High-temporal resolution functional PET/MRI reveals coupling between human metabolic and hemodynamic brain response.

PURPOSE: Positron emission tomography (PET) provides precise molecular information on physiological processes, but its low temporal resolution is a major obstacle. Consequently, we characterized the metabolic response of the human brain to working memory performance using an optimized functional PET (fPET) framework at a temporal resolution of 3 s. METHODS: Thirty-five healthy volunteers underwent fPET with [18F]FDG bolus plus constant infusion, 19 of those at a hybrid PET/MRI scanner. During the scan, an n-back working memory paradigm was completed. fPET data were reconstructed to 3 s temporal resolution and processed with a novel sliding window filter to increase signal to noise ratio. BOLD fMRI signals were acquired at 2 s. RESULTS: Consistent with simulated kinetic modeling, we observed a constant increase in the [18F]FDG signal during task execution, followed by a rapid return to baseline after stimulation ceased. These task-specific changes were robustly observed in brain regions involved in working memory processing. The simultaneous acquisition of BOLD fMRI revealed that the temporal coupling between hemodynamic and metabolic signals in the primary motor cortex was related to individual behavioral performance during working memory. Furthermore, task-induced BOLD deactivations in the posteromedial default mode network were accompanied by distinct temporal patterns in glucose metabolism, which were dependent on the metabolic demands of the corresponding task-positive networks. CONCLUSIONS: In sum, the proposed approach enables the advancement from parallel to truly synchronized investigation of metabolic and hemodynamic responses during cognitive processing. This allows to capture unique information in the temporal domain, which is not accessible to conventional PET imaging.

Whole-body metabolic connectivity framework with functional PET.

The nervous and circulatory system interconnects the various organs of the human body, building hierarchically organized subsystems, enabling fine-tuned, metabolically expensive brain-body and inter-organ crosstalk to appropriately adapt to internal and external demands. A deviation or failure in the function of a single organ or subsystem could trigger unforeseen biases or dysfunctions of the entire network, leading to maladaptive physiological or psychological responses. Therefore, quantifying these networks in healthy individuals and patients may help further our understanding of complex disorders involving body-brain crosstalk. Here we present a generalized framework to automatically estimate metabolic inter-organ connectivity utilizing whole-body functional positron emission tomography (fPET). The developed framework was applied to 16 healthy subjects (mean age ± SD, 25 ± 6 years; 13 female) that underwent one dynamic 18F-FDG PET/CT scan. Multiple procedures of organ segmentation (manual, automatic, circular volumes) and connectivity estimation (polynomial fitting, spatiotemporal filtering, covariance matrices) were compared to provide an optimized thorough overview of the workflow. The proposed approach was able to estimate the metabolic connectivity patterns within brain regions and organs as well as their interactions. Automated organ delineation, but not simplified circular volumes, showed high agreement with manual delineation. Polynomial fitting yielded similar connectivity as spatiotemporal filtering at the individual subject level. Furthermore, connectivity measures and group-level covariance matrices did not match. The strongest brain-body connectivity was observed for the liver and kidneys. The proposed framework offers novel opportunities towards analyzing metabolic function from a systemic, hierarchical perspective in a multitude of physiological pathological states.

Regional gene expression patterns are associated with task-specific brain activation during reward and emotion processing measured with functional MRI.

The exploration of the spatial relationship between gene expression profiles and task-evoked response patterns known to be altered in neuropsychiatric disorders, for example depression, can guide the development of more targeted therapies. Here, we estimated the correlation between human transcriptome data and two different brain activation maps measured with functional magnetic resonance imaging (fMRI) in healthy subjects. Whole-brain activation patterns evoked during an emotional face recognition task were associated with topological mRNA expression of genes involved in cellular transport. In contrast, fMRI activation patterns related to the acceptance of monetary rewards were associated with genes implicated in cellular localization processes, metabolism, translation, and synapse regulation. An overlap of these genes with risk genes from major depressive disorder genome-wide association studies revealed the involvement of the master regulators TCF4 and PAX6 in emotion and reward processing. Overall, the identification of stable relationships between spatial gene expression profiles and fMRI data may reshape the prospects for imaging transcriptomics studies.

Association of dopamine D2/3 receptor binding potential measured using PET and [11C]-(+)-PHNO with post-mortem DRD2/3 gene expression in the human brain.

Open access post-mortem transcriptome atlases such as the Allen Human Brain Atlas (AHBA) can inform us about mRNA expression of numerous proteins of interest across the whole brain, while in vivo protein binding in the human brain can be quantified by means of neuroreceptor positron emission tomography (PET). By combining both modalities, the association between regional gene expression and receptor distribution in the living brain can be approximated. Here, we compare the characteristics of D2 and D3 dopamine receptor distribution by applying the dopamine D2/3 receptor agonist radioligand [11C]-(+)-PHNO and human gene expression data. Since [11C]-(+)-PHNO has a higher affinity for D3 compared to D2 receptors, we hypothesized that there is a stronger relationship between D2/3 non-displaceable binding potentials (BPND) and D3 mRNA expression. To investigate the relationship between D2/3 BPND and mRNA expression of DRD2 and DRD3 we performed [11C]-(+)-PHNO PET scans in 27 healthy subjects (12 females) and extracted gene expression data from the AHBA. We also calculated D2/D3 mRNA expression ratios to imitate the mixed D2/3 signal of [11C]-(+)-PHNO. In accordance with our a priori hypothesis, a strong correlation between [11C]-(+)-PHNO and DRD3 expression was found. However, there was no significant correlation with DRD2 expression. Calculated D2/D3 mRNA expression ratios also showed a positive correlation with [11C]-(+)-PHNO binding, reflecting the mixed D2/3 signal of the radioligand. Our study supports the usefulness of combining gene expression data from open access brain atlases with in vivo imaging data in order to gain more detailed knowledge on neurotransmitter signaling.

The pulvinar nucleus and antidepressant treatment: dynamic modeling of antidepressant response and remission with ultra-high field functional MRI.

Functional magnetic resonance imaging (fMRI) successfully disentangled neuronal pathophysiology of major depression (MD), but only a few fMRI studies have investigated correlates and predictors of remission. Moreover, most studies have used clinical outcome parameters from two time points, which do not optimally depict differential response times. Therefore, we aimed to detect neuronal correlates of response and remission in an antidepressant treatment study with 7 T fMRI, potentially harnessing advances in detection power and spatial specificity. Moreover, we modeled outcome parameters from multiple study visits during a 12-week antidepressant fMRI study in 26 acute (aMD) patients compared to 36 stable remitted (rMD) patients and 33 healthy control subjects (HC). During an electrical painful stimulation task, significantly higher baseline activity in aMD compared to HC and rMD in the medial thalamic nuclei of the pulvinar was detected (p = 0.004, FWE-corrected), which was reduced by treatment. Moreover, clinical response followed a sigmoid function with a plateau phase in the beginning, a rapid decline and a further plateau at treatment end. By modeling the dynamic speed of response with fMRI-data, perigenual anterior cingulate activity after treatment was significantly associated with antidepressant response (p < 0.001, FWE-corrected). Temporoparietal junction (TPJ) baseline activity significantly predicted non-remission after 2 antidepressant trials (p = 0.005, FWE-corrected). The results underline the importance of the medial thalamus, attention networks in MD and antidepressant treatment. Moreover, by using a sigmoid model, this study provides a novel method to analyze the dynamic nature of response and remission for future trials.

Correction to: The pulvinar nucleus and antidepressant treatment: dynamic modeling of antidepressant response and remission with ultra-high field functional MRI.

The author list was presented as last name, first name. The names should have been listed as:Christoph Kraus, Manfred Klöbl, Martin Tik, Bastian Auer, Thomas Vanicek, Nicole Geissberger, Daniela M. Pfabigan, Andreas Hahn, Michael Woletz, Katharina Paul, Arkadiusz Komorowski, Siegfried Kasper, Christian Windischberger, Claus Lamm, Rupert Lanzenberger.

The Efficacy of Light Therapy in the Treatment of Seasonal Affective Disorder: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Bright light therapy (BLT) has been used as a treatment for seasonal affective disorder (SAD) for over 30 years. This meta-analysis was aimed to assess the efficacy of BLT in the treatment of SAD in adults. METHOD: We performed a systematic literature search including randomized, single- or double-blind clinical trials investigating BLT (≥1,000 lx, light box or light visor) against dim light (≤400 lx) or sham/low-density negative ion generators as placebo. Only first-period data were used from crossover trials. The primary outcome was the post-treatment depression score measured by validated scales, and the secondary outcome was the rate of response to treatment. RESULTS: A total of 19 studies finally met our predefined inclusion criteria. BLT was superior over placebo with a standardized mean difference of -0.37 (95% CI: -0.63 to -0.12) for depression ratings (18 studies, 610 patients) and a risk ratio of 1.42 (95% CI: 1.08-1.85) for response to active treatment (16 studies, 559 patients). We found no evidence for a publication bias, but moderate heterogeneity of the studies and a moderate-to-high risk of bias. CONCLUSIONS: BLT can be regarded as an effective treatment for SAD, but the available evidence stems from methodologically heterogeneous studies with small-to-medium sample sizes, necessitating larger high-quality clinical trials.

Hippocampal Subfields in Acute and Remitted Depression-an Ultra-High Field Magnetic Resonance Imaging Study.

BACKGROUND: Studies investigating hippocampal volume changes after treatment with serotonergic antidepressants in patients with major depressive disorder yielded inconsistent results, and effects on hippocampal subfields are unclear. METHODS: To detail treatment effects on total hippocampal and subfield volumes, we conducted an open-label study with escitalopram followed by venlafaxine upon nonresponse in 20 unmedicated patients with major depressive disorder. Before and after 12 weeks treatment, we measured total hippocampal formation volumes and subfield volumes with ultra-high field (7 Tesla), T1-weighted, structural magnetic resonance imaging, and FreeSurfer. Twenty-eight remitted patients and 22 healthy subjects were included as controls. We hypothesized to detect increased volumes after treatment in major depressive disorder. RESULTS: We did not detect treatment-related changes of total hippocampal or subfield volumes in patients with major depressive disorder. Secondary results indicated that the control group of untreated, stable remitted patients, compared with healthy controls, had larger volumes of the right hippocampal-amygdaloid transition area and right fissure at both measurement time points. Depressed patients exhibited larger volumes of the right subiculum compared with healthy controls at MRI-2. Exploratory data analyses indicated lower baseline volumes in the subgroup of remitting (n = 10) vs nonremitting (n = 10) acute patients. CONCLUSIONS: The results demonstrate that monoaminergic antidepressant treatment in major depressive disorder patients was not associated with volume changes in hippocampal subfields. Studies with larger sample sizes to detect smaller effects as well as other imaging modalities are needed to further assess the impact of antidepressant treatment on hippocampal subfields.

The use of surface electromyography in rehabilitating rheumatic patients after knee arthroplasty (pilot study).

OBJECTIVES: The aim of the conducted research was to assess muscle performance in rheumatic patients qualified for knee arthroplasty before and after surgical treatment. MATERIAL AND METHODS: Patients with the diagnosis of rheumatoid arthritis or a degenerative joint disease qualified for surgical treatment were examined. Three groups were analysed: 1) a control group, 2) a group of patients qualified for knee arthroplasty (G1), 3) a group of patients with one knee joint endoprosthesis qualified for the second surgery (G2). The study was carried out through a portable surface electromyography system from Noraxon U.S.A. INC., Clinical DTS and using surface electrodes. The surface electromyography (sEMG) examination was conducted twice: before and on the 10th day after the surgery. The study concerned the quadriceps femoris muscle, i.e. its straight and medial head in both lower limbs during isometric tension and active movement. RESULTS: The comparison of the examined muscles' activity in the control group revealed greatly increased activity during isometric tension than during active movement in both muscles. In the G1 group, the comparison of the average values of isometric tension of the examined muscles before the surgery showed slight differences between the healthy limb and the one qualified for the surgical treatment. After the surgery, significant asymmetry between the average values achieved by the healthy and the operated limb could be identified in both muscles. In the G2 group, muscle activity within the currently operated limb revealed only slight differences between the limbs before the surgery. After the surgery, there was an increase in muscle activity within the previously operated limb. CONCLUSIONS: Considerably higher average values of muscle activity during the isometric tension, when compared to the active movement in a sitting position, indicate the necessity of more widespread use of isometric tension in rehabilitating patients after knee arthroplasty.

Spatial analysis and high resolution mapping of the human whole-brain transcriptome for integrative analysis in neuroimaging.

The quantification of big pools of diverse molecules provides important insights on brain function, but is often restricted to a limited number of observations, which impairs integration with other modalities. To resolve this issue, a method allowing for the prediction of mRNA expression in the entire brain based on microarray data provided in the Allen Human Brain Atlas was developed. Microarray data of 3702 samples from 6 brain donors was registered to MNI and cortical surface space using FreeSurfer. For each of 18,686 genes, spatial dependence of transcription was assessed using variogram modelling. Variogram models were employed in Gaussian process regression to calculate best linear unbiased predictions for gene expression at all locations represented in well-established imaging atlases for cortex, subcortical structures and cerebellum. For validation, predicted whole-brain transcription of the HTR1A gene was correlated with [carbonyl-11C]WAY-100635 positron emission tomography data collected from 30 healthy subjects. Prediction results showed minimal bias ranging within ±0.016 (cortical surface), ±0.12 (subcortical regions) and ±0.14 (cerebellum) in units of log2 expression intensity for all genes. Across genes, the correlation of predicted and observed mRNA expression in leave-one-out cross-validation correlated with the strength of spatial dependence (cortical surface: r = 0.91, subcortical regions: r = 0.85, cerebellum: r = 0.84). 816 out of 18,686 genes exhibited a high spatial dependence accounting for more than 50% of variance in the difference of gene expression on the cortical surface. In subcortical regions and cerebellum, different sets of genes were implicated by high spatially structured variability. For the serotonin 1A receptor, correlation between PET binding potentials and predicted comprehensive mRNA expression was markedly higher (Spearman ρ = 0.72 for cortical surface, ρ = 0.84 for subcortical regions) than correlation of PET and discrete samples only (ρ = 0.55 and ρ = 0.63, respectively). Prediction of mRNA expression in the entire human brain allows for intuitive visualization of gene transcription and seamless integration in multimodal analysis without bias arising from non-uniform distribution of available samples. Extension of this methodology promises to facilitate translation of omics research and enable investigation of human brain function at a systems level.

Risk of falls in the rheumatic patient at geriatric age.

Evaluating the risk of falling of a geriatric rheumatic patient plays an essential role not only in planning and carrying out the physiotherapeutic process. The consequences of falls may be different and, although they do not always result in serious repercussions such as fractures or injuries, it is sufficient that they generate the fear of falling and cause a significant reduction in physical activity. Assessing functional capacity to define the risk of falling is of utmost importance in the case of patients after joint arthroplasty surgeries. The specificity of rheumatic patient's falls is determined by numerous factors. It is not always possible to avoid them. However, it becomes vital to include fall prevention in the rehabilitation process as well as to prepare the house for the needs of an elderly person so that they are safe and as self-dependent as possible.

Physical activity in the elderly who underwent joint replacement surgery in the course of rheumatic diseases.

According to the forecasts of the Central Statistical Office of Poland, in 2030 people at the age of 65 and older will account for 23.8%, i.e. their number will amount to approx. 8.5 m people. Geriatric rheumatic patients more often decide to undergo surgical joint replacement. According to the National Health Fund, the number of joint replacement services provided in 2014 increased by 93%, as compared to 2005. Improving the physical performance of this constantly expanding group of patients requires taking into account many factors to raise their functional status, reduce the risk of falling, teach rules of proper functioning with an artificial joint and encourage unassisted physical activity. Restoring fitness and independence is a difficult but necessary task due to an increasing number of seniors with replaced joint.

Psychiatric and legal considerations for ketamine treatment within prison settings.

The fundamental right to equivalence of health care in prison settings encompasses the provision of medication to address mental health conditions. Considering the increased risk for self-harm among individuals dealing with depression, the limited effectiveness of conservative antidepressants is a major challenge in psychiatry. The high prevalence of suicidal tendencies within prison populations underscores the imperative for state-of-the-art pharmacological treatment to uphold adequate health care standards. Notably, the denial of access to effective medication could be deemed a violation of human rights of people living in prison according to international treaties, domestic law, and United Nations normative standards of detention. This article presents the authors' perspective on the accessibility of ketamine treatment in prison settings, discussing psychiatric and legal considerations as well as current challenges in this context. Implementing novel psychopharmacological interventions may alleviate the distress experienced by individuals struggling with depressive symptoms and suicidality. At the same time, unprecedented treatment alternatives bring along potential issues, including limited understanding of long-term effects and the risk of abuse. Given the scarce data-availability, a pressing need exists for further research on the benefits and risks of ketamine treatment within prison populations.

The impact of the COVID-19 pandemic on the psychosocial rehabilitation of forensic psychiatric patients in Austria.

The coronavirus disease 2019 (COVID-19) pandemic led to increased psychological distress and far-reaching restrictions of freedom. In March 2020, Austrian penal authorities enacted various safety and protection measures to mitigate the propagation of COVID-19. While infection rates in penal institutions were low, restrictive conditions of detention limited the forensic care of offenders. This retrospective longitudinal observational study aimed to evaluate the impact of the pandemic on the psychosocial rehabilitation in forensic psychiatry. Administrative and clinical data obtained from 97 males treated at an inpatient forensic mental health institution were compared before (January 2019 - mid-March 2020) and after (mid-March 2020 - May 2021) the enactment of pandemic-related restrictive measures. The study outcomes related to rehabilitative activities, social contacts, psychopathological stability, and compliance with institutional regulations. During the pandemic, a decrease in individual one-day temporary releases (64 vs. 3, p < .001) and one-day group excursions (103 vs. 10, p < .001) was observed. Likewise, visits by relatives (1440 vs. 429, p < .001) and legal guardians (286 vs. 130, p = .009) decreased. Regarding compliance with institutional regulations, illegal activities decreased from 27 to 8 after enactment of restrictive measures (p = .024). In contrast, long-term temporary releases (122 vs. 188 weeks, p = .131) and admissions to the acute ward (141 vs. 143, p = .712) remained unchanged. Overall, this study demonstrates the substantial impact of COVID-19 on the psychosocial care of forensic psychiatric patients and implies the necessity for guidelines to uphold an appropriate standard of forensic rehabilitation during future pandemics.

Comparison of cardiac image-derived input functions for quantitative whole body [18F]FDG imaging with arterial blood sampling.

Introduction: Dynamic positron emission tomography (PET) and the application of kinetic models can provide important quantitative information based on its temporal information. This however requires arterial blood sampling, which can be challenging to acquire. Nowadays, state-of-the-art PET/CT systems offer fully automated, whole-body (WB) kinetic modelling protocols using image-derived input functions (IDIF) to replace arterial blood sampling. Here, we compared the validity of an automatic WB kinetic model protocol to the reference standard arterial input function (AIF) for both clinical and research settings. Methods: Sixteen healthy participants underwent dynamic WB [18F]FDG scans using a continuous bed motion PET/CT system with simultaneous arterial blood sampling. Multiple processing pipelines that included automatic and manually generated IDIFs derived from the aorta and left ventricle, with and without motion correction were compared to the AIF. Subsequently generated quantitative images of glucose metabolism were compared to evaluate performance of the different input functions. Results: We observed moderate to high correlations between IDIFs and the AIF regarding area under the curve (r = 0.49-0.89) as well as for the cerebral metabolic rate of glucose (CMRGlu) (r = 0.68-0.95). Manual placing of IDIFs and motion correction further improved their similarity to the AIF. Discussion: In general, the automatic vendor protocol is a feasible approach for the quantification of CMRGlu for both, clinical and research settings where expertise or time is not available. However, we advise on a rigorous inspection of the placement of the volume of interest, the resulting IDIF, and the quantitative values to ensure valid interpretations. In protocols requiring longer scan times or where cohorts are prone to involuntary movement, manual IDIF definition with additional motion correction is recommended, as this has greater accuracy and reliability.

7T imaging of the wrist.

Ultra-high-field magnetic resonance (MR) imaging provides a high signal-to-noise ratio and thus is expected to be superior to 1.5T and 3T MR systems that are currently used in daily routine. For use in the musculoskeletal system, expectations are high, particularly for smaller joints such as the wrist, because of the small size of the visualized anatomical structures, where high spatial resolution imaging is mandatory. However, there are technical challenges associated with ultra-high-field MR, and much of the necessary basic research has been done. This article reviews the literature of the past 10 years of research in this field, which reveals a promising pattern of continuing improvements and further developments. For this reason, it is likely that, in the near future, studies with larger study populations and more clinically driven research questions will follow.

Acute and subsequent continuation electroconvulsive therapy elevates serum BDNF levels in patients with major depression.

INTRODUCTION: The induction of brain-derived neurotrophic factor (BDNF) release and subsequent restoration of neuroplastic homeostasis may underlie the effects of electroconvulsive therapy (ECT). OBJECTIVES: We aimed to assess serum and plasma BDNF levels during the course of acute ECT, as well as before and after subsequent continuation ECT, in patients with depression. METHODS: We included 24 patients with major depressive disorder (mean age ±â€¯SD: 54.5 ±â€¯13.7; f/m: 17/7; baseline 17-item Hamilton Depression Rating Scale score of 26.79 ±â€¯4.01). Serum and plasma BDNF (sBDNF, pBDNF) levels were assessed at nine time-points before, during, and after acute ECT series. Data were analysed using linear regression and linear mixed models, which were adjusted for multiple comparisons via Bonferroni correction. Five patients received continuation ECT subsequent to the acute ECT series. In these patients, BDNF levels were assessed before and after each two continuation ECT sessions using Wilcoxon signed-rank tests. RESULTS: Relative to baseline (mean ng/ml ±SD: 24.68 ±â€¯14.40), sBDNF levels were significantly higher 1 day (33.04 ±â€¯14.11, p = 0.013, corrected), 1 week (37.03 ±â€¯10.29, p < 0.001, corrected), and 1 month (41.05 ±â€¯10.67, p = 0.008, corrected) after the final ECT session, while pBDNF levels did not significantly differ (p > 0.1). Furthermore, our results indicated that sBDNF levels increased after each continuation ECT session. There was no significant association between sBDNF levels and clinical parameters or treatment response. CONCLUSION: The absence of an association between changes in sBDNF levels and depressive symptoms challenges the proposed concept of sBDNF/pBDNF as key markers of the effects of ECT.

Brain monoamine oxidase A in seasonal affective disorder and treatment with bright light therapy.

Increased cerebral monoamine oxidase A (MAO-A) levels have been shown in non-seasonal depression using positron emission tomography (PET). Seasonal affective disorder (SAD) is a sub-form of major depressive disorder and is typically treated with bright light therapy (BLT). The serotonergic system is affected by season and light. Hence, this study aims to assess the relevance of brain MAO-A levels to the pathophysiology and treatment of SAD. Changes to cerebral MAO-A distribution (1) in SAD in comparison to healthy controls (HC), (2) after treatment with BLT and (3) between the seasons, were investigated in 24 patients with SAD and 27 HC using [11C]harmine PET. PET scans were performed in fall/winter before and after 3 weeks of placebo-controlled BLT, as well as in spring/summer. Cerebral MAO-A distribution volume (VT, an index of MAO-A density) did not differ between patients and HC at any of the three time-points. However, MAO-A VT decreased from fall/winter to spring/summer in the HC group (F1, 187.84 = 4.79, p < 0.050), while SAD showed no change. In addition, BLT, but not placebo, resulted in a significant reduction in MAO-A VT (F1, 208.92 = 25.96, p < 0.001). This is the first study to demonstrate an influence of BLT on human cerebral MAO-A levels in vivo. Furthermore, we show that SAD may lack seasonal dynamics in brain MAO-A levels. The lack of a cross-sectional difference between patients and HC, in contrast to studies in non-seasonal depression, may be due to the milder symptoms typically shown by patients with SAD.