Somatosensory cortex microstimulation modulates primary motor and ventral premotor cortex neurons with extensive spatial convergence and divergence.

Intracortical microstimulation (ICMS) is known to affect distant neurons transynaptically, yet the extent to which ICMS pulses delivered in one cortical area modulate neurons in other cortical areas remains largely unknown. Here we assessed how the individual pulses of multi-channel ICMS trains delivered in the upper extremity representation of the macaque primary somatosensory area (S1) modulate neuron firing in the primary motor cortex (M1) and in the ventral premotor cortex (PMv). S1-ICMS pulses modulated the majority of units recorded both in the M1 upper extremity representation and in PMv, producing more inhibition than excitation. Effects converged on individual neurons in both M1 and PMv from extensive S1 territories. Conversely, effects of ICMS delivered in a small region of S1 diverged to wide territories in both M1 and PMv. The effects of this direct modulation of M1 and PMv neurons produced by multi-electrode S1-ICMS like that used here may need to be taken into account by bidirectional brain-computer interfaces that decode intended movements from neural activity in these cortical motor areas. Significance Statement: Although ICMS is known to produce effects transynaptically, relatively little is known about how ICMS in one cortical area affects neurons in other cortical areas. We show that the effects of multi-channel ICMS in a small patch of S1 diverge to affect neurons distributed widely in both M1 and PMv, and conversely, individual neurons in each of these areas can be affected by ICMS converging from much of the S1 upper extremity representation. Such direct effects of ICMS may complicate the decoding of motor intent from M1 or PMv when artificial sensation is delivered via S1-ICMS in bidirectional brain-computer interfaces.

Young adults who improve performance during dual-task walking show more flexible reallocation of cognitive resources: a mobile brain-body imaging (MoBI) study.

INTRODUCTION: In young adults, pairing a cognitive task with walking can have different effects on gait and cognitive task performance. In some cases, performance clearly declines whereas in others compensatory mechanisms maintain performance. This study investigates the preliminary finding of behavioral improvement in Go/NoGo response inhibition task performance during walking compared with sitting, which was observed at the piloting stage. MATERIALS AND METHODS: Mobile brain/body imaging (MoBI) was used to record electroencephalographic (EEG) activity, 3-dimensional (3D) gait kinematics and behavioral responses in the cognitive task, during sitting or walking on a treadmill. RESULTS: In a cohort of 26 young adults, 14 participants improved in measures of cognitive task performance while walking compared with sitting. These participants exhibited walking-related EEG amplitude reductions over frontal scalp regions during key stages of inhibitory control (conflict monitoring, control implementation, and pre-motor stages), accompanied by reduced stride-to-stride variability and faster responses to stimuli compared with those who did not improve. In contrast, 12 participants who did not improve exhibited no EEG amplitude differences across physical condition. DISCUSSION: The neural activity changes associated with performance improvement during dual tasking hold promise as cognitive flexibility markers that can potentially help assess cognitive decline in aging and neurodegeneration.

Investigating How Auditory and Visual Stimuli Promote Recovery After Stress With Potential Applications for Workplace Stress and Burnout: Protocol for a Randomized Trial.

Background: Work-related stress is one of the top sources of stress amongst working adults. Relaxation rooms are one organizational strategy being used to reduce workplace stress. Amongst healthcare workers, relaxation rooms have been shown to improve perceived stress levels after 15 min of use. However, few studies have examined physiological and cognitive changes after stress, which may inform why relaxation rooms reduce perceived stress. Understanding the biological mechanisms governing why perceived stress improves when using a relaxation room could lead to more effective strategies to address workplace stress. Objective: The purpose of this research study is to understand how physiological measures, cognitive performance, and perceived stress change after acute stress and whether certain sensory features of a relaxation room are more effective at promoting recovery from stress. Methods: 80 healthy adults will perform a stress induction task (Trier Social Stress Test, TSST) to evaluate how physiological and cognitive responses after stress are affected by sensory features of a relaxation room. After the stress induction task, participants will recover for 40 min in a MindBreaks™ relaxation room containing auditory and visual stimuli designed to promote relaxation. Participants will be randomized into four cohorts to experience auditory and visual stimuli; auditory stimuli; visual stimuli; or no stimuli in the room. Measures of heart rate and neural activity will be continuously monitored using wearable devices. Participants will perform working memory assessments and rate their perceived stress levels throughout the experiment. These measures will be compared before and after the stress induction task to determine how different sensory stimuli affect the rate at which individuals recover. Results: Recruitment started in December 2021 and will continue until December 2022 or until enrollment is completed. Final data collection and subsequent analysis are anticipated by December 2022. We expect all trial results will be available by early 2023. Discussion: Findings will provide data and information about which sensory features of a relaxation room are most effective at promoting recovery after acute stress. This information will be useful in determining how these features might be effective at creating individualized and organizational strategies for mitigating the effects of workplace stress.

Neural markers of proactive and reactive cognitive control are altered during walking: A Mobile Brain-Body Imaging (MoBI) study.

The processing of sensory information and the generation of motor commands needed to produce coordinated actions can interfere with ongoing cognitive tasks. Even simple motor behaviors like walking can alter cognitive task performance. This cognitive-motor interference (CMI) could arise from disruption of planning in anticipation of carrying out the task (proactive control) and/or from disruption of the execution of the task (reactive control). In young healthy adults, walking-induced interference with behavioral performance may not be readily observable because flexibility in neural circuits can compensate for the added demands of simultaneous loads. In this study, cognitive-motor loads were systematically increased during cued task-switching while underlying neurophysiologic changes in proactive and reactive mechanisms were measured. Brain activity was recorded from 22 healthy young adults using 64-channel electroencephalography (EEG) based Mobile Brain/Body Imaging (MoBI) as they alternately sat or walked during performance of cued task-switching. Walking altered neurophysiological indices of both proactive and reactive control. Walking amplified cue-evoked late fontal slow waves, and reduced the amplitude of target-evoked fronto-central N2 and parietal P3. The effects of walking on evoked neural responses systematically increased as the task became increasingly difficult. This may provide an objective brain marker of increasing cognitive load, and may prove to be useful in identifying seemingly healthy individuals who are currently able to disguise ongoing degenerative processes through active compensation. If, however, degeneration continues unabated these people may reach a compensatory limit at which point both cognitive performance and control of coordinated actions may decline rapidly.

Injecting Information into the Mammalian Cortex: Progress, Challenges, and Promise.

For 150 years artificial stimulation has been used to study the function of the nervous system. Such stimulation-whether electrical or optogenetic-eventually may be used in neuroprosthetic devices to replace lost sensory inputs and to otherwise introduce information into the nervous system. Efforts toward this goal can be classified broadly as either biomimetic or arbitrary. Biomimetic stimulation aims to mimic patterns of natural neural activity, so that the subject immediately experiences the artificial stimulation as if it were natural sensation. Arbitrary stimulation, in contrast, makes no attempt to mimic natural patterns of neural activity. Instead, different stimuli-at different locations and/or in different patterns-are assigned different meanings randomly. The subject's time and effort then are required to learn to interpret different stimuli, a process that engages the brain's inherent plasticity. Here we will examine progress in using artificial stimulation to inject information into the cerebral cortex and discuss the challenges for and the promise of future development.

Using the MoBI motion capture system to rapidly and accurately localize EEG electrodes in anatomic space.

During mobile brain/body imaging (MoBI) experiments, electroencephalography and motion capture systems are used in concert to record high temporal resolution neural activity and movement kinematics while participants perform demanding perceptual and cognitive tasks in a naturalistic environment. A typical MoBI setup involves positioning multi-channel electrode caps based on anatomical fiducials as well as experimenter and participant intuition regarding the scalp midpoint location (i.e., Cz). Researchers often use the "template" electrode locations provided by the manufacturer, however, the "actual" electrode locations can vary based on each participant's head morphology. Accounting for differences in head morphologies could provide more accurate clinical diagnostic information when using MoBI to identify neurological deficits in patients with motor, sensory, or cognitive impairments. Here, we asked whether the existing motion capture system used in a MoBI setup could be easily adapted to improve spatial localization of electrodes across participants without requiring additional or specialized equipment that might impede clinical adoption. Using standard electrode configurations, infrared markers were placed on a subset of electrodes and anatomical fiducials, and the remaining electrode locations were estimated using spherical or ellipsoid models. We identified differences in event-related potentials between "template" and "actual" electrode locations during a Go/No-Go task (p < 9.8e-5) and an object-manipulation task (p < 9.8e-5). Thus, the motion capture system already used in MoBI experiments can be effectively deployed to accurately register and quantify the neural activity. Improving the spatial localization without needing specialized hardware or additional setup time to the workflow has important real-world implications for translating MoBI to clinical environments.

Utilizing High-Density Electroencephalography and Motion Capture Technology to Characterize Sensorimotor Integration While Performing Complex Actions.

Studies of sensorimotor integration often use sensory stimuli that require a simple motor response, such as a reach or a grasp. Recent advances in neural recording techniques, motion capture technologies, and time-synchronization methods enable studying sensorimotor integration using more complex sensory stimuli and performed actions. Here, we demonstrate that prehensile actions that require using complex sensory instructions for manipulating different objects can be characterized using high-density electroencephalography and motion capture systems. In 20 participants, we presented stimuli in different sensory modalities (visual, auditory) containing different contextual information about the object with which to interact. Neural signals recorded near motor cortex and posterior parietal cortex discharged based on both the instruction delivered and object manipulated. Additionally, kinematics of the wrist movements could be discriminated between participants. These findings demonstrate a proof-of-concept behavioral paradigm for studying sensorimotor integration of multidimensional sensory stimuli to perform complex movements. The designed framework will prove vital for studying neural control of movements in clinical populations in which sensorimotor integration is impaired due to information no longer being communicated correctly between brain regions (e.g. stroke). Such a framework is the first step towards developing a neural rehabilitative system for restoring function more effectively.

Mirror neurons precede non-mirror neurons during action execution.

Mirror neurons are thought to represent an individual's ability to understand the actions of others by discharging as one individual performs or observes another individual performing an action. Studies typically have focused on mirror neuron activity during action observation, examining activity during action execution primarily to validate mirror neuron involvement in the motor act. As a result, little is known about the precise role of mirror neurons during action execution. In this study, during execution of reach-grasp-manipulate movements, we found activity of mirror neurons generally preceded that of non-mirror neurons. Not only did the onset of task-related modulation occur earlier in mirror neurons, but state transitions detected by hidden Markov models also occurred earlier in mirror neuron populations. Our findings suggest that mirror neurons may be at the forefront of action execution.NEW & NOTEWORTHY Mirror neurons commonly are thought to provide a neural substrate for understanding the actions of others, but mirror neurons also are active during action execution, when additional, non-mirror neurons are active as well. Examining the timing of activity during execution of a naturalistic reach-grasp-manipulate task, we found that mirror neuron activity precedes that of non-mirror neurons at both the unit and the population level. Thus mirror neurons may be at the leading edge of action execution.

How is electrical stimulation of the brain experienced, and how can we tell? Selected considerations on sensorimotor function and speech.

Electrical stimulation of the nervous system is a powerful tool for localizing and examining the function of numerous brain regions. Delivered to certain regions of the cerebral cortex, electrical stimulation can evoke a variety of first-order effects, including observable movements or an urge to move, or somatosensory, visual, or auditory percepts. In still other regions the subject may be oblivious to the stimulation. Often overlooked, however, is whether the subject is aware of the stimulation, and if so, how the stimulation is experienced by the subject. In this review of how electrical stimulation has been used to study selected aspects of sensorimotor and language function, we raise questions that future studies might address concerning the subjects' second-order experiences of intention and agency regarding evoked movements, of the naturalness of evoked sensory percepts, and of other qualia that might be evoked in the absence of an overt first-order experience.

Mirror Neuron Populations Represent Sequences of Behavioral Epochs During Both Execution and Observation.

Mirror neurons (MNs) have the distinguishing characteristic of modulating during both execution and observation of an action. Although most studies of MNs have focused on various features of the observed movement, MNs also may monitor the behavioral circumstances in which the movement is embedded, including time periods preceding and following the observed movement. Here, we recorded multiple MNs simultaneously from implanted electrode arrays as two male monkeys executed and observed a reach, grasp, and manipulate task involving different target objects. MNs were recorded from premotor cortex (PM-MNs) and primary motor cortex (M1-MNs). During execution trials, hidden Markov models (HMMs) applied to the activity of either PM-MN or M1-MN populations most often detected sequences of four hidden states, which we named according to the behavioral epoch during which each state began: initial, reaction, movement, and final. The hidden states of MN populations thus reflected not only the movement, but also three behavioral epochs during which no movement occurred. HMMs trained on execution trials could decode similar sequences of hidden states in observation trials, with complete hidden state sequences decoded more frequently from PM-MN populations than from M1-MN populations. Moreover, population trajectories projected in a 2D plane defined by execution trials were preserved in observation trials more for PM-MN than for M1-MN populations. These results suggest that MN populations represent entire behavioral sequences, including both movement and non-movement. PM-MN populations showed greater similarity than M1-MN populations in their representation of behavioral sequences during execution versus observation.SIGNIFICANCE STATEMENT Mirror neurons (MNs) are thought to provide a neural mechanism for understanding the actions of others. However, for an action to be understood, both the movement per se and the non-movement context before and after the movement need to be represented. We found that simultaneously recorded MN populations encoded sequential hidden neural states corresponding approximately to sequential behavioral epochs of a reach, grasp, and manipulate task. During observation trials, hidden state sequences were similar to those identified in execution trials. Hidden state similarity was stronger for MN populations in premotor cortex than for those in primary motor cortex. Execution/observation similarity of hidden state sequences may contribute to understanding the actions of others without actually performing the action oneself.

Injecting Instructions into Premotor Cortex.

The premotor cortex (PM) receives inputs from parietal cortical areas representing processed visuospatial information, translates that information into programs for particular movements, and communicates those programs to the primary motor cortex (M1) for execution. Consistent with this general function, intracortical microstimulation (ICMS) in the PM of sufficient frequency, amplitude, and duration has been shown to evoke complex movements of the arm and hand that vary systematically depending on the locus of stimulation. Using frequencies and amplitudes too low to evoke muscle activity, however, we found that ICMS in the PM can provide instructions to perform specific reach, grasp, and manipulate movements. These instructed actions were not fixed but rather were learned through associations between the arbitrary stimulation locations and particular movements. Low-amplitude ICMS at different PM locations thus evokes distinguishable experiences that can become associated with specific movements arbitrarily, providing a novel means of injecting information into the nervous system.

A Mixed-Signal VLSI System for Producing Temporally Adapting Intraspinal Microstimulation Patterns for Locomotion.

Neural pathways can be artificially activated through the use of electrical stimulation. For individuals with a spinal cord injury, intraspinal microstimulation, using electrical currents on the order of 125 µ A, can produce muscle contractions and joint torques in the lower extremities suitable for restoring walking. The work presented here demonstrates an integrated circuit implementing a state-based control strategy where sensory feedback and intrinsic feed forward control shape the stimulation waveforms produced on-chip. Fabricated in a 0.5 µ m process, the device was successfully used in vivo to produce walking movements in a model of spinal cord injury. This work represents progress towards an implantable solution to be used for restoring walking in individuals with spinal cord injuries.

Restoring stepping after spinal cord injury using intraspinal microstimulation and novel control strategies.

The overall objective of this project is to develop a feedback-driven intraspinal microstimulation (ISMS) system. We hypothesize that ISMS will enhance the functionality of stepping by reducing muscle fatigue and producing synergistic movements by activating neural networks in the spinal cord. In the present pilot study, the controller was tested with ISMS and external sensors (force plates, gyroscopes, and accelerometers). Cats were partially supported in a sling and bi-laterally stepped overground on a 4-m instrumented walkway. The walkway had variable friction. Limb angle was controlled to within 10° even in the presence of variable friction. Peak ground reaction forces in each limb were approximately 12% of body weight (12.5% was full load bearing in this experimental setup); rarely, the total supportive force briefly decreased to as low as 4.1%. Magnetic resonance images were acquired of the excised spinal cord and the implanted array. The majority of electrodes (75%) were implanted successfully into their target regions. This represents the first successful application of ISMS for overground walking.