Brain Mechanisms of Virtual Reality Breathing Versus Traditional Mindful Breathing in Pain Modulation: Observational Functional Near-infrared Spectroscopy Study.

BACKGROUND: Pain is a complex experience that involves sensory-discriminative and cognitive-emotional neuronal processes. It has long been known across cultures that pain can be relieved by mindful breathing (MB). There is a common assumption that MB exerts its analgesic effect through interoception. Interoception refers to consciously refocusing the mind's attention to the physical sensation of internal organ function. OBJECTIVE: In this study, we dissect the cortical analgesic processes by imaging the brains of healthy subjects exposed to traditional MB (TMB) and compare them with another group for which we augmented MB to an outside sensory experience via virtual reality breathing (VRB). METHODS: The VRB protocol involved in-house-developed virtual reality 3D lungs that synchronized with the participants' breathing cycles in real time, providing them with an immersive visual-auditory exteroception of their breathing. RESULTS: We found that both breathing interventions led to a significant increase in pain thresholds after week-long practices, as measured by a thermal quantitative sensory test. However, the underlying analgesic brain mechanisms were opposite, as revealed by functional near-infrared spectroscopy data. In the TMB practice, the anterior prefrontal cortex uniquely modulated the premotor cortex. This increased its functional connection with the primary somatosensory cortex (S1), thereby facilitating the S1-based sensory-interoceptive processing of breathing but inhibiting its other role in sensory-discriminative pain processing. In contrast, virtual reality induced an immersive 3D exteroception with augmented visual-auditory cortical activations, which diminished the functional connection with the S1 and consequently weakened the pain processing function of the S1. CONCLUSIONS: In summary, our study suggested two analgesic neuromechanisms of VRB and TMB practices-exteroception and interoception-that distinctively modulated the S1 processing of the ascending noxious inputs. This is in line with the concept of dualism (Yin and Yang).

Sensory-Discriminative Three-Dimensional Body Pain Mobile App Measures Versus Traditional Pain Measurement With a Visual Analog Scale: Validation Study.

BACKGROUND: To quantify pain severity in patients and the efficacy treatments, researchers and clinicians apply tools such as the traditional visual analog scale (VAS) that leads to inaccurate interpretation of the main sensory pain. OBJECTIVE: This study aimed to validate the pain measurements of a neuroscience-based 3D body pain mobile app called GeoPain. METHODS: Patients with temporomandibular disorder (TMD) were assessed using GeoPain measures in comparison to VAS and positive and negative affect schedule (PANAS), pain and mood scales, respectively. Principal component analysis (PCA), scatter score analysis, Pearson methods, and effect size were used to determine the correlation between GeoPain and VAS measures. RESULTS: The PCA resulted in two main orthogonal components: first principal component (PC1) and second principal component (PC2). PC1 comprises a combination score of all GeoPain measures, which had a high internal consistency and clustered together in TMD pain. PC2 included VAS and PANAS. All loading coefficients for GeoPain measures in PC1 were above 0.70, with low loadings for VAS and PANAS. Meanwhile, PC2 was dominated by a VAS and PANAS coefficient >0.4. Repeated measure analysis revealed a strong correlation between the VAS and mood scores from PANAS over time, which might be related to the subjectivity of the VAS measure, whereas sensory-discriminative GeoPain measures, not VAS, demonstrated an association between chronicity and TMD pain in locations spread away from the most commonly reported area or pain epicenter (P=.01). Analysis using VAS did not detect an association at baseline between TMD and chronic pain. The long-term reliability (lag >1 day) was consistently high for the pain area and intensity number summation (PAINS) with lag autocorrelations averaging between 0.7 and 0.8, and greater than the autocorrelations for VAS averaging between 0.3 and 0.6. The combination of higher reliability for PAINS and its objectivity, displayed by the lack of association with PANAS as compared with VAS, indicated that PAINS has better sensitivity and reliability for measuring treatment effect over time for sensory-discriminative pain. The effect sizes for PAINS were larger than those for VAS, consequently requiring smaller sample sizes to assess the analgesic efficacy of treatment if PAINS was used versus VAS. The PAINS effect size was 0.51 SD for both facial sides and 0.60 SD for the right side versus 0.35 SD for VAS. Therefore, the sample size required to detect such effect sizes with 80% power would be n=125 per group for VAS, but as low as n=44 per group for PAINS, which is almost a third of the sample size needed by VAS. CONCLUSIONS: GeoPain demonstrates precision and reliability as a 3D mobile interface for measuring and analyzing sensory-discriminative aspects of subregional pain in terms of its severity and response to treatment, without being influenced by mood variations from patients.

Feasibility of a Real-Time Clinical Augmented Reality and Artificial Intelligence Framework for Pain Detection and Localization From the Brain.

BACKGROUND: For many years, clinicians have been seeking for objective pain assessment solutions via neuroimaging techniques, focusing on the brain to detect human pain. Unfortunately, most of those techniques are not applicable in the clinical environment or lack accuracy. OBJECTIVE: This study aimed to test the feasibility of a mobile neuroimaging-based clinical augmented reality (AR) and artificial intelligence (AI) framework, CLARAi, for objective pain detection and also localization direct from the patient's brain in real time. METHODS: Clinical dental pain was triggered in 21 patients by hypersensitive tooth stimulation with 20 consecutive descending cold stimulations (32°C-0°C). We used a portable optical neuroimaging technology, functional near-infrared spectroscopy, to gauge their cortical activity during evoked acute clinical pain. The data were decoded using a neural network (NN)-based AI algorithm to classify hemodynamic response data into pain and no-pain brain states in real time. We tested the performance of several networks (NN with 7 layers, 6 layers, 5 layers, 3 layers, recurrent NN, and long short-term memory network) upon reorganized data features on pain diction and localization in a simulated real-time environment. In addition, we also tested the feasibility of transmitting the neuroimaging data to an AR device, HoloLens, in the same simulated environment, allowing visualization of the ongoing cortical activity on a 3-dimensional brain template virtually plotted on the patients' head during clinical consult. RESULTS: The artificial neutral network (3-layer NN) achieved an optimal classification accuracy at 80.37% (126,000/156,680) for pain and no pain discrimination, with positive likelihood ratio (PLR) at 2.35. We further explored a 3-class localization task of left/right side pain and no-pain states, and convolutional NN-6 (6-layer NN) achieved highest classification accuracy at 74.23% (1040/1401) with PLR at 2.02. CONCLUSIONS: Additional studies are needed to optimize and validate our prototype CLARAi framework for other pains and neurologic disorders. However, we presented an innovative and feasible neuroimaging-based AR/AI concept that can potentially transform the human brain into an objective target to visualize and precisely measure and localize pain in real time where it is most needed: in the doctor's office. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/13594.

Electronic device use by individuals with traumatic spinal cord injury.

OBJECTIVE: To describe use of several electronic devices among individuals with traumatic spinal cord injury (SCI). STUDY DESIGN: Cross-sectional survey. SETTING: Community. METHODS: Potential participants consisted of all individuals with traumatic SCI, ages 7 and older, who had received care through a large academic medical center in the Midwest between January 1, 2003, and January 2, 2013. All eligible individuals received the survey as part of a four-stage mailing that asked questions about electronic device use in addition to questions about demographic and injury-related characteristics. RESULTS: Mailings were sent to 820 individuals; of those, 451 completed and returned the survey. Descriptive and nonparametric statistics were performed. Individuals with high-level tetraplegia were less likely to use tablet and handheld electronic devices than individuals at all other SCI levels. Individuals aged 65 years and older were less likely to own or use tablet computers and handheld devices than all other age groups. CONCLUSION: While electronic devices hold considerable potential as a treatment modality for individuals who have sustained SCI, there is diversity in the particular electronic devices that are used by such individuals due to injury-related characteristics and age.

µ-Opioid activation in the midbrain during migraine allodynia - brief report II.

We investigated in vivo the allodynic response of the central µ-opioid system during spontaneous migraine headaches, following a sustained pain threshold challenge on the trigeminal ophthalmic region. Six migraineurs were scanned during the ictal and interictal phases using positron emission tomography (PET) with the selective µ-opioid receptor (µOR) radiotracer [11C]carfentanil. Females were scanned during the mid-late follicular phase of two separate cycles. Patients showed ictal trigeminal allodynia during the thermal challenge that was concurrent and positively correlated with µOR activation in the midbrain, extending from red nucleus to ventrolateral periaqueductal gray matter. These findings demonstrate for the first time in vivo the high µOR activation in the migraineurs' brains in response to their allodynic experience.

Association of µ-Opioid Activation in the Prefrontal Cortex with Spontaneous Migraine Attacks - Brief Report I.

We evaluated in vivo the µ-opioid system during spontaneous episodic migraine headaches. Seven patients were scanned at different phases of their migraine using Positron Emission Tomography with the selective µ-opioid receptor (µOR) radiotracer [11C]carfentanil. In the ictal phase, there was µOR activation in the medial prefrontal cortex, which was strongly associated with the µOR availability level during the interictal phase. Furthermore, µ-opioid binding changes showed moderate negative correlation with the combined extension and severity of the attacks. These results indicate for the first time that there is high µOR activation in the migraineurs' brains during headache attacks in response to their pain.

3D-neuronavigation in vivo through a patient's brain during a spontaneous migraine headache.

A growing body of research, generated primarily from MRI-based studies, shows that migraine appears to occur, and possibly endure, due to the alteration of specific neural processes in the central nervous system. However, information is lacking on the molecular impact of these changes, especially on the endogenous opioid system during migraine headaches, and neuronavigation through these changes has never been done. This study aimed to investigate, using a novel 3D immersive and interactive neuronavigation (3D-IIN) approach, the endogenous µ-opioid transmission in the brain during a migraine headache attack in vivo. This is arguably one of the most central neuromechanisms associated with pain regulation, affecting multiple elements of the pain experience and analgesia. A 36 year-old female, who has been suffering with migraine for 10 years, was scanned in the typical headache (ictal) and nonheadache (interictal) migraine phases using Positron Emission Tomography (PET) with the selective radiotracer [(11)C]carfentanil, which allowed us to measure µ-opioid receptor availability in the brain (non-displaceable binding potential - µOR BPND). The short-life radiotracer was produced by a cyclotron and chemical synthesis apparatus on campus located in close proximity to the imaging facility. Both PET scans, interictal and ictal, were scheduled during separate mid-late follicular phases of the patient's menstrual cycle. During the ictal PET session her spontaneous headache attack reached severe intensity levels; progressing to nausea and vomiting at the end of the scan session. There were reductions in µOR BPND in the pain-modulatory regions of the endogenous µ-opioid system during the ictal phase, including the cingulate cortex, nucleus accumbens (NAcc), thalamus (Thal), and periaqueductal gray matter (PAG); indicating that µORs were already occupied by endogenous opioids released in response to the ongoing pain. To our knowledge, this is the first time that changes in µOR BPND during a migraine headache attack have been neuronavigated using a novel 3D approach. This method allows for interactive research and educational exploration of a migraine attack in an actual patient's neuroimaging dataset.

Reduced basal ganglia µ-opioid receptor availability in trigeminal neuropathic pain: a pilot study.

BACKGROUND: Although neuroimaging techniques have provided insights into the function of brain regions involved in Trigeminal Neuropathic Pain (TNP) in humans, there is little understanding of the molecular mechanisms affected during the course of this disorder. Understanding these processes is crucial to determine the systems involved in the development and persistence of TNP. FINDINGS: In this study, we examined the regional µ-opioid receptor (µOR) availability in vivo (non-displaceable binding potential BPND) of TNP patients with positron emission tomography (PET) using the µOR selective radioligand [11C]carfentanil. Four TNP patients and eight gender and age-matched healthy controls were examined with PET. Patients with TNP showed reduced µOR BPND in the left nucleus accumbens (NAc), an area known to be involved in pain modulation and reward/aversive behaviors. In addition, the µOR BPND in the NAc was negatively correlated with the McGill sensory and total pain ratings in the TNP patients. CONCLUSIONS: Our findings give preliminary evidence that the clinical pain in TNP patients can be related to alterations in the endogenous µ-opioid system, rather than only to the peripheral pathology. The decreased availability of µORs found in TNP patients, and its inverse relationship to clinical pain levels, provide insights into the central mechanisms related to this condition. The results also expand our understanding about the impact of chronic pain on the limbic system.

Discovering hidden relationships between renal diseases and regulated genes through 3D network visualizations.

BACKGROUND: In a recent study, two-dimensional (2D) network layouts were used to visualize and quantitatively analyze the relationship between chronic renal diseases and regulated genes. The results revealed complex relationships between disease type, gene specificity, and gene regulation type, which led to important insights about the underlying biological pathways. Here we describe an attempt to extend our understanding of these complex relationships by reanalyzing the data using three-dimensional (3D) network layouts, displayed through 2D and 3D viewing methods. FINDINGS: The 3D network layout (displayed through the 3D viewing method) revealed that genes implicated in many diseases (non-specific genes) tended to be predominantly down-regulated, whereas genes regulated in a few diseases (disease-specific genes) tended to be up-regulated. This new global relationship was quantitatively validated through comparison to 1000 random permutations of networks of the same size and distribution. Our new finding appeared to be the result of using specific features of the 3D viewing method to analyze the 3D renal network. CONCLUSIONS: The global relationship between gene regulation and gene specificity is the first clue from human studies that there exist common mechanisms across several renal diseases, which suggest hypotheses for the underlying mechanisms. Furthermore, the study suggests hypotheses for why the 3D visualization helped to make salient a new regularity that was difficult to detect in 2D. Future research that tests these hypotheses should enable a more systematic understanding of when and how to use 3D network visualizations to reveal complex regularities in biological networks.

Virtual reality triage training provides a viable solution for disaster-preparedness.

OBJECTIVES: The objective of this study was to compare the relative impact of two simulation-based methods for training emergency medicine (EM) residents in disaster triage using the Simple Triage and Rapid Treatment (START) algorithm, full-immersion virtual reality (VR), and standardized patient (SP) drill. Specifically, are there differences between the triage performances and posttest results of the two groups, and do both methods differentiate between learners of variable experience levels? METHODS: Fifteen Postgraduate Year 1 (PGY1) to PGY4 EM residents were randomly assigned to two groups: VR or SP. In the VR group, the learners were effectively surrounded by a virtual mass disaster environment projected on four walls, ceiling, and floor and performed triage by interacting with virtual patients in avatar form. The second group performed likewise in a live disaster drill using SP victims. Setting and patient presentations were identical between the two modalities. Resident performance of triage during the drills and knowledge of the START triage algorithm pre/post drill completion were assessed. Analyses included descriptive statistics and measures of association (effect size). RESULTS: The mean pretest scores were similar between the SP and VR groups. There were no significant differences between the triage performances of the VR and SP groups, but the data showed an effect in favor of the SP group performance on the posttest. CONCLUSIONS: Virtual reality can provide a feasible alternative for training EM personnel in mass disaster triage, comparing favorably to SP drills. Virtual reality provides flexible, consistent, on-demand training options, using a stable, repeatable platform essential for the development of assessment protocols and performance standards.

Development of a language-independent functional evaluation.

UNLABELLED: Haig AJ, Jayarajan S, Maslowski E, Yamakawa KS, Tinney M, Beier KP, Juang D, Chan L, Boggess T, Loar J, Owusu-Ansah B, Kalpakjian C. Development of a language-independent functional evaluation. OBJECTIVE: To design, validate, and critique a tool for self-report of physical functioning that is independent of language and literacy. DESIGN: Software design and 2 prospective trials followed by redesign. SETTING: United States and African university hospitals. PARTICIPANTS: Outpatient and inpatient competent adults with diverse physical impairments. INTERVENTIONS: (1) Software design process leading to a Preliminary Language-Independent Functional Evaluation (Pre-L.I.F.E.); (2) patient surveys using a printed Pre-L.I.F.E. and a computer-animated Pre-L.I.F.E. tested in random order, followed by a questionnaire version of the standard Barthel Index; and (3) software redesign based on objective and qualitative experiences with Pre-L.I.F.E. MAIN OUTCOME MEASURES: Validation of the general concept that written and spoken language can be eliminated in assessment of function. Development of a refined Language-Independent Functional Evaluation (L.I.F.E.). RESULTS: A viable Pre-L.I.F.E. software was built based on design parameters of the clinical team. Fifty Americans and 51 Africans demonstrated excellent (Cronbach alpha>0.8 Americans) and good (alpha>.425 Africans) reliability. In general, the relations between Pre-L.I.F.E. and Barthel scores were excellent in the United States (interclass correlation coefficient for stair climbing, .959) but somewhat less good in Africa, with elimination functions very poorly related. The computer-animated Pre-L.I.F.E. was faster and trended to be more reliable than the printed Pre-L.I.F.E. in both the United States and Africa. Redesign meetings corrected statistical and qualitative challenges, resulting in a new tool, the L.I.F.E. CONCLUSIONS: Literacy and language translation can be eliminated from some aspects of functional assessment. The new L.I.F.E., based on solid empirical evidence and design principles, may be a practical solution to assessment of function in the global culture.