It is also not clear whether a low dose delivered to a larger vo

It is also not clear whether a low dose delivered to a larger volume in intensity modulated plans compared with simpler plans might reduce the possibility of a compensatory increase in kidney function. Nevertheless, a decrease in relative function of the irradiated kidney concurrent with a reduction in global renal function is probably a reasonable indicator of accumulating renal dysfunction. In summary, this report provides important evidence that radiation nephropathy can be predicted Inhibitors,research,lifescience,medical a priori based on dosimetric parameters and can be documented early using scintigraphic and biochemical

parameters. In the absence of either conclusive and validated dosimetric parameters or pharmacologic radiation mitigators/protectors, the primary driver in regards to sparing renal toxicity is the clinical judgment of the treating physician. The data presented here will serve to guide the treating physician. Footnotes No conflicts of interest.
The synthesis, processing and action of microRNAs is simplistically depicted in figure 1. Functionally Inhibitors,research,lifescience,medical active microRNAs, or mature microRNAs, are 18-22 nucleotide-long, single-stranded RNA molecules with 5′ phosphate and 3′ hydroxyl groups. A nascent mature microRNA, however, arises in pair as a double-stranded Inhibitors,research,lifescience,medical RNA molecule known as a microRNA/microRNA-star (*) duplex from a single precursor RNA (pre-microRNA). Pre-microRNAs are ~60-80 nucleotide-long with

a hairpin-like stem-loop secondary structure. Endoribonulease activity of a cytoplasmic RNAse III enzyme, Dicer, causes the release of the microRNA/microRNA* duplex-bearing stems from the stem-loop structures of pre-microRNAs. Pre-microRNAs

themselves are generated Inhibitors,research,lifescience,medical in the nucleus by the action of another RNAse III endoribonuclease, Drosha, on much longer, primary RNA molecules (pri-microRNAs) that are transcribed by RNA polymerases II and III from microRNA-encoding genes (6), (7). Two nucleotide-long 3′ overhangs on pre-microRNAs are recognized by the Exportin 5 transporter protein which shuttles them into the cytoplasm (8). Many other proteins are involved in this pathway for microRNA genesis. They include the Inhibitors,research,lifescience,medical Sodium butyrate Ran guanosine triphosphatase, which participates in the nuclear export of pre-microRNAs, and the double-stranded RNA-binding proteins DGCR8 (DiGeorge critical Selleckchem SB202190 region 8) and TRBP (transactivating response RNA binding protein), which work alongside Drosha and Dicer, respectively. Though most microRNAs arise in this framework, exceptions have been observed. For instance, maturation of microRNA miR-451 does not require the Dicer-mediated cleavage (9), and the precursor of microRNA miR-1234 is actually an intron (a ‘mirtron’) that is spliced out of the mRNA of a protein-coding gene (10). The sequences of mature microRNAs can get modified through 3’ uridylation or adenylation, or nucleotide substitution, with possible effects on their turnover as well as function (11). Figure 1.

Using a randomization scheme for

the initial algorithmic

Using a randomization scheme for

the initial algorithmic settings, we generated 100 sets of dynamic adjustments in enzyme activities that led to metabolite concentration trends consistent with observations. The overall result thus consisted of a band for each enzyme activity, within which about 90% of all solutions laid, as well as the average trend in each enzyme activity (Figure 5). Details of this analysis will be shown elsewhere. Figure 5 Examples of three classes of heat-induced changes in enzyme activities within sphingolipid metabolism. Heat stress causes the activities of: phosphoserine phosphatase to increase (a); diacylglycerol Inhibitors,research,lifescience,medical (DAG) ethanolamine phosphotransferase to decrease ( … The results are quite intriguing Inhibitors,research,lifescience,medical in detail, because they reveal the balance of three selleck compound forces acting, on the enzymes, induced by heat: Increased activity according to an enzyme’s Q10 value, as alluded to in Equation (2); diminished activity due to partial protein unfolding, an altered

half-life of the corresponding protein and/or mRNA, and/or a reduced production; and change in enzyme activity due to gene expression. As an example for the first category, the activity of phosphoserine phosphatase increases about three-fold and remains at this activity level for at least 30 min (Figure 5a). An example of the second category is diacylglycerol Inhibitors,research,lifescience,medical (DAG) ethanolamine phosphotransferase, whose activity

Inhibitors,research,lifescience,medical was inferred to decrease, after a brief initial increase according to its Q10 (Figure 5b). Sphingoid-1-phosphate phosphatase falls into the third category (Figure 5c). Initially its activity drops quickly, but after about 25 min not only recovers but increases well over its baseline activity. Of note is that these results were extracted from the concentration time series data and the dynamic model strictly by computational means and without additional information. 4. Conclusions In the Inhibitors,research,lifescience,medical past, the effects of heat stress adaptation in the central carbon metabolism of yeast cells have been modeled by forward approaches, that is, by constructing models from their components and subsequently assessing the effects of heat. Several of these studies were ultimately based on a steady-state metabolic model of glycolysis published by Curto et al. [59]. After extensions and adjustments, these models were subjected see more to what-if simulations and to validation tests of the consistency between model predictions and known information about the physiology of heat stress adaptation. An example of this strategy is [48]. The Sorribas group [45,46,47,52] improved on these early studies by developing rigorous optimization methods to explore the space of reasonable combinations of gene expression profiles and study the feasibility of each profile according to a priori established criteria.

The morphine+naloxone group of rats additionally received naloxon

The morphine+naloxone group of rats additionally received naloxone (5 mg/kg) at the end of the protocol. The control group rats received no injections or intervention. The amygdala and CA1 regions of the morphine, saline-treated and intact animals were isolated and prepared for real-time PCR analysis. Results: Administration of naloxone induced withdrawal signs in morphine-treated animals. The results showed a significant decrease in Inhibitors,research,lifescience,medical TRPV1 gene expression in the amygdala (P<0.05) but not the CA1 region of morphine dependent rats. Conclusion: TRPV1 receptors may be involved in morphine-induced dependence. Keywords:

Vanilloid receptor subtype 1, CA1 region, Amygdala, Morphine, Rats Introduction Opioids are important drugs in the treatment of moderate to severe pain. However, chronic use of opioids results in the development of antinociceptive tolerance and physical dependence. Dependence is revealed by a complex withdrawal syndrome associating physical (or somatic) signs with an intensely aversive emotional state.1 Historically, adenylyl cyclase, potassium and calcium channels, and the Inhibitors,research,lifescience,medical transmitter release have been considered in both opioid-induced analgesia and in antinociceptive tolerance. Today, diverse systems and targets are further implicated in the development Inhibitors,research,lifescience,medical of opioid dependence. Transient receptor potential

vanilloid type 1 (TRPV1) is a member of a large family of ligand-gated ion channels. It is activated by capsaicin, the pungent ingredient found in hot chili peppers, resiniferatoxin (RTX), noxious heat (>43°C), low pH2 and numerous mediators.3 These selleck kinase inhibitor channels are expressed in many brain regions4 with the highest level of TRPV1-like immunostaining in the hippocampus and cortex.5 While most studies on TRPV1 Inhibitors,research,lifescience,medical receptors have been conducted at the

level of the spinal cord and peripheral structures, few studies have focused on brain structures. There is several evidence regarding the existence of a functional interaction Inhibitors,research,lifescience,medical between opioid and TRPV1 receptors. For example, Endres-Becker et al.6have reported morphine reduced capsaicin-induced thermal allodynia. Furthermore, Chen and pan found that blockade expression of TRPV1 in the dorsal root ganglion (DRG) increases the analgesic effects of opioids.7 TRPV1, therefore, seems to have an antagonist effect on opioids. On the other hand, it has been documented that excessive and chronic administration of opioids can lead to increased pain;8 knock out TRPV1 mice Oxymatrine do not develop this pain increase.9 It may be concluded that TRPV1 channels also play an important role in increased pain following chronic administration of opioids. Co-localization of TRPV1 and mu-opioid receptors (MOR) in DRG10 and the decrease in opioid ligand affinity in the rat brain upon capsaicin treatments11 also suggest the existence of a functional interaction. Previous studies have shown the involvement of both dorsal hippocampus and amygdala in opioid-induced conditioned place preference (reward).

For more information about light

For more information about light therapy, see the multilingual nonprofit Web site where questionnaires arc available for downloading, and join the discussion forum at:
Sleep is vital for normal health and well-being. Without sufficient sleep, adults often experience functional decrements that may lead to accidents,1 increased risks for physical2,4 and mental illness,3,5,6 decreased cognitive PF-562271 purchase performance4,7 (especially with aging8), and increased mortality.9 A recent Centers for Disease Control (CDC) analysis of 2006 data from the Behavioral Risk Factor Surveillance System (BRFSS) also determined that women are at higher risk of sleep

disturbance (12.4%) Inhibitors,research,lifescience,medical than males (9.9%)10 and therefore, understanding the factors that impact sleep in women is an important focus for clinical research.11 Women report more sleep disturbance than men, but objective measures show

less sleep disturbance.12,13 Measured objectively Inhibitors,research,lifescience,medical by polysomnography (PSG), sleep shows changes in architecture and distribution of sleep stages across the lifespan. For example, a meta-analysis by Ohayon et al14 showed that important sleep measures such as total sleep time (TST), sleep efficiency (SE), percentage of slow- wave sleep (SWS), percentage of REM sleep, and REM latency significantly decreased with advancing age in adults. Inhibitors,research,lifescience,medical Conversely, measures of sleep typically associated with less restful sleep (sleep latency [SL], Stage 1% and Stage 2% sleep, and wake after sleep onset [WASO] times) significantly increased with age. Furthermore, Ohayon et al found differences in quantitative sleep measures related to gender.

Generally speaking, both sexes showed similar effects of aging on most sleep variables; Inhibitors,research,lifescience,medical however, larger effect sizes were observed in women for TST, SE, Stage 1 percentage, and REM latency, suggesting Inhibitors,research,lifescience,medical that aging had a greater impact on these variables in women than men. As well, women appeared to have longer TST and SL, lower Stage 2 percentage sleep, and greater percentage of SWS than agematched men. to In addition to age-related changes, women also experience gender-specific physiological changes that potentially disrupt their sleep. Changes during the menstrual cycle,15 pregnancy,16 in the postpartum period,17 and at menopause18 are associated with alterations in qualitative and quantitative sleep measures. Women are also more predisposed to develop depressed mood,19 especially during these periods of hormonal change20 which may further compromise their nighttime sleep. Nevertheless, while subjective reports of sleep disturbances in association with disturbed mood, aging, and altered reproductive status (RS) are widely reported, carefully controlled studies of objectively measured sleep alterations associated with alterations in mood and RS are uncommon (see review in ref 21).

The underlying mechanism

responsible for muscle weakness

The underlying mechanism

responsible for muscle weakness and wasting remains to be established. Recent findings suggest that DM mutations can affect gene expression in multiple ways. Altered activity and/or localization of MBNL1 and CELF1 may alter transcription, translation and cell signaling (68, 69). Moreover it has been demonstrated that in DM1 the highly regulated pathways of miRNA is altered in skeletal muscle and heart tissue potentially contributing to DM1 pathogenetic mechanisms and in DM2 skeletal Inhibitors,research,lifescience,medical muscle (70-73). Another open question in the field of DM is to clarify the pathomecanisms underlying the phenotypic differences between DM1 and DM2. Clinical signs in DM1 and DM2 are similar, Inhibitors,research,lifescience,medical but there are some distinguishing features: DM2 is generally

less severe and lacks a prevalent congenital form. This suggests that other cellular and molecular pathways are involved besides the shared toxic-RNA gain of function hypothesized. Disease-specific selleck inhibitor manifestations may result from differences in spatial and Inhibitors,research,lifescience,medical temporal expression patterns of DMPK and CNBP genes. Similarly, changes in the expression of neighbouring genes may define diseasespecific manifestations. Importantly, the role of CELF1 in DM2 is particularly intriguing with contradictory results being reported (54, 59, 62). Another possible explanation for the clinical differences between the two DM forms is the reduction of DMPK or ZNF9 protein levels in DM1 and DM2 respectively (3, 74-76). Indeed both knockout mouse models for DMPK and ZNF9 show the phenotypic aspects Inhibitors,research,lifescience,medical of DM (77, 78). Taken together these observations seem indicate that the emerging pathways of molecular pathogenesis are far more complex than previously appreciated. Diagnostics Inhibitors,research,lifescience,medical Laboratory tests As for all genetics diseases with identified mutation, the typical DM1 and DM2 diagnostic method is mutation verification by genetic tests. In the case of DM1, symptoms and family history are often clear and distinctive enough to make a clinical diagnosis, and the mutation

can be confirmed by PCR and Southern Blot analysis. PCR analysis is used to detect repeat lengths less than 100 and Southern blot analysis to detect larger expansions. Predictive testing in asymptomatic relatives as well as prenatal and preimplantation diagnosis can also be only performed. On the contrary, the wide clinical spectrum of DM2 phenotype makes the clinical diagnosis more difficult. Moreover conventional PCR and Southern blot analysis are not adequate for a definitive molecular diagnosis in DM2 due to the extremely large size and somatic instability of the expansion mutation (9, 46). The copy number of DM2 CCTG is below 30 in phenotypically normal individuals and up 11.000 in patients (79).

hcp med harvard edu/ncs/) and the National Health and Nutrition E and the National Health and Nutrition Examination Survey (NHANES) ( nchs/nhanes.htm) should begin to address

the gap in knowledge regarding the epidemiology of adolescent mood disorders in the US. Global progress There is an increasing effort, to identify gaps in our knowledge of the state of child mental health at the global level as well. The Atlas Project, run by the WHO,87,117 recently find more collected information on cultural factors associated with the burden and impairment, of mental disorders in children and adolescents in 66 countries. Although there were differences in policies and programs across low and high income countries, they found that there Inhibitors,research,lifescience,medical was a general lack of specific policies, data-gathering capacity, and continuum of care for children.87 There have also been collaborative efforts to increase awareness of child mental disorders across the world. For example, through the auspices Inhibitors,research,lifescience,medical of the World Psychiatric Association,

the WHO, and the International Association of Child and Adolescent. Psychiatry and Inhibitors,research,lifescience,medical Allied Professionals, a Child Mental Health Task Force was formed to educate and develop programs to disseminate awareness of child mental health in nine different, countries around the world.124 While there is still a large amount, of change and progress that needs to be made in the area of child and adolescent mental health, studies and programs such as these arc moving the global community in the right direction. Selected abbreviations and acronyms Inhibitors,research,lifescience,medical ADHD attention deficit-hyperactivity disorder CD conduct disorder GAD generalized anxiety disorder MDD major depressive disorder ODD oppositional-defiant disorder

psychopathology has identified the defining clinical and contextual features of depression in youngsters. In particular, empirical studies have characterized the longitudinal course of depressive illness and common patterns of co-occurring psychiatric conditions. Inhibitors,research,lifescience,medical The functional consequences of early-onset illness have also been documented. A growing body of research is identifying the neurobiological and many psychological correlates. In addition, studies are beginning to identify specific genetic and experiential risk factors. In general, the core patterns of depressive disorders across the lifespan are emerging. This paper details the phenomenology, correlates, clinical course, and consequences of pediatric depression, highlighting the similarities and differences in the characteristics of depression among children, adolescents, and adults. A few caveats are warranted before proceeding to the following sections. The term “depression” refers to unipolar mood disorders only. Up to now, most of the research on pediatric depression was conducted in major depressive disorder, and therefore, the reported findings are primarily for this condition.

D3 and D4 lymphadenectomies include their respective compartments

D3 and D4 lymphadenectomies include their respective compartments. AJCC criteria designates involvement of hepatoduodenal, retropancreatic, mesenteric, and para-aortic nodes (i.e., compartment III and IV) as distant metastases (9). CT criteria for lymph node metastases include size, shape, central necrosis and heterogeneity (13), (14). When these characteristics are present there is a strong correlation with metastatic involvement. However, CT sensitivity suffers because a small tumor burden in a lymph node is unlikely to produce

Inhibitors,research,lifescience,medical the morphological changes sufficient to satisfy CT criteria. In concept, PET seems an excellent adjunct therapy to detect these anatomically small but potentially metabolically active focuses of metastatic disease. However, the relatively poor spatial resolution of PET makes it less effective because of the difficulty of distinguishing Inhibitors,research,lifescience,medical compartment I and II nodes from the primary tumor itself. The real value of PET may be in the detection of “distant” Inhibitors,research,lifescience,medical metastatic disease in compartments III and

IV and not amenable to surgical resection with a standard D2 lymphadenectomy. Identification of further spread with PET imaging may influence surgical planning for a more aggressive lymphadenectomy or the decision to avoid surgery altogether as futile and unnecessarily morbid (15). Solid organ metastasis from the stomach occurs most commonly in the liver via hematogenous dissemination through the portal vein (16), (17). Lymphatic and peritoneal dissemination are also Inhibitors,research,lifescience,medical common pathways of spread in gastric malignancy. Although distant metastases are frequently detectable using contrast CT, PET is perhaps most useful in the detection of

these distant sites of solid organ metastases. A meta-analysis by Kinkel designated PET as the most sensitive noninvasive imaging modality for this purpose (18). Because radio-tracer is distributed throughout the body, larger volumes can be more Inhibitors,research,lifescience,medical easily scanned than is practical with CT. Peritoneal dissemination is a poor prognostic factor. Detection of peritoneal metastases may change the surgical strategy from curative to palliative or deter the surgeon through from laparotomy altogether. Increasingly sophisticated CT scans facilitate diagnosis of peritoneal metastases prior to visual inspection during surgery. PET may give additional sensitivity to CT. Diffuse uptake of tracer that obscures the serpiginous DAPT secretase cost outline of the bowel may be an indicator of peritoneal metastases, as well as discrete areas of local uptake along areas within the peritoneal cavity that are otherwise anatomically unexplained (i.e. outside expected nodal stations or solid viscera) (11). Response to therapy PET may predict response to preoperative chemotherapy in gastric cancer. Ott et al.

21 The study showed

that the incidence of PONV ranged fro

21 The study showed

that the incidence of PONV ranged from 12% to 35%. The study shows that patients who experienced PONV might have received higher doses of opioids. In an earlier study on volunteers, a high incidence of nausea was observed.11 and persisted for hours in some of the subjects. However, some of the subjects in that study,11 received much higher doses of remifentanil than that used in the present study. Also, In our study, there was no significant difference between the three groups in terms of pain score at all the Inhibitors,research,lifescience,medical times. The mean VAS for pain and meperidine consumption in group R was insignificantly more than that in group F at recovery and 4 hour after surgery. Similar to our findings, an earlier study found that compared to remifentanil, fentayl used for balanced anesthesia could produce a better early postoperative analgesia.3 The differential effects of remifentanil may be Inhibitors,research,lifescience,medical due to its short half-life, which influences the time course of pain Caspase activation relief compared Inhibitors,research,lifescience,medical to longer acting opioids.1 The findings of the present study should be

considered in light of two limitations. One limitation is that the effect of opioids on clinical outcome variables such as time to discharge or number of unexpected hospital readmissions could not be addressed, because all patients remained in the hospital for 24 hours after discharge from the recovery Inhibitors,research,lifescience,medical area. The second limitation is the lack of both strict follows up methodology and proper statistical power and small sample size. Therefore, further studies with different methodologies and appropriate sample size might be required to evaluate PONV and pain. Conclusion The Inhibitors,research,lifescience,medical findings of the

present study may suggest that compared with fentanyl, remifentanil had no effect on PONV and postoperative pain relief. They also show that early postoperative analgesia was better with fentanyl, and postoperative meperidine consumption was significantly less with fentanyl than with remifentanil or combined fentayl and morphine. Conflict of Interest: None declared
Coagulase-negative staphylococci (CoNS) are the major causes of hospital acquired infections, and are often isolated from neonates, immunocompromised individuals and patients with indwelling prosthetic devices.1,2 Among Terminal deoxynucleotidyl transferase the CoNS, Staphylococcus epidermidis is frequently associated with bacteremia, urinary tract infections and infections associated with indwelling medical devices.3 The major concern with regard to the treatment of staphylococcal infections is antibiotic resistance among the clinical isolates. Indeed, over 90% of all nosocomial isolates are resistant to penicillin and an increasing number are becoming resistant to the semisynthetic, β-lactamase resistant derivatives represented by oxacillin.

Nanoxel-PM is efficacious and less toxic than free docetaxel form

Nanoxel-PM is efficacious and less toxic than free docetaxel formulation and was evaluated in comparison with Taxotere in preclinical studies. Nanoxel-PM can reduce sideeffects of hypersensitivity reactions and fluid retention while retaining antitumor efficacy in cancer patients [22]. Further studies led to the development of new formulations of liposomal paclitaxel. The special CH5424802 datasheet composition of the liposomal membrane which contains high doses

of paclitaxel could reduce the aggregation giving the molecule higher stability and confers an increase of efficacy in animal models as in human tumors [23]. An hydrotropic polymer micelle Inhibitors,research,lifescience,medical system has also been developed for delivery of poorly water-soluble drugs as paclitaxel. This polymer showed not only higher loading capacity but also enhanced physical stability in aqueous media and provides an alternative approach for formulation Inhibitors,research,lifescience,medical of poorly soluble drugs [24, 25]. 3. Nab-Paclitaxel in Breast Cancer Treatment Breast cancer (BC) is the most common cancer in female patients and follows lung cancer as the most common cause of female cancer death. While only 5–7% of BC patients present metastatic disease (mBC) at diagnosis and more than 30% presenting localized disease will eventually recur, 5 year survival of advanced disease is

Inhibitors,research,lifescience,medical less than 20% [33]. Current treatment of advanced breast cancer is mainly aimed to ameliorate quality of life and prolong survival. Treatment choice is not an easy task in terms of drug selection and combination. Chemotherapy plays an essential role for the treatment of Inhibitors,research,lifescience,medical mBC. Among anticancer drugs, taxanes are

considered the most effective, while their use involves long infusion time, neurotoxicity, and high risk of hypersensitivity reactions [8, 34, 35]. These latter effects are due to allergic reactions induced by the use of solubilizing agents (as chromophores) and Inhibitors,research,lifescience,medical today are less common due to the use in the clinical practice of corticosteroids and antihistamines [36]. In order to overcome these important limitations, a major interest is devoted to novel drugs as nab-paclitaxel, eribulin, ixabepilone, PARP inhibitors, and new HER 2 inhibitors as lapatinib, pertuzumab, TDM1, and neratinib [37–43]. Following phase I studies, PDK4 by Ibrahim et al. in 2002 [19] and by Teng et al in 2004 [44], which led to MTD identification at 300mg/m2 in the three weekly schedule with neurotoxicity as dose limiting toxicity, Nyman et al. in 2005 [45] identify in the weekly schedule the MTD at 100mg/sqm for highly pretreated patients and 150mg/m2 for nonhighly pretreated patients with grade 4 neutropenia and grade 3 neuropathy as DLT with earlier onset at higher dosages. The pivotal phase 3 study was published in 2005 where Gradishar et al.

Low-frequency signal drift was removed using a high-pass filter (

Low-frequency signal drift was removed using a high-pass filter (cutoff = 128 sec) and an autoregressive modeling (AR [1]) of temporal autocorrelations was applied. At the first level, subject-specific Cilengitide nmr contrast images were generated for each working-memory load condition versus baseline. Each working-memory load versus baseline contrast was then entered into second-level GLM ANOVAs to obtain SPM-F maps that investigated: (1) the main effect Inhibitors,research,lifescience,medical of task; (2) the main effect of group (PD-Off, Controls); (3) the group by task interaction (PD-Off, Controls × high-, medium-, and low-load working memory); (4) the main effect of treatment (PD-Off, PD-On); and

(5) the treatment by task interaction (PD-Off, PD-On × high-, medium-, and low-load working memory). Furthermore, to account for possible effects of behavioral variability on brain activations, analyses (2), (3), (4), and (5) were repeated including RT and accuracy as variables of no interest. Of note,

Inhibitors,research,lifescience,medical we also tested for linear and quadratic interactive effects between medication and DAT-BPND values Inhibitors,research,lifescience,medical on striatal BOLD responses in the PD group. The SPM model included two separate regressors for each patient: (1) the DAT-BPND values (testing for linear effects); (2) the square of these values (testing for quadratic functions). This way, it is possible to investigate linear fits (excluding quadratic ones) and vice versa (i.e., testing for quadratic effects factoring out linear ones). This method has been used before Inhibitors,research,lifescience,medical in fMRI studies exploring linear and nonlinear relations between drug effects on clinical variables in PD patients (Rowe et al. 2008). The same method was also used to study linear and quadratic effects of disease duration. Analyses exploring activations within the whole brain were thresholded at P < 0.05, family-wise error (FWE), whole-brain correction. In addition, given our strong a priori hypotheses on specific Inhibitors,research,lifescience,medical PFC and striatal regions, we employed a ROI approach. ROIs included

the anterior cingulate cortex (ACC); the superior, MTMR9 middle, and inferior frontal gyrus (SFG, MFG, IFG); the caudate; and putamen and were created using the “aal.02” atlas ( (Tzourio-Mazoyer et al. 2002). The statistical threshold for ROI analyses was set at P < 0.05, FWE, small volume correction (svc) (Worsley et al. 1996; Friston 1997). Because 12 ROIs (six on the left, six on the right) with different size were defined, we treated them as separate hypotheses and further adjusted the significance for multiple comparison testing using Dunn–Sidak correction (Howell et al. 2007). Finally, for explorative purposes only, we also report brain regions not predicted a priori but that met a threshold of P < 0.001, uncorrected, >10 contiguous voxels.