Neural adaptation of the reward system in primary dysmenorrhea.

Introduction: The brain's reward system (RS) reacts differently to pain and its alleviation. This study examined the correlation between RS activity and behavior during both painful and pain-free periods in individuals with primary dysmenorrhea (PDM) to elucidate their varying responses throughout the menstrual cycle. Methods: Ninety-two individuals with PDM and 90 control participants underwent resting-state functional magnetic resonance imaging (rsfMRI) scans during their menstrual and peri-ovulatory phases. Regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) analyses were used to evaluate RS responses. Psychological evaluations were conducted using the McGill Pain Questionnaire and the Pain Catastrophizing Scale. Results: ReHo analysis showed higher values in the left putamen and right amygdala of the PDM group during the peri-ovulatory phase compared to the menstrual phase. ALFF analysis revealed lower values in the putamen of the PDM group compared to controls, regardless of phase. ReHo and ALFF values in the putamen, amygdala, and nucleus accumbens were positively correlated with pain scales during menstruation, while ALFF values in the ventral tegmental area inversely correlated with pain intensity. Those with severe PDM (pain intensity ≥7) displayed distinct amygdala ALFF patterns between pain and pain-free phases. PDM participants also had lower ReHo values in the left insula during menstruation, with no direct correlation to pain compared to controls. Discussion: Our study highlights the pivotal role of the RS in dysmenorrhea management, exhibiting varied responses between menstrual discomfort and non-painful periods among individuals with PDM. During menstruation, the RS triggers mechanisms for pain avoidance and cognitive coping strategies, while it transitions to processing rewards during the peri-ovulatory phase. This demonstrates the flexibility of the RS in adapting to the recurring pain experienced by those with PDM.

Long-term musical training induces white matter plasticity in emotion and language networks.

Numerous studies have reported that long-term musical training can affect brain functionality and induce structural alterations in the brain. Singing is a form of vocal musical expression with an unparalleled capacity for communicating emotion; however, there has been relatively little research on neuroplasticity at the network level in vocalists (i.e., noninstrumental musicians). Our objective in this study was to elucidate changes in the neural network architecture following long-term training in the musical arts. We employed a framework based on graph theory to depict the connectivity and efficiency of structural networks in the brain, based on diffusion-weighted images obtained from 35 vocalists, 27 pianists, and 33 nonmusicians. Our results revealed that musical training (both voice and piano) could enhance connectivity among emotion-related regions of the brain, such as the amygdala. We also discovered that voice training reshaped the architecture of experience-dependent networks, such as those involved in vocal motor control, sensory feedback, and language processing. It appears that vocal-related changes in areas such as the insula, paracentral lobule, supramarginal gyrus, and putamen are associated with functional segregation, multisensory integration, and enhanced network interconnectivity. These results suggest that long-term musical training can strengthen or prune white matter connectivity networks in an experience-dependent manner.

From "Aha!" to "Haha!" Using Humor to Cope with Negative Stimuli.

Humor has been considered an effective emotion regulation strategy, and some behavioral studies have examined its superior effects on negative emotion regulation. However, its neural mechanisms remain unknown. Our functional magnetic resonance imaging study directly compared the emotion regulation effects and neural bases of humorous coping (reappraisal) and ordinary reappraisal following exposure to negative pictures. The behavioral results suggested that humorous reappraisal was more effective in downregulating negative emotions and upregulating positive emotions both in the short and long term. We also found 2 cooperative neural pathways involved in coping with negative stimuli by means of humor: the "hippocampal-thalamic-frontal pathway" and the "amygdala-cerebellar pathway." The former is associated with the restructuring of mental representations of negative situations and accompanied by an insightful ("Aha!") experience, while the latter is associated with humorous emotional release and accompanied by an expression of laughter ("Haha!"). Furthermore, the degree of hippocampal functional connectivity with both the thalamus and frontal cortex was positively correlated with changes in positive emotion, and this result implied that the degree of emotion regulation could be strongly directly related to the depth of cognitive reconstruction. These findings highlight that regulating negative emotions with humor involves cognitive restructuring and the release of positive emotions.

Analgesic effects of repetitive transcranial magnetic stimulation on modified 2010 criteria-diagnosed fibromyalgia: Pilot study.

AIM: Fibromyalgia is often comorbid with depression, and less than half those patients achieve satisfactory improvement after adequate pharmacological intervention. The investigation of repetitive transcranial magnetic stimulation (rTMS) at left dorsolateral prefrontal cortex for modified-2010 American College of Rheumatology (ACR) fibromyalgia and major depressive disorder (MDD) is still in its infancy. METHODS: In this double-blind, randomized, sham-control study, subjects diagnosed with ACR-2010 fibromyalgia and DSM-IV-TR MDD were recruited and received either active or sham interventions for 2 weeks. Hamilton Depression Rating Scale (HDRS) and the 10-cm visual analogue pain scale were evaluated at baseline, week 1, and week 2. Multivariable generalized estimating equations analysis was performed for the association between depression and pain scores at each checkpoint. RESULTS: Twenty subjects were recruited. There was a significant difference over the 2 weeks between the rTMS and sham stimulation groups (P = 0.029), but subgroup analyses were further performed due to significant interaction of group and HDRS on pain outcomes (P = 0.020). The active group had significant improvement in pain at week 2 compared with week 1 (P = 0.021), but the control group did not have any improvement in pain (P = 0.585). Of the mild-moderate depression patients, the pain score in the active group was significantly lower than in the sham group at week 1 (P = 0.001) and at week 2 (P < 0.001). For the severe depression group, there was significantly lower pain over the 2 weeks in the active group (P = 0.045) but the sham group had significantly relapsing pain at week 2 (P < 0.001). CONCLUSION: Left prefrontal rTMS has an analgesic effect in modified-ACR 2010-defined fibromyalgia and MDD patients. Further investigation is required, however, in order to determine how to regulate the different rTMS treatment protocols according to individual baseline depression severity in patients with MDD and fibromyalgia.

Neuroimaging Studies of Primary Dysmenorrhea.

Primary dysmenorrhea (PDM), cyclic menstrual pain in the absence of pelvic anomalies, is one of the most common gynecological disorders in reproductive females. Classified as chronic pelvic pain syndrome, PDM encompasses recurrent spontaneous painful ("on") and pain-free ("off") states and is thus a good clinical model to study state- and trait-related changes of pain in the brain. In this chapter, we summarize state-of-the-art neuroimaging studies of primary dysmenorrhea from phenotype and endophenotype to genotype facets. Structural and functional brain alterations associated with primary dysmenorrhea are discussed.

Cognition-Modulated Frontal Activity in Prediction and Augmentation of Antidepressant Efficacy: A Randomized Controlled Pilot Study.

Higher rostral anterior cingulate cortex (rACC) activity correlated with frontal theta power (frontalθ) is associated with better antidepressant responses. The antidepressant efficacy of repetitive transcranial magnetic stimulation (rTMS) varied widely; however, the effects of TMS might be modulated by manipulating the pretreatment neural states. Therefore, we conducted a pilot study to investigate whether manipulated frontalθ before rTMS treatment could predict and augment antidepressant responses. A computerized rACC-engaging cognitive task (RECT) was exploited continuously for 10 min to patients with major depressive disorder. In total, 36 patients were randomized to 3 groups (Group-A: RECT[active] + rTMS[active]; Group-B: RECT[sham] + rTMS[active]; Group-C: RECT[active] + rTMS[sham]). Frontalθ and whole-brain glucose uptakes were assessed. We found that the RECT-modulated increases in frontalθ correlated well with rACC glucose uptakes. The treatment responders demonstrated a significant increase in frontalθ after RECT. Post-RECT frontalθ had good sensitivity/specificity in predicting antidepressant responses to rTMS. Group-A had more reduction in total depression scores, had more responders, and was more likely to achieve remission than other groups (Group-A [41.6%] > Group-B [16.6%] > Group-C [0%], P < 0.05). A significant enhancement in the post-1st-rTMS frontalθ was observed in Group-A responders but not in Group-B responders, supporting the argument that RECT-modulated rTMS augmented rTMS efficacy. In conclusion, this study suggests that manipulating pre-rTMS neural activity could predict and augment antidepressant effects to rTMS treatment.

Prefrontal glucose metabolism in medication-resistant major depression.

BACKGROUND: Medication-resistant depression (MRD) is associated with poorer attentional performance and immense socioeconomic costs. AIMS: We aimed to investigate the central pathophysiology of MRD, previously linked to impaired prefrontal cortex function. METHOD: A total of 54 participants (22 with MRD, 16 with non-resistant depression, 16 healthy controls) were recruited. Non-MRD status was confirmed by a prospective 6-week antidepressant trial. All medication-free participants underwent a go/no-go task to study prefrontal cortical function (attention) and positron emission tomography scans to study regional cerebral glucose metabolism (rCMglu) at rest. RESULTS: The MRD group had worse attentional ratings and decreased rCMglu compared with the non-MRD and control groups. Attentional performance was positively associated with prefrontal cortex rCMglu. The prefrontal cortex differences between MRD and non-MRD groups remained after adjusting for past depressive episodes (F(1,35) = 4.154, P = 0.043). CONCLUSIONS: Pronounced hypofrontality, with the associated attentional deficits, has a key role in the neuropathology of medication-resistant depression.

Functional dysconnection in the prefrontal-amygdala circuitry in unaffected siblings of patients with bipolar I disorder.

OBJECTIVES: Bipolar I disorder (BD) is a highly heritable disorder characterized by mood swings between high-energy and low-energy states. Amygdala hyperactivity and cortical inhibitory hypoactivity [e.g., of the dorsolateral prefrontal cortex (dlPFC)] have been found in patients with BD, as evidenced by their abnormal resting-state functional connectivity (FC) and glucose utilization (GU). However, it has not been determined whether functional abnormalities of the dlPFC-amygdala circuit exist in unaffected, healthy siblings of the patients with BD (BDsib). METHODS: Twenty euthymic patients with BD, 20 unaffected matching BDsib of the patient group, and 20 well-matched healthy control subjects were recruited. We investigated seed-based FC (seeds: dlPFC) with resting-state functional magnetic resonance imaging and GU in the regions of interest (e.g., dlPFC and amygdala) using (18) F-fluorodeoxyglucose positron emission tomography. RESULTS: The FC in the dlPFC (right)-amygdala circuit was statistically abnormal in patients with BD and BDsib, but only the patients with BD demonstrated hypoactive GU bilaterally in the dlPFC and hyperactive GU bilaterally in the amygdala. Facilitating differentiation between the BD groups, the altered FC between dlPFC (right) and amygdala (left) was even more prominent in the patients with BD (p < 0.05). CONCLUSIONS: There was a dysfunctional connection with intact GU in the dlPFC-amygdala circuit of the BDsib, which highlights the vulnerability in families with BD. Diminished top-down control from the bilateral dlPFC, which prevents adequate inhibition of limbic hyperactivity, might mediate the development of BD.

Efficacy of prefrontal theta-burst stimulation in refractory depression: a randomized sham-controlled study.

Theta-burst transcranial magnetic stimulation could modulate cortical excitability and has the potential to treat refractory depression. However, there has been a lack of large randomized studies of the antidepressant efficacy of different forms of theta-burst stimulation, such as intermittent and continuous theta-burst stimulation. A randomized sham-controlled study was conducted to investigate antidepressant efficacy of theta-burst stimulation and to compare efficacy among left-prefrontal intermittent theta-burst stimulation, right-prefrontal continuous theta-burst stimulation and a combination of them in patients showing different levels of antidepressant refractoriness. A group of 60 treatment-refractory patients with recurrent major depressive disorder were recruited and randomized to four groups (Group A: continuous theta-burst stimulation; Group B: intermittent theta-burst stimulation; Group C: a combination of continuous and intermittent theta-burst stimulation; and Group D: sham theta-burst stimulation; 15 patients were included in each group). After 2 weeks of theta-burst stimulation treatment, depression improved in all groups. Groups B and C had better antidepressant responses (as reflected by % decreases in depression score) than Groups A and D (P = 0.001, post hoc analysis: B > A, B > D, C > A, and C > D), even after controlling for age and refractoriness scores. The mean antidepressant effect was highest in Group C and followed by that in Group B. Additionally, a significant placebo effect was found in patients with low refractoriness; this disappeared in patients with moderate-to-high refractoriness. A significant correlation existed between refractoriness scores and treatment responses. Treatment refractoriness was a significant factor negatively predicting efficacy of theta-burst stimulation (P = 0.039). This randomized sham-controlled study demonstrated that active theta-burst stimulation is a well-tolerated form of repetitive transcranial magnetic stimulation and has good antidepressant efficacy, particularly in depressed subjects within a certain range of treatment refractoriness.

Extractions of steady-state auditory evoked fields in normal subjects and tinnitus patients using complementary ensemble empirical mode decomposition.

BACKGROUND: Auditory steady-state response (ASSR) induced by repetitive auditory stimulus is commonly used for audiometric testing. ASSR can be measured using electro-encephalography (EEG) and magnetoencephalography (MEG), referred to as steady-state auditory evoked potential (SSAEP) and steady-state auditory evoked field (SSAEF), respectively. However, the signal level of SSAEP and SSAEF are weak so that signal processing technique is required to increase its signal-to-noise ratio. In this study, a complementary ensemble empirical mode decomposition (CEEMD)-based approach is proposed in MEG study and the extraction of SSAEF has been demonstrated in normal subjects and tinnitus patients. METHODS: The CEEMD utilizes noise assisted data analysis (NADA) approach by adding positive and negative noise to decompose MEG signals into complementary intrinsic mode functions (IMF). Ten subjects (five normal and five tinnitus patients) were studied. The auditory stimulus was designed as 1 kHz carrier frequency with 37 Hz modulation frequency. Two channels in the vicinities of right and left temporal areas were chosen as channel-of-interests (COI) and decomposed into IMFs. The spatial distribution of each IMF was correlated with a pair of left- and right-hemisphere spatial templates, designed from each subject's N100m responses in pure-tone auditory stimulation. IMFs with spatial distributions highly correlated with spatial templates were identified using K-means and those SSAEF-related IMFs were used to reconstruct noise-suppressed SSAEFs. RESULTS: The current strengths estimated from CEEMD processed SSAEF showed neural activities greater or comparable to those processed by conventional filtering method. Both the normal and tinnitus groups showed the phenomenon of right-hemisphere dominance. The mean current strengths of auditory-induced neural activities in tinnitus group were larger than the normal group. CONCLUSIONS: The present study proposes an effective method for SSAEF extraction. The enhanced SSAEF in tinnitus group echoes the decreased inhibition in tinnitus's central auditory structures as reported in previous studies.

Effects of far-infrared radiation on heart rate variability and central manifestations in healthy subjects: a resting-fMRI study.

The aim of this study was to investigate the autonomic responses and central manifestations by peripheral FIR stimulation. Ten subjects (mean ± SD age 26.2 ± 3.52 years) received FIR stimulation at left median nerve territory for 40 min. Electrocardiograph was continuously recorded and heart rate variability (HRV) were analyzed. By using a 3 T-MRI scanner, three sessions of resting-state functional magnetic resonance images (fMRI) were acquired, namely, before (baseline-FIR), immediately after (IA-FIR) and 15 min after FIR was turned off (Post-FIR). The fractional amplitude of low-frequency (0.01-0.08 Hz) fluctuation (fALFF) of each session to evaluate the intensity of resting-brain activity in each session was analyzed. Our results showed that FIR stimulation induced significant HRV responses such as an increasing trend of nLF and LF/HF ratio, while FIR increased fALFF in right superior front gyrus, middle frontal gyrus and decreased the resting brain activity at fusiform gyrus, extrastriae cortex, inferior temporal gyrus and middle temporal gyrus, especially 15 min after FIR was turned off. We conclude that the central manifestation and the autonomic responses are prominent during and after FIR stimulation, which provide important mechanistic explanation on human disorder treated by such energy medicine.

Decoding and encoding of visual patterns using magnetoencephalographic data represented in manifolds.

Visual decoding and encoding are crucial aspects in investigating the representation of visual information in the human brain. This paper proposes a bidirectional model for decoding and encoding of visual stimulus based on manifold representation of the temporal and spatial information extracted from magnetoencephalographic data. In the proposed decoding process, principal component analysis is applied to extract temporal principal components (TPCs) from the visual cortical activity estimated by a beamforming method. The spatial distribution of each TPC is in a high-dimensional space and can be mapped to the corresponding spatiotemporal component (STC) on a low-dimensional manifold. Once the linear mapping between the STC and the wavelet coefficients of the stimulus image is determined, the decoding process can synthesize an image resembling the stimulus image. The encoding process is performed by reversing the mapping or transformation in the decoding model and can predict the spatiotemporal brain activity from a stimulus image. In our experiments using visual stimuli containing eleven combinations of checkerboard patches, the information of spatial layout in the stimulus image was revealed in the embedded manifold. The correlation between the reconstructed and original images was 0.71 and the correlation map between the predicted and original brain activity was highly correlated to the map between the original brain activity for different stimuli (r=0.89). These results suggest that the temporal component is important in visual processing and manifolds can well represent the information related to visual perception.

EEG coherences of the default mode network among patients comorbid with major depressive disorder and anxiety symptoms.

BACKGROUND: Higher functional connectivity within the default mode network (DMN) has been found in functional magnetic resonance imaging (fMRI) studies of major depressive disorder (MDD). We used electroencephalogram (EEG) coherence as an index of functional connectivity to examine group differences in DMN between the MDD and healthy control (HC) groups during the resting state. METHODS: MDD patients with comorbid anxiety symptoms (n = 154) and healthy controls (n = 165) completed the questionnaires of depression, anxiety, and rumination. A 19-channel EEG recording was measured under resting state for all participants. EEG coherences of the delta, theta, alpha, beta, and high beta in the anterior DMN (aDMN), posterior DMN (pDMN), aDMN-pDMN, DMN-parahippocampal gyrus (PHG), and DMN-temporal gyrus were compared between the two groups. The correlations between rumination, anxiety, and DMN coherence were examined in the MDD group. RESULTS: (1) No difference was found in the delta, theta, alpha, and beta within the DMN brain regions between the two groups; the MDD group showed higher high beta coherence within DMN brain regions than the HC group. (2) Rumination was negatively correlated with theta coherence of aDMN, and positively correlated with beta coherence of aDMN and with alpha coherence of pDMN and DMN-PHG. (3) Anxiety was positively correlated with high beta coherence of aDMN, pDMN, and DMN-PHG. CONCLUSIONS: MDD patients with comorbid anxiety symptoms exhibited hypercoherence within the DMN brain regions. Hypercoherences were related to symptoms of rumination, and anxiety may be a biomarker for MDD patients with comorbid anxiety symptoms.

The rhythmic mind: brain functions of percussionists in improvisation.

Introduction: Percussionists stand out for their expertise in rhythm, with the network for musical rhythm (NMR) serving a vital neurological function in their improvisation, which is deeply rooted in comprehensive musical knowledge. Our research examines the central representations of various improvisation tactics used by percussionists and investigates the interactions between the NMR and other relevant neural networks. Methods: Twenty-five percussionists participated in functional magnetic resonance imaging (fMRI) sessions, which included two cognitive strategies of improvisation. Structural improvisation (SIMP) emphasized rhythmic patterns, while free improvisation (FIMP) focused on musical spontaneity. Sight-reading scenario served as the reference condition. Paired t-tests were utilized for comparative analyses. Results: The findings revealed a dynamic interplay characterized by increased activity in the executive control network and NMR, along with decreased activity in the default mode network during SIMP. During FIMP, heightened activity was observed in the executive control network, NMR, limbic, and memory systems. In both SIMP vs. sight-reading and FIMP vs. sight-reading comparisons, the visual network's activity decreased, a trend also observed in the comparative analysis of FIMP vs. SIMP. Discussion: In SIMP, percussionists leverage external rhythmic signals, resulting in heightened NMR and ECN activity and reduced DMN activity. In contrast, FIMP is characterized by a rise in activity within the NMR, ECN, limbic system, memory system, and reward system, underscoring the vital roles of motivation and memory in the rapid production of spontaneous musical ideas within set frameworks. The diminished activity in the visual network during FIMP compared to SIMP suggests less reliance on visual stimuli in FIMP. These findings suggest that various improvisational tactics may engage different neural pathways.

Embodied metacognition as strengthened functional connection between neural correlates of metacognition and dance in dancers: exploring creativity implications.

Introduction: Dance education fosters embodied metacognition, enhancing student's creativity. This study examines the crucial role of functional connectivity (FC) between the neural correlates of metacognition (NCM) and dance (NCD) as the neurological foundation for dancers' embodied metacognition. The investigation also explores whether these consolidated FCs inform the general creativity in dancers. Methods: The research involved 29 dancers and 28 non-dancer controls. The study examined resting-state connections of the NCM through seed-based FC analysis. Correlation analyses were employed to investigate the connections between the targeted NCM-NCD FCs, initiated from the a priori NCM seed, and general creativity. Results: Dancers demonstrated heightened FC between NCM and NCD compared to non-dancer controls. The targeted regions included the putamen, globus pallidus, posterior cerebellum, and anterior insula of NCD. The dancers exhibited higher originality scores. In dancers, the enhanced FC showed a negative correlation with originality and a positive correlation with flexibility. Conversely, the controls exhibited no significant correlations. Discussion: Extended dance training enhances the NCM-NCD connection signifying embodied metacognition. This interconnectedness may serve as the neural predisposition for fostering general creativity performance in dancers. Dancers with heightened levels of originality could leverage the relatively weaker NCM-NCD FCs to facilitate better integration and coordination of creative cognitive processes. Our findings suggest that the consolidated functional connections as sculpted by domain-specific training may inform general creativity.

Inner sense of rhythm: percussionist brain activity during rhythmic encoding and synchronization.

Introduction: The main objective of this research is to explore the core cognitive mechanisms utilized by exceptionally skilled percussionists as they navigate complex rhythms. Our specific focus is on understanding the dynamic interactions among brain regions, respectively, related to externally directed cognition (EDC), internally directed cognition (IDC), and rhythm processing, defined as the neural correlates of rhythm processing (NCRP). Methods: The research involved 26 participants each in the percussionist group (PG) and control group (CG), who underwent task-functional magnetic resonance imaging (fMRI) sessions focusing on rhythm encoding and synchronization. Comparative analyses were performed between the two groups under each of these conditions. Results: Rhythmic encoding showed decreased activity in EDC areas, specifically in the right calcarine cortex, left middle occipital gyrus, right fusiform gyrus, and left inferior parietal lobule, along with reduced NCRP activity in the left dorsal premotor, right sensorimotor cortex, and left superior parietal lobule. During rhythmic synchronization, there was increased activity in IDC areas, particularly in the default mode network, and in NCRP areas including the left inferior frontal gyrus and bilateral putamen. Conversely, EDC areas like the right dorsolateral prefrontal gyrus, right superior temporal gyrus, right middle occipital gyrus, and bilateral inferior parietal lobule showed decreased activity, as did NCRP areas including the bilateral dorsal premotor cortex, bilateral ventral insula, bilateral inferior frontal gyrus, and left superior parietal lobule. Discussion: PG's rhythm encoding is characterized by reduced cognitive effort compared to CG, as evidenced by decreased activity in brain regions associated with EDC and the NCRP. Rhythmic synchronization reveals up-regulated IDC, down-regulated EDC involvement, and dynamic interplay among regions with the NCRP, suggesting that PG engages in both automatic and spontaneous processing simultaneously. These findings provide valuable insights into expert performance and present opportunities for improving music education.

Reward system neurodynamics during menstrual pain modulated by COMT Val158Met polymorphisms.

Introduction: Primary dysmenorrhea (PDM), characterized by cyclic pain, may involve pain modulation within the reward system (RS). The Catechol-O-methyltransferase (COMT) Val158Met polymorphism, which significantly influences dopamine activity, is linked to the regulation of both acute and chronic pain. This study examines the differential neurodynamic modulation in the RS associated with COMT Val158Met polymorphisms during menstrual pain among PDM subjects. Method: Ninety-one PDM subjects underwent resting-state fMRI during menstruation and were genotyped for COMT Val158Met polymorphisms. The amplitude of low-frequency fluctuation (ALFF) and functional connectivity (FC) analyses were used to assess the RS response. Psychological evaluations included the McGill Pain Questionnaire, Pain Catastrophizing Scale, Beck Anxiety Inventory, and Beck Depression Inventory. Result: Val/Val homozygotes (n = 50) and Met carriers (n = 41) showed no significant differences in McGill Pain Questionnaire, Beck Anxiety Inventory, and Beck Depression Inventory. However, Met carriers exhibited lower scores on the Pain Catastrophizing Scale. Distinct FC patterns was observed between Val/Val homozygotes and Met carriers, specifically between the nucleus accumbens (NAc) and prefrontal cortex, NAc and inferior parietal lobe, ventral tegmental area (VTA) and prefrontal cortex, VTA and precentral gyrus, and VTA and superior parietal lobe. Only Met carriers showed significant correlations between ALFF and FC values of the NAc and VTA with pain-related metrics (McGill Pain Questionnaire and Pain Catastrophizing Scale scores). NAc ALFF and NAc-prefrontal cortex FC values positively correlated with pain-related metrics, while VTA ALFF and VTA-prefrontal cortex and VTA-superior parietal lobe FC values negatively correlated with pain-related metrics. Discussion: This study reveals that the COMT Val158Met polymorphism results in genotype-specific functional changes in the brain's RS during menstrual pain. In Met carriers, engagement of these regions is potentially linked to motivational reward-seeking and top-down modulation. This polymorphism likely influences the RS's responses, significantly contributing to individual differences in pain regulation.

Neuromagnetic index of hemispheric asymmetry predicting long-term outcome in sudden hearing loss.

The neuromagnetic index of hemispheric asymmetry in terms of ipsilateral/contralateral ratio at acute stage was previously revealed to prognosticate the 1-month hearing outcome of acute unilateral idiopathic sudden sensorineural hearing loss (ISSNHL), showing a dynamic relationship between top- and down-levels of auditory pathway. However, the prognostic effect of reorganization pattern for the long-term results remained elusive. This study aimed to probe the prognosticating relevance of hemispheric asymmetry to the hearing at chronic stage of ISSNHL. Using magnetoencephalography (MEG), inter-hemispheric differences in peak dipole of N100m responses to monaural tones were evaluated in 21 controls and 21 ISSNHL patients at initial and final (12 months later) stages. Predictive value of hemispheric asymmetry was assessed by correlating hearing level and ipsilateral/contralateral ratio (I/C) of N100m latency and amplitude. Healthy-side dominance of N100m was observed in ISSNHL initially, and remained in three final prognostic subgroups (complete, partial, and no recovery) of ISSNHL. The initial I/C(amplitude) on affected-ear stimulation strongly correlated with the hearing level of final stage in ISSNHL. However, there was no prognostic effect of hemispheric asymmetry pattern for the 12-month hearing improvement. The heterogeneity between neuromagnetic index and hearing levels possibly echoed different pathogeneses of ISSNHL. Since a restored hearing status did not necessarily lead toward a normal functional organization, the dynamics of hemispheric asymmetry could actually index a central resilient reorganization in the brain for sound processing in ISSNHL. Our finding showed not only a clinically relevant measure to predict final hearing of ISSNHL, but also a linkage between central plasticity and cochlear lesion. This finding suggests a new perspective, and perhaps new interventions, to diagnose and treat unilateral ISSNHL.

fMRI hemodynamics accurately reflects neuronal timing in the human brain measured by MEG.

Neuronal activation sequence information is essential for understanding brain functions. Extracting such timing information from blood oxygenation level dependent (BOLD) fMRI is confounded by interregional neurovascular differences and poorly understood relations between BOLD and electrophysiological response delays. Here, we recorded whole-head BOLD fMRI at 100 ms resolution and magnetoencephalography (MEG) during a visuomotor reaction-time task. Both methods detected the same activation sequence across five regions, from visual towards motor cortices, with linearly correlated interregional BOLD and MEG response delays. The smallest significant interregional BOLD delay was 100 ms; all delays ≥400 ms were significant. Switching the order of external events reversed the sequence of BOLD activations, indicating that interregional neurovascular differences did not confound the results. This may open new avenues for using fMRI to follow rapid activation sequences in the brain.

Spinal microglia initiate and maintain hyperalgesia in a rat model of chronic pancreatitis.

BACKGROUND & AIMS: The chronic, persistent pain associated with chronic pancreatitis (CP) has many characteristics of neuropathic pain, initiated and maintained by the activation of spinal microglia. We investigated whether activated microglia in the thoracic spinal cord contribute to chronic pain in a rat model of CP. METHODS: CP was induced in Sprague-Dawley rats by an intraductal injection of 2% trinitrobenzene sulfonic acid. Hyperalgesia was assessed by the measurement of mechanical sensitivity of the abdomen and nocifensive behavior to electrical stimulation of the pancreas. Three weeks after induction of CP, spinal samples were analyzed by immunostaining and immunoblot analyses for levels of CD11 (a marker of microglia, determined with the antibody OX42) and phosphorylated p38 (P-p38, a marker of activation of p38 mitogen-activated protein kinase signaling). We examined the effects of minocycline (inhibitor of microglia) and fractalkine (microglia-activating factor) on visceral hyperalgesia in rats with CP. RESULTS: Rats with CP had increased sensitivity and nociceptive behaviors to mechanical probing of the abdomen and electrical stimulation of the pancreas. The dorsal horn of the thoracic spinal cords of rats with CP contained activated microglia (based on increased staining with OX42), with an ameboid appearance. Levels of P-p38 increased in rats with CP and colocalized with OX42-positive cells. Intrathecal injection of minocycline reversed and prevented the increase of nocifensive behaviors and levels of P-p38 in rats with CP. Fractalkine induced hyperalgesia in rats without CP, which was blocked by minocycline. CONCLUSIONS: Activated spinal microglia have important roles in maintaining and initiating chronic pain in a rat model of CP. Microglia might be a target for treatment of hyperalgesia caused by pancreatic inflammation.