Evaluation of the pain matrix using EEG source localization: a feasibility study.

OBJECTIVES: An extensive neuroimaging literature on chronic pain demonstrates increased cerebral blood flow and metabolism consistent with increased neuronal activity in the structures comprising the "pain matrix"; furthermore, some of these regions have been shown to encode pain intensity. It is the objective of this study to demonstrate the feasibility of using quantitative electroencephalography (EEG) source localization to reflect and to quantify activity in the pain matrix. METHODS: Eyes closed resting EEG was recorded from 19 standardized scalp locations, in a pilot sample of five patients with chronic neuropathic pain, before and after pain reduction. Quantitative electro encephalography (QEEG) source localization was computed estimating the mathematically most probable source generators of EEG surface potentials in each state. Sources identified in this way have been demonstrated to coregister with those identified by neuroimaging methods. RESULTS: QEEG sources demonstrated frequency specific increased neuronal activity in the baseline high pain state in structures including the thalamus, somatosensory cortex, anterior and posterior insula, medial and lateral prefrontal cortex and cingulate. Significant reduction of activation in these regions was seen when pain was reduced (≥50% on subjective ratings). CONCLUSION: The areas that were activated in the high pain state localized to the same regions reported by other neuroimaging methods and with frequency specificity. The frequency and regionally specific activation may indicate distinctive patterns of pathophysiology underlying the pain matrix. Although in a small number of patients, this work suggests that QEEG may be a useful tool in the exploration and quantification of the pain matrix in a clinical setting.

Exploration of the Pathophysiology of Chronic Pain Using Quantitative EEG Source Localization.

Chronic pain affects more than 35% of the US adult population representing a major public health imperative. Currently, there are no objective means for identifying the presence of pain, nor for quantifying pain severity. Through a better understanding of the pathophysiology of pain, objective indicators of pain might be forthcoming. Brain mechanisms mediating the painful state were imaged in this study, using source localization of the EEG. In a population of 77 chronic pain patients, significant overactivation of the "Pain Matrix" or pain network, was found in brain regions including, the anterior cingulate, anterior and posterior insula, parietal lobule, thalamus, S1, and dorsolateral prefrontal cortex (DLPFC), consistent with those reported with conventional functional imaging, and extended to include the mid and posterior cingulate, suggesting that the increased temporal resolution of electrophysiological measures may allow a more precise identification of the pain network. Significant differences between those who self-report high and low pain were reported for some of the regions of interest (ROIs), maximally on left hemisphere in the DLPFC, suggesting encoding of pain intensity occurs in a subset of pain network ROIs. Furthermore, a preliminary multivariate logistic regression analysis was used to select quantitative-EEG features which demonstrated a highly significant predictive relationship of self-reported pain scores. Findings support the potential to derive a quantitative measure of the severity of pain using information extracted from a multivariate descriptor of the abnormal overactivation. Furthermore, the frequency specific (theta/low alpha band) overactivation in the regions reported, while not providing direct evidence, are consistent with a model of thalamocortical dysrhythmia as the potential mechanism of the neuropathic painful condition.

The Brain Tumor Cooperative Group NIH Trial 87-01: a randomized comparison of surgery, external radiotherapy, and carmustine versus surgery, interstitial radiotherapy boost, external radiation therapy, and carmustine.

OBJECTIVE: The objective of the Brain Tumor Cooperative Group NIH Trial 87-01 trial was to investigate the effect of additional implanted radiation therapy in newly diagnosed patients with pathologically confirmed malignant gliomas. METHODS: The study involved a randomized comparison of surgery, external beam radiotherapy, and carmustine (BCNU) versus surgery, external beam therapy, interstitial radiotherapy boost, and BCNU in newly diagnosed malignant gliomas. (125)I was chosen as best suited for this effort because it allowed preimplantation planning and postimplantation quality assurance review. Two hundred ninety-nine patients met the eligibility criteria and were randomized into the two arms of the study between December 1987 and April 1994. Follow-up continued for an additional 3 years. Twenty-nine patients were identified as having committed protocol violations and were excluded, resulting in 270 subjects in the Valid Study Group. One hundred thirty-seven patients received external beam radiation and BCNU, and 133 underwent the (125)I implantation plus external beam radiation and BCNU therapy. RESULTS: The overall median survival for the Valid Study Group was 64.3 weeks. The median survival for patients receiving additional therapy of (125)I was 68.1 weeks, and median survival for those receiving only external beam radiation and BCNU was 58.8 weeks. The cumulative proportion surviving between the two treatment groups was not statistically significantly different (log-rank test, P = 0.101). As in other studies in the literature, age, Karnofsky score, and pathology were predictors of mortality. Additional analyses incorporating an adjustment for these prognostic variables, either in a stratified analysis or Cox proportional hazards model, did not result in statistically significant differences in the cumulative proportion of patients surviving between the two treatment groups. CONCLUSION: We conclude that there is no long-term survival advantage of increased radiation dose with (125)I seeds in newly diagnosed glioma patients.