A Comparison of Wearable Tonometry, Photoplethysmography, and Electrocardiography for Cuffless Measurement of Blood Pressure in an Ambulatory Setting.

OBJECTIVE: While non-invasive, cuffless blood pressure (BP) measurement has demonstrated relevancy in controlled environments, ambulatory measurement is important for hypertension diagnosis and control. We present both in-lab and ambulatory BP estimation results from a diverse cohort of participants. METHODS: Participants (N=1125, aged 21-85, 49.2% female, multiple hypertensive categories) had BP measured in-lab over a 24-hour period with a subset also receiving ambulatory measurements. Radial tonometry, photoplethysmography (PPG), electrocardiography (ECG), and accelerometry signals were collected simultaneously with auscultatory or oscillometric references for systolic (SBP) and diastolic blood pressure (DBP). Predictive models to estimate BP using a variety of sensor-based feature groups were evaluated against challenging baselines. RESULTS: Despite limited availability, tonometry-derived features showed superior performance compared to other feature groups and baselines, yieldingprediction errors of 0.32 ±9.8 mmHg SBP and 0.54 ±7.7 mmHg DBP in-lab, and 0.86 ±8.7 mmHg SBP and 0.75 ±5.9 mmHg DBP for 24-hour averages. SBP error standard deviation (SD) was reduced in normotensive (in-lab: 8.1 mmHg, 24-hr: 7.2 mmHg) and younger (in-lab: 7.8 mmHg, 24-hr: 6.7 mmHg) subpopulations. SBP SD was further reduced 15-20% when constrained to the calibration posture alone. CONCLUSION: Performance for normotensive and younger participants was superior to the general population across all feature groups. Reference type, posture relative to calibration, and controlled vs. ambulatory setting all impacted BP errors. SIGNIFICANCE: Results highlight the need for demographically diverse populations and challenging evaluation settings for BP estimation studies. We present the first public dataset of ambulatory tonometry and cuffless BP over a 24-hour period to aid in future cardiovascular research.

Cortical Topography of Error-Related High-Frequency Potentials During Erroneous Control in a Continuous Control Brain-Computer Interface.

Brain-computer interfaces (BCIs) benefit greatly from performance feedback, but current systems lack automatic, task-independent feedback. Cortical responses elicited from user error have the potential to serve as state-based feedback to BCI decoders. To gain a better understanding of local error potentials, we investigate responsive cortical power underlying error-related potentials (ErrPs) from the human cortex during a one-dimensional center-out BCI task, tracking the topography of high-gamma (70-100 Hz) band power (HBP) specific to BCI error. We measured electrocorticography (ECoG) in three human subjects during dynamic, continuous control over BCI cursor velocity. Subjects used motor imagery and rest to move the cursor toward and subsequently dwell within a target region. We then identified and labeled epochs where the BCI decoder incorrectly moved the cursor in the direction opposite of the subject's expectations (i.e., BCI error). We found increased HBP in various cortical areas 100-500 ms following BCI error with respect to epochs of correct, intended control. Significant responses were noted in primary somatosensory, motor, premotor, and parietal areas and generally regardless of whether the subject was using motor imagery or rest to move the cursor toward the target. Parts of somatosensory, temporal, and parietal areas exclusively had increased HBP when subjects were using motor imagery. In contrast, only part of the parietal cortex near the angular gyrus exclusively had an increase in HBP during rest. This investigation is, to our knowledge, the first to explore cortical fields changes in the context of continuous control in ECoG BCI. We present topographical changes in HBP characteristic specific to the generation of error. By focusing on continuous control, instead of on discrete control for simple selection, we investigate a more naturalistic setting and provide high ecological validity for characterizing error potentials. Such potentials could be considered as design elements for co-adaptive BCIs in the future as task-independent feedback to the decoder, allowing for more robust and individualized BCIs.

Context-dependent relationship in high-resolution micro-ECoG studies during finger movements.

OBJECTIVE: The activation of the sensorimotor cortex as measured by electrocorticographic (ECoG) signals has been correlated with contralateral hand movements in humans, as precisely as the level of individual digits. However, the relationship between individual and multiple synergistic finger movements and the neural signal as detected by ECoG has not been fully explored. The authors used intraoperative high-resolution micro-ECoG (µECoG) on the sensorimotor cortex to link neural signals to finger movements across several context-specific motor tasks. METHODS: Three neurosurgical patients with cortical lesions over eloquent regions participated. During awake craniotomy, a sensorimotor cortex area of hand movement was localized by high-frequency responses measured by an 8 × 8 µECoG grid of 3-mm interelectrode spacing. Patients performed a flexion movement of the thumb or index finger, or a pinch movement of both, based on a visual cue. High-gamma (HG; 70-230 Hz) filtered µECoG was used to identify dominant electrodes associated with thumb and index movement. Hand movements were recorded by a dataglove simultaneously with µECoG recording. RESULTS: In all 3 patients, the electrodes controlling thumb and index finger movements were identifiable approximately 3-6-mm apart by the HG-filtered µECoG signal. For HG power of cortical activation measured with µECoG, the thumb and index signals in the pinch movement were similar to those observed during thumb-only and index-only movement, respectively (all p > 0.05). Index finger movements, measured by the dataglove joint angles, were similar in both the index-only and pinch movements (p > 0.05). However, despite similar activation across the conditions, markedly decreased thumb movement was observed in pinch relative to independent thumb-only movement (all p < 0.05). CONCLUSIONS: HG-filtered µECoG signals effectively identify dominant regions associated with thumb and index finger movement. For pinch, the µECoG signal comprises a combination of the signals from individual thumb and index movements. However, while the relationship between the index finger joint angle and HG-filtered signal remains consistent between conditions, there is not a fixed relationship for thumb movement. Although the HG-filtered µECoG signal is similar in both thumb-only and pinch conditions, the actual thumb movement is markedly smaller in the pinch condition than in the thumb-only condition. This implies a nonlinear relationship between the cortical signal and the motor output for some, but importantly not all, movement types. This analysis provides insight into the tuning of the motor cortex toward specific types of motor behaviors.

BCI Use and Its Relation to Adaptation in Cortical Networks.

Brain-computer interfaces (BCIs) carry great potential in the treatment of motor impairments. As a new motor output, BCIs interface with the native motor system, but acquisition of BCI proficiency requires a degree of learning to integrate this new function. In this review, we discuss how BCI designs often take advantage of the brain's motor system infrastructure as sources of command signals. We highlight a growing body of literature examining how this approach leads to changes in activity across cortex, including beyond motor regions, as a result of learning the new skill of BCI control. We discuss the previous research identifying patterns of neural activity associated with BCI skill acquisition and use that closely resembles those associated with learning traditional native motor tasks. We then discuss recent work in animals probing changes in connectivity of the BCI control site, which were linked to BCI skill acquisition, and use this as a foundation for our original work in humans. We present our novel work showing changes in resting state connectivity across cortex following the BCI learning process. We find substantial, heterogeneous changes in connectivity across regions and frequencies, including interactions that do not involve the BCI control site. We conclude from our review and original work that BCI skill acquisition may potentially lead to significant changes in evoked and resting state connectivity across multiple cortical regions. We recommend that future studies of BCIs look beyond motor regions to fully describe the cortical networks involved and long-term adaptations resulting from BCI skill acquisition.

Cortico-Cortical Interactions during Acquisition and Use of a Neuroprosthetic Skill.

A motor cortex-based brain-computer interface (BCI) creates a novel real world output directly from cortical activity. Use of a BCI has been demonstrated to be a learned skill that involves recruitment of neural populations that are directly linked to BCI control as well as those that are not. The nature of interactions between these populations, however, remains largely unknown. Here, we employed a data-driven approach to assess the interaction between both local and remote cortical areas during the use of an electrocorticographic BCI, a method which allows direct sampling of cortical surface potentials. Comparing the area controlling the BCI with remote areas, we evaluated relationships between the amplitude envelopes of band limited powers as well as non-linear phase-phase interactions. We found amplitude-amplitude interactions in the high gamma (HG, 70-150 Hz) range that were primarily located in the posterior portion of the frontal lobe, near the controlling site, and non-linear phase-phase interactions involving multiple frequencies (cross-frequency coupling between 8-11 Hz and 70-90 Hz) taking place over larger cortical distances. Further, strength of the amplitude-amplitude interactions decreased with time, whereas the phase-phase interactions did not. These findings suggest multiple modes of cortical communication taking place during BCI use that are specialized for function and depend on interaction distance.

Regional Patterns of Cortical Phase Synchrony in the Resting State.

Synchronized phase estimates between oscillating neuronal signals at the macroscale level reflect coordinated activities between neuronal assemblies. Recent electrophysiological evidence suggests the presence of significant spontaneous phase synchrony within the resting state. The purpose of this study was to investigate phase synchrony, including directional interactions, in resting state subdural electrocorticographic recordings to better characterize patterns of regional phase interactions across the lateral cortical surface during the resting state. We estimated spontaneous phase locking value (PLV) as a measure of functional connectivity, and phase slope index (PSI) as a measure of pseudo-causal phase interactions, across a broad range of canonical frequency bands and the modulation of the amplitude envelope of high gamma (amHG), a band that is believed to best reflect the physiological processes giving rise to the functional magnetic resonance imaging BOLD signal. Long-distance interactions had higher PLVs in slower frequencies (≤theta) than in higher ones (≥beta) with amHG behaving more like slow frequencies, and a general trend of increasing frequency band of significant PLVs when moving across the lateral surface along an anterior-posterior axis. Moreover, there was a strong trend of frontal-to-parietal directional phase synchronization, measured by PSI across multiple frequencies. These findings, which are likely indicative of coordinated and structured spontaneous cortical interactions, are important in the study of time scales and directional nature of resting state functional connectivity, and may ultimately contribute to a better understanding of how spontaneous synchrony is linked to variation in regional architecture across the lateral cortical surface.

Directional patterns of cross frequency phase and amplitude coupling within the resting state mimic patterns of fMRI functional connectivity.

Functional imaging investigations into the brain's resting state interactions have yielded a wealth of insight into the intrinsic and dynamic neural architecture supporting cognition and behavior. Electrophysiological studies however have highlighted the fact that synchrony across large-scale cortical systems is composed of spontaneous interactions occurring at timescales beyond the traditional resolution of fMRI, a feature that limits the capacity of fMRI to draw inference on the true directional relationship between network nodes. To approach the question of directionality in resting state signals, we recorded resting state functional MRI (rsfMRI) and electrocorticography (ECoG) from four human subjects undergoing invasive epilepsy monitoring. Using a seed-point based approach, we employed phase-amplitude coupling (PAC) and biPhase Locking Values (bPLV), two measures of cross-frequency coupling (CFC) to explore both outgoing and incoming connections between the seed and all non-seed, site electrodes. We observed robust PAC between a wide range of low-frequency phase and high frequency amplitude estimates. However, significant bPLV, a CFC measure of phase-phase synchrony, was only observed at specific narrow low and high frequency bandwidths. Furthermore, the spatial patterns of outgoing PAC connectivity were most closely associated with the rsfMRI connectivity maps. Our results support the hypothesis that PAC is relatively ubiquitous phenomenon serving as a mechanism for coordinating high-frequency amplitudes across distant neuronal assemblies even in absence of overt task structure. Additionally, we demonstrate that the spatial distribution of a seed-point rsfMRI sensorimotor network is strikingly similar to specific patterns of directional PAC. Specifically, the high frequency activities of distal patches of cortex owning membership in a rsfMRI sensorimotor network were most likely to be entrained to the phase of a low frequency rhythm engendered from the neural populations at the seed-point, suggestive of greater directional coupling from the seed out to the site electrodes.

Comparison of subdural and subgaleal recordings of cortical high-gamma activity in humans.

OBJECTIVE: The purpose of this study is to determine the relationship between cortical electrophysiological (CE) signals recorded from the surface of the brain (subdural electrocorticography, or ECoG) and signals recorded extracranially from the subgaleal (SG) space. METHODS: We simultaneously recorded several hours of continuous ECoG and SG signals from 3 human pediatric subjects, and compared power spectra of signals between a differential SG montage and several differential ECoG montages to determine the nature of the transfer function between them. RESULTS: We demonstrate the presence of CE signals in the SG montage in the high-gamma range (HG, 70-110 Hz), and the transfer function between 70 and 110 Hz is best characterized as a linear function of frequency. We also test an alternative transfer function, i.e. a single pole filter, to test the hypothesis of frequency dependent attenuation in that range, but find this model to be inferior to the linear model. CONCLUSIONS: Our findings indicate that SG electrodes are capable of recording HG signals without frequency distortion compared with ECoG electrodes. SIGNIFICANCE: HG signals could be recorded minimally invasively from outside the skull, which could be important for clinical care or brain-computer interface applications.

Sequential activation of premotor, primary somatosensory and primary motor areas in humans during cued finger movements.

OBJECTIVE: Human voluntary movements are a final product of complex interactions between multiple sensory, cognitive and motor areas of central nervous system. The objective was to investigate temporal sequence of activation of premotor (PM), primary motor (M1) and somatosensory (S1) areas during cued finger movements. METHODS: Electrocorticography (ECoG) was used to measure activation timing in human PM, S1, and M1 neurons in preparation for finger movements in 5 subjects with subdural grids for seizure localization. Cortical activation was determined by the onset of high gamma (HG) oscillation (70-150Hz). The three cortical regions were mapped anatomically using a common brain atlas and confirmed independently with direct electrical cortical stimulation, somatosensory evoked potentials and detection of HG response to tactile stimulation. Subjects were given visual cues to flex each finger or pinch the thumb and index finger. Movements were captured with a dataglove and time-locked with ECoG. A windowed covariance metric was used to identify the rising slope of HG power between two electrodes and compute time lag. Statistical constraints were applied to the time estimates to combat the noise. Rank sum testing was used to verify the sequential activation of cortical regions across 5 subjects. RESULTS: In all 5 subjects, HG activation in PM preceded S1 by an average of 53±13ms (P=0.03), PM preceded M1 by 180±40ms (P=0.001) and S1 activation preceded M1 by 136±40ms (P=0.04). CONCLUSIONS: Sequential HG activation of PM, S1 and M1 regions in preparation for movements is reported. Activity in S1 prior to any overt body movements supports the notion that these neurons may encode sensory information in anticipation of movements, i.e., an efference copy. Our analysis suggests that S1 modulation likely originates from PM. SIGNIFICANCE: First electrophysiological evidence of efference copy in humans.

Brain-computer interfaces: a powerful tool for scientific inquiry.

Brain-computer interfaces (BCIs) are devices that record from the nervous system, provide input directly to the nervous system, or do both. Sensory BCIs such as cochlear implants have already had notable clinical success and motor BCIs have shown great promise for helping patients with severe motor deficits. Clinical and engineering outcomes aside, BCIs can also be tremendously powerful tools for scientific inquiry into the workings of the nervous system. They allow researchers to inject and record information at various stages of the system, permitting investigation of the brain in vivo and facilitating the reverse engineering of brain function. Most notably, BCIs are emerging as a novel experimental tool for investigating the tremendous adaptive capacity of the nervous system.

Distributed cortical adaptation during learning of a brain-computer interface task.

The majority of subjects who attempt to learn control of a brain-computer interface (BCI) can do so with adequate training. Much like when one learns to type or ride a bicycle, BCI users report transitioning from a deliberate, cognitively focused mindset to near automatic control as training progresses. What are the neural correlates of this process of BCI skill acquisition? Seven subjects were implanted with electrocorticography (ECoG) electrodes and had multiple opportunities to practice a 1D BCI task. As subjects became proficient, strong initial task-related activation was followed by lessening of activation in prefrontal cortex, premotor cortex, and posterior parietal cortex, areas that have previously been implicated in the cognitive phase of motor sequence learning and abstract task learning. These results demonstrate that, although the use of a BCI only requires modulation of a local population of neurons, a distributed network of cortical areas is involved in the acquisition of BCI proficiency.