a role in helping us realize all of our possibilities.”


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When you buy an aquarium fish, did you know that it has traveled from a fish farm to a wholesaler to a pet store before it got to you? That means that there’s a high likelihood that it may have picked up some kind of internal or external parasite along the way. Wild-caught fish are especially prone to carrying parasites, if not multiple types at the same time. Unfortunately, most of the time aquarium fish don’t stay at the store long enough to make sure they are free of parasitic diseases. If your fish has visible parasites on its body, a swollen abdomen, skinny disease, hole-in-the-head, or strange-looking, discolored poop, you may need to treat it with one of the following antiparasitic medications.
Hikari is well-known for their high-quality fish foods, but they also produce excellent fish medications under their Aquarium Solutions and Pond Solutions product lines. After testing dozens of ich medicines in the United States, we have determined that Ich-X is one of the most effective formulations for treating ich (or white spot disease), other external protozoan parasites, and mild fungal infections. In fact, we use Ich-X to proactively treat all fish that enter our fish store before they get sold to customers. Its active ingredients are formaldehyde and malachite green chloride, and it is safe for scaleless fish, invertebrates, and live plants.
If your fish looks like it’s covered in little, white grains of salt, it could be ich and needs to be treated immediately. That’s why it’s good to always have first aid medications like Ich-X on hand.
There are two types of Ich-X: Aquarium Solutions Ich-X for home aquariums and Pond Solutions Ich-X for ponds and larger tanks that contain 50 gallons or more. To use Aquarium Solutions Ich-X, follow these steps:
Pond Solutions Ich-X is stronger than Aquarium Solutions Ich-X, so use the same directions but with a dosing concentration of 1 teaspoon (5 ml) of medicine per 50 gallons of water. For more details on how to recognize and treat ich, read our full article here.
Fritz ParaCleanse is another well-tested medication that we use to preventatively treat all new fish that enter our retail store, and it can be safely used in conjunction with Ich-X. It is used to cure internal parasites and some external parasites, such as:
ParaCleanse contains praziquantel to take care of worms and flukes, as well as metronidazole to kill certain bacteria and protozoans. It is safe for scaleless fish, fish fry, snails, shrimp, and aquarium plants. If you suspect your fish has one of these parasites, follow the manufacturer’s directions and do not treat with half doses (or else the medicine may not be effective).
Tapeworms eggs are not affected by most medications, so we have to wait until the new worms hatch and can be treated. That is why we recommend redosing after 2 weeks once they have hatched.
ParaCleanse is not very harsh, so multiple treatments are generally safe for your fish. However, it can be a little expensive on the wallet, so try putting your fish in a smaller quarantine tank so that there is less water volume to dose.
Is it better to medicate the fish’s water or their food? Medicated fish food is a little tricky to manage. Sick fish often won’t eat very much (or at all) because they don’t feel well. Also, it can be hard to monitor how much medicated food each fish is getting, so some fish may be consuming too much medicine while others are consuming too little. If you are only treating one fish that is still eating well, then medicated food might be a viable option. If you are treating multiple animals, we recommend medications that dissolve in the water and treat the whole tank so that we can ensure every animal gets the right concentration.
How does this treatment plan work with the quarantine med trio? If you have proactively treated your new fish with a 7-day soak using ParaCleanse, Ich-X, and Maracyn, then follow the above instructions starting with Step 5.
PraziPro has a higher concentration of praziquantel, so we recommend using it when ParaCleanse isn’t quite strong enough or if we’re seeing a problem with certain shrimp parasites like Vorticella and Scutalleria japonica.
Similar to ParaCleanse, PraziPro is safe for fish, invertebrates, plants, and beneficial bacteria, and it’s primarily used to treat tapeworms, flukes, flatworms, and turbellarians. To use PraziPro, follow these steps:
Wild-caught fish often contain lots of parasites that may require three rounds of treatment to fully deworm.
In our personal tanks, we’ve use PraziPro as part of the deworming process for our puffers. First, we treat ParaCleanse for 5 days and then wait two weeks. Then we do a second 5-day treatment of ParaCleanse and then wait a month. Afterwards, we use the 7-day treatment of PraziPro as our final deworming step.
Pond Solutions CyroPro is specially formulated to treat external parasites like fish lice (e.g., Argulus species) and anchor worms (e.g., Lernaea species). The active ingredient of cyromazine works by preventing parasitic insects and crustaceans from molting their exoskeletons. Therefore, it is safe for fish, plants, and snails, but consider removing your shrimp, crayfish, and other crustaceans before treatment.
External parasites like fish lice (seen above) and anchor worms are visible to the naked eye and are often found on pond fish like goldfish and koi.
The water changes before each dose of CyroPro helps to refresh dissolved oxygen levels, remove excess nutrients, and reduce the population of water-borne parasites.
If you do not have access to these medications, aquarium salt is useful for the treatment of external parasites (but isn’t as effective for internal parasites). The salt works by dehydrating the parasites to death before the fish (which have more mass and stored water) are affected. For complete instructions, see our full article on how to treat sick fish with salt.
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domain: pet


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When moms and dads of youngsters with autism know their kid has been actually identified, the 1st inquiry they talk to is “what next?” autism-care center
They might intend to make an effort a variety of treatments as well as procedures. Just before deciding which procedure to seek, they need to know how each type of treatment works and what analysis has discovered about its effectiveness. Hopebridge Autism Therapy
Applied Habits Analysis (ABA).
Applied Habits Evaluation (ABA) is just one of the most commonly made use of treatments for kids along with autism. It uses a range of strategies to help autistic little ones know new abilities.
A typical plan for an autistic kid entails as high as 40 hrs a week of treatment delivered through approved ABA specialists. They develop a direction program that breaks social skills, as an example, into small actions and also awards the little one for finishing each measure.
Along with discovering socially acceptable actions, ABA additionally focuses on teaching the child to stay clear of and switch out problematic actions. Making use of the concepts of operant conditioning and respondent conditioning, the therapist may alter the patient’s habits through coupling a stimulation along with a desired habits.
To see to it that ABA strategies are effective, the specialist should very carefully notice the patient’s behavior and also environment to identify the root cause. This is performed by carrying out an FBA (functional personality assessment).
Drugs are commonly made use of as a therapy for autistic youngsters and also grownups, along with behavior modifications. They are actually made to decrease signs and symptoms of autism, making it much easier for them to obtain the support they require coming from various other procedure procedures.
The absolute most usual sorts of medications are actually antipsychotics, energizers, antidepressants, mood backings, anticonvulsants, as well as anti-anxiety medications. They are actually typically suggested through a pediatric professional and also are best matched to your child’s one-of-a-kind demands.
Anomalous antipsychotics risperidone (Risperdal) as well as aripiprazole (Abilify) are FDA-approved to help reduce frustration in 5-to-16-year-old youngsters with autism. They can additionally decrease attention deficit disorder, stereotyped behaviors, and also minimize drawback and also hostility.
SSRIs are actually another course of antidepressants that are actually typically used for people along with autism. They can easily improve eye connect with, lower twitches, as well as increase social communications.
There are a number of types of psychological approaches that could be made use of to aid youngsters along with autism. One common type of therapy is used behavior analysis (ABA), which involves utilizing beneficial encouragement approaches, such as praise, high-fives or even healthy and balanced handles, to promote p’s and q’s and prevent bad ones.
ABA is commonly utilized to address kids along with autism, as it has actually revealed to become effective in creating social capabilities, foreign language capability, as well as favorable behaviors. ABA therapy is generally combined with other treatments, consisting of distinct trial training (DTT) or Early Demanding Behavior Assistance (EIBI).
Cognitive behavioral therapy may be a helpful treatment for more mature grownups and youngsters detected with autism. It aids people understand and also handle their emotional states and also discover exactly how to deal with stressful circumstances.
Investigation shows that youngsters along with autism profit from starting therapy as quickly as they are identified. This is actually due to the fact that their intellects create a lot faster at this grow older and also will possess much less problem regulating habits than children who have actually not been actually dealt with.
Complementary as well as Substitute Procedures.
Numerous loved ones of kids with autism use complementary and also alternative procedures (CAMERA) such as special diet plans, diet supplements, chiropractic care, creature therapy, arts treatment, mindfulness, and also leisure treatments. It is essential to consult with your child’s doctor before you begin any sort of web cam treatment for your little one.
There is actually no evidence that web cam therapies help with primary symptoms of autism, and they ought to not be used as opposed to effective behavior techniques or medication for various other clinical disorders that may co-occur with ASD.
Nevertheless, there is actually some restricted research showing that CAM can easily assist with specific indicators connected to autism. Two Web cam treatments– n-acetylcysteine and also methylcobalamin– have actually been shown to lessen frustration in folks with ASD.

domain: medical