High resolution anatomical and quantitative MRI of the entire human occipital lobe ex vivo at 9.4T.

Several magnetic resonance imaging (MRI) contrasts are sensitive to myelin content in gray matter in vivo which has ignited ambitions of MRI-based in vivo cortical histology. Ultra-high field (UHF) MRI, at fields of 7T and beyond, is crucial to provide the resolution and contrast needed to sample contrasts over the depth of the cortex and get closer to layer resolved imaging. Ex vivo MRI of human post mortem samples is an important stepping stone to investigate MRI contrast in the cortex, validate it against histology techniques applied in situ to the same tissue, and investigate the resolutions needed to translate ex vivo findings to in vivo UHF MRI. Here, we investigate key technology to extend such UHF studies to large human brain samples while maintaining high resolution, which allows investigation of the layered architecture of several cortical areas over their entire 3D extent and their complete borders where architecture changes. A 16 channel cylindrical phased array radiofrequency (RF) receive coil was constructed to image a large post mortem occipital lobe sample (~80×80×80mm3) in a wide-bore 9.4T human scanner with the aim of achieving high-resolution anatomical and quantitative MR images. Compared with a human head coil at 9.4T, the maximum Signal-to-Noise ratio (SNR) was increased by a factor of about five in the peripheral cortex. Although the transmit profile with a circularly polarized transmit mode at 9.4T is relatively inhomogeneous over the large sample, this challenge was successfully resolved with parallel transmit using the kT-points method. Using this setup, we achieved 60µm anatomical images for the entire occipital lobe showing increased spatial definition of cortical details compared to lower resolutions. In addition, we were able to achieve sufficient control over SNR, B0 and B1 homogeneity and multi-contrast sampling to perform quantitative T2* mapping over the same volume at 200µm. Markov Chain Monte Carlo sampling provided maximum posterior estimates of quantitative T2* and their uncertainty, allowing delineation of the stria of Gennari over the entire length and width of the calcarine sulcus. We discuss how custom RF receive coil arrays built to specific large post mortem sample sizes can provide a platform for UHF cortical layer-specific quantitative MRI over large fields of view.

Robust and fast nonlinear optimization of diffusion MRI microstructure models.

Advances in biophysical multi-compartment modeling for diffusion MRI (dMRI) have gained popularity because of greater specificity than DTI in relating the dMRI signal to underlying cellular microstructure. A large range of these diffusion microstructure models have been developed and each of the popular models comes with its own, often different, optimization algorithm, noise model and initialization strategy to estimate its parameter maps. Since data fit, accuracy and precision is hard to verify, this creates additional challenges to comparability and generalization of results from diffusion microstructure models. In addition, non-linear optimization is computationally expensive leading to very long run times, which can be prohibitive in large group or population studies. In this technical note we investigate the performance of several optimization algorithms and initialization strategies over a few of the most popular diffusion microstructure models, including NODDI and CHARMED. We evaluate whether a single well performing optimization approach exists that could be applied to many models and would equate both run time and fit aspects. All models, algorithms and strategies were implemented on the Graphics Processing Unit (GPU) to remove run time constraints, with which we achieve whole brain dataset fits in seconds to minutes. We then evaluated fit, accuracy, precision and run time for different models of differing complexity against three common optimization algorithms and three parameter initialization strategies. Variability of the achieved quality of fit in actual data was evaluated on ten subjects of each of two population studies with a different acquisition protocol. We find that optimization algorithms and multi-step optimization approaches have a considerable influence on performance and stability over subjects and over acquisition protocols. The gradient-free Powell conjugate-direction algorithm was found to outperform other common algorithms in terms of run time, fit, accuracy and precision. Parameter initialization approaches were found to be relevant especially for more complex models, such as those involving several fiber orientations per voxel. For these, a fitting cascade initializing or fixing parameter values in a later optimization step from simpler models in an earlier optimization step further improved run time, fit, accuracy and precision compared to a single step fit. This establishes and makes available standards by which robust fit and accuracy can be achieved in shorter run times. This is especially relevant for the use of diffusion microstructure modeling in large group or population studies and in combining microstructure parameter maps with tractography results.

[Lipoid Pneumonia Associated with Lipid-Containing Nasal Sprays and Nose Drops]. / Lipidpneumonie durch Lipid-haltige Nasensprays und -tropfen.

BACKGROUND: Regularly updating the German pharmacopoeia on contemporary preparations DAC/NRF, chapter "Nasal Applications" and the recommendations on "Nasal Oils" as well as "Nasal Ointments and Emulsions", the issue of the risk of lipoid pneumonia associated with the use of plant oils and when compared to mineral oils arose. MATERIAL AND METHODS: We searched different databases: the "Grosse Deutsche Arzneimittelspezialitäten-Taxe" containing all products available in German pharmacies, the Cochrane Library, the pharmacovigilance-database of the BfArM, and Medline to evaluate the benefit/risk-ratio of plant oils in nasal drops and sprays. RESULTS: In German pharmacies, a number of both, mineral oil-containing drugs for nasal application and plant oil-containing medical devices are available. The risk of lipoid pneumonia described for mineral oil-containing nasal products can not entirely be transferred to plant oil-containing products. However, evidence from the literature suggests a risk for lipoid pneumonia, which needs to be considered given the non-proven efficacy of such medical devices in the majority of proposed indications. To minimize risks, recommendations are made for patient groups that should not use lipid-containing nasal products. CONCLUSIONS: Acknowledging the potential lethal outcome of lipoid pneumonia, a demanding diagnosis, and absence of a specific therapy, lipid-containing nasal products should be used only with great caution. Based on the current knowledge, the statements regarding the risk of lipoid pneumonia for lipid-containing nasal products in the DAC/NRF should not be modified.

Greater effects of high- compared with moderate-intensity interval training on cardio-metabolic variables, blood leptin concentration and ratings of perceived exertion in obese adolescent females.

This study examined the effects of high- vs. moderate-intensity interval training on cardiovascular fitness, leptin levels and ratings of perceived exertion (RPE) in obese female adolescents. Forty-seven participants were randomly assigned to one of three groups receiving either a 1:1 ratio of 15 s of effort comprising moderate-intensity interval training (MIIT at 80% maximal aerobic speed: MAS) or high-intensity interval training (HIIT at 100% MAS), with matched 15 s recovery at 50% MAS, thrice weekly, or a no-training control group. The HIIT and MIIT groups showed improved (p < 0.05) body mass (BM), BMI Z-score, and percentage of body fat (%BF). Only the HIIT group showed decreased waist circumference (WC) (p = 0.017). The effect of exercise on maximal oxygen uptake (VO2max) was significant (p = 0.019, ES = 0.48 and p = 0.010, ES = 0.57, HIIT and MIIT, respectively). The decrease of rate-pressure product (RPP) (p < 0.05, ES = 0.53 and ES = 0.46, HIIT and MIIT, respectively) followed the positive changes in resting heart rate and blood pressures. Blood glucose, insulin level and the homeostasis model assessment index for insulin decreased (p < 0.05) in both training groups. Significant decreases occurred in blood leptin (p = 0.021, ES = 0.67 and p = 0.011, ES = 0.73) and in RPE (p = 0.001, ES = 0.76 and p = 0.017, ES = 0.57) in HIIT and MIIT, respectively. In the post-intervention period, blood leptin was strongly associated with %BF (p < 0.001) and VO2max (p < 0.01) in the HIIT and MIIT groups, respectively, while RPE was strongly associated with BM (p < 0.01) in the HIIT group. The results suggest that high-intensity interval training may produce more positive effects on health determinants in comparison with the same training mode at a moderate intensity.

Altered mesocorticolimbic functional connectivity in psychotic disorder: an analysis of proxy genetic and environmental effects.

BACKGROUND: Altered dopaminergic neurotransmission in the mesocorticolimbic (MCL) system may mediate psychotic symptoms. In addition, pharmacological dopaminergic manipulation may coincide with altered functional connectivity (fc) 'in rest'. We set out to test whether MCL-fc is conditional on (familial risk for) psychotic disorder and/or interactions with environmental exposures. METHOD: Resting-state functional magnetic resonance imaging data were obtained from 63 patients with psychotic disorder, 73 non-psychotic siblings of patients with psychotic disorder and 59 healthy controls. With the nucleus accumbens (NAcc) as seed region, fc within the MCL system was estimated. Regression analyses adjusting for a priori hypothesized confounders were used to assess group differences in MCL connectivity as well as gene (group) × environmental exposure interactions (G × E) (i.e., to cannabis, developmental trauma and urbanicity). RESULTS: Compared with controls, patients and siblings had decreased fc between the right NAcc seed and the right orbitofrontal cortex (OFC) as well as the left middle cingulate cortex (MCC). Siblings showed decreased connectivity between the NAcc seed and lentiform nucleus compared with patients and controls. In addition, patients had decreased left NAcc connectivity compared with siblings in the left middle frontal gyrus. There was no evidence for a significant interaction between group and the three environmental exposures in the model of MCL-fc. CONCLUSIONS: Reduced NAcc-OFC/MCC connectivity was seen in patients and siblings, suggesting that altered OFC connectivity and MCC connectivity are vulnerability markers for psychotic disorder. Differential exposure to environmental risk factors did not make an impact on the association between familial risk and MCL connectivity.

Real-time fMRI neurofeedback: progress and challenges.

In February of 2012, the first international conference on real time functional magnetic resonance imaging (rtfMRI) neurofeedback was held at the Swiss Federal Institute of Technology Zurich (ETHZ), Switzerland. This review summarizes progress in the field, introduces current debates, elucidates open questions, and offers viewpoints derived from the conference. The review offers perspectives on study design, scientific and clinical applications, rtfMRI learning mechanisms and future outlook.

Upregulation of emotion areas through neurofeedback with a focus on positive mood.

Real-time functional magnetic resonance imaging can be used to feed back signal changes from the brain to participants such that they can train to modulate activation levels in specific brain areas. Here we present the first study combining up-regulation of brain areas for positive emotions with psychometric measures to assess the effect of successful self-regulation on subsequent mood. We localized brain areas associated with positive emotions through presentation of standardized pictures with positive valence. Participants up-regulated activation levels in their target area during specific periods, alternating with rest. Participants attained reliable self-control of the target area by the last of three seven-minute runs. This training effect was supported by an extensive network outside the targeted brain region, including higher sensory areas, paralimbic and orbitofrontal cortex. Self-control of emotion areas was not accompanied by clear changes in self-reported emotions; trend-level improvements on depression scores were counteracted by increases on measures of fatigue, resulting in no overall mood improvement. It is possible that benefits of self-control of emotion networks may only appear in people who display abnormal emotional homeostasis. The use of only a single, short, training session, overlap between positive and negative emotion networks and aversive reactions to the scanning environment may have prevented the detection of subtle changes in mood.

Tease or threat? Judging social interactions from bodily expressions.

We casually observe many interactions that do not really concern us. Yet sometimes we need to be able to rapidly appraise whether an interaction between two people represents a real threat for one of them rather than an innocent tease. Using functional magnetic resonance imaging, we investigated whether small differences in the body language of two interacting people are picked up by the brain even if observers are performing an unrelated task. Fourteen participants were scanned while watching 3-s movies (192 trials and 96 scrambles) showing a male person either threatening or teasing a female one. In one task condition, observers categorized the interaction as threatening or teasing, and in the other, they monitored randomly appearing dots and categorized the color. Our results clearly show that right amygdala responds more to threatening than to teasing situations irrespective of the observers' task. When observers' attention is not explicitly directed to the situation, this heightened amygdala activation goes together with increased activity in body sensitive regions in fusiform gyrus, extrastriate body area-human motion complex and superior temporal sulcus and is associated with a better behavioral performance of the participants during threatening situations. In addition, regions involved in action observation (inferior frontal gyrus, temporoparietal junction, and inferior parietal lobe) and preparation (premotor, putamen) show increased activation for threat videos. Also regions involved in processing moral violations (temporoparietal junction, hypothalamus) reacted selectively to the threatening interactions. Taken together, our results show which brain regions react selectively to witnessing a threatening interaction even if the situation is not attended because the observers perform an unrelated task.

Neurofeedback: A promising tool for the self-regulation of emotion networks.

Real-time functional magnetic resonance imaging (fMRI) affords the opportunity to explore the feasibility of self-regulation of functional brain networks through neurofeedback. We localised emotion networks individually in thirteen participants using fMRI and trained them to upregulate target areas, including the insula and amygdala. Participants achieved a high degree of control of these networks after a brief training period. We observed activation increases during periods of upregulation of emotion networks in the precuneus and medial prefrontal cortex and, with increasing training success, in the ventral striatum. These findings demonstrate the feasibility of fMRI-based neurofeedback of emotion networks and suggest a possible development into a therapeutic tool.

Acute stress and food-related reward activation in the brain during food choice during eating in the absence of hunger.

BACKGROUND: Stress results in eating in the absence of hunger, possibly related to food reward perception. HYPOTHESIS: Stress decreases food reward perception. AIM: Determine the effect of acute stress on food choice and food choice reward-related brain activity. SUBJECTS: Nine females (BMI = 21.5 + or - 2.2 kg/m(2), age = 24.3 + or - 3.5 years). PROCEDURE: Fasted subjects came twice to randomly complete either a rest or stress condition. Per session, two functional MRI scans were made, wherein the subjects chose the subsequent meal (food images). The rewarding value of the food was measured as liking and wanting. Food characteristics (for example, crispiness, fullness of taste and so on), energy intake, amount of each macronutrient chosen, plasma cortisol and Visual Analog Scale (VAS) hunger and satiety were measured. RESULTS: Fasted state was confirmed by high hunger (80 + or - 5 mm VAS). Breakfast energy intake (3 + or - 1 MJ) and liking were similar in all conditions. Wanting was lower postprandially (Delta = -0.3 items/category, P<0.01). Breakfast decreased hunger (-42 mm VAS, P<0.01). Postprandially, energy intake (-1.1 MJ), protein intake (-14.7 g) and carbohydrate intake (-32.7 g all P<0.05) were lower. Fat intake was not different (-7.3, P = 0.4). Putamen activity was not lower postprandially. Cortisol levels were increased in the stress condition (Area under the curve of cortisol: DeltaAUC = +2.2 x 10(4) nmol min(-1) l(-1), P<0.05). Satiety was lower after breakfast (-8 mm VAS, P<0.01). Postprandial energy intake, protein intake and carbohydrate intake were relatively higher compared with the rest condition, resulting from more choice for crispiness and fullness of taste (P<0.05). Brain activation was reduced in reward areas: amygdala, hippocampus and cingulate cortex (AUC = -13.33, -1.34, -2.56% blood oxygen level dependent (BOLD) s for choosing breakfast and AUC = -9.31, -1.25, -2.34%BOLD s<0.05 for choosing the second meal). Putamen activation was decreased postprandially (AUC = -1.2%BOLD s, P<0.05). CONCLUSION: Reward signaling and reward sensitivity were significantly lower under stress, coinciding with increased energy intake from food choice for more crispiness and fullness of taste. The changes in putamen activation may reflect specifically decreased reward prediction sensitivity.

Inverse mapping the neuronal substrates of face categorizations.

Face perception is a complex process involving a network of brain structures, dynamically processing information to enable judgments about a face to be made (e.g., familiarity, identity, and expression). Here we introduce an analysis methodology that makes it possible to directly study this information processing in the brain from spatially and temporally resolved magnetoencephalographic signals. We apply our methodology to the study of 2 face categorization tasks, gender and expressiveness, and track the processing of 3 key visual features that underlie behavioral performance, over time and throughout the cortex. We find information processing correlates beginning from 90 ms following stimulus onset, where features are processed in isolation in occipital extrastriate regions. Over time, processing of successively more features and feature combinations takes place in occipitotemporal regions, with maximal information processing of visual information coinciding with the well-established face-selective M170 component at 170 ms. Later still, around 250-400 ms, cortical activity responds significantly more to task-specific features and their complex combinations. These results indicate a complex process of visual information processing during face perception with face parts processed in isolation at very early stages, and task-specific processing of combinations of features taking place within 300 ms. Crucially, our approach specifically establishes which information in the visual stimulus the brain signal is responding to and how this varies with time, cortical location, and task demands to establish a more precise tracking of information processing mechanisms in the cortex during face perception.

Visual word form processing deficits driven by severity of reading impairments in children with developmental dyslexia.

The visual word form area (VWFA) in the left ventral occipito-temporal (vOT) cortex is key to fluent reading in children and adults. Diminished VWFA activation during print processing tasks is a common finding in subjects with severe reading problems. Here, we report fMRI data from a multicentre study with 140 children in primary school (7.9-12.2 years; 55 children with dyslexia, 73 typical readers, 12 intermediate readers). All performed a semantic task on visually presented words and a matched control task on symbol strings. With this large group of children, including the entire spectrum from severely impaired to highly fluent readers, we aimed to clarify the association of reading fluency and left vOT activation during visual word processing. The results of this study confirm reduced word-sensitive activation within the left vOT in children with dyslexia. Interestingly, the association of reading skills and left vOT activation was especially strong and spatially extended in children with dyslexia. Thus, deficits in basic visual word form processing increase with the severity of reading disability but seem only weakly associated with fluency within the typical reading range suggesting a linear dependence of reading scores with VFWA activation only in the poorest readers.

Activation of Heschl's gyrus during auditory hallucinations.

Apart from being a common feature of mental illness, auditory hallucinations provide an intriguing model for the study of internally generated sensory perceptions that are attributed to external sources. Until now, the knowledge about the cortical network that supports such hallucinations has been restricted by methodological limitations. Here, we describe an experiment with paranoid schizophrenic patients whose on- and offset of auditory hallucinations could be monitored within one functional magnetic resonance imaging (fMRI) session. We demonstrate an increase of the blood oxygen level-dependent (BOLD) signal in Heschl's gyrus during the patients' hallucinations. Our results provide direct evidence of the involvement of primary auditory areas in auditory verbal hallucinations and establish novel constraints for psychopathological models.

Rapid feature selective neuronal synchronization through correlated latency shifting.

Spontaneous brain activity could affect processing if it were structured. We show that neuron pairs in cat primary visual cortex exhibited correlated fluctuations in response latency, particularly when they had overlapping receptive fields or similar orientation preferences. Correlations occurred within and across hemispheres, but only when local field potentials (LFPs) oscillated in the gamma-frequency range (40-70 Hz). In this range, LFP fluctuations preceding response onset predicted response latencies; negative (positive) LFPs were associated with early (late) responses. Oscillations below 10 Hz caused covariations in response amplitude, but exhibited no columnar selectivity or coordinating effect on latencies. Thus, during high gamma activity, spontaneous activity exhibits distinct, column-specific correlation patterns. Consequently, cortical cells undergo coherent fluctuations in excitability that enhance temporal coherence of responses to contours that are spatially contiguous or have similar orientation. Because synchronized responses are more likely than dispersed responses to undergo rapid and joint processing, spontaneous activity may be important in early visual processes.

High density lipoprotein metabolism in man.

The turnover of (125)I-high density lipoprotein (HDL) was examined in a total of 14 studies in eight normal volunteers in an attempt to determine the metabolic relationship between apolipoproteins A-I (apoA-I) and A-II (apoA-II) of HDL and to define further some of the determinants of HDL metabolism. All subjects were first studied under conditions of an isocaloric balanced diet (40% fat, 40% carbohydrate). Four were then studied with an 80% carbohydrate diet, and two were studied while receiving nicotinic acid (1 g three times daily) and ingesting the same isocaloric balanced diet. The decay of autologous (125)I-HDL and the appearance of urinary radioactivity were followed for at least 2 wk in each study. ApoA-I and apoA-II were isolated by Sephadex G-200 chromatography from serial plasma samples in each study. The specific activities of these peptides were then measured directly. It was found that the decay of specific activity of apoA-I and apoA-II were parallel to one another in all studies. The mean half-life of the terminal portion of decay was 5.8 days during the studies with a balanced diet.Mathematical modeling of the decay of plasma radioactivity and appearance of urinary radioactivity was most consistent with a two-compartment model. One compartment is within the plasma and exchanges with a nonplasma component. Catabolism occurs from both of these compartments. With a balanced isocaloric diet, the mean synthetic rate for HDL protein was 8.51 mg/kg per day. HDL synthesis was not altered by the high carbohydrate diet and was only slightly decreased by nicotinic acid treatment. These perturbations had effects on HDL catabolic pathways that were reciprocal in many respects. With an 80% carbohydrate diet, the rate of catabolism from the plasma compartment rose by a mean of 39.1%; with nicotinic acid treatment, it fell by 42.2%. Changes in the rate of catabolism from the second compartment were generally opposite those in the rate of catabolism from the plasma compartment, suggesting that these two catabolic pathways may be reciprocally regulated.

Curved Beam Computed Tomography based Structural Rigidity Analysis of Bones with Simulated Lytic Defect: A Comparative Study with Finite Element Analysis.

In this paper, a CT based structural rigidity analysis (CTRA) method that incorporates bone intrinsic local curvature is introduced to assess the compressive failure load of human femur with simulated lytic defects. The proposed CTRA is based on a three dimensional curved beam theory to obtain critical stresses within the human femur model. To test the proposed method, ten human cadaveric femurs with and without simulated defects were mechanically tested under axial compression to failure. Quantitative computed tomography images were acquired from the samples, and CTRA and finite element analysis were performed to obtain the failure load as well as rigidities in both straight and curved cross sections. Experimental results were compared to the results obtained from FEA and CTRA. The failure loads predicated by curved beam CTRA and FEA are in agreement with experimental results. The results also show that the proposed method is an efficient and reliable method to find both the location and magnitude of failure load. Moreover, the results show that the proposed curved CTRA outperforms the regular straight beam CTRA, which ignores the bone intrinsic curvature and can be used as a useful tool in clinical practices.

Seasonal tertiary wastewater treatment in California: an analysis of public health benefits and costs.

A number of communities in the Central Valley of California have requested that seasonally based effluent limits be developed for their wastewater treatment facilities. These seasonal limits would be based on disinfected secondary treatment during the winter and disinfected tertiary treatment during the rest of the year. Such a request for seasonal limits raises a significant water quality policy question with regard to the costs and relative benefits of tertiary treatment during the winter season. A benefit-cost analysis for winter season tertiary wastewater treatment in California's Central Valley is presented here. The assumed societal benefit of winter tertiary treatment is enhanced water quality for recreational purposes, and thus reduced risk to public health. Based on the results of this analysis, between four and sixteen million recreation events would need to occur annually region-wide during the winter to justify the costs of winter tertiary treatment. A similar method and the information described herein could be used by the state water quality regulatory agency to develop a risk-based policy to consider seasonal limits.

Detection of pyrrolizidine alkaloids in German licensed herbal medicinal teas.

BACKGROUND: Because of the hepatotoxic, mutagenic, and cancerogenic effects of pyrrolizidine alkaloids (PAs) the German Federal Institute for Risk Assessment (BfR) recommends not to exceed a daily PA intake of 0.007 µg/kg body weight (0.42 µg/60 kg adult). In a recent study conducted by the BfR, up to 5647 µg PA/kg dried herbal material were detected in tea products marketed as food. PURPOSE: The present study aimed at elucidating whether medicinal teas licensed or registered as medicinal products contain PAs as well. STUDY DESIGN: One hundred sixty-nine different commercially available medicinal teas, i.e. 19 nettle (Urtica dioica L.), 12 fennel (Foeniculum vulgare Mill.), 14 chamomile (Matricaria recutita L.), 11 melissa (Melissa officinalis L.) and 4 peppermint (Mentha piperita L.) teas as well as 109 tea mixtures were analyzed for the presence of 23 commercially available PAs. METHOD: LC/MS was used for the determination of the PAs RESULTS: In general, the total PA contents ranging 0-5668 µg/kg. Thirty percent of the tested single-ingredient tea products and 56.9% of the tested medicinal tea mixtures were found to contain PA concentrations above the limit of quantification (LOQ) of 10 µg/kg. In 11 medicinal teas PA contents >300 µg/kg dry herb were determined thus exceeding the recommended limit for PA intake by BfR. In addition three products of the investigated tea mixtures revealed extremely high PA contents of 4227, 5137, and 5668 µg/kg. Generally, single-ingredient tea products contained much less or even no detectable amounts of PAs when compared to the tea mixtures. PAs in the range between 13 and 1080 µg/kg were also detected in five analyzed aqueous herbal infusions of the medicinal tea mixture products with the highest PA content. Two out of the five investigated herbal infusions exceeded the recommended BfR limit for PA intake. CONCLUSION: This study demonstrates clearly that also medicinal teas licensed as medicinal products may partly contain high amounts of PAs exceeding current recommendations. For that reason manufacturers are advised to carry out more rigorous quality control tests devoted to the detection of PAs. This is very important to minimize PAs in medicinal teas accounting for possible additional exposure of the consumer to PAs from other food sources (e.g. honey).

Cognitive correlates of frontoparietal network connectivity 'at rest' in individuals with differential risk for psychotic disorder.

Altered frontoparietal network functional connectivity (FPN-fc) has been associated with neurocognitive dysfunction in individuals with (risk for) psychotic disorder. Cannabis use is associated with cognitive and FPN-fc alterations in healthy individuals, but it is not known whether cannabis exposure moderates the FPN-fc-cognition association. We studied FPN-fc in relation to psychosis risk, as well as the moderating effects of psychosis risk and cannabis use on the association between FPN-fc and (social) cognition. This was done by collecting resting-state fMRI scans and (social) cognitive test results from 63 patients with psychotic disorder, 73 unaffected siblings and 59 controls. Dorsolateral prefrontal cortex (DLPFC) seed-based correlation analyses were used to estimate FPN-fc group differences. Additionally, group×FPN-fc and cannabis×FPN-fc interactions in models of cognition were assessed with regression models. Results showed that DLPFC-fc with the left precuneus, right inferior parietal lobule, right middle temporal gyrus (MTG), inferior frontal gyrus (IFG) regions and right insula was decreased in patients compared to controls. Siblings had reduced DLPFC-fc with the right MTG, left middle frontal gyrus, right superior frontal gyrus, IFG regions, and right insula compared to controls, with an intermediate position between patients and controls for DLPFC-IFG/MTG and insula-fc. There were no significant FPN-fc×group or FPN-fc×cannabis interactions in models of cognition. Reduced DLPFC-insula-fc was associated with worse social cognition in the total sample. In conclusion, besides patient- and sibling-specific FPN-fc alterations, there was evidence for trait-related alterations. FPN-fc-cognition associations were not conditional on familial liability or cannabis use. Lower FPN-fc was associated with lower emotion processing in the total group.