IMPORTANCE Progressive supranuclear palsy (PSP) is a 4-repeat tauopathy. Region-specific tau aggregates establish the neuropathologic diagnosis of definite PSP post mortem. Future interventional trials against tau in PSP would strongly benefit from biomarkers that support diagnosis.OBJECTIVE To investigate the potential of the novel tau radiotracer 18 F-PI-2620 as a biomarker in patients with clinically diagnosed PSP. DESIGN, SETTING, AND PARTICIPANTSIn this cross-sectional study, participants underwent dynamic 18 F-PI-2620 positron emission tomography (PET) from 0 to 60 minutes after injection at 5 different centers (3 in Germany, 1 in the US, and 1 in Australia). Patients with PSP (including those with Richardson syndrome [RS]) according to Movement Disorder Society PSP criteria were examined together with healthy controls and controls with disease. Four additionally referred individuals with PSP-RS and 2 with PSP-non-RS were excluded from final data analysis owing to incomplete dynamic PET scans.

The major goal of the evaluation in presurgical epilepsy diagnosis for medically intractable patients is the precise reconstruction of the epileptogenic foci, preferably with non-invasive methods. This paper evaluates whether surface electroencephalography (EEG) source analysis based on a 1mm anisotropic finite element (FE) head model can provide additional guidance for presurgical epilepsy diagnosis and whether it is practically feasible in daily routine. A 1mm hexahedra FE volume conductor model of the patient's head with special focus on accurately modeling the compartments skull, cerebrospinal fluid (CSF) and the anisotropic conducting brain tissues was constructed using non-linearly co-registered T1-, T2-and diffusion-tensor-magnetic resonance imaging data. The electrodes of intra-cranial EEG (iEEG) measurements were extracted from a co-registered computed tomography image. Goal function scan (GFS), minimum norm least squares (MNLS), standardized low resolution electromagnetic tomography (sLORETA) and spatio-temporal current dipole modeling inverse methods were then applied to the peak of the averaged ictal discharges EEG data. MNLS and sLORETA pointed to a single center of activity. Moving and rotating single dipole fits resulted in an explained variance of more than 97%. The non-invasive EEG source analysis methods localized at the border of the lesion and at the border of the iEEG electrodes which mainly received ictal discharges. Source orientation was towards the epileptogenic tissue. For the reconstructed superficial source, brain conductivity anisotropy and the lesion conductivity had only a minor influence, whereas a correct modeling of the highly conducting CSF compartment and the anisotropic skull was found to be important. The proposed FE forward modeling approach strongly simplifies meshing and reduces run-time (37 Milliseconds for one forward computation in the model with 3.1 Million unknowns), corroborating the practical feasibility of the approach.

Recent studies have shown that drug‐induced spatial alteration patterns in resting state functional activity as measured using magnetic resonance imaging (rsfMRI) are associated with the distribution of specific receptor systems targeted by respective compounds. Based on this approach, we introduce a toolbox (JuSpace) allowing for cross‐modal correlation of MRI‐based measures with nuclear imaging derived estimates covering various neurotransmitter systems including dopaminergic, serotonergic, noradrenergic, and GABAergic (gamma‐aminobutric acid) neurotransmission. We apply JuSpace to two datasets covering Parkinson's disease patients (PD) and risperidone‐induced changes in rsfMRI and cerebral blood flow (CBF). Consistently with the predominant neurodegeneration of dopaminergic and serotonergic system in PD, we find significant spatial associations between rsfMRI activity alterations in PD and dopaminergic (D2) and serotonergic systems (5‐HT1b). Risperidone induced CBF alterations were correlated with its main targets in serotonergic and dopaminergic systems. JuSpace provides a biologically meaningful framework for linking neuroimaging to underlying neurotransmitter information.

Bariatric surgery remains the single most effective long-term treatment modality for morbid obesity, achieved mainly by lowering caloric intake through as yet ill-defined mechanisms. Here we show in rats that Roux-en-Y gastric bypass (RYGB)-like rerouting of ingested fat mobilizes lower small intestine production of the fat-satiety molecule oleoylethanolamide (OEA). This was associated with vagus nerve-driven increases in dorsal striatal dopamine release. We also demonstrate that RYGB upregulates striatal dopamine 1 receptor (D1R) expression specifically under high-fat diet feeding conditions. Mechanistically, interfering with local OEA, vagal, and dorsal striatal D1R signaling negated the beneficial effects of RYGB on fat intake and preferences. These findings delineate a molecular/systems pathway through which bariatric surgery improves feeding behavior and may aid in the development of novel weight loss strategies that similarly modify brain reward circuits compromised in obesity.

Recent studies have shown that drug-induced spatial alteration patterns in resting state functional activity as measured using magnetic resonance imaging (MRI) are associated with the distribution of specific receptor systems targeted by respective compounds. Based on this approach, we introduce a Matlab-based toolbox (JuSpace) allowing for cross-modal correlation of MRI-based measures with positron emission tomography (PET) and single photon emission computed tomography (SPECT) derived estimates covering various receptor systems including dopaminergic, serotonergic, noradrenergic, and GABAergic (gamma-aminobutric acid) neurotransmission. We apply JuSpace to two datasets covering Parkinson's disease patients (PD) on and off levodopa and risperidone-induced changes in rsfMRI and cerebral blood flow (CBF). We correlate rsfMRI derived PD-and levodopa-induced local activity alterations with PET and SPECT maps covering the above neurotransmitter systems.Similarly, we correlate the effects of risperidone on CBF with respective maps. Consistently with the predominant neurodegeneration of dopaminergic and serotonergic system in PD, we find significant spatial associations between rsfMRI activity alterations in PD on and off levodopa and dopaminergic (D2) and serotonergic systems (5-HT1b). Consistently with its mechanism of action, risperidone induced CBF alterations were correlated with key targets of serotonergic and dopaminergic systems. The JuSpace toolbox provides an easy framework for correlation of spatial alteration patterns across different neuroimaging modalities with PET derived receptor maps. Taken together, toolbox allows for cross-modal biologically meaningful evaluation and interpretation of image-derived spatial alteration patterns.

Whether α4β2 nicotinic acetylcholine receptor (α4β2-nAChR) expression is reduced in early Alzheimer’s disease is controversial. Using (-)-[18F]Flubatine PET, Sabri, Meyer et al. report α4β2-nAChR deficiency in mild Alzheimer’s dementia, especially within the basal forebrain-cortical and septohippocampal cholinergic projections. Reduced α4β2-nAChR availability correlates with impaired episodic memory and executive function/working memory.

Purpose The brain noradrenaline (NA) system plays an important role in the central nervous control of energy balance and is thus implicated in the pathogenesis of obesity. The specific processes modulated by this neurotransmitter which lead to obesity and overeating are still a matter of debate. Methods We tested the hypothesis that in vivo NA transporter (NAT) availability is changed in obesity by using positron emission tomography (PET) and S, S-[11C]O-methylreboxetine (MRB) in twenty subjects comprising ten highly obese (body mass index BMI > 35 kg/m2), metabolically healthy, non-depressed individuals and ten non-obese (BMI < 30 kg/m2) healthy controls. Results Overall, we found no significant differences in binding potential (BPND) values between obese and non-obese individuals in the investigated brain regions, including the NAT-rich thalamus (0.40 ± 0.14 vs. 0.41 ± 0.18; p = 0.84) though additional discriminant analysis correctly identified individual group affiliation based on regional BPND in all but one (control) case. Furthermore, inter-regional correlation analyses indicated different BPND patterns between both groups but this did not survive testing for multiple comparions. Conclusions Our data do not find an overall involvement of NAT changes in human obesity. However, preliminary secondary findings of distinct regional and associative patterns warrant further investigation.

Neocortical atrophy reduces PET signal intensity, potentially affecting the diagnostic efficacy of β-amyloid (Aβ) brain PET imaging. This study investigated whether partial-volume effect correction (PVEC), adjusting for this atrophy bias, improves the accuracy of 18 F-florbetaben Aβ PET. Methods: We analyzed 18 F-florbetaben PET and MRI data obtained from 3 cohorts. The first was 10 patients with probable Alzheimer disease (AD) and 10 age-matched healthy controls (HCs), the second was 31 subjects who underwent in vivo imaging and postmortem histopathology for Aβ plaques, and the third was 5 subjects who underwent PET and MRI at baseline and 1 y later. The imaging data were coregistered and segmented. PVEC was performed using the voxel-based modified Müller-Gärtner method (PVELab, SPM8). From the PET data, regional and composite SUV ratios (SUVRs) with and without PVEC were obtained. In the MRI data, mesial temporal lobe atrophy was determined by the Scheltens mesial temporal atrophy scale and gray matter volumes by voxel-based morphometry. Results: In cohort 1, PVEC increased the effect on AD-versus-HC discrimination from a Cohen d value of 1.68 to 2.0 for composite SUVRs and from 0.04 to 1.04 for mesial temporal cortex SUVRs. The PVEC-related increase in mesial temporal cortex SUVR correlated with the Scheltens score (r 5 0.84, P , 0.001), and that of composite SUVR correlated with the composite gray matter volume (r 5 −0.75, P , 0.001). In cohort 2, PVEC increased the correlation coefficient between mesial temporal cortex SUVR and histopathology score for Aβ plaque load from 0.28 (P 5 0.09) to 0.37 (P 5 0.03). In cohort 3, PVEC did not affect the composite SUVR dynamics over time for the Aβ-negative subject. This finding was in contrast to the 4 Aβ-positive subjects, in 2 of whom PVEC changed the composite SUVR dynamics. Conclusion: The influence of PVEC on 18 F-florbetaben PET data is associated with the degree of brain atrophy. Thus, PVEC increases the ability of 18 F-florbetaben PET to discriminate between AD patients and HCs, to detect Aβ plaques in the atrophic mesial temporal cortex, and potentially to evaluate changes in brain Aβ load over time. As such, the use of PVEC should be considered for quantitative 18 F-florbetaben PET scans, especially in assessing patients with brain atrophy.