02933nas a2200181 4500008004100000245013500041210006900176300001100245490000700256520224100263100001702504700002102521700002102542700002202563700002402585700001702609856012502626 2025 eng d00aFrequency dependence of cortical somatosensory evoked response to peripheral nerve stimulation with controlled afferent excitation0 aFrequency dependence of cortical somatosensory evoked response t a0260350 v223 aObjective: H-reflex targeted neuroplasticity (HrTNP) protocols comprise a promising rehabilitation approach to improve motor function after brain or spinal injury. In this operant conditioning protocol, concurrent measurement of cortical responses, such as somatosensory evoked potentials (SEPs), would be useful for examining supraspinal involvement and neuroplasticity mechanisms. To date, this potential has not been exploited. However, the stimulation parameters used in the HrTNP protocol deviate from the classically recommended settings for SEP measurements. Most notably, it demands a much longer pulse width, higher stimulation intensity, and lower frequency than traditional SEP settings. In this paper, we report SEP measurements performed within the HrTNP stimulation parameter constraints, specifically characterizing the effect of stimulation frequency. Approach: SEPs were acquired for tibial nerve stimulation at three stimulation frequencies (0.2, 1, and 2 Hz) in 13 subjects while maintaining the afferent volley by controlling the direct soleus muscle response via the Evoked Potential Operant Conditioning System. The amplitude and latency of the short-latency P40 and mid-latency N70 SEP components were measured at the central scalp region using non-invasive electroencephalography. Main results: As frequency rose from 0.2 Hz, P40 amplitude and latency did not change. In contrast, N70 amplitude decreased significantly (39% decrease at 1 Hz, and 57% decrease at 2 Hz), presumably due to gating effects. N70 latency was not affected. Across all three frequencies, N70 amplitude increased significantly with stimulation intensity and correlated with M-wave amplitude. Significance: We assess SEPs within an HrTNP protocol, focusing on P40 and N70, elicited with controlled afferent excitation at three stimulation frequencies. HrTNP conditioning protocols show promise for enhancing motor function after brain and spinal injuries. While SEPs offer valuable insights into supraspinal involvement, the stimulation parameters in HrTNP often differ from standard SEP measurement protocols. We address these deviations and provide recommendations for effectively integrating SEP assessments into HrTNP studies. 1 aGupta, Disha1 aBrangaccio, Jodi1 aMojtabavi, Helia1 aCarp, Jonathan, S1 aWolpaw, Jonathan, R1 aHill, Jeremy uhttps://www.neurotechcenter.org/publications/2025/frequency-dependence-cortical-somatosensory-evoked-response-peripheral02783nas a2200157 4500008004100000245011100041210006900152490000700221520216800228100002702396700002202423700002302445700001702468700001702485856012302502 2025 eng d00aTest-retest reliability of kinematic and EEG low-beta spectral features in a robot-based arm movement task0 aTestretest reliability of kinematic and EEG lowbeta spectral fea0 v113 aObjective.Low-beta (Lβ, 13-20 Hz) power plays a key role in upper-limb motor control and afferent processing, making it a strong candidate for a neurophysiological biomarker. We investigate the test-retest reliability of Lβpower and kinematic features from a robotic task over extended intervals between sessions to assess its potential for tracking longitudinal changes in sensorimotor function.Approach.We designed and optimized a testing protocol to evaluate Lβpower and kinematic features (maximal and mean speed, reaction time, and movement duration) in ten right-handed healthy individuals that performed a planar center-out task using a robotic device and EEG for data collection. The task was performed with both hands, and the experiment was repeated approximately 40 days later under similar conditions, to resemble real-life intervention periods. We first characterized the selected features within the task context for each session, then assessed intersession agreement, the test-retest reliability (Intraclass Correlation Coefficient, ICC), and established threshold values for meaningful changes in Lβpower using Bland-Altman plots and repeatability coefficients.Main Results.Lβpower showed the expected contralateral reduction during movement preparation and onset. Both Lβpower and kinematic features exhibited good to excellent test-retest reliability (ICC > 0.8), displaying no significant intersession differences. Kinematic results align with prior literature, reinforcing the robustness of these measures in tracking motor performance over time. Changes in Lβpower between sessions exceeding 11.4% for right-arm and 16.5% for left-arm movements reflect meaningful intersession differences.Significance.This study provides evidence that Lβpower remains stable over extended intersession intervals comparable to rehabilitation timelines. The strong reliability of both Lβpower and kinematic features supports their use in monitoring upper-extremity sensorimotor function longitudinally, with Lβpower emerging as a promising biomarker for tracking therapeutic outcomes, postulating it as a reliable feature for long-term applications. 1 aRueda-Parra, Sebastian1 aHardesty, Russell1 aGemoets, Darren, E1 aHill, Jeremy1 aGupta, Disha uhttps://www.neurotechcenter.org/publications/2025/test-retest-reliability-kinematic-and-eeg-low-beta-spectral-features02631nas a2200313 4500008004100000022001400041245013200055210006900187260001600256520153300272100002401805700002201829700002001851700002001871700002201891700001701913700002301930700002201953700001801975700002301993700001902016700001902035700002402054700002002078700002302098700002102121710006202142856011302204 2024 eng d a1556-096100aBrain-Computer Interfaces for Communication in Patients with Disorders of Consciousness: A Gap Analysis and Scientific Roadmap.0 aBrainComputer Interfaces for Communication in Patients with Diso c2024 Jan 293 a

BACKGROUND: We developed a gap analysis that examines the role of brain-computer interfaces (BCI) in patients with disorders of consciousness (DoC), focusing on their assessment, establishment of communication, and engagement with their environment.

METHODS: The Curing Coma Campaign convened a Coma Science work group that included 16 clinicians and neuroscientists with expertise in DoC. The work group met online biweekly and performed a gap analysis of the primary question.

RESULTS: We outline a roadmap for assessing BCI readiness in patients with DoC and for advancing the use of BCI devices in patients with DoC. Additionally, we discuss preliminary studies that inform development of BCI solutions for communication and assessment of readiness for use of BCIs in DoC study participants. Special emphasis is placed on the challenges posed by the complex pathophysiologies caused by heterogeneous brain injuries and their impact on neuronal signaling. The differences between one-way and two-way communication are specifically considered. Possible implanted and noninvasive BCI solutions for acute and chronic DoC in adult and pediatric populations are also addressed.

CONCLUSIONS: We identify clinical and technical gaps hindering the use of BCI in patients with DoC in each of these contexts and provide a roadmap for research aimed at improving communication for adults and children with DoC, spanning the clinical spectrum from intensive care unit to chronic care.

1 aSchiff, Nicholas, D1 aDiringer, Michael1 aDiserens, Karin1 aEdlow, Brian, L1 aGosseries, Olivia1 aHill, Jeremy1 aHochberg, Leigh, R1 aIsmail, Fatima, Y1 aMeyer, Ivo, A1 aMikell, Charles, B1 aMofakham, Sima1 aMolteni, Erika1 aPolizzotto, Leonard1 aShah, Sudhin, A1 aStevens, Robert, D1 aThengone, Daniel1 aand the Curing Coma Campaign and its Contributing Members uhttps://www.neurotechcenter.org/publications/2024/brain-computer-interfaces-communication-patients-disorders03132nas a2200433 4500008004100000022001400041245013100055210006900186260001200255300001100267490000800278520179900286653000902085653001002094653001502104653001902119653003002138653002302168653001802191653001102209653002902220100001702249700001902266700002202285700001902307700001702326700002602343700001802369700002702387700002002414700002102434700001802455700002102473700001702494700002402511700001902535700002002554856012402574 2023 eng d a1095-957200aComparisons of electrophysiological markers of impaired executive attention after traumatic brain injury and in healthy aging.0 aComparisons of electrophysiological markers of impaired executiv c07/2023 a1201260 v2743 a

Executive attention impairments are a persistent and debilitating consequence of traumatic brain injury (TBI). To make headway towards treating and predicting outcomes following heterogeneous TBI, cognitive impairment specific pathophysiology first needs to be characterized. In a prospective observational study, we measured EEG during the attention network test aimed at detecting alerting, orienting, executive attention and processing speed. The sample (N = 110) of subjects aged 18-86 included those with and without traumatic brain injury: n = 27, complicated mild TBI; n = 5, moderate TBI; n = 10, severe TBI; n = 63, non-brain-injured controls. Subjects with TBI had impairments in processing speed and executive attention. Electrophysiological markers of executive attention processing in the midline frontal regions reveal that, as a group, those with TBI and elderly non-brain-injured controls have reduced responses. We also note that those with TBI and elderly controls have responses that are similar for both low and high-demand trials. In subjects with moderate-severe TBI, reductions in frontal cortical activation and performance profiles are both similar to that of controls who are ∼4 to 7 years older. Our specific observations of frontal response reductions in subjects with TBI and in older adults is consistent with the suggested role of the anterior forebrain mesocircuit as underlying cognitive impairments. Our results provide novel correlative data linking specific pathophysiological mechanisms underlying domain-specific cognitive deficits following TBI and with normal aging. Collectively, our findings provide biomarkers that may serve to track therapeutic interventions and guide development of targeted therapeutics following brain injuries.

10aAged10aAging10aBiomarkers10aBrain Injuries10aBrain Injuries, Traumatic10aExecutive Function10aHealthy Aging10aHumans10aNeuropsychological Tests1 aKim, Nayoung1 aJamison, Keith1 aJaywant, Abhishek1 aGaretti, Jacob1 aBlunt, Emily1 aRoyChoudhury, Arindam1 aButler, Tracy1 aDams-O'Connor, Kristen1 aKhedr, Shahenda1 aChen, Chun-Cheng1 aShetty, Teena1 aWinchell, Robert1 aHill, Jeremy1 aSchiff, Nicholas, D1 aKuceyeski, Amy1 aShah, Sudhin, A uhttps://www.neurotechcenter.org/publications/2023/comparisons-electrophysiological-markers-impaired-executive-attention03030nas a2200265 4500008004100000022001400041245016500055210006900220260001600289490000700305520208500312653002502397653002102422653001302443653001102456653002102467653002202488653002602510100002502536700001702561700002202578700002202600700002202622856012002644 2023 eng d a1741-255200aMethods for automated delineation and assessment of EMG responses evoked by peripheral nerve stimulation in diagnostic and closed-loop therapeutic applications.0 aMethods for automated delineation and assessment of EMG response c2023 Jul 210 v203 a

Surface electromyography measurements of the Hoffmann (H-) reflex are essential in a wide range of neuroscientific and clinical applications. One promising emerging therapeutic application is H-reflex operant conditioning, whereby a person is trained to modulate the H-reflex, with generalized beneficial effects on sensorimotor function in chronic neuromuscular disorders. Both traditional diagnostic and novel realtime therapeutic applications rely on accurate definitions of the H-reflex and M-wave temporal bounds, which currently depend on expert case-by-case judgment. The current study automates such judgments.Our novel wavelet-based algorithm automatically determines temporal extent and amplitude of the human soleus H-reflex and M-wave. In each of 20 participants, the algorithm was trained on data from a preliminary 3 or 4 min recruitment-curve measurement. Output was evaluated on parametric fits to subsequent sessions' recruitment curves (92 curves across all participants) and on the conditioning protocol's subsequent baseline trials (∼1200 per participant) performed near. Results were compared against the original temporal bounds estimated at the time, and against retrospective estimates made by an expert 6 years later.Automatic bounds agreed well with manual estimates: 95% lay within ±2.5 ms. The resulting H-reflex magnitude estimates showed excellent agreement (97.5% average across participants) between automatic and retrospective bounds regarding which trials would be considered successful for operant conditioning. Recruitment-curve parameters also agreed well between automatic and manual methods: 95% of the automatic estimates of the current required to elicitfell within±1.4%of the retrospective estimate; for the 'threshold' current that produced an M-wave 10% of maximum, this value was±3.5%.Such dependable automation of M-wave and H-reflex definition should make both established and emerging H-reflex protocols considerably less vulnerable to inter-personnel variability and human error, increasing translational potential.

10aElectric Stimulation10aElectromyography10aH-Reflex10aHumans10aMuscle, Skeletal10aPeripheral Nerves10aRetrospective Studies1 aMcKinnon, Michael, L1 aHill, Jeremy1 aCarp, Jonathan, S1 aDellenbach, Blair1 aThompson, Aiko, K uhttps://www.neurotechcenter.org/publications/2023/methods-automated-delineation-and-assessment-emg-responses-evoked02630nas a2200289 4500008004100000022001400041245009200055210006900147260001300216300001200229490000700241520171500248100001701963700002201980700001902002700001902021700001802040700002102058700001702079700002302096700001902119700002002138700002402158700001702182700002002199856012102219 2022 eng d a2163-040200aCognitive-Motor Dissociation Following Pediatric Brain Injury: What About the Children?0 aCognitiveMotor Dissociation Following Pediatric Brain Injury Wha c2022 Jun a248-2570 v123 a

BACKGROUND AND OBJECTIVES: Following severe brain injury, up to 16% of adults showing no clinical signs of cognitive function nonetheless have preserved cognitive capacities detectable via neuroimaging and neurophysiology; this has been designated cognitive-motor dissociation (CMD). Pediatric medicine lacks both practice guidelines for identifying covert cognition and epidemiologic data regarding CMD prevalence.

METHODS: We applied a diverse battery of neuroimaging and neurophysiologic tests to evaluate 2 adolescents (aged 15 and 18 years) who had shown no clinical evidence of preserved cognitive function following brain injury at age 9 and 13 years, respectively. Clinical evaluations were consistent with minimally conscious state (minus) and vegetative state, respectively.

RESULTS: Both participants' EEG, and 1 participant's fMRI, provided evidence that they could understand commands and make consistent voluntary decisions to follow them. Both participants' EEG demonstrated larger-than-expected responses to auditory stimuli and intact semantic processing of words in context.

DISCUSSION: These converging lines of evidence lead us to conclude that both participants had preserved cognitive function dissociated from their motor output. Throughout the 5+ years since injury, communication attempts and therapy had remained uninformed by such objective evidence of their cognitive abilities. Proper diagnosis of CMD is an ethical imperative. Children with covert cognition reflect a vulnerable and isolated population; the methods outlined here provide a first step in identifying such persons to advance efforts to alleviate their condition.

1 aKim, Nayoung1 aO'Sullivan, James1 aOlafson, Emily1 aCaliendo, Eric1 aNowak, Sophie1 aVoss, Henning, U1 aLowder, Ryan1 aWatson, William, D1 aIvanidze, Jana1 aFins, Joseph, J1 aSchiff, Nicholas, D1 aHill, Jeremy1 aShah, Sudhin, A uhttps://www.neurotechcenter.org/publications/2022/cognitive-motor-dissociation-following-pediatric-brain-injury-what03130nas a2200313 4500008004100000022001400041245013900055210006900194260001500263520206900278653002002347653002602367653002102393653002202414653001302436653001102449653002702460653002502487100001702512700001702529700001902546700002402565700002302589700002102612700001402633700002402647700002202671856012302693 2022 eng d a1940-087X00aThe Evoked Potential Operant Conditioning System (EPOCS): A Research Tool and an Emerging Therapy for Chronic Neuromuscular Disorders.0 aEvoked Potential Operant Conditioning System EPOCS A Research To c2022 08 253 a

The Evoked Potential Operant Conditioning System (EPOCS) is a software tool that implements protocols for operantly conditioning stimulus-triggered muscle responses in people with neuromuscular disorders, which in turn can improve sensorimotor function when applied appropriately. EPOCS monitors the state of specific target muscles-e.g., from surface electromyography (EMG) while standing, or from gait cycle measurements while walking on a treadmill-and automatically triggers calibrated stimulation when pre-defined conditions are met. It provides two forms of feedback that enable a person to learn to modulate the targeted pathway's excitability. First, it continuously monitors ongoing EMG activity in the target muscle, guiding the person to produce a consistent level of activity suitable for conditioning. Second, it provides immediate feedback of the response size following each stimulation and indicates whether it has reached the target value. To illustrate its use, this article describes a protocol through which a person can learn to decrease the size of the Hoffmann reflex-the electrically-elicited analog of the spinal stretch reflex-in the soleus muscle. Down-conditioning this pathway's excitability can improve walking in people with spastic gait due to incomplete spinal cord injury. The article demonstrates how to set up the equipment; how to place stimulating and recording electrodes; and how to use the free software to optimize electrode placement, measure the recruitment curve of direct motor and reflex responses, measure the response without operant conditioning, condition the reflex, and analyze the resulting data. It illustrates how the reflex changes over multiple sessions and how walking improves. It also discusses how the system can be applied to other kinds of evoked responses and to other kinds of stimulation, e.g., motor evoked potentials to transcranial magnetic stimulation; how it can address various clinical problems; and how it can support research studies of sensorimotor function in health and disease.

10aChronic Disease10aConditioning, Operant10aElectromyography10aEvoked Potentials10aH-Reflex10aHumans10aNeuromuscular Diseases10aSpinal Cord Injuries1 aHill, Jeremy1 aGupta, Disha1 aEftekhar, Amir1 aBrangaccio, Jodi, A1 aNorton, James, J S1 aMcLeod, Michelle1 aFake, Tim1 aWolpaw, Jonathan, R1 aThompson, Aiko, K uhttps://www.neurotechcenter.org/publications/2022/evoked-potential-operant-conditioning-system-epocs-research-tool-and02884nas a2200217 4500008004100000022001400041245008200055210006900137260001200206300001200218490000700230520217300237100001702410700002002427700001902447700001802466700002402484700002002508700001702528856012102545 2022 eng d a2163-040200aObjective Neurophysiologic Markers of Cognition After Pediatric Brain Injury.0 aObjective Neurophysiologic Markers of Cognition After Pediatric  c10/2022 a352-3640 v123 a

BACKGROUND AND OBJECTIVES: Following brain injury, clinical assessments of residual and emerging cognitive function are difficult and fraught with errors. In adults, recent American Academy of Neurology (AAN) practice guidelines recommend objective neuroimaging and neurophysiologic measures to support diagnosis. Equivalent measures are lacking in pediatrics-an especially great challenge due to the combined heterogeneity of both brain injury and pediatric development. Therefore, we aim to establish quantitative, clinically practicable measures of cognitive function following pediatric brain injury.

METHODS: Participants with and without brain injury were aged 8-18 years, clinically classified according to cognitive recovery state: N = 8 in disorders of consciousness (DoC), N = 7 in confusional state, N = 19 cognitively impaired, and N = 13 typically developing uninjured controls. We prospectively measured electroencephalographic markers of sensory processing and attention in an auditory oddball paradigm, and of covert movement attempts in a command-following paradigm.

RESULTS: In 3 participants with DoC, EEG markers of active attempted command following revealed cognitive function that clinical assessment had failed to detect. These same 3 individuals could also be distinguished from the rest of their group by 2 event-related potentials that correlate with sensory processing and orienting attention in the oddball paradigm. Considered across the whole participant group, magnitudes of these 2 ERP markers significantly increased as cognitive recovery progressed (ANOVA: each < 0.001); viewed jointly, the 2 ERP markers cleanly delineated the 4 cognitive states.

DISCUSSION: Despite heterogeneity of brain injuries and brain development, our objective EEG markers reflected cognitive recovery independent of motor function. Two of these markers required no active participation. Together, they allowed us to identify 3 individuals who meet the criteria for cognitive-motor dissociation. To diagnose, prognose, and track cognitive recovery accurately, such markers should be used in pediatrics.

1 aKim, Nayoung1 aWatson, William1 aCaliendo, Eric1 aNowak, Sophie1 aSchiff, Nicholas, D1 aShah, Sudhin, A1 aHill, Jeremy uhttps://www.neurotechcenter.org/publications/2022/objective-neurophysiologic-markers-cognition-after-pediatric-brain02629nas a2200169 4500008004100000022001400041245004900055210004600104260001200150300001100162490000600173520212600179100001702305700002302322700002002345856009402365 2021 eng d a2405-844000aaudiomath: A neuroscientist's sound toolkit.0 aaudiomath A neuroscientists sound toolkit c02/2021 ae062360 v73 a

In neuroscientific experiments and applications, working with auditory stimuli demands software tools for generation and acquisition of raw audio, for composition and tailoring of that material into finished stimuli, for precisely timed presentation of the stimuli, and for experimental session recording. Numerous programming tools exist to approach these tasks, but their differing specializations and conventions demand extra time and effort for integration. In particular, verifying stimulus timing requires extensive engineering effort when developing new applications. This paper has two purposes. The first is to present (https://pypi.org/project/audiomath), a sound software library for Python that prioritizes the needs of neuroscientists. It minimizes programming effort by providing a simple object-oriented interface that unifies functionality for audio generation, manipulation, visualization, decoding, encoding, recording, and playback. It also incorporates specialized tools for measuring and optimizing stimulus timing. The second purpose is to relay what we have learned, during development and application of the software, about the twin challenges of delivering stimuli precisely at a certain time, and of precisely measuring the time at which stimuli were delivered. We provide a primer on these problems and the possible approaches to them. We then report audio latency measurements across a range of hardware, operating systems and settings, to illustrate the ways in which hardware and software factors interact to affect stimulus presentation performance, and the resulting pitfalls for the programmer and experimenter. In particular, we highlight the potential conflict between demands for low latency, low variability in latency ("jitter"), cooperativeness, and robustness. We report the ways in which can help to map this territory and provide a simplified path toward each application's particular priority. By unifying audio-related functionality and providing specialized diagnostic tools, both simplifies and potentiates the development of neuroscientific applications in Python.

1 aHill, Jeremy1 aMooney, Scott, W J1 aPrusky, Glen, T uhttps://www.neurotechcenter.org/publications/2021/audiomath-neuroscientists-sound-toolkit