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Many believe that an increase in the public confidence in the investigation of sexual crimes, and in conviction rates, will lead to an increase in the reporting of these crimes. Consequently, Forensic Science Providers are continually striving to make improvements in evidence recovery and examination and the subsequent interpretation of evidence. One development is in methods that enable an individual to self-sample. However, in cases where a complainant has self-sampled, questions of when the samples were taken, how they were stored and so on, can be legitimately raised. Additionally the continuity and integrity of evidential samples may be questioned resulting in them not being acceptable to the courts and potential evidence could therefore be lost. There is a large emotional and psychological impact of sexual assault and rape and no complainant who reports a sexual assault and recovers material should have that evidence inadmissible to a court. Specialised units for victims of alleged sexual violence are available and offer far more than the recovery of evidential samples. This commentary on behalf of the Faculty of Forensicamp; Legal Medicine (FFLM) and the Association of Forensic Science Providers Body Fluid Forum (AFSP BFF) highlights the need for after care for the victims of sexual assault and why all evidence recovered in cases of alleged sexual assault and sexual violence should be obtained in line with best practice protocols.

This paper demonstrates a logical framework for evaluating forensic evidence, first described by Cook et al. [1,2], using a casework example of an alleged sexual assault involving semen transfer. Here we show in real time how the case strategy can change with additional information and how to use available experience and published data to interpret the findings obtained, given the background information provided. The findings of the case are interpreted using the Bayesian approach and are reported by giving the strength of support of scientific findings for one proposition rather than a competing proposition, as per the European Network of Forensic Science Institutes (ENSFI) guideline for evaluative reporting. We believe that using this paper as a template will aid other Forensic Science Practitioners (FSP) to add value and weight to their work by assisting them in evaluating and interpreting their own findings.

Consistent with the idea that curiosity enhances information seeking, it has been shown that activity within both the dopaminergic circuit and hippocampus supports curiosity-enhanced learning. However, the role of whole-brain mechanisms involved in cognitive control (fronto-parietal network; FPN) and memory integration (default mode network; DMN) that might underpin curiosity states and their effects on memory remain elusive. We hypothesised that the FPN and DMN should distinguish between high- and low-curiosity conditions and be recruited more heavily for later remembered information associated with high-curiosity. Here, we used functional magnetic resonance imaging whilst participants completed a trivia paradigm, in which we presented trivia questions associated with high- and low-curiosity, followed by the associated answer. After a short delay, we tested memory for trivia answers. We adopted a network-based parcellation of the brain into subnetworks of the FPN and DMN to examine how neural activity within, and functional connectivity between, each subnetwork predicts curiosity-enhanced memory. Across elicitation and relief of curiosity, we found focal recruitment of FPNA and widespread recruitment of DMN subnetworks in support of curiosity and curiosity-enhanced memory. Most importantly, during the elicitation of curiosity, functional subcortical connectivity and across cortical networks, but not subcortical-cortical coupling, correlated with curiosity-enhanced memory. However, during the relief of curiosity, coupling between subcortical regions and DMNA emerged in support of curiosity-enhanced memory. Taken together, our results provide the first evidence about how neuromodulatory mechanisms via the hippocampal-dopaminergic circuit trigger states of curiosity and thereby communicate to higher-order cortical regions to facilitate curiosity-enhanced memory.Significant statementDoes neural activity within, and functional connectivity between, the dopaminergic-hippocampal network, fronto-parietal network (FPN), and default mode network (DMN) underpin curiosity states and their effects on memory? Here, we show how the dopaminergic system together with the hippocampus interact specifically with subnetwork DMNA potentially reflecting how subcortical regions support the enhancement of memory intergration of semantic information associated with curiosity. As DMNA (the core DMN subnetwork) was also functionally coupled with the whole DMN network and the semantic control network (FPNA), these findings provide a plausible neuromodulatory mechanism through which hippocampal-dopaminergic input triggers curiosity and then communicates to higher-order brain regions via DMNA to facilitate curiosity-enhanced memory.

Summary A core goal in cognitive neuroscience is identifying the physical substrates of the patterns of thought that occupy our daily lives. Contemporary views suggest that the landscape of ongoing experience is heterogeneous and can be influenced by features of both the person and the context. This perspective piece considers recent work that explicitly accounts for both the heterogeneity of the experience and context dependence of patterns of ongoing thought. These studies reveal that systems linked to attention and control are important for organizing experience in response to changing environmental demands. These studies also establish a role of the default mode network beyond task-negative or purely episodic content, for example, implicating it in the level of vivid detail in experience in both task contexts and in spontaneous self-generated experiential states. Together, this work demonstrates that the landscape of ongoing thought is reflected in the activity of multiple neural systems, and it is important to distinguish between processes contributing to how the experience unfolds from those linked to how these experiences are regulated., Cognitive Neuroscience; Psychology; Techniques in Neuroscience

Curiosity states benefit memory for curiosity target information, but also incidental information presented during curiosity states. Curiosity-related activity in dopaminergic regions and the hippocampus predicts such curiosity-enhanced memory for incidental information. However, it is not known whether incidental curiosity-enhanced memory depends on when incidental information during curiosity states is encountered. Here, participants incidentally encoded unrelated face images at different time points while they anticipated answers to trivia questions. Across two experiments, we found memory enhancements for unrelated faces presented during high- compared to low-curiosity states, but only when a face was presented shortly after a trivia question. This incidental curiosity-enhanced memory was independent of the type of encoding judgement and was evident both after a short (Experiment 1) and a 24-hour delay (Experiment 2). The findings suggest that processes associated with the elicitation of curiosity - but not processes preceding the satisfaction of curiosity - enhance memory for incidental information.

Neural activity within the default mode network (DMN) is widely assumed to relate to processing during off-task states, however it remains unclear whether this association emerges from a shared role in self or social content that is common in these conditions. In the current study, we examine the possibility that the role of the DMN in ongoing thought emerges from contributions to specific features of off-task experience such as self-relevant or social content. A group of participants described their experiences while performing a laboratory task over a period of days. In a different session, neural activity was measured while participants performed Self/Other judgements (e.g., Does the word ‘Honest’ apply to you (Self condition) or Barack Obama (Other condition)). Despite the prominence of social and personal content in off-task reports, there was no association with neural activity during off-task trait adjective judgements. Instead, during both Self and Other judgements we found recruitment of caudal posterior cingulate cortex—a core DMN hub—was above baseline for individuals whose laboratory experiences were characterised as detailed. These data provide little support for a role of the DMN in self or other content in the off-task state and instead suggest a role in how on-going thought is represented.

When environments lack compelling goals, humans often let their minds wander to thoughts with greater personal relevance; however, we currently do not understand how this context-dependent prioritisation process operates. Dorsolateral prefrontal cortex (DLPFC) maintains goal representations in a context-dependent manner. Here, we show this region is involved in prioritising off-task thought in an analogous way. In a whole brain analysis we established that neural activity in DLPFC is high both when ‘on-task’ under demanding conditions and ‘off-task’ in a non-demanding task. Furthermore, individuals who increase off-task thought when external demands decrease, show lower correlation between neural signals linked to external tasks and lateral regions of the DMN within DLPFC, as well as less cortical grey matter in regions sensitive to these external task relevant signals. We conclude humans prioritise daydreaming when environmental demands decrease by aligning cognition with their personal goals using DLPFC., The authors show that the dorsolateral prefrontal cortex (DLPFC) is involved in both on-task thought during increased environmental demands, and off-task thought during decreased demand–suggesting a role for the DLPFC in prioritising goals in a context-dependent manner.

The ability to visualise different people and places in imagination is a core element of human cognition. Contemporary neuroimaging research highlights regions of primary visual cortex as important in instantiating images in the mind’s eye. Here we combine task-based functional magnetic resonance imaging with measures of intrinsic brain organisation to show the ventral attention, or salience, network, also plays an important role in visual imagination. In a task-based study we replicated prior observations of regions of medial occipital cortex, including Brodmann Area 17, showing greater neural activity during imagination than when perceiving similar stimuli. In addition, we found regions of the ventral attention network, and in particular right dorsolateral prefrontal cortex (BA 9/46), were activated by the same acts of imagination. In a subsequent resting-state study, we demonstrated medial occipital cortex regions form a functional network with regions of the ventral attention network that were also active during imagination. Furthermore, this pattern was maximised in an overlapping region of right dorsolateral prefrontal cortex for individuals whose self-reported imagery had stronger negative affect. Together these data suggest visual imagination relies on functional interactions between regions of primary visual cortex with the ventral attention system, and in particular, with a region of right dorsolateral prefrontal cortex.

This study is the first to examine the background level of male DNA on underpants worn by females in the absence of sexual contact. Here, we examined 103 samples from the inside front of underpants from 85 female volunteers. Samples were examined for the presence of male DNA using NGM SElect and PowerPlex Y23 kits. Only five samples gave a "complete" Y-STR profile, even though 83.5% of our volunteers cohabited with a male. In all cases where a partner reference sample was available, the Y-STR profile matched the cohabiting partner. We have demonstrated that a Y-STR profile is not expected on the inside front of underpants worn by females after social contact alone. The results of this study are informative for evaluating the significance of a Y-STR profile on underpants in cases of alleged sexual assault.

Neural activity within the default mode network (DMN) is widely assumed to relate to processing during off-task states, however it remains unclear whether this association emerges from a shared role in self or social cognition. In the current study, we examine the possibility that the role of the DMN in ongoing thought emerges from contributions to specific features of off-task experience such as self-relevant or social content. A group of participants described their experiences while performing a laboratory task over a period of days. In a different session, neural activity was measured while participants performed self/other judgements. Despite the prominence of social and personal content in off-task reports, there was no association with neural activity during off-task trait adjective judgements. Instead, during both self and other judgements we found recruitment of caudal posterior cingulate cortex - a core DMN hub - was above baseline for individuals whose laboratory experiences were characterised as detailed. These data provide little support for a role of the DMN in self or other content in the off-task state and instead suggest a role in how on-going thought is represented.

Highlights • Variations in semantic performance are reflected in resting-state networks. • Inferior frontal connectivity predicts verbal fluency performance. • Connectivity between visual and anterior temporal areas predicts synonym judgement., Efficient semantic cognition depends on accessing and selecting conceptual knowledge relevant to the current task or context. This study explored the neurocognitive architecture that supports this function by examining how individual variation in functional brain organisation predicts comprehension and semantic generation. Participants underwent resting state functional magnetic resonance imaging (fMRI) and, on separate days, performed written synonym judgement, and letter and category fluency tasks. We found that better synonym judgement for high frequency items was linked to greater functional coupling between posterior fusiform and anterior superior temporal cortex (aSTG), which might index orthographic-to-semantic access. However, stronger coupling between aSTG and ventromedial prefrontal cortex was associated with poor performance on the same trials, potentially reflecting greater difficulty in focussing retrieval on relevant features for high frequency items that appear in a greater range of contexts. Fluency performance was instead linked to variations in the functional coupling of the inferior frontal gyrus (IFG); anterior IFG was more coupled to regions of primary visual cortex for individuals who were good at category fluency, while poor letter fluency was predicted by stronger coupling between posterior IFG and retrosplenial cortex. These results show that individual differences in functional connectivity at rest predict semantic performance and are consistent with a component process account of semantic cognition in which representational information is shaped by control processes to fit the current requirements, in both comprehension and fluency tasks.

Human cognition is flexible - drawing on both sensory input, and representations from memory, to successfully navigate complex environments. Contemporary accounts suggest this flexibility is possible because neural function is organized into a hierarchy. Neural regions are organized along a macroscale gradient, anchored at one end by unimodal systems involved with perception and action, and at the other by transmodal systems, including the default mode network, supporting cognition less directly tied to immediate stimulus input. The current study tested whether this cortical hierarchy captures modes of behaviour that depend on immediate input, as well as those that depend on representations from memory. Participants made decisions regarding the location or identity of shapes using information in the environment (0-back) or from a prior trial (1-back). Using task based imaging we established that, regardless of the nature of the decision, medial and lateral visual cortex were recruited when decisions rely on immediate input, while transmodal regions were recruited when judgments depend on information from the prior trial. Using principal components analysis, we demonstrated that shifting decision-making from perception to memory altered the focus of neural activity from unimodal to transmodal regions (and vice versa). Notably, the more pronounced these shifts in neural activity from unimodal to transmodal regions when decisions relied on memory, the more efficiently individuals performed this task. These data illustrate how the macroscale organization of neural function into a hierarchy allows cognition to rely on input, or information from memory, in a flexible and efficient manner.

Regions of transmodal cortex, in particular the default mode network (DMN), have historically been argued to serve functions unrelated to task performance, in part because of associations with naturally occurring periods of off-task thought. In contrast, contemporary views of the DMN suggest it plays an integrative role in cognition that emerges from its location at the top of a cortical hierarchy and its relative isolation from systems directly involved in perception and action. The combination of these topographical features may allow the DMN to support abstract representations derived from lower levels in the hierarchy and so reflect the broader cognitive landscape. To investigate these contrasting views of DMN function, we sampled experience as participants performed tasks varying in their working-memory load while inside an fMRI scanner. We used self-report data to establish dimensions of thought that describe levels of detail, the relationship to a task, the modality of thought, and its emotional qualities. We used representational similarity analysis to examine correspondences between patterns of neural activity and each dimension of thought. Our results were inconsistent with a task-negative view of DMN function. Distinctions between on- and off-task thought were associated with patterns of consistent neural activity in regions adjacent to unimodal cortex, including motor and premotor cortex. Detail in ongoing thought was associated with patterns of activity within the DMN during periods of working-memory maintenance. These results demonstrate a contribution of the DMN to ongoing cognition extending beyond task-unrelated processing that can include detailed experiences occurring under active task conditions.

The IStructE Pai Lin Li Travel Award funded the author for an investigation into current practice precast concrete construction in the USA. The Federal Highways Administration (FHWA) in the USA has invested heavily in research into precast concrete construction through its Accelerated Bridge Construction (ABC) programme. The FHWA’s research has had a focus on innovative techniques for joining structural precast concrete elements together.Grouted splice couplers and Ultra-High Performance Concrete are the two key enabling techniques that were investigated in this research. The replacement of 6 36m span bridges over Interstate 78 in Pennsylvania used these techniques and completed each bridge replacement in 40 days. This paper investigates the development of these techniques, the benefits they could have on the UK construction industry and what actions need to be taken to realise those benefits.

The tendency for the mind to wander to concerns other than the task at hand is a fundamental feature of human cognition, yet the consequences of variations in its experiential content for psychological functioning are not well understood. Here, we adopted multivariate pattern analysis to simultaneously decompose experience-sampling data and neural functional-connectivity data, which revealed dimensions that simultaneously describe individual variation in self-reported experience and default-mode-network connectivity. We identified dimensions corresponding to traits of positive-habitual thoughts and spontaneous task-unrelated thoughts. These dimensions were uniquely related to aspects of cognition, such as executive control and the ability to generate information in a creative fashion, and independently distinguished well-being measures. These data provide the most convincing evidence to date for an ontological view of the mind-wandering state as encompassing a broad range of different experiences and show that this heterogeneity underlies mind wandering’s complex relationship to psychological functioning.

We often think about people, places and events that are outside of our immediate environment. Although prior studies have explored how we can reduce the occurrence of these experiences, the neurocognitive process through which they are produced are less understood. The current study builds on developmental and evolutionary evidence that language helps organise and express our thoughts. Behaviorally, we found the occurrence of task unrelated thought (TUT) in easy situations was associated with thinking in words. Using experience sampling data, in combination with online measures of neural function, we established that activity in a region of anterior cingulate cortex / medial-prefrontal cortex (mPFC) tracked with changes in the expression of TUT. This region is at the intersection of two mPFC clusters identified through their association with variation in aspects of spontaneous thought: thinking in words (dorsal) and mental time travel (ventral). Finally, using meta-analytic decoding we confirmed the dorsal/ventral distinction within mPFC corresponding to a functional difference between domains linked to language and meaning and those linked to memory and scene construction. This evidence suggests a role for mPFC in the expression of TUT that may emerge from interactions with distributed neural signals reflecting processes such as language and memory.

The default mode network supports a variety of mental operations such as semantic processing, episodic memory retrieval, mental time travel and mind-wandering, yet the commonalities between these functions remains unclear. One possibility is that the default mode network supports cognition that is independent of the immediate environment; alternatively or additionally, it might support higher-order conceptual representations that draw together multiple features. We tested these accounts using a novel paradigm that contrasted decisions based on perceptual and conceptual features, while separately manipulating whether these decisions were driven by features in the environment or recovered from memory. Task-based fMRI identified regions that responded when stimulus independence and semantic retrieval were combined: these included left and right angular gyri and left middle temporal gyrus. Although these sites were within the default mode network, they showed a stronger response to demanding memory judgements than to an easier perceptual task, contrary to the view that they support automatic aspects of cognition. In a subsequent analysis, we showed that these regions were located at the extreme end of a macroscale gradient, which describes gradual transitions from sensorimotor to transmodal cortex. This shift in the focus of neural activity towards transmodal default mode regions might reflect isolation from specific sensory inputs, both when decisions are guided by conceptual as opposed to perceptual features and when cognitive states are generated in the absence of input.

The transfer of DNA from hands to objects by holding or touching has been examined in the past. The main purpose of this study was to examine the variation in the amount of DNA transferred from hands to glass, fabric and wood. The study involved 300 volunteers (100 for glass, 100 for fabric and 100 for wood) 50% of which were male and 50% female. The volunteers held the material for 60s. The DNA was recovered from the objects using a minitape lift, quantified using the Quantifiler kit assay, extracted using a 'Qiagen(®) QIAamp DNA mini kit' and amplified using the AmpFlSTR(®) SGM Plus™ Amplification Kit at 28 cycles. The results show that using ANOVA there was a significant difference (F=8.2, p

Variations in genes associated with cholesterol homeostasis have been reported to modify the risk of developing Alzheimer disease (AD). To date there have been few investigations into variations in genes directly involved in cholesterol biosynthesis and AD. We investigated the influence of the -911C>A polymorphism (rs3761740) in the hydroxy-methyl-glutaryl CoA reductase (HMGCR) gene promoter on basal and regulated transcription, plasma cholesterol levels and the association with AD. Under in vitro conditions the A allele was found to be significantly more responsive to SREBP-2 mediated regulation than the C allele. In an age and sex matched case-control study, the genotype distribution and allele frequency of this polymorphism were not associated with AD (OR=1.03; 95% CI=0.72-1.48). However, we did find evidence supporting an interaction between the HMGCR A allele, the APOE E4 allele and an altered risk of AD (OR=2.41; 95% CI=0.93-6.22).

Mevalonate kinase (MVK) catalyses an early step in cholesterol biosynthesis converting mevalonate to phosphomevalonate. Cob(I)alamin adenosyltransferase (MMAB) converts cob(I)alamin to adenosylcobalamin, functionally required for mitochondrial methylmalonyl-CoA mutase activity and succinyl-CoA formation. These two synthenic genes are found in a head-to-head formation on chromosome 12 in man and chromosome 5 in mouse. The 330bp intergenic region showed several conserved NF-Y sites indicative of potential bidirectional regulatory SREBP synergism. Both MVK and MMAB appear to be regulated in a similar manner, to a large extent by SREBP-2, since their tissue expression pattern was similar and both genes were suppressed by an excess of cholesterol as well as SREBP-2 knockdown. Statin treatment in mice upregulated both Mvk and Mmab mRNA levels indicating that this treatment may be useful in inborn errors of cblB complementation associated with methylmalonic aciduria as well as hyper IgD and periodic fever syndrome (HIDS).

Squalene epoxidase (SE) is one of the most highly regulated enzymes of the cholesterol biosynthesis pathway. Here we identify the molecular basis for SREBP-2 synergy with NF-Y as the prime regulator of SE gene transcription. As expected cholesterol markedly suppressed transcriptional activity, while SREBP-1a, -1c and -2 activated it. Knock down of SREBP-2 mRNA resulted in an 85% reduction in SE expression. Interspecies comparison of SE promoter sequences identified two conserved putative NF-Y sites that were found to be important for maximal SREBP dependent gene activation and one novel conserved sterol response element (SRE). Altogether three novel SREs were identified within a 205 bp region of the SE promoter. Each of the SREs was capable of binding SREBP-2 but mutation of all three, singly or in combination, did not completely eliminate the SREBP response. Our results demonstrate the critical dependence of this 205 bp region for sterol dependent regulation of SE and uncover a possible framework for SREBP-promoter interaction, including a potent synergy with NF-Y that may be of principal importance.

As previously reported by us, mice with targeted disruption of the CYP8B1 gene (CYP8B1-/-) fail to produce cholic acid (CA), upregulate their bile acid synthesis, reduce the absorption of dietary cholesterol and, after cholesterol feeding, accumulate less liver cholesterol than wild-type (CYP8B1+/+) mice. In the present study, cholesterol-enriched diet (0.5%) or administration of a synthetic liver X receptor (LXR) agonist strongly upregulated CYP7A1 expression in CYP8B1-/- mice, compared to CYP8B1+/+ mice. Cholesterol-fed CYP8B1-/- mice also showed a significant rise in HDL cholesterol and increased levels of liver ABCA1 mRNA. A combined CA (0.25%)/cholesterol (0.5%) diet enhanced absorption of intestinal cholesterol in both groups of mice, increased their liver cholesterol content, and reduced their expression of CYP7A1 mRNA. The ABCG5/G8 liver mRNA was increased in both groups of mice, but cholesterol crystals were only observed in bile from the CYP8B1+/+ mice. The results demonstrate the cholesterol-sparing effects of CA: enhanced absorption and reduced conversion into bile acids. Farnesoid X receptor (FXR)-mediated suppression of CYP7A1 in mice seems to be a predominant mechanism for regulation of bile acid synthesis under normal conditions and, as confirmed, able to override LXR-mediated mechanisms. Interaction between FXR- and LXR-mediated stimuli might also regulate expression of liver ABCG5/G8.

Promoter polymorphisms in microsomal triglyceride transfer protein (MTTP) have been associated with decreased plasma lipids but an increased risk for ischemic heart disease (IHD), indicating that MTTP influences the susceptibility for IHD independent of plasma lipids. The objective of this study was to characterize the functional promoter polymorphism in MTTP predisposing to IHD and its underlying mechanism. Use of pyrosequencing technology revealed that presence of the minor alleles of the promoter polymorphisms -493G>T and -164T>C result in lower transcription of MTTP in vivo in the heart, liver, and macrophages. In vitro experiments indicated that the minor -164C allele mediates the lower gene expression and that C/EBP binds to the polymorphic region in an allele-specific manner. Furthermore, homozygous carriers of the -164C were found to have increased risk for IHD as shown in a case-control study including a total of 544 IHD patients and 544 healthy control subjects. We concluded that carriers of the minor -164C allele have lower expression of MTTP in the heart, mediated at least partly by the transcription factor CCAAT/enhancer binding protein, and that reduced concentration of MTTP in the myocardium may contribute to IHD upon ischemic damage.

We studied bile acid and cholesterol metabolism in insulin-dependent diabetes utilizing genetically modified mice unable to synthesize cholic acid (Cyp8b1−/−). Diabetes was induced in Cyp8b1−/− and wild type animals (Cyp8b1+/+) by alloxan, and the mice were fed normal or cholesterol-enriched diet for 10 weeks. The serum levels of cholesterol were strongly increased in diabetic Cyp8b1+/+ mice fed cholesterol, while diabetic Cyp8b1−/− mice did not show any aberrations regardless of the diet. Diabetic cholesterol-fed Cyp8b1+/+ mice had much higher biliary cholesterol and cholesterol saturation index than all other groups, their bile contained a large number of cholesterol crystals, and their canalicular cholesterol transporter Abcg5/g8 mRNA levels were much higher. Cyp7a1 mRNA levels were similar in all diabetic mice but higher compared to non-diabetic animals. The results indicate a critical role for cholic acid for the development of hypercholesterolemia and gallstones in our animal model.

To study the effects of cholic acid (CA) feeding on hepatic cholesterol metabolism, male sterol 12alpha-hydroxylase (CYP8B1) knockout (-/-) mice and wildtype controls (+/+) were fed either a control diet or the same diet supplemented with CA (0.1% or 0.5% w/w) or cholesterol (1% w/w). During feeding of the control diet, cholesterol synthesis was increased in CYP8B1-/- compared to +/+ mice. Both cholesterol and CA feeding down regulated mRNA expression of cholesterogenic genes and hepatic de novo cholesterol synthesis as also reflected by a concomitant decrease in the nuclear factor SREBP-2 precursor protein and increased hepatic free cholesterol levels. Mice with an intact CYP8B1 gene (CYP8B1+/+ and C57Bl/6 mice) accumulated higher concentrations of cholesteryl esters (24- and 25-fold, respectively) in their livers compared to CYP8B1-/- mice (8-fold). Feeding of CA increased intestinal cholesterol absorption in CYP8B1+/+ mice by 23% and in CYP8B1-/- mice by 50%. While plasma cholesterol did not differ between CYP8B1+/+ and -/- mice under control conditions and cholesterol feeding a decrease was seen in CYP8B1-/- but not CYP8B1+/+ mice fed CA. This study indicates that CA is an important determinant for intestinal cholesterol absorption and that the levels of the transcription factor SREBP-2 in the liver are dependent upon the combined effect of CA on intestinal cholesterol absorption and CYP7A1. The possibility is discussed that inhibition of CYP8B1 and thus CA synthesis may be beneficial for the treatment of hyperlipidemic disorders.

We frequently guide our decisions about when and how to act based on the meanings of perceptual inputs: we might avoid treading on a flower, but not on a leaf. However, most research on response inhibition has used simple perceptual stimuli devoid of meaning. In two Go/No-Go experiments, we examined whether the neural mechanisms supporting response inhibition are influenced by the relevance of meaning to the decision, and by presentation modality (whether concepts were presented as words or images). In an on-line fMRI experiment, we found common regions for response inhibition across perceptual and conceptual decisions. These included the bilateral intraparietal sulcus and the right inferior frontal sulcus, whose neural responses have been linked to diverse cognitive demands in previous studies. In addition, we identified a cluster in ventral lateral occipital cortex that was sensitive to the modality of input, with a stronger response to No-Go than Go trials for meaningful images, compared to words with the same semantic content. In a second experiment, using resting-state fMRI, we explored how individual variation in the intrinsic connectivity of these activated regions related to variation in behavioural performance. Participants who showed stronger connectivity between common inhibition regions and limbic areas in medial temporal and subgenual anterior cingulate cortex were better at inhibition when this was driven by the meaning of the items. In addition, regions with a specific role in picture inhibition were more connected to a cluster in the thalamus/caudate for participants who were better at performing the picture task outside of the scanner. Together these studies indicate that the capacity to appropriately withhold action depends on interactions between common control regions, which are important across multiple types of input and decision, and other brain regions linked to specific inputs (i.e., visual features) or representations (e.g., memory).