Journal of Neurophysiology

Tanis, Daniel; Calalo, Jan A.; Cashaback, Joshua G. A.; Kurtzer, Isaac L.

doi: 10.1152/jn.00435.2022pmid: 36448693

The timing of motor commands is critical for task performance. A well-known example is rapidly raising the arm while standing upright. Here, reaction forces from the arm movement to the body are countered by leg and trunk muscle activity starting before any sensory feedback from the perturbation and often before the onset of arm muscle activity. Despite decades of research on the patterns, modifiability, and neural basis of these "anticipatory postural adjustments" it remains unclear why asynchronous motor commands occur. Simple accuracy considerations appear unlikely since temporally advanced motor commands displace the body from its initial position. Effort is a credible and overlooked factor that has successfully explained coordination patterns of many behaviors including gait and reaching. We provide the first use of optimal control to address this question. Feedforward commands were applied to a body mass mechanically linked to a rapidly moved limb mass. We determined the feedforward actions with the lowest cost according to an explicit criterion, accuracy alone versus accuracy + effort. Accuracy costs alone led to synchronous activation of the body and limb controllers. Adding effort to the cost resulted in body commands preceding limb commands. This sequence takes advantage of the body's momentum in one direction to counter the limb's reaction force in the opposite direction, allowing a lower peak command and lower integral. With a combined accuracy + effort cost, temporal advancement was further impacted by various task goals and plant dynamics, replicating previous findings and suggesting further studies utilizing optimal control principles.

Villamar, Zoe; Ludvig, Daniel; Perreault, Eric J.

doi: 10.1152/jn.00171.2022pmid: 36475940

The spinal stretch reflex is a fundamental building block of motor function, with a sensitivity that varies continuously during movement and when changing between movement and posture. Many have investigated task-dependent reflex sensitivity, but few have provided simple, quantitative analyses of the relationship between the volitional control and stretch reflex sensitivity throughout tasks that require coordinated activity of several muscles. Here we develop such an analysis and use it to test the hypothesis that modulation of reflex sensitivity during movement can be explained by the balance of activity within agonist and antagonist muscles better than by activity only in the muscle homonymous with the reflex. Subjects completed hundreds of flexion and extension movements as small, pseudo-random perturbations of elbow angle were applied to obtain estimates of stretch reflex amplitude throughout the movement. A subset of subjects performed a postural control task at muscle activities matched to those during movement. We found that reflex modulation during movement can be described by background activity in antagonist muscles about the elbow much better than by activity only in the muscle homonymous to the reflex (p<0.001). Agonist muscle activity enhanced reflex sensitivity whereas antagonist activity suppressed it. Surprisingly, the magnitude of these effects was similar, suggesting a balance of control between agonists and antagonists very different from the dominance of sensitivity to homonymous activity during posture. This balance is due to a large decrease in sensitivity to homonymous muscle activity during movement rather than substantial changes in the influence of antagonistic muscle activity.

DiNicola, Lauren M.; Ariyo, Oluwatobi I.; Buckner, Randy L.

doi: 10.1152/jn.00211.2022pmid: 36197013

Multiple large-scale networks populate human association cortex. Here we explored the functional properties of these networks by exploiting trial-to-trial variation in component processing demands. In two behavioral studies (N=136 and N=238), participants quantified strategies used to solve individual task trials that spanned remembering, imagining future scenarios, and various control trials. These trials were also all scanned in an independent sample of functional MRI participants (N=10), each with sufficient data to precisely define within-individual networks. Stable latent factors varied across trials and correlated with trial-level functional responses selectively across networks. One network linked to parahippocampal cortex, labeled Default Network A (DN-A), tracked scene construction, including for control trials that possessed minimal episodic memory demands. To the degree a trial encouraged participants to construct a mental scene with imagery and awareness about spatial locations of objects or places, the response in DN-A increased. The juxtaposed Default Network B (DN-B) showed no such response but varied in relation to social processing demands. Another adjacent network, labeled Frontoparietal Network B (FPN-B), robustly correlated with trial difficulty. These results support that DN-A and DN-B are specialized networks differentially supporting information processing within spatial and social domains. Both networks are dissociable from a closely juxtaposed domain-general control network that tracks cognitive effort.

Wingrove, Joel; de Hoog, Eric; Spencer, Gaynor E.

doi: 10.1152/jn.00270.2022pmid: 36448682

Retinoic acid, the active metabolite of vitamin A, is important for vertebrate cognition and hippocampal plasticity, but few studies have examined its role in invertebrate learning and memory, and its actions in the invertebrate CNS are currently unknown. Using the mollusc Lymnaea stagnalis, we examined operant conditioning of the respiratory behaviour, controlled by a well-defined central pattern generator (CPG), and used citral to inhibit retinoic acid signaling. Both citral and vehicle-treated animals showed normal learning, but citral-treated animals failed to exhibit long-term memory at 24 hrs. Cohorts of citral or vehicle-treated animals were dissected into semi-intact preparations, either 1 hr after training, or after the memory-test 24 hrs later. Simultaneous electrophysiological recordings from the CPG pacemaker cell (RPeD1) and an identified motorneuron (VI) were made whilst monitoring respiratory activity (pneumostome opening). Activity of the CPG pneumostome opener interneuron (IP3) was also monitored indirectly. Vehicle-treated conditioned preparations showed significant changes in network parameters immediately after learning, such as reduced motorneuron bursting activity (from IP3 input), delayed pneumostome opening, and a decoupling of coincident IP3 input within the network. However, citral-treated preparations failed to exhibit these network changes and more closely resembled naïve preparations. Importantly, these citral-induced differences were manifested immediately after training and before any overt changes in the behavioural response (memory impairment). These studies shed light on where and when retinoid signaling might affect a central pattern generating network to promote memory formation during conditioning of a homeostatic behaviour.

Brihmat, Nabila; Allexandre, Didier; Bayram, Mehmed B.; Saleh, Soha; Guan, Xiaofei; Yue, Guang H.; Zhong, Jian; Forrest, Gail F.

doi: 10.1152/jn.00268.2022pmid: 36475885

Background and objectives: High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) remains a promising strategy for neurorehabilitation. The stimulation intensity (SI) influences the after-effects observed. Here, we examined if single sessions of a HF-rTMS protocol, administered at different suprathreshold SI, can be safely administered to able-bodied (AB) individuals. Methods: Six right-handed men were included in this pilot study. HF-rTMS was delivered over the left M1, in 10 trains of 75 biphasic stimuli at 15 Hz, at 105 to 120% of the individual resting motor threshold (RMT). Participants and EMG were monitored to control for signs of spread of excitation and brief EMG burst (BEB) post-stimulation. TMS side-effects questionnaires and the numeric rating scale (NRS) were administered during each session. Additionally, we assessed CSE and motor performance changes with measures of resting (rMEP) and active (aMEP) motor evoked potential and grip strength and the Box and Block test (BBT) scores, respectively. Results: Overall, the sessions were tolerated and feasible without any pain development. EMG analysis during HF-rTMS revealed increased BEB frequency with SI. Statistical models revealed an increase of CSE at rest (rMEP) but not during active muscle contraction (aMEP). No linear relationship was observed between HF-rTMS intensity and rMEP increase. No significant changes were highlighted for motor performance measures. Conclusion: Although feasible and tolerable by the AB tested, the results demonstrate that when administered at suprathreshold SI, 15 Hz-rTMS reveals signs of persistent excitation, suggesting that safety precautions and close monitoring of participants should be performed when testing such stimulation protocols.

McIntosh, James R.; Joiner, Evan F.; Goldberg, Jacob L.; Murray, Lynda M.; Yasin, Bushra; Mendiratta, Anil; Karceski, Steven C.; Thuet, Earl; Modik, Oleg; Shelkov, Evgeny; Lombardi, Joseph M.; Sardar, Zeeshan M.; Lehman, Ronald A.; Mandigo, Christopher; Riew, K. Daniel; Harel, Noam Y.; Virk, Michael S.; Carmel, Jason B.

Hardesty, Russell L.; Ellaway, Peter H.; Gritsenko, Valeriya

doi: 10.1152/jn.00367.2021pmid: 36448705

The neural control of posture and movement is interdependent. During voluntary movement, the neural motor command is executed by the motor cortex through the corticospinal tract and its collaterals and subcortical targets. Here we address the question that the control mechanism for the postural adjustments at non-moving joints is also involved in overcoming gravity at the moving joints. We used single-pulse transcranial magnetic stimulation to measure the corticospinal excitability in humans during postural and reaching tasks. We hypothesized that the corticospinal excitability is proportional to background muscle activity and the gravity-related joint moments during both static postures and reaching movements. To test this hypothesis, we used visual targets in virtual reality to instruct five postures and three movements with or against gravity. We then measured the amplitude and gain of motor evoked potentials in multiple arm and hand muscles at several phases of the reaching motion and during static postures. The stimulation caused motor evoked potentials in all muscles that were proportional to the muscle activity. During both static postures and reaching movements, the muscle activity and the corticospinal contribution to these muscles changed in proportion with the postural moments needed to support the arm against gravity, supporting the hypothesis. Notably, these changes happened not only in antigravity muscles. Altogether, these results provide evidence that the changes in corticospinal excitability cause muscle co-contraction that modulates limb stiffness. This suggests that the motor cortex is involved in producing postural adjustments that support the arm against gravity during posture maintenance and reaching.

Peña-Pérez, Nuria; Eden, Jonathan; Ivanova, Ekaterina; Farkhatdinov, Ildar; Burdet, Etienne

doi: 10.1152/jn.00057.2022pmid: 36475891

Bilateral training systems look to promote the paretic hand´s use in individuals with hemiplegia. While this is normally achieved using mechanical coupling (i.e., a physical connection between the hands), a virtual reality system relying on virtual coupling (i.e., through a shared virtual object) would be simpler to use and prevent slacking. However, it is not clear whether different coupling modes differently impact task performance and effort distribution between the hands. We explored how 18 healthy right-handed participants changed their motor behaviours in response to the uninstructed addition of mechanical coupling, and virtual coupling using a shared cursor mapped to the average hands' position. In a second experiment, we then studied the impact of connection stiffness on performance, perception, and effort imbalance. The results indicated that both coupling types can induce the hands to actively contribute to the task. However, the task asymmetry introduced by using a cursor mapped to either the left or right hand only modulated the hands' contribution when not mechanically coupled. The tracking performance was similar for all coupling types, independent of the connection stiffness, although the mechanical coupling was preferred and induced the hands to move with greater correlation. These findings suggest that virtual coupling can induce the hands to actively contribute to a task in healthy participants without hindering their performance. Further investigation on the coupling types' impact on the performance and hands' effort distribution in patients with hemiplegia could allow for the design of simpler training systems that promote the affected hand's use.

Moskowitz, Joshua B.; Berger, Sarah A.; Fooken, Jolande; Castelhano, Monica S.; Gallivan, Jason P.; Flanagan, J. Randall

doi: 10.1152/jn.00305.2022pmid: 36475897

Real world search behaviour often involves limb movements, either during search or following search. Here we investigated whether movement-related costs influence search behaviour in two kinds of search tasks. In our visual search tasks, participants made saccades to find a target object among distractors and then moved a cursor, controlled by the handle of a robotic manipulandum, to the target. In our manual search tasks, participants moved the cursor to perform the search, placing it onto objects to reveal their identity as either a target or a distractor. In all tasks, there were multiple targets. Across experiments, we manipulated either the effort or time costs associated with movement such that these costs varied across the search space. We varied effort by applying different resistive forces to the handle and we varied time costs by altering the speed of the cursor. Our analysis of cursor and eye movements during manual and visual search, respectively, showed that effort influenced manual search but did not influence visual search. In contrast, time costs influenced both visual and manual search. Our results demonstrate that, in addition to perceptual and cognitive factors, movement-related costs can also influence search behaviour.

Do, Quan; Li, Yutong; Kane, Gary A.; McGuire, Joseph T.; Scott, Benjamin B.

doi: 10.1152/jn.00124.2022pmid: 36475830

Evidence accumulation, an essential component of perception and decision making, is frequently studied using psychophysical tasks involving noisy or ambiguous stimuli. In these tasks, participants typically receive verbal or written instructions that describe the strategy that should be used to guide decisions. While convenient and effective, explicit instructions can influence learning and decision-making strategies, and can limit comparisons with animal models, in which behaviors are reinforced through feedback. Here, we developed an online video game and nonverbal training pipeline, inspired by pulse-based tasks for rodents, as an alternative to traditional psychophysical tasks used to study evidence accumulation. Using this game, we collected behavioral data from hundreds of participants trained with an explicit description of the decision rule or with experiential feedback. Participants trained using feedback alone learned the game rules rapidly, used similar strategies and displayed similar biases to those who received explicit instructions. Finally, by leveraging data across hundreds of participants, we show that perceptual judgements were well described by an accumulation process in which noise scaled non-linearly with evidence, consistent with previous animal studies, but inconsistent with diffusion models widely used to describe perceptual decisions in humans. These results challenge the conventional description of the accumulation process and suggest that online games provide a valuable platform to examine perceptual decision making and learning in humans. In addition, the feedback-based training pipeline developed for this game may be useful for evaluating perceptual decision making in human populations with difficulty following verbal instructions.