Individuals carrying the short allele of a common polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) exhibit heightened amygdala responses to passive stimulation with aversive emotional material. In turn, the level of amygdala activation in response to emotion can be decreased by will, for example by using cognitive emotion regulation strategies. In the present study, 37 female subjects (s-carriers: n=21; l/l-homozygotes: n=16) performed an emotion regulation task during functional magnetic resonance imaging to determine whether cognitive emotion regulation can modulate the genetically determined amygdala hyperreactivity in 5-HTTLPR short allele carriers. Our results demonstrate that cognitive emotion regulation diminishes the difference in amygdala reactivity to threat-related stimuli between 5-HTTLPR genotype groups. Furthermore, we also provide evidence that the effect of cognitive regulation is mediated through altered coupling between the amygdala and prefrontal regulatory regions. Our findings demonstrate that while the presence of the 5-HTTLPR short allele leads to heightened responses in the amygdala, cognitive regulation can modify genetically mediated effects upon brain function by volitionally altering prefrontal-amygdala connectivity.

Controversy surrounds the role of human medial frontal cortex in controlling actions. Although damage to this area leads to severe difficulties in spontaneously initiating actions, the precise mechanisms underlying such "volitional" deficits remain to be established. Previous studies have implicated the medial frontal cortex in conflict monitoring and the control of voluntary action, suggesting that these key processes are functionally related or share neural substrates. Here, we combine a novel behavioral paradigm with functional imaging of the oculomotor system to reveal, for the first time, a functional subdivision of the pre-supplementary motor area (pre-SMA) into anatomically distinct areas that respond exclusively to either volition or conflict. We also demonstrate that activity in the supplementary eye field (SEF) distinguishes between success and failure in changing voluntary action plans during conflict, suggesting a role for the SEF in implementing the resolution of conflicting actions. We propose a functional architecture of human medial frontal cortex that incorporates the generation of action plans and the resolution of conflict.

Insight into motivational processes may be gained by examining measures of willingness to exert effort for rewards, which have been linked to neuropsychiatric symptoms of anhedonia and apathy. However, while much work has focused on the development of models of motivation based on classic tasks of externally-generated levels of effort for reward, there has been less focus on the question of self-generated motivation or volition. We developed a task that aims to capture separate measures of self-generated and externally-generated motivation, with two task variants for physical and cognitive effort, and sought to test and validate this measure in two populations of healthy volunteers (N = 27 and N = 28). Similar to previous reports, a sigmoid function represented a better overall fit to the effort-reward data than a linear or Weibull model. Individual sigmoid function shapes were governed by two free parameters: bias (the amount of reward needed for effort initiation) and reward insensitivity (the amount of increase in reward needed to accelerate effort expenditure). For both physical and cognitive effort, bias was higher in the self-generated condition, indicating reduced self-generated volitional effort initiation, compared to externally-generated effort initiation, across effort domains. Bias against initial effort initiation in the self-generated condition was related to a specific dimensional measure of anticipatory anhedonia. For physical effort only, reward insensitivity was also higher in the self-generated condition compared to the externally-generated motivation condition, indicating lower self-generated effort acceleration. This work provides a novel objective measure of self-generated motivation that may provide insights into mechanisms of anhedonia and related symptoms.

Spinal cord injury (SCI) results in the partial or complete loss of movement and sensation below the level of injury. In individuals with cervical level SCI, there is a great need for voluntary command generation for environmental control, self-mobility, or computer access to improve their independence and quality of life. Brain-computer interfacing is one way of generating these voluntary command signals. As an alternative, this study investigates the feasibility of utilizing descending signals in the dorsolateral spinal cord tracts above the point of injury as a means of generating volitional motor control signals.

In animal models of depression, depression is defined as performance on a learning task. That task is typically escaping a mild electric shock in a shuttle cage by moving from one side of the cage to the other. Ovarian hormones influence learning in other kinds of tasks, and these hormones are associated with depressive symptoms in humans. The role of these hormones in shuttle-cage escape learning, however, is less clear. This study manipulated estradiol and progesterone in ovariectomized female rats to examine their performance in shuttle-cage escape learning without intentionally inducing a depressive-like state. Progesterone, not estradiol, within four hours of testing affected latencies to escape. The improvement produced by progesterone was in the decision to act, not in the speed of learning or speed of escaping. This parallels depression in humans in that depressed people are slower in volition, in their decisions to take action.

The purpose of this study was to validate the Volition in Exercise Questionnaire in Italian language (VEQ-I). The translation and cultural adaptation of the VEQ-I was conducted using the forward-backward translation method. VEQ-I eighteen items correspond to the six-factors structure of the original version. The construct validity was verified by the confirmatory factor analysis (CFA) (CFI = 0.960; TLI = 0.943; RMSEA = 0.039; and SRMR = 0.040). The eighteen items were well distributed in six subscales and the six-factors structure of the questionnaire was supported. Internal Consistency value of the questionnaire was investigated for each subscale of the VEQ-I. Cronbach's alpha and Omega values of the Reasons, Postponing Training, Unrelated Thoughts, Self-Confidence, Approval from Others and Coping with Failure subscales were 0.76 (α) and 0.76 (ω), 0.76 (α) and 0.76 (ω), 0.87 (α) and 0.88 (ω), 0.85 (α) and 0.85 (ω), 0.70 (α) and 0.72 (ω) and 0.74 (α) and 0.74 (ω), respectively. They were acceptable in all the six subscales. The concurrent validity was assessed using the correlation among the subscales of VEQ-I measures and those contained in two questionnaires: Psychobiosocial States in Physical Education (PBS-SPE) and Exercise Motivations Inventory (EMI-2).

Music contests are a means of discovering talents and promoting musical abilities. Participation in a contest is usually preceded by many years of practice requiring a high level of motivation and a supportive environment, especially regarding family. Despite the importance participation in music contests may have for musical development, there is a considerable research deficit. The annual music contest "Jugend musiziert" (youth making music) is the most important musical competition for highly gifted young musicians in Germany. There has been comprehensive research on the participants of "Jugend musiziert" by Hans Günther Bastian in the 1980s and 1990s, but since then, only very little research has been published. In 2017, we started a large-scale study on the participants at the national level, covering a broad range of topics, including sociocultural background, development and learning, performance practice, personality traits, motivation, and musical performance anxiety. A standardized paper-pencil questionnaire was administered to approximately 2,260 participants and a total of 1,143 valid questionnaires was returned (age 9-24 years; M = 15; SD = 2.1, female = 62%). Using principal component, variance, correlation, and linear discriminant analyses, interdependencies between practice time and motivational factors were analyzed in this paper. Concerning practice time, major differences between participants of different contest categories became clear, with classical musicians practicing the most. Practice time, as well as parental support and supervision, correlated with age: Older participants spent, on average, more hours practicing and received less support and supervision. Challenge was the most important incentive for all participants, but more decisive for participants in the classical solo contest than in the ensemble category. Female participants were more prone to fear incentives than males. Participants who practiced a lot scored higher on general flow than the participants with a smaller amount of practice and also showed significantly more perseverance. Moreover, participants of the pop solo contest experienced more general flow than all other participants; ensemble players showed more social focus than participants in the classical solo contest. All in all, participants of different contest categories could be discerned by practice time and prototypical motivational aspects.

The number of older people with multiple health problems is increasing worldwide. This creates a strain on clinicians and the health service when delivering clinical care to this patient group, who themselves carry a large treatment burden. Despite shared decision-making being acknowledged by healthcare organisations as a priority feature of clinical care, older patients with multimorbidity are less often involved in decision-making when compared with younger patients, with some evidence suggesting associated health inequalities. Interventions aimed at facilitating shared decision-making between doctors and patients are outdated in their assessments of today's older patient population who need support in prioritising complex care needs in order to maximise quality of life and day-to-day function.

Nucleosomes consist of small fragments of DNA wrapped around a histone octamer core. Diseases such as cancer or inflammation lead to cell death, which causes fragmentation and release of nucleosomes into the blood. The Nu.Q™ technology measures circulating nucleosome levels and exploits the different compositions of cancer derived nucleosomes in blood to detect and identify cancer even at early stages. The objectives of this study are to identify the optimal sample type for the Nu.Q™ H3.1 assay and to determine if it can accurately detect nucleosomes in the blood of healthy canines as well as those with cancer.

During cell death, nucleosomes, the basic structural unit of chromatin, are released into the blood stream and elevated levels have been found in the plasma of patients with solid cancers. In this study, we demonstrate an increase in cell free circulating H3.1-nucleosomes levels in plasma samples from patients with hematological malignancy, non-Hodgkin lymphoma (NHL), relative to healthy donors. As histone post-translational modifications (PTMs) of circulating nucleosomes are described as potential biomarkers of various solid cancers, we investigated the epigenetic profile of nucleosomes from NHL patients following nucleosome enrichment (Nu.Q® capture) combined with mass spectrometry. Eight histones PTMs, including the acetylation of histone H3 at lysine 9, 14 and 18 as well as the methylation state of histone H3 at lysine 9, 27 and 36, were identified at a higher level in the plasma of NHL patients compared to healthy donors. These results were confirmed in a larger clinical cohort by immunoassay. Subsequently, the temporal profile of these histone PTMs in NHL patients undergoing treatment course highlighted the potential use of these new biomarkers to monitor treatment response and/or disease progression. Our results substantiate that levels of H3.1-nucleosomes are particularly elevated in NHL patients and may be a useful diagnostic tool. Moreover, our work emphasizes the crucial roles of the epigenetic marks present on circulating nucleosomes to detect and monitor tumor progression and/or treatment response of non-Hodgkin Lymphoma.

The severity of coronavirus disease 2019 (COVID-19) varies significantly with cases spanning from asymptomatic to lethal with a subset of individuals developing Severe Acute Respiratory Syndrome (SARS) and death from respiratory failure. To determine whether global nucleosome and citrullinated nucleosome levels were elevated in COVID-19 patients, we tested two independent cohorts of COVID-19 positive patients with quantitative nucleosome immunoassays and found that nucleosomes were highly elevated in plasma of COVID-19 patients with a severe course of the disease relative to healthy controls and that both histone 3.1 variant and citrullinated nucleosomes increase with disease severity. Elevated citrullination of circulating nucleosomes is indicative of neutrophil extracellular trap formation, neutrophil activation and NETosis in severely affected individuals. Importantly, using hospital setting (outpatient, inpatient or ICU) as a proxy for disease severity, nucleosome levels increased with disease severity and may serve as a guiding biomarker for treatment. Owing to the limited availability of mechanical ventilators and extracorporal membrane oxygenation (ECMO) equipment, there is an urgent need for effective tools to rapidly assess disease severity and guide treatment selection. Based on our studies of two independent cohorts of COVID-19 patients from Belgium and Germany, we suggest further investigation of circulating nucleosomes and citrullination as biomarkers for clinical triage, treatment allocation and clinical drug discovery.

Hematopoietic malignancies are extremely common in pet dogs and represent nearly 30% of the malignancies diagnosed in this population each year. Clinicians commonly use existing tools such as physical exam findings, radiographs, ultrasound and baseline blood work to monitor these patients for treatment response and remission. Circulating biomarkers, such as prostate specific antigen or carcinoembryonic antigen, can be useful tools for monitoring treatment response and remission status in human cancer patients. To date, there has a been a lack of useful circulating biomarkers available to veterinary oncology patients.

Alteration of epigenetic modifications plays an important role in human cancer. Notably, the dysregulation of histone post-translational modifications (PTMs) has been associated with several cancers including colorectal cancer (CRC). However, the signature of histone PTMs on circulating nucleosomes is still not well described. We have developed a fast and robust enrichment method to isolate circulating nucleosomes from plasma for further downstream proteomic analysis. This method enabled us to quantify the global alterations of histone PTMs from 9 CRC patients and 9 healthy donors. Among 54 histone proteoforms identified and quantified in plasma samples, 13 histone PTMs were distinctive in CRC. Notably, methylation of histone H3K9 and H3K27, acetylation of histone H3 and citrullination of histone H2A1R3 were upregulated in plasma of CRC patients. A comparative analysis of paired samples identified 3 common histone PTMs in plasma and tumor tissue including the methylation and acetylation state of lysine 27 of histone H3. Moreover, we highlight for the first time that histone H2A1R3 citrulline is a modification upregulated in CRC patients. This new method presented herein allows the detection and quantification of histone variants and histone PTMs from circulating nucleosomes in plasma samples and could be used for biomarker discovery of cancer.

Although growing research indicates that certain personality traits change over the lifespan, implicit motives are often deemed to be rather stable personality characteristics. Researchers have been interested in implicit motives for several decades, but our understanding of how these dispositions change still lacks clarity. This article gives an overview and a discussion of the current evidence for the stability of and the changes in implicit motives. After elaborating on the theoretical background of the motive construct and its measurement, we present an overview of studies that have investigated the trainability of implicit motives and their dispositional stability and changes using cross-sectional and longitudinal methods. Although the results are inconclusive concerning the direction of change, the reviewed studies suggest that implicit motives adapt to life circumstances much like other personality traits. This review sets out to contribute to a better understanding of the functioning of implicit motives and to present a roadmap for further research.

Nucleosomes consist of DNA wrapped around a histone octamer core like beads on a string so that DNA can be condensed as chromatin into chromosomes. Diseases such as cancer or inflammation lead to cell death where chromatin is fragmentated and released as mononucleosomes into the blood. The Nu.Q™ H3.1 assay measures total nucleosome concentration in plasma of humans and has been used to detect and identify cancer even at early stages. The objectives of this study were to determine if nucleosome levels could be used to distinguish between healthy dogs and dogs with various stages of lymphoma (LSA) using the Nu.Q™ H3.1 assay. A total of 126 dogs diagnosed with LSA and 134 healthy controls were recruited for this study. Plasma was collected from each dog and stored in K2-EDTA tubes. The LSA patient samples were recruited from TAMU or purchased from various biobanks. All control cases were recruited from TAMU.

Nucleosomes consist of DNA wrapped around a histone octamer core like thread on a spool to condense DNA as chromatin into chromosomes. Diseases such as cancer or inflammation lead to cell death, chromatin fragmentation and release of nucleosomes into the blood. The Nu.Q™ platform measures circulating nucleosomes in the blood of humans that result from disease and has been used to detect and identify cancer even at early stages. The objectives of this study are to quantify and better characterize nucleosomes in dogs with various stages of hemangiosarcoma (HSA) using this ELISA-based assay. Samples from 77 dogs with a confirmed diagnosis of hemangiosarcoma and 134 healthy controls were utilized for this study. The HSA samples were recruited from the Texas A&M University Small Animal Clinic (TAMU-SAC) or purchased from biobanks. All control samples were recruited from the TAMU-SAC.

In everyday life, we often deliberate about affective outcomes of decisions which can be described as ambivalent; i.e. positive and negative at the same time. For example, when looking forward to meet a dear friend at her/his favorite concert although one dislikes the music that is being performed. Thus, anticipation of bivalent emotions and their volitional regulation is an important ingredient of everyday choices. However, previous studies investigating neural substrates involved in anticipating emotional events mostly focused on anticipating either negative emotions (punishment) or positive emotions (reward) in isolation, thus inducing either of them separately. Furthermore, these studies rather focused on the effortful down-regulation of affect (i.e. reducing negative or positive affect), whereas such conflict situations may also require us to deploy attention on and thereby upregulate anticipated emotions in order to resolve a decision conflict (e.g., by focusing on positive consequences while orienting away from negative consequences of that same situation). To address this gap, we performed a series of three fMRI-experiments using simple visual and auditory stimuli in order to (i) determine the neural correlates involved when anticipating a bivalent affective outcome that is both positive and negative at the same time - related to a conflict situation and (ii) investigate their malleability during anticipation via voluntary emotion regulation using attentional focusing. In these studies, we (i) demonstrate that brain areas involved in anticipating positive (ventral striatum) and negative (anterior insula) emotional events are co-activated when anticipating the occurrence of both punishment and reward at the same time and (ii) provide evidence that attention on either the positive or the negative correlates with a shift in activations of these co-activated neural networks and associated anticipated emotions towards either the positive (increased activity in ventral striatum, ventromedial prefrontal cortex, posterior cingulate cortex) or the negative (increased activity in insula) aspect of the upcoming bivalent outcome. In summary, we provide self-report and neural evidence for the assumption that affective brain systems associated with the processing of bivalent anticipated emotions can be voluntarily controlled by cognitive emotion regulation strategies.

This study examined a model of meaningful work among a diverse sample of working adults. From the perspectives of Self-Determination Theory and the Psychology of Working Framework, we tested a structural model with social class and work volition predicting SDT motivation variables, which in turn predicted meaningful work. Partially supporting hypotheses, work volition was positively related to internal regulation and negatively related to amotivation, whereas social class was positively related to external regulation and amotivation. In turn, internal regulation was positively related to meaningful work, whereas external regulation and amotivation were negatively related to meaningful work. Indirect effects from work volition to meaningful work via internal regulation and amotivation were significant, and indirect effects from social class to meaningful work via external regulation and amotivation were significant. This study highlights the important relations between SDT motivation variables and meaningful work, especially the large positive relation between internal regulation and meaningful work. However, results also reveal that work volition and social class may play critical roles in predicting internal regulation, external regulation, and amotivation.

Bilingual speakers may select between two languages either on demand (forced language selection) or on their own volition (free language selection). However, the neural substrates underlying free and forced language selection may differ. While the neural substrates underlying forced language selection have been well-explored with language switching paradigms, those underlying free language selection have remained unclear. Using a modified digit-naming switching paradigm, we addressed the neural substrates underlying free language selection by contrasting free language switching with forced language switching. For a digit-pair trial, Chinese-English bilinguals named each digit in Chinese or English either on demand under forced language selection condition or on their own volition under free language selection condition. The results revealed activation in the frontoparietal regions that mediate volition of language selection. Furthermore, a comparison of free and forced language switching demonstrated differences in the patterns of brain activation. Additionally, free language switching showed reduced switching costs as compared to forced language switching. These findings suggest differences between the mechanism(s) underlying free and forced language switching. As such, the current study suggests interactivity between control of volition and control of language switching in free language selection, providing insights into a model of bilingual language control.

Recent advances in basic research have unveiled several strategies for improving the sensitivity and specificity of cell-free DNA (cfDNA) based assays, which is a prerequisite for broadening its clinical use. Included among these strategies is leveraging knowledge of both the biogenesis and physico-chemical properties of cfDNA towards the identification of better disease-defining features and optimization of methods. While good progress has been made on this front, much of cfDNA biology remains uncharted. Here, we correlated serial measurements of cfDNA size, concentration and nucleosome histone modifications with various cellular parameters, including cell growth rate, viability, apoptosis, necrosis, and cell cycle phase in three different cell lines. Collectively, the picture emerged that temporal changes in cfDNA levels are rather irregular and not the result of constitutive release from live cells. Instead, changes in cfDNA levels correlated with intermittent cell death events, wherein apoptosis contributed more to cfDNA release in non-cancer cells and necrosis more in cancer cells. Interestingly, the presence of a ~ 3 kbp cfDNA population, which is often deemed to originate from accidental cell lysis or active release, was found to originate from necrosis. High-resolution analysis of this cfDNA population revealed an underlying DNA laddering pattern consisting of several oligo-nucleosomes, identical to those generated by apoptosis. This suggests that necrosis may contribute significantly to the pool of mono-nucleosomal cfDNA fragments that are generally interrogated for cancer mutational profiling. Furthermore, since active steps are often taken to exclude longer oligo-nucleosomes from clinical biospecimens and subsequent assays this raises the question of whether important pathological information is lost.