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Background: Gastrointestinal dysfunction and related clinical symptoms are common in Parkinson’s disease (PD), but the underlying mechanisms are still poorly understood. Objective: In this study, we investigated how PD affects the postprandial vascular response in the splanchnic circulation. Methods: 23 patients with PD in the “ON-medication” state and 23 age- and sex-matched healthy control participants underwent serial phase-contrast magnetic resonance imaging (PC-MRI) to measure the postprandial blood flow response in the superior mesenteric artery (SMA). Participants ingested a standardized liquid test meal (∼400 kcal) and underwent four PC-MRI runs within the following hour. Each PC-MRI run consisted of six consecutive measurements of SMA blood flow. Results: In both groups, standardized food intake triggered an increase of blood flow in the SMA, but absolute and relative increases in blood flow were attenuated in patients compared to the control group (p

BACKGROUND AND AIMS Non-alcoholic fatty liver disease (NAFLD) is suggested as being a risk factor for chronic kidney disease (CKD). The incidence of NAFLD is rising globally parallel to the increasing incidences of obesity and type 2 diabetes. As diabetes remains the leading cause of CKD the co-existence of NAFLD, CKD and type 2 diabetes needs to be explored. Here, we evaluated the prevalence of hepatic steatosis in patients with type 2 diabetes and CKD and patients with type 2 diabetes without CKD. METHOD This cross-sectional study included 50 patients with type 2 diabetes and CKD stages 3–5 and 50 patients with type 2 diabetes without CKD. Liver fat content was estimated by proton magnetic resonance spectroscopy (1H-MRS) and magnetic resonance imaging proton density fat fraction (MRI-PDFF) by the multi-echo Dixon-technique in a 3 Tesla full-body MRI scanner. Hepatic steatosis was defined as ≥ 5.56% liver fat. Further, continuous glucose monitoring (CGM) was performed for 4 days. RESULTS Mean age 72.0 ± 4.9 years and body mass index (BMI) 28.6 ± 3.5 kg/m2 in patients with CKD, and mean age 65.9 ± 7.8 years and BMI 27.0 ± 4.0 kg/m2 in patients without CKD with a predominance of men in both groups. Hepatic steatosis was identified in 22 (44%) patients with CKD and 19 (38%) patients without CKD (P = 0.68). Median (IQR) values of percentage liver fat were 4.7% (3.0–8.5) and 4.1% (2.9–7.7) in patients with and without CKD, respectively, corresponding to 5.3% higher levels of hepatic fat percentage in patients with CKD [95% confidence interval (CI) −23; 45, P = 0.75]. Mean sensor glucose from CGM was 9.0 ± 1.6 mmol/L and 8.7 ± 1.8 mmol/L in patients with and without CKD, respectively (P = 0.47). There was no statistically significant difference between the two groups regarding the percentage of time spent in different CGM ranges: time-below-range, 10.0 mmol/L (P = 0.20). Pooled data from both groups showed no significant association between the mean sensor glucose from CGM and hepatic fat percentages (P = 0.38). CONCLUSION These findings do not support any association between hepatic steatosis and CKD stages 3–5 in patients with type 2 diabetes.

People are better at approaching appetitive cues signaling reward and avoiding aversive cues signaling punishment than vice versa. This action bias has previously been shown in approach-avoidance tasks involving arm movements in response to appetitive or aversive cues. It is not known whether appetitive or aversive stimuli also bias more distal dexterous actions, such as gripping and slipping, in a similar manner. To test this hypothesis, we designed a novel task involving grip force control (gripping and slipping) to probe gripping-related approach and avoidance behavior. 32 male volunteers, aged 18–40 years, were instructed to either grip (“approach”) or slip (”avoid”) a grip-force device with their right thumb and index finger at the sight of positive or negative images. In one version of this pincer grip task, participants were responding to graspable objects and in another version of the task they were responding to happy or angry faces. Bayesian repeated measures Analysis of variance revealed extreme evidence for an interaction between response type and cue valence (Bayes factor = 296). Participants were faster to respond in affect-congruent conditions (“approach appetitive,” “avoid aversive”) than in affect-incongruent conditions (“approach aversive,” “avoid appetitive”). This bias toward faster response times for affect-congruent conditions was present regardless of whether it was a graspable object or a face signaling valence. Since our results mirror the approach and avoidance effects previously observed for arm movements, we conclude that a tendency favoring affectively congruent cue-response mappings is an inherent feature of motor control and thus also includes precision grip.

Magnetic resonance imaging is today the most versatile imaging method for characterization of multiple sclerosis (MS) in vivo, but clinical examinations lack sensitivity to capture changes in the tissue microstructure. Using a multi-dimensional microstructural imaging approach, we demonstrate how it is possible to obtain more specific and broader microstructural insights about the underlying pathology of MS. For this we use a comprehensive battery of conventional and novel diffusion weighted imaging and quantitative MRI sequences each capable of explaining different and complementary microstructural properties. This allows us to explore the underlying pathology of MS, which is normally only accessible with histology.

The goal of this work was to investigate iron deposition in the basal ganglia and thalamus in symptomatic and asymptomatic leucine-rich repeat kinase 2 (LRRK2) and Parkin-associated Parkinson's disease (PD), using R2* relaxometry rate.Twenty subjects with genetic PD (four symptomatic and two asymptomatic Parkin subjects, nine symptomatic and five asymptomatic LRRK2 subjects) were compared with 20 patients with idiopathic PD (IPD) and 20 healthy subjects. Images were obtained at 3 teslas, using multi-echo T2 and T2* sequences. R2 and R2* values were calculated in the substantia nigra (SN), the striatum, the globus pallidus, and the thalamus.The R2* values in the SN were increased in IPD and mutation-carrying patients as compared with controls and in mutation-carrying patients as compared with IPD. Asymptomatic mutation carriers showed higher R2* values than controls and did not differ from IPD patients. No changes were seen in the other structures or in R2 values.These results are consistent with increased iron load in LRRK2- and Parkin-mutation carriers. The increased R2* in asymptomatic PD-mutation carriers suggests that iron deposition occurs early during the preclinical phase of the disease. R2* measurements may be used as markers for investigating nigrostriatal damage in preclinical mutation-carrying patients.

The pineal gland (CP) is located centrally in the brain and produces melatonin. Cysts and concrements are frequent findings on MRI but their significance is still unclear. The visualization of CP is difficult due to its location and surrounding structures and so far, no standardized method exists. New studies suggest a correlation between CP-morphology and melatonin secretion as well as a connection between melatonin, disturbed circadian rhythm, and the development of cancer and cardiovascular diseases, underlining the need for a standardized approach to CP on MRI.

Photosensitivity or photoparoxysmal response (PPR) is an electroencephalography trait that is highly associated with idiopathic generalized epilepsies (IGEs) and characterized by changes in cortical excitability in response to photic stimulation. Studying functional and structural changes of PPR might provide important insights into the pathogenesis of IGE. Recent studies revealed a functional network consisting of occipital, parietal, and precentral areas that might be implicated in PPR. Herein, we investigate the microstructural changes associated with PPR.Twelve healthy subjects with PPR, nine patients with IGE and PPR (IGE-PPR group), and 18 healthy controls were studied with diffusion magnetic resonance imaging. Tract-based spatial statistics were used to test for regional differences in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity, and radial diffusivity between groups.Subjects with PPR exhibited higher FA in the right precentral juxtacortical white matter and higher MD in lateral occipital areas relative to controls. Patients with IGE-patients showed additional increases in regional FA in the thalamus and juxtacortical precentral and parietal areas. Both subjects with PPR and patients with IGE-PPR presented axial and radial diffusivity changes in the occipital regions.Our results show that PPR is associated with subcortical microstructural changes in precentral, parietal, and occipital regions. The coexistence of PPR and IGE is associated with white matter abnormalities in the thalamus and precuneus. PPR and epilepsy share similar functional and structural networks in widespread cortical and subcortical areas.

Olfaction is typically impaired in idiopathic Parkinson's disease (IPD), but its role is uncertain in monogenic PD. Diminished color discrimination has been suggested as another early sign of dopaminergic dysfunction but not been systematically studied. Furthermore, it is unknown whether both deficits are linked. We examined 100 patients with IPD, 27 manifesting mutation carriers (MC), 20 nonmanifesting mutation carriers (NMC), and 110 controls. Participants underwent a standardized neurological examination, the University of Pennsylvania Smell Identification Test (UPSIT), the Farnsworth-Munsell (FM) color discrimination test, and mutation testing in known PD genes. The monogenic group consisted of 15 Parkin (6MC/9NMC), 17 PINK1 (10MC/7NMC), 8 LRRK2 (4MC/4NMC), 3 SNCA (MC), and 4 ATP13A2 (MC) carriers. Olfaction was most impaired in IPD (UPSIT percentiles 10.1 ± 13.5) compared with all other groups (MC 13.8 ± 11.9, NMC 19.6 ± 13.0, controls 33.8 ± 22.4). Within MC, carriers of two mutations in Parkin and PINK1 showed higher UPSIT percentiles than LRRK2 and SNCA carriers. Color discrimination was reduced in IPD (FM total error score 134.8 ± 92.7). In MC (122.4 ± 142.4), the reduction was most pronounced in LRRK2, NMC (80.0 ± 38.8) were comparable with controls (97.2 ± 61.1). UPSIT and FM scores were correlated in the control (r = -0.305; P = 0.002) and the IPD group (r = -0.303; P = 0.006) but not among mutation carriers. First, we confirmed olfaction and color discrimination to be impaired in IPD and suggest olfaction to be a premotor sign. Second, olfaction differed between carriers with one and two mutations in Parkin/PINK1-associated PD. Third, olfaction and color discrimination impairment do not necessarily evolve in parallel.

The assessment of sexual orientation is of importance to the diagnosis and treatment of sex offenders and paraphilic disorders. Phallometry is considered gold standard in objectifying sexual orientation, yet this measurement has been criticized because of its intrusiveness and limited reliability.To evaluate whether the spatial response pattern to sexual stimuli as revealed by a change in blood oxygen level-dependent (BOLD) signal can be used for individual classification of sexual orientation.We used a preexisting functional MRI (fMRI) data set that had been acquired in a nonclinical sample of 12 heterosexual men and 14 homosexual men. During fMRI, participants were briefly exposed to pictures of same-sex and opposite-sex genitals. Data analysis involved four steps: (i) differences in the BOLD response to female and male sexual stimuli were calculated for each subject; (ii) these contrast images were entered into a group analysis to calculate whole-brain difference maps between homosexual and heterosexual participants; (iii) a single expression value was computed for each subject expressing its correspondence to the group result; and (iv) based on these expression values, Fisher's linear discriminant analysis and the kappa-nearest neighbor classification method were used to predict the sexual orientation of each subject.Sensitivity and specificity of the two classification methods in predicting individual sexual orientation.Both classification methods performed well in predicting individual sexual orientation with a mean accuracy of85% (Fisher's linear discriminant analysis: 92% sensitivity, 85% specificity; kappa-nearest neighbor classification: 88% sensitivity, 92% specificity).Despite the small sample size, the functional response patterns of the brain to sexual stimuli contained sufficient information to predict individual sexual orientation with high accuracy. These results suggest that fMRI-based classification methods hold promise for the diagnosis of paraphilic disorders (e.g., pedophilia).

Photosensitive individuals respond with epileptiform electroencephalography (EEG) discharges to intermittent photic stimulation. The pathogenetic mechanisms underlying this photoparoxysmal response (PPR) remain to be clarified. We investigated the involvement of magnocellular and parvocellular pathways in the processing of nonprovocative visual stimuli in healthy subjects with different phenotypic expressions of PPR (15 individuals with a local PPR, i.e. occipital discharges only, and 15 with a PPR propagating to anterior brain regions) and in 17 PPR-negative healthy controls using pattern-reversal visual evoked potentials (VEP). Checkerboard stimulation was performed at a low and a high spatial frequency to preferentially activate the magnocellular and parvocellular pathways. VEP habituation was also assessed over 15 blocks (each 100 trials) of recording. PPR-positive individuals with propagating PPR showed an increase in the N75-P100 and P100-N135 VEP components for both spatial frequencies, whereas individuals with a local PPR had normal VEP amplitudes. Individuals with propagating PPR also showed a stronger VEP habituation and reported more aversive sensations during continuous visual stimulation with the high spatial frequency checkerboard. The selective increase in VEP amplitudes in individuals with propagating PPR corroborates the notion that PPR with propagation is pathophysiologically distinct from local PPR. The increase in VEP amplitudes was independent of the spatial frequency of visual stimulation, indicating an increased neuronal excitability in both the parvocellular and magnocellular pathways. The stronger habituation in these individuals may reflect a compensatory mechanism to stabilize excitability in the visual system.

Patients with mild cognitive impairment (MCI) represent a risk population for progressing to dementia of the Alzheimer type (DAT). However, clinical criteria do not ensure reliable individual prognosis in these patients. The objective of this longitudinal, prospective study was to examine the value of (18)F-FDG PET of cerebral glucose metabolism and of genetic susceptibility, as defined by an APOEepsilon4-positive genotype, with regard to the early diagnosis of DAT in patients with MCI.In 30 patients with the diagnosis of MCI (16 female, 14 male; age, 70 +/- 8 y), baseline and follow-up examinations (mean observation period, 16 mo) were performed. In all patients, the APOE genotype was assessed and cerebral glucose metabolism was evaluated at baseline using cranial (18)F-FDG PET. Individual PET data were screened for findings suggestive of Alzheimer's disease (AD), with the help of an automated computer program. After stereotactical normalization of the PET images, this program performs an observer-independent statistical comparison with an age-matched reference database (n = 22).In 43% of all MCI subjects, a PET scan suggestive of AD pathology according to our predefined criteria was observed at baseline (PET+); 57% of all MCI patients were carriers of the APOE epsilon4 allele (e4+). In 40% of all patients, progression of symptoms within the observation period justified the clinical diagnosis of probable DAT at the time of follow-up reevaluation. Statistical evaluation revealed the best results for PET with regard to early diagnosis of DAT in MCI patients (sensitivity, 92%; specificity, 89%). Classification according to the APOE genotype was significantly less successful (sensitivity, 75%; specificity, 56%). However, a combination of both diagnostic tests allowed early diagnosis with either very high specificity (PET+ AND e4+: sensitivity, 67%; specificity, 100%) or very high sensitivity (PET+ OR e4+: sensitivity, 100%; specificity, 44%).(18)F-FDG PET of cerebral glucose metabolism is a valuable diagnostic tool for the prediction of clinical outcome in individual MCI patients. Results are superior to the exclusive assessment of the APOE genotype. A combination of both functional imaging and genotyping may allow an early high-risk or low-risk stratification of patients with either very high sensitivity or very high specificity. This may be valuable, for example, for patient selection in scientific studies.

Functional magnetic resonance imaging (fMRI) can be applied to study the functional connectivity of the neural elements which form complex network at a whole brain level. Most analyses of functional resting state networks (RSN) have been based on the analysis of correlation between the temporal dynamics of various regions of the brain. While these models can identify coherently behaving groups in terms of correlation they give little insight into how these groups interact. In this paper we take a different view on the analysis of functional resting state networks. Starting from the definition of resting state as functional coherent groups we search for functional units of the brain that communicate with other parts of the brain in a coherent manner as measured by mutual information. We use the infinite relational model (IRM) to quantify functional coherent groups of resting state networks and demonstrate how the extracted component interactions can be used to discriminate between functional resting state activity in multiple sclerosis and normal subjects.

MRCDI is a novel technique for non-invasive measurement of weak currents in the human head, which is important in several neuroscience applications. Here, we present reliable in-vivo MRCDI measurements in the human brain based on SSFP-FID, yielding an unprecedented accuracy. We demonstrate the destructive influences of stray magnetic fields caused by the current passing through feeding cables, and propose a correction method. Also, we show inter-individual differences in MRCDI measurements for two different current proles, and compare the measurements with simulations based on individualized head models. The simulations of the current-induced magnetic fields show good agreement with in-vivo brain measurements.

Musicians typically show enhanced pitch-discrimination ability compared to non-musicians, consistent with the fact that musicians are more sensitive to some acoustic features critical for both speech and music processing. However, it is still unclear which mechanisms underlie this perceptual enhancement. In a previous behavioral study, musicians showed an increased pitch-discrimination performance for both resolved and unresolved complex tones suggesting an enhanced neural representation of pitch at central stages of the auditory system. The aim of this study was to clarify whether musicians show (i) differential neural activation in response to complex tones as compared to non-musicians and/or (ii) finer fundamental frequency (F0) representation in the auditory cortex. Assuming that the right auditory cortex is specialized in processing fine spectral changes, we hypothesized that an enhanced F0 representation in musicians would be associated with a stronger right-lateralized response to complex tones compared to non-musicians. Fundamental frequency (F0) discrimination thresholds were obtained for harmonic complex tones with F0s of 100 and 500 Hz, filtered in either a low or a high frequency region to vary the resolvability of audible harmonics. A sparse-sampling eventrelated functional magnetic resonance imaging (fMRI) paradigm was used to measure neural activation in all listeners while performing the same pitch-discrimination task for conditions of varying resolvability. The task difficulty was individually adjusted according to the previously obtained F0 discrimination thresholds. Preliminary results from 6 listeners (3 musicians and 3 non-musicians) showed that the behavioral discrimination thresholds of musicians were, on average, lower than the thresholds of non-musicians by about a factor of 2.3, independent of harmonic resolvability. A group analysis on the 6 listeners revealed no differential neural activation for resolved vs unresolved conditions, suggesting that cortical responses did not increase with increasing stimulus resolvability, when adjusting for the task difficulty across conditions and participants. A significant effect of processing demand, i.e., task demand estimated from both stimulus resolvability and task difficulty, was observed in both auditory cortices, with a larger neural activation in the right auditory region. Additionally, no differential activation was observed in the musicians vs. the non-musicians. Overall, these preliminary findings suggest an involvement of a postero-lateral region in both auditory cortices during a pitchdiscrimination task with conditions of varying processing demand. Cortical responses were larger in the right than in the left auditory cortex, suggesting an increasing activation of the right-lateralized pitch-sensitive cortical areas with increasing taskprocessing demand.

MRCDI is a novel technique, utilizing dierent phase-sensitive MR methods for non-invasive measurements of weak currents in the human body, which is important in several neuroscience applications. Here, we compare the in-vivo performance of two dierent MR methods, multi-echo spin echo (MESE) and steady-state free precession free induction decay (SSFP-FID), with single- vs. multi-gradient-echo readouts. We demonstrate that multi-gradient-echo readouts improve both methods. We validate the linear dependence of the measured current-induced magnetic eld on the injected current strength for both methods, and propose the more ecientSSFP-FID method as being well suited for highly sensitive single-slice human in-vivo MRCDI.