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      Pain phenotypes classified by machine learning using electroencephalography features

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          Abstract

          Pain is a multidimensional experience mediated by distributed neural networks in the brain. To study this phenomenon, EEGs were collected from 20 subjects with chronic lumbar radiculopathy, 20 age and gender matched healthy subjects, and 17 subjects with chronic lumbar pain scheduled to receive an implanted spinal cord stimulator. Analysis of power spectral density, coherence, and phase-amplitude coupling using conventional statistics showed that there were no significant differences between the radiculopathy and control groups after correcting for multiple comparisons. However, analysis of transient spectral events showed that there were differences between these two groups in terms of the number, power, and frequency-span of events in a low gamma band. Finally, we trained a binary support vector machine to classify radiculopathy versus healthy subjects, as well as a 3-way classifier for subjects in the 3 groups. Both classifiers performed significantly better than chance, indicating that EEG features contain relevant information pertaining to sensory states, and may be used to help distinguish between pain states when other clinical signs are inconclusive.

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          Most cited references59

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          Measuring phase-amplitude coupling between neuronal oscillations of different frequencies.

          Neuronal oscillations of different frequencies can interact in several ways. There has been particular interest in the modulation of the amplitude of high-frequency oscillations by the phase of low-frequency oscillations, since recent evidence suggests a functional role for this type of cross-frequency coupling (CFC). Phase-amplitude coupling has been reported in continuous electrophysiological signals obtained from the brain at both local and macroscopic levels. In the present work, we present a new measure for assessing phase-amplitude CFC. This measure is defined as an adaptation of the Kullback-Leibler distance-a function that is used to infer the distance between two distributions-and calculates how much an empirical amplitude distribution-like function over phase bins deviates from the uniform distribution. We show that a CFC measure defined this way is well suited for assessing the intensity of phase-amplitude coupling. We also review seven other CFC measures; we show that, by some performance benchmarks, our measure is especially attractive for this task. We also discuss some technical aspects related to the measure, such as the length of the epochs used for these analyses and the utility of surrogate control analyses. Finally, we apply the measure and a related CFC tool to actual hippocampal recordings obtained from freely moving rats and show, for the first time, that the CA3 and CA1 regions present different CFC characteristics.
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            Points of Significance: Statistics versus machine learning

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              Towards a theory of chronic pain.

              In this review, we integrate recent human and animal studies from the viewpoint of chronic pain. First, we briefly review the impact of chronic pain on society and address current pitfalls of its definition and clinical management. Second, we examine pain mechanisms via nociceptive information transmission cephalad and its impact and interaction with the cortex. Third, we present recent discoveries on the active role of the cortex in chronic pain, with findings indicating that the human cortex continuously reorganizes as it lives in chronic pain. We also introduce data emphasizing that distinct chronic pain conditions impact on the cortex in unique patterns. Fourth, animal studies regarding nociceptive transmission, recent evidence for supraspinal reorganization during pain, the necessity of descending modulation for maintenance of neuropathic behavior, and the impact of cortical manipulations on neuropathic pain is also reviewed. We further expound on the notion that chronic pain can be reformulated within the context of learning and memory, and demonstrate the relevance of the idea in the design of novel pharmacotherapies. Lastly, we integrate the human and animal data into a unified working model outlining the mechanism by which acute pain transitions into a chronic state. It incorporates knowledge of underlying brain structures and their reorganization, and also includes specific variations as a function of pain persistence and injury type, thereby providing mechanistic descriptions of several unique chronic pain conditions within a single model.
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                Author and article information

                Journal
                9215515
                20498
                Neuroimage
                Neuroimage
                NeuroImage
                1053-8119
                1095-9572
                23 April 2022
                December 2020
                29 August 2020
                09 May 2022
                : 223
                : 117256
                Affiliations
                [a ]Department of Neurosurgery, Rhode Island Hospital, Providence, RI, United States
                [b ]Department of Neuroscience, Brown University, Providence, RI, United States
                [c ]Laboratory for Pharmacology, Asahi Kasei Pharma Corporation, Mifuku, Shizuoka, Japan
                [d ]Boston Scientific Neuromodulation, Valencia, CA, United States
                Author notes

                Author contributions

                JL contributed to pre-processing, statistical analysis, and machine learning sections, to the data collection, and to the writing of the paper.

                MME contributed to data collection and recruitment.

                RVT contributed to the spectral event analysis and to writing the paper.

                JWL contributed to statistical analysis and machine learning sections.

                MM, SK, and SY contributed to study design.

                KAS and AGC contributed to participant identification and recruitment.

                WG, KHS, BAC, and RE contributed to study design.

                SRJ contributed to spectral event analysis and oversight.

                DAB contributed to oversight.

                CYS contributed to study design and oversight, and to writing the paper.

                [* ]Corresponding author. carl_saab@ 123456brown.edu (C.Y. Saab).
                Article
                NIHMS1797911
                10.1016/j.neuroimage.2020.117256
                9084327
                32871260
                aa7b87a4-9698-46b7-8ee8-ae15e0e05a12

                This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/)

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