Differential activation of lateral parabrachial nuclei and their limbic projections during head compared with body pain: A 7-Tesla functional magnetic resonance imaging study.

Pain is a complex experience that involves sensory, emotional, and motivational components. It has been suggested that pain arising from the head and orofacial regions evokes stronger emotional responses than pain from the body. Indeed, recent work in rodents reports different patterns of activation in ascending pain pathways during noxious stimulation of the skin of the face when compared to noxious stimulation of the body. Such differences may dictate different activation patterns in higher brain regions, specifically in those areas processing the affective component of pain. We aimed to use ultra-high field functional magnetic resonance imaging (fMRI at 7-Tesla) to determine whether noxious thermal stimuli applied to the surface of the face and body evoke differential activation patterns within the ascending pain pathway in awake humans (n=16). Compared to the body, noxious heat stimulation to the face evoked more widespread signal changes in prefrontal cortical regions and numerous brainstem and subcortical limbic areas. Moreover, facial pain evoked significantly different signal changes in the lateral parabrachial nucleus, substantia nigra, paraventricular hypothalamus, and paraventricular thalamus, to those evoked by body pain. These results are consistent with recent preclinical findings of differential activation in the brainstem and subcortical limbic nuclei and associated cortices during cutaneous pain of the face when compared with the body. The findings suggest one potential mechanism by which facial pain could evoke a greater emotional impact than that evoked by body pain.

Correlation of Posterior Tibial Tendon Ultrasound with Calcaneal Inclination Angle in Indonesian Professional Athletes with Medial Ankle Pain.

Background: Adult-acquired flatfoot deformity (AAFD) is characterized by partial or complete flattening of the longitudinal medial arch, which develops after maturity. AAFD secondary to posterior tibialis tendon dysfunction (PTTD) is one of professional athletes' most common foot and ankle pathologies. Different modalities and procedures can be used to establish the diagnosis of AAFD and PTTD. However, imaging measurements such as the calcaneal inclination index and ultrasonography (US) of the posterior tibialis tendon (PTT) in professional athletes with medial ankle and focal pain along the PTT have yet to be widely studied. This study investigates the correlation of PTT ultrasound for evaluating PTTD with calcaneal inclination angle (CIA) for evaluating AAFD in professional athletes with medial ankle and focal pain along the PTT. Through this study, clinicians and radiologists may benefit from considering AAFD in athletes with PTTD. Methods: 112 Indonesian professional athletes with medial ankle or foot pain and focal pain along the direction of the PTT underwent foot radiography using the CIA and ankle ultrasound to observe PTT abnormalities. Results: A negative correlation between fluid thickness surrounding the PTT and the CIA (p<0.001; 95% CI - 0.945, - 0.885), as well as a negative correlation between PTT thickness and CIA (p<0.001, 95% CI - 0.926, - 0.845), with a correlation coefficient (r) of - 0.921 and - 0.892, respectively. No significant correlation was found between PTT tear and CIA (p = 0.728; 95% CI -0.223, - 0.159; r - 0.033). Conclusion: This study showed a negative correlation between PTTD and AAFD via ultrasound and CIA in professional athletes with medial ankle and focal pain along the PTT. A better understanding of PTTD and AAFD imaging will lead to more effective management and prompt treatment.

Mechanical pain sensitivity is associated with hippocampal structural integrity.

ABSTRACT: Rodents and human studies indicate that the hippocampus, a brain region necessary for memory processing, responds to noxious stimuli. However, the hippocampus has yet to be considered a key brain region directly involved in the human pain experience. One approach to answer this question is to perform quantitative sensory testing on patients with hippocampal damage-ie, medial temporal lobe epilepsy. Some case studies and case series have performed such tests in a handful of patients with various types of epilepsy and have reported mixed results. Here, we aimed to determine whether mechanical pain sensitivity was altered in patients diagnosed with temporal lobe epilepsy. We first investigated whether mechanical pain sensitivity in patients with temporal lobe epilepsy differs from that of healthy individuals. Next, in patients with temporal lobe epilepsy, we evaluated whether the degree of pain sensitivity is associated with the degree of hippocampal integrity. Structural integrity was based on hippocampal volume, and functional integrity was based on verbal and visuospatial memory scores. Our findings show that patients with temporal lobe epilepsy have lower mechanical pain sensitivity than healthy individuals. Only left hippocampal volume was positively associated with mechanical pain sensitivity-the greater the hippocampal damage, the lower the sensitivity to mechanical pain. Hippocampal measures of functional integrity were not significantly associated with mechanical pain sensitivity, suggesting that the mechanisms of hippocampal pain processing may be different than its memory functions. Future studies are necessary to determine the mechanisms of pain processing in the hippocampus.

Do we empathize humanoid robots and humans in the same way? Behavioral and multimodal brain imaging investigations.

Humanoid robots have been designed to look more and more like humans to meet social demands. How do people empathize humanoid robots who look the same as but are essentially different from humans? We addressed this issue by examining subjective feelings, electrophysiological activities, and functional magnetic resonance imaging signals during perception of pain and neutral expressions of faces that were recognized as patients or humanoid robots. We found that healthy adults reported deceased feelings of understanding and sharing of humanoid robots' compared to patients' pain. Moreover, humanoid robot (vs. patient) identities reduced long-latency electrophysiological responses and blood oxygenation level-dependent signals in the left temporoparietal junction in response to pain (vs. neutral) expressions. Furthermore, we showed evidence that humanoid robot identities inhibited a causal input from the right ventral lateral prefrontal cortex to the left temporoparietal junction, contrasting the opposite effect produced by patient identities. These results suggest a neural model of modulations of empathy by humanoid robot identity through interactions between the cognitive and affective empathy networks, which provides a neurocognitive basis for understanding human-robot interactions.

Ultrasound imaging and shear wave elastography for the differential diagnosis of heel pain: a comparative cross-sectional study.

PURPOSE: In correlation with magnetic resonance imaging (MRI), this study attempts to assess the effectiveness of the diagnostic of ultrasonography (US) features and shear wave elastography (SWE) in determining the different causes of heel pain. MATERIALS AND METHODS: 55 heels with a mean age of 38.33 ± 10.8 were included in the study (10 control cases and 41 cases, 4 of which had bilateral heel pain). There were 23 female cases (56.1%) and 18 male cases (43.95%). Examinations using shear wave elastography (SWE) and ultrasound (US) were done in different positions. MRI and the obtained data were correlated. RESULTS: When used to diagnose different heel pain causes, ultrasound demonstrated great sensitivity and specificity. SWE demonstrated a good correlation with MRI findings and enhanced the ultrasound's diagnostic precision in identifying plantar fasciitis early on (increased accuracy from 88.9 to 93.33% with 100% sensitivity and 83.3% specificity) and Achilles tendinopathy (increased accuracy from 88.9 to 97.8 with 94.7% sensitivity and 100% specificity). CONCLUSION: In summary, we concluded that heel pain can be efficiently examined by both ultrasound (US) and shear wave elastography (SWE) with the former being used as the primary effective tool and the latter being done to increase diagnostic accuracy. We also concluded that SWE improved the ultrasound's diagnostic precision in identifying patients with early plantar fasciitis and Achilles tendinopathy and showed a robust relationship with clinical outcomes, enhancing patient evaluation and follow-up.

Identifying significant structural factors associated with knee pain severity in patients with osteoarthritis using machine learning.

Our main objective was to use machine learning methods to identify significant structural factors associated with pain severity in knee osteoarthritis patients. Additionally, we assessed the potential of various classes of imaging data using machine learning techniques to gauge knee pain severity. The data of semi-quantitative assessments of knee radiographs, semi-quantitative assessments of knee magnetic resonance imaging (MRI), and MRI images from 567 individuals in the Osteoarthritis Initiative (OAI) were utilized to train a series of machine learning models. Models were constructed using five machine learning methods: random forests (RF), support vector machines (SVM), logistic regression (LR), decision tree (DT), and Bayesian (Bayes). Employing tenfold cross-validation, we selected the best-performing models based on the area under the curve (AUC). The study results indicate no significant difference in performance among models using different imaging data. Subsequently, we employed a convolutional neural network (CNN) to extract features from magnetic resonance imaging (MRI), and class activation mapping (CAM) was utilized to generate saliency maps, highlighting regions associated with knee pain severity. A radiologist reviewed the images, identifying specific lesions colocalized with the CAM. The review of 421 knees revealed that effusion/synovitis (30.9%) and cartilage loss (30.6%) were the most frequent abnormalities associated with pain severity. Our study suggests cartilage loss and synovitis/effusion lesions as significant structural factors affecting pain severity in patients with knee osteoarthritis. Furthermore, our study highlights the potential of machine learning for assessing knee pain severity using radiographs.

Predictive models of radiographic progression and pain progression in patients with knee osteoarthritis: data from the FNIH OA biomarkers consortium project.

OBJECTIVES: The progression of knee osteoarthritis (OA) can be defined as either radiographic progression or pain progression. This study aimed to construct models to predict radiographic progression and pain progression in patients with knee OA. METHODS: We retrieved data from the FNIH OA Biomarkers Consortium project, a nested case-control study. A total of 600 subjects with mild to moderate OA (Kellgren-Lawrence grade of 1, 2, or 3) in one target knee were enrolled. The patients were classified as radiographic progressors (n = 297), non-radiographic progressors (n = 303), pain progressors (n = 297), or non-pain progressors (n = 303) according to the change in the minimum joint space width of the medial compartment and the WOMAC pain score during the follow-up period of 24-48 months. Initially, 376 variables concerning demographics, clinical questionnaires, imaging measurements, and biochemical markers were included. We developed predictive models based on multivariate logistic regression analysis and visualized the models with nomograms. We also tested whether adding changes in predictors from baseline to 24 months would improve the predictive efficacy of the models. RESULTS: The predictive models of radiographic progression and pain progression consisted of 8 and 10 variables, respectively, with area under curve (AUC) values of 0.77 and 0.76, respectively. Incorporating the change in the WOMAC pain score from baseline to 24 months into the pain progression predictive model significantly improved the predictive effectiveness (AUC = 0.86). CONCLUSIONS: We identified risk factors for imaging progression and pain progression in patients with knee OA over a 2- to 4-year period, and provided effective predictive models, which could help identify patients at high risk of progression.

Divergent association between pain intensity and resting-state fMRI-based brain entropy in different age groups.

Pain is a multidimensional subjective experience sustained by multiple brain regions involved in different aspects of pain experience. We used brain entropy (BEN) estimated from resting-state fMRI (rsfMRI) data to investigate the neural correlates of pain experience. BEN was estimated from rs-fMRI data provided by two datasets with different age range: the Human Connectome Project-Young Adult (HCP-YA) and the Human Connectome project-Aging (HCP-A) datasets. Retrospective assessment of experienced pain intensity was retrieved from both datasets. No main effect of pain intensity was observed. The interaction between pain and age, however, was related to increased BEN in several pain-related brain regions, reflecting greater variability of spontaneous brain activity. Dividing the sample into a young adult group (YG) and a middle age-aging group (MAG) resulted in two divergent patterns of pain-BEN association: In the YG, pain intensity was related to reduced BEN in brain regions involved in the sensory processing of pain; in the MAG, pain was associated with increased BEN in areas related to both sensory and cognitive aspects of pain experience.

Effects of meditation on neural responses to pain: A systematic review and meta-analysis of fMRI studies.

This systematic review investigates the impact of meditation on neural responses to pain, as measured by functional magnetic resonance imaging (fMRI). Up to March 2024, we conducted searches across four databases for human studies implementing fMRI to assess the efficacy of meditation for pain relief. Eighteen studies met the inclusion criteria. Our systematic review indicates that activation of the insula, anterior cingulate cortex, and orbitofrontal cortex is positively associated with meditation for pain relief, while activity in regions like the amygdala and medial prefrontal cortex is negatively correlated with pain relief. Meta-analyses consistently reveal the involvement of various brain regions, including the insula, putamen, amygdala, anterior cingulate cortex, precentral gyrus, postcentral gyrus, inferior parietal lobule, superior temporal gyrus, inferior frontal gyrus, and caudate nucleus, in meditation-induced alleviation of pain. These findings suggest ccthat meditation acts on specific brain regions related to pain, mood, and cognition, providing insight into the potential mechanisms underlying the pain-alleviating effects of meditation on both pain sensations and emotional experiences.

The usefulness of ultrasound in identifying the underlying findings linked to pain in podagra patients.

AIM: To explore whether ultrasound (US) can be employed to identify the underlying characteristics associated with pain in patients with podagra by evaluating the relationship between ultrasound findings and clinical pain. MATERIAL AND METHODS:  Patients with podagra were recruited and grouped into a pain group (G1, 82 patients) and a non pain group (G2, 123 patients). US features were collected and compared. US data were analyzed by binary logistic regression analysis and ROC analysis. Interobserver reliability was assessed, too. RESULTS: A total of 205 patients (196 male and 9 female) were enrolled in this study. In multivariate analysis, the thickness of the synovium (OR=1.928, CI=1.074-3.463), CD (color Doppler) signal of the synovium (OR=1.458, CI=1.011-2.103), and CD signal of the tophi (OR=1.576, CI=1.142-2.177) were identified as risk factors for clinical pain. Areas under the ROC curves (AUC) were 0.713, 0.686 and 0.641 for the three indicators, respectively. The best cutoff points were 1 mm for the thickness of the synovium, grade 1 for the CD signal of the synovium and grade 2 for the CD signal of the tophi. CONCLUSIONS: Ultrasound can provide valuable information for determining underlying features associated with pain in patients with podagra.

The effect of spinal correction surgery on the tractography data of the pain pathway in scoliosis patients: a preliminary report.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: Pain in individuals with opered scoliosis is usually evaluated with a postural analysis or questionnaire. In this study, we evaluated pain in individuals with scoliosis who underwent spinal correction surgery by tractography and compared it with individuals with non-opered scoliosis and healthy individuals. DESIGN: Fifteen healthy individuals, 15 non-operated scoliosis patients and 15 operated scoliosis patients were included in the study. METHODS: All female participants in this prospectively planned study used their right hand as the dominant hand. Bilateral tractography analysis of the pain pathways was performed with DSI Studio software using brain magnetic resonance images (MRI) of the participants. Statistical analysis of the study was performed with IBM SPSS 23.0 and p<0.05 values were considered significant. RESULTS: It was observed that the tractography values of the operated scoliosis group were similar to the control group (p˃0.05). In the non-operated scoliosis group, tractography findings related to nerve conduction velocity such as fiber count, fiber ratio and axial diffusivity (AD) were found to be higher than the other two groups (p<0.05). Fractional anisotropy (FA) values of the unoperated scoliosis group were significantly different between the pain pathways projected from the right/left side of the body (p<0.05). CONCLUSION: The fact that the pain path tractography values of patients with scoliosis who underwent surgery were similar to those of healthy individuals may be evidence of decreased pain sensation reaching the brain. Surgery may be a good choice in the treatment of pain in patients with scoliosis.

Individual differences of white matter characteristic along the anterior insula-based fiber tract circuit for pain empathy in healthy women and women with primary dysmenorrhea.

Pain empathy, defined as the ability of one person to understand another person's pain, shows large individual variations. The anterior insula is the core region of the pain empathy network. However, the relationship between white matter (WM) properties of the fiber tracts connecting the anterior insula with other cortical regions and an individual's ability to modulate pain empathy remains largely unclear. In this study, we outline an automatic seed-based fiber streamline (sFS) analysis method and multivariate pattern analysis (MVPA) to predict the levels of pain empathy in healthy women and women with primary dysmenorrhoea (PDM). Using the sFS method, the anterior insula-based fiber tract network was divided into five fiber cluster groups. In healthy women, interindividual differences in pain empathy were predicted only by the WM properties of the five fiber cluster groups, suggesting that interindividual differences in pain empathy may rely on the connectivity of the anterior insula-based fiber tract network. In women with PDM, pain empathy could be predicted by a single cluster group. The mean WM properties along the anterior insular-rostroventral area of the inferior parietal lobule further mediated the effect of pain on empathy in patients with PDM. Our results suggest that chronic periodic pain may lead to maladaptive plastic changes, which could further impair empathy by making women with PDM feel more pain when they see other people experiencing pain. Our study also addresses an important gap in the analysis of the microstructural characteristics of seed-based fiber tract network.

Causal interactions in brain networks predict pain levels in trigeminal neuralgia.

Trigeminal neuralgia (TN) is a highly debilitating facial pain condition. Magnetic resonance imaging (MRI) is the main method for generating insights into the central mechanisms of TN pain in humans. Studies have found both structural and functional abnormalities in various brain structures in TN patients as compared with healthy controls. Whereas studies have also examined aberrations in brain networks in TN, no studies have to date investigated causal interactions in these brain networks and related these causal interactions to the levels of TN pain. We recorded fMRI data from 39 TN patients who either rested comfortably in the scanner during the resting state session or tracked their pain levels during the pain tracking session. Applying Granger causality to analyze the data and requiring consistent findings across the two scanning sessions, we found 5 causal interactions, including: (1) Thalamus → dACC, (2) Caudate → Inferior temporal gyrus, (3) Precentral gyrus → Inferior temporal gyrus, (4) Supramarginal gyrus → Inferior temporal gyrus, and (5) Bankssts → Inferior temporal gyrus, that were consistently associated with the levels of pain experienced by the patients. Utilizing these 5 causal interactions as predictor variables and the pain score as the predicted variable in a linear multiple regression model, we found that in both pain tracking and resting state sessions, the model was able to explain ∼36 % of the variance in pain levels, and importantly, the model trained on the 5 causal interaction values from one session was able to predict pain levels using the 5 causal interaction values from the other session, thereby cross-validating the models. These results, obtained by applying novel analytical methods to neuroimaging data, provide important insights into the pathophysiology of TN and could inform future studies aimed at developing innovative therapies for treating TN.

Identification of group differences in predictive anticipatory biasing of pain during uncertainty: preparing for the worst but hoping for the best.

ABSTRACT: Pain anticipation during conditions of uncertainty can unveil intrinsic biases, and understanding these biases can guide pain treatment interventions. This study used machine learning and functional magnetic resonance imaging to predict anticipatory responses in a pain anticipation experiment. One hundred forty-seven participants that included healthy controls (n = 57) and individuals with current and/or past mental health diagnosis (n = 90) received cues indicating upcoming pain stimuli: 2 cues predicted high and low temperatures, while a third cue introduced uncertainty. Accurate differentiation of neural patterns associated with specific anticipatory conditions was observed, involving activation in the anterior short gyrus of the insula and the nucleus accumbens. Three distinct response profiles emerged: subjects with a negative bias towards high pain anticipation, those with a positive bias towards low pain anticipation, and individuals whose predictions during uncertainty were unbiased. These profiles remained stable over one year, were consistent across diagnosed psychopathologies, and correlated with cognitive coping styles and underlying insula anatomy. The findings suggest that individualized and stable pain anticipation occurs in uncertain conditions.

Preoperative fatty infiltration of paraspinal muscles assessed by MRI is associated with less improvement of leg pain 2 years after surgery for lumbar spinal stenosis.

PURPOSE: Fatty infiltration (FI) of the paraspinal muscles may associate with pain and surgical complications in patients with lumbar spinal stenosis (LSS). We evaluated the prognostic influence of MRI-assessed paraspinal muscles' FI on pain or disability 2 years after surgery for LSS. METHODS: A muscle fat index (MFI) was calculated (by dividing signal intensity of psoas to multifidus and erector spinae) on preoperative axial T2-weighted MRI of patients with LSS. Pain and disability 2 years after surgery were assessed using the Oswestry disability index, the Zurich claudication questionnaire and numeric rating scales for leg and back pain. Multivariate linear and logistic regression analyses (adjusted for preoperative outcome scores, age, body mass index, sex, smoking status, grade of spinal stenosis, disc degeneration and facet joint osteoarthritis) were used to assess the associations between MFI and patient-reported clinical outcomes. In the logistic regression models, odds ratios (OR) and 95% confidence intervals (CI) were calculated for associations between the MFI and ≥ 30% improvement of the outcomes (dichotomised into yes/no). RESULTS: A total of 243 patients were evaluated (mean age 66.6 ± 8.5 years), 49% females (119). Preoperative MFI and postoperative leg pain were significantly associated, both with leg pain as continuous (coefficient - 3.20, 95% CI - 5.61, - 0.80) and dichotomised (OR 1.51, 95% CI 1.17, 1.95) scores. Associations between the MFI and the other outcome measures were not statistically significant. CONCLUSION: Preoperative FI of the paraspinal muscles on MRI showed statistically significant association with postoperative NRS leg pain but not with ODI or ZCQ.

Ultrasonography in plantar fibromatosis: the conduit between heel pain and 'catwalk'.

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Prevalence of radiographic appendicular osteoarthritis and associated clinical signs in young dogs.

This study aimed to determine the prevalence of osteoarthritis (OA) and associated clinical signs in young dogs. Owners of dogs aged 8 months-4 years from a single practice, were contacted in random order, to participate in a general health screen. Clinical and orthopedic examinations were performed. Each joint was scored for pain reactions (0-4). Orthogonal radiographs of all joints were made under sedation. Each joint was scored for radiographic OA (rOA) severity on an 11-point scale. Clinical OA (cOA) was defined as an overlap of rOA and joint pain in ≥ 1 joint. Owners completed OA questionnaires. The owners of 123 dogs agreed to participate. Overall, 39.8% (49/123) of dogs had rOA in ≥ 1 joint, and 16.3% (20/123) or 23.6% (29/123) dogs had cOA, depending on the cut-off value of joint pain; moderate (2), or mild (1), respectively. Owners of dogs with cOA observed signs of impairment in approximately 30% of cases. Only 2 dogs with cOA were receiving OA pain management. The most commonly affected joints in descending order of frequency were elbow, hip, tarsus, and stifle. Radiographically visible OA is common in young dogs, and 40-60% of dogs with rOA had cOA. However, OA-pain appears underdiagnosed and undertreated in young dogs.

The Neural Correlates of Individual Differences in Reinforcement Learning during Pain Avoidance and Reward Seeking.

Organisms learn to gain reward and avoid punishment through action-outcome associations. Reinforcement learning (RL) offers a critical framework to understand individual differences in this associative learning by assessing learning rate, action bias, pavlovian factor (i.e., the extent to which action values are influenced by stimulus values), and subjective impact of outcomes (i.e., motivation to seek reward and avoid punishment). Nevertheless, how these individual-level metrics are represented in the brain remains unclear. The current study leveraged fMRI in healthy humans and a probabilistic learning go/no-go task to characterize the neural correlates involved in learning to seek reward and avoid pain. Behaviorally, participants showed a higher learning rate during pain avoidance relative to reward seeking. Additionally, the subjective impact of outcomes was greater for reward trials and associated with lower response randomness. Our imaging findings showed that individual differences in learning rate and performance accuracy during avoidance learning were positively associated with activities of the dorsal anterior cingulate cortex, midcingulate cortex, and postcentral gyrus. In contrast, the pavlovian factor was represented in the precentral gyrus and superior frontal gyrus (SFG) during pain avoidance and reward seeking, respectively. Individual variation of the subjective impact of outcomes was positively predicted by activation of the left posterior cingulate cortex. Finally, action bias was represented by the supplementary motor area (SMA) and pre-SMA whereas the SFG played a role in restraining this action tendency. Together, these findings highlight for the first time the neural substrates of individual differences in the computational processes during RL.

Structural and functional changes of anterior cingulate cortex subregions in migraine without aura: relationships with pain sensation and pain emotion.

Migraine without aura is a multidimensional neurological disorder characterized by sensory, emotional, and cognitive symptoms linked to structural and functional abnormalities in the anterior cingulate cortex. Anterior cingulate cortex subregions play differential roles in the clinical symptoms of migraine without aura; however, the specific patterns and mechanisms remain unclear. In this study, voxel-based morphometry and seed-based functional connectivity were used to investigate structural and functional alterations in the anterior cingulate cortex subdivisions in 50 patients with migraine without aura and 50 matched healthy controls. Compared with healthy controls, patients exhibited (1) decreased gray matter volume in the subgenual anterior cingulate cortex, (2) increased functional connectivity between the bilateral subgenual anterior cingulate cortex and right middle frontal gyrus, and between the posterior part of anterior cingulate cortex and right middle frontal gyrus, orbital part, and (3) decreased functional connectivity between the anterior cingulate cortex and left anterior cingulate and paracingulate gyri. Notably, left subgenual anterior cingulate cortex was correlated with the duration of each attack, whereas the right subgenual anterior cingulate cortex was associated with migraine-specific quality-of-life questionnaire (emotion) and self-rating anxiety scale scores. Our findings provide new evidence supporting the hypothesis of abnormal anterior cingulate cortex subcircuitry, revealing structural and functional abnormalities in its subregions and emphasizing the potential involvement of the left subgenual anterior cingulate cortex-related pain sensation subcircuit and right subgenual anterior cingulate cortex -related pain emotion subcircuit in migraine.