Several studies have reported reduced cerebral gray matter (GM) volume/density in chronic pain conditions, but there is limited research on plasticity of the human cortex in response to psychological interventions. We investigated GM changes after cognitive behavioral therapy (CBT) in patients with chronic pain. We used voxel based morphometry (VBM) to compare anatomical MRI scans of 13 patients with mixed chronic pain types before and after an 11-week CBT treatment and to 13 healthy control participants. CBT led to significant improvements in clinical measures. Patients did not differ from healthy controls in GM anywhere in the brain. After treatment, patients had increased GM in bilateral dorsolateral prefrontal (DLPFC), posterior parietal (PPC), subgenual anterior cingulate (ACC)/orbitofrontal, and sensorimotor cortices, as well as hippocampus, and reduced GM in supplementary motor area. In most of these areas showing GM increases, GM became significantly higher than in controls. Decreased pain catastrophizing was associated with increased GM in left DLPFC and ventrolateral prefrontal (VLPFC), right PPC, somatosensory cortex, and pregenual ACC. While future studies with additional control groups will be needed to determine the specific roles of CBT on GM and brain function, we propose that increased GM in the PFC and PPC reflects greater top-down control over pain and cognitive reappraisal of pain, and that changes in somatosensory cortices reflect alterations in the perception of noxious signals. Perspective An 11-week CBT intervention for coping with chronic pain resulted in increased gray matter volume in prefrontal and somatosensory brain regions, as well as increased dorsolateral prefrontal volume associated with reduced pain catastrophizing. These results add to mounting evidence that CBT can be a valuable treatment option for chronic pain.

To investigate the neuroanatomical and functional brain changes in migraine patients relative to healthy controls, we used a combined analytical approach including voxel- and surface-based morphometry along with resting-state functional connectivity to determine whether areas showing structural alterations in patients also showed abnormal functional connectivity. Additionally, we wanted to assess whether these structural and functional changes were associated with group differences in pain catastrophizing and migraine-related disease variables in patients. We acquired T1-weighted anatomical and functional magnetic resonance imaging scans during rest in human subjects with a diagnosis of migraine and healthy controls. Structural analyses revealed greater left hippocampal gray matter volume and reduced cortical thickness in the left anterior midcingulate in patients compared with controls. We also observed negative associations between pain catastrophizing and migraine disease variables and gray matter in areas implicated in processing the sensory, affective, and cognitive aspects of pain in patients. Functional connectivity analyses showed that migraine patients displayed disrupted connectivity between default mode, salience, cognitive, visuospatial, and sensorimotor networks, which was associated with group differences in pain catastrophizing and migraine-related disease variables in patients. Together, our findings show widespread morphological and functional brain abnormalities in migraineurs in affective, cognitive, visual, and pain-related brain areas, which are associated with increased pain catastrophizing, disease chronicity, and severity of symptoms, suggesting that these structural and functional changes may be a consequence of repeated, long-term nociceptive signaling leading to increased pain sensitivity, mood disturbances, and maladaptive coping strategies to deal with unrelenting pain.

The identification of neurobiological markers that predict individual predisposition to pain are not only important for development of effective pain treatments, but would also yield a more complete understanding of how pain is implemented in the brain. In the current study using electroencephalography (EEG), we investigated the relationship between the peak frequency of alpha activity over sensorimotor cortex and pain intensity during capsaicin-heat pain (C-HP), a prolonged pain model known to induce spinal central sensitization in primates. We found that peak alpha frequency (PAF) recorded during a pain-free period preceding the induction of prolonged pain correlated with subsequent pain intensity reports: slower peak frequency at pain-free state was associated with higher pain during the prolonged pain condition. Moreover, the degree to which PAF decreased between pain-free and prolonged pain states was correlated with pain intensity. These two metrics were statistically uncorrelated and in combination were able to account for 50% of the variability in pain intensity. Altogether, our findings suggest that pain-free state PAF over relevant sensory systems could serve as a marker of individual predisposition to prolonged pain. Moreover, slowing of PAF in response to prolonged pain could represent an objective marker for subjective pain intensity. Our findings potentially lead the way for investigations in clinical populations in which alpha oscillations and the brain areas contributing to their generation are used in identifying and formulating treatment strategies for patients more likely to develop chronic pain.

Burning mouth syndrome (BMS) is a debilitating, idiopathic chronic pain condition. For many BMS patients, burning oral pain begins in late morning and becomes more intense throughout the day, peaking by late afternoon or evening. We investigated brain gray matter volume (GMV) with voxel-based morphometry (VBM), white matter fractional anisotropy (FA) with diffusion tensor imaging (DTI), and functional connectivity in resting state functional MRI (rsfMRI) in a tightly screened, homogeneous sample of 9 female, postmenopausal/perimenopausal BMS patients and 9 matched healthy control subjects. Patients underwent 2 scanning sessions in the same day: in the morning, when ongoing pain/burning was low, and in the afternoon, when pain/burning was significantly higher. Patients had increased GMV and lower FA in the hippocampus (Hc), and decreased GMV in the medial prefrontal cortex (mPFC). rsfMRI revealed altered connectivity patterns in different states of pain/burning, with increased connectivity between mPFC (a node in the default mode network) and anterior cingulate cortex, occipital cortex, ventromedial PFC, and bilateral Hc/amygdala in the afternoon compared with the morning session. Furthermore, mPFC-Hc connectivity was higher in BMS patients than control subjects for the afternoon but not the morning session. mPFC-Hc connectivity was related to Beck depression inventory scores both between groups and between burning states within patients, suggesting that depression and anxiety partially explain pain-related brain dysfunction in BMS. Overall, we provide multiple lines of evidence supporting aberrant structure and function in the mPFC and Hc, and implicate a circuit involving the mPFC and Hc in regulating mood and depressive symptoms in BMS.

Longitudinal Data in Two Groups Longitudinal Data in Two Groups with interaction of covariate by group 42 Adapting the CAT12 workflow for unusual populations Customized Tissue Probability Maps 46 Customized DARTEL-template Other variants of computational morphometry Deformation-based morphometry (DBM) Surface-based morphometry (SBM) Region of interest (ROI) analysis Additional information on native, normalized and modulated volumes Naming convention of output files Calling CAT from the UNIX command line Technical information CAT12 Citation References 1 Note to filter sizes for Gaussian smoothing Due to the high accuracy of the spatial registration approaches used in CAT12, you can also try to use smaller filter sizes. However, for very small filter sizes or even no filtering, you have to apply a non-parametric permutation test such as the TFCE-statistics. Please also note that for the analysis of cortical folding measures such as gyrification or cortical complexity the filter sizes have to be larger (i.e. in the range of 15-25mm). This is due to the underlying nature of this measure that reflects contributions from both sulci as well as gyri. Therefore, the filter size should exceed the distance between a gyral crown and a sulcal fundus.