Anterior Cingulate Research Articles

The analgesic effect of acupuncture in neuropathic pain: regulatory mechanisms of DNA methylation in the brain

Abstract Recent research has demonstrated that chronic pain, resulting from peripheral nerve injury, leads to various symptoms, including not only allodynia and hyperalgesia but also anxiety, depression, and cognitive impairment. These symptoms are believed to arise due to alterations in gene expression and neural function, mediated by epigenetic changes in chromatin structure. Emerging evidence suggests that acupuncture can modulate DNA methylation within the central nervous system, contributing to pain relief and the mitigation of comorbidities. Specifically, acupuncture has been shown to adjust the DNA methylation of genes related to mitochondrial dysfunction, oxidative phosphorylation, and inflammation pathways within cortical regions, such as the prefrontal cortex, anterior cingulate cortex, and primary somatosensory cortex. In addition, it influences the DNA methylation of genes associated with neurogenesis in hippocampal neurons. This evidence indicates that acupuncture, a treatment with fewer side effects compared with conventional medications, could offer an effective strategy for pain management.

The regulatory effect of the anterior cingulate cortex on helping behavior in juvenile social isolation model mice

Social isolation during adolescence negatively impacts the development of adult social behaviors. However, the exact link between social experiences during adolescence and social behaviors in adulthood is not fully understood. In the present study, we investigated how isolation during juvenility affects harm avoidance behavior in a mouse model of juvenile social isolation. We found that mice subjected to social isolation as juveniles display atypical harm avoidance behaviors and that neurons in the anterior cingulate cortex are involved in these abnormal behaviors. Furthermore, we discovered that the chemogenetic activation of anterior cingulate cortex pyramidal neurons can rescue impaired harm-avoidance behaviors in these mice. Our findings provide valuable insights into the potential mechanisms underlying the impact of social experiences on behavior and brain function. Understanding how social isolation during crucial developmental periods can lead to alterations in behavior opens up new avenues for exploring therapeutic interventions for neuropsychiatric disorders characterized by impaired prosocial behaviors.

Social risk coding by amygdala activity and connectivity with dorsal anterior cingulate cortex.

Risk is a fundamental factor affecting individual and social economic decisions, but its neural correlates are largely unexplored in the social domain. The amygdala, together with the dorsal anterior cingulate cortex (dACC), is thought to play a central role in risk taking. Here, we investigated in human volunteers (n=20; 11 females) how risk (defined as variance of reward probability distributions) in a social situation affects decisions and concomitant neural activity as measured with fMRI. We found separate variance-risk signals for social and non-social outcomes in the amygdala. Specifically, amygdala activity increased parametrically with social reward variance of presented choice options and on separate trials with non-social reward variance. Behaviorally, 75% of participants were averse to social risk as estimated in a Becker-DeGroot-Marschak auction-like procedure. The stronger this aversion, the more negative was the coupling between risk-related amygdala regions and dACC. This negative relation was significant for social risk attitude but not for the attitude towards variance-risk in juice outcomes. Our results indicate that the amygdala and its coupling with dACC process objective and subjectively evaluated social risk. Moreover, while social risk can be captured with a framework originally established by finance theory for non-social risk, the amygdala appears to processes social risk largely separately from non-social risk.Significance statement Risk-the uncertainty of outcomes-has profound effects on decision-making and behavior. In social situations, uncertainty about others' behavior ('social risk') similarly guides our decisions and can contribute to social anxiety. Surprisingly little is known about the neural mechanisms processing social risk. Here we investigated neural activity when humans evaluated social risk derived from the uncertainty of personal compliments received from social partners. Activity in the amygdala, a brain structure implicated in emotion and social behavior, reflected social risk levels. Amygdala functional connectivity to the anterior cingulate cortex reflected individuals' aversion to social risk. Our findings extend risk evaluation into the social domain and pave the way for investigating social risk attitude in mental-health impairments, including social anxiety.

Effects of electroacupuncture at auricular points on excitability of glutamatergic neurons in the anterior cingulate cortex of posttraumatic stress disorder mice

To elucidate the relationship between the auricular point stimulation and the activity of glutamatergic neurons in the anterior cingulate cortex (ACC) from the perspective of intrinsic excitability plasticity of neurons in mice with posttraumatic stress disorder (PTSD), so as to explore the underlying mechanisms of acupuncture at auricular points in improving emotional diseases induced by PTSD. C57BL/6J male mice were randomly divided into control, PTSD model, sham electroacupuncture (EA), and EA groups, with 5 mice in each group. The glutamatergic neurons were labelled by injection of AAV2/9-CaMKⅡα-EGFP viral fluid into the bilateral ACC. Fourteen days after the injection, the PTSD model was established by single prolonged stress (restraint stress, forced swimming, ether exposure) and plantar electrical shock. EA (2 Hz/15 Hz, 1 mA) was applied to bilateral "Xin" points and the center of auriculae of auricular concha area for 30 min, once daily for 7 days. Mice of the sham EA group were anesthetized for 30 min per day for 7 days, but no EA treatments were given. The anxiety-like behavior of mice was evaluated by open field (OF) and elevated plus maze (EPM) tests after 2 weeks of modeling. The whole-cell patch-clamp method was used to record the intrinsic excitability level of ACC glutamatergic neurons. Compared with the control group, the dwell time and locomotor distance in the central area of the OF, the dwell time and entry times percentage in the open arms of the EPM in the model group were significantly reduced (P<0.001, P<0.01). At the same time, the intrinsic excitability of ACC glutamatergic neurons in model mice was suppressed, presenting as enhanced rheobase currents (P<0.01) and decreased spike number (P<0.05, P<0.01, P<0.001). Compared with the model group, the dwell time and locomotor distance in the central area of the OF, the dwell time and entry times percentage in the open arms of the elevated plus maze were significantly increased (P<0.001, P<0.01), and the intrinsic excitability of ACC glutamatergic neurons was significantly improved, presenting as reduced rheobase currents (P<0.05) and an increased spike number (P<0.05) in the EA group. Compared with the sham EA group, the dwell time and locomotor distance in the central area of the OF, the dwell time and entry times percentage in the open arms of the EPM were significantly increased (P<0.001, P<0.01) in the EA group, and the intrinsic excitability of ACC glutamatergic neurons was significantly improved, presenting as reduced rheobase currents (P<0.01) and an increased spike number (P<0.05). EA of auricular points can effectively alleviate the anxiety-like behavior of PTSD mice and increase the intrinsic excitability level of glutamatergic neurons in ACC, which may be one of the neural mechanisms of auricular point stimulation in the treatment of emotional diseases.

Charting brain GABA and glutamate levels across psychiatric disorders by quantitative analysis of 121 1H-MRS studies.

Psychiatric diagnosis is based on categorical diagnostic classification, yet similarities in genetics and clinical features across disorders suggest that these classifications share commonalities in neurobiology, particularly regarding neurotransmitters. Glutamate (Glu) and gamma-aminobutyric acid (GABA), the brain's primary excitatory and inhibitory neurotransmitters, play critical roles in brain function and physiological processes. We examined the levels of Glu, combined glutamate and glutamine (Glx), and GABA across psychiatric disorders by pooling data from 121 1H-MRS studies and further divided the sample based on Axis I disorders. Statistically significant differences in GABA levels were found in the combined psychiatric group compared with healthy controls (Hedge's g = -0.112, p = 0.008). Further analyses based on brain regions showed that brain GABA levels significantly differed across Axis I disorders and controls in the parieto-occipital cortex (Hedge's g = 0.277, p = 0.019). Furthermore, GABA levels were reduced in affective disorders in the occipital cortex (Hedge's g = -0.468, p = 0.043). Reductions in Glx levels were found in neurodevelopmental disorders (Hedge's g = -0.287, p = 0.022). Analysis focusing on brain regions suggested that Glx levels decreased in the frontal cortex (Hedge's g = -0.226, p = 0.025), and the reduction of Glu levels in patients with affective disorders in the frontal cortex is marginally significant (Hedge's g = -0.172, p = 0.052). When analyzing the anterior cingulate cortex and prefrontal cortex separately, reductions were only found in GABA levels in the former (Hedge's g = - 0.191, p = 0.009) across all disorders. Altered glutamatergic and GABAergic metabolites were found across psychiatric disorders, indicating shared dysfunction. We found reduced GABA levels across psychiatric disorders and lower Glu levels in affective disorders. These results highlight the significance of GABA and Glu in psychiatric etiology and partially support rethinking current diagnostic categories.

Placebo Effects: Neurological Mechanisms Inducing Physiological, Organic, and Belief Responses—A Prospective Analysis

The placebo effect can induce physiological or clinical neurological and organic responses despite the recipient receiving no active ingredients; these responses are based instead on the recipient’s perceptions. Placebo effects come from the rostral anterior cingulate cortex, pontine nucleus, and cerebellum of the brain; this information provides a better understanding of placebo effects and can also help us understand the mechanism of the modulation of neurotransmitters from the use of psychedelic substances, activity of selective serotonin reuptake inhibitors, the process of transcranial magnetic stimulation, and deep brain stimulation, as well as aid in developing novel therapies, challenging the validity of controlled clinical trials (RCTs) that the regulatory agencies now appreciate. Education about how placebo effects bring in social, political, and religious beliefs and whether these can be modulated may help reduce global confrontations.

Exercise-induced reductions in central command network cerebral blood flow assessed with arterial spin labeling MRI

Abstract Habitual aerobic exercise positively impacts brain health. However, less is known about the acute effects of exercise on regional cerebral blood flow (CBF). Most studies have used exercise methods that required a 10-minute or longer delay before acquiring CBF data or methods that assessed global, rather than regional, CBF. In the current feasibility study, an aerobic exercise stimulus was administered using an MRI-compatible cardio step module connected to the MRI table. This allowed participants (N = 12, mean age = 20 years) to exercise at light-to-moderate intensity while in the bore of the MRI scanner. Pseudo-continuous arterial spin labeling MRI with multiple delays was collected on a 3T Siemens MRI scanner immediately pre- and post-exercise. CBF and arterial transit time changes were examined within the central command network, which impacts motor and cardiovascular systems during exercise. Associations with perceived exertion and cardiorespiratory fitness were assessed. CBF in central command regions decreased following exercise, with greater decreases in regions associated with cardiovascular control. For example, CBF in the left insula decreased by -9.03 ± 8.69 mL/100g/min (-11.45%, p &amp;lt; 0.01); CBF in the left and right rostral anterior cingulate decreased by -4.91 ± 6.08 mL/100g/min (-6.17%, p = 0.02) and by -5.04 ± 6.34 mL/100g/min (-7.43%, p = 0.02); and CBF in the left lateral orbitofrontal cortex decreased by -7.30 ± 8.11 mL/100g/min (-9.50%, p = 0.01). Decreased CBF was also associated with greater ratings of perceived exertion in cardiovascular command regions including right insula (r = -0.67, p = 0.03), medial orbitofrontal cortex (r = -0.64, p = 0.04), and lateral orbitofrontal cortex (r = -0.75, p = 0.01). The current study further demonstrates the feasibility of assessing CBF immediately following exercise using an exercise stimulus in the bore of the MRI scanner. These results contribute to a small but growing body of literature describing cerebral hemodynamics immediately following exercise.

Connectivity-Based Real-Time Functional Magnetic Resonance Imaging Neurofeedback in Nicotine Users: Mechanistic and Clinical Effects of Regulating a Meta-Analytically Defined Target Network in a Double-Blind Controlled Trial.

One of the fundamental questions in real-time functional magnetic resonance imaging neurofeedback (rt-fMRI NF) investigations is the definition of a suitable neural target for training. Previously, we applied a meta-analytical approach to define a network-level target for connectivity-based rt-fMRI NF in substance use disorders. The analysis yielded consistent connectivity alterations between the insula and anterior cingulate cortex (ACC) as well as the dorsal striatum and the ACC. In the current investigation, we addressed the feasibility of regulating this network and its functional relevance using connectivity-based neurofeedback. In a double-blind, sham-controlled design, 60 nicotine users were randomly assigned to the experimental or sham control group for one NF training session. The preregistered primary outcome was defined as improved inhibitory control performance after regulation of the target network compared to sham control. Secondary outcomes were (1) neurofeedback-specific changes in functional connectivity of the target network; (2) changes in smoking behavior and impulsivity measures; and (3) changes in resting-state connectivity profiles. Our results indicated no differences in behavioral measures after receiving feedback from the target network compared to the sham feedback. Target network connectivity was increased during regulation blocks compared to rest blocks, however, the experimental and sham groups could regulate to a similar degree. Accordingly, the observed activation patterns may be related to the mental strategies used during regulation attempts irrespective of the group assignment. We discuss several crucial factors regarding the efficacy of a single-session connectivity-based neurofeedback for the target network. This includes high fluctuation in the connectivity values of the target network that may impact controllability of the signal. To our knowledge, this investigation is the first randomized, double-blind controlled real-time fMRI study in nicotine users. This raises the question of whether previously observed effects in nicotine users are specific to the neurofeedback signal or reflect more general self-regulation attempts.

Application of proton magnetic resonance spectroscopy in metabolic alterations of prefrontal white and gray matter in depression adolescents

BACKGROUND Cases of depression among adolescents are gradually increasing. The study of the physiological basis of cognitive function from a biochemical perspective has therefore been garnering increasing attention. Depression has been hypothesized to be associated with the brain biochemical metabolism of the anterior cingulate gyrus, frontal lobe white matter, and the thalamus. AIM To explore the application of proton magnetic resonance spectroscopy (1H-MRS) in the metabolic alterations in the prefrontal white matter (PWM) and gray matter (GM) in adolescents with depression. METHODS 1H-MRS was performed for semi-quantitative analysis of the biochemical metabolites N-acetylaspartate (NAA), choline (Cho) complexes, creatine (Cr), and myo-inositol (mI) in bilateral PWM, anterior cingulate GM, and thalami of 31 adolescent patients with depression (research group) and 35 healthy adolescents (control group), and the NAA/Cr, Cho/Cr, and mI/Cr ratios were calculated. Meanwhile, Hamilton Depression Scale (HAMD) and Wechsler Memory Scale were used to assess the degree of depression and memory function in all adolescents. The correlation of brain metabolite levels with scale scores was also analyzed. RESULTS The research group had markedly higher HAMD-24 scores and lower memory quotient (MQ) compared with the control group (P &lt; 0.05). Adolescents with depression were found to have lower bilateral PWM NAA/Cr and Cho/Cr ratios compared with healthy adolescents (P &lt; 0.05). The mI/Cr ratios were found to be similar in both groups (P &gt; 0.05). The bilateral anterior cingulate GM NAA/Cr, Cho/Cr, and mI/Cr also did not demonstrate marked differences (P &gt; 0.05). No statistical inter-group difference was determined in NAA/Cr of the bilateral thalami (P &gt; 0.05), while bilateral thalamic Cho/Cr and mI/Cr were reduced in teenagers with depression compared with healthy adolescents (P &lt; 0.05). A significant negative correlation was observed between the HAMD-24 scores in adolescents with depression with bilateral PWM NAA/Cr and Cho/Cr and were inversely linked to bilateral thalamic Cho/Cr and mI/Cr (P &lt; 0.05). In adolescents with depressions, MQ positively correlated with right PWH NAA/Cr, left PWH Cho/Cr, and bilateral thalamic Cho/Cr and mI/Cr. CONCLUSION PWM and thalamic metabolic abnormalities might influence teen depression, and the reduction in bilateral PWM NAA/Cr and Cho/Cr could be related to the neuropathology of adolescents with depression suffering from memory impairment. There exists a possibility of dysfunction of nerve cell membrane phospholipids in the thalami of adolescent patients with depression.

A top-down slow breathing circuit that alleviates negative affect in mice.

Although breathing is primarily automatic, its modulation by behavior and emotions suggests cortical inputs to brainstem respiratory networks, which hitherto have received little characterization. Here we identify in mice a top-down breathing pathway from dorsal anterior cingulate cortex (dACC) neurons to pontine reticular nucleus GABAergic inhibitory neurons (PnCGABA), which then project to the ventrolateral medulla (VLM). dACC→PnC activity correlates with slow breathing cycles and volitional orofacial behaviors and is influenced by anxiogenic conditions. Optogenetic stimulation of the dACC→PnCGABA→VLM circuit simultaneously slows breathing and suppresses anxiety-like behaviors, whereas optogenetic inhibition increases both breathing rate and anxiety-like behaviors. These findings suggest that the dACC→PnCGABA→VLM circuit has a crucial role in coordinating slow breathing and reducing negative affect. Our study elucidates a circuit basis for top-down control of breathing, which can influence emotional states.

Altered Neural Processing of Interoception in Patients With Functional Neurological Disorder: A Task-Based fMRI Study.

Research suggests that disrupted interoception contributes to the development and maintenance of functional neurological disorder (FND); however, no functional neuroimaging studies have examined the processing of interoceptive signals in patients with FND. The authors examined univariate and multivariate functional MRI neural responses of 38 patients with mixed FND and 38 healthy control individuals (HCs) during a task exploring goal-directed attention to cardiac interoception-versus-control (exteroception or rest) conditions. The relationships between interoception-related neural responses, heartbeat-counting accuracy, and interoceptive trait prediction error (ITPE) were also investigated for FND patients. When attention was directed to heartbeat signals versus exteroception or rest tasks, FND patients showed decreased neural activations (and reduced coactivations) in the right anterior insula and bilateral dorsal anterior cingulate cortices (among other areas), compared with HCs. For FND patients, heartbeat-counting accuracy was positively correlated with right anterior insula and ventromedial prefrontal activations during interoception versus rest. Cardiac interoceptive accuracy was also correlated with bilateral dorsal anterior cingulate activations in the interoception-versus-exteroception contrast, and neural activations were correlated with ITPE scores, showing inverse relationships to those observed for heartbeat-counting accuracy. This study identified state and trait interoceptive disruptions in FND patients. Convergent between- and within-group findings contextualize the pathophysiological role of cingulo-insular (salience network) areas across the spectrum of functional seizures and functional movement disorder. These findings provide a starting point for the future development of comprehensive neurophysiological assessments of interoception for FND patients, features that also warrant research as potential prognostic and monitoring biomarkers.

Electroacupuncture Regulates Cannabinoid Receptor 1 Expression in a Mouse Fibromyalgia Model: Pharmacological and Chemogenetic Modulation.

Fibromyalgia is a chronic illness usually accompanied by long-lasting, general pain throughout the body, often accompanied by anxiety, depression, fatigue, and sleep disruption. Meanwhile, doctors and scientists have not entirely discovered detailed mechanisms; patients always have an exaggerated sensation to pervasive pain without satisfied medical service. Given the lack of knowledge on its underlying mechanism, current treatments aim to provide pain and/or symptom relief. The present study aimed to clarify the role of cannabinoid receptor 1 (CB1) signaling in a mouse fibromyalgia pain model. To develop the mouse fibromyalgia model, mice were subjected to intermittent cold stress (ICS). Our results indicated that mechanical (2.09 ± 0.09 g) and thermal hyperalgesia (4.77 ± 0.29 s), which were evaluated by von Frey and Hargraves' tests, were induced by ICS, suggesting successful modeling. The hurting replies were then provoked by electroacupuncture (EA) but not for sham EA mice. Further, in a Western blot analysis, we found significantly decreased CB1 protein levels in the thalamus, somatosensory cortex, and anterior cingulate cortex. In addition, the levels of pain-related protein kinases and transcription factor were increased. Treatment with EA reliably increased CB1 expression in various brain regions sequentially alleviated by nociceptive mediators. Furthermore, the administration of a CB1 agonist significantly attenuated fibromyalgia pain, reversed EA analgesia by the CB1 antagonist, and further reversed the chemogenetic inhibition of SSC. Our innovative findings evidence the role of CB1 signaling in the interaction of EA and fibromyalgia, suggesting its potential for clinical trials and as a treatment target.

Neurometabolic Profile in Obese Patients: A Cerebral Multi-Voxel Magnetic Resonance Spectroscopy Study.

Background and Objectives: Obesity-related chronic inflammation may lead to neuroinflammation and neurodegeneration. This study aimed to evaluate the neurometabolic profile of obese patients using cerebral multivoxel magnetic resonance spectroscopy (mvMRS) and assess correlations between brain metabolites and obesity markers, including body mass index (BMI), waist circumference, waist-hip ratio, body fat percentage, and indicators of metabolic syndrome (e.g., triglycerides, HDL cholesterol, fasting blood glucose, insulin, and insulin resistance index (HOMA-IR)). Materials and Methods: This prospective study involved 100 participants, stratified into two groups: 50 obese individuals (BMI ≥ 30 kg/m2) and 50 controls (18.5 ≤ BMI < 25 kg/m2). Anthropometric measurements, body fat percentage, and biochemical markers were evaluated. All subjects underwent long- and short-echo mvMRS analysis of the frontal and parietal supracallosal subcortical and deep white matter, as well as the cingulate gyrus, analyzing NAA/Cr, Cho/Cr, and mI/Cr ratios, along with absolute concentrations of NAA and Cho. Results: Obese participants exhibited significantly decreased NAA/Cr and Cho/Cr ratios in the deep white matter of the right cerebral hemisphere (p < 0.001), while absolute concentrations of NAA and Cho did not differ significantly between groups (p > 0.05). NAA levels showed negative correlations with more reliable obesity parameters (waist circumference and waist-to-hip ratio) but not with BMI, particularly in the deep frontal white matter and dorsal anterior cingulate gyrus of the left cerebral hemisphere. Notably, insulin demonstrated a significant negative impact on NAA (ρ = -0.409 and ρ = -0.410; p < 0.01) and Cho levels (ρ = -0.403 and ρ = -0.392; p < 0.01) at these locations in obese individuals. Conclusions: Central obesity and hyperinsulinemia negatively affect specific brain regions associated with cognitive and emotional processing, while BMI is not a reliable parameter for assessing brain metabolism.

Noradrenergic alpha-2a receptor stimulation enhances prediction error signaling and updating of attention sets in anterior cingulate cortex and striatum

The noradrenergic system is believed to support behavioral flexibility. A possible source mediating improved flexibility are α2A adrenoceptors (α2AR) in prefrontal cortex (PFC) or the anterior cingulate cortex (ACC). We tested this hypothesis by stimulating α2ARs using Guanfacine during attentional set shifting in male nonhuman primates. We found that α2AR stimulation improved learning from errors and updating attention sets. Neural recordings in the ACC, dorsolateral PFC, and the striatum showed that α2AR stimulation selectively enhanced neural signaling of prediction errors in neurons of the ACC and the striatum, but not in dlPFC. This modulation was accompanied by enhanced encoding of attended target features and particularly apparent in putative fast-spiking interneurons, pointing to an interneuron mediated mechanism of α2AR action. These results reveal that α2A receptors are part of the causal chain of flexibly updating attention sets through an enhancement of outcomes and prediction error signaling in ACC and striatum.

The Neural Basis and Computational Models of Metacognition

Abstract: The ability to reflect on ones own thinking is what makes human cognition "meta." Metacognition, the capability to assess, reflect on, and control first-order cognitive processes, is essential for flexible and adaptive behaviors across various contexts. This review explores the neural mechanisms and computational models underpinning metacognition. The involvement of brain regions, including the insula, precuneus, medial prefrontal cortex, and dorsolateral prefrontal cortex in metacognitive judgments is examined. How distinct regions support both domain-general and domain-specific metacognitive processes is also explored. Furthermore, the neural correlates of metacognitive executive functions, such as error monitoring and cognitive control, are investigated, with a focus on the prefrontal and anterior cingulate cortex and their roles in regulating working memory and performance monitoring. This review also discusses the Bayesian models of human metacognitive processes proposed by Fleming and Daw. Studies on human metacognition have significant implications for the development of artificial intelligence, evidenced by the H-CogAff architecture, revealing how integrating metacognitive frameworks could enhance AIs transparency, reasoning, adaptability, and perception. The findings suggest that investigating the neural mechanisms and computational models of metacognition is crucial not only for understanding human cognitive processes but also for improving the resilience and flexibility of AI systems. Future studies in this field should expand the scope by integrating broader and more qualitative dimensions, such as affective self-assessment and social cognition, while maintaining the precision of current evaluation approaches.

Altered parasympathetic outflow and central sensitization response to continuous pain in cyclic vomiting syndrome: a functional magnetic resonance imaging study.

Cyclic vomiting syndrome (CVS) is a disorder of brain-gut interaction characterized by recurrent episodes of nausea and vomiting interspersed with asymptomatic periods and associated with autonomic nervous system dysfunction. We examined the dysautonomic response to noxious stimuli seen in CVS patients using our previously validated approach to integrate peripheral autonomic outflow metrics, temporal summation of pain, and brain fMRI. BOLD fMRI and ECG were acquired from CVS patients and healthy adults during a rest condition and a sustained cuff pressure pain stimulus at the leg. After the latter scan, participants rated pain for the full 6-minute pain stimulus as well as first, middle, and last two-minutes to calculate temporal summation. During sustained pain, patients (n=13) exhibited greater reduction in heart rate variability within the high-frequency range (HF-HRV) and reduced anticorrelation between HF-HRV and fMRI signal in the anterior insula, pregenual anterior cingulate cortex, and ventrolateral and dorsolateral prefrontal cortex relative to healthy adults (n=13). Compared to healthy adults (n=14), patients (n=14) exhibited increasing pain intensity over the course of sustained cuff pressure. Seed-based functional connectivity analysis revealed for healthy adults (n=13), pain sensitization correlated with pain-induced increases in connectivity between primary somatosensory cortex and regions of interest in both left anterior insula/posterior orbitofrontal cortex and right pre-supplementary motor area, while this correlation was disrupted in CVS (n=10). Our results support altered central coding of nociceptive stimuli and autonomic responsivity of CVS patients in key brain regions implicated in autonomic control and interoception.

Hippocampal area CA2 activity supports social investigation following an acute social stress.

Neuronal activity in the hippocampus is critical for many types of memory acquisition and retrieval and influences an animal's response to stress. Moreover, the molecularly distinct principal neurons of hippocampal area CA2 are required for social recognition memory and aggression in mice. To interrogate the effects of stress on CA2-dependent behaviors, we chemogenetically manipulated neuronal activity in vivo during an acute, socially derived stressor and tested whether memory for the defeat was influenced. One day after an acute social defeat (aSD), defeated mice spent significantly less time investigating another mouse when compared to non-defeated control mice. We found that this avoidant phenotype persisted for up to one month following a single defeat encounter. When CA2 pyramidal neuron activity was inhibited with Gi-DREADD receptors during the defeat, subject mice exhibited a significantly higher amount of social avoidance one day later when compared to defeated littermates not expressing DREADDs. Moreover, CA2 inhibition during defeat caused a reduction in submissive defense behaviors in response to aggression. In vitro electrophysiology and tracing experiments revealed a circuit wherein CA2 neurons connect to caudal CA1 projection neurons that, in turn, project to corticolimbic regions including the anterior cingulate cortex. Finally, socially avoidant, defeated mice exhibited significant reductions in cFos expression in caudal hippocampal and limbic brain areas during a social investigation task 24 h after aSD. Taken together, these results indicate that CA2 neuronal activity is required to support behavioral resilience following an acute social stressor and that submissive defensive behavior during the defeat (vs. fleeing) is a predictor of future resilience to social stress. Furthermore, CA2 preferentially targets a population of caudal CA1 projection neurons that contact cortical brain regions where activity is modulated by an acute social stressor.

Shedding Light on the Neurocognitive Explorations of Interpreting: What Do We Know from Brain-Based Research?

Interpreting is highly complex and cognitively demanding, arousing interest from the neuroimaging community. In the past three decades, dozens of investigations have been done to figure out how one language transfers into another in the brain. This article reviews the published studies concerning interpreting, shedding light on interpreting asymmetry effect, the neural plasticity and the brain regions activated during interpreting tasks. Based on the findings in previous studies, the article argues that interpreting training and practice might contribute to neuroplasticity both functionally and structurally. It also suggests that apart from traditional language areas, the prefrontal cortex, the superior temporal gyrus, the inferior parietal lobule and the anterior cingulate cortex also play a key role during the rendering process.

Modulation of neural networks and symptom correlated in fibromyalgia: A randomized double-blind multi-group explanatory clinical trial of home-based transcranial direct current stimulation.

Transcranial direct current stimulation (tDCS) might modulate neural activity and promote neural plasticity in patients with fibromyalgia (FM). This multi-group randomized clinical trial compared home-based active tDCS (HB-a-tDCS) on the left dorsolateral prefrontal cortex (l-DLPFC) or home-based sham tDCS (HB-s-tDCS), and HB-a-tDCS or HB-s-tDCS on the primary motor cortex (M1) in the connectivity analyses in eight regions of interest (ROIs) across eight resting-state electroencephalography (EEG) frequencies. We included 48 women with FM, aged 30 to 65, randomly assigned to 2:1:2:1 to receive 20 sessions during 20 minutes of HB-a-tDCS 2mA or HB-s-tDCS, over l-DLPFC or M1, respectively. EEG recordings were obtained before and after treatment with eyes open (EO) and eyes closed (EC). In the EC condition, comparing pre to post-treatment, the HB-a-tDCS on l-DLPFC decreased the lagged coherence connectivity in the delta frequency band between the right insula and left anterior cingulate cortex (ACC) (t = -3.542, p = .048). The l-DLPFC HB-a-tDCS compared to HB-s-tDCS decreased the lagged coherence connectivity in the delta frequency band between the right insula and left ACC (t = -4.000, p = .017). In the EO condition, the l-DLPFC HB-a-tDCS compared to M1 HB-s-tDCS increased the lagged coherence connectivity between the l-DLPFC and left ACC in the theta band (t = -4.059, p = .048). Regression analysis demonstrated that the HB-a-tDCS effect on the l-DLPFC was positively correlated with sleep quality. On the other hand, the HB-a-tDCS on l-DLPFC and HB-s-tDCS on M1 were positively correlated with pain catastrophizing. These results show that HB-a-tDCS affects the neural connectivity between parts of the brain that control pain's emotional and attentional aspects, which are most noticeable at lower EEG frequencies in a rest state. This effect on neural oscillations could serve as a neural marker associated with its efficacy in alleviating fibromyalgia symptoms. identifier [NCT03843203].

Potential effects of peripheral neuropathy on brain function in patients with type 2 diabetes mellitus.

The mechanisms associated between diabetic peripheral neuropathy (DPN) and various brain function abnormalities in patients remains unclear. This study attempted to indirectly evaluate the effect of DPN on brain function in patients with type 2 diabetes mellitus (T2DM) by characterizing the resting-state functional connectivity (FC) of the lower limb sensorimotor cortex (LSM). Forty-four T2DM patients with diabetic peripheral neuropathy (DPN), 39 T2DM patients without diabetic peripheral neuropathy (ND), and 43 healthy controls (HCs) underwent a neuropsychological assessment and resting-state functional magnetic resonance imaging examinations to examine the differences in FC between the LSM and the whole brain. The relationships of FC with clinical/cognitive variables were examined. In comparison with the HCs group, the ND group showed reduced FC of the LSM with the right lateral occipitotemporal cortex (LOTC) and increased FC with the medial superior frontal gyrus (SFGmed), while the DPN group showed reduced FC of the LSM with the right cerebellar lobule VI, the right LOTC, the rostral prefrontal cortex (rPFC), and the anterior cingulate gyrus (ACC). Moreover, in comparison with the ND group, the DPN group showed reduced FC of the LSM with the ACC, SFGmed, and rPFC. In the DPN group, the FC between the LSM and right cerebellar lobule VI was significantly correlated with fasting blood glucose levels (r = -0.490, p = 0.001), and that between the LSM and ACC was significantly correlated with the Montreal Cognitive Assessment score (r = 0.479, p = 0.001). Patients with T2DM may show abnormal motion-related visual perceptual function before the appearance of DPN. Importantly, DPN can influence the brain regions that maintain motion and motor control, and this effect is not limited to motor function, which may be the central neuropathological basis for diabetic peripheral neuropathy.