How negative affect does and does not lead to binge eating-The importance of craving and negative urgency in bulimia nervosa.

Studies suggest that negative affect (NA) can trigger binge eating (BE) in patients with bulimia nervosa (BN). Important factors in this relation between NA and BE could be craving (an intense desire for a BE episode) and negative urgency (the tendency to act rashly when NA is high). Therefore, this study wants to firstly explore the relations between NA, craving, rash action, and BE in daily life and secondly whether craving and rash action mediate the relationship between NA and BE. A sample of 70 female patients with BN and 76 female healthy controls (HC) took part in an experience sampling study where they reported on momentary NA, craving, rash action, and eating behaviors in daily life in a burst-measurement design over a period of 12 months. Assessments occurred eight times a day on Thursdays, Fridays, and Saturdays in seven bursts of 3 weeks, all separated by 5-week periods of no assessment. First, NA predicted subsequent rash action in the whole sample but this was more pronounced in patients with BN. Second, NA predicted subsequent craving in patients with BN, but not in HC. Third, rash action and craving predicted subsequent BE in patients with BN. Fourth, NA had competing effects on eating in patients with BN, predicting subsequent BE through rash action and craving, but also predicting subsequent not eating. These results suggest that NA can lead to BE in daily life through rash action and craving, but that NA can also lead to dietary restriction. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Simultaneous 18F-FDG PET/MR metabolic and structural changes in visual snow syndrome and diagnostic use.

PURPOSE: Visual snow syndrome (VSS) is a recently recognized chronic neurologic condition characterized by the constant perceiving of tiny flickering dots throughout the entire visual field. Metabolic overactivity and grey matter volume increase in the lingual gyrus has been reported. We investigated this by 18F-FDG PET/MR in comparison to healthy controls. Aside from voxel-based characterization, the classification accuracy of volume-of-interest (VOI)-based multimodal assessment was evaluated, also in comparison with visual analysis. METHODS: Simultaneous 18F-FDG PET and MR imaging was performed in 7 patients with VSS (24.6 ± 5.7 years; 5 M/2F) and 15 age-matched healthy controls (CON) (28.0 ± 5.3 years; 8 M/7F). SPM12 and voxel-based morphometric analysis was performed. A VOI-based discriminant analysis was performed with relative 18F-FDG uptake, MR grey matter (GM) volumes and their combination. A visual analysis was done by two blinded experienced readers. RESULTS: Relative increased hypermetabolism was found in VSS patients in the lingual gyrus and cuneus (pFWE < 0.05, peak change + 24%), and hypometabolism in the mesiotemporal cortex (pheight,uncorr < 0.001, peak change - 14%). VSS patients also had increased GM volume in the limbic system and frontotemporal cortex bilaterally (pFWE < 0.05), and in the left secondary and associative visual cortex and in the left lingual gyrus (pheight,uncorr < 0.001). Discriminant analysis resulted in 100% correct classification accuracy for 18F-FDG with lingual gyrus, cuneus and lateral occipital lobe (BA 17 and BA 18) as main discriminators. Unimodal MR- and combined 18F-FDG + MR classification resulted in an accuracy of 91% and 95%, respectively. Visual analysis of 18F-FDG was highly observer dependent. CONCLUSION: Patients with VSS have highly significant structural and metabolic abnormalities in the visual and limbic system. VOI-based discriminant analysis of 18F-FDG PET allows reliable individual classification versus controls, whereas visual analysis of experienced observers was highly variable. Further investigation in larger series, also in comparison to VSS mimicking disorders such as migraine, is warranted. TRAIL REGISTRATION: Retrospectively registered at clinicaltrials.gov under NCT05569733 on Oct 5, 2022.

The Relationships between Dopaminergic, Glutamatergic, and Cognitive Functioning in 22q11.2 Deletion Syndrome: A Cross-Sectional, Multimodal 1H-MRS and 18F-Fallypride PET Study.

BACKGROUND: Individuals with 22q11.2 deletion syndrome (22q11DS) are at increased risk of developing psychosis and cognitive impairments, which may be related to dopaminergic and glutamatergic abnormalities. Therefore, in this exploratory study, we examined the association between dopaminergic and glutamatergic functioning in 22q11DS. Additionally, the associations between glutamatergic functioning and brain volumes in 22q11DS and healthy controls (HC), as well as those between dopaminergic and cognitive functioning in 22q11DS, were also examined. METHODS: In this cross-sectional, multimodal imaging study, glutamate, glutamine, and their combined concentration (Glx) were assessed in the anterior cingulate cortex (ACC) and striatum in 17 22q11DS patients and 20 HC using 7T proton magnetic resonance spectroscopy. Ten 22q11DS patients also underwent 18F-fallypride positron emission tomography to measure dopamine D2/3 receptor (D2/3R) availability in the ACC and striatum. Cognitive performance was assessed with the Cambridge Neuropsychological Test Automated Battery. RESULTS: No significant associations were found between ACC or striatal (1) glutamate, glutamine, or Glx concentrations and (2) D2/3R availability. In HC but not in 22q11DS patients, we found a significant relationship between ACC volume and ACC glutamate, glutamine, and Glx concentration. In addition, some aspects of cognitive functioning were significantly associated with D2/3R availability in 22q11DS. However, none of the associations remained significant after Bonferroni correction. CONCLUSIONS: Although our results did not reach statistical significance, our findings suggest an association between glutamatergic functioning and brain volume in HC but not in 22q11DS. Additionally, D2/3R availability seems to be related to cognitive functioning in 22q11DS. Studies in larger samples are needed to further elucidate our findings.

Spatial decrease of synaptic density in amnestic mild cognitive impairment follows the tau build-up pattern.

Next to amyloid and tau, synaptic loss is a key pathological hallmark in Alzheimer's disease, closely related to cognitive dysfunction and neurodegeneration. Tau is thought to cause synaptic loss, but this has not been experimentally verified in vivo. In a 2-year follow-up study, dual tracer PET-MR was performed in 12 amnestic MCI patients using 18F-MK-6240 for tau and 11C-UCB-J for SV2A as a proxy for synaptic density. Tau already accumulated in the neocortex at baseline with progression in Braak V/VI at follow-up. While synaptic loss was limited to limbic regions at baseline, it followed the specific tau pattern to stage IV/V regions two years later, indicating that tau spread might drive synaptic vulnerability. Moreover, synaptic density changes correlated to changes in cognitive function. This study shows for the first time in vivo that synaptic loss regionally follows tau accumulation after two years, providing a disease-modifying window of opportunity for (combined) tau-targeting therapies.

The neurobiological reward system and binge eating: A critical systematic review of neuroimaging studies.

OBJECTIVE: Changes in reward processing are hypothesized to play a role in the onset and maintenance of binge eating (BE). However, despite an increasing number of studies investigating the neurobiological reward system in individuals who binge eat, no comprehensive systematic review exists on this topic. Therefore, this review has the following objectives: (1) identify structural and functional changes in the brain reward system, either during rest or while performing a task; and (2) formulate directions for future research. METHODS: A search was conducted of articles published until March 31, 2022. Neuroimaging studies were eligible if they wanted to study the reward system and included a group of individuals who binge eat together with a comparator group. Their results were summarized in a narrative synthesis. RESULTS: A total of 58 articles were included. At rest, individuals who binge eat displayed a lower striatal dopamine release, a change in the volume of the striatum, frontal cortex, and insula, as well as a lower frontostriatal connectivity. While performing a task, there was a higher activity of the brain reward system when anticipating or receiving food, more model-free reinforcement learning, and more habitual behavior. Most studies only included one patient group, used general reward-related measures, and did not evaluate the impact of comorbidities, illness duration, race, or sex. DISCUSSION: Confirming previous hypotheses, this review finds structural and functional changes in the neurobiological reward system in BE. Future studies should compare disorders, use measures that are specific to BE, and investigate the impact of confounding factors. PUBLIC SIGNIFICANCE STATEMENT: This systematic review finds that individuals who binge eat display structural and functional changes in the brain reward system. These changes could be related to a higher sensitivity to food, relying more on previous experiences when making decisions, and more habitual behavior. Future studies should use a task that is specific to binge eating, look across different patient groups, and investigate the impact of comorbidities, illness duration, race, and sex.

OBJETIVO: Se plantea la hipótesis de que los cambios en el procesamiento de la recompensa desempeñan un papel en el inicio y mantenimiento de los atracones (BE). Sin embargo, a pesar de un número creciente de estudios que investigan el sistema de recompensa neurobiológica en individuos que comen en atracones, no existe una revisión sistemática exhaustiva sobre este tema. Por lo tanto, esta revisión tiene los siguientes objetivos: (1) identificar cambios estructurales y funcionales en el sistema de recompensa cerebral, ya sea en reposo o mientras se realiza una tarea; (2) formular direcciones para futuras investigaciones. MÉTODOS: Se realizó una búsqueda de artículos publicados hasta el 31 de marzo de 2022. Los estudios de neuroimagen eran elegibles si querían estudiar el sistema de recompensa e incluían a un grupo de individuos que comían en atracón junto con un grupo de comparación. Sus resultados se resumieron en una síntesis narrativa. RESULTADOS: Se incluyeron un total de 58 artículos. En reposo, los individuos que comen en atracón mostraron una menor liberación de dopamina estriatal, un cambio en el volumen del cuerpo estriado, la corteza frontal y la ínsula, así como una menor conectividad frontostriatal. Al realizar una tarea, hubo una mayor actividad del sistema de recompensa cerebral al anticipar o recibir alimentos, más aprendizaje de refuerzo sin modelos y un comportamiento más habitual. La mayoría de los estudios sólo incluyeron un grupo de pacientes, utilizaron medidas generales relacionadas con la recompensa y no evaluaron el impacto de las comorbilidades, la duración de la enfermedad, la raza o el sexo. DISCUSIÓN: Confirmando hipótesis anteriores, esta revisión encuentra cambios estructurales y funcionales del sistema de recompensa neurobiológica en BE. Los estudios futuros deben comparar los trastornos, utilizar medidas que sean específicas para el comer en atracones e investigar el impacto de los factores de confusión.

Cannabinoid receptor availability modulates the magnitude of dopamine release in vivo in the human reward system: A preliminary multitracer positron emission tomography study.

The established role of dopamine (DA) in the mediation of reward and positive reinforcement, reward processing is strongly influenced by the type 1 cannabinoid receptors (CB1 Rs). Although considerable preclinical evidence has demonstrated several functional CB1 R-DA interactions, the relation between human CB1 R availability, DA release capacity and drug-reinforcing effects has been never investigated so far. Here, we perform a multitracer [18 F]MK-9470 and [18 F]fallypride positron emission tomography (PET) study in 10 healthy male subjects using a placebo-controlled and single-blinded amphetamine (AMPH) (30 mg) administration paradigm to (1) investigate possible functional interactions between CB1 R expression levels and DA release capacity in a normo-DAergic state, relating in vivo AMPH-induced DA release to CB1 R availability, and (2) to test the hypothesis that the influence of striatal DAergic signalling on the positive reinforcing effects of AMPH may be regulated by prefrontal CB1 R levels. Compared with placebo, AMPH significantly reduced [18 F]fallypride binding potential (hence increase DA release; ΔBPND ranging from -6.1% to -9.6%) in both striatal (p < 0.005, corrected for multiple comparisons) and limbic extrastriatal regions (p ≤ 0.04, uncorrected). Subjects who reported a greater dopaminergic response in the putamen also showed higher CB1 R availability in the medial and dorsolateral prefrontal cortex (r = 0.72; p = 0.02), which are regions involved in salience attribution, motivation and decision making. On the other hand, the magnitude of DA release was greater in those subjects with lower CB1 R availability in the anterior cingulate cortex (ACC) (r = -0.66; p = 0.03). Also, the correlation between the DA release in the nucleus accumbens with the subjective AMPH effect liking was mediated through the CB1 R availability in the ACC (c' = -0.76; p = 0.01). Our small preliminary study reports for the first time that the human prefrontal CB1 R availability is a determinant of DA release within both the ventral and dorsal reward corticostriatal circuit, contributing to a number of studies supporting the existence of an interaction between CB1 R and DA receptors at the molecular and behavioural level. These preliminary findings warrant further investigation in pathological conditions characterized by hypo/hyper excitability to DA release such as addiction and schizophrenia.

Regional glucose metabolic decreases with ageing are associated with microstructural white matter changes: a simultaneous PET/MR study.

PURPOSE: Human ageing is associated with a regional reduction in cerebral neuronal activity as assessed by numerous studies on brain glucose metabolism and perfusion, grey matter (GM) density and white matter (WM) integrity. As glucose metabolism may impact energetics to maintain myelin integrity, but changes in functional connectivity may also alter regional metabolism, we conducted a cross-sectional simultaneous FDG PET/MR study in a large cohort of healthy volunteers with a wide age range, to directly assess the underlying associations between reduced glucose metabolism, GM atrophy and decreased WM integrity in a single ageing cohort. METHODS: In 94 healthy subjects between 19.9 and 82.5 years (mean 50.1 ± 17.1; 47 M/47F, MMSE ≥ 28), simultaneous FDG-PET, structural MR and diffusion tensor imaging (DTI) were performed. Voxel-wise associations between age and grey matter (GM) density, RBV partial-volume corrected (PVC) glucose metabolism, white matter (WM) fractional anisotropy (FA) and mean diffusivity (MD), and age were assessed. Clusters representing changes in glucose metabolism correlating significantly with ageing were used as seed regions for tractography. Both linear and quadratic ageing models were investigated. RESULTS: An expected age-related reduction in GM density was observed bilaterally in the frontal, lateral and medial temporal cortex, striatum and cerebellum. After PVC, relative FDG uptake was negatively correlated with age in the inferior and midfrontal, cingulate and parietal cortex and subcortical regions, bilaterally. FA decreased with age throughout the entire brain WM. Four white matter tracts were identified connecting brain regions with declining glucose metabolism with age. Within these, relative FDG uptake in both origin and target clusters correlated positively with FA (0.32 ≤ r ≤ 0.71) and negatively with MD (- 0.75 ≤ r ≤ - 0.41). CONCLUSION: After appropriate PVC, we demonstrated that regional cerebral glucose metabolic declines with age and that these changes are related to microstructural changes in the interconnecting WM tracts. The temporal course and potential causality between ageing effects on glucose metabolism and WM integrity should be further investigated in longitudinal cohort PET/MR studies.

Effects of chronic voluntary alcohol consumption on PDE10A availability: a longitudinal behavioral and [18F]JNJ42259152 PET study in rats.

PURPOSE: Phosphodiesterase 10A (PDE10A) is a dual substrate enzyme highly enriched in dopamine-receptive striatal medium spiny neurons, which are involved in psychiatric disorders such as alcohol use disorders (AUD). Although preclinical studies suggest a correlation of PDE10A mRNA expression in neuronal and behavioral responses to alcohol intake, little is known about the effects of alcohol exposure on in vivo PDE10A activity in relation to apparent risk factors for AUD such as decision-making and anxiety. METHODS: We performed a longitudinal [18F]JNJ42259152 microPET study to evaluate PDE10A changes over a 9-week intermittent access to alcohol model, including 6 weeks of alcohol exposure, 2 weeks of abstinence followed by 1 week relapse. Parametric PDE10A-binding potential (BPND) images were generated using a Logan reference tissue model with cerebellum as reference region and were analyzed using both a volume-of-interest and voxel-based approach. Moreover, individual decision-making and anxiety levels were assessed with the rat Iowa Gambling Task and open-field test over the IAE model. RESULTS: We observed an increased alcohol preference especially in those animals that exhibited poor initial decision-making. The first 2 weeks of alcohol exposure resulted in an increased striatal PDE10A binding (> 10%). Comparing PDE10A-binding potential after 2 versus 4 weeks of exposure showed a significant decreased PDE10A in the caudate-putamen and nucleus accumbens (pFWE-corrected < 0.05). This striatal PDE10A decrease was related to alcohol consumption and preference. Normalization of striatal PDE10A to initial levels was observed after 1 week of relapse, apart from the globus pallidus. CONCLUSION: This study shows that chronic voluntary alcohol consumption induces a reversible increased PDE10A enzymatic availability in the striatum, which is related to the amount of alcohol preference. Thus, PDE10A-mediated signaling plays an important role in modulating the reinforcing effects of alcohol, and the data suggest that PDE10A inhibition may have beneficial behavioral effects on alcohol intake.

Twelve-Week Yoga vs. Aerobic Cycling Initiation in Sedentary Healthy Subjects: A Behavioral and Multiparametric Interventional PET/MR Study.

Interventional yoga studies with an active control group remain scarce and are important to clarify the underlying neurobiology. We conducted an interventional study in healthy controls using simultaneous positron emission tomography/magnetic resonance (PET/MR) imaging and psychometric scales. Thirty healthy, female volunteers (28.4 ± 8.4 years) participated and were randomly assigned to a 12-week yoga or indoor cycling intervention. Before and after the intervention, [18F]FDG and [11C]UCB-J PET was performed on a simultaneous GE Signa PET/MR with volumetric imaging. Psychometric scales were evaluated on affect, mindfulness, stress, worrying, self-compassion, and interoceptive awareness. Yoga subjects scored higher on interoceptive awareness compared to baseline (p < 0.001). Cognitive (P = 0.009) and overall cognitive functioning (P = 0.01) improved after the yoga intervention compared to the cycling group. We did not observe significant differences in glucose metabolism, synaptic density, or gray matter (GM) volume. The indoor cycling group did not show changes in psychometric variables, but significant increases in relative glucose metabolism were observed in the parahippocampal/fusiform gyrus and cerebellum (P < 0.001). In conclusion, 12 weeks of yoga practice has significant effects on interoceptive awareness and perceived cognitive function in starters. Longer interventions and/or higher frequency of yoga practice may be needed to detect cerebral metabolic and/or morphologic effects on the macroscopic level.

How COVID-19 lockdown measures could impact patients with bulimia nervosa: Exploratory results from an ongoing experience sampling method study.

OBJECTIVE: The impact of COVID-19 lockdown measures on patients with an eating disorder remains unclear, but preliminary results indicate that some patients could be more vulnerable to experience an increase in eating disorder pathology than others. To provide possible directions for future research, this report explored the impact of the Belgian COVID-19 lockdown measures on patients with bulimia nervosa (BN). METHODS: The data of 15 female patients with BN from an ongoing experience sampling method study were analyzed. Mixed effects models compared surroundings, social context, negative affect (NA), positive affect (PA) and binge eating before and after the implementation of the lockdown measures. RESULTS: After the implementation of the lockdown measures, significant changes in surroundings and social context were found as well as an increase in NA and decrease in PA. Patients who experienced a higher binge eating frequency during the lockdown also experienced a stronger change in NA and PA. CONCLUSIONS: Future research should also look at changes in surroundings, social context, affect and how these interact with factors such as personality traits and coping styles when investigating why some patients are more susceptible to the negative effects of lockdown measures than others.

Synaptic density in healthy human aging is not influenced by age or sex: a 11C-UCB-J PET study.

RATIONALE: 11C-UCB-J binds to synaptic vesicle glycoprotein 2A, a protein ubiquitously expressed in presynaptic nerve terminals, and can therefore serve as in vivo proxy of synaptic density. There are discrepancies in postmortem data on stability of synaptic density with healthy aging. In this study, healthy aging and sex as potential modifiers of 11C-UCB-J binding were investigated in healthy volunteers over 7 adult decades, assuming that the number of SV2A vesicles per synapse is not influenced by age or sex. METHODS: 80 healthy volunteers underwent 11C-UCB-J PET and structural T1 and T2 MR imaging. Grey matter changes with aging were firstly evaluated by voxel-based morphometry (VBM). Parametric 11C-UCB-J standardized uptake value ratio (SUVR) images were calculated using the centrum semiovale as reference tissue. To correct for atrophy-related partial volume effects, a region-based voxel-wise type partial volume correction (PVC) was applied in FreeSurfer. The correlations of 11C-UCB-J binding with age and with sex were investigated by a voxel-based and volume-of-interest (VOI)-based approach, and with and without PVC to assess the contribution of underlying morphology changes upon aging. RESULTS: Full results were available for 78 participants (19-85y; 33 M/45 F). VBM grey matter concentration changes with aging were most predominant in the perisylvian and frontal regions. After PVC, no significantly decreased 11C-UCB-J SUVR with aging was found in the voxel-based analysis, whereas the VOI-based analysis showed a slight decrease in the caudate nucleus (-1.7% decrease per decade, p= 0.0025) only. There was no association between sex and 11C-UCB-J SUVR, nor an interaction between aging and sex for this parameter. CONCLUSION: In vivo, PET using 11C-UCB-J does not support a cortical decrease of synaptic density with aging, whereas subcortically a small effect with aging in the caudate nucleus was observed. In addition, no association between synaptic density and sex was detected, which allows pooling of datasets of both sexes.

In vivo synaptic density relates to glucose metabolism at rest in healthy subjects, but is strongly modulated by regional differences.

Preclinical and postmortem studies have suggested that regional synaptic density and glucose consumption (CMRGlc) are strongly related. However, the relation between synaptic density and cerebral glucose metabolism in the human brain has not directly been assessed in vivo. Using [11C]UCB-J binding to synaptic vesicle glycoprotein 2 A (SV2A) as indicator for synaptic density and [18F]FDG for measuring cerebral glucose consumption, we studied twenty healthy female subjects (age 29.6 ± 9.9 yrs) who underwent a single-day dual-tracer protocol (GE Signa PET-MR). Global measures of absolute and relative CMRGlc and specific binding of [11C]UCB-J were indeed highly significantly correlated (r > 0.47, p < 0.001). However, regional differences in relative [18F]FDG and [11C]UCB-J uptake were observed, with up to 19% higher [11C]UCB-J uptake in the medial temporal lobe (MTL) and up to 17% higher glucose metabolism in frontal and motor-related areas and thalamus. This pattern has a considerable overlap with the brain regions showing different levels of aerobic glycolysis. Regionally varying energy demands of inhibitory and excitatory synapses at rest may also contribute to this difference. Being unaffected by astroglial and/or microglial energy demands, changes in synaptic density in the MTL may therefore be more sensitive to early detection of pathological conditions compared to changes in glucose metabolism.

Methods for Quantifying Neurotransmitter Dynamics in the Living Brain With PET Imaging.

Positron emission tomography (PET) neuroimaging in neuropsychiatry is a powerful tool for the quantification of molecular brain targets to characterize disease, assess disease subtype differences, evaluate short- and long-term effects of treatments, or even to measure neurotransmitter levels in healthy and psychiatric conditions. In this work, we present different methodological approaches (time-invariant models and models with time-varying terms) that have been used to measure dynamic changes in neurotransmitter levels induced by pharmacological or behavioral challenges in humans. The developments and potential use of hybrid PET/magnetic resonance imaging (MRI) for neurotransmission brain research will also be highlighted.

What Has Neuroimaging Taught Us on the Neurobiology of Yoga? A Review.

Yoga is becoming increasingly popular worldwide, with several implicated physical and mental benefits. Here we provide a comprehensive and critical review of the research generated from the existing neuroimaging literature in studies of yoga practitioners. We reviewed 34 international peer-reviewed neuroimaging studies of yoga using magnetic resonance imaging (MRI), positron emission tomography (PET), or single-photon emission computed tomography (SPECT): 11 morphological and 26 functional studies, including three studies that were classified as both morphological and functional. Consistent findings include increased gray matter volume in the insula and hippocampus, increased activation of prefrontal cortical regions, and functional connectivity changes mainly within the default mode network. There is quite some variability in the neuroimaging findings that partially reflects different yoga styles and approaches, as well as sample size limitations. Direct comparator groups such as physical activity are scarcely used so far. Finally, hypotheses on the underlying neurobiology derived from the imaging findings are discussed in the light of the potential beneficial effects of yoga.

In vivo synaptic density loss is related to tau deposition in amnestic mild cognitive impairment.

OBJECTIVE: To investigate in vivo whether synaptic loss and neurofibrillary tangle load spatially overlap and correlate with clinical symptoms in patients with amnestic mild cognitive impairment (aMCI). METHODS: In this cross-sectional study, 10 patients with aMCI and 10 healthy controls underwent triple PET-MRI with 11C-UCB-J (synaptic vesicle protein 2A), 18F-MK-6240 (tau deposition), and 11C-Pittsburgh compound B (ß-amyloid) and neuropsychological assessment. Gray matter atrophy was assessed by voxel-based morphometry with T1-weighted MRIs. Voxel-wise and volume-of-interest analyses were conducted on PET data. The interrelationship of synaptic density and tau deposition was investigated. We also investigated correlations of 18F-MK-6240 and 11C-UCB-J binding with cognitive performance. RESULTS: Compared to controls, patients with aMCI showed a decreased 11C-UCB-J binding mainly in substructures of the medial temporal lobe (MTL; 48%-51%, p cluster = 0.02). Increased 18F-MK6240 binding in the same region was observed (42%-44%, p cluster = 0.0003), spreading to association cortices. In the MTL, higher 18F-MK-6240 binding inversely related to lower 11C-UCB-J binding (p = 0.02, r = -0.76). Decreased performance on cognitive tests was associated with both increased 18F-MK-6240 and decreased 11C-UCB-J binding in the hippocampus (p < 0.01, r > 0.7), although in a multivariate analysis only 18F-MK-6240 binding was significantly related to cognitive performance. CONCLUSIONS: Patients with aMCI have high tau deposition and synaptic density loss mainly in key regions known to be involved in early cognitive impairment, indicating that these are interrelated in the MTL, while tau binding had already spread toward association cortices. Longitudinal data are needed to provide further insight into the temporal aspects of this relationship.

Use of Multimodal Imaging and Clinical Biomarkers in Presymptomatic Carriers of C9orf72 Repeat Expansion.

Importance: During a time with the potential for novel treatment strategies, early detection of disease manifestations at an individual level in presymptomatic carriers of a hexanucleotide repeat expansion in the C9orf72 gene (preSxC9) is becoming increasingly relevant. Objectives: To evaluate changes in glucose metabolism before symptom onset of amyotrophic lateral sclerosis or frontotemporal dementia in preSxC9 using simultaneous fluorine 18-labeled fluorodeoxyglucose ([18F]FDG positron emission tomographic (PET) and magnetic resonance imaging as well as the mutation's association with clinical and fluid biomarkers. Design, Setting, and Participants: A prospective, case-control study enrolled 46 participants from November 30, 2015, until December 11, 2018. The study was conducted at the neuromuscular reference center of the University Hospitals Leuven, Leuven, Belgium. Main Outcomes and Measures: Neuroimaging data were spatially normalized and analyzed at the voxel level at a height threshold of P < .001, cluster-level familywise error-corrected threshold of P < .05, and statistical significance was set at P < .05 for the volume-of-interest level analysis, using Benjamini-Hochberg correction for multiple correction. W-score maps were computed using the individuals serving as controls as a reference to quantify the degree of [18F]FDG PET abnormality. The threshold for abnormality on the W-score maps was designated as an absolute W-score greater than or equal to 1.96. Neurofilament levels and performance on cognitive and neurologic examinations were determined. All hypothesis tests were 1-sided. Results: Of the 42 included participants, there were 17 with the preSxC9 mutation (12 women [71%]; mean [SD] age, 51 [9] years) and 25 healthy controls (12 women [48%]; mean [SD] age, 47 [10] years). Compared with control participants, significant clusters of relative hypometabolism were found in frontotemporal regions, basal ganglia, and thalami of preSxC9 participants and relative hypermetabolism in the peri-Rolandic region, superior frontal gyrus, and precuneus cortex. W-score frequency maps revealed reduced glucose metabolism with local maxima in the insular cortices, central opercular cortex, and thalami in up to 82% of preSxC9 participants and increased glucose metabolism in the precentral gyrus and precuneus cortex in up to 71% of preSxC9 participants. Other findings in the preSxC9 group were upper motor neuron involvement in 10 participants (59%), cognitive abnormalities in 5 participants (29%), and elevated neurofilament levels in 3 of 16 individuals (19%) who underwent lumbar puncture. Conclusions and Relevance: The results suggest that [18F]FDG PET can identify glucose metabolic changes in preSxC9 at an individual level, preceding significantly elevated neurofilament levels and onset of symptoms.

Long-term Ashtanga yoga practice decreases medial temporal and brainstem glucose metabolism in relation to years of experience.

BACKGROUND: Yoga is increasingly popular worldwide with several physical and mental benefits, but the underlying neurobiology remains unclear. Whereas many studies have focused on pure meditational aspects, the triad of yoga includes meditation, postures, and breathing. We conducted a cross-sectional study comparing experienced yoga practitioners to yoga-naive healthy subjects using a multiparametric 2 × 2 design with simultaneous positron emission tomography/magnetic resonance (PET/MR) imaging. METHODS: 18F-FDG PET, morphometric and diffusion tensor imaging, resting state fMRI, and MR spectroscopy were acquired in 10 experienced (4.8 ± 2.3 years of regular yoga experience) yoga practitioners and 15 matched controls in rest and after a single practice (yoga practice and physical exercise, respectively). RESULTS: In rest, decreased regional glucose metabolism in the medial temporal cortex, striatum, and brainstem was observed in yoga practitioners compared to controls (p < 0.0001), with a significant inverse correlation of resting parahippocampal and brainstem metabolism with years of regular yoga practice (ρ < - 0.63, p < 0.05). A single yoga practice resulted in significant hypermetabolism in the cerebellum (p < 0.0001). None of the MR measures differed, both at rest and after intervention. CONCLUSIONS: Experienced yoga practitioners show regional long-term decreases in glucose metabolism related to years of practice. To elucidate a potential causality, a prospective longitudinal study in yoga-naive individuals is warranted.

Direct prospective comparison of 18F-FDG PET and arterial spin labelling MR using simultaneous PET/MR in patients referred for diagnosis of dementia.

PURPOSE: 18F-FDG PET is routinely used as an imaging marker in the early and differential diagnosis of dementing disorders and has incremental value over the clinical neurological and neuropsychological evaluation. Perfusion MR imaging by means of arterial spin labelling (ASL) is an alternative modality to indirectly measure neuronal functioning and could be used as complement measurement in a single MR session in the workup of dementia. Using simultaneous PET-MR, we performed a direct head-to-head comparison between enhanced multiplane tagging ASL (eASL) and 18F-FDG PET in a true clinical context of subjects referred for suspicion of neurodegenerative dementia. METHODS: Twenty-seven patients underwent a 20-min 18F-FDG PET/MR and simultaneously acquired eASL on a GE Signa PET/MR. Data were compared with 30 screened age- and gender-matched healthy controls. Both integral eASL and 18F-FDG datasets were analysed visually by two readers unaware of the final clinical diagnosis, either in normal/abnormal classes, or full differential diagnosis (normal, Alzheimer type dementia [AD], dementia with Lewy Bodies [LBD], frontotemporal dementia [FTD] or other). Reader confidence was assessed with a rating scale (range 1-4). Data were also analysed semiquantitatively by VOI and voxel-based analyses. RESULTS: The ground truth diagnosis for the patient group resulted in 14 patients with a neurodegenerative cognitive disorder (AD, FTD, LBD) and 13 patients with no arguments for an underlying neurodegenerative cause. Visual analysis resulted in equal specificity (0.70) for differentiating normal and abnormal cases between the two modalities, but in a higher sensitivity (0.93), confidence rating (0.64) and interobserver agreement for 18F-FDG PET compared with eASL. The same was true for assigning a specific differential diagnosis (sensitivity: and 0.39 for 18F-FDG PET and eASL, respectively). Semiquantitative analyses revealed prototypical patterns for AD and FTD, with both higher volumes of abnormality and intensity differences on 18F-FDG PET. CONCLUSION: In a direct head-to-head comparison on a simultaneous GE Signa PET/MR, 18F-FDG PET performed better compared with ASL in terms of sensitivity and reader confidence, as well as volume and intensity of abnormalities. However, using pure semiquantitative analysis, similar diagnostic accuracy between the two modalities was obtained. Therefore, ASL may still serve as complement to neuroreceptor or protein deposition PET studies when a single simultaneous investigation is warranted.

Lower [18F]fallypride binding to dopamine D2/3 receptors in frontal brain areas in adults with 22q11.2 deletion syndrome: a positron emission tomography study.

BACKGROUND: The 22q11.2 deletion syndrome (22q11DS) is caused by a deletion on chromosome 22 locus q11.2. This copy number variant results in haplo-insufficiency of the catechol-O-methyltransferase (COMT) gene, and is associated with a significant increase in the risk for developing cognitive impairments and psychosis. The COMT gene encodes an enzyme that primarily modulates clearance of dopamine (DA) from the synaptic cleft, especially in the prefrontal cortical areas. Consequently, extracellular DA levels may be increased in prefrontal brain areas in 22q11DS, which may underlie the well-documented susceptibility for cognitive impairments and psychosis in affected individuals. This study aims to examine DA D2/3 receptor binding in frontal brain regions in adults with 22q11DS, as a proxy of frontal DA levels. METHODS: The study was performed in 14 non-psychotic, relatively high functioning adults with 22q11DS and 16 age- and gender-matched healthy controls (HCs), who underwent DA D2/3 receptor [18F]fallypride PET imaging. Frontal binding potential (BPND) was used as the main outcome measure. RESULTS: BPND was significantly lower in adults with 22q11DS compared with HCs in the prefrontal cortex and the anterior cingulate gyrus. After Bonferroni correction significance remained for the anterior cingulate gyrus. There were no between-group differences in BPND in the orbitofrontal cortex and anterior cingulate cortex. CONCLUSIONS: This study is the first to demonstrate lower frontal D2/3 receptor binding in adults with 22q11DS. It suggests that a 22q11.2 deletion affects frontal dopaminergic neurotransmission.