Cep57 regulates human centrosomes through multivalent interactions.

Human Cep57 is a coiled-coil scaffold at the pericentriolar matrix (PCM), controlling centriole duplication and centrosome maturation for faithful cell division. Genetic truncation mutations of Cep57 are associated with the mosaic-variegated aneuploidy (MVA) syndrome. During interphase, Cep57 forms a complex with Cep63 and Cep152, serving as regulators for centrosome maturation. However, the molecular interplay of Cep57 with these essential scaffolding proteins remains unclear. Here, we demonstrate that Cep57 undergoes liquid-liquid phase separation (LLPS) driven by three critical domains (NTD, CTD, and polybasic LMN). In vitro Cep57 condensates catalyze microtubule nucleation via the LMN motif-mediated tubulin concentration. In cells, the LMN motif is required for centrosomal microtubule aster formation. Moreover, Cep63 restricts Cep57 assembly, expansion, and microtubule polymerization activity. Overexpression of competitive constructs for multivalent interactions, including an MVA mutation, leads to excessive centrosome duplication. In Cep57-depleted cells, self-assembly mutants failed to rescue centriole disengagement and PCM disorganization. Thus, Cep57's multivalent interactions are pivotal for maintaining the accurate structural and functional integrity of human centrosomes.

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.

Measurements of venous oxygen saturation in the superior sagittal sinus using conventional 3D multiple gradient-echo MRI: Effects of flow velocity and acceleration.

PURPOSE: This work investigates the effects of flow acceleration in the superior sagittal sinus on slice-dependent variations in venous oxygen saturation (SvO2 ) estimations using susceptibility-based MR oximetry. METHODS: Three-dimensional multiple gradient-echo images, with first-order flow compensation along the anterior-posterior readout direction for the first echo, were acquired twice from 15 healthy volunteers. For all slices, phases within the superior sagittal sinus were fitted using linear regression across four TEs to obtain the Pearson's correlation coefficients (PCCs), the largest of which corresponded to minimum acceleration influence. SvO2 derived from odd echoes on this slice was used to assess interscan difference, and compared with the central 15th slice for slice-dependent difference, both using Bland-Altman analysis. Within-scan interslice SvO2 consistency was examined versus PCC. Multislice-averaged SvO2 values were then computed from slices with PCCs above a certain threshold. RESULTS: Slice-dependent difference in SvO2 varied from -16.2% to 21.5% at two SDs, in agreement with a recent report, and about twice larger than interscan differences for the automatically selected slice (-7.5% to 10.3%) and for the central 15th slice (-8.0% to 8.8%). For slices with PCCs higher than -0.98, interslice SvO2 deviations were all found to be less than 5.0%. Multislice-averaged SvO2 with PCCs higher than -0.98 further reduced interscan difference to -4.7% to 8.2%. CONCLUSION: Slice-dependent variations in SvO2 may partly be explained by the effects of flow acceleration. Our method may enable conventional 3D multiple gradient echo to be used for SvO2 estimations in the presence of pulsatile flow.

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.

Cognitive and epilepsy outcomes after epilepsy surgery caused by focal cortical dysplasia in children: early intervention maybe better.

BACKGROUND: Focal cortical dysplasia (FCD) is a specific malformation of cortical development harboring intrinsic epileptogenicity, and most of the patients develop drug-resistant epilepsy in early childhood. The detrimental effects of early and frequent seizures on cognitive function in children are significant clinical issues. In this study, we evaluate the effects of early surgical intervention of FCD on epilepsy outcome and cognitive development. METHODS: From 2006 to 2013, 30 children younger than 18 years old underwent resective surgery for FCDs at Taipei Veterans General Hospital. The mean age at surgery was 10.0 years (range 1.7 to 17.6 years). There were 21 boys and 9 girls. In this retrospective clinical study, seizure outcome, cognitive function, and quality of life were evaluated. To evaluate the effects to outcomes on early interventions, the patients were categorized into four groups according to age of seizure onset, duration of seizure before surgery, and severity of cognitive deficits. RESULTS: Eleven of 22 (50 %) patients demonstrated developmental delay preoperatively. The Engel seizure outcome achievements were class I in 21 (70 %), class II in 2 (7 %), class III in 6 (20 %), and class IV in 1 (3 %) patients. The locations of FCDs resected were in the frontal lobe in 18 cases, temporal lobe in 7, parietal lobe in 2, and in bilobes including frontoparietal lobe in 2 and parieto-occipital lobes in 1. Eight cases that had FCDs involved in the rolandic cortex presented hemiparesis before surgical resection. Motor function in four of them improved after operation. The histopathological types of FCDs were type Ia in 1, type Ib in 7, type IIa in 7, type IIb in 12, and type III in 3 patients. FCDs were completely resected in 20 patients. Eighteen (90 %) of them were seizure free (p < 0.001) with three patients that received more than one surgery to accomplish complete resection. The patients who had early seizure onset, no significant cognitive function deficit, and early surgical intervention with complete resection in less than 2 years of seizure duration showed best outcomes on seizure control, cognitive function, and quality of life. CONCLUSION: Delay in cognitive development and poor quality of life is common in children treated for FCDs. Early surgical intervention and complete resection of the lesion help for a better seizure control, cognitive function development, and quality of life. FCDs involved eloquent cortex may not prohibit complete resection for better outcomes.

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.

Water signal attenuation by D2O infusion as a novel contrast mechanism for 1H perfusion MRI.

Deuterium oxide (D2 O), which is commercially available and nonradioactive, was proposed as a perfusion tracer before the clinical usage of conventional gadolinium-based MRI contrast agents. However, the sensitivity of direct deuterium detection is the major challenge for its application. In this study, we propose a contrast-enhanced strategy to indirectly trace administered D2 O by monitoring the signal attenuation of (1) H MRI. Experiments on D2 O concentration phantoms and in vivo rat brains were conducted to prove the concept of the proposed contrast mechanism. An average maximum signal drop ratio of 5.25 ± 0.91% was detected on (1) H MR images of rat brains with 2 mL of D2 O administered per 100 g of body weight. As a diffusible tracer for perfusion, D2 O infusion is a practicable method for the assessment of tissue perfusion and has the potential to provide different information from gadolinium-based contrast agents, which have limited permeability for blood vessels. Furthermore, the observed negative relaxivities of D2 O reveal the (1) H-D exchange effect. Therefore, applications of perfusion MRI with D2 O as a contrast agent are worthy of further investigation.

Trait representation of embodied cognition in dancers pivoting on the extended mirror neuron system: a resting-state fMRI study.

Introduction: Dance is an art form that integrates the body and mind through movement. Dancers develop exceptional physical and mental abilities that involve various neurocognitive processes linked to embodied cognition. We propose that dancers' primary trait representation is movement-actuated and relies on the extended mirror neuron system (eMNS). Methods: A total of 29 dancers and 28 non-dancer controls were recruited. A hierarchical approach of intra-regional and inter-regional functional connectivity (FC) analysis was adopted to probe trait-like neurodynamics within and between regions in the eMNS during rest. Correlation analyses were employed to examine the associations between dance training, creativity, and the FC within and between different brain regions. Results: Within the eMNS, dancers exhibited increased intra-regional FC in various brain regions compared to non-dancers. These regions include the left inferior frontal gyrus, left ventral premotor cortex, left anterior insula, left posterior cerebellum (crus II), and bilateral basal ganglia (putamen and globus pallidus). Dancers also exhibited greater intrinsic inter-regional FC between the cerebellum and the core/limbic mirror areas within the eMNS. In dancers, there was a negative correlation observed between practice intensity and the intrinsic FC within the eMNS involving the cerebellum and basal ganglia. Additionally, FCs from the basal ganglia to the dorsolateral prefrontal cortex were found to be negatively correlated with originality in dancers. Discussion: Our results highlight the proficient communication within the cortical-subcortical hierarchy of the eMNS in dancers, linked to the automaticity and cognitive-motor interactions acquired through training. Altered functional couplings in the eMNS can be regarded as a unique neural signature specific to virtuoso dancers, which might predispose them for skilled dancing performance, perception, and creation.

Enhanced intrinsic functional connectivity in the visual system of visual artist: Implications for creativity.

Introduction: This study sought to elucidate the cognitive traits of visual artists (VAs) from the perspective of visual creativity and the visual system (i.e., the most fundamental neural correlate). Methods: We examined the local and long-distance intrinsic functional connectivity (FC) of the visual system to unravel changes in brain traits among VAs. Twenty-seven university students majoring in visual arts and 27 non-artist controls were enrolled. Results: VAs presented enhanced local FC in the right superior parietal lobule, right precuneus, left inferior temporal gyrus (ITG), left superior parietal lobule, left angular gyrus, and left middle occipital gyrus. VAs also presented enhanced FC with the ITG that targeted the visual area (occipital gyrus and cuneus), which appears to be associated with visual creativity. Discussion: The visual creativity of VAs was correlated with strength of intrinsic functional connectivity in the visual system. Learning-induced neuroplasticity as a trait change observed in VAs can be attributed to the macroscopic consolidation of consociated neural circuits that are engaged over long-term training in the visual arts and aesthetic experience. The consolidated network can be regarded as virtuoso-specific neural fingerprint.

Corrigendum: Enhanced intrinsic functional connectivity in the visual system of visual artist: implications for creativity.

[This corrects the article DOI: 10.3389/fnins.2023.1114771.].

Enhanced white matter fiber tract of the cortical visual system in visual artists: implications for creativity.

Introduction: This study aimed to examine the white matter characteristics of visual artists (VAs) in terms of visual creativity and the structural connectivity within the cortical visual system. Methods: Diffusion spectrum imaging was utilized to examine the changes in white matter within the cortical visual system of a group of VAs (n = 25) in comparison to a group of healthy controls matched for age and education (n = 24). To assess the integrity of white matter and its relationship with visual creativity, we conducted a comprehensive analysis using region-based and track-specific tractographic examinations. Results: Our study uncovered that VAs demonstrated increased normalized quantitative anisotropy in specific brain regions, including the right inferior temporal gyrus and right lateral occipital gyrus, along with the corresponding white matter fiber tracts connecting these regions. These enhancements within the cortical visual system were also found to be correlated with measures of visual creativity obtained through psychological assessments. Discussion: The noted enhancement in the white matter within the cortical visual system of VAs, along with its association with visual creativity, is consistent with earlier research demonstrating heightened functional connectivity in the same system among VAs. Our study's findings suggest a link between the visual creativity of VAs and structural alterations within the brain's visual system.

Changes in resting-state functional connectivity in nonacute sciatica with acupuncture modulation: A preliminary study.

AIMS: To investigate the functional connectivity (FC) in nonacute sciatica and the neuronal correlation of acupuncture analgesia. METHODS: A prospective study employing resting-state functional magnetic resonance imaging was conducted. Twelve sciatica patients were enrolled to receive six or 18 acupoints of acupuncture treatment twice a week for 4 weeks. Regional homogeneity (ReHo) and seed-based FC were performed. RESULTS: Regional homogeneity analysis demonstrated a greater alteration in the right posterior cingulate cortex (PCC) during the pre-acupuncture phase than during the postacupuncture phase. Compared to that of healthy controls, the PCC-seeded FC (default mode network, DMN) of sciatica patients exhibited hyperconnectivity of PCC-FC with the PCC-bilateral insula, cerebellum, inferior parietal lobule, right medial prefrontal cortex, and dorsal anterior cingulate cortex during the pre-acupuncture phase as well as hypoconnectivity of PCC-FC with the right cerebellum, left precuneus, and left dorsal medial prefrontal cortex during the postacupuncture phase. Correlation analysis between PCC-seeded FC and behavior measurements revealed a positive association with the duration of sciatica in the right inferior parietal lobule prior to acupuncture treatment. CONCLUSIONS: Acupuncture in chronic sciatica patients is associated with normalized DMN activity and modulation of descending pain processing. The changes in the subclinical endophenotype of brain FC after acupuncture treatment may provide clues for understanding the mechanism of acupuncture-mediated analgesia in chronic pain.

Abnormal cerebral metabolism during menstrual pain in primary dysmenorrhea.

Primary dysmenorrhea (PDM, menstrual pain without pelvic abnormality) is the most common gynecological disorder for women in the reproductive age. It is characterized by cramping pain and enhanced pain sensitivity during the menstruation period. PDM has been associated with peripheral and central sensitization. Abnormal brain mechanisms may further contribute to development and maintenance of the state. Using fluoro-deoxyglucose positron emission tomography, increased activity was observed in prefrontal/orbitofrontal regions and left ventral posterior thalamus while decreased activity mainly was observed in sensorimotor regions of the left hemisphere at onset compared to offset of PDM. These results were specific to menstrual pain and were not found in menstrual matched controls. Orbitofrontal activities were positively related to while somatosensory activities where negatively related to subjective pain ratings. These results show that ongoing menstrual pain in PDM is accompanied by abnormal brain metabolism. Disinhibition of thalamo-orbitofrontal-prefrontal networks may contribute to the generation of pain and hyperalgesia in PDM possibly by maintaining spinal and thalamic sensitization while increasing negative affect. Excessive excitatory input during menstrual pain may induce compensatory inhibitory mechanism in several somatic sensorimotor regions.

Quantification of non-water-suppressed MR spectra with correction for motion-induced signal reduction.

Intrascan subject movement in clinical MR spectroscopic examinations may result in inconsistent water suppression that distorts the metabolite signals, frame-to-frame variations in spectral phase and frequency, and consequent reductions in the signal-to-noise ratio due to destructive averaging. Frame-to-frame phase/frequency corrections, although reported to be successful in achieving constructive averaging, rely on consistent water suppression, which may be difficult in the presence of intrascan motion. In this study, motion correction using non-water-suppressed data acquisition is proposed to overcome the above difficulties. The time-domain matrix-pencil postprocessing method was used to extract water signals from the non-water-suppressed spectroscopic data, followed by phase and frequency corrections of the metabolite signals based on information obtained from the water signals. From in vivo experiments on seven healthy subjects at 3.0 T, quantification of metabolites using the unsuppressed water signal as a reference showed improved correlation with water-suppressed data acquired in the absence of motion (R(2) = 0.9669; slope = 0.94). The metabolite concentrations derived using the proposed approach were in good agreement with literature values. Computer simulations under various degrees of frequency and phase variations further demonstrated robust performance of the time-domain postprocessing approach.

Sensory acquisition in the cerebellum: an FMRI study of cerebrocerebellar interaction during visual duration discrimination.

It has been suggested that the cerebellum participates in diverse neuropsychological functions by adjusting the sensory information acquired for the connected brain regions to support its processing capabilities. Nevertheless, the knowledge of how the cerebellum is modulated by the sensory information is far from clear. Function magnetic resonance imaging was exploited to investigate how the cerebellum activity and cerebrocerebellum interaction can be affected by the interaction between visual size and duration information during visual duration discrimination. The present findings support the sensory acquisition hypothesis that the cerebellum, together with extensive cortical networks, yields higher activation with incongruent sensory information to cope with increasing cortical computational demand. Furthermore, comprehensive intracerebellum connections are engaged in tasks with congruent sensory information for saving cortical computation with integrated sensory information.

Female menstrual phases modulate human prefrontal asymmetry: a magnetoencephalographic study.

We previously reported that the trait/baseline prefrontal cortex (PFC) activity expresses a dynamic plasticity during female menstrual cycle. The shift of asymmetric lateralization of PFC baseline activity pinpoints a possible emotional regulation of negative affection. The current emotional Go/NoGo study aimed to investigate the state PFC responses of different menstrual phases during fear facial stimulation in fourteen healthy women. Our data disclosed that the menstrual cycle was coupled with a shift of asymmetric lateralization of frontal activation across different menstrual phases. Evoked magnetic field activity in the time window 200-300 ms (M1) and 300-450 ms (M2) after stimulus onset demonstrated significant interactions between hemispheric side and menstrual phase. The right hemispheric dominance in periovulatory phase (OV) changed to left hemispheric dominance in menstrual (MC) phase. Significant association between the anxiety score and the left PFC activation was particularly observed in MC phase. Our study revealed a plastic resilience of functional organization of human brain and a dynamic automaticity of inter-hemispheric synergism for possible adaptive regulation under the aversive confrontation in accordance with hormonal fluctuation during the menstrual cycle.

Differing Spontaneous Brain Activity in Healthy Adults with Two Different Body Constitutions: A Resting-State Functional Magnetic Resonance Imaging Study.

Traditional Chinese medicine (TCM) practitioners assess body constitution (BC) as a treatment basis for maintaining body homeostasis. We investigated patterns in spontaneous brain activity in different BC groups using resting-state functional magnetic resonance imaging (rsfMRI) and determined the relationship between these patterns and quality of life (QOL). Thirty-two healthy individuals divided into two groups (body constitution questionnaire (BCQ)-gentleness [BCQ-G] and BCQ-deficiency [BCQ-D]) based on the body constitution questionnaire (BCQ) underwent rsfMRI to analyze regional homogeneity (ReHo) and the amplitude of low-frequency fluctuation (ALFF). The World Health Organization Quality of Life Instruments (brief edition) scale was used to evaluate the QOL. The BCQ-G group (n = 18) had significantly greater ReHo values in the right postcentral gyrus and lower ALFF values in the brainstem than the BCQ-D group (n = 14). In the BCQ-D group, decreased ReHo of the postcentral gyrus correlated with better physiological functioning; increased ALFF in the brainstem correlated with poor QOL. BCQ-subgroup analysis revealed a nonsignificant correlation between ReHo and Yang deficiency/phlegm and stasis (Phl & STA). Nonetheless, the BCQ-D group showed a positive correlation between ALFF and Phl & STA in the parahippocampus. This study identified differences between BCQ-G and BCQ-D types of healthy adults based on the rsfMRI analysis. The different BCQ types with varied brain endophenotypes may elucidate individualized TCM treatment strategies.

The resting frontal alpha asymmetry across the menstrual cycle: a magnetoencephalographic study.

Gonadotropic hormones play an important role in the regulation of emotion. Previous studies have demonstrated that estrogen can modulate appetitive (approach/positive) and aversive (avoidance/negative) affective behaviors during the menstrual cycle. Frontal alpha asymmetry (a measure of relative difference of the alpha power between the two anterior hemispheres) has been associated with the trait and state reactivity of different affective styles. We studied the pattern change of frontal alpha asymmetry across the menstrual cycle. 16 healthy women participated in this resting magneto-encephalographic (MEG) study during the peri-ovulatory (OV) and menstrual (MC) phases. Our results showed significant interaction of resting MEG alpha activity between hemispheric side and menstrual phases. Difference in spontaneous frontal alpha asymmetry pattern across the menstrual cycle was also noted. Relatively higher right frontal activity was found during the OV phase; relatively higher left frontal activity was noted during the MC phase. The alteration of frontal alpha asymmetry might serve a sub-clinical correlate for hormonal modulation effect on dynamic brain organization for the predisposition and conceptualization of different affective styles across the menstrual cycle.

Unaltered intrinsic functional brain architecture in young women with primary dysmenorrhea.

Primary dysmenorrhea (PDM), painful menstruation without organic causes, is the most prevalent gynecological problem in women of reproductive age. Dysmenorrhea later in life often co-occurs with many chronic functional pain disorders, and chronic functional pain disorders exhibit altered large-scale connectedness between distributed brain regions. It is unknown whether the young PDM females exhibit alterations in the global and local connectivity properties of brain functional networks. Fifty-seven otherwise healthy young PDM females and 62 age- and education-matched control females participated in the present resting-state functional magnetic resonance imaging study. We used graph theoretical network analysis to investigate the global and regional network metrics and modular structure of the resting-state brain functional networks in young PDM females. The functional network was constructed by the interregional functional connectivity among parcellated brain regions. The global and regional network metrics and modular structure of the resting-state brain functional networks were not altered in young PDM females at our detection threshold (medium to large effect size differences [Cohen's d ≥ 0.52]). It is plausible that the absence of significant changes in the intrinsic functional brain architecture allows young PDM females to maintain normal psychosocial outcomes during the pain-free follicular phase.

Central modulation of pain evoked from myofascial trigger point.

OBJECTIVES: Low-intensity low-frequency electrostimulation delivered within a myofascial trigger point (MTP) has been used as intervention to deactivate MTPs. The therapeutic effect has been suggested to be due to peripheral mechanisms. However, nonpainful stimuli are also known to reduce simultaneous pain through central effects. The primary objective of the present study was to assess if central pain modulation occurs after intervention with low-intensity electrostimulation within an MTP. We hypothesized that intervention induces pain inhibition via the periaqueductal gray (PAG). METHODS: Twenty-four patients with myofascial pain syndrome participated in the study. During functional magnetic resonance scanning, painful (high-intensity) intramuscular electrostimulation was delivered at random intervals (mean interstimulus interval=10.2 s) within an MTP of the upper left trapezius muscle. In-between scanning sessions, intervention (intramuscular electrostimulation, low-intensity, interstimulus interval=0.5 s) was applied to the same area. Patients were divided into responders and nonresponders according to their change in pressure pain thresholds relative to intervention. In addition to a whole brain search, a region of interest approach was also implemented to test the effect of intervention on PAG signal change. RESULTS: The main findings were: (1) intervention modulated PAG activity to painful stimuli more in responders than in nonresponders, (2) change in PAG activity from the whole patient population correlated with change in pressure pain threshold, and (3) a network known to regulate affective qualities of the pain experience was (subsignificantly) engaged more in responders than in nonresponders. DISCUSSION: The applied intervention most likely involves supraspinal pain control mechanisms related to both antinociception and regulation of pain affect.