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Relationships between gross motor skills and cardiovascular fitness with visuospatial working memory (VSWM) in children are hypothesized to be mediated by underlying functional brain mechanisms. Because there is little experimental evidence to support this mechanism, the present study was designed to investigate the relationships of gross motor skills and cardiovascular fitness with VSWM-related brain activation in 8- to 10-year-old children. Functional magnetic resonance imaging data obtained during a VSWM-task were analyzed for 80 children from grades 3 (47.5%) and 4 of 21 primary schools in the Netherlands (51.3% girls). Gross motor skills (Korper Koordinationstest für Kinder and Bruininks-Oseretsky Test of Motor Proficiency - 2nd Edition) and cardiovascular fitness (20-meter Shuttle Run Test) were assessed. VSWM-related brain activation was found in a network involving the angular gyrus, the superior parietal cortex, and the thalamus; deactivation was found in the inferior and middle temporal gyri. Although behavioral results showed significant relations of gross motor skills and cardiovascular fitness with VSWM performance, gross motor skills and cardiovascular fitness were not related to VSWM-related brain activation. Therefore, we could not confirm the hypothesis that brain activation underlies the relationship of gross motor skills and cardiovascular fitness with VSWM performance. Our results suggest that either the effects of physical activity on cognition do not necessarily go via changes in gross motor skills and/or cardiovascular fitness, or that brain activation patterns as measured with the blood-oxygen-level dependent (BOLD) signal may not be the mechanism underlying the relationships of gross motor skills and cardiovascular fitness with VSWM.

Neural plasticity due to hearing loss results in tonotopic map changes. Several studies have suggested a relation between hearing loss-induced tonotopic reorganization and tinnitus. This large fMRI study on humans was intended to clarify the relations between hearing loss, tinnitus, and tonotopic reorganization. To determine the differential effect of hearing loss and tinnitus, both male and female participants with bilateral high-frequency hearing loss, with and without tinnitus, and a control group were included. In a total of 90 participants, bilateral cortical responses to sound stimulation were measured with loudness-matched pure-tone stimuli (0.25-8 kHz). In the bilateral auditory cortices, the high-frequency sound-evoked activation level was higher in both hearing-impaired participant groups, compared with the control group. This was most prominent in the hearing loss group without tinnitus. Similarly, the tonotopic maps for the hearing loss without tinnitus group were significantly different from the controls, whereas the maps of those with tinnitus were not. These results show that higher response amplitudes and map reorganization are a characteristic of hearing loss, not of tinnitus. Both tonotopic maps and response amplitudes of tinnitus participants appear intermediate to the controls and hearing loss without tinnitus group. This observation suggests a connection between tinnitus and an incomplete form of central compensation to hearing loss, rather than excessive adaptation. One implication of this may be that treatments for tinnitus shift their focus toward enhancing the cortical plasticity, instead of reversing it. SIGNIFICANCE STATEMENT Tinnitus, a common and potentially devastating condition, is the presence of a "phantom" sound that often accompanies hearing loss. Hearing loss is known to induce plastic changes in cortical and subcortical areas. Although plasticity is a valuable trait that allows the human brain to rewire and recover from injury and sensory deprivation, it can lead to tinnitus as an unwanted side effect. In this large fMRI study, we provide evidence that tinnitus is related to a more conservative form of reorganization than in hearing loss without tinnitus. This result contrasts with the previous notion that tinnitus is related to excessive reorganization. As a consequence, treatments for tinnitus may need to enhance the cortical plasticity, rather than reverse it., (Copyright © 2020 the authors.)

The characterization of receptive field (RF) properties is fundamental to understanding the neural basis of sensory and cognitive behaviour. The combination of non-invasive imaging, such as fMRI, with biologically inspired neural modelling has enabled the estimation of population RFs directly in humans. However, current approaches require making numerous a priori assumptions, so these cannot reveal unpredicted properties, such as fragmented RFs or subpopulations. This is a critical limitation in studies on adaptation, pathology or reorganization. Here, we introduce micro-probing (MP), a technique for fine-grained and largely assumption free characterization of multiple pRFs within a voxel. It overcomes many limitations of current approaches by enabling detection of unexpected RF shapes, properties and subpopulations, by enhancing the spatial detail with which we analyze the data. MP is based on tiny, fixed-size, Gaussian models that efficiently sample the entire visual space and create fine-grained probe maps. Subsequently, we derived population receptive fields (pRFs) from these maps. We demonstrate the scope of our method through simulations and by mapping the visual fields of healthy participants and of a patient group with highly abnormal RFs due to a congenital pathway disorder. Without using specific stimuli or adapted models, MP mapped the bilateral pRFs characteristic of observers with albinism. In healthy observers, MP revealed that voxels may capture the activity of multiple subpopulations RFs that sample distinct regions of the visual field. Thus, MP provides a versatile framework to visualize, analyze and model, without restrictions, the diverse RFs of cortical subpopulations in health and disease., Competing Interests: Declaration of competing interest None., (Copyright © 2019. Published by Elsevier Inc.)

Rationale: In Parkinson's disease (PD), spatial covariance analysis of 18 F-FDG PET data has consistently revealed a characteristic PD-related brain pattern (PDRP). By quantifying PDRP expression on a scan-by-scan basis, this technique allows objective assessment of disease activity in individual subjects. We provide a further validation of the PDRP by applying spatial covariance analysis to PD cohorts from the Netherlands (NL), Italy (IT), and Spain (SP)., Methods: The PDRP NL was previously identified (17 controls, 19 PD) and its expression was determined in 19 healthy controls and 20 PD patients from the Netherlands. The PDRP IT was identified in 20 controls and 20 "de-novo" PD patients from an Italian cohort. A further 24 controls and 18 "de-novo" Italian patients were used for validation. The PDRP SP was identified in 19 controls and 19 PD patients from a Spanish cohort with late-stage PD. Thirty Spanish PD patients were used for validation. Patterns of the three centers were visually compared and then cross-validated. Furthermore, PDRP expression was determined in 8 patients with multiple system atrophy., Results: A PDRP could be identified in each cohort. Each PDRP was characterized by relative hypermetabolism in the thalamus, putamen/pallidum, pons, cerebellum, and motor cortex. These changes co-varied with variable degrees of hypometabolism in posterior parietal, occipital, and frontal cortices. Frontal hypometabolism was less pronounced in "de-novo" PD subjects (Italian cohort). Occipital hypometabolism was more pronounced in late-stage PD subjects (Spanish cohort). PDRP IT , PDRP NL , and PDRP SP were significantly expressed in PD patients compared with controls in validation cohorts from the same center (P < 0.0001), and maintained significance on cross-validation (P < 0.005). PDRP expression was absent in MSA., Conclusion: The PDRP is a reproducible disease characteristic across PD populations and scanning platforms globally. Further study is needed to identify the topography of specific PD subtypes, and to identify and correct for center-specific effects.

Unsolved questions in computational visual neuroscience research are whether and how neurons and their connecting cortical networks can adapt when normal vision is compromised by a neurodevelopmental disorder or damage to the visual system. This question on neuroplasticity is particularly relevant in the context of rehabilitation therapies that attempt to overcome limitations or damage, through either perceptual training or retinal and cortical implants. Studies on cortical neuroplasticity have generally made the assumption that neuronal population properties and the resulting visual field maps are stable in healthy observers. Consequently, differences in the estimates of these properties between patients and healthy observers have been taken as a straightforward indication for neuroplasticity. However, recent studies imply that the modeled neuronal properties and the cortical visual maps vary substantially within healthy participants, e.g., in response to specific stimuli or under the influence of cognitive factors such as attention. Although notable advances have been made to improve the reliability of stimulus-driven approaches, the reliance on the visual input remains a challenge for the interpretability of the obtained results. Therefore, we argue that there is an important role in the study of cortical neuroplasticity for approaches that assess intracortical signal processing and circuitry models that can link visual cortex anatomy, function, and dynamics., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2019 Joana Carvalho et al.)

Over the last years convolutional neural networks (CNNs) have shown remarkable results in different image classification tasks, including medical imaging. One area that has been less explored with CNNs is Positron Emission Tomography (PET). Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) is a PET technique employed to obtain a representation of brain metabolic function. In this study we employed 3D CNNs in FDG-PET brain images with the purpose of discriminating patients diagnosed with Parkinson's disease (PD) from controls. We employed Scaled Subprofile Modeling using Principal Component Analysis as a preprocessing step to focus on specific brain regions and limit the number of voxels that are used as input for the CNNs, thereby increasing the signal-to-noise ratio in our data. We performed hyperparameter optimization on three CNN architectures to estimate the classification accuracy of the networks on new data. The best performance that we obtained was accuracy = 0 . 8 6 and area under the receiver operating characteristic curve ( AUC ROC ) = 0 . 9 4 on the test set. We believe that, with larger datasets, PD patients could be reliably distinguished from controls by FDG-PET scans alone and that this technique could be applied to more clinically challenging tasks, like the differential diagnosis of neurological disorders with similar symptoms, such as PD, Progressive Supranuclear Palsy (PSP) and Multiple System Atrophy (MSA).

Two prominent strategies that the human visual system uses to reduce incoming information are spatial integration and selective attention. Whereas spatial integration summarizes and combines information over the visual field, selective attention can single it out for scrutiny. The way in which these well-known mechanisms-with rather opposing effects-interact remains largely unknown. To address this, we had observers perform a gaze-contingent search task that nudged them to deploy either spatial or feature-based attention to maximize performance. We found that, depending on the type of attention employed, visual spatial integration strength changed either in a strong and localized or a more modest and global manner compared with a baseline condition. Population code modeling revealed that a single mechanism can account for both observations: Attention acts beyond the neuronal encoding stage to tune the spatial integration weights of neural populations. Our study shows how attention and integration interact to optimize the information flow through the brain.

Introduction: The implementation of spatial-covariance [ 18 F]fluorodeoxyglucose positron emission tomography-based disease-related metabolic brain patterns as biomarkers has been hampered by intercenter imaging differences. Within the scope of the JPND-PETMETPAT working group, we illustrate the impact of these differences on Parkinson's disease-related pattern (PDRP) expression scores., Methods: Five healthy controls, 5 patients with idiopathic rapid eye movement sleep behavior disorder, and 5 patients with Parkinson's disease were scanned on one positron emission tomography/computed tomography system with multiple image reconstructions. In addition, one Hoffman 3D Brain Phantom was scanned on several positron emission tomography/computed tomography systems using various reconstructions. Effects of image contrast on PDRP scores were also examined., Results: Human and phantom raw PDRP scores were systematically influenced by scanner and reconstruction effects. PDRP scores correlated inversely to image contrast. A Gaussian spatial filter reduced contrast while decreasing intercenter score differences., Discussion: Image contrast should be considered in harmonization efforts. A Gaussian filter may reduce noise and intercenter effects without sacrificing sensitivity. Phantom measurements will be important for correcting PDRP score offsets.

The occurrence of a stressful event is considered to increase the risk of developing depression. In the present study we explore whether the breakup of a romantic relationship can be used as an experimental model to study a depression-like state during a period of stress in individuals without a psychiatric disorder. The primary aim of our study was to investigate: 1) whether individuals with a recent romantic relationship breakup (''heartbreak") demonstrate symptoms of depression, 2) how to describe heartbreak characteristics based on data from a comprehensive questionnaire battery, and 3) whether this description can capture severity of depression symptoms. Secondary, we were interested in gender differences with regard to the above study objectives. Subjects who have experienced a relationship breakup in the preceding six months (N = 71) or are in a romantic relationship (N = 46) participated in our study. A questionnaire battery was administered to acquire information related to depression, mood, the breakup and (former) relationship. Principal Component Analysis with Procrustes bootstrapping was performed to extract components from the questionnaire data. Even though our sample of individuals who recently have experienced a relationship breakup can be on average considered non-depressed, group-level depression scores were elevated compared to individuals in a relationship (p = .001) and 26.8% reported symptoms corresponding to mild, moderate or severe depression. We described heartbreak by two principal components interpreted as ''sudden loss" and ''lack of positive affect", respectively. Highly significant correlations between the component scores and depression scores were found (p < .001 and p < .001, respectively), although these correlations differed between the genders. Based on these findings, we propose that the experience of a romantic relationship breakup is a viable experimental model to examine symptoms of depression in individuals without a psychiatric disorder. This way, stress-related coping and depression vulnerability can be studied in further research., Competing Interests: The authors have declared that no competing interests exist.

The aim of this study was to investigate whether apathy in schizophrenia is associated with rigidity in behavior and brain functioning. To this end, we studied associations between variability in dynamic functional connectivity (DFC) in relevant functional brain networks, apathy, and variability in physical activity in schizophrenia. Thirty-one patients with schizophrenia, scoring high on apathy, were included and wore an actigraph. Activity variability was calculated on the activity counts using the root of the Mean Squared Successive Difference (MSSD). Furthermore, we calculated DFC on resting-state data as phase interactions between blood oxygen-level dependent (BOLD) signals of 270 brain regions per volume. Variability (MSSD) in DFC was calculated for 3 networks, including the default-mode network (DMN), frontoparietal network, and salience-reward network (SRN). Finally, we calculated correlations between these DFC estimates and apathy and activity variability. First, lower activity variability was associated with higher levels of apathy. Second, higher levels of apathy were associated with lower variability in DFC in the DMN and SRN. Third, higher activity variability was associated with higher variability in DFC in the SRN. In conclusion, patients with schizophrenia and more severe levels of apathy showed less variability in their physical activity and more rigid functional brain network behavior in the DMN and SRN. These networks have been shown relevant for self-reflection, mental simulation, and reward processing, processes that are pivotal for self-initiated goal-directed behavior. Functional rigidity of these networks may therefore contribute to reduced goal-directed behavior, which is characteristic for these patients., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Although it is often assumed that valence processing in the prefrontal cortex (PFC) is similar for stimuli originating from different sensory modalities, evidence supporting this view is lacking. To address this, we recruited 20 male participants and used a delayed-response fMRI design to test whether perceived pleasantness of flavors and images is similarly processed in the PFC. As predicted, significant correlations were observed between image and flavor pleasantness ratings, and PFC response to these stimuli; however, these responses were spatially different, with flavor pleasantness reflected in more ventrally located PFC regions than image pleasantness. These results indicate that, contrary to the general assumption of a singular circuit representing pleasantness, distinct PFC circuits are recruited depending upon stimulus modality. We argue that the ventral-dorsal distinction may be attributed to a difference in proximal versus distal stimulus representations., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Despite their wide-spread use, only limited information is available on the comparative test-retest reliability of task-based functional and resting state magnetic resonance imaging measures of blood oxygen level dependence (tb-fMRI and rs-fMRI) and cerebral blood flow (CBF) using arterial spin labeling. This information is critical to designing properly powered longitudinal studies. Here we comprehensively quantified and compared the test-retest reliability and reproducibility performance of 8 commonly applied fMRI tasks, 6 rs-fMRI metrics and CBF in 30 healthy volunteers. We find large variability in test-retest reliability performance across the different tb-fMRI paradigms and rs-fMRI metrics, ranging from poor to excellent. A larger extent of activation in tb-fMRI is linked to higher between-subject reliability of the respective task suggesting that differences in the amount of activation may be used as a first reliability estimate of novel tb-fMRI paradigms. For rs-fMRI, a good reliability of local activity estimates is paralleled by poor performance of global connectivity metrics. Evaluated CBF measures provide in general a good to excellent test-reliability matching or surpassing the best performing tb-fMRI and rs-fMRI metrics. This comprehensive effort allows for direct comparisons of test-retest reliability between the evaluated MRI domains and measures to aid the design of future tb-fMRI, rs-fMRI and CBF studies., Competing Interests: SH, FS, CL, GG, NS SAS, AB and JD are current or former full-time employees of F. Hoffmann-La Roche, Basel, Switzerland. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Idiopathic REM sleep behavior disorder (iRBD) is considered a prodromal stage of Parkinson disease (PD) and other Lewy body disorders. Spatial covariance analysis of 18 F-FDG PET data has disclosed a specific brain pattern of altered glucose metabolism in PD. In this study, we identify the metabolic pattern underlying iRBD and compare it with the known PD pattern. To understand the relevance of the iRBD pattern to disease progression, we studied the expression of the iRBD pattern in de novo PD patients. Methods: The iRBD-related pattern was identified in 18 F-FDG PET scans of 21 patients with polysomnographically confirmed iRBD and 19 controls using spatial covariance analysis. Expression of the iRBD-related pattern was subsequently computed in 18 F-FDG PET scans of 44 controls and 38 de novo, treatment-naïve PD patients. Of these 38 PD patients, 24 had probable REM sleep behavior disorder (RBD) according to the Mayo Sleep Questionnaire. Neuropsychologic evaluation showed mild cognitive impairment in 20 PD patients (PD-MCI), of whom 16 also had concomitant RBD and roughly half (11/20) had bilateral motor symptoms. Results: The iRBD-related pattern was characterized by relative hypermetabolism in the cerebellum, brain stem, thalamus, sensorimotor cortex, and hippocampus, and by relative hypometabolism in the middle cingulate, temporal, occipital, and parietal cortices. This topography partially overlapped with the PD-related pattern (PDRP). The iRBD-related pattern was significantly expressed in PD patients compared with controls ( P < 0.0001). iRBD-related pattern expression was not significantly different between PD patients with and without probable RBD, or between PD patients with unilateral or bilateral parkinsonism. iRBD-related pattern (iRBDRP) expression was higher in PD-MCI patients than in PD patients with preserved cognition ( P = 0.001). Subject scores on the iRBD-related pattern were highly correlated to subject scores on the PDRP ( r = 0.94, P < 0.0001). Conclusion: Our results show that the iRBDRP is an early manifestation of the PDRP. Expression of both PDRP and iRBDRP was higher in patients with a more severe form of PD (PD-MCI), which indicates that expression of the 2 patterns increases with disease severity., (© 2018 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: In ADPKD patients total kidney volume (TKV) measurement using MRI is performed to predict rate of disease progression. Historically T1 weighted images (T1) were used, but the methodology of T2 weighted imaging (T2) has evolved. We compared the performance of both sequences., Methods: 40 ADPKD patients underwent an abdominal MRI at baseline and follow-up. TKV was measured by manual tracing with Analyze Direct 11.0 software. Three readers established intra- and interreader coefficients of variation (CV). T1 and T2 measured kidney volumes and growth rates were compared with ICC and Bland-Altman analyses., Results: Participants were 49.7 ± 7.0 years of age, 55.0% female, with estimated GFR of 50.1 ± 11.5 mL/min/1.73 m 2 . CVs were low and comparable for T2 and T1 (intrareader: 0.83% [0.48-1.79] vs. 1.15% [0.34-1.77], P = 0.9, interreader: 2.18% [1.59-2.61] vs. 1.69% [1.07-3.87], P = 0.9). TKV was clinically similar, but statistically significantly different between T2 and T1: 1867 [1172-2721] vs. 1932 [1180-2551] mL, respectively (P = 0.006), with a bias of only 0.8% and high agreement (ICC 0.997). Percentage kidney growth during 2.2 ± 0.3 years was similar for T2 and T1 (9.3 ± 10.6% vs. 7.8 ± 9.9%, P = 0.1, respectively), with a bias of 1.5% and high agreement (ICC 0.843). T2 was more often of sufficient quality for volume measurement (86.7% vs. 71.1%, P < 0.001)., Conclusions: In patients with ADPKD, measurement of kidney volume and growth rate performs similarly when using T2 compared to T1 weighted images, although T2 performs better on secondary outcome parameters; they are more often of sufficient quality for volume measurement and result in slightly lower intra- and interreader variability.

Resting-state fMRI is widely used to study brain function and connectivity. However, interpreting patterns of resting state (RS) fMRI activity remains challenging as they may arise from different neuronal mechanisms than those triggered by exogenous events. Currently, this limits the use of RS-fMRI for understanding cortical function in health and disease. Here, we examine the phase synchronization (PS) properties of blood-oxygen level dependent (BOLD) signals obtained during visual field mapping (VFM) and RS with 7T fMRI. This data-driven approach exploits spatiotemporal covariations in the phase of BOLD recordings to establish the presence of clusters of synchronized activity. We find that, in both VFM and RS data, selecting the most synchronized neighboring recording sites identifies spatially localized PS clusters that follow the topographic organization of the visual cortex. However, in activity obtained during VFM, PS is spatially more extensive than in RS activity, likely reflecting stimulus-driven interactions between local responses. Nevertheless, the similarity of the PS clusters obtained for RS and stimulus-driven fMRI suggest that they share a common neuroanatomical origin. Our finding justifies and facilitates direct comparison of RS and stimulus-evoked activity., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: We aimed to uncover the pattern of network-level changes in neuronal function in Spinocerebellar ataxia type 3 (SCA3)., Methods: 17 genetically-confirmed SCA3 patients and 16 controls underwent structural MRI and static resting-state [ 18 F]‑Fluoro‑deoxyglucose Positron Emission Tomography (FDG-PET) imaging. A SCA3-related pattern (SCA3-RP) was identified using a multivariate method (scaled subprofile model and principal component analysis (SSM PCA)). Participants were evaluated with the Scale for Assessment and Rating of Ataxia (SARA) and with neuropsychological examination including tests for language, executive dysfunction, memory, and information processing speed. The relationships between SCA3-RP expression and clinical scores were explored. Voxel based morphology (VBM) was applied on MRI-T1 images to assess possible correlations between FDG reduction and grey matter atrophy., Results: The SCA3-RP disclosed relative hypometabolism of the cerebellum, caudate nucleus and posterior parietal cortex, and relatively increased metabolism in somatosensory areas and the limbic system. This topography, which was not explained by regional atrophy, correlated significantly with ataxia (SARA) scores (ρ = 0.72; P  = 0.001). SCA3 patients showed significant deficits in executive function and information processing speed, but only letter fluency correlated with SCA3-RP expression (ρ = 0.51; P  = 0.04, uncorrected for multiple comparisons)., Conclusion: The SCA3 metabolic profile reflects network-level alterations which are primarily associated with the motor features of the disease. Striatum decreases additional to cerebellar hypometabolism underscores an intrinsic extrapyramidal involvement in SCA3. Cerebellar-posterior parietal hypometabolism together with anterior parietal (sensory) cortex hypermetabolism may reflect a shift from impaired feedforward to compensatory feedback processing in higher-order motor control. The demonstrated SCA3-RP provides basic insight in cerebral network changes in this disease.

Neuroticism and genetic variation in the serotonin-transporter (SLC6A4) and catechol-O-methyltransferase (COMT) gene are risk factors for psychopathology. Alterations in the functional integration and segregation of neural circuits have recently been found in individuals scoring higher on neuroticism. The aim of the current study was to investigate how genetic risk factors impact functional network organization and whether genetic risk factors moderate the association between neuroticism and functional network organization. We applied graph theory analysis on resting-state fMRI data in a sample of 120 women selected based on their neuroticism score, and genotyped two polymorphisms: 5-HTTLPR (S-carriers and L-homozygotes) and COMT (rs4680-rs165599; COMT risk group and COMT non-risk group). For the 5-HTTLPR polymorphism, we found that subnetworks related to cognitive control show less connections with other subnetworks in S-carriers compared to L-homozygotes. The COMT polymorphism moderated the association between neuroticism and functional network organization. We found that neuroticism was associated with lower efficiency coefficients in visual and somatosensory-motor subnetworks in the COMT risk group compared to the COMT non-risk group. The findings of altered topology of specific subnetworks point to different cognitive-emotional processes that may be affected in relation to the genetic risk factors, concerning emotion regulation in S-carriers (5-HTTLPR) and emotional salience processing in COMT risk carriers.

Background & Aims: Taste and smell changes due to chemotherapy may contribute to the high prevalence of overweight in testicular cancer patients (TCPs). This study investigates the taste and smell function, dietary intake, food preference, and body composition in TCPs before, during, and up to 1 year after cisplatin-based chemotherapy., Methods: Twenty-one consecutive TCPs participated. At baseline TCPs were compared to healthy controls (N = 48). Taste strips and 'Sniffin' Sticks' were used to determine psychophysical taste and smell function. Subjective taste, smell, appetite, and hunger were assessed using a questionnaire. Dietary intake was analyzed using a food frequency questionnaire. Food preference was assessed using food pictures varying in taste (sweet/savoury) and fat or protein content. A Dual-Energy X-ray Absorptiometry (DEXA) scan was performed to measure whole body composition., Results: Compared to controls, TCPs had a lower smell threshold (P = 0.045) and lower preference for high fat sweet foods at baseline (P = 0.024). Over time, intra-individual psychophysical taste and smell function was highly variable. The salty taste threshold increased at completion of chemotherapy compared to baseline (P = 0.006). A transient decrease of subjective taste, appetite, and hunger feelings was observed per chemotherapy cycle. The percentage of fat mass increased during chemotherapy compared to baseline, while the lean mass and bone density decreased (P < 0.05)., Conclusions: Coping strategies regarding subjective taste impairment should especially be provided during the first week of each chemotherapy cycle. Since the body composition of TCPs already had changed at completion of chemotherapy, intervention strategies to limit the impact of cardiovascular risk factors should probably start during treatment., (Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Remitted patients with major depressive disorder (rMDD) often report more fluctuations in mood as residual symptomatology. It is unclear how this affective instability is associated with information processing related to the default mode (DMS), salience/reward (SRS), and frontoparietal (FPS) subnetworks in rMDD patients at high risk of recurrence (rrMDD). Sixty-two unipolar, drug-free rrMDD patients (⩾2 MDD episodes) and 41 healthy controls (HCs) were recruited. We used experience sampling methodology to monitor mood/cognitions (10 times a day for 6 days) and calculated affective instability using the mean adjusted absolute successive difference. Subsequently, we collected resting-state functional magnetic resonance imaging data and performed graph theory to obtain network metrics of integration within (local efficiency) the DMS, SRS, and FPS, and between (participation coefficient) these subnetworks and others. In rrMDD patients compared with HCs, we found that affective instability was increased in most negative mood/cognition variables and that the DMS had less connections with other subnetworks. Furthermore, we found that rrMDD patients, who showed more instability in feeling down and irritated, had less connections between the SRS and other subnetworks and higher local efficiency coefficients in the FPS, respectively. In conclusion, rrMDD patients, compared with HCs, are less stable in their negative mood and these dynamics are related to differences in information processing within- and between-specific functional subnetworks. These results are a first step to gain a better understanding of how mood fluctuations in real life are represented in the brain and provide insights into the vulnerability profile of MDD.

Background: Idiopathic REM sleep behavior disorder is a prodromal stage of Parkinson's disease and dementia with Lewy bodies. Hyposmia, reduced dopamine transporter binding, and expression of the brain metabolic PD-related pattern were each associated with increased risk of conversion to PD. The objective of this study was to study the relationship between the PD-related pattern, dopamine transporter binding, and olfaction in idiopathic REM sleep behavior disorder., Methods: In this cross-sectional study, 21 idiopathic REM sleep behavior disorder subjects underwent 18 F-fluorodeoxyglucose PET, dopamine transporter imaging, and olfactory testing. For reference, we included 18 F-fluorodeoxyglucose PET data of 19 controls, 20 PD patients, and 22 patients with dementia with Lewy bodies. PD-related pattern expression z-scores were computed from all PET scans., Results: PD-related pattern expression was higher in idiopathic REM sleep behavior disorder subjects compared with controls (P = 0.048), but lower compared with PD (P = 0.001) and dementia with Lewy bodies (P < 0.0001). PD-related pattern expression was higher in idiopathic REM sleep behavior disorder subjects with hyposmia and in subjects with an abnormal dopamine transporter scan (P < 0.05, uncorrected)., Conclusion: PD-related pattern expression, dopamine transporter binding, and olfaction may provide complementary information for predicting phenoconversion. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society., (© 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.)

The ventral emotion network-encompassing the amygdala, insula, ventral striatum, and ventral regions of the prefrontal cortex-has been associated with the identification of emotional significance of perceived external stimuli and the production of affective states. Functional magnetic resonance imaging (fMRI) studies investigating chemosensory stimuli have associated parts of this network with pleasantness coding. In the current study, we independently analyzed two datasets in which we measured brain responses to flavor stimuli in young adult men. In the first dataset, participants evaluated eight regular off the shelf drinking products while participants evaluated six less familiar oral nutritional supplements (ONS) in the second dataset. Participants provided pleasantness ratings 20 seconds after tasting. Using independent component analysis (ICA) and mixed effect models, we identified one brain network in the regular products dataset that was associated with flavor pleasantness. This network was very similar to the ventral emotion network. Although we identified an identical network in the ONS dataset using ICA, we found no linear relation between activation of any network and pleasantness scores within this dataset. Our results indicate that flavor pleasantness is processed in a network encompassing amygdala, ventral prefrontal, insular, striatal and parahippocampal regions for familiar drinking products. For more unfamiliar ONS products the association is not obvious, which could be related to the unfamiliarity of these products.

A metallic taste is reported by cancer patients as a side effect of systemic therapy. Despite the high prevalence, this taste alteration has received limited attention. The present study investigated: 1) the prevalence of metallic taste in cancer patients treated with systemic therapy; 2) possible predictors of metallic taste; and 3) characteristics of metallic taste. A heterogeneous population of 127 cancer patients, who had received systemic treatment in the past year or were still on treatment, completed a questionnaire developed for this study. Fifty-eight of 127 (46%) patients reported taste changes in the preceding week. Of these patients, 20 (34%) reported a metallic taste. Patients treated with chemotherapy, concomitant radiotherapy, as well as targeted therapy reported metallic taste. Women experienced metallic taste more often than men. Patients experiencing a metallic taste also reported more frequently that they were bothered by sour food and that everything tasted bitter. The experience of metallic taste was highly variable among patients. In conclusion, metallic taste is a frequently experienced taste alteration by cancer patients. Patients treated with chemotherapy, concomitant radiotherapy, and targeted therapy are all at risk for this taste alteration. However, not all patients reported this alteration as bothersome.

Purpose: Oral nutritional supplements (ONS) are commonly prescribed to malnourished patients to improve their nutritional status. Taste and smell changes in patients with cancer can affect the palatability of ONS. The present study investigated: (1) the palatability of six ONS in testicular cancer patients before, during the first two cycles, and after chemotherapy; (2) the relation between the palatability and taste and smell function; (3) the metallic taste of these ONS., Methods: Twenty-one testicular cancer patients undergoing first-line cisplatin-based chemotherapy participated. Two milk-based (vanilla; strawberry), two juice-based (apple; orange), and two yoghurt-based (vanilla-lemon; peach-orange) ONS were tested. A questionnaire was used to assess the palatability of ONS and to which extent the attribute 'metallic' was applicable. Taste and smell function were measured using taste strips and 'Sniffin' Sticks', respectively., Results: The palatability of ONS was highly variable among patients. The milk-based strawberry ONS was preferred most before, during, and after chemotherapy. The liking of the milk-based vanilla ONS tended to decrease over time (p = 0.053), whereas the liking of the other ONS remained stable. A higher smell threshold and a lower sour taste threshold were correlated to a decreased liking of the milk-based vanilla ONS. The two juice-based ONS tended to taste more metallic during than before chemotherapy., Conclusion: Health care professionals and patients should be aware that the palatability of ONS can change over time. Regular structured contact between health care professionals and patients regarding the choice of ONS seems warranted.

Background: Chemotherapy can affect taste and smell function. This may contribute to the high prevalence of overweight and metabolic syndrome in testicular cancer survivors (TCS). Aims of the study were to evaluate taste and smell function and possible consequences for dietary intake, food preference, and body composition in TCS treated with cisplatin-based chemotherapy., Methods: Fifty TCS, 1-7 years post-chemotherapy, and 50 age-matched healthy men participated. Taste and smell function were measured using taste strips and 'Sniffin' Sticks', respectively. Dietary intake was investigated using a food frequency questionnaire. Food preference was assessed using food pictures varying in taste (sweet/savoury) and fat or protein content. Dual-Energy X-ray Absorptiometry was performed to measure body composition. Presence of metabolic syndrome and hypogonadism were assessed., Results: TCS had a lower total taste function, a higher bitter taste threshold, higher Body Mass Index (BMI), and more (abdominal) fat than controls (p < 0.05). No differences in smell function and dietary intake were found. Testosterone level was an important determinant of body composition in TCS (p = 0.016)., Conclusion: Although taste function was impaired in TCS, this was not related to a different dietary intake compared to controls. Lower testosterone levels were associated with a higher BMI, fat mass, and abdominal fat distribution in TCS., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: The hippocampus is one of the brain regions that is involved in several pathophysiological theories about bipolar disorder (BD), such as the neuroinflammation theory and the corticolimbic metabolic dysregulation theory. We compared hippocampal volume and hippocampal metabolites in bipolar I disorder (BD-I) patients versus healthy controls (HCs) with magnetic resonance imaging (MRI) and spectroscopy (MRS). We post hoc investigated whether hippocampal volume and hippocampal metabolites were associated with microglial activation and explored if potential illness modifying factors affected these hippocampal measurements and whether these were associated with experienced mood and functioning., Materials and Methods: Twenty-two BD-I patients and twenty-four HCs were included in the analyses. All subjects underwent psychiatric interviews as well as an MRI scan, including a T1 scan and PRESS magnetic resonance spectroscopy (MRS). Volumetric analysis was performed with Freesurfer. MRS quantification was performed with LC Model. A subgroup of 14 patients and 11 HCs also underwent a successful [(11)C]-(R)-PK11195 neuroinflammation positron emission tomography scan., Results: In contrast to our hypothesis, hippocampal volumes were not decreased in patients compared to HC after correcting for individual whole-brain volume variations. We demonstrated decreased N-acetylaspartate (NAA)+N-acetyl-aspartyl-glutamate (NAAG) and creatine (Cr)+phosphocreatine (PCr) concentrations in the left hippocampus. In the explorative analyses in the left hippocampus we identified positive associations between microglial activation and the NAA+NAAG concentration, between alcohol use and NAA+NAAG concentration, between microglial activation and the depression score and a negative relation between Cr+PCr concentration and experienced occupational disability. Duration of illness associated positively with volume bilaterally., Conclusion: Compared to HCs, the decreased NAA+NAAG concentration in the left hippocampus of BD-I patients suggests a decreased neuronal integrity in this region. In addition we found a positive relation between microglial activation and neuronal integrity in vivo, corresponding to a differentiated microglial function where some microglia induce apoptosis while others stimulate neurogenesis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Several studies suggest different functional roles for the medial and the lateral sections of the ventral visual cortex in object recognition. Texture and surface information is processed in medial sections, while shape information is processed in lateral sections. This begs the question whether and how these functionally specialized sections interact with each other and with early visual cortex to facilitate object recognition. In the current research, we set out to answer this question. In an fMRI study, 13 subjects viewed and recognized images of objects and animals that were gradually revealed from noise while their brains were being scanned. We applied dynamic causal modeling (DCM)-a method to characterize network interactions-to determine the modulatory effect of object recognition on a network comprising the primary visual cortex (V1), the lingual gyrus (LG) in medial ventral cortex and the lateral occipital cortex (LO). We found that object recognition modulated the bilateral connectivity between LG and LO. Moreover, the feed-forward connectivity from V1 to LG and LO was modulated, while there was no evidence for feedback from these regions to V1 during object recognition. In particular, the interaction between medial and lateral areas supports a framework in which visual recognition of objects is achieved by networked regions that integrate information on image statistics, scene content and shape-rather than by a single categorically specialized region-within the ventral visual cortex.

Background: Abnormal brain activations during processing of emotional facial expressions in depressed patients have been demonstrated. We investigated the natural course of brain activation in response to emotional faces in depression, indexed by functional magnetic resonance imaging (fMRI) scans preceding and following change in depressive state. We hypothesized a decrease in activation in the amygdala, anterior cingulate cortex (ACC), and insula with a decrease in depressive pathology., Methods: A 2-year longitudinal fMRI study was conducted as part of the Netherlands Study of Depression and Anxiety. We included 32 healthy controls and 49 depressed patients. During the second scan, 27 patients were in remission (remitters), the other 22 were not (nonremitters). All participants viewed faces with emotional expressions during scanning., Results: Rostral ACC activation during processing of happy faces was predictive of a decrease in depressive state (PFWE = .003). In addition, remitters showed decreased activation of the insula over time (PFWE = .016), specifically during happy faces. Nonremitters displayed increased abnormalities in emotion recognition circuitry during the second scan compared to the first. No effect of selective serotonin reuptake inhibitor use was observed., Conclusions: Our results demonstrate that rostral ACC activation may predict changes in depressive state even at 2-year outcome. The association between change in depressed state and change in insula activation provides further evidence for the role of the insula in a network maintaining emotional and motivational states., (© 2015 Wiley Periodicals, Inc.)

A key property of human visual behavior is the very frequent movement of our eyes to potentially relevant information in the environment. Observers thus continuously have to prioritize information for directing their eyes to. Research in this field has been hampered by a lack of appropriate measures and tools. Here, we propose and validate a novel measure of priority that takes advantage of the variability in the natural viewing behavior of individual observers. In short, our measure assumes that priority is low when observers' gaze behavior is inconsistent and high when it is very consistent. We calculated priority for gaze data obtained during an experiment in which participants viewed dynamic natural scenes while we simultaneously recorded their gaze position and brain activity using functional magnetic resonance imaging. Our priority measure shows only limited correlation with various saliency, surprise, and motion measures, indicating it is assessing a distinct property of visual behavior. Finally, we correlated our priority measure with the BOLD signal, thereby revealing activity in a select number of human occipital and parietal areas. This suggests the presence of a cortical network involved in computing and representing viewing priority. We conclude that our new analysis method allows for empirically establishing the priority of events in near-natural vision paradigms.

Background: In autosomal dominant polycystic kidney disease (ADPKD), obtaining measured total kidney volume (mTKV) by magnetic resonance (MR) imaging and manual tracing is time consuming. Two alternative MR imaging methods have recently been proposed to estimate TKV (eTKVellipsoid and eTKVPANK), which require less time., Study Design: Cross-sectional and longitudinal diagnostic test study., Setting & Participants: Patients with ADPKD with a wide range of kidney function and an approved T2-weighted MR image obtained at the University Medical Centers of Groningen, Leiden, Nijmegen, and Rotterdam, the Netherlands, in 2007 to 2014. Test set for assessing reproducibility, n=10; cohort for cross-sectional analyses, n=220; and cohort for longitudinal analyses, n=48., Index Tests: Average times for eTKVellipsoid and eTKVPANK were 5 and 15 minutes, respectively. Bias is defined as (mTKV - eTKV)/mTKV × 100%; precision, as one standard deviation of bias., Reference Tests: mTKV using manual tracing to calculate the area within kidney boundaries times slice thickness. Average time for mTKV was 55 minutes., Results: In the test set, intra- and intercoefficients of variation for mTKV, eTKVellipsoid, and eTKVPANK were 1.8% and 2.3%, 3.9% and 6.3%, and 3.0% and 3.4%, respectively. In cross-sectional analysis, baseline mTKV, eTKVellipsoid, and eTKVPANK were 1.96 (IQR, 1.28-2.82), 1.93 (IQR, 1.25-2.82), and 1.81 (IQR, 1.17-2.62) L, respectively. In cross-sectional analysis, bias was 0.02% ± 3.2%, 1.4% ± 9.2%, and 4.6% ± 7.6% for repeat mTKV, eTKVellipsoid, and eTKVPANK, respectively. In longitudinal analysis, no significant differences were observed between percentage change in mTKV (16.7% ± 17.1%) and percentage change in eTKVellipsoid (19.3% ± 16.1%) and eTKVPANK (17.8% ± 16.1%) over 3 years., Limitations: Results for follow-up data should be interpreted with caution because of the limited number of patients., Conclusions: Both methods for eTKV perform relatively well compared to mTKV and can detect change in TKV over time. Because eTKVellipsoid requires less time than eTKVPANK, we suggest that this method may be preferable in clinical care., (Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

The primary gustatory area is located in the insular cortex. Although the insular cortex has been the topic of multiple parcellation studies, its functional specialization regarding taste processing received relatively little attention. Studies investigating the brain response to taste suggested that the insular cortex is involved in processing multiple characteristics of a taste stimulus, such as its quality, intensity, and pleasantness. In the current functional magnetic resonance study, younger and older adult male subjects were exposed to four basic tastes in five increasing concentrations. We applied a data-driven analysis to obtain insular response maps, which showed that the insular cortex processes the presence of taste, its corresponding pleasantness, as well as its concentration. More specifically, the left and right insular cortices are differentially engaged in processing the aforementioned taste characteristics: representations of the presence of a taste stimulus as well as its corresponding pleasantness dominate in the left insular cortex, whereas taste concentration processing dominates in the right insular cortex. These results were similar across both age groups. Our results fit well within previous cytoarchitectural studies and show insular lateralization in processing different aspects of taste stimuli in men., (Copyright © 2015. Published by Elsevier Inc.)

Background: Prefrontal cortical dysfunction is frequently reported in schizophrenia and is thought to underlie negative symptoms of schizophrenia. Repetitive Transcranial Magnetic Stimulation (rTMS) can modulate neuronal activity and has been shown to improve negative symptoms in patients with schizophrenia, but the underlying neural mechanism is unknown., Objective: To examine whether 3weeks of 10Hz rTMS treatment of the bilateral dorsolateral prefrontal cortex (DLPFC) would improve frontal brain activation in patients with negative symptoms of schizophrenia, as measured by functional magnetic resonance imaging (fMRI) during the Tower of London (ToL) task., Methods: 24 patients with the diagnosis of schizophrenia with moderate to severe negative symptoms (Positive and Negative Syndrome Scale (PANSS) negative subscale≥15) participated. Patients were randomized to a 3-week (15day) course of active or sham rTMS. All patients performed the ToL task during fMRI scanning both pre-treatment and post-treatment. Differences in brain activation between the two groups were compared non-parametrically., Results: After rTMS treatment, brain activity in the active group increased in the right DLPFC and the right medial frontal gyrus as compared to the sham group. In addition, the groups significantly differed with regard to activation change in the left posterior cingulate, with decreased activation in the active and increased activation in the sham group., Conclusions: Treatment with rTMS over the DLPFC may have the potential for increasing task-related activation in frontal areas in patients with schizophrenia. Effects of different rTMS parameters and fMRI tasks targeting relevant brain circuitry deserve further investigation., Trial Registration: Nederlands Trial Register, registration number: NTR1261., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Ageing affects taste perception as shown in psychophysical studies, however, underlying structural and functional mechanisms of these changes are still largely unknown. To investigate the neurobiology of age-related differences associated with processing of basic tastes, we measured brain activation (i.e. fMRI-BOLD activity) during tasting of four increasing concentrations of sweet, sour, salty, and bitter tastes in young (average 23 years of age) and older (average 65 years of age) adults. The current study highlighted age-related differences in taste perception at the different higher order brain areas of the taste pathway. We found that the taste information delivered to the brain in young and older adults was not different, as illustrated by the absence of age effects in NTS and VPM activity. Our results indicate that multisensory integration changes with age; older adults showed less brain activation to integrate both taste and somatosensory information. Furthermore, older adults directed less attention to the taste stimulus; therefore attention had to be reallocated by the older individuals in order to perceive the tastes. In addition, we considered that the observed age-related differences in brain activation between taste concentrations in the amygdala reflect its involvement in processing both concentration and pleasantness of taste. Finally, we state the importance of homeostatic mechanisms in understanding the taste quality specificity in age related differences in taste perception., (Copyright © 2015. Published by Elsevier Inc.)

Unfair treatment may evoke more negative emotions in individuals scoring higher on neuroticism, thereby possibly impacting their decision-making in these situations. To investigate the neural basis of social decision-making in these individuals, we examined interpersonal reactions to unfairness in the Ultimatum Game (UG). We measured brain activation with fMRI in 120 participants selected based on their neuroticism score, while they made decisions to accept or reject proposals that were either fair or unfair. The anterior insula and anterior cingulate cortex were more activated during the processing of unfair offers, consistent with prior UG studies. Furthermore, we found more activation in parietal and temporal regions for the two most common decisions (fair accept and unfair reject), involving areas related to perceptual decision-making. Conversely, during the decision to accept unfair offers, individuals recruited more frontal regions previously associated with decision-making and the implementation of reappraisal in the UG. High compared to low neurotic individuals did not show differential activation patterns during the proposal of unfair offers; however, they did show lower activation in the right dorsal striatum (putamen) during the acceptance of unfair offers. This brain region has been involved in the formation of stimulus-action-reward associations and motivation/arousal. In conclusion, the findings suggest that both high and low neurotic individuals recruit brain regions signaling social norm violations in response to unfair offers. However, when it comes to decision-making, it seems that neural circuitry related to reward and motivation is altered in individuals scoring higher on neuroticism, when accepting an unfair offer.

Background: Visualization of the precise course of the visual pathways is relevant to prevent damage that may inflict visual field deficits during neurosurgical resections. In particular the optic radiations (OR) are susceptible to such damage during neurosurgery. Cortical pathways can be mapped in vivo, by using Diffusion Tensor Imaging (DTI). Visualization of these pathways would be potentially helpful to prevent neurosurgical visual morbidity. In this study an anatomical dissection of the visual pathways was compared to DTI fiber tractography (DTI-FT) data of four human brains. The feasibility of a definition of a Safety Zone is investigated., Methods: Four adult brains were dissected using Klingler's fiber dissection method, which allowed preparation of the OR. Measurements before and after dissection were used to establish distances from the cortex to the OR. DTI-scans were also obtained from these brains to determine the same distances., Results: Measurements from specific landmark points on the cortex to the lateral border of the OR were performed in four brains. Analysis through DTI tractography corresponded with the dissection results. Based on the combined results of both dissection and DTI-FT, we defined a quantitative surgical Safety Zone with respect to various anatomical landmarks (in particular the ventricle system)., Conclusion: We conclude that there is a good correlation between the visualizations of the optic pathways based on dissection and DTI. Furthermore, we conclude that defining a neurosurgical Safety Zone which could preserve the integrity of the OR during surgery, based on the combination of DTI-FT images and dissection is feasible.

Aging affects functional connectivity between brain areas, however, a complete picture of how aging affects integration of information within and between functional networks is missing. We used complex network measures, derived from a brain-wide graph, to provide a comprehensive overview of age-related changes in functional connectivity. Functional connectivity in young and older participants was assessed during resting-state fMRI. The results show that aging has a large impact, not only on connectivity within functional networks but also on connectivity between the different functional networks in the brain. Brain networks in the elderly showed decreased modularity (less distinct functional networks) and decreased local efficiency. Connectivity decreased with age within networks supporting higher level cognitive functions, that is, within the default mode, cingulo-opercular and fronto-parietal control networks. Conversely, no changes in connectivity within the somatomotor and visual networks, networks implicated in primary information processing, were observed. Connectivity between these networks even increased with age. A brain-wide analysis approach of functional connectivity in the aging brain thus seems fundamental in understanding how age affects integration of information., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The primary somatosensory cortex (SI) plays a critical role in somatosensation as well as in action performance and social cognition. Although the SI has been a major target of experimental and clinical research using non-invasive transcranial magnetic stimulation (TMS), to date information on the effect of TMS over the SI on its resting-state functional connectivity is very scant. Here, we explored whether continuous theta burst stimulation (cTBS), a repetitive TMS protocol, administered over the SI can change the functional connectivity of the brain at rest, as measured using resting-state functional magnetic resonance imaging (rs-fMRI). In a randomized order on two different days we administered active TMS or sham TMS over the left SI. TMS was delivered off-line before scanning by means of cTBS. The target area was selected previously and individually for each subject as the part of the SI activated both when the participant executes and observes actions. Three analytical approaches, both theory driven (partial correlations and seed based whole brain regression) and more data driven (Independent Component Analysis), indicated a reduction in functional connectivity between the stimulated part of the SI and several brain regions functionally associated with the SI including the dorsal premotor cortex, the cerebellum, basal ganglia, and anterior cingulate cortex. These findings highlight the impact of cTBS delivered over the SI on its functional connectivity at rest. Our data may have implications for experimental and therapeutic applications of cTBS over the SI., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: A recent study showed that tolvaptan, a vasopressin V2 receptor antagonist, decreased total kidney volume (TKV) growth and estimated glomerular filtration rate (GFR) loss in autosomal dominant polycystic kidney disease (ADPKD) with creatinine clearance≥60mL/min. The aim of our study was to determine whether the renal hemodynamic effects and pharmacodynamic efficacy of tolvaptan in ADPKD are dependent on GFR., Study Design: Clinical trial with comparisons before and after treatment., Setting & Participants: Patients with ADPKD with a wide range of measured GFRs (mGFRs; 18-148 mL/min) in a hospital setting., Intervention: Participants were studied at baseline and after 3 weeks of treatment with tolvaptan given in increasing dosages, if tolerated (doses of 60, 90, and 120mg/d in weeks 1, 2, and 3, respectively)., Outcomes: Change in markers for aquaresis (free-water clearance, urine and plasma osmolality, 24-hour urine volume, and plasma copeptin) and kidney injury (TKV and kidney injury biomarkers)., Measurements: GFR was measured by (125)I-iothalamate clearance; TKV, by magnetic resonance imaging; biomarker excretion, by enzyme-linked immunosorbent assay; and osmolality, by freezing point depression., Results: In 27 participants (52% men; aged 46±10 years; mGFR, 69±39mL/min; TKV, 2.15 [IQR, 1.10-2.77] L), treatment with tolvaptan led to an increase in urine volume and free-water clearance and a decrease in urine osmolality, TKV, and kidney injury marker excretion. Changes in urine volume and osmolality with treatment were less in participants with lower baseline mGFRs (both P<0.01). However, change in fractional free-water clearance was greater at lower baseline mGFRs (P=0.001), suggesting that participants with decreased GFRs responded more to tolvaptan per functioning nephron., Limitations: Limited sample size, no control group., Conclusions: In patients with ADPKD with decreased kidney function, response to tolvaptan is lower for TKV, urinary volume, and osmolality, but larger for fractional free-water clearance. This latter finding suggests that patients with ADPKD with lower GFRs might benefit from long-term treatment with tolvaptan, as has been observed for patients with preserved GFRs., (Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

It has been proposed that the neural basis for cognitive vulnerability to depression involves an imbalance in frontolimbic activity during the processing of cues with a negative affective value. Although the question is central to cognitive theory, whether this association is amplified by diagnosis of an affective disorder or recent life stress has not been investigated. A composite cognitive vulnerability score based on questionnaire assessment was used to predict neural responses to negative emotional stimuli in N = 112 participants. Potential moderating effects of psychiatric diagnosis and negative life events were examined. Main and interaction effects were tested against a threshold of p < .05, family-wise error (FWE) corrected at the cluster level, and the results were small-volume corrected in regions of interest. Cognitive vulnerability predicted higher activation of superior parietal areas (p(FWE) < .01) for negative than for positive faces. The association was significantly stronger in healthy participants. For negative versus control stimuli, cognitive vulnerability predicted higher ventrolateral prefrontal and subgenual anterior cingulate activation (p(FWE) < .05) to equal extents in both groups. We found no evidence for an association with amygdala activation. Life events did not moderate the findings. We concluded that cognitive vulnerability was associated with higher activation of frontoparietal areas during an implicit emotional task. These higher levels of activation may potentially reflect increased effort being required to ignore irrelevant negative emotional information in vulnerable populations.

Patients with schizophrenia often suffer from apathy: a quantitative reduction of voluntary, goal-directed behaviors that impairs daily functioning. We hypothesized that schizophrenia patients with high levels of apathy would show decreased activation in brain regions involved in planning and goal-directed behavior. Patients with schizophrenia or psychotic spectrum disorder (n=47) and healthy controls (n=20) performed the Tower of London (ToL) task during fMRI scanning using arterial spin labeling. To investigate the relationship between apathy and planning in patients, a proxy measure of apathy based on the Positive and Negative syndrome Scale was regressed against the task-related brain activation. Brain activation was also compared between patients and healthy controls. Higher levels of apathy were associated with less task-related activation within the inferior parietal lobule precuneus and thalamus. Compared to controls, patients showed lower activation in lateral prefrontal regions, parietal and motor areas, and a higher activation of medial frontal areas. Apathy was related to abnormal activation in thalamus and parietal regions during the ToL task. This supports the hypothesis that impaired function of brain regions involved in planning and goal-directed behavior may underlie apathy in schizophrenia. Moreover, impaired lateral prefrontal activation in schizophrenia patients compared to controls is consistent with the hypofrontality model of schizophrenia. In contrast, stronger medial frontal activation in patients may be related to increased effort to perform a task with conflicting task solutions., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Metallic taste is a taste alteration frequently reported by cancer patients treated with chemotherapy. Attention to this side effect of chemotherapy is limited. This review addresses the definition, assessment methods, prevalence, duration, etiology, and management strategies of metallic taste in chemotherapy treated cancer patients., Methods: Literature search for metallic taste and chemotherapy was performed in PubMed up to September 2014, resulting in 184 articles of which 13 articles fulfilled the inclusion criteria: English publications addressing metallic taste in cancer patients treated with FDA-approved chemotherapy. An additional search in Google Scholar, in related articles of both search engines, and subsequent in the reference lists, resulted in 13 additional articles included in this review. Cancer patient forums were visited to explore management strategies., Findings: Prevalence of metallic taste ranged from 9.7% to 78% among patients with various cancers, chemotherapy treatments, and treatment phases. No studies have been performed to investigate the influence of metallic taste on dietary intake, body weight, and quality of life. Several management strategies can be recommended for cancer patients: using plastic utensils, eating cold or frozen foods, adding strong herbs, spices, sweetener or acid to foods, eating sweet and sour foods, using 'miracle fruit' supplements, and rinsing with chelating agents., Interpretation: Although metallic taste is a frequent side effect of chemotherapy and a much discussed topic on cancer patient forums, literature regarding metallic taste among chemotherapy treated cancer patients is scarce. More awareness for this side effect can improve the support for these patients., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Medical imaging techniques like fluorodeoxyglucose positron emission tomography (FDG-PET) have been used to aid in the differential diagnosis of neurodegenerative brain diseases. In this study, the objective is to classify FDG-PET brain scans of subjects with Parkinsonian syndromes (Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy) compared to healthy controls. The scaled subprofile model/principal component analysis (SSM/PCA) method was applied to FDG-PET brain image data to obtain covariance patterns and corresponding subject scores. The latter were used as features for supervised classification by the C4.5 decision tree method. Leave-one-out cross validation was applied to determine classifier performance. We carried out a comparison with other types of classifiers. The big advantage of decision tree classification is that the results are easy to understand by humans. A visual representation of decision trees strongly supports the interpretation process, which is very important in the context of medical diagnosis. Further improvements are suggested based on enlarging the number of the training data, enhancing the decision tree method by bagging, and adding additional features based on (f)MRI data.

Visual object recognition occurs at the intersection of visual perception and visual cognition. It typically occurs very fast and it has therefore been difficult to disentangle its constituent processes. Recognition time can be extended when using images with emergent properties, suggesting they may help examining how visual recognition unfolds over time. Until now, their use has been constrained by limited availability. We used a set of stimuli with emergent properties-akin to the famous Gestalt image of a Dalmatian-in combination with eye tracking to examine the processes underlying object recognition. To test whether cognitive processes influenced eye movement behavior during recognition, an unprimed and three primed groups were included. Recognition times were relatively long (median ∼ 5s for the unprimed group), confirming the object's emergent properties. Surprisingly, within the first 500 ms, the majority of fixations were already aimed at the object. Computational models of saliency could not explain these initial fixations. This suggests that observers relied on image statistics not captured by saliency models. For the primed groups, recognition times were reduced. However, threshold-free cluster enhancement-based analysis of the time courses indicated that viewing behavior did not differ between the groups, neither during the initial viewing nor around the moment of recognition. This implies that eye movements are mainly driven by perceptual processes and not affected by cognition. It further suggests that priming mainly boosts the observer's confidence in the decision reached. We conclude that emerging images can be a useful tool to dissociate the perceptual and cognitive contributions to visual object recognition.

The personality trait neuroticism is a potent risk marker for psychopathology. Although the neurobiological basis remains unclear, studies have suggested that alterations in connectivity may underlie it. Therefore, the aim of the current study was to shed more light on the functional network organization in neuroticism. To this end, we applied graph theory on resting-state functional magnetic resonance imaging (fMRI) data in 120 women selected based on their neuroticism score. Binary and weighted brain-wide graphs were constructed to examine changes in the functional network structure and functional connectivity strength. Furthermore, graphs were partitioned into modules to specifically investigate connectivity within and between functional subnetworks related to emotion processing and cognitive control. Subsequently, complex network measures (ie, efficiency and modularity) were calculated on the brain-wide graphs and modules, and correlated with neuroticism scores. Compared with low neurotic individuals, high neurotic individuals exhibited a whole-brain network structure resembling more that of a random network and had overall weaker functional connections. Furthermore, in these high neurotic individuals, functional subnetworks could be delineated less clearly and the majority of these subnetworks showed lower efficiency, while the affective subnetwork showed higher efficiency. In addition, the cingulo-operculum subnetwork demonstrated more ties with other functional subnetworks in association with neuroticism. In conclusion, the 'neurotic brain' has a less than optimal functional network organization and shows signs of functional disconnectivity. Moreover, in high compared with low neurotic individuals, emotion and salience subnetworks have a more prominent role in the information exchange, while sensory(-motor) and cognitive control subnetworks have a less prominent role.

In the current study we show that non-verbal food-evoked emotion scores significantly improve food choice prediction over merely liking scores. Previous research has shown that liking measures correlate with choice. However, liking is no strong predictor for food choice in real life environments. Therefore, the focus within recent studies shifted towards using emotion-profiling methods that successfully can discriminate between products that are equally liked. However, it is unclear how well scores from emotion-profiling methods predict actual food choice and/or consumption. To test this, we proposed to decompose emotion scores into valence and arousal scores using Principal Component Analysis (PCA) and apply Multinomial Logit Models (MLM) to estimate food choice using liking, valence, and arousal as possible predictors. For this analysis, we used an existing data set comprised of liking and food-evoked emotions scores from 123 participants, who rated 7 unlabeled breakfast drinks. Liking scores were measured using a 100-mm visual analogue scale, while food-evoked emotions were measured using 2 existing emotion-profiling methods: a verbal and a non-verbal method (EsSense Profile and PrEmo, respectively). After 7 days, participants were asked to choose 1 breakfast drink from the experiment to consume during breakfast in a simulated restaurant environment. Cross validation showed that we were able to correctly predict individualized food choice (1 out of 7 products) for over 50% of the participants. This number increased to nearly 80% when looking at the top 2 candidates. Model comparisons showed that evoked emotions better predict food choice than perceived liking alone. However, the strongest predictive strength was achieved by the combination of evoked emotions and liking. Furthermore we showed that non-verbal food-evoked emotion scores more accurately predict food choice than verbal food-evoked emotions scores.

Recent studies have shown that aging has a large impact on connectivity within and between functional networks. An open question is whether elderly still have the flexibility to adapt functional network connectivity (FNC) to the demands of the task at hand. To study this, we collected fMRI data in younger and older participants during resting state, a selective attention (SA) task and an n-back working memory task with varying levels of difficulty. Spatial independent component (IC) analysis was used to identify functional networks over all participants and all conditions. Dual regression was used to obtain participant and task specific time-courses per IC. Subsequently, functional connectivity was computed between all ICs in each of the tasks. Based on these functional connectivity matrices, a scaled version of the eigenvector centrality (SEC) was used to measure the total influence of each IC in the complete graph of ICs. The results demonstrated that elderly remain able to adapt FNC to task demands. However, there was an age-related shift in the impetus for FNC change. Older participants showed the maximal change in SEC patterns between resting state and the SA task. Young participants, showed the largest shift in SEC patterns between the less demanding SA task and the more demanding 2-back task. Our results suggest that increased FNC changes from resting state to low demanding tasks in elderly reflect recruitment of additional resources, compared with young adults. The lack of change between the low and high demanding tasks suggests that elderly reach a resource ceiling., (Copyright © 2013 Wiley Periodicals, Inc.)

Introduction: Under normal conditions, the spatial distribution of resting cerebral blood flow and cerebral metabolic rate of glucose are closely related. A relatively new magnetic resonance (MR) technique, pseudo-continuous arterial spin labeling (PCASL), can be used to measure regional brain perfusion. We identified a Parkinson's disease (PD)-related perfusion and metabolic covariance pattern in the same patients using PCASL and FDG-PET imaging and assessed (dis)similarities in the disease-related pattern between perfusion and metabolism in PD patients., Methods: Nineteen PD patients and seventeen healthy controls underwent [(18)F]-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging. Of 14 PD patients and all healthy controls PCASL-MRI could be obtained. Data were analyzed using scaled subprofile model/principal component analysis (SSM/PCA)., Results: Unique Parkinson's disease-related perfusion and metabolic covariance patterns were identified using PCASL and FDG-PET in the same patients. The PD-related metabolic covariance brain pattern is in high accordance with previously reports. Also our disease-related perfusion pattern is comparable to the earlier described perfusion pattern. The most marked difference between our perfusion and metabolic patterns is the larger perfusion decrease in cortical regions including the insula., Conclusion: We identified PD-related perfusion and metabolic brain patterns using PCASL and FDG-PET in the same patients which were comparable with results of existing research. In this respect, PCASL appears to be a promising addition in the early diagnosis of individual parkinsonian patients.

The ability to suppress irrelevant information declines with age, while the ability to enhance relevant information remains largely intact. We examined mechanisms behind this dissociation in an fMRI study, using a selective attention task in which relevant and irrelevant information appeared simultaneously. Slowing of response times due to distraction by irrelevant targets was larger in older than younger participants. Increased distraction was related to larger increases in activity and connectivity in areas of the dorsal attention network, indicating a more pronounced (re-)orientation of attention. The decreases in accuracy in target compared to nontarget trials were smaller in older compared to younger participants. In older adults we found increased recruitment of areas in the fronto-parietal control network (FPCN) during target detection. Moreover, older adults showed increased connectivity between the FPCN, supporting cognitive control, and somatomotor areas implicated in response selection and execution. This connectivity increase was related to improved target detection, suggesting that older adults engage additional cognitive control, which might enable the observed intact performance in detecting and responding to target stimuli., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Radial expanding optic flow is a visual consequence of forward locomotion. Presented on screen, it generates illusionary forward self-motion, pointing at a close vision-gait interrelation. As particularly parkinsonian gait is vulnerable to external stimuli, effects of optic flow on motor-related cerebral circuitry were explored with functional magnetic resonance imaging in healthy controls (HC) and patients with Parkinson's disease (PD). Fifteen HC and 22 PD patients, of which 7 experienced freezing of gait (FOG), watched wide-field flow, interruptions by narrowing or deceleration and equivalent control conditions with static dots. Statistical parametric mapping revealed that wide-field flow interruption evoked activation of the (pre-)supplementary motor area (SMA) in HC, which was decreased in PD. During wide-field flow, dorsal occipito-parietal activations were reduced in PD relative to HC, with stronger functional connectivity between right visual motion area V5, pre-SMA and cerebellum (in PD without FOG). Non-specific 'changes' in stimulus patterns activated dorsolateral fronto-parietal regions and the fusiform gyrus. This attention-associated network was stronger activated in HC than in PD. PD patients thus appeared compromised in recruiting medial frontal regions facilitating internally generated virtual locomotion when visual motion support falls away. Reduced dorsal visual and parietal activations during wide-field optic flow in PD were explained by impaired feedforward visual and visuomotor processing within a magnocellular (visual motion) functional chain. Compensation of impaired feedforward processing by distant fronto-cerebellar circuitry in PD is consistent with motor responses to visual motion stimuli being either too strong or too weak. The 'change'-related activations pointed at covert (stimulus-driven) attention.