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Machine learning-based prediction of clinical pain using multimodal neuroimaging and autonomic metrics.

ABSTRACT: Although self-report pain ratings are the gold standard in clinical pain assessment, they are inherently subjective in nature and significantly influenced by multidimensional contextual variables. Although objective biomarkers for pain could substantially aid pain diagnosis and development of novel therapies, reliable markers for clinical pain have been elusive. In this study, individualized physical maneuvers were used to exacerbate clinical pain in patients with chronic low back pain (N = 53), thereby experimentally producing lower and higher pain states. Multivariate machine-learning models were then built from brain imaging (resting-state blood-oxygenation-level-dependent and arterial spin labeling functional imaging) and autonomic activity (heart rate variability) features to predict within-patient clinical pain intensity states (ie, lower vs higher pain) and were then applied to predict between-patient clinical pain ratings with independent training and testing data sets. Within-patient classification between lower and higher clinical pain intensity states showed best performance (accuracy = 92.45%, area under the curve = 0.97) when all 3 multimodal parameters were combined. Between-patient prediction of clinical pain intensity using independent training and testing data sets also demonstrated significant prediction across pain ratings using the combined model (Pearson's r = 0.63). Classification of increased pain was weighted by elevated cerebral blood flow in the thalamus, and prefrontal and posterior cingulate cortices, and increased primary somatosensory connectivity to frontoinsular cortex. Our machine-learning approach introduces a model with putative biomarkers for clinical pain and multiple clinical applications alongside self-report, from pain assessment in noncommunicative patients to identification of objective pain endophenotypes that can be used in future longitudinal research aimed at discovery of new approaches to combat chronic pain.

SUBMITTER: Lee J

PROVIDER: S-EPMC6377310 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Machine learning-based prediction of clinical pain using multimodal neuroimaging and autonomic metrics.

Lee Jeungchan J Mawla Ishtiaq I Kim Jieun J Loggia Marco L ML Ortiz Ana A Jung Changjin C Chan Suk-Tak ST Gerber Jessica J Schmithorst Vincent J VJ Edwards Robert R RR Wasan Ajay D AD Berna Chantal C Kong Jian J Kaptchuk Ted J TJ Gollub Randy L RL Rosen Bruce R BR Napadow Vitaly V

Pain 20190301 3

Although self-report pain ratings are the gold standard in clinical pain assessment, they are inherently subjective in nature and significantly influenced by multidimensional contextual variables. Although objective biomarkers for pain could substantially aid pain diagnosis and development of novel therapies, reliable markers for clinical pain have been elusive. In this study, individualized physical maneuvers were used to exacerbate clinical pain in patients with chronic low back pain (N = 53), ...[more]

PMID: 30540621

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Project description:IntroductionChronic musculoskeletal pain is a prevalent condition impacting around 20% of people globally; resulting in patients living with pain, fatigue, restricted social and employment capacity, and reduced quality of life. Interdisciplinary multimodal pain treatment programs have been shown to provide positive outcomes by supporting patients modify their behavior and improve pain management through focusing attention on specific patient valued goals rather than fighting pain.MethodsGiven the complex nature of chronic pain there is no single clinical measure to assess outcomes from multimodal pain programs. Using Centre for Integral Rehabilitation data from 2019-2021 (n = 2,364), we developed a multidimensional machine learning framework of 13 outcome measures across 5 clinically relevant domains including activity/disability, pain, fatigue, coping and quality of life. Machine learning models for each endpoint were separately trained using the most important 30 of 55 demographic and baseline variables based on minimum redundancy maximum relevance feature selection. Five-fold cross validation identified best performing algorithms which were rerun on deidentified source data to verify prognostic accuracy.ResultsIndividual algorithm performance ranged from 0.49 to 0.65 AUC reflecting characteristic outcome variation across patients, and unbalanced training data with high positive proportions of up to 86% for some measures. As expected, no single outcome provided a reliable indicator, however the complete set of algorithms established a stratified prognostic patient profile. Patient level validation achieved consistent prognostic assessment of outcomes for 75.3% of the study group (n = 1,953). Clinician review of a sample of predicted negative patients (n = 81) independently confirmed algorithm accuracy and suggests the prognostic profile is potentially valuable for patient selection and goal setting.DiscussionThese results indicate that although no single algorithm was individually conclusive, the complete stratified profile consistently identified patient outcomes. Our predictive profile provides promising positive contribution for clinicians and patients to assist with personalized assessment and goal setting, program engagement and improved patient outcomes.

Project description:Diagnosis, clinical management and research of psychiatric disorders remain subjective - largely guided by historically developed categories which may not effectively capture underlying pathophysiological mechanisms of dysfunction. Here, we report a novel approach of identifying and validating distinct and biologically meaningful clinical phenotypes of bipolar disorders using both unsupervised and supervised machine learning techniques. First, neurocognitive data were analyzed using an unsupervised machine learning approach and two distinct clinical phenotypes identified namely; phenotype I and phenotype II. Second, diffusion weighted imaging scans were pre-processed using the tract-based spatial statistics (TBSS) method and 'skeletonized' white matter fractional anisotropy (FA) and mean diffusivity (MD) maps extracted. The 'skeletonized' white matter FA and MD maps were entered into the Elastic Net machine learning algorithm to distinguish individual subjects' phenotypic labels (e.g. phenotype I vs. phenotype II). This calculation was performed to ascertain whether the identified clinical phenotypes were biologically distinct. Original neurocognitive measurements distinguished individual subjects' phenotypic labels with 94% accuracy (sensitivity=92%, specificity=97%). TBSS derived FA and MD measurements predicted individual subjects' phenotypic labels with 76% and 65% accuracy respectively. In addition, individual subjects belonging to phenotypes I and II were distinguished from healthy controls with 57% and 92% accuracy respectively. Neurocognitive task variables identified as most relevant in distinguishing phenotypic labels included; Affective Go/No-Go (AGN), Cambridge Gambling Task (CGT) coupled with inferior fronto-occipital fasciculus and callosal white matter pathways. These results suggest that there may exist two biologically distinct clinical phenotypes in bipolar disorders which can be identified from healthy controls with high accuracy and at an individual subject level. We suggest a strong clinical utility of the proposed approach in defining and validating biologically meaningful and less heterogeneous clinical sub-phenotypes of major psychiatric disorders.

Project description:Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent and heterogeneous neurodevelopmental disorder, which is diagnosed using subjective symptom reports. Machine learning classifiers have been utilized to assist in the development of neuroimaging-based biomarkers for objective diagnosis of ADHD. However, existing basic model-based studies in ADHD report suboptimal classification performances and inconclusive results, mainly due to the limited flexibility for each type of basic classifier to appropriately handle multi-dimensional source features with varying properties. This study applied ensemble learning techniques (ELTs), a meta-algorithm that combine several basic machine learning models into one predictive model in order to decrease variance, bias, or improve predictions, in multimodal neuroimaging data collected from 72 young adults, including 36 probands (18 remitters and 18 persisters of childhood ADHD) and 36 group-matched controls. All currently available optimization strategies for ELTs (i.e., voting, bagging, boosting and stacking techniques) were tested in a pool of semifinal classification results generated by seven basic classifiers. The high-dimensional neuroimaging features for classification included regional cortical gray matter (GM) thickness and surface area, GM volume of subcortical structures, volume and fractional anisotropy of major white matter fiber tracts, pair-wise regional connectivity and global/nodal topological properties of the functional brain network for cue-evoked attention process. As a result, the bagging-based ELT with the base model of support vector machine achieved the best results, with significant improvement of the area under the receiver of operating characteristic curve (0.89 for ADHD vs. controls and 0.9 for ADHD persisters vs. remitters). Features of nodal efficiency in right inferior frontal gyrus, right middle frontal (MFG)-inferior parietal (IPL) functional connectivity, and right amygdala volume significantly contributed to accurate discrimination between ADHD probands and controls; higher nodal efficiency of right MFG greatly contributed to inattentive and hyperactive/impulsive symptom remission, while higher right MFG-IPL functional connectivity strongly linked to symptom persistence in adults with childhood ADHD. Considering their improved robustness than the commonly implemented basic classifiers, findings suggest that ELTs may have the potential to identify more reliable neurobiological markers for neurodevelopmental disorders.

Dataset Information

Machine learning-based prediction of clinical pain using multimodal neuroimaging and autonomic metrics.

Publications

Machine learning-based prediction of clinical pain using multimodal neuroimaging and autonomic metrics.

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