Limbic Areas Research Articles

Cortical Serotonergic and Catecholaminergic Denervation in MPTP-Treated Parkinsonian Monkeys.

Decreased cortical serotonergic and catecholaminergic innervation of the frontal cortex has been reported at early stages of Parkinson's disease (PD). However, the limited availability of animal models that exhibit these pathological features has hampered our understanding of the functional significance of these changes during the course of the disease. In the present study, we assessed longitudinal changes in cortical serotonin and catecholamine innervation in motor-symptomatic and asymptomatic monkeys chronically treated with low doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Densitometry and unbiased stereological techniques were used to quantify changes in serotonin and tyrosine hydroxylase (TH) immunoreactivity in frontal cortices of 3 control monkeys and 3 groups of MPTP-treated monkeys (motor-asymptomatic [N = 2], mild parkinsonian [N = 3], and moderate parkinsonian [N = 3]). Our findings revealed a significant decrease (P<0.001) in serotonin innervation of motor (Areas 4 and 6), dorsolateral prefrontal (Areas 9 and 46), and limbic (Areas 24 and 25) cortical areas in motor-asymptomatic MPTP-treated monkeys. Both groups of symptomatic MPTP-treated animals displayed further serotonin denervation in these cortical regions (P<0.0001). A significant loss of serotonin-positive dorsal raphe neurons was found in the moderate parkinsonian group. On the other hand, the intensity of cortical TH immunostaining was not significantly affected in motor asymptomatic MPTP-treated monkeys, but underwent a significant reduction in the moderate symptomatic group (P<0.05). Our results indicate that chronic intoxication with MPTP induces early pathology in the corticopetal serotonergic system, which may contribute to early non-motor symptoms in PD.

Autoimmune encephalitis and related disorders: A retrospective study of 43 cases in a tertiary hospital

BackgroundDespite progresses in autoimmune encephalitis and related disorders (AERD), they remain a major challenge in daily clinical practice. ObjectivesTo describe a tertiary hospital's longitudinal experience in AERD between 2005 and 2020. MethodsSingle-centre retrospective analysis of 43 patients. Results43 patients were included, 55.8% with positive antibodies (10 antiGAD, 4 antiNMDAR, 2 antiGABABR, 2 antiLGI1, 2 antiCASPR2, 1 antiIgLON5, 1 antiHu, 1 antiYo, 1 antiCV2 and 1 antiMa2, detecting coexisting antibodies in one patient: antiNMDAR+antiGABABR); 28% with negative antibodies; and 16.2% with steroid responsive encephalitis associated to antithyroid antibodies (SREAT). The median age was 62 years-old [14–88]. Females (62.8%) outnumbered males (37.2%). Limbic encephalitis was the most common clinical syndrome (60.5%), followed by SREAT (16.2%), autoimmune cerebellitis (9.3%), stiff-person syndrome (7%), antiNMDAR-encephalitis (5%) and antiIgLON5 encephalopathy (2%). CSF showed pleocytosis and/or hyperproteinorrhachia in 54.2%. MRI was unremarkable in 60%. Brain SPECT/PET showed hyperperfusion/hypermetabolism of limbic areas in 60% of patients to whom it was performed. Antibody-positivity was significantly associated with satisfaction of diagnostic criteria at high levels of certainty (p < 0.001). Treatment escalation was more frequent in antibody-positive patients. The creation of a Neuroimmunology Unit improved diagnostic and treatment approaches. ConclusionsAERD's diagnosis and treatment have significantly improved over the last years. However, several limitations remain, particularly concerning antibody-negative AERD. The proposed diagnostic criteria might be still too reliant on antibody-positivity. Antibody-status seems to condition treatment escalation. The creation of a Neuroimmunology Unit optimized AERD's management in clinical practice.

Serotonergic and Dopaminergic Lesions Underlying Parkinsonian Neuropsychiatric Signs.

Parkinson's disease (PD) is characterized by heterogeneous motor and nonmotor manifestations related to alterations in monoaminergic neurotransmission systems. Nevertheless, the characterization of concomitant dopaminergic and serotonergic dysfunction after different durations of Parkinson's disease, as well as their respective involvement in the expression and severity of neuropsychiatric signs, has gained little attention so far. To fill this gap, we conducted a cross-sectional study combining clinical and dual-tracer positron emission tomography (PET) neuroimaging approaches, using radioligands of dopamine ([11 C]-N-(3-iodoprop-2E-enyl)-2-beta-carbomethoxy-3-beta-(4-methylphenyl)-nortropane) ([11 C]PE2I) and serotonin ([11 C]-N,N-dimethyl-2-(-2-amino-4-cyanophenylthio)-benzylamine) ([11 C]DASB) reuptake, after different durations of Parkinson's disease (ie, in short-disease duration drug-naive de novo (n=27, 0-2 years-duration), suffering from apathy (n=14) or not (n=13); intermediate-disease duration (n=15, 4-7 years-duration) and long-disease duration, non-demented (n=15, 8-10 years-duration) patients). Fifteen age-matched healthy subjects were also enrolled. The main findings are threefold: (1) both dopaminergic and serotonergic lesions worsen with the duration of Parkinson's disease, spreading from midbrain/subcortical to cortical regions; (2) the presence of apathy at PD onset is associated with more severe cortical and subcortical serotonergic and dopaminergic disruption, similar to the denervation pattern observed in intermediate-disease duration patients; and (3) the severity of parkinsonian apathy, depression, and trait-anxiety appears primarily related to serotonergic alteration within corticostriatal limbic areas. Altogether, these findings highlight the prominent role of serotonergic degeneration in the expression of several neuropsychiatric symptoms occurring after different durations of Parkinson's disease. © 2021 International Parkinson and Movement Disorder Society.

Quantitative synthetic MRI reveals grey matter abnormalities in children with drug-naïve attention-deficit/hyperactivity disorder.

To investigate the quantitative profiles of brain grey matter (GM) in pediatric drug-naïve ADHD patients using synthetic magnetic resonance imaging (SyMRI). A total of 37 drug-naïve pediatric ADHD and 27 age- and gender-matched healthy controls (HC) were enrolled in this study. Each subject underwent both SyMRI and conventional 3D T1-FSPGR scans. Quantitative parameters, T1 and T2 maps, were extracted from the SyMRI data. Between-group quantitative maps were compared using a general linear model analysis. Pearson correlation analysis was conducted to assess the association between significantly altered MR indices and clinical measurements in ADHD. Compared with the HC group, altered T1 and T2 relaxometry times in the ADHD group were mainly distributed in GM regions of the cerebellum, attention and execution control network, default mode network, and limbic areas. Moreover, the T1 value of the right cerebellum 8 was negatively correlated with the attention concentration level in ADHD (R = 0.140, P = 0.0225). With regards to T2 map, the associations were observed between the attention level of ADHD patients and left fusiform gyrus (R = 0.251, P = 0.0016), and right cerebellum crus2 (R = 0.142, P = 0.0214). Altered T1, T2 values found in specific regions of GM, including cerebellum, attention and execution control network, default mode network, and limbic areas, may reveal widespread micromorphology changes, i.e., brain iron deficiency, low myelin content, and enlarged vascular interstitial space in ADHD patients. Thus, T1, T2 values might be promising imaging markers for future ADHD studies.

Deep Learning-Based Assessment of Brain Connectivity Related to Obstructive Sleep Apnea and Daytime Sleepiness.

PurposeObstructive sleep apnea (OSA) is associated with altered pairwise connections between brain regions, which might explain cognitive impairment and daytime sleepiness. By adopting a deep learning method, we investigated brain connectivity related to the severity of OSA and daytime sleepiness.Patients and MethodsA cross-sectional design applied a deep learning model on structural brain networks obtained from 553 subjects (age, 59.2 ± 7.4 years; men, 35.6%). The model performance was evaluated with the Pearson’s correlation coefficient (R) and probability of absolute error less than standard deviation (PAE<SD) between the estimated and the actual scores. In addition, we investigated sex effects on deep learning outputs for OSA and daytime sleepiness and examined the differences in brain connectivity related to daytime sleepiness between OSA and non-OSA groups.ResultsWe achieved a meaningful R (up to 0.74) and PAE<SD (up to 0.92) in a test dataset of whole group and subgroups. Motor, frontal and limbic areas, and default mode network were the prominent hubs of important connectivity to predict OSA severity and daytime sleepiness. Sex affected brain connectivity relevant to OSA severity as well as daytime sleepiness. Brain connectivity associated with daytime sleepiness also differed by the presence vs absence of OSA.ConclusionA deep learning method can assess the association of brain network characteristics with OSA severity and daytime sleepiness and specify the relevant brain connectivity.

Selective Serotonin Reuptake Inhibitors and Clozapine: Clinically Relevant Interactions and Considerations.

The monoamine hypothesis of depression attributes the symptoms of major depressive disorders to imbalances of serotonin, noradrenaline, and dopamine in the limbic areas of the brain. The preferential targeting of serotonin receptor (SERT) by selective serotonin reuptake inhibitors (SSRIs) has offered an opportunity to reduce the range of these side effects and improve patient adherence to pharmacotherapy. Clozapine remains an effective drug against treatment-resistant schizophrenia, defined as failing treatment with at least two different antipsychotic medications. Patients with schizophrenia who display a constellation of negative symptoms respond poorly to antipsychotic monotherapy. Negative symptoms include the diminution of motivation, interest, or expression. Conversely to the depressive symptomology of interest presently, supplementation of antipsychotics with SSRIs in schizophrenic patients with negative symptoms lead to synergistic improvements in the function of these patients. Fluvoxamine is one of the most potent inhibitors of CYP1A2 and can lead to an increase in clozapine levels. Similar increases in serum clozapine were detected in two patients taking sertraline. However, studies have been contradictory as well, showing no such increases, which are worrying. Clinicians should be aware that clozapine levels should be monitored with any coadministration with SSRIs.

Urocortin-3 neurons in the mouse perifornical area promote infant-directed neglect and aggression.

While recent studies have uncovered dedicated neural pathways mediating the positive control of parenting, the regulation of infant-directed aggression and how it relates to adult-adult aggression is poorly understood. Here we show that urocortin-3 (Ucn3)-expressing neurons in the hypothalamic perifornical area (PeFAUcn3) are activated during infant-directed attacks in males and females, but not other behaviors. Functional manipulations of PeFAUcn3 neurons demonstrate the role of this population in the negative control of parenting in both sexes. PeFAUcn3 neurons receive input from areas associated with vomeronasal sensing, stress, and parenting, and send projections to hypothalamic and limbic areas. Optogenetic activation of PeFAUcn3 axon terminals in these regions triggers various aspects of infant-directed agonistic responses, such as neglect, repulsion, and aggression. Thus, PeFAUcn3 neurons emerge as a dedicated circuit component controlling infant-directed neglect and aggression, providing a new framework to understand the positive and negative regulation of parenting in health and disease.

Pattern of TAAR5 Expression in the Human Brain Based on Transcriptome Datasets Analysis.

Trace amine-associated receptors (TAAR) recognize organic compounds, including primary, secondary, and tertiary amines. The TAAR5 receptor is known to be involved in the olfactory sensing of innate socially relevant odors encoded by volatile amines. However, emerging data point to the involvement of TAAR5 in brain functions, particularly in the emotional behaviors mediated by the limbic system which suggests its potential contribution to the pathogenesis of neuropsychiatric diseases. TAAR5 expression was explored in datasets available in the Gene Expression Omnibus, Allen Brain Atlas, and Human Protein Atlas databases. Transcriptomic data demonstrate ubiquitous low TAAR5 expression in the cortical and limbic brain areas, the amygdala and the hippocampus, the nucleus accumbens, the thalamus, the hypothalamus, the basal ganglia, the cerebellum, the substantia nigra, and the white matter. Altered TAAR5 expression is identified in Down syndrome, major depressive disorder, or HIV-associated encephalitis. Taken together, these data indicate that TAAR5 in humans is expressed not only in the olfactory system but also in certain brain structures, including the limbic regions receiving olfactory input and involved in critical brain functions. Thus, TAAR5 can potentially be involved in the pathogenesis of brain disorders and represents a valuable novel target for neuropsychopharmacology.

Conditional Inactivation of Limbic Neuropeptide Y-1 Receptors Increases Vulnerability to Diet-Induced Obesity in Male Mice.

NPY and its Y1 cognate receptor (Y1R) have been shown to be involved in the regulation of stress, anxiety, depression and energy homeostasis. We previously demonstrated that conditional knockout of Npy1r gene in the excitatory neurons of the forebrain of adolescent male mice (Npy1rrfb mice) decreased body weight growth and adipose tissue and increased anxiety. In the present study, we used the same conditional system to examine whether the targeted disruption of the Npy1r gene in limbic areas might affect susceptibility to obesity and associated disorders during adulthood in response to a 3-week high-fat diet (HFD) regimen. We demonstrated that following HFD exposure, Npy1rrfb male mice showed increased body weight, visceral adipose tissue, and blood glucose levels, hyperphagia and a dysregulation of calory intake as compared to control Npy1r2lox mice. These results suggest that low expression of Npy1r in limbic areas impairs habituation to high caloric food and causes high susceptibility to diet-induced obesity and glucose intolerance in male mice, uncovering a specific contribution of the limbic Npy1r gene in the dysregulation of the eating/satiety balance.

Dreaming the unrepressed unconscious and beyond: repression vs dissociation in the oneiric functioning of severe patients.

Starting with Freud and Jung, dreams have always been considered a core source of information for psychoanalysis. Nowadays, neuroscientific findings suggest that dreams are related especially to limbic and right emotional brain circuit, and that during REM stages they engage self-related and visual internally generated processing. These neuroscientific findings together with contemporary psychoanalysis suggest that dreams are related to the sense of self and serve the purpose of re-integrating and re-structuring the integrity of the psyche. However, while dreams are still viewed as ‘the via regia to the unconscious’, it is the unconscious that has been reconsidered. The repressed unconscious seems to be related with left brain activity while the unrepressed unconscious based on dissociation seems to be associated with limbic and cortical areas of the right hemisphere. This notion of the unconscious might be seen as an implicit self-system encoded in the right brain that evolves in the interaction with a primary caregiver developing through preverbal and bodily stages of maturation enhanced by signals of dual communication. What kind of dreams for which unconscious? What are the differences regarding the capacity to dream for neurotic and borderline personality organizations? Our research aims to integrate psychodynamics, infant research, and neuroscientific findings to better understand the role of dreams in the assessment and treatment of, especially, traumatized and borderline patients. The capacity to dream is here proposed as a sort of enacted manifestation of emotional memories for the development of a more cohesive, coherent and symbolic vs fragmented, diffuse and alexithymic sense of self.

Evolution of prefrontal cortex.

Subdivisions of the prefrontal cortex (PFC) evolved at different times. Agranular parts of the PFC emerged in early mammals, and rodents, primates, and other modern mammals share them by inheritance. These are limbic areas and include the agranular orbital cortex and agranular medial frontal cortex (areas 24, 32, and 25). Rodent research provides valuable insights into the structure, functions, and development of these shared areas, but it contributes less to parts of the PFC that are specific to primates, namely, the granular, isocortical PFC that dominates the frontal lobe in humans. The first granular PFC areas evolved either in early primates or in the last common ancestor of primates and tree shrews. Additional granular PFC areas emerged in the primate stem lineage, as represented by modern strepsirrhines. Other granular PFC areas evolved in simians, the group that includes apes, humans, and monkeys. In general, PFC accreted new areas along a roughly posterior to anterior trajectory during primate evolution. A major expansion of the granular PFC occurred in humans in concert with other association areas, with modifications of corticocortical connectivity and gene expression, although current evidence does not support the addition of a large number of new, human-specific PFC areas.

The olfactory bulbectomy disease model: A Re-evaluation.

The olfactory bulbectomized rodent has long been one of the preferred animal models of depression and certain other neuropsychiatric diseases. In fact, it is considered unparalleled, by some, in the search for antidepressant medication and the literature generated about the model is prodigious. We have revisited the “syndrome” of behavioral sequela following bulbectomy choosing ecologically valid tests likely to be underpinned with evolutionarily preserved neural circuits. Our test battery included measurements of activity, intermale aggression, pleasure seeking, stress/fear and non-spatial memory. The emphasis was on the timetable of syndrome emergence, since this has been understudied and bears on the widely held belief that non-olfactory effects dominate. Our results largely agree with previous reports describing the behavioral syndrome in that we document bulbectomized mice as hyperactive, non-aggressive and fearless. However, we did not find deficits in memory as have frequently been reported in previous studies. Notably, our results revealed that some syndrome behaviors—including the hallmark of hyperactivity—appear immediately or soon after surgery. This rapid appearance casts doubt on the widely held view that compensatory reorganization of limbic and prefrontal cortical areas following bulbectomy underlies the syndrome. Rather, hyperactivity, non-aggressiveness, reduced fear and diminished sucrose preference in the olfactory bulbectomized mouse find ready explanations in the loss of smell that is the immediate and irreversible outcome of bulbectomy. Finally, after a critical consideration of the literature and our results, we conclude that the olfactory bulbectomy model lacks the validity and simplicity previously credited to it. Indeed, we deem this lesion unsuitable as a model of most neuropsychiatric diseases since its effects are at least as complex and misunderstood as the disorders it is purported to model.

Placental CRH as a Signal of Pregnancy Adversity and Impact on Fetal Neurodevelopment.

Early life is a period of considerable plasticity and vulnerability and insults during that period can disrupt the homeostatic equilibrium of the developing organism, resulting in adverse developmental programming and enhanced susceptibility to disease. Fetal exposure to prenatal stress can impede optimum brain development and deranged mother’s hypothalamic–pituitary–adrenal axis (HPA axis) stress responses can alter the neurodevelopmental trajectories of the offspring. Corticotropin-releasing hormone (CRH) and glucocorticoids, regulate fetal neurogenesis and while CRH exerts neuroprotective actions, increased levels of stress hormones have been associated with fetal brain structural alterations such as reduced cortical volume, impoverishment of neuronal density in the limbic brain areas and alterations in neuronal circuitry, synaptic plasticity, neurotransmission and G-protein coupled receptor (GPCR) signalling. Emerging evidence highlight the role of epigenetic changes in fetal brain programming, as stress-induced methylation of genes encoding molecules that are implicated in HPA axis and major neurodevelopmental processes. These serve as molecular memories and have been associated with long term modifications of the offspring’s stress regulatory system and increased susceptibility to psychosomatic disorders later in life. This review summarises our current understanding on the roles of CRH and other mediators of stress responses on fetal neurodevelopment.

Perineuronal Net Receptor PTPσ Regulates Retention of Memories.

Perineuronal nets (PNNs) have an important physiological role in the retention of learning by restricting cognitive flexibility. Their deposition peaks after developmental periods of intensive learning, usually in late childhood, and they help in long-term preservation of newly acquired skills and information. Modulation of PNN function by various techniques enhances plasticity and regulates the retention of memories, which may be beneficial when memory persistence entails negative symptoms such as post-traumatic stress disorder (PTSD). In this study, we investigated the role of PTPσ [receptor-type tyrosine-protein phosphatase S, a phosphatase that is activated by binding of chondroitin sulfate proteoglycans (CSPGs) from PNNs] in retention of memories using Novel Object Recognition and Fear Conditioning models. We observed that mice haploinsufficient for PTPRS gene (PTPσ+/–), although having improved short-term object recognition memory, display impaired long-term memory in both Novel Object Recognition and Fear Conditioning paradigm, as compared to WT littermates. However, PTPσ+/– mice did not show any differences in behavioral tests that do not heavily rely on cognitive flexibility, such as Elevated Plus Maze, Open Field, Marble Burying, and Forced Swimming Test. Since PTPσ has been shown to interact with and dephosphorylate TRKB, we investigated activation of this receptor and its downstream pathways in limbic areas known to be associated with memory. We found that phosphorylation of TRKB and PLCγ are increased in the hippocampus, prefrontal cortex, and amygdaloid complex of PTPσ+/– mice, but other TRKB-mediated signaling pathways are not affected. Our data suggest that PTPσ downregulation promotes TRKB phosphorylation in different brain areas, improves short-term memory performance but disrupts long-term memory retention in the tested animal models. Inhibition of PTPσ or disruption of PNN-PTPσ-TRKB complex might be a potential target for disorders where negative modulation of the acquired memories can be beneficial.

Lifestyle Interventions Improving Cannabinoid Tone During COVID-19 Lockdowns May Enhance Compliance With Preventive Regulations and Decrease Psychophysical Health Complications.

Studies investigating the psychosomatic effects of social isolation in animals have shown that one of the physiologic system that gets disrupted by this environment-affective change is the Endocannabinoid System. As the levels of endocannabinoids change in limbic areas and prefrontal cortex during stressful times, so is the subject more prone to fearful and negative thoughts and aggressive behavior. The interplay of social isolation on the hypothalamic-pituitary-adrenal axis and cannabinoid tone triggers a vicious cycle which further impairs the natural body's homeostatic neuroendocrine levels and provokes a series of risk factors for developing health complications. In this paper, we explore the psychosomatic impact of prolonged quarantine in healthy individuals, and propose management and coping strategies that may improve endocannabinoid tone, such as integration of probiotics, cannabidiol, meditation, and physical exercise interventions with the aim of supporting interpersonal, individual, and professional adherence with COVID-19 emergency public measures whilst minimizing their psycho-physical impact.

Connectome analysis of male world-class gymnasts using probabilistic multishell, multitissue constrained spherical deconvolution tracking.

In athletes, long‐term intensive training has been shown to increase unparalleled athletic ability and might induce brain plasticity. We evaluated the structural connectome of world‐class gymnasts (WCGs), as mapped by diffusion‐weighted magnetic resonance imaging probabilistic tractography and a multishell, multitissue constrained spherical deconvolution method to increase the precision of tractography at the tissue interfaces. The connectome was mapped in 10 Japanese male WCGs and in 10 age‐matched male controls. Network‐based statistic identified subnetworks with increased connectivity density in WCGs, involving the sensorimotor, default mode, attentional, visual, and limbic areas. It also revealed a significant association between the structural connectivity of some brain structures with functions closely related to the gymnastic skills and the D‐score, which is used as an index of the gymnasts' specific physical abilities for each apparatus. Furthermore, graph theory analysis demonstrated the characteristics of brain anatomical topology in the WCGs. They displayed significantly increased global connectivity strength with decreased characteristic path length at the global level and higher nodal strength and degree in the sensorimotor, default mode, attention, and limbic/subcortical areas at the local level as compared with controls. Together, these findings extend the current understanding of neural mechanisms that distinguish WCGs from controls and suggest brain anatomical network plasticity in WCGs resulting from long‐term intensive training. Future studies should assess the contribution of genetic or early‐life environmental factors in the brain network organization of WCGs. Furthermore, the indices of brain topology (i.e., connection density and graph theory indices) could become markers for the objective evaluation of gymnastic performance.

Minor Changes in Erythrocyte Osmotic Fragility in Trace Amine-Associated Receptor 5 (TAAR5) Knockout Mice.

Trace amine-associated receptors (TAARs) are a group of G protein-coupled receptors that are expressed in the olfactory epithelium, central nervous system, and periphery. TAAR family generally consists of nine types of receptors (TAAR1-9), which can detect biogenic amines. During the last 5 years, the TAAR5 receptor became one of the most intriguing receptors in this subfamily. Recent studies revealed that TAAR5 is involved not only in sensing socially relevant odors but also in the regulation of dopamine and serotonin transmission, emotional regulation, and adult neurogenesis by providing significant input from the olfactory system to the limbic brain areas. Such results indicate that future antagonistic TAAR5-based therapies may have high pharmacological potential in the field of neuropsychiatric disorders. TAAR5 is known to be expressed in leucocytes as well. To evaluate potential hematological side effects of such future treatments we analyzed several hematological parameters in mice lacking TAAR5. In these mutants, we observed minor but significant changes in the osmotic fragility test of erythrocytes and hematocrit levels. At the same time, analysis of other parameters including complete blood count and reticulocyte levels showed no significant alterations in TAAR5 knockout mice. Thus, TAAR5 gene knockout leads to minor negative changes in the erythropoiesis or eryptosis processes, and further research in that field is needed. The impact of TAAR5 deficiency on other hematological parameters seems minimal. Such negative, albeit minor, effects of TAAR5 deficiency should be taken into account during future TAAR5-based therapy development.

Anterior Cingulate Cortex Activity During Rest Is Related to Alterations in Pain Perception in Aging.

Alterations in the affective component of pain perception are related to the development of chronic pain and may contribute to the increased vulnerability to pain observed in aging. The present study analyzed age-related changes in resting-state brain activity and their possible relation to an increased pain perception in older adults. For this purpose, we compared EEG current source density and fMRI functional-connectivity at rest in older (n = 20, 66.21 ± 3.08 years) and younger adults (n = 21, 20.71 ± 2.30 years) and correlated those brain activity parameters with pain intensity and unpleasantness ratings elicited by painful stimulation. We found an age-related increase in beta2 and beta3 activity in temporal, frontal, and limbic areas, and a decrease in alpha activity in frontal areas. Moreover, older participants displayed increased functional connectivity in the anterior cingulate cortex (ACC) and the insula with precentral and postcentral gyrus. Finally, ACC beta3 activity was positively correlated with pain intensity and unpleasantness ratings in older, and ACC-precentral/postcentral gyrus connectivity was positively correlated with unpleasantness ratings in older and younger participants. These results reveal that ACC resting-state hyperactivity is a stable trait of brain aging and may underlie their characteristic altered pain perception.

Neural Responses of Pet Dogs Witnessing Their Caregiver's Positive Interactions with a Conspecific: An fMRI Study.

We have limited knowledge on how dogs perceive humans and their actions. Various researchers investigated how they process human facial expressions, but their brain responses to complex social scenarios remain unclear. While undergoing fMRI, we exposed pet dogs to videos showing positive social and neutral nonsocial interactions between their caregivers and another conspecific. Our main interest was how the dogs responded to their caregivers (compared to a stranger) engaging in a pleasant interaction with another dog that could be seen as social rival. We hypothesized that the dogs would show activation increases in limbic areas such as the amygdala, hypothalamus, and insula and likely show higher attention and arousal during the positive caregiver–dog interaction. When contrasting the social with the nonsocial interaction, we found increased activations in the left amygdala and the insular cortex. Crucially, the dogs’ hypothalamus showed strongest activation when the caregiver engaged in a positive social interaction. These findings indicate that dogs are sensitive to social affective human–dog interactions and likely show higher valence attribution and arousal in a situation possibly perceived as a potential threat to their caregiver bonds. Our study provides a first window into the neural correlates of social and emotional processing in dogs.

Brain Knows Who Is on the Same Wavelength: Resting-State Connectivity Can Predict Compatibility of a Female-Male Relationship.

Prediction of the initial compatibility of heterosexual individuals based on self-reported traits and preferences has not been successful, even with significantly developed information technology. To overcome the limitations of self-reported measures and predict compatibility, we used functional connectivity profiles from resting-state functional magnetic resonance imaging (fMRI) data that carry rich individual-specific information sufficient to predict psychological constructs and activation patterns during social cognitive tasks. Several days after collecting data from resting-state fMRIs, participants undertook a speed-dating experiment in which they had a 3-min speed date with every other opposite-sex participant. Our machine learning algorithm successfully predicted whether pairs in the experiment were compatible or not using (dis)similarity of functional connectivity profiles obtained before the experiment. The similarity and dissimilarity of functional connectivity between individuals and these multivariate relationships contributed to the prediction, hence suggesting the importance of complementarity (observed as dissimilarity) as well as the similarity between an individual and a potential partner during the initial attraction phase. The result indicates that the salience network, limbic areas, and cerebellum are especially important for the feeling of compatibility. This research emphasizes the utility of neural information to predict complex phenomena in a social environment that behavioral measures alone cannot predict.