In this study, we investigated how empathic neural responses unfold over time in different empathy networks when viewing same-race and other-race individuals in dynamic painful conditions. We recorded magnetoencephalography signals from Chinese adults when viewing video clips showing a dynamic painful (or non-painful) stimulation to Asian and White models' faces to trigger painful (or neutral) expressions. We found that perceived dynamic pain in Asian models modulated neural activities in the visual cortex at 100 ms-200 ms, in the orbitofrontal and subgenual anterior cingulate cortices at 150 ms-200 ms, in the anterior cingulate cortex around 250 ms-350 ms, and in the temporoparietal junction and middle temporal gyrus around 600 ms after video onset. Perceived dynamic pain in White models modulated activities in the visual, anterior cingulate, and primary sensory cortices after 500 ms. Our findings unraveled earlier dynamic activities in multiple neural circuits in response to same-race (vs other-race) individuals in dynamic painful situations.
Adult ; Humans ; Brain Mapping ; Pain ; Empathy ; Racism ; Gyrus Cinguli/physiology* ; Magnetic Resonance Imaging ; Brain/physiology*

Itch is an unpleasant sensation that provokes the desire to scratch. While acute itch serves as a protective system to warn the body of external irritating agents, chronic itch is a debilitating but poorly-treated clinical disease leading to repetitive scratching and skin lesions. However, the neural mechanisms underlying the pathophysiology of chronic itch remain mysterious. Here, we identified a cell type-dependent role of the anterior cingulate cortex (ACC) in controlling chronic itch-related excessive scratching behaviors in mice. Moreover, we delineated a neural circuit originating from excitatory neurons of the ACC to the ventral tegmental area (VTA) that was critically involved in chronic itch. Furthermore, we demonstrate that the ACC→VTA circuit also selectively modulated histaminergic acute itch. Finally, the ACC neurons were shown to predominantly innervate the non-dopaminergic neurons of the VTA. Taken together, our findings uncover a cortex-midbrain circuit for chronic itch-evoked scratching behaviors and shed novel insights on therapeutic intervention.
Mice ; Animals ; Gyrus Cinguli/physiology* ; Pruritus/pathology* ; Mesencephalon ; Cerebral Cortex/pathology* ; Neurons/pathology*

This study aimed to investigate the effect of treadmill exercise on neuropathic pain and to determine whether mitophagy of the anterior cingulate cortex (ACC) contributes to exercise-mediated amelioration of neuropathic pain. Chronic constriction injury of the sciatic nerve (CCI) was used to establish a neuropathic pain model in Sprague-Dawley (SD) rats. Von-Frey filaments were used to assess the mechanical paw withdrawal threshold (PWT), and a thermal radiation meter was used to assess the thermal paw withdrawal latency (PWL) in rats. qPCR was used to evaluate the mRNA levels of Pink1, Parkin, Fundc1, and Bnip3. Western blot was used to evaluate the protein levels of PINK1 and PARKIN. To determine the impact of the mitophagy inducer carbonyl cyanide m-chlorophenylhydrazone (CCCP) on pain behaviors in CCI rats, 24 SD rats were randomly divided into CCI drug control group (CCI+Veh group), CCI+CCCP low-dose group (CCI+CCCP0.25), CCI+CCCP medium-dose group (CCI+CCCP2.5), and CCI+CCCP high-dose group (CCI+CCCP5). Pain behaviors were assessed on 0, 1, 3, 5, and 7 days after modeling. To explore whether exercise regulates pain through mitophagy, 24 SD rats were divided into sham, CCI, and CCI+Exercise (CCI+Exe) groups. The rats in the CCI+Exe group underwent 4-week low-moderate treadmill training one week after modeling. The mechanical pain and thermal pain behaviors of the rats in each group were assessed on 0, 7, 14, 21, and 35 days after modeling. Western blot was used to detect the levels of the mitophagy-related proteins PINK1, PARKIN, LC3 II/LC3 I, and P62 in ACC tissues. Transmission electron microscopy was used to observe the ultrastructure of mitochondrial morphology in the ACC. The results showed that: (1) Compared with the sham group, the pain thresholds of the ipsilateral side of the CCI group decreased significantly (P < 0.001). Meanwhile, the mRNA and protein levels of Pink1 were significantly higher, and those of Parkin were lower in the CCI group (P < 0.05). (2) Compared with the CCI+Veh group, each CCCP-dose group showed higher mechanical and thermal pain thresholds, and the levels of PINK1 and LC3 II/LC3 I were elevated significantly (P < 0.05, P < 0.01). (3) The pain thresholds of the CCI+Exe group increased significantly compared with those of the CCI group after treadmill intervention (P < 0.001, P < 0.01). Compared with the CCI group, the protein levels of PINK1 and P62 were decreased (P < 0.001, P < 0.01), and the protein levels of PARKIN and LC3 II/LC3 I were increased in the CCI+Exe group (P < 0.01, P < 0.05). Rod-shaped mitochondria were observed in the ACC of CCI+Exe group, and there were little mitochondrial fragmentation, swelling, or vacuoles. The results suggest that the mitochondrial PINK1/PARKIN autophagy pathway is blocked in the ACC of neuropathic pain model rats. Treadmill exercise could restore mitochondrial homeostasis and relieve neuropathic pain via the PINK1/PARKIN pathway.
Rats ; Animals ; Mitophagy/physiology* ; Rats, Sprague-Dawley ; Carbonyl Cyanide m-Chlorophenyl Hydrazone/pharmacology* ; Gyrus Cinguli ; Neuralgia ; Ubiquitin-Protein Ligases/metabolism* ; Protein Kinases ; Membrane Proteins/metabolism* ; Mitochondrial Proteins/metabolism*

Increasing studies have provided cognitive and neuron evidence for not only the similarities, but also the differences between physical pain and social pain in the brain basis. Comparing the similarities and differences of the brain basis of physical pain and social pain helps us to clarify the mechanism of the occurrence and change of pain, and provide theoretical evidence for clinical pain treatment. In this review, we summarized studies to delineate the brain mechanisms of physical pain and social pain. Through the review of existing studies, we found that both physical pain and social pain can invoke the same brain regions that process emotional experience (the dorsal anterior cingulate cortex, anterior insula), emotion regulation (lateral prefrontal cortex) and somatosensory (the posterior insula, secondary sensory cortex). However, the voxel-level activated patterns of physical and social pain differ in the same brain region (dorsal anterior cingulate gyrus, dorsolateral prefrontal cortex, etc.), and the overlapping brain regions (for example, ventrolateral prefrontal cortex) have varied effect on these two types of pain. In addition, studies have shown that the brain activation pattern for social pain may be influenced by the experimental paradigm. Future studies should actively adopt a data-driven way to examine the brain basis of physical pain and social pain, especially the nerve activation mode, aiming to consummate the theory of pain.
Brain ; Gyrus Cinguli ; Humans ; Magnetic Resonance Imaging ; Pain/psychology* ; Prefrontal Cortex/physiology*

Micturition is a complex process involving the bladder, spinal cord, and the brain. Highly sophisticated central neural program controls bladder function by utilizing multiple brain regions, including pons and suprapontine structures. Periaqueductal grey, insula, anterior cingulate cortex, and medial prefrontal cortex are components of suprapontine micturition centers. Under pathologic conditions such as epilepsy, urinary dysfunction is a frequent symptom and it seems to be associated with increased suprapontine cortical activity. Interestingly, micturition can also trigger seizures known as reflex epilepsy. During voiding behavior, frontotemporal cortical activation has been reported and it may induce reflex seizures. As current researches are only limited to present clinical cases, more rigorous investigations are needed to elucidate biological mechanisms of micturition to advance our knowledge on the process of micturition in physiology and pathology.
Brain ; Epilepsy* ; Epilepsy, Reflex ; Gyrus Cinguli ; Pathology ; Physiology ; Pons ; Prefrontal Cortex ; Reflex ; Seizures ; Spinal Cord ; Urinary Bladder ; Urination*

PURPOSE: Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer's disease and have been correlated with memory function. Although regions representing glucose hypometabolism in patients with Alzheimer's disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervation and glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changes caused by cholinergic deficits. MATERIALS AND METHODS: We lesioned basal forebrain cholinergic neurons in rats using 192 immunoglobulin G-saporin. After 3 weeks, lesioned animals underwent water maze testing or were analyzed by 18F-2-fluoro-2-deoxyglucose positron emission tomography. RESULTS: During water maze probe testing, performance of the lesioned group decreased with respect to time spent in the target quadrant and platform zone. Cingulate cortex glucose metabolism in the lesioned group decreased, compared with the normal group. Additionally, acetylcholinesterase activity and glutamate decarboxylase 65/67 expression declined in the cingulate cortex. CONCLUSION: Our results reveal that spatial memory impairment in animals with selective basal forebrain cholinergic neuron damage is associated with a functional decline in the GABAergic and cholinergic system associated with cingulate cortex glucose hypometabolism.
Acetylcholine/metabolism ; Alzheimer Disease ; Animals ; Antibodies, Monoclonal/*pharmacology ; Basal Forebrain/*drug effects/metabolism ; Cholinergic Agents/administration & dosage/*pharmacology ; Cholinergic Neurons/*drug effects/metabolism ; Fluorodeoxyglucose F18 ; GABAergic Neurons/*drug effects/metabolism ; Glucose/*metabolism ; Gyrus Cinguli/*drug effects/metabolism ; Humans ; Injections ; Maze Learning ; Motor Activity/physiology ; Positron-Emission Tomography ; Rats ; Ribosome Inactivating Proteins, Type 1/*pharmacology

This study sought to reveal the difference of brain functions at resting-state between subjects with sub-health and normal controls by using the functional magnetic resonance imaging (fMRI) technology. Resting-state fMRI scans were performed on 24 subjects of sub-health and on 24 healthy controls with gender, age and education matched with the sub-health persons. Compared to the healthy controls, the sub-health group showed significantly higher regional homogeneity (ReHo) in the left post-central gyrus and the right post-central gyrus. On the other hand, the sub-health group showed significantly lower ReHo in the left superior frontal gyrus, in the right anterior cingulated cortex and ventra anterior cingulate gyrus, in the left dorsolateral frontal gyrus, and in the right middle temporal gyrus. The Significant difference in ReHo suggests that the sub-health persons have abnormalities in certain brain regions. It is proved that its specific action and meaning deserves further assessment.
Brain ; physiology ; physiopathology ; Brain Mapping ; Case-Control Studies ; Cerebral Cortex ; Frontal Lobe ; Gyrus Cinguli ; Humans ; Magnetic Resonance Imaging ; Parietal Lobe

Empathy, a basic prosocial behavior, is referred to as an ability to understand and share others' emotional state. Generally, empathy is also a social-behavioral basis of altruism. In contrast, impairment of empathy development may be associated with autism, narcissism, alexithymia, personality disorder, schizophrenia and depression. Thus, study of the brain mechanisms of empathy has great importance to not only scientific and clinical advances but also social harmony. However, research on empathy has long been avoided due to the fact that it has been considered as a distinct feature of human beings from animals, leading to paucity of knowledge in the field. In 2006, a Canadian group from McGill University found that a mouse in pain could be shared by its paired cagemate, but not a paired stranger, showing decreased pain threshold and increased pain responses through emotional contagion while they were socially interacting. In 2014, we further found that a rat in pain could also be shared by its paired cagemate 30 min after social interaction, showing long-term decreased pain threshold and increased pain responses, suggesting persistence of empathy for pain (empathic memory). We also mapped out that the medial prefrontal cortex, including the anterior cingulate cortex, prelimbic cortex and infralimbic cortex, is involved in empathy for pain in rats, suggesting that a neural network may be associated with development of pain empathy in the CNS. In the present brief review, we give a brief outline of the advances and challenges in study of empathy for pain in humans and animals, and try to provide a novel bio-psychosocial-behavioral model for study of pain and its emotional comorbidity using laboratory animals.
Animals ; Cerebral Cortex ; physiology ; Emotions ; Empathy ; Gyrus Cinguli ; physiology ; Humans ; Mice ; Models, Animal ; Pain ; Pain Threshold ; Prefrontal Cortex ; physiology ; Rats

Brain-derived neurotrophic factor (BDNF), a small dimeric secretory protein, plays a vital role in activity-dependent synaptic plasticity, learning and memory. It has been shown that BDNF in the hippocampus and amygdala participates in the formation of fear memory. However, little is known about the functional role of BDNF in the anterior cingulate cortex (ACC). To address this question, we examined the mRNA and protein levels of BDNF in the ACC of rats at various time points after fear conditioning, using quantitative real-time PCR and enzyme-linked immunosorbent assay (ELISA). The results showed that BDNF exhibited a temporally specific increase in both mRNA and protein levels after CS (tone) and US (foot shock) was paired. Such increase did not occur after the animals were exposed to CS or US alone. When BDNF antibody was locally infused into the ACC prior to CS-US pairing, both contextual and auditory fear memories were severely impaired. Taken together, these results suggest that BDNF in the ACC is required for the formation of fear memory.
Animals ; Brain-Derived Neurotrophic Factor ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Fear ; Gyrus Cinguli ; metabolism ; Memory ; physiology ; RNA, Messenger ; metabolism ; Rats ; Real-Time Polymerase Chain Reaction

Using intracellular potential recording technique in vivo, a series of hyperpolarizing and depolarizing currents at different intensities with a 50-ms duration were injected to somatic nociceptive neurons (SNNs) and somatic non-nociceptive neurons (SNNNs) in the anterior cingulate gyrus (ACG) of cats. The membrane electrical responses of the neurons were recorded, and the membrane electrical parameters of the neurons were calculated for comparative study on membrane electrical properties of SNNs and SNNNs of the ACG. A total of 188 ACG neurons from 57 cats were recorded. Among the 188 neurons, 172 (91.5%) and 16 (8.5%) were SNNs and SNNNs, respectively. The I-V curves of SNNs and SNNNs in the ACG were "S" shapes. When the absolute value of injected current intensity was less than or equal to 1 nA (≤ 1 nA), the I and V of I-V curves of both SNNs and SNNNs were linearly correlated (rSNNs = 0.99, rSNNNs = 0.99). When the absolute value of injected current intensity was more than 1 nA, both SNNs and SNNNs showed a certain inward or outward rectification behavior. Compared with SNNNs, SNNs had stronger rectification and lower adaptability (P < 0.01). With the increase of injected current intensity, the changes of frequency of discharges of SNNs were higher than those of SNNNs. In addition, the membrane resistance (Rm), the membrane capacity (Cm) and the time constant (τ) of SNNs were larger than those of SNNNs (P < 0.05 or P < 0.01). The differences in the membrane electrical properties between SNNs and SNNNs in the ACG suggested the disparity in neuronal cell size and cell membrane structure between them. The results of this study provided the experimental basis for deeply elucidating the mechanisms of somatic nociceptive sensation and characteristics on the membrane electrical aspects of ACG neurons.
Animals ; Cats ; Gyrus Cinguli ; cytology ; Membrane Potentials ; Neurons ; physiology ; Nociceptors ; physiology