Todd Coleman

All Publications

• Spontaneous enteric nervous system activity generates contractile patterns prior to maturation of gastrointestinal motility. Neurogastroenterology and motility Dershowitz, L. B., Bueno Garcia, H., Perley, A. S., Coleman, T. P., Kaltschmidt, J. A. 2024: e14890

  Abstract

  Spontaneous neuronal network activity is essential to the functional maturation of central and peripheral circuits, yet whether this is a feature of enteric nervous system development has yet to be established. Although enteric neurons are known exhibit electrophysiological properties early in embryonic development, no connection has been drawn between this neuronal activity and the development of gastrointestinal (GI) motility patterns.We use ex vivo GI motility assays with newly developed unbiased computational analyses to identify GI motility patterns across mouse embryonic development.We find a previously unknown pattern of neurogenic contractions termed "clustered ripples" that arises spontaneously at embryonic day 16.5, an age earlier than any identified mature GI motility patterns. We further show that these contractions are driven by nicotinic cholinergic signaling.Clustered ripples are neurogenic contractile activity that arise from spontaneous ENS activity and precede all known forms of neurogenic GI motility. This earliest motility pattern requires nicotinic cholinergic signaling, which may inform pharmacology for enhancing GI motility in preterm infants.

  View details for DOI 10.1111/nmo.14890

  View details for PubMedID 39118231

• Non-invasive ventral cervical magnetoneurography as a proxy of in vivo lipopolysaccharide-induced inflammation. Communications biology Bu, Y., Burks, J., Yang, K., Prince, J., Borna, A., Coe, C. L., Simmons, A., Tu, X. M., Baker, D., Kimball, D., Rao, R., Shah, V., Huang, M., Schwindt, P., Coleman, T. P., Lerman, I. 2024; 7 (1): 893

  Abstract

  Maintenance of autonomic homeostasis is continuously calibrated by sensory fibers of the vagus nerve and sympathetic chain that convey compound action potentials (CAPs) to the central nervous system. Lipopolysaccharide (LPS) intravenous challenge reliably elicits a robust inflammatory response that can resemble systemic inflammation and acute endotoxemia. Here, we administered LPS intravenously in nine healthy subjects while recording ventral cervical magnetoneurography (vcMNG)-derived CAPs at the rostral Right Nodose Ganglion (RNG) and the caudal Right Carotid Artery (RCA) with optically pumped magnetometers (OPM). We observed vcMNG RNG and RCA neural firing rates that tracked changes in TNF-α levels in the systemic circulation. Further, endotype subgroups based on high and low IL-6 responders segregate RNG CAP frequency (at 30-120 min) and based on high and low IL-10 response discriminate RCA CAP frequency (at 0-30 min). These vcMNG tools may enhance understanding and management of the neuroimmune axis that can guide personalized treatment based on an individual's distinct endophenotype.

  View details for DOI 10.1038/s42003-024-06435-8

  View details for PubMedID 39075164

  View details for PubMedCentralID 3278937

• An exact mathematical description of computation with transient spatiotemporal dynamics in a complex-valued neural network COMMUNICATIONS PHYSICS Budzinski, R. C., Busch, A. N., Mestern, S., Martin, E., Liboni, L. B., Pasini, F. W., Minac, J., Coleman, T., Inoue, W., Muller, L. E. 2024; 7 (1)

  View details for DOI 10.1038/s42005-024-01728-0

  View details for Web of Science ID 001271213100003

• Machine learning based DNA melt curve profiling enables automated novel genotype detection. BMC bioinformatics Boussina, A., Langouche, L., Obirieze, A. C., Sinha, M., Mack, H., Leineweber, W., Aralar, A., Pride, D. T., Coleman, T. P., Fraley, S. I. 2024; 25 (1): 185

  Abstract

  Surveillance for genetic variation of microbial pathogens, both within and among species, plays an important role in informing research, diagnostic, prevention, and treatment activities for disease control. However, large-scale systematic screening for novel genotypes remains challenging in part due to technological limitations. Towards addressing this challenge, we present an advancement in universal microbial high resolution melting (HRM) analysis that is capable of accomplishing both known genotype identification and novel genotype detection. Specifically, this novel surveillance functionality is achieved through time-series modeling of sequence-defined HRM curves, which is uniquely enabled by the large-scale melt curve datasets generated using our high-throughput digital HRM platform. Taking the detection of bacterial genotypes as a model application, we demonstrate that our algorithms accomplish an overall classification accuracy over 99.7% and perform novelty detection with a sensitivity of 0.96, specificity of 0.96 and Youden index of 0.92. Since HRM-based DNA profiling is an inexpensive and rapid technique, our results add support for the feasibility of its use in surveillance applications.

  View details for DOI 10.1186/s12859-024-05747-0

  View details for PubMedID 38730317

• Emerging wearable technologies for multisystem monitoring and treatment of Parkinson's disease: a narrative review. Frontiers in network physiology Kehnemouyi, Y. M., Coleman, T. P., Tass, P. A. 2024; 4: 1354211

  Abstract

  Parkinson's disease (PD) is a chronic movement disorder characterized by a variety of motor and nonmotor comorbidities, including cognitive impairment, gastrointestinal (GI) dysfunction, and autonomic/sleep disturbances. Symptoms typically fluctuate with different settings and environmental factors and thus need to be consistently monitored. Current methods, however, rely on infrequent rating scales performed in clinic. The advent of wearable technologies presents a new avenue to track objective measures of PD comorbidities longitudinally and more frequently. This narrative review discusses and proposes emerging wearable technologies that can monitor manifestations of motor, cognitive, GI, and autonomic/sleep comorbidities throughout the daily lives of PD individuals. This can provide more wholistic insight into real-time physiological versus pathological function with the potential to better assess treatments during clinical trials and allow physicians to optimize treatment regimens. Additionally, this narrative review briefly examines novel applications of wearables as therapy for PD patients.

  View details for DOI 10.3389/fnetp.2024.1354211

  View details for PubMedID 38414636

  View details for PubMedCentralID PMC10896901

• A mutual information measure of phase-amplitude coupling using gamma generalized linear models. Frontiers in computational neuroscience Perley, A. S., Coleman, T. P. 2024; 18: 1392655

  Abstract

  Introduction: Cross frequency coupling (CFC) between electrophysiological signals in the brain is a long-studied phenomenon and its abnormalities have been observed in conditions such as Parkinson's disease and epilepsy. More recently, CFC has been observed in stomach-brain electrophysiologic studies and thus becomes an enticing possible target for diseases involving aberrations of the gut-brain axis. However, current methods of detecting coupling, specifically phase-amplitude coupling (PAC), do not attempt to capture the phase and amplitude statistical relationships.Methods: In this paper, we first demonstrate a method of modeling these joint statistics with a flexible parametric approach, where we model the conditional distribution of amplitude given phase using a gamma distributed generalized linear model (GLM) with a Fourier basis of regressors. We perform model selection with minimum description length (MDL) principle, demonstrate a method for assessing goodness-of-fit (GOF), and showcase the efficacy of this approach in multiple electroencephalography (EEG) datasets. Secondly, we showcase how we can utilize the mutual information, which operates on the joint distribution, as a canonical measure of coupling, as it is non-zero and non-negative if and only if the phase and amplitude are not statistically independent. In addition, we build off of previous work by Martinez-Cancino et al., and Voytek et al., and show that the information density, evaluated using our method along the given sample path, is a promising measure of time-resolved PAC.Results: Using synthetically generated gut-brain coupled signals, we demonstrate that our method outperforms the existing gold-standard methods for detectable low-levels of phase-amplitude coupling through receiver operating characteristic (ROC) curve analysis. To validate our method, we test on invasive EEG recordings by generating comodulograms, and compare our method to the gold standard PAC measure, Modulation Index, demonstrating comparable performance in exploratory analysis. Furthermore, to showcase its use in joint gut-brain electrophysiology data, we generate topoplots of simultaneous high-density EEG and electrgastrography recordings and reproduce seminal work by Richter et al. that demonstrated the existence of gut-brain PAC. Using simulated data, we validate our method for different types of time-varying coupling and then demonstrate its performance to track time-varying PAC in sleep spindle EEG and mismatch negativity (MMN) datasets.Conclusions: Our new measure of PAC using Gamma GLMs and mutual information demonstrates a promising new way to compute PAC values using the full joint distribution on amplitude and phase. Our measure outperforms the most common existing measures of PAC, and show promising results in identifying time varying PAC in electrophysiological datasets. In addition, we provide for using our method with multiple comparisons and show that our measure potentially has more statistical power in electrophysiologic recordings using simultaneous gut-brain datasets.

  View details for DOI 10.3389/fncom.2024.1392655

  View details for PubMedID 38841426

• Spontaneous enteric nervous system activity precedes maturation of gastrointestinal motility. bioRxiv : the preprint server for biology Dershowitz, L. B., Garcia, H. B., Perley, A. S., Coleman, T. P., Kaltschmidt, J. A. 2023

  Abstract

  Spontaneous neuronal network activity is essential in development of central and peripheral circuits, yet whether this is a feature of enteric nervous system development has yet to be established. Using ex vivo gastrointestinal (GI) motility assays with unbiased computational analyses, we identify a previously unknown pattern of spontaneous neurogenic GI motility. We further show that this motility is driven by cholinergic signaling, which may inform GI pharmacology for preterm patients.

  View details for DOI 10.1101/2023.08.03.551847

  View details for PubMedID 37577464

  View details for PubMedCentralID PMC10418201

• Exploring the Gut-Brain Connection in Gastroparesis with Autonomic and Gastric Myoelectric Monitoring. IEEE transactions on bio-medical engineering Subramanian, S., Kunkel, D. C., Nguyen, L., Coleman, T. P. 2023; PP

  Abstract

  OBJECTIVE: The goal of this study was to identify autonomic and gastric myoelectric biomarkers from throughout the day that differentiate patients with gastroparesis, diabetics without gastroparesis, and healthy controls, while providing insight into etiology.METHODS: We collected 19 24-hour recordings of electrocardiogram (ECG) and electrogastrogram (EGG) data from healthy controls and patients with diabetic or idiopathic gastroparesis. We used physiologically and statistically rigorous models to extract autonomic and gastric myoelectric information from the ECG and EGG data, respectively. From these, we constructed quantitative indices which differentiated the distinct groups and demonstrated their application in automatic classification paradigms and as quantitative summary scores.RESULTS: We identified several differentiators that separate healthy controls from gastroparetic patient groups, specifically around sleep and meals. We also demonstrated the downstream utility of these differentiators in automatic classification and quantitative scoring paradigms. Even with this small pilot dataset, automated classifiers achieved an accuracy of 79% separating autonomic phenotypes and 65% separating gastrointestinal phenotypes. We also achieved 89% accuracy separating controls from gastroparetic patients in general and 90% accuracy separating diabetics with and without gastroparesis. These differentiators also suggested varying etiologies for different phenotypes.CONCLUSION: The differentiators we identified were able to successfully distinguish between several autonomic and gastrointestinal (GI) phenotypes using data collected while at-home with non-invasive sensors.SIGNIFICANCE: Autonomic and gastric myoelectric differentiators, obtained using at-home recording of fully non-invasive signals, can be the first step towards dynamic quantitative markers to track severity, disease progression, and treatment response for combined autonomic and GI phenotypes.

  View details for DOI 10.1109/TBME.2023.3285491

  View details for PubMedID 37310840

• Differentiation of Bolus Texture During Deglutition via High-Density Surface Electromyography: A Pilot Study. The Laryngoscope Ornelas, G., Bueno Garcia, H., Bracken, D. J., Linnemeyer-Risser, K., Coleman, T. P., Weissbrod, P. A. 2023

  Abstract

  OBJECTIVE: Swallowing is a complex neuromuscular task. There is limited spatiotemporal data on normative surface electromyographic signal during swallow, particularly across standard textures. We hypothesize the pattern of electromyographic signal of the anterior neck varies cranio-caudally, that laterality can be evaluated, and categorization of bolus texture can be differentiated by high-density surface electromyography (HDsEMG) through signal analysis.METHODS: An HDsEMG grid of 20 electrodes captured electromyographic activity in eight healthy adult subjects across 240 total swallows. Participants swallowed five standard textures: saliva, thin liquid, puree, mixed consistency, and dry solid. Data were bandpass filtered, underwent functional alignment of signal, and then placed into binary classifier receiver operating characteristic (ROC) curves. Muscular activity was visualized by creating two-dimensional EMG heat maps.RESULTS: Signal analysis results demonstrated a positive correlation between signal amplitude and bolus texture. Greater differences of amplitude in the cranial most region of the array when compared to the caudal most region were noted in all subjects. Lateral comparison of the array revealed symmetric power levels across all subjects and textures. ROC curves demonstrated the ability to correctly classify textures within subjects in 6 of 10 texture comparisons.CONCLUSION: This pilot study suggests that utilizing HDsEMG during deglutition can noninvasively differentiate swallows of varying texture noninvasively. This may prove useful in future diagnostic and behavioral swallow applications.LEVEL OF EVIDENCE: Level 4 Laryngoscope, 2023.

  View details for DOI 10.1002/lary.30589

  View details for PubMedID 36734335

• Exploring the aperiodic nature of parasympathetic activity during sleep in idiopathic gastroparesis. Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference Subramanian, S., Kunkel, D. C., Coleman, T. P. 2023; 2023: 1-4

  Abstract

  The parasympathetic nervous system is necessary to regulate both sleep and digestion. Investigating abnormalities during the controlled setting of sleep can shed light on digestion, specifically for patients with idiopathic gastroparesis. In this study, we specifically investigate heartbeat-derived parasympathetic activity during sleep at very low frequencies, relevant to sleep cycle regulation. To do this, we adapt a method that extracts both periodic and aperiodic information from the power spectral density and recognize that the aperiodic activity may contain information relevant to very low frequencies. After testing on both synthetic noise data (pink and white) and overnight data from seven healthy controls and idiopathic gastroparetics, we find that the healthy controls' low-frequency aperiodic activity reflects pink noise structure, while the majority of the patients' aperiodic activity reflects white noise structure. At these low frequencies, these differences suggest differences in autonomic sleep cycle regulation.Clinical Relevance- This methodology can be optimized to track the health of the parasympathetic nervous system and suggest whether individual disease etiology is autonomic-related.

  View details for DOI 10.1109/EMBC40787.2023.10340046

  View details for PubMedID 38083696

• Non-Nutritive Suckling System for Real-Time Characterization of Intraoral Vacuum Profile in Full Term Neonates. IEEE journal of translational engineering in health and medicine Truong, P., Walsh, E., Scott, V. P., Coleman, T., Tilvawala, G., Friend, J. 2023; 11: 107-115

  Abstract

  Infant breastfeeding diagnostics remain subjective due to the absence of instrumentation to objectively measure and understand infant oral motor skills and suckling characteristics. Qualitative diagnostic exams, such as the digital suck assessment which relies upon a clinician's gloved finger inserted into the infant's mouth, produce a diversity of diagnoses and intervention pathways due to their subjective nature. In this paper, we report on the design of a non-nutritive suckling (NNS) system which quantifies and analyzes quantitative intraoral vacuum and sucking patterns of full-term neonates in real time. In our study, we evaluate thirty neonate suckling profiles to demonstrate the technical and clinical feasibility of the system. We successfully extract the mean suck vacuum, maximum suck vacuum, frequency, burst duration, number of sucks per burst, number of sucks per minute, and number of bursts per minute. In addition, we highlight the discovery of three intraoral vacuum profile shapes that are found to be correlated to different levels of suckling characteristics. These results establish a framework for future studies to evaluate oromotor dysfunction that affect the appearance of these signals based on established normal profiles. Ultimately, with the ability to easily and quickly capture intraoral vacuum data, clinicians can more accurately perform suckling assessments to provide timely intervention and assist mothers and infants towards successful breastfeeding outcomes.

  View details for DOI 10.1109/JTEHM.2022.3231788

  View details for PubMedID 36619906

• A Convex Formulation of Point Process Heartbeat Dynamics using a Gamma Generalized Linear Model Perley, A., Subramanian, S., Coleman, T. P., IEEE IEEE. 2023

  View details for DOI 10.1109/BSN58485.2023.10331291

  View details for Web of Science ID 001116732100062

• Simultaneous Gut-Brain Electrophysiology Shows Cognition and Satiety Specific Coupling. Sensors (Basel, Switzerland) Balasubramani, P. P., Walke, A., Grennan, G., Perley, A., Purpura, S., Ramanathan, D., Coleman, T. P., Mishra, J. 2022; 22 (23)

  Abstract

  Recent studies, using high resolution magnetoencephalography (MEG) and electrogastrography (EGG), have shown that during resting state, rhythmic gastric physiological signals are linked with cortical brain oscillations. Yet, gut-brain coupling has not been investigated with electroencephalography (EEG) during cognitive brain engagement or during hunger-related gut engagement. In this study in 14 young adults (7 females, mean ± SD age 25.71 ± 8.32 years), we study gut-brain coupling using simultaneous EEG and EGG during hunger and satiety states measured in separate visits, and compare responses both while resting as well as during a cognitively demanding working memory task. We find that EGG-EEG phase-amplitude coupling (PAC) differs based on both satiety state and cognitive effort, with greater PAC modulation observed in the resting state relative to working memory. We find a significant interaction between gut satiation levels and cognitive states in the left fronto-central brain region, with larger cognitive demand based differences in the hunger state. Furthermore, strength of PAC correlated with behavioral performance during the working memory task. Altogether, these results highlight the role of gut-brain interactions in cognition and demonstrate the feasibility of these recordings using scalable sensors.

  View details for DOI 10.3390/s22239242

  View details for PubMedID 36501942

• Wireless Heart Sensor for Capturing Cardiac Orienting Response for Prediction of Neurodevelopmental Delay in Infants. Sensors (Basel, Switzerland) Aguilar-Rivera, M., Kable, J. A., Yevtushok, L., Kulikovsky, Y., Zymak-Zakutnya, N., Dubchak, I., Akhmedzhanova, D., Wertelecki, W., Chambers, C., Coleman, T. P. 2022; 22 (23)

  Abstract

  Early identification of infants at risk of neurodevelopmental delay is an essential public health aim. Such a diagnosis allows early interventions for infants that maximally take advantage of the neural plasticity in the developing brain. Using standardized physiological developmental tests, such as the assessment of neurophysiological response to environmental events using cardiac orienting responses (CORs), is a promising and effective approach for early recognition of neurodevelopmental delay. Previous CORs have been collected on children using large bulky equipment that would not be feasible for widespread screening in routine clinical visits. We developed a portable wireless electrocardiogram (ECG) system along with a custom application for IOS tablets that, in tandem, can extract CORs with sufficient physiologic and timing accuracy to reflect the well-characterized ECG response to both auditory and visual stimuli. The sensor described here serves as an initial step in determining the extent to which COR tools are cost-effective for the early screening of children to determine who is at risk of developing neurocognitive deficits and may benefit from early interventions. We demonstrated that our approach, based on a wireless heartbeat sensor system and a custom mobile application for stimulus display and data recording, is sufficient to capture CORs from infants. The COR monitoring approach described here with mobile technology is an example of a desired standardized physiologic assessment that is a cost-and-time efficient, scalable method for early recognition of neurodevelopmental delay.

  View details for DOI 10.3390/s22239140

  View details for PubMedID 36501842

• A flexible adhesive surface electrode array capable of cervical electroneurography duringasequentialautonomic stress challenge. Scientific reports Bu, Y., Kurniawan, J. F., Prince, J., Nguyen, A. K., Ho, B., Sit, N. L., Pham, T., Wu, V. M., Tjhia, B., Shin, A. J., Wu, T., Tu, X. M., Rao, R., Coleman, T. P., Lerman, I. 2022; 12 (1): 19467

  Abstract

  This study introduces a flexible, adhesive-integrated electrode array that was developed to enable non-invasive monitoring of cervical nerve activity. The device uses silver-silver chloride as the electrode material of choice and combines it with an electrode array consisting of a customized biopotential data acquisition unit and integrated graphical user interface (GUI) for visualization of real-time monitoring. Preliminary testing demonstrated this electrode design can achieve a high signal to noise ratio during cervical neural recordings. To demonstrate the capability of the surface electrodes to detect changes in cervical neuronal activity, the cold-pressor test (CPT) and a timed respiratory challenge were employed as stressors to the autonomic nervous system. This sensor system recording, a new technique, was termed Cervical Electroneurography (CEN). By applying a custom spike sorting algorithm to the electrode measurements, neural activity was classified in two ways: (1) pre-to-post CPT, and (2) during a timed respiratory challenge. Unique to this work: (1) rostral to caudal channel position-specific (cephalad to caudal) firing patterns and (2) cross challenge biotype-specific change in average CEN firing, were observed with both CPT and the timed respiratory challenge. Future work is planned to develop an ambulatory CEN recording device that could provide immediate notification of autonomic nervous system activity changes that might indicate autonomic dysregulation in healthy subjects and clinical disease states.

  View details for DOI 10.1038/s41598-022-21817-w

  View details for PubMedID 36376365

• Modeling relationships between rhythmic processes and neuronal spike timing. Journal of neurophysiology Riviere, P. D., Schamberg, G., Coleman, T. P., Rangel, L. 2022

  Abstract

  Neurons are embedded in complex networks, where they participate in repetitive, coordinated interactions with other neurons. Neuronal spike timing is thus predictably constrained by a range of ionic currents that shape activity at both short (milliseconds) and longer (tens to hundreds of milliseconds) timescales, but we lack analytical tools to rigorously identify these relationships. Here, we innovate a modeling approach to test the relationship between oscillations in the local field potential (LFP) and neuronal spike timing. We use kernel density estimation to relate single neuron spike timing and the phase of LFP rhythms (in simulated and hippocampal CA1 neuronal spike trains). We then combine phase and short (3 ms) spike history information within a logistic regression framework ("phaseSH models"), and show that models that leverage refractory constraints and oscillatory phase information can effectively test whether-and the degree to which-rhythmic currents (as measured from the LFP) reliably explain variance in neuronal spike trains. This approach allows researchers to systematically test the relationship between oscillatory activity and neuronal spiking dynamics as they unfold over time and as they shift to adapt to distinct behavioral conditions.

  View details for DOI 10.1152/jn.00423.2021

  View details for PubMedID 35858125

• A Mutual Information Measure of Phase-Amplitude Coupling using High Dimensional Sparse Models. Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference Perley, A., Coleman, T. P. 2022; 2022: 21-24

  Abstract

  Cross frequency coupling (CFC) between electrophysiological signals in the brain has been observed and it's abnormalities have been observed in conditions such as Parkinson's disease and epilepsy. More recently, CFC has been observed in stomach-brain electrophysiologic studies and thus becomes an enticing possible target for diseases involving aberrations of the gut-brain axis. However, current methods of detecting coupling do not attempt to capture the underlying statistical relationships that give rise to this coupling. In this paper, we demonstrate a new method of calculating phase amplitude coupling by estimating the mutual information between phase and amplitude, using a flexible parametric modeling approach. Specifically, we develop an exponential generalized linear model (GLM) to model amplitude given phase, using a high dimensional basis of von-Mises function regressors and l1 regularized model selection. Using synthetically generated gut-brain coupled signals, we demonstrate that our method outperforms the existing gold-standard methods for detectable low-levels of phase amplitude coupling through receiver operating characteristic (ROC) curve analysis.

  View details for DOI 10.1109/EMBC48229.2022.9871816

  View details for PubMedID 36086427

• Automated classification of sleep and wake from single day triaxial accelerometer data. Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference Subramanian, S., Coleman, T. P. 2022; 2022: 3665-3668

  Abstract

  Actigraphy allows for the remote monitoring of subjects' activity for clinical and research purposes. However, most standard methods are built for proprietary measures from specific devices that are not widely used. In this study, we develop an algorithm for classifying sleep and awake using a single day of triaxial accelerometer data, which can be acquired from all smart devices. This algorithm consists of two stages, clustering and hidden Markov modeling, and outperforms standard algorithms in sensitivity (94%), specificity (93 %), and overall accuracy (93%) across seven subjects. This method can help automate actigraphy analyses at scale using widely available technology using even a single day's worth of data. Clinical Relevance- Automated monitoring of patients' activity at home can help track recovery trajectories after surgery and injury, disease progression, treatment response.

  View details for DOI 10.1109/EMBC48229.2022.9871823

  View details for PubMedID 36086032

• Peripheral Nerve Magnetoneurography With Optically Pumped Magnetometers. Frontiers in physiology Bu, Y., Prince, J., Mojtahed, H., Kimball, D., Shah, V., Coleman, T., Sarkar, M., Rao, R., Huang, M., Schwindt, P., Borna, A., Lerman, I. 2022; 13: 798376

  Abstract

  Electrodiagnosis is routinely integrated into clinical neurophysiology practice for peripheral nerve disease diagnoses, such as neuropathy, demyelinating disorders, nerve entrapment/impingement, plexopathy, or radiculopathy. Measured with conventional surface electrodes, the propagation of peripheral nerve action potentials along a nerve is the result of ionic current flow which, according to Ampere's Law, generates a small magnetic field that is also detected as an "action current" by magnetometers, such as superconducting quantum interference device (SQUID) Magnetoencephalography (MEG) systems. Optically pumped magnetometers (OPMs) are an emerging class of quantum magnetic sensors with a demonstrated sensitivity at the 1 fT/Hz level, capable of cortical action current detection. But OPMs were ostensibly constrained to low bandwidth therefore precluding their use in peripheral nerve electrodiagnosis. With careful OPM bandwidth characterization, we hypothesized OPMs may also detect compound action current signatures consistent with both Sensory Nerve Action Potential (SNAP) and the Hoffmann Reflex (H-Reflex). In as much, our work confirms OPMs enabled with expanded bandwidth can detect the magnetic signature of both the SNAP and H-Reflex. Taken together, OPMs now show potential as an emerging electrodiagnostic tool.

  View details for DOI 10.3389/fphys.2022.798376

  View details for PubMedID 35370794

• Robust Regression and Optimal Transport Methods to Predict Gastrointestinal Disease Etiology from High Resolution EGG and Symptom Severity IEEE Transactions on Biomedical Engineering Agrusa, A. S., Kunkel, D. C., Coleman, T. P. 2022

  View details for DOI 10.1109/TBME.2022.3167338

• Electrochemical performance study of Ag/AgCl and Au flexible electrodes for unobtrusive monitoring of human biopotentials Nano Select Kurniawan, J. F., Allegra, A., Pham, T., Nguyen, A. K., Sit, N. L., Tjhia, B., Shin, A. J., Coleman, T. P. 2022
• Passive longitudinal weight and cardiopulmonary monitoring in the home bed. Scientific reports Harrington, N., Bui, Q. M., Wei, Z., Hernandez-Pacheco, B., DeYoung, P. N., Wassell, A., Duwaik, B., Desai, A. S., Bhatt, D. L., Agnihotri, P., Owens, R. L., Coleman, T. P., King, K. R. 1800; 11 (1): 24376

  Abstract

  Home health monitoring has the potential to improve outpatient management of chronic cardiopulmonary diseases such as heart failure. However, it is often limited by the need for adherence to self-measurement, charging and self-application of wearables, or usage of apps. Here, we describe a non-contact, adherence-independent sensor, that when placed beneath the legs of a patient's home bed, longitudinally monitors total body weight, detailed respiratory signals, and ballistocardiograms for months, without requiring any active patient participation. Accompanying algorithms separate weight and respiratory signals when the bed is shared by a partner or a pet. Validation studies demonstrate quantitative equivalence to commercial sensors during overnight sleep studies. The feasibility of detecting obstructive and central apneas, cardiopulmonary coupling, and the hemodynamic consequences of non-sustained ventricular tachycardia is also established. Real-world durability is demonstrated by 3months of in-home monitoring in an example patient with heart failure and ischemic cardiomyopathy as he recovers from coronary artery bypass grafting surgery. BedScales is the first sensor to measure adherence-independent total body weight as well as longitudinal cardiopulmonary physiology. As such, it has the potential to create a multidimensional picture of chronic disease, learn signatures of impending hospitalization, and enable optimization of care in the home.

  View details for DOI 10.1038/s41598-021-03105-1

  View details for PubMedID 34934065

• Macrophage calcium reporter mice reveal immune cell communication in vitro and in vivo. Cell reports methods Taghdiri, N., Calcagno, D. M., Fu, Z., Huang, K., Kohler, R. H., Weissleder, R., Coleman, T. P., King, K. R. 1800; 1 (8)

  Abstract

  Cell communication underlies emergent functions in diverse cell types and tissues. Recent evidence suggests that macrophages are organized in communicating networks, but new tools are needed to quantitatively characterize the resulting cellular conversations. Here, we infer cell communication from spatiotemporal correlations of intracellular calcium dynamics that are non-destructively imaged across cell populations expressing genetically encoded calcium indicators. We describe a hematopoietic calcium reporter mouse (Csf1rCreGCaMP5fl) and a computational analysis pipeline for inferring communication between reporter cells based on "excess synchrony." We observed signals suggestive of cell communication in macrophages treated with immune-stimulatory DNA in vitro and tumor-associated immune cells imaged in a dorsal window chamber model in vivo. Together, the methods described here expand the toolkit for discovery of cell communication events in macrophages and other immune cells.

  View details for DOI 10.1016/j.crmeth.2021.100132

  View details for PubMedID 35079727

• Statistical uncertainty quantification to augment clinical decision support: a first implementation in sleep medicine. NPJ digital medicine Kang, D. Y., DeYoung, P. N., Tantiongloc, J., Coleman, T. P., Owens, R. L. 2021; 4 (1): 142

  Abstract

  Machine learning has the potential to change the practice of medicine, particularly in areas that require pattern recognition (e.g. radiology). Although automated classification is unlikely to be perfect, few modern machine learning tools have the ability to assess their own classification confidence to recognize uncertainty that might need human review. Using automated single-channel sleep staging as a first implementation, we demonstrated that uncertainty information (as quantified using Shannon entropy) can be utilized in a "human in the loop" methodology to promote targeted review of uncertain sleep stage classifications on an epoch-by-epoch basis. Across 20 sleep studies, this feedback methodology proved capable of improving scoring agreement with the gold standard over automated scoring alone (average improvement in Cohen's Kappa of 0.28), in a fraction of the scoring time compared to full manual review (60% reduction). In summary, our uncertainty-based clinician-in-the-loop framework promotes the improvement of medical classification accuracy/confidence in a cost-effective and economically resourceful manner.

  View details for DOI 10.1038/s41746-021-00515-3

  View details for PubMedID 34593972

• Miniaturized wireless gastric pacing via inductive power transfer with non-invasive monitoring using cutaneous Electrogastrography. Bioelectronic medicine Perley, A., Roustaei, M., Aguilar-Rivera, M., Kunkel, D. C., Hsiai, T. K., Coleman, T. P., Abiri, P. 2021; 7 (1): 12

  Abstract

  BACKGROUND: Gastroparesis is a debilitating disease that is often refractory to pharmacotherapy. While gastric electrical stimulation has been studied as a potential treatment, current devices are limited by surgical complications and an incomplete understanding of the mechanism by which electrical stimulation affects physiology.METHODS: A leadless inductively-powered pacemaker was implanted on the gastric serosa in an anesthetized pig. Wireless pacing was performed at transmitter-to-receiver distances up to 20mm, frequency of 0.05Hz, and pulse width of 400ms. Electrogastrogram (EGG) recordings using cutaneous and serosal electrode arrays were analyzed to compute spectral and spatial statistical parameters associated with the slow wave.RESULTS: Our data demonstrated evident change in EGG signal patterns upon initiation of pacing. A buffer period was noted before a pattern of entrainment appeared with consistent and low variability in slow wave direction. A spectral power increase in the EGG frequency band during entrainment also suggested that pacing increased strength of the slow wave.CONCLUSION: Our preliminary in vivo study using wireless pacing and concurrent EGG recording established the foundations for a minimally invasive approach to understand and optimize the effect of pacing on gastric motor activity as a means to treat conditions of gastric dysmotility.

  View details for DOI 10.1186/s42234-021-00074-8

  View details for PubMedID 34425917

• An Adhesive-Integrated Stretchable Silver-Silver Chloride Electrode Array for Unobtrusive Monitoring of Gastric Neuromuscular Activity ADVANCED MATERIALS TECHNOLOGIES Kurniawan, J. F., Tjhia, B., Wu, V. M., Shin, A., Sit, N. J., Pham, T., Nguyen, A., Li, C., Kumar, R., Aguilar-Rivera, M., Lerman, I., Kunkel, D. C., Coleman, T. P. 2021; 6 (5)

  View details for DOI 10.1002/admt.202001229

  View details for Web of Science ID 000637686600001

• Sampling, variational Bayesian inference, and conditioned stochastic differential equations Coleman, T. P., Raginsky, M., IEEE IEEE. 2021: 3054-3059

  View details for DOI 10.1109/CDC45484.2021.9683159

  View details for Web of Science ID 000781990302116

• Building a Simple and Versatile Illumination System for Optogenetic Experiments JOVE-JOURNAL OF VISUALIZED EXPERIMENTS Kyriakakis, P., de Cossio, L., Howard, P., Kouv, S., Catanho, M., Hu, V. J., Kyriakakis, R., Allen, M. E., Ma, Y., Aguilar-Rivera, M., Coleman, T. P. 2021

  Abstract

  Controlling biological processes using light has increased the accuracy and speed with which researchers can manipulate many biological processes. Optical control allows for an unprecedented ability to dissect function and holds the potential for enabling novel genetic therapies. However, optogenetic experiments require adequate light sources with spatial, temporal, or intensity control, often a bottleneck for researchers. Here we detail how to build a low-cost and versatile LED illumination system that is easily customizable for different available optogenetic tools. This system is configurable for manual or computer control with adjustable LED intensity. We provide an illustrated step-by-step guide for building the circuit, making it computer-controlled, and constructing the LEDs. To facilitate the assembly of this device, we also discuss some basic soldering techniques and explain the circuitry used to control the LEDs. Using our open-source user interface, users can automate precise timing and pulsing of light on a personal computer (PC) or an inexpensive tablet. This automation makes the system useful for experiments that use LEDs to control genes, signaling pathways, and other cellular activities that span large time scales. For this protocol, no prior expertise in electronics is required to build all the parts needed or to use the illumination system to perform optogenetic experiments.

  View details for DOI 10.3791/61914

  View details for Web of Science ID 000646171700033

  View details for PubMedID 33522514

• Interoceptive insular cortex participates in sensory processing of gastrointestinal malaise and associated behaviors SCIENTIFIC REPORTS Aguilar-Rivera, M., Kim, S., Coleman, T. P., Maldonado, P. E., Torrealba, F. 2020; 10 (1): 21642

  Abstract

  The insular cortex plays a central role in the perception and regulation of bodily needs and emotions. Its modular arrangement, corresponding with different sensory modalities, denotes a complex organization, and reveals it to be a hub that is able to coordinate autonomic and behavioral responses to many types of stimuli. Yet, little is known about the dynamics of its electrical activity at the neuronal level. We recorded single neurons in behaving rats from the posterior insula cortex (pIC), a subdivision considered as a primary interoceptive cortex, during gastrointestinal (GI) malaise, a state akin to the emotion of disgust in humans. We found that a large proportion of pIC neurons were modulated during the rodent compensatory behaviors of lying on belly (LOB) and Pica. Furthermore, we demonstrated that LOB was correlated with low-frequency oscillations in the field potentials and spikes at the theta (8 Hz) band, and that low-frequency electrical microstimulation of pIC elicited LOB and Pica. These findings demonstrate that pIC neurons play a critical role in GI malaise perception, and that the pIC influences the expression of behaviors that alleviate GI malaise. Our model provides an accessible approach at the single cell level to study innate emotional behaviors, currently elusive in humans.

  View details for DOI 10.1038/s41598-020-78200-w

  View details for Web of Science ID 000609190900002

  View details for PubMedID 33303809

  View details for PubMedCentralID PMC7730439

• Data-driven noise modeling of digital DNA melting analysis enables prediction of sequence discriminating power BIOINFORMATICS Langouche, L., Aralar, A., Sinha, M., Lawrence, S. M., Fraley, S., Coleman, T. P. 2020; 36 (22-23): 5337-5343

  Abstract

  The need to rapidly screen complex samples for a wide range of nucleic acid targets, like infectious diseases, remains unmet. Digital High-Resolution Melt (dHRM) is an emerging technology with potential to meet this need by accomplishing broad-based, rapid nucleic acid sequence identification. Here, we set out to develop a computational framework for estimating the resolving power of dHRM technology for defined sequence profiling tasks. By deriving noise models from experimentally generated dHRM datasets and applying these to in silico predicted melt curves, we enable the production of synthetic dHRM datasets that faithfully recapitulate real-world variations arising from sample and machine variables. We then use these datasets to identify the most challenging melt curve classification tasks likely to arise for a given application and test the performance of benchmark classifiers.This toolbox enables the in silico design and testing of broad-based dHRM screening assays and the selection of optimal classifiers. For an example application of screening common human bacterial pathogens, we show that human pathogens having the most similar sequences and melt curves are still reliably identifiable in the presence of experimental noise. Further, we find that ensemble methods outperform whole series classifiers for this task and are in some cases able to resolve melt curves with single-nucleotide resolution.Data and code available on https://github.com/lenlan/dHRM-noise-modeling.Supplementary data are available at Bioinformatics online.

  View details for DOI 10.1093/bioinformatics/btaa1053

  View details for Web of Science ID 000661074700011

  View details for PubMedID 33355665

  View details for PubMedCentralID PMC8016452

• Direct and Indirect Effects-An Information Theoretic Perspective ENTROPY Schamberg, G., Chapman, W., Xie, S., Coleman, T. P. 2020; 22 (8)

  Abstract

  Information theoretic (IT) approaches to quantifying causal influences have experienced some popularity in the literature, in both theoretical and applied (e.g., neuroscience and climate science) domains. While these causal measures are desirable in that they are model agnostic and can capture non-linear interactions, they are fundamentally different from common statistical notions of causal influence in that they (1) compare distributions over the effect rather than values of the effect and (2) are defined with respect to random variables representing a cause rather than specific values of a cause. We here present IT measures of direct, indirect, and total causal effects. The proposed measures are unlike existing IT techniques in that they enable measuring causal effects that are defined with respect to specific values of a cause while still offering the flexibility and general applicability of IT techniques. We provide an identifiability result and demonstrate application of the proposed measures in estimating the causal effect of the El Niño-Southern Oscillation on temperature anomalies in the North American Pacific Northwest.

  View details for DOI 10.3390/e22080854

  View details for Web of Science ID 000564152800001

  View details for PubMedID 33286625

  View details for PubMedCentralID PMC7517455

• Measuring Sample Path Causal Influences With Relative Entropy IEEE TRANSACTIONS ON INFORMATION THEORY Schamberg, G., Coleman, T. P. 2020; 66 (5): 2777-2798

  View details for DOI 10.1109/TIT.2019.2945290

  View details for Web of Science ID 000530268900015

• Smart Electronic Eyedrop Bottle for Unobtrusive Monitoring of Glaucoma Medication Adherence SENSORS Aguilar-Rivera, M., Erudaitius, D. T., Wu, V. M., Tantiongloc, J. C., Kang, D. Y., Coleman, T. P., Baxter, S. L., Weinreb, R. N. 2020; 20 (9)

  Abstract

  Glaucoma, the leading cause of irreversible blindness, affects >70 million people worldwide. Lowering intraocular pressure via topical administration of eye drops is the most common first-line therapy for glaucoma. This treatment paradigm has notoriously high non-adherence rates: ranging from 30% to 80%. The advent of smart phone enabled technologies creates promise for improving eyedrop adherence. However, previous eyedrop electronic monitoring solutions had awkward medication bottle adjuncts and crude software for monitoring the administration of a drop that adversely affected their ability to foster sustainable improvements in adherence. The current work begins to address this unmet need for wireless technology by creating a "smart drop" bottle. This medication bottle is instrumented with sensing electronics that enable detection of each eyedrop administered while maintaining the shape and size of the bottle. This is achieved by a thin electronic force sensor wrapped around the bottle and underneath the label, interfaced with a thin electronic circuit underneath the bottle that allows for detection and wireless transmission to a smart-phone application. We demonstrate 100% success rate of wireless communication over 75 feet with <1% false positive and false negative rates of single drop deliveries, thus providing a viable solution for eyedrop monitoring for glaucoma patients.

  View details for DOI 10.3390/s20092570

  View details for Web of Science ID 000537106200134

  View details for PubMedID 32366013

  View details for PubMedCentralID PMC7248824

• A Deep Convolutional Neural Network Approach to Classify Normal and Abnormal Gastric Slow Wave Initiation From the High Resolution Electrogastrogram IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING Agrusa, A. S., Gharibans, A. A., Allegra, A. A., Kunkel, D. C., Coleman, T. P. 2020; 67 (3): 854-867

  Abstract

  Gastric slow wave abnormalities have been associated with gastric motility disorders. Invasive studies in humans have described normal and abnormal propagation of the slow wave. This study aims to disambiguate the abnormally functioning wave from one of normalcy using multi-electrode abdominal waveforms of the electrogastrogram (EGG).Human stomach and abdominal models are extracted from computed tomography scans. Normal and abnormal slow waves are simulated along stomach surfaces. Current dipoles at the stomachs surface are propagated to virtual electrodes on the abdomen with a forward model. We establish a deep convolutional neural network (CNN) framework to classify normal and abnormal slow waves from the multi-electrode waveforms. We investigate the effects of non-idealized measurements on performance, including shifted electrode array positioning, smaller array sizes, high body mass index (BMI), and low signal-to-noise ratio (SNR). We compare the performance of our deep CNN to a linear discriminant classifier using wave propagation spatial features.A deep CNN framework demonstrated robust classification, with accuracy above 90% for all SNR above 0 dB, horizontal shifts within 3 cm, vertical shifts within 6 cm, and abdominal tissue depth within 6 cm. The linear discriminant classifier was much more vulnerable to SNR, electrode placement, and BMI.This is the first study to attempt and, moreover, succeed in using a deep CNN to disambiguate normal and abnormal gastric slow wave patterns from high-resolution EGG data.These findings suggest that multi-electrode cutaneous abdominal recordings have the potential to serve as widely deployable clinical screening tools for gastrointestinal foregut disorders.

  View details for DOI 10.1109/TBME.2019.2922235

  View details for Web of Science ID 000526271800020

  View details for PubMedID 31199249

• Spatial Patterns From High-Resolution Electrogastrography Correlate With Severity of Symptoms in Patients With Functional Dyspepsia and Gastroparesis CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Gharibans, A. A., Coleman, T. P., Mousa, H., Kunkel, D. C. 2019; 17 (13): 2668-2677

  Abstract

  Invasive gastric electrical mapping has revealed spatial abnormalities of the slow wave in subjects with gastroparesis and functional gastrointestinal disorders. Cutaneous high-resolution electrogastrography (HR-EGG) is a non-invasive method that can detect spatial features of the gastric slow wave. We performed HR-EGG in subjects with active foregut symptoms to evaluate associations between gastric myoelectric abnormalities, symptoms (based on a validated questionnaire), and gastric emptying.We performed a case-control study of 32 subjects, including 7 healthy individuals (controls), 7 subjects with functional dyspepsia and normal gastric emptying, and 18 subjects with gastroparesis, from a tertiary care program. All subjects were assessed by computed tomography imaging of the abdomen and HR-EGG and completed the PAGI-SYM questionnaire on foregut symptoms, which includes the gastroparesis cardinal symptom index. We performed volume reconstruction of the torso and stomach from computed tomography images to guide accurate placement of the HR-EGG array.Spatial slow-wave abnormalities were detected in 44% of subjects with foregut symptoms. Moreover, subjects with a higher percentage of slow waves with aberrant propagation direction had a higher total gastroparesis cardinal symptom index score (r = 0.56; P < .001) and more severe abdominal pain (r = 0.46; P = .009). We found no correlation between symptoms and traditional EGG parameters.In case-control study, we found that the genesis of symptoms of functional dyspepsia and gastroparesis is likely multifactorial, including possible contribution from gastric myoelectric dysfunction. Abnormal spatial parameters, detected by cutaneous HR-EGG, correlated with severity of upper gastrointestinal symptoms, regardless of gastric emptying. This noninvasive, repeatable approach might be used to identify patients for whom gastric myoelectric dysfunction contributes to functional dyspepsia and gastroparesis.

  View details for DOI 10.1016/j.cgh.2019.04.039

  View details for Web of Science ID 000497972200016

  View details for PubMedID 31009794

• Bayesian inverse methods for spatiotemporal characterization of gastric electrical activity from cutaneous multi-electrode recordings PLOS ONE Allegra, A. B., Gharibans, A. A., Schamberg, G. E., Kunkel, D. C., Coleman, T. P. 2019; 14 (10): e0220315

  Abstract

  Gastrointestinal (GI) problems give rise to 10 percent of initial patient visits to their physician. Although blockages and infections are easy to diagnose, more than half of GI disorders involve abnormal functioning of the GI tract, where diagnosis entails subjective symptom-based questionnaires or objective but invasive, intermittent procedures in specialized centers. Although common procedures capture motor aspects of gastric function, which do not correlate with symptoms or treatment response, recent findings with invasive electrical recordings show that spatiotemporal patterns of the gastric slow wave are associated with diagnosis, symptoms, and treatment response. We here consider developing non-invasive approaches to extract this information. Using CT scans from human subjects, we simulate normative and disordered gastric surface electrical activity along with associated abdominal activity. We employ Bayesian inference to solve the ill-posed inverse problem of estimating gastric surface activity from cutaneous recordings. We utilize a prior distribution on the spatiotemporal activity pertaining to sparsity in the number of wavefronts on the stomach surface, and smooth evolution of these wavefronts across time. We implement an efficient procedure to construct the Bayes optimal estimate and demonstrate its superiority compared to other commonly used inverse methods, for both normal and disordered gastric activity. Region-specific wave direction information is calculated and consistent with the simulated normative and disordered cases. We apply these methods to cutaneous multi-electrode recordings of two human subjects with the same clinical description of motor function, but different diagnosis of underlying cause. Our method finds statistically significant wave propagation in all stomach regions for both subjects, anterograde activity throughout for the subject with diabetic gastroparesis, and retrograde activity in some regions for the subject with idiopathic gastroparesis. These findings provide a further step towards towards non-invasive phenotyping of gastric function and indicate the long-term potential for enabling population health opportunities with objective GI assessment.

  View details for DOI 10.1371/journal.pone.0220315

  View details for Web of Science ID 000532565400002

  View details for PubMedID 31609972

  View details for PubMedCentralID PMC6791545

• High-density surface electromyography: A visualization method of laryngeal muscle activity Bracken, D. J., Ornelas, G., Coleman, T. P., Weissbrod, P. A. WILEY. 2019: 2347-2353

  Abstract

  Laryngeal muscle activation is a complex and dynamic process. Current evaluation methods include needle and surface electromyography (sEMG). Limitations of needle electromyography include patient discomfort, interpretive complexity, and limited duration of recording. sEMG demonstrates interpretive challenges given loss of spatial selectivity. Application of high-density sEMG (HD sEMG) arrays were evaluated for potential to compensate for spatial selectivity loss while retaining benefits of noninvasive monitoring.Basic science.Ten adults performed phonatory tasks while a 20-channel array recorded spatiotemporal data of the anterior neck. Data were processed to provide average spectral power of each electrode. Comparison was made between rest, low-, and high-pitch phonation. Two-dimensional (2D) spectral energy maps were created to evaluate use in gross identification of muscle location.Three phonatory tasks yielded spectral power measures across the HD sEMG array. Each electrode within the array demonstrated unique power values across all subjects (P < .001). Comparison of each electrode to itself across phonatory tasks yielded differences in all subjects during rest versus low versus high, rest versus low, and rest versus high and in 9/10 subjects (P < .001) for low versus high phonation. Symmetry of HD sEMG signal was noted. Review of 2D coronal energy maps allowed for gross identification of cricothyroid muscle amidst anterior strap musculature.HD sEMG can be used to identify differences in anterior neck muscle activity between rest, low-, and high-pitch phonation. HD sEMG of the anterior neck holds potential to enhance diagnostic and therapeutic monitoring for pathologies of laryngeal function.NA Laryngoscope, 129:2347-2353, 2019.

  View details for DOI 10.1002/lary.27784

  View details for Web of Science ID 000488184200039

  View details for PubMedID 30663053

• A Distributed Framework for the Construction of Transport Maps. Neural computation Mesa, D. A., Tantiongloc, J. n., Mendoza, M. n., Kim, S. n., P Coleman, T. n. 2019; 31 (4): 613–52

  Abstract

  The need to reason about uncertainty in large, complex, and multimodal data sets has become increasingly common across modern scientific environments. The ability to transform samples from one distribution P to another distribution Q enables the solution to many problems in machine learning (e.g., Bayesian inference, generative modeling) and has been actively pursued from theoretical, computational, and application perspectives across the fields of information theory, computer science, and biology. Performing such transformations in general still leads to computational difficulties, especially in high dimensions. Here, we consider the problem of computing such "measure transport maps" with efficient and parallelizable methods. Under the mild assumptions that P need not be known but can be sampled from and that the density of Q is known up to a proportionality constant, and that Q is log-concave, we provide in this work a convex optimization problem pertaining to relative entropy minimization. We show how an empirical minimization formulation and polynomial chaos map parameterization can allow for learning a transport map between P and Q with distributed and scalable methods. We also leverage findings from nonequilibrium thermodynamics to represent the transport map as a composition of simpler maps, each of which is learned sequentially with a transport cost regularized version of the aforementioned problem formulation. We provide examples of our framework within the context of Bayesian inference for the Boston housing data set and generative modeling for handwritten digit images from the MNIST data set.

  View details for PubMedID 30764740

• A flexible likelihood approach for predicting neural spiking activity from oscillatory phase JOURNAL OF NEUROSCIENCE METHODS Johnson, T. D., Coleman, T. P., Rangel, L. M. 2019; 311: 307-317

  Abstract

  The synchronous ionic currents that give rise to neural oscillations have complex influences on neuronal spiking activity that are challenging to characterize.Here we present a method to estimate probabilistic relationships between neural spiking activity and the phase of field oscillations using a generalized linear model (GLM) with an overcomplete basis of circular functions. We first use an L1-regularized maximum likelihood procedure to select an active set of regressors from the overcomplete set and perform model fitting using standard maximum likelihood estimation. An information theoretic model selection procedure is then used to identify an optimal subset of regressors and associated coefficients that minimize overfitting. To assess goodness of fit, we apply the time-rescaling theorem and compare model predictions to original data using quantile-quantile plots.Spike-phase relationships in synthetic data were robustly characterized. When applied to in vivo hippocampal data from an awake behaving rat, our method captured a multimodal relationship between the spiking activity of a CA1 interneuron, a theta (5-10 Hz) rhythm, and a nested high gamma (65-135 Hz) rhythm.Previous methods for characterizing spike-phase relationships are often only suitable for unimodal relationships, impose specific relationship shapes, or have limited ability to assess the accuracy or fit of their characterizations.This method advances the way spike-phase relationships are visualized and quantified, and captures multimodal spike-phase relationships, including relationships with multiple nested rhythms. Overall, our method is a powerful tool for revealing a wide range of neural circuit interactions.

  View details for DOI 10.1016/j.jneumeth.2018.10.028

  View details for Web of Science ID 000452935000036

  View details for PubMedID 30367887

  View details for PubMedCentralID PMC6387742

• A High-Resolution Digital DNA Melting Platform for Robust Sequence Profiling and Enhanced Genotype Discrimination SLAS TECHNOLOGY Sinha, M., Mack, H., Coleman, T. P., Fraley, S. 2018; 23 (6): 580-591

  Abstract

  DNA melting analysis provides a rapid method for genotyping a target amplicon directly after PCR amplification. To transform melt genotyping into a broad-based profiling approach for heterogeneous samples, we previously proposed the integration of universal PCR and melt analysis with digital PCR. Here, we advanced this concept by developing a high-resolution digital melt platform with precise thermal control to accomplish reliable, high-throughput heat ramping of microfluidic chip digital PCR reactions. Using synthetic DNA oligos with defined melting temperatures, we characterized sources of melting variability and minimized run-to-run variations. Within-run comparisons throughout a 20,000-reaction chip revealed that high-melting-temperature sequences were significantly less prone to melt variation. Further optimization using bacterial 16S amplicons revealed a strong dependence of the number of melting transitions on the heating rate during curve generation. These studies show that reliable high-resolution melt curve genotyping can be achieved in digital, picoliter-scale reactions and demonstrate that rate-dependent melt signatures may be useful for enhancing automated melt genotyping.

  View details for DOI 10.1177/2472630318769846

  View details for Web of Science ID 000452285600009

  View details for PubMedID 29652558

• The activity of discrete sets of neurons in the posterior insula correlates with the behavioral expression and extinction of conditioned fear JOURNAL OF NEUROPHYSIOLOGY Patricio Casanova, J., Aguilar-Rivera, M., de los Angeles Rodriguez, M., Coleman, T. P., Torrealba, F. 2018; 120 (4): 1906-1913

  Abstract

  The interoceptive insular cortex is known to be involved in the perception of bodily states and emotions. Increasing evidence points to an additional role for the insula in the storage of fear memories. However, the activity of the insula during fear expression has not been studied. We addressed this issue by recording single units from the posterior insular cortex (pIC) of awake behaving rats expressing conditioned fear during its extinction. We found a set of pIC units showing either significant increase or decrease in activity during high fear expression to the auditory cue ("freezing units"). Firing rate of freezing units showed high correlation with freezing and outlasted the duration of the auditory cue. In turn, a different set of units showed either significant increase or decrease in activity during low fear state ("extinction units"). These findings show that expression of conditioned freezing is accompanied with changes in pIC neural activity and suggest that the pIC is important to regulate the behavioral expression of fear memory. NEW & NOTEWORTHY Here, we show novel single-unit data from the interoceptive insula underlying the behavioral expression of fear. We show that different populations of neurons in the insula codify expression and extinction of conditioned fear. Our data add further support for the insula as an important player in the regulation of emotions.

  View details for DOI 10.1152/jn.00318.2018

  View details for Web of Science ID 000451350100039

  View details for PubMedID 30133379

  View details for PubMedCentralID PMC6230801

• A Modularized Efficient Framework for Non-Markov Time Series Estimation IEEE TRANSACTIONS ON SIGNAL PROCESSING Schamberg, G., Ba, D., Coleman, T. P. 2018; 66 (12): 3140-3154

  View details for DOI 10.1109/TSP.2018.2793870

  View details for Web of Science ID 000431530200004

• A State Space and Density Estimation Framework for Sleep Staging in Obstructive Sleep Apnea IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING Kang, D. Y., DeYoung, P. N., Malhotra, A., Owens, R. L., Coleman, T. P. 2018; 65 (6): 1201-1212

  Abstract

  Although the importance of sleep is increasingly recognized, the lack of robust and efficient algorithms hinders scalable sleep assessment in healthy persons and those with sleep disorders. Polysomnography (PSG) and visual/manual scoring remain the gold standard in sleep evaluation, but more efficient/automated systems are needed. Most previous works have demonstrated algorithms in high agreement with the gold standard in healthy/normal (HN) individuals-not those with sleep disorders.This paper presents a statistical framework that automatically estimates whole-night sleep architecture in patients with obstructive sleep apnea (OSA)-the most common sleep disorder. Single-channel frontal electroencephalography was extracted from 65 HN/OSA sleep studies, and decomposed into 11 spectral features in 60 903 30 s sleep epochs. The algorithm leveraged kernel density estimation to generate stage-specific likelihoods, and a 5-state hidden Markov model to estimate per-night sleep architecture.Comparisons to full PSG expert scoring revealed the algorithm was in fair agreement with the gold standard (median Cohen's kappa = 0.53). Further, analysis revealed modest decreases in median scoring agreement as OSA severity increased from HN (kappa = 0.63) to severe (kappa = 0.47). A separate implementation on HN data from the Physionet Sleep-EDF Database resulted in a median kappa = 0.65, further indicating the algorithm's broad applicability.Results of this work indicate the proposed single-channel framework can emulate expert-level scoring of sleep architecture in OSA.Algorithms constructed to more accurately model physiological variability during sleep may help advance automated sleep assessment, for practical and general use in sleep medicine.

  View details for DOI 10.1109/TBME.2017.2702123

  View details for Web of Science ID 000432982200003

  View details for PubMedID 28499990

  View details for PubMedCentralID PMC5677582

• Epidermal Electrode Technology for Detecting Ultrasonic Perturbation of Sensory Brain Activity IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING Huang, S., Fisher, J. N., Ye, M., Kim, Y., Ma, R., Nabili, M., Krauthamer, V., Myers, M. R., Coleman, T. P., Welle, C. G. 2018; 65 (6): 1272-1280

  Abstract

  We aim to demonstrate the in vivo capability of a wearable sensor technology to detect localized perturbations of sensory-evoked brain activity.Cortical somatosensory evoked potentials (SSEPs) were recorded in mice via wearable, flexible epidermal electrode arrays. We then utilized the sensors to explore the effects of transcranial focused ultrasound, which noninvasively induced neural perturbation. SSEPs recorded with flexible epidermal sensors were quantified and benchmarked against those recorded with invasive epidural electrodes.We found that cortical SSEPs recorded by flexible epidermal sensors were stimulus frequency dependent. Immediately following controlled, focal ultrasound perturbation, the sensors detected significant SSEP modulation, which consisted of dynamic amplitude decreases and altered stimulus-frequency dependence. These modifications were also dependent on the ultrasound perturbation dosage. The effects were consistent with those recorded with invasive electrodes, albeit with roughly one order of magnitude lower signal-to-noise ratio.We found that flexible epidermal sensors reported multiple SSEP parameters that were sensitive to focused ultrasound. This work therefore 1) establishes that epidermal electrodes are appropriate for monitoring the integrity of major CNS functionalities through SSEP; and 2) leveraged this technology to explore ultrasound-induced neuromodulation. The sensor technology is well suited for this application because the sensor electrical properties are uninfluenced by direct exposure to ultrasound irradiation.The sensors and experimental paradigm we present involve standard, safe clinical neurological assessment methods and are thus applicable to a wide range of future translational studies in humans with any manner of health condition.

  View details for DOI 10.1109/TBME.2017.2713647

  View details for Web of Science ID 000432982200010

  View details for PubMedID 28858781

• In-Home Sleep Recordings in Military Veterans With Posttraumatic Stress Disorder Reveal Less REM and Deep Sleep < 1 Hz FRONTIERS IN HUMAN NEUROSCIENCE Onton, J. A., Matthews, S. C., Kang, D. Y., Coleman, T. P. 2018; 12: 196

  Abstract

  Veterans with posttraumatic stress disorder (PTSD) often report suboptimal sleep quality, often described as lack of restfulness for unknown reasons. These experiences are sometimes difficult to objectively quantify in sleep lab assessments. Here, we used a streamlined sleep assessment tool to record in-home 2-channel electroencephalogram (EEG) with concurrent collection of electrodermal activity (EDA) and acceleration. Data from a single forehead channel were transformed into a whole-night spectrogram, and sleep stages were classified using a fully automated algorithm. For this study, 71 control subjects and 60 military-related PTSD subjects were analyzed for percentage of time spent in Light, Hi Deep (1-3 Hz), Lo Deep (<1 Hz), and rapid eye movement (REM) sleep stages, as well as sleep efficiency and fragmentation. The results showed a significant tendency for PTSD sleepers to spend a smaller percentage of the night in REM (p < 0.0001) and Lo Deep (p = 0.001) sleep, while spending a larger percentage of the night in Hi Deep (p < 0.0001) sleep. The percentage of combined Hi+Lo Deep sleep did not differ between groups. All sleepers usually showed EDA peaks during Lo, but not Hi, Deep sleep; however, PTSD sleepers were more likely to lack EDA peaks altogether, which usually coincided with a lack of Lo Deep sleep. Linear regressions with all subjects showed that a decreased percentage of REM sleep in PTSD sleepers was accounted for by age, prazosin, SSRIs and SNRIs (p < 0.02), while decreased Lo Deep and increased Hi Deep in the PTSD group could not be accounted for by any factor in this study (p < 0.005). Linear regression models with only the PTSD group showed that decreased REM correlated with self-reported depression, as measured with the Depression, Anxiety, and Stress Scales (DASS; p < 0.00001). DASS anxiety was associated with increased REM time (p < 0.0001). This study shows altered sleep patterns in sleepers with PTSD that can be partially accounted for by age and medication use; however, differences in deep sleep related to PTSD could not be linked to any known factor. With several medications [prazosin, selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs); p < 0.03], as well as SSRIs were associated with less sleep efficiency (b = -3.3 ± 0.95; p = 0.0005) and more sleep fragmentation (b = -1.7 ± 0.51; p = 0.0009). Anti-psychotics were associated with less sleep efficiency (b = -4.9 ± 1.4; p = 0.0004). Sleep efficiency was negatively impacted by SSRIs, antipsychotic medications, and depression (p < 0.008). Increased sleep fragmentation was associated with SSRIs, SNRIs, and anxiety (p < 0.009), while prazosin and antipsychotic medications correlated with decreased sleep fragmentation (p < 0.05).

  View details for DOI 10.3389/fnhum.2018.00196

  View details for Web of Science ID 000431896300001

  View details for PubMedID 29867419

  View details for PubMedCentralID PMC5958207

• Emerging Technologies for Molecular Diagnosis of Sepsis CLINICAL MICROBIOLOGY REVIEWS Sinha, M., Jupe, J., Mack, H., Coleman, T. P., Lawrence, S. M., Fraley, S. I. 2018; 31 (2)

  Abstract

  Rapid and accurate profiling of infection-causing pathogens remains a significant challenge in modern health care. Despite advances in molecular diagnostic techniques, blood culture analysis remains the gold standard for diagnosing sepsis. However, this method is too slow and cumbersome to significantly influence the initial management of patients. The swift initiation of precise and targeted antibiotic therapies depends on the ability of a sepsis diagnostic test to capture clinically relevant organisms along with antimicrobial resistance within 1 to 3 h. The administration of appropriate, narrow-spectrum antibiotics demands that such a test be extremely sensitive with a high negative predictive value. In addition, it should utilize small sample volumes and detect polymicrobial infections and contaminants. All of this must be accomplished with a platform that is easily integrated into the clinical workflow. In this review, we outline the limitations of routine blood culture testing and discuss how emerging sepsis technologies are converging on the characteristics of the ideal sepsis diagnostic test. We include seven molecular technologies that have been validated on clinical blood specimens or mock samples using human blood. In addition, we discuss advances in machine learning technologies that use electronic medical record data to provide contextual evaluation support for clinical decision-making.

  View details for DOI 10.1128/CMR.00089-17

  View details for Web of Science ID 000427924600007

  View details for PubMedID 29490932

  View details for PubMedCentralID PMC5967692

• Artifact Rejection Methodology Enables Continuous, Noninvasive Measurement of Gastric Myoelectric Activity in Ambulatory Subjects SCIENTIFIC REPORTS Gharibans, A. A., Smarr, B. L., Kunkel, D. C., Kriegsfeld, L. J., Mousa, H. M., Coleman, T. P. 2018; 8: 5019

  Abstract

  The increasing prevalence of functional and motility gastrointestinal (GI) disorders is at odds with bottlenecks in their diagnosis, treatment, and follow-up. Lack of noninvasive approaches means that only specialized centers can perform objective assessment procedures. Abnormal GI muscular activity, which is coordinated by electrical slow-waves, may play a key role in symptoms. As such, the electrogastrogram (EGG), a noninvasive means to continuously monitor gastric electrical activity, can be used to inform diagnoses over broader populations. However, it is seldom used due to technical issues: inconsistent results from single-channel measurements and signal artifacts that make interpretation difficult and limit prolonged monitoring. Here, we overcome these limitations with a wearable multi-channel system and artifact removal signal processing methods. Our approach yields an increase of 0.56 in the mean correlation coefficient between EGG and the clinical "gold standard", gastric manometry, across 11 subjects (p < 0.001). We also demonstrate this system's usage for ambulatory monitoring, which reveals myoelectric dynamics in response to meals akin to gastric emptying patterns and circadian-related oscillations. Our approach is noninvasive, easy to administer, and has promise to widen the scope of populations with GI disorders for which clinicians can screen patients, diagnose disorders, and refine treatments objectively.

  View details for DOI 10.1038/s41598-018-23302-9

  View details for Web of Science ID 000428032400004

  View details for PubMedID 29568042

  View details for PubMedCentralID PMC5864836

• Biosynthesis of Orthogonal Molecules Using Ferredoxin and Ferredoxin-NADP(+) Reductase Systems Enables Genetically Encoded PhyB Optogenetics ACS SYNTHETIC BIOLOGY Kyriakakis, P., Catanho, M., Hoffner, N., Thavarajah, W., Hu, V. J., Chao, S., Hsu, A., Pham, V., Naghavian, L., Dozier, L. E., Patrick, G. N., Coleman, T. P. 2018; 7 (2): 706-717

  Abstract

  Transplanting metabolic reactions from one species into another has many uses as a research tool with applications ranging from optogenetics to crop production. Ferredoxin (Fd), the enzyme that most often supplies electrons to these reactions, is often overlooked when transplanting enzymes from one species to another because most cells already contain endogenous Fd. However, we have shown that the production of chromophores used in Phytochrome B (PhyB) optogenetics is greatly enhanced in mammalian cells by expressing bacterial and plant Fds with ferredoxin-NADP+ reductases (FNR). We delineated the rate limiting factors and found that the main metabolic precursor, heme, was not the primary limiting factor for producing either the cyanobacterial or plant chromophores, phycocyanobilin or phytochromobilin, respectively. In fact, Fd is limiting, followed by Fd+FNR and finally heme. Using these findings, we optimized the PCB production system and combined it with a tissue penetrating red/far-red sensing PhyB optogenetic gene switch in animal cells. We further characterized this system in several mammalian cell lines using red and far-red light. Importantly, we found that the light-switchable gene system remains active for several hours upon illumination, even with a short light pulse, and requires very small amounts of light for maximal activation. Boosting chromophore production by matching metabolic pathways with specific ferredoxin systems will enable the unparalleled use of the many PhyB optogenetic tools and has broader implications for optimizing synthetic metabolic pathways.

  View details for DOI 10.1021/acssynbio.7b00413

  View details for Web of Science ID 000426012600042

  View details for PubMedID 29301067

  View details for PubMedCentralID PMC5820651

• Scalable Manufacturing of Solderable and Stretchable Physiologic Sensing Systems ADVANCED MATERIALS Kim, Y., Lu, J., Shih, B., Gharibans, A., Zou, Z., Matsuno, K., Aguilera, R., Han, Y., Meek, A., Xiao, J., Tolley, M. T., Coleman, T. P. 2017; 29 (39)

  Abstract

  Methods for microfabrication of solderable and stretchable sensing systems (S4s) and a scaled production of adhesive-integrated active S4s for health monitoring are presented. S4s' excellent solderability is achieved by the sputter-deposited nickel-vanadium and gold pad metal layers and copper interconnection. The donor substrate, which is modified with "PI islands" to become selectively adhesive for the S4s, allows the heterogeneous devices to be integrated with large-area adhesives for packaging. The feasibility for S4-based health monitoring is demonstrated by developing an S4 integrated with a strain gauge and an onboard optical indication circuit. Owing to S4s' compatibility with the standard printed circuit board assembly processes, a variety of commercially available surface mount chip components, such as the wafer level chip scale packages, chip resistors, and light-emitting diodes, can be reflow-soldered onto S4s without modifications, demonstrating the versatile and modular nature of S4s. Tegaderm-integrated S4 respiration sensors are tested for robustness for cyclic deformation, maximum stretchability, durability, and biocompatibility for multiday wear time. The results of the tests and demonstration of the respiration sensing indicate that the adhesive-integrated S4s can provide end users a way for unobtrusive health monitoring.

  View details for DOI 10.1002/adma.201701312

  View details for Web of Science ID 000412925600006

  View details for PubMedID 28837756

• High-Resolution Electrogastrogram: A Novel, Noninvasive Method for Determining Gastric Slow-Wave Direction and Speed IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING Gharibans, A. A., Kim, S., Kunkel, D. C., Coleman, T. P. 2017; 64 (4): 807-815

  Abstract

  Despite its simplicity and noninvasiveness, the use of the electrogastrogram (EGG) remains limited in clinical practice for assessing gastric disorders. Recent studies have characterized the occurrence of spatial gastric myoelectric abnormalities that are ignored by typical approaches relying on time-frequency analysis of single channels. In this paper we present the highresolution (HR) EGG, which utilizes an array of electrodes to estimate the direction and speed of gastric slow-waves. The approach was verified on a forward electrophysiology model of the stomach, demonstrating that an accurate assessment of slow-wave propagation can be made. Furthermore, we tested the methodology on eight healthy adults and calculated propagation directions (181 ± 29 degrees) and speeds (3.7 ± 0.5 mm/s) that are consistent with serosal recordings of slow-waves described in the literature. By overcoming the limitations of current methods, HR-EGG is a fully automated tool that may unveil new classes of gastric abnormalities. This could lead to a better diagnosis of diseases and inspire novel drugs and therapies, ultimately improving clinical outcomes.

  View details for DOI 10.1109/TBME.2016.2579310

  View details for Web of Science ID 000398738300008

  View details for PubMedID 27305668

  View details for PubMedCentralID PMC5474202

• An Information and Control Framework for Optimizing User-Compliant Human-Computer Interfaces PROCEEDINGS OF THE IEEE Tantiongloc, J., Mesa, D. A., Ma, R., Kim, S., Alzate, C. H., Camacho, J. J., Manian, V., Coleman, T. P. 2017; 105 (2): 273-285

  View details for DOI 10.1109/JPROC.2016.2608723

  View details for Web of Science ID 000394532000008

• The Use of Cardiac Orienting Responses as an Early and Scalable Biomarker of Alcohol-Related Neurodevelopmental Impairment ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH Mesa, D. A., Kable, J. A., Coles, C. D., Jones, K., Yevtushok, L., Kulikovsky, Y., Wertelecki, W., Coleman, T. P., Chambers, C. D., CIFASD 2017; 41 (1): 128-138

  Abstract

  Considered the leading cause of developmental disabilities worldwide, fetal alcohol spectrum disorders (FASD) are a global health problem. To take advantage of neural plasticity, early identification of affected infants is critical. The cardiac orienting response (COR) has been shown to be sensitive to the effects of prenatal alcohol exposure and is an inexpensive, easy to administer assessment tool. The purpose of this study was to evaluate the COR effectiveness in assessing individual risk of developmental delay.As part of an ongoing longitudinal cohort study in Ukraine, live-born infants of women with some to heavy amounts of alcohol consumption in pregnancy were recruited and compared to infants of women who consumed low or no alcohol. At 6 and 12 months, infants were evaluated with the Bayley Scales of Infant Development-II. CORs were also collected during a habituation/dishabituation learning paradigm. Using a supervised logistic regression classifier, we compared the predictive utility of the COR indices to that of the 6-month Bayley scores for identification of developmental delay based on 12-month Bayley scores. Heart rate collected at each second (Standard COR) was compared to key features (Key COR) extracted from the response.Negative predictive values (NPV) were 85% for Standard COR, 82% for Key COR, and 77% for the Bayley, and positive predictive values (PPV) were 66% for Standard COR, 62% for Key COR, and 43% for the Bayley.Predictive analysis based on the COR resulted in better NPV and PPV than the 6-month Bayley score. As the resources required to obtain a Bayley score are substantially more than in a COR-based paradigm, the findings are suggestive of its utility as an early scalable screening tool based on the COR. Further work is needed to test its long-term predictive accuracy.

  View details for DOI 10.1111/acer.13261

  View details for Web of Science ID 000393890700014

  View details for PubMedID 27883195

  View details for PubMedCentralID PMC5205554

• Visualization of Whole-Night Sleep EEG From 2-Channel Mobile Recording Device Reveals Distinct Deep Sleep Stages with Differential Electrodermal Activity FRONTIERS IN HUMAN NEUROSCIENCE Onton, J. A., Kang, D. Y., Coleman, T. P. 2016; 10: 605

  Abstract

  Brain activity during sleep is a powerful marker of overall health, but sleep lab testing is prohibitively expensive and only indicated for major sleep disorders. This report demonstrates that mobile 2-channel in-home electroencephalogram (EEG) recording devices provided sufficient information to detect and visualize sleep EEG. Displaying whole-night sleep EEG in a spectral display allowed for quick assessment of general sleep stability, cycle lengths, stage lengths, dominant frequencies and other indices of sleep quality. By visualizing spectral data down to 0.1 Hz, a differentiation emerged between slow-wave sleep with dominant frequency between 0.1-1 Hz or 1-3 Hz, but rarely both. Thus, we present here the new designations, Hi and Lo Deep sleep, according to the frequency range with dominant power. Simultaneously recorded electrodermal activity (EDA) was primarily associated with Lo Deep and very rarely with Hi Deep or any other stage. Therefore, Hi and Lo Deep sleep appear to be physiologically distinct states that may serve unique functions during sleep. We developed an algorithm to classify five stages (Awake, Light, Hi Deep, Lo Deep and rapid eye movement (REM)) using a Hidden Markov Model (HMM), model fitting with the expectation-maximization (EM) algorithm, and estimation of the most likely sleep state sequence by the Viterbi algorithm. The resulting automatically generated sleep hypnogram can help clinicians interpret the spectral display and help researchers computationally quantify sleep stages across participants. In conclusion, this study demonstrates the feasibility of in-home sleep EEG collection, a rapid and informative sleep report format, and novel deep sleep designations accounting for spectral and physiological differences.

  View details for DOI 10.3389/fnhum.2016.00605

  View details for Web of Science ID 000388762000001

  View details for PubMedID 27965558

  View details for PubMedCentralID PMC5126123

• Learning Minimal Latent Directed Information Polytrees NEURAL COMPUTATION Etesami, J., Kiyavash, N., Coleman, T. 2016; 28 (9): 1723-1768

  Abstract

  We propose an approach for learning latent directed polytrees as long as there exists an appropriately defined discrepancy measure between the observed nodes. Specifically, we use our approach for learning directed information polytrees where samples are available from only a subset of processes. Directed information trees are a new type of probabilistic graphical models that represent the causal dynamics among a set of random processes in a stochastic system. We prove that the approach is consistent for learning minimal latent directed trees. We analyze the sample complexity of the learning task when the empirical estimator of mutual information is used as the discrepancy measure.

  View details for DOI 10.1162/NECO_a_00874

  View details for Web of Science ID 000383599800001

  View details for PubMedID 27391682

• Directed Information Graphs IEEE TRANSACTIONS ON INFORMATION THEORY Quinn, C. J., Kiyavash, N., Coleman, T. P. 2015; 61 (12): 6887-6909

  View details for DOI 10.1109/TIT.2015.2478440

  View details for Web of Science ID 000368420200031

• Scalable Microfabrication Procedures for Adhesive-Integrated Flexible and Stretchable Electronic Sensors SENSORS Kang, D. Y., Kim, Y., Ornelas, G., Sinha, M., Naidu, K., Coleman, T. P. 2015; 15 (9): 23459-23476

  Abstract

  New classes of ultrathin flexible and stretchable devices have changed the way modern electronics are designed to interact with their target systems. Though more and more novel technologies surface and steer the way we think about future electronics, there exists an unmet need in regards to optimizing the fabrication procedures for these devices so that large-scale industrial translation is realistic. This article presents an unconventional approach for facile microfabrication and processing of adhesive-peeled (AP) flexible sensors. By assembling AP sensors on a weakly-adhering substrate in an inverted fashion, we demonstrate a procedure with 50% reduced end-to-end processing time that achieves greater levels of fabrication yield. The methodology is used to demonstrate the fabrication of electrical and mechanical flexible and stretchable AP sensors that are peeled-off their carrier substrates by consumer adhesives. In using this approach, we outline the manner by which adhesion is maintained and buckling is reduced for gold film processing on polydimethylsiloxane substrates. In addition, we demonstrate the compatibility of our methodology with large-scale post-processing using a roll-to-roll approach.

  View details for DOI 10.3390/s150923459

  View details for Web of Science ID 000362512200125

  View details for PubMedID 26389915

  View details for PubMedCentralID PMC4610501

• Large-scale spatiotemporal spike patterning consistent with wave propagation in motor cortex NATURE COMMUNICATIONS Takahashi, K., Kim, S., Coleman, T. P., Brown, K. A., Suminski, A. J., Best, M. D., Hatsopoulos, N. G. 2015; 6: 7169

  Abstract

  Aggregate signals in cortex are known to be spatiotemporally organized as propagating waves across the cortical surface, but it remains unclear whether the same is true for spiking activity in individual neurons. Furthermore, the functional interactions between cortical neurons are well documented but their spatial arrangement on the cortical surface has been largely ignored. Here we use a functional network analysis to demonstrate that a subset of motor cortical neurons in non-human primates spatially coordinate their spiking activity in a manner that closely matches wave propagation measured in the beta oscillatory band of the local field potential. We also demonstrate that sequential spiking of pairs of neuron contains task-relevant information that peaks when the neurons are spatially oriented along the wave axis. We hypothesize that the spatial anisotropy of spike patterning may reflect the underlying organization of motor cortex and may be a general property shared by other cortical areas.

  View details for DOI 10.1038/ncomms8169

  View details for Web of Science ID 000355534400006

  View details for PubMedID 25994554

  View details for PubMedCentralID PMC4443713

• An Optimizer's Approach to Stochastic Control Problems With Nonclassical Information Structures IEEE TRANSACTIONS ON AUTOMATIC CONTROL Kulkarni, A. A., Coleman, T. P. 2015; 60 (4): 937-949

  View details for DOI 10.1109/TAC.2014.2362596

  View details for Web of Science ID 000351731600004

• Efficient Total Probability Prediction via Convex Optimization and Optimal Transport Kim, S., Mesa, D., Coleman, T., IEEE IEEE. 2015: 681-685

  View details for Web of Science ID 000380904700136

• A Scalable Framework to Transform Samples from One Continuous Distribution to Another Mesa, D., Kim, S., Coleman, T., IEEE IEEE. 2015: 676-680

  View details for Web of Science ID 000380904700135

• EEG Gamma Band Oscillations Differentiate the Planning of Spatially Directed Movements of the Arm Versus Eye: Multivariate Empirical Mode Decomposition Analysis IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING Park, C., Plank, M., Snider, J., Kim, S., Huang, H., Gepshtein, S., Coleman, T. P., Poizner, H. 2014; 22 (5): 1083-1096

  Abstract

  The neural dynamics underlying the coordination of spatially-directed limb and eye movements in humans is not well understood. Part of the difficulty has been a lack of signal processing tools suitable for the analysis of nonstationary electroencephalographic (EEG) signals. Here, we use multivariate empirical mode decomposition (MEMD), a data-driven approach that does not employ predefined basis functions. High-density EEG, and arm and eye movements were synchronously recorded in 10 subjects performing time-constrained reaching and/or eye movements. Subjects were allowed to move both the hand and the eyes, only the hand, or only the eyes following a 500-700 ms delay interval where the hand and gaze remained on a central fixation cross. An additional condition involved a nonspatially-directed "lift" movement of the hand. The neural activity during a 500 ms delay interval was decomposed into intrinsic mode functions (IMFs) using MEMD. Classification analysis revealed that gamma band (30 Hz) IMFs produced more classifiable features differentiating the EEG according to the different upcoming movements. A benchmark test using conventional algorithms demonstrated that MEMD was the best algorithm for extracting oscillatory bands from EEG, yielding the best classification of the different movement conditions. The gamma rhythm decomposed using MEMD showed a higher correlation with the eventual movement accuracy than any other band rhythm and than any other algorithm.

  View details for DOI 10.1109/TNSRE.2014.2332450

  View details for Web of Science ID 000342080400020

  View details for PubMedID 25014959

• Dynamic and Succinct Statistical Analysis of Neuroscience Data PROCEEDINGS OF THE IEEE Kim, S., Quinn, C. J., Kiyavash, N., Coleman, T. P. 2014; 102 (5): 683-698

  View details for DOI 10.1109/JPROC.2014.2307888

  View details for Web of Science ID 000336915700005

• Fractal design concepts for stretchable electronics NATURE COMMUNICATIONS Fan, J. A., Yeo, W., Su, Y., Hattori, Y., Lee, W., Jung, S., Zhang, Y., Liu, Z., Cheng, H., Falgout, L., Bajema, M., Coleman, T., Gregoire, D., Larsen, R. J., Huang, Y., Rogers, J. A. 2014; 5

  Abstract

  Stretchable electronics provide a foundation for applications that exceed the scope of conventional wafer and circuit board technologies due to their unique capacity to integrate with soft materials and curvilinear surfaces. The range of possibilities is predicated on the development of device architectures that simultaneously offer advanced electronic function and compliant mechanics. Here we report that thin films of hard electronic materials patterned in deterministic fractal motifs and bonded to elastomers enable unusual mechanics with important implications in stretchable device design. In particular, we demonstrate the utility of Peano, Greek cross, Vicsek and other fractal constructs to yield space-filling structures of electronic materials, including monocrystalline silicon, for electrophysiological sensors, precision monitors and actuators, and radio frequency antennas. These devices support conformal mounting on the skin and have unique properties such as invisibility under magnetic resonance imaging. The results suggest that fractal-based layouts represent important strategies for hard-soft materials integration.

  View details for DOI 10.1038/ncomms4266

  View details for Web of Science ID 000332667600013

  View details for PubMedID 24509865

• Grand Challenges in Mapping the Human Brain: NSF Workshop Report IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING He, B., Coleman, T., Genin, G. M., Glover, G., Hu, X., Johnson, N., Liu, T., Makeig, S., Sajda, P., Ye, K. 2013; 60 (11): 2983-2992

  Abstract

  This report summarizes the outcomes of the NSF Workshop on Mapping and Engineering the Brain, held at Arlington, VA, during August 13-14, 2013. Three grand challenges were identified, including high spatiotemporal resolution neuroimaging, perturbation-based neuroimaging, and neuroimaging in naturalistic environments. It was highlighted that each grand challenge requires groundbreaking discoveries, enabling technologies, appropriate knowledge transfer, and multi- and transdisciplinary education and training for success.

  View details for DOI 10.1109/TBME.2013.2283970

  View details for Web of Science ID 000325974500001

  View details for PubMedID 24108705

• Efficient Methods to Compute Optimal Tree Approximations of Directed Information Graphs IEEE TRANSACTIONS ON SIGNAL PROCESSING Quinn, C. J., Kiyavash, N., Coleman, T. P. 2013; 61 (12): 3173-3182

  View details for DOI 10.1109/TSP.2013.2259161

  View details for Web of Science ID 000320135200013

• A Timing Channel Spyware for the CSMA/CA Protocol IEEE TRANSACTIONS ON INFORMATION FORENSICS AND SECURITY Kiyavash, N., Koushanfar, F., Coleman, T. P., Rodrigues, M. 2013; 8 (3): 477-487

  View details for DOI 10.1109/TIFS.2013.2238930

  View details for Web of Science ID 000318597400005

• Bit-Wise Unequal Error Protection for Variable-Length Block Codes With Feedback IEEE TRANSACTIONS ON INFORMATION THEORY Nakiboglu, B., Gorantla, S. K., Zheng, L., Coleman, T. P. 2013; 59 (3): 1475-1504

  View details for DOI 10.1109/TIT.2012.2227671

  View details for Web of Science ID 000315120400017

• Robust Directed Tree Approximations for Networks of Stochastic Processes Quinn, C. J., Etesami, J., Kiyavash, N., Coleman, T. P., IEEE IEEE. 2013: 2254-2258

  View details for Web of Science ID 000348913402077

• Circadian Rhythm of Redox State Regulates Excitability in Suprachiasmatic Nucleus Neurons SCIENCE Wang, T. A., Yu, Y. V., Govindaiah, G., Ye, X., Artinian, L., Coleman, T. P., Sweedler, J. V., Cox, C. L., Gillette, M. U. 2012; 337 (6096): 839-842

  Abstract

  Daily rhythms of mammalian physiology, metabolism, and behavior parallel the day-night cycle. They are orchestrated by a central circadian clock in the brain, the suprachiasmatic nucleus (SCN). Transcription of clock genes is sensitive to metabolic changes in reduction and oxidation (redox); however, circadian cycles in protein oxidation have been reported in anucleate cells, where no transcription occurs. We investigated whether the SCN also expresses redox cycles and how such metabolic oscillations might affect neuronal physiology. We detected self-sustained circadian rhythms of SCN redox state that required the molecular clockwork. The redox oscillation could determine the excitability of SCN neurons through nontranscriptional modulation of multiple potassium (K(+)) channels. Thus, dynamic regulation of SCN excitability appears to be closely tied to metabolism that engages the clockwork machinery.

  View details for DOI 10.1126/science.1222826

  View details for Web of Science ID 000307535600042

  View details for PubMedID 22859819

  View details for PubMedCentralID PMC3490628

• Characterizing the Efficacy of the NRL Network Pump in Mitigating Covert Timing Channels IEEE TRANSACTIONS ON INFORMATION FORENSICS AND SECURITY Gorantla, S. K., Kadloor, S., Kiyavash, N., Coleman, T. P., Moskowitz, I. S., Kang, M. H. 2012; 7 (1): 64-75

  View details for DOI 10.1109/TIFS.2011.2163398

  View details for Web of Science ID 000299438100007

• An Optimizer's Approach to Stochastic Control Problems with Nonclassical Information Structures Kulkarni, A. A., Coleman, T. P., IEEE IEEE. 2012: 154-159

  View details for Web of Science ID 000327200400026

• A Stochastic Control Approach to Optimally Designing Hierarchical Flash Sets in P300 Communication Prostheses IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING Ma, R., Aghasadeghi, N., Jarzebowski, J., Bretl, T., Coleman, T. P. 2012; 20 (1): 102-112

  Abstract

  The P300-based speller is a well-established brain-computer interface for communication. It displays a matrix of objects on the computer screen, flashes each object in sequence, and looks for a P300 response induced by flashing the desired object. Most existing P300 spellers uses a fixed set of flash objects. We demonstrate that performance can be significantly improved by sequential selections from a hierarchy of flash sets containing variable number of objects. Theoretically, the optimal hierarchy of flash sets--with respect to a given statistical language model--can be found by solving a stochastic control problem of low computational complexity. Experimentally, statistical analysis demonstrates that the average time per output character at 85% accuracy is reduced by over 50% using our variable-flash-set approach as compared to traditional fixed-flash-set spellers.

  View details for DOI 10.1109/TNSRE.2011.2179560

  View details for Web of Science ID 000299512300013

  View details for PubMedID 22203722

• A Message-Passing Approach to Combating Desynchronization Attacks IEEE TRANSACTIONS ON INFORMATION FORENSICS AND SECURITY Sadasivam, S., Moulin, P., Coleman, T. P. 2011; 6 (3): 894-905

  View details for DOI 10.1109/TIFS.2011.2129511

  View details for Web of Science ID 000293924700003

• Epidermal Electronics SCIENCE Kim, D., Lu, N., Ma, R., Kim, Y., Kim, R., Wang, S., Wu, J., Won, S., Tao, H., Islam, A., Yu, K., Kim, T., Chowdhury, R., Ying, M., Xu, L., Li, M., Chung, H., Keum, H., McCormick, M., Liu, P., Zhang, Y., Omenetto, F. G., Huang, Y., Coleman, T., Rogers, J. A. 2011; 333 (6044): 838-843

  Abstract

  We report classes of electronic systems that achieve thicknesses, effective elastic moduli, bending stiffnesses, and areal mass densities matched to the epidermis. Unlike traditional wafer-based technologies, laminating such devices onto the skin leads to conformal contact and adequate adhesion based on van der Waals interactions alone, in a manner that is mechanically invisible to the user. We describe systems incorporating electrophysiological, temperature, and strain sensors, as well as transistors, light-emitting diodes, photodetectors, radio frequency inductors, capacitors, oscillators, and rectifying diodes. Solar cells and wireless coils provide options for power supply. We used this type of technology to measure electrical activity produced by the heart, brain, and skeletal muscles and show that the resulting data contain sufficient information for an unusual type of computer game controller.

  View details for DOI 10.1126/science.1206157

  View details for Web of Science ID 000293785400031

  View details for PubMedID 21836009

• Estimating the directed information to infer causal relationships in ensemble neural spike train recordings JOURNAL OF COMPUTATIONAL NEUROSCIENCE Quinn, C. J., Coleman, T. P., Kiyavash, N., Hatsopoulos, N. G. 2011; 30 (1): 17-44

  Abstract

  Advances in recording technologies have given neuroscience researchers access to large amounts of data, in particular, simultaneous, individual recordings of large groups of neurons in different parts of the brain. A variety of quantitative techniques have been utilized to analyze the spiking activities of the neurons to elucidate the functional connectivity of the recorded neurons. In the past, researchers have used correlative measures. More recently, to better capture the dynamic, complex relationships present in the data, neuroscientists have employed causal measures-most of which are variants of Granger causality-with limited success. This paper motivates the directed information, an information and control theoretic concept, as a modality-independent embodiment of Granger's original notion of causality. Key properties include: (a) it is nonzero if and only if one process causally influences another, and (b) its specific value can be interpreted as the strength of a causal relationship. We next describe how the causally conditioned directed information between two processes given knowledge of others provides a network version of causality: it is nonzero if and only if, in the presence of the present and past of other processes, one process causally influences another. This notion is shown to be able to differentiate between true direct causal influences, common inputs, and cascade effects in more two processes. We next describe a procedure to estimate the directed information on neural spike trains using point process generalized linear models, maximum likelihood estimation and information-theoretic model order selection. We demonstrate that on a simulated network of neurons, it (a) correctly identifies all pairwise causal relationships and (b) correctly identifies network causal relationships. This procedure is then used to analyze ensemble spike train recordings in primary motor cortex of an awake monkey while performing target reaching tasks, uncovering causal relationships whose directionality are consistent with predictions made from the wave propagation of simultaneously recorded local field potentials.

  View details for DOI 10.1007/s10827-010-0247-2

  View details for Web of Science ID 000287458400003

  View details for PubMedID 20582566

  View details for PubMedCentralID PMC3171872

• A Feedback Information-Theoretic Approach to the Design of Brain-Computer Interfaces INTERNATIONAL JOURNAL OF HUMAN-COMPUTER INTERACTION Omar, C., Akce, A., Johnson, M., Bretl, T., Ma, R., Maclin, E., McCormick, M., Coleman, T. P. 2011; 27 (1): 5-23

  View details for DOI 10.1080/10447318.2011.535749

  View details for Web of Science ID 000286819400002

• A Computationally Efficient Method for Nonparametric Modeling of Neural Spiking Activity with Point Processes NEURAL COMPUTATION Coleman, T. P., Sarma, S. S. 2010; 22 (8): 2002-2030

  Abstract

  Point-process models have been shown to be useful in characterizing neural spiking activity as a function of extrinsic and intrinsic factors. Most point-process models of neural activity are parametric, as they are often efficiently computable. However, if the actual point process does not lie in the assumed parametric class of functions, misleading inferences can arise. Nonparametric methods are attractive due to fewer assumptions, but computation in general grows with the size of the data. We propose a computationally efficient method for nonparametric maximum likelihood estimation when the conditional intensity function, which characterizes the point process in its entirety, is assumed to be a Lipschitz continuous function but otherwise arbitrary. We show that by exploiting much structure, the problem becomes efficiently solvable. We next demonstrate a model selection procedure to estimate the Lipshitz parameter from data, akin to the minimum description length principle and demonstrate consistency of our estimator under appropriate assumptions. Finally, we illustrate the effectiveness of our method with simulated neural spiking data, goldfish retinal ganglion neural data, and activity recorded in CA1 hippocampal neurons from an awake behaving rat. For the simulated data set, our method uncovers a more compact representation of the conditional intensity function when it exists. For the goldfish and rat neural data sets, we show that our nonparametric method gives a superior absolute goodness-of-fit measure used for point processes than the most common parametric and splines-based approaches.

  View details for DOI 10.1162/NECO_a_00001-Coleman

  View details for Web of Science ID 000279109600003

  View details for PubMedID 20438334

• A dynamical point process model of auditory nerve spiking in response to complex sounds JOURNAL OF COMPUTATIONAL NEUROSCIENCE Trevino, A., Coleman, T. P., Allen, J. 2010; 29 (1-2): 193-201

  Abstract

  In this paper, we develop a dynamical point process model for how complex sounds are represented by neural spiking in auditory nerve fibers. Although many models have been proposed, our point process model is the first to capture elements of spontaneous rate, refractory effects, frequency selectivity, phase locking at low frequencies, and short-term adaptation, all within a compact parametric approach. Using a generalized linear model for the point process conditional intensity, driven by extrinsic covariates, previous spiking, and an input-dependent charging/discharging capacitor model, our approach robustly captures the aforementioned features on datasets taken at the auditory nerve of chinchilla in response to speech inputs. We confirm the goodness of fit of our approach using the Time-Rescaling Theorem for point processes.

  View details for DOI 10.1007/s10827-009-0146-6

  View details for Web of Science ID 000281563500015

  View details for PubMedID 19353258

  View details for PubMedCentralID PMC4138954

• Introduction to the Special Issue on Information Theory in Molecular Biology and Neuroscience IEEE TRANSACTIONS ON INFORMATION THEORY Milenkovic, O., Alterovitz, G., Battail, G., Coleman, T. P., Hagenauer, J., Meyn, S. P., Price, N., Ramoni, M. F., Shmulevich, I., Szpankowski, W. 2010; 56 (2): 649-652

  View details for DOI 10.1109/TIT.2009.2036971

  View details for Web of Science ID 000275032900001

• Joint Source-Channel Coding for Transmitting Correlated Sources Over Broadcast Networks Coleman, T. P., Martinian, E., Ordentlich, E. IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. 2009: 3864-3868

  View details for DOI 10.1109/TIT.2009.2023722

  View details for Web of Science ID 000268107200034

• A Low-Complexity Universal Scheme for Rate-Constrained Distributed Regression Using a Wireless Sensor Network Fernandes, A. L., Raginsky, M., Coleman, T. P. IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. 2009: 1731-1744

  View details for DOI 10.1109/TSP.2009.2013897

  View details for Web of Science ID 000265437900007

• Low-complexity approaches to Slepian-Wolf near-lossless distributed data compression Coleman, T. P., Lee, A. H., Medard, M., Effros, M. IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. 2006: 3546-3561

  View details for DOI 10.1109/TIT.2006.878215

  View details for Web of Science ID 000239408700010

• A distributed scheme for achieving energy-delay tradeoffs with multiple service classes over a dynamically varying network IEEE JOURNAL ON SELECTED AREAS IN COMMUNICATIONS Coleman, T. P., Medard, M. 2004; 22 (5): 929-941

  View details for DOI 10.1109/JSAC.2004.826930

  View details for Web of Science ID 000221947000011

• Capacity of time-slotted ALOHA packetized multiple-access systems over the AWGN channel IEEE TRANSACTIONS ON WIRELESS COMMUNICATIONS Medard, M., Huang, J. Y., Goldsmith, A. J., Meyn, S. P., Coleman, T. P. 2004; 3 (2): 486-499

  View details for DOI 10.1109/TWC.2003.8921175

  View details for Web of Science ID 000220158400018