The Human Centromedial Amygdala Contributes to Negative Prediction Error Signaling during Appetitive and Aversive Pavlovian Gustatory Learning.

Prediction error (PE) is the mismatch between a prior expectation and reality, and it lies at the core of associative learning about aversive and appetitive stimuli. Human studies on fear learning have linked the amygdala to aversive PEs. In contrast, the relationship between the amygdala and PE in appetitive settings and stimuli, unlike those that induce fear, has received less research attention. Animal studies show that the amygdala is a functionally heterogeneous structure. Nevertheless, the role of the amygdala nuclei in PE signaling remains unknown in humans. To clarify the role of two subdivisions of the human amygdala, the centromedial amygdala (CMA) and basolateral amygdala (BLA), in appetitive and aversive PE signaling, we used gustatory pavlovian learning involving eating-related naturalistic outcomes. Thirty-eight right-handed individuals (19 females) participated in the study. We found that surprise with neutral feedback when a reward is expected triggers activity within the left and right CMA. When an aversive outcome is expected, surprise with neutral feedback triggers activity only within the left CMA. Notably, the BLA was not activated by those conditions. Thus, the CMA engages in negative PE signaling during appetitive and aversive gustatory pavlovian learning, whereas the BLA is not critical for this process. In addition, PE-related activity within the left CMA during aversive learning is negatively correlated with neuroticism and positively correlated with extraversion. The findings indicate the importance of the CMA in gustatory learning when the value of outcomes changes and have implications for understanding psychological conditions that manifest perturbed processing of negative PEs.SIGNIFICANCE STATEMENT A discrepancy between a prediction and an actual outcome (PE) plays a crucial role in learning. Learning improves when an outcome is more significant than expected (positive PE) and worsens when it is smaller than expected (negative PE). We found that the negative PE during appetitive and aversive taste learning is associated with increased activity of the CMA, which suggests that the CMA controls taste learning. Our findings may have implications for understanding psychological states associated with deficient learning from negative PEs, such as obesity and addictive behaviors.

The Clinical Significance and Involvement in Molecular Cancer Processes of Chemokine CXCL1 in Selected Tumors.

Chemokines play a key role in cancer processes, with CXCL1 being a well-studied example. Due to the lack of a complete summary of CXCL1's role in cancer in the literature, in this study, we examine the significance of CXCL1 in various cancers such as bladder, glioblastoma, hemangioendothelioma, leukemias, Kaposi's sarcoma, lung, osteosarcoma, renal, and skin cancers (malignant melanoma, basal cell carcinoma, and squamous cell carcinoma), along with thyroid cancer. We focus on understanding how CXCL1 is involved in the cancer processes of these specific types of tumors. We look at how CXCL1 affects cancer cells, including their proliferation, migration, EMT, and metastasis. We also explore how CXCL1 influences other cells connected to tumors, like promoting angiogenesis, recruiting neutrophils, and affecting immune cell functions. Additionally, we discuss the clinical aspects by exploring how CXCL1 levels relate to cancer staging, lymph node metastasis, patient outcomes, chemoresistance, and radioresistance.

The Importance of CXCL1 in Physiology and Noncancerous Diseases of Bone, Bone Marrow, Muscle and the Nervous System.

This review describes the role of CXCL1, a chemokine crucial in inflammation as a chemoattractant for neutrophils, in physiology and in selected major non-cancer diseases. Due to the vast amount of available information, we focus on the role CXCL1 plays in the physiology of bones, bone marrow, muscle and the nervous system. For this reason, we describe its effects on hematopoietic stem cells, myoblasts, oligodendrocyte progenitors and osteoclast precursors. We also present the involvement of CXCL1 in diseases of selected tissues and organs including Alzheimer's disease, epilepsy, herpes simplex virus type 1 (HSV-1) encephalitis, ischemic stroke, major depression, multiple sclerosis, neuromyelitis optica, neuropathic pain, osteoporosis, prion diseases, rheumatoid arthritis, tick-borne encephalitis (TBE), traumatic spinal cord injury and West Nile fever.

The Importance of CXCL1 in the Physiological State and in Noncancer Diseases of the Oral Cavity and Abdominal Organs.

CXCL1 is a CXC chemokine, CXCR2 ligand and chemotactic factor for neutrophils. In this paper, we present a review of the role of the chemokine CXCL1 in physiology and in selected major non-cancer diseases of the oral cavity and abdominal organs (gingiva, salivary glands, stomach, liver, pancreas, intestines, and kidneys). We focus on the importance of CXCL1 on implantation and placentation as well as on human pluripotent stem cells. We also show the significance of CXCL1 in selected diseases of the abdominal organs, including the gastrointestinal tract and oral cavity (periodontal diseases, periodontitis, Sjögren syndrome, Helicobacter pylori infection, diabetes, liver cirrhosis, alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), HBV and HCV infection, liver ischemia and reperfusion injury, inflammatory bowel disease (Crohn's disease and ulcerative colitis), obesity and overweight, kidney transplantation and ischemic-reperfusion injury, endometriosis and adenomyosis).

Parcellation of the human amygdala using recurrence quantification analysis.

Several previous attempts have been made to divide the human amygdala into smaller subregions based on the unique functional properties of the subregions. Although these attempts have provided valuable insight into the functional heterogeneity in this structure, the possibility that spatial patterns of functional characteristics can quickly change over time has rarely been considered in previous studies. In the present study, we explicitly account for the dynamic nature of amygdala activity. Our goal was not only to develop another parcellation method but also to augment existing methods with novel information about amygdala subdivisions. We performed state-specific amygdala parcellation using resting-state fMRI (rsfMRI) data and recurrence quantification analysis (RQA). RsfMRI data from 102 subjects were acquired with a 3T Trio Siemens scanner. We analyzed values of several RQA measures across all voxels in the amygdala and found two amygdala subdivisions, the ventrolateral (VL) and dorsomedial (DM) subdivisions, that differ with respect to one of the RQA measures, Shannon's entropy of diagonal lines. Compared to the DM subdivision, the VL subdivision can be characterized by a higher value of entropy. The results suggest that VL activity is determined and influenced by more brain structures than is DM activity. To assess the biological validity of the obtained subdivisions, we compared them with histological atlases and currently available parcellations based on structural connectivity patterns (Anatomy Probability Maps) and cytoarchitectonic features (SPM Anatomy toolbox). Moreover, we examined their cortical and subcortical functional connectivity. The obtained results are similar to those previously reported on parcellation performed on the basis of structural connectivity patterns. Functional connectivity analysis revealed that the VL subdivision has strong connections to several cortical areas, whereas the DM subdivision is mainly connected to subcortical regions. This finding suggests that the VL subdivision corresponds to the basolateral subdivision of the amygdala (BLA), while the DM subdivision has some characteristics typical of the centromedial amygdala (CMA). The similarity in functional connectivity patterns between the VL subdivision and BLA, as well as between the DM subdivision and CMA, confirm the utility of our parcellation method. Overall, the study shows that parcellation based on BOLD signal dynamics is a powerful tool for identifying distinct functional systems within the amygdala. This tool might be useful for future research on functional brain organization.

The subjective amplitude of the diurnal rhythm matters - Chronobiological insights for neuroimaging studies.

Multiple aspects of human psychophysiology, including mood and cognition, are subjected to diurnal rhythms. While the previous magnetic resonance imaging (MRI) studies have focused solely on the morningness-eveningness (ME) preference dichotomy, i.e. the circadian phase, the second key dimension of the diurnal rhythms, i.e. the strength of these preferences (amplitude; AM), has been completely overlooked. Uncovering the neural correlates of AM is especially important considering its link with negative emotionality. Structural T1-weighted neuroimaging data from 79 early (EC) and 74 late (LC) chronotypes were analysed to compare grey matter (GM) volume and cortical thickness. The study aimed to elucidate whether the subjective AM and its interaction with ME was a significant predictor of individual brain structure. Both GM volume and cortical thickness of the left primary visual cortex was negatively correlated with AM scores across the entire sample. Furthermore, EC and LC differed in their association between AM scores and the GM volume in the right middle temporal gyrus, with the positive and negative correlations reported respectively in the two groups. The current study underlines the importance of the visual system in circadian rhythmicity and provides possible neural correlates for AM-related differences in negative affect processing. Furthermore, the presence of the opposite correlations between brain anatomy and AM in the two groups suggests that the behavioural and neuronal chronotype differences might become more pronounced in individuals with extreme diurnal differences in mood and cognition, highlighting the necessity to additionally account for AM in neuroimaging studies.

Dissociable contributions of the left and right posterior medial orbitofrontal cortex in motivational control of goal-directed behavior.

Several findings from both human neuroimaging and nonhuman primate studies suggest that the posterior medial orbitofrontal cortex (OFC) may be critical for the motivational control of goal-directed behavior. The present study was conducted to clarify the role of the left and right posterior medial OFC in that function by examining the effects of focal unilateral lesions to this region on the performance on an incentive working memory task. The study covered patients who had undergone surgery for an ACoA aneurysm and normal control subjects (C). The patients were subdivided into three groups: those with resection of the left (LGR+) or right (RGR+) posterior part of the gyrus rectus, and without such a resection (GR-). Participants performed a 2-back working memory task under three motivational conditions (penalty, reward, and no-incentive). The C group performed worse in the penalty condition and better in the reward condition as compared to the no-incentive condition. Similar results were obtained for the GR- group. Performance of the LGR+ group did not depend on incentive manipulations, whereas the RGR+ group performed better in both the penalty and reward conditions than in the no-incentive condition. The results show that the posterior medial OFC is involved in the motivational modulation of working memory performance. Our findings also suggest that the left posterior medial OFC plays a crucial role in this function, whereas the right posterior medial OFC is particularly involved in the processing of the punishing aspect of salient events and it probably mediates in guiding behavior on the basis of negative outcomes of action.

Lactation milk yield prediction in primiparous cows on a farm using the seasonal auto-regressive integrated moving average model, nonlinear autoregressive exogenous artificial neural networks and Wood's model.

OBJECTIVE: The aim of the present study was to compare the effectiveness of three approaches (the seasonal auto-regressive integrated moving average [SARIMA] model, the nonlinear autoregressive exogenous [NARX] artificial neural networks and Wood's model) to the prediction of milk yield during lactation. METHODS: The dataset comprised monthly test-day records from 965 Polish Holstein-Friesian Black-and-White primiparous cows. The milk yields from cows in their first lactation (from 5 to 305 days in milk) were used. Each lactation was divided into ten lactation stages of approximately 30 days. Two age groups and four calving seasons were distinguished. The records collected between 2009 and 2015 were used for model fitting and those from 2016 for the verification of predictive performance. RESULTS: No significant differences between the predicted and the real values were found. The predictions generated by SARIMA were slightly more accurate, although they did not differ significantly from those produced by the NARX and Wood's models. SARIMA had a slightly better performance, especially in the initial periods, whereas the NARX and Wood's models in the later ones. CONCLUSION: The use of SARIMA was more time-consuming than that of NARX and Wood's model. The application of the SARIMA, NARX and Wood's models (after their implementation in a user-friendly software) may allow farmers to estimate milk yield of cows that begin production for the first time.

The effect of peptide absorption on PepT1 gene expression and digestive system hormones in rainbow trout (Oncorhynchus mykiss).

The present study evaluates the effect of protein source (dipeptides, free amino acids, and intact protein) on development and growth of Salmonid fish alevin. Specifically, we follow the expression of oligopeptide transporter protein PepT1 in the intestine of rainbow trout (Oncorhynchus mykiss). Fish were fed exogenously one of four diets: three formulated (lysyl-glycine dipeptide supplemented diet - PP, free lysine and glycine supplemented diet - AA, control diet with no lysine - CON) or commercial starter (Aller Futura - AF). Fish increased mean body weight 8 fold with PP- and AA-supplemented diets resulting in significantly higher weight gain than fish fed CON. Statistical analysis revealed a significant increase in relative PepT1 expression of fish fed experimental diets. Immunohistochemical staining with PepT1 antibody showed the presence of the transporter protein in the brush border membrane of the proximal intestinal enterocytes of fish from all experimental groups. Leptin immunoreactivity occurred not only in the gastric glands but also in proximal intestine and pyloric caeca of fish fed PP, AA and AF diets. Leptin immunoreactivity was also observed in hepatocyte cytoplasm and pancreatic acinar cells. Gastrin/CCK immunoreactive cells were present in the proximal intestine and pyloric caeca.

Empathy in Facial Mimicry of Fear and Disgust: Simultaneous EMG-fMRI Recordings During Observation of Static and Dynamic Facial Expressions.

Real-life faces are dynamic by nature, particularly when expressing emotion. Increasing evidence suggests that the perception of dynamic displays enhances facial mimicry and induces activation in widespread brain structures considered to be part of the mirror neuron system, a neuronal network linked to empathy. The present study is the first to investigate the relations among facial muscle responses, brain activity, and empathy traits while participants observed static and dynamic (videos) facial expressions of fear and disgust. During display presentation, blood-oxygen level-dependent (BOLD) signal as well as muscle reactions of the corrugator supercilii and levator labii were recorded simultaneously from 46 healthy individuals (21 females). It was shown that both fear and disgust faces caused activity in the corrugator supercilii muscle, while perception of disgust produced facial activity additionally in the levator labii muscle, supporting a specific pattern of facial mimicry for these emotions. Moreover, individuals with higher, compared to individuals with lower, empathy traits showed greater activity in the corrugator supercilii and levator labii muscles; however, these responses were not differentiable between static and dynamic mode. Conversely, neuroimaging data revealed motion and emotional-related brain structures in response to dynamic rather than static stimuli among high empathy individuals. In line with this, there was a correlation between electromyography (EMG) responses and brain activity suggesting that the Mirror Neuron System, the anterior insula and the amygdala might constitute the neural correlates of automatic facial mimicry for fear and disgust. These results revealed that the dynamic property of (emotional) stimuli facilitates the emotional-related processing of facial expressions, especially among whose with high trait empathy.

The effect of motivation on working memory: an fMRI and SEM study.

This study investigated the effective connectivity between prefrontal regions of human brain supporting motivational influence on working memory. Functional magnetic resonance imaging (fMRI) and structural equation modeling (SEM) were used to examine the interaction between the lateral orbitofrontal (OFC), medial OFC, and dorsolateral prefrontal (DLPFC) regions in the left and right hemisphere during performance of the verbal 2-back working memory task under two reinforcement conditions. The "low-motivation" condition was not associated with monetary reinforcement, while the "high-motivation" condition involved the probability of winning a certain amount of money. In the "low-motivation" condition, the OFC regions in both hemispheres positively influenced the left DLPFC activity. In the "high-motivation" condition, the connectivity in the network including the right OFC regions and left DLPFC changed from positive to negative, whereas the positive connectivity in the network composed of the left OFC and left DLPFC became slightly enhanced compared with the "low-motivation" condition. However, only the connection between the right lateral OFC and left DLPFC showed a significant condition-dependent change in the strength of influence conveyed through the pathway. This change appears to be the functional correlate of motivational influence on verbal working memory.

Nonverbal deficits in explicit and implicit memory of Parkinson's disease patients.

This study examined verbal and nonverbal aspects of explicit and implicit memory in a sample of 19 Parkinson's disease (PD) patients and 21 control subjects. For implicit memory evaluation, we used a Mirror Reading (MR) task employing verbal material as well as a nonverbal Serial Reaction Time (SRT) task. For explicit memory measurement we applied a word pairs task (verbal) and pairs of a Japanese ideograms task (nonverbal). The PD patients displayed impairments in the nonverbal tasks only, namely, in the SRT task and the pairs of Japanese ideograms task. No correlation between Wisconsin Card Sorting Test (WCST) scores and the results of tasks in which PD patients displayed deficits (SRT and pairs of Japanese ideograms) were discovered. Interestingly, such a correlation was found in the case of MR and words pairs tasks, which did not distinguish PD patients from control group.

Neural Correlates of Facial Mimicry: Simultaneous Measurements of EMG and BOLD Responses during Perception of Dynamic Compared to Static Facial Expressions.

Facial mimicry (FM) is an automatic response to imitate the facial expressions of others. However, neural correlates of the phenomenon are as yet not well established. We investigated this issue using simultaneously recorded EMG and BOLD signals during perception of dynamic and static emotional facial expressions of happiness and anger. During display presentations, BOLD signals and zygomaticus major (ZM), corrugator supercilii (CS) and orbicularis oculi (OO) EMG responses were recorded simultaneously from 46 healthy individuals. Subjects reacted spontaneously to happy facial expressions with increased EMG activity in ZM and OO muscles and decreased CS activity, which was interpreted as FM. Facial muscle responses correlated with BOLD activity in regions associated with motor simulation of facial expressions [i.e., inferior frontal gyrus, a classical Mirror Neuron System (MNS)]. Further, we also found correlations for regions associated with emotional processing (i.e., insula, part of the extended MNS). It is concluded that FM involves both motor and emotional brain structures, especially during perception of natural emotional expressions.

Cognitive inhibition in patients with medial orbitofrontal damage.

Inhibition underlies cognitive processes such as overcoming habitual responses, suppressing of goal-irrelevant information, and switching of attention between stimuli or task rules. These processes are thought to depend on the frontal lobes. However, the precise role of the ventral frontal regions (orbitofrontal cortex) in these processes remains elusive. In the present study, our goal was to clarify the role of the orbitofrontal cortex in cognitive inhibition by examining the effects of focal lesions to the medial orbitofrontal cortex (posterior part of the gyrus rectus) on performance in tasks that required inhibitory control. Patients who had undergone surgery for an anterior communicating artery aneurysm and normal control subjects (C) participated in the study. The patients were subdivided into three groups: those with resection of the left (LGR+) or right (RGR+) gyrus rectus, and without such a resection (GR-). The Stroop Color-Word test, Trail Making B test, and the Category test were used as instruments for assessing response inhibition, switching between concrete stimuli, and switching between abstract task rules, respectively. In addition, the Digit Symbol test was used to examine sustained attention and processing speed. In the Stroop Color-Word test, the RGR+ group performed worse than all other groups. In the Trail Making B test, the RGR+ and LGR+ groups performed worse than both the GR- and C groups. In the Category test and Digit Symbol test, the groups did not differ significantly from each other. Our study indicates a specific contribution of the medial orbitofrontal cortex to response inhibition and stimulus-based switching of attention.

Functional organization of the human amygdala in appetitive learning.

The amygdala is a small subcortical structure located bilaterally in medial temporal lobes. It is a key region for emotional processes and some forms of associative learning. In particular, the role of the amygdala in processing of negative emotions and aversive learning has been shown in numerous studies. However, involvement of this structure in processing of positive affect and appetitive learning is not fully understood. Previous experiments in animals are not consistent. While some authors implicate only the centromedial part of the amygdala in appetitive learning, the others suggest contribution of both centromedial and basolateral subregions. Although from the evolutionary perspective appetitive learning is equally important as aversive learning, research on the role of the human amygdala and its subregions in appetitive learning is undertaken relatively rarely and the results are not conclusive. Therefore, the aim of this review is twofold: to summarize the current knowledge in this field and to indicate and discuss the factors, which might affect the observed level of the amygdala activity during appetitive learning in humans.

More intelligent extraverts are more likely to deceive.

The tendency to lie is a part of personality. But are personality traits the only factors that make some people lie more often than others? We propose that cognitive abilities have equal importance. People with higher cognitive abilities are better, and thus more effective liars. This might reinforce using lies to solve problems. Yet, there is no empirical research that shows this relationship in healthy adults. Here we present three studies in which the participants had free choice about their honesty. We related differences in cognitive abilities and personality to the odds of lying. Results show that personality and intelligence are both important. People low on agreeableness and intelligent extraverts are most likely to lie. This suggests that intelligence might mediate the relationship between personality traits and lying frequency. While personality traits set general behavioral tendencies, intelligence and environment set boundaries.

Lateralization of repetition effects in event-related potentials to words in left- and right-handed women.

In our previous event-related potential (ERP) study [A. Nowicka, I. Szatkowska, Memory-induced modulation of event-related potentials in frontal cortex of human subjects: a divided visual field study, Neurosci. Lett. 359 (2004) 171-174], word repetition effects in right-handed males were observed only in case of the direct stimulation of the left (competent) hemisphere. Since the left-handedness and the factor of female gender may determine the lateralization of verbal functions, the goal of the present study was to test the sensitivity of the ERP repetition effects to the visual field of word presentation in the group of left- and right-handed women. ERPs were recorded from symmetrical sites over the left and right hemisphere. Target words were presented in the left (LVF) or right (RVF) visual hemifield. Subjects' were instructed to recognize the target word on a response card. A substantial portion of words was repeated twice. Words elicited different ERPs at frontal sites when presented the first and second times: ERPs were more positive to the repeated stimulus than to its first occurrence. However, in right-handed participants, repetition effects were only observed when target words were presented to the RVF whereas in left-handed participants, repetition effects were only observed when target words were presented to the LVF. These findings are indicative of the asymmetrical involvement of the two hemispheres in memory-induced modulation of brain activity related to verbal processing in left- and right-handed women.

[Growth hormone signaling pathways]. / Szlaki sygnalowe hormonu wzrostu.

The substantial improvement in the studies on a very complicated mechanism-- growth hormone signaling in a cell, has been noted in last decade. GH-induced signaling is characterized by activation of several pathways, including extracellular signal-regulated kinase (ERK), the signal transducer and activator of transcription and phosphatidylinositol-3 kinase (PI3) pathways. This review shows a current model of the growth hormone receptor dimerization, rotation of subunits and JAK2 kinase activation as the initial steps in the cascade of events. In the next stages of the signaling process, the GH-(GHR)2-(JAK2)2 complex may activate signaling molecules such as Stat, IRS-1 and IRS-2, and particularly all cascade proteins that activate MAP kinase. These pathways regulate basal cellular functions including target gene transcription, enzymatic activity and metabolite transport. Therefore growth hormone is considered as a major regulator of postnatal growth and metabolism, probably for mammary gland growth and development too.

Do Dynamic Compared to Static Facial Expressions of Happiness and Anger Reveal Enhanced Facial Mimicry?

Facial mimicry is the spontaneous response to others' facial expressions by mirroring or matching the interaction partner. Recent evidence suggested that mimicry may not be only an automatic reaction but could be dependent on many factors, including social context, type of task in which the participant is engaged, or stimulus properties (dynamic vs static presentation). In the present study, we investigated the impact of dynamic facial expression and sex differences on facial mimicry and judgment of emotional intensity. Electromyography recordings were recorded from the corrugator supercilii, zygomaticus major, and orbicularis oculi muscles during passive observation of static and dynamic images of happiness and anger. The ratings of the emotional intensity of facial expressions were also analysed. As predicted, dynamic expressions were rated as more intense than static ones. Compared to static images, dynamic displays of happiness also evoked stronger activity in the zygomaticus major and orbicularis oculi, suggesting that subjects experienced positive emotion. No muscles showed mimicry activity in response to angry faces. Moreover, we found that women exhibited greater zygomaticus major muscle activity in response to dynamic happiness stimuli than static stimuli. Our data support the hypothesis that people mimic positive emotions and confirm the importance of dynamic stimuli in some emotional processing.

Emotional Empathy and Facial Mimicry for Static and Dynamic Facial Expressions of Fear and Disgust.

Facial mimicry is the tendency to imitate the emotional facial expressions of others. Increasing evidence suggests that the perception of dynamic displays leads to enhanced facial mimicry, especially for happiness and anger. However, little is known about the impact of dynamic stimuli on facial mimicry for fear and disgust. To investigate this issue, facial EMG responses were recorded in the corrugator supercilii, levator labii, and lateral frontalis muscles, while participants viewed static (photos) and dynamic (videos) facial emotional expressions. Moreover, we tested whether emotional empathy modulated facial mimicry for emotional facial expressions. In accordance with our predictions, the highly empathic group responded with larger activity in the corrugator supercilii and levator labii muscles. Moreover, dynamic compared to static facial expressions of fear revealed enhanced mimicry in the high-empathic group in the frontalis and corrugator supercilii muscles. In the low-empathic group the facial reactions were not differentiated between fear and disgust for both dynamic and static facial expressions. We conclude that highly empathic subjects are more sensitive in their facial reactions to the facial expressions of fear and disgust compared to low empathetic counterparts. Our data confirms that personal characteristics, i.e., empathy traits as well as modality of the presented stimuli, modulate the strength of facial mimicry. In addition, measures of EMG activity of the levator labii and frontalis muscles may be a useful index of empathic responses of fear and disgust.