Noninvasive brain stimulation has been widely used for adults with stroke to improve upper limb motor function. A recent study by Kirton and colleagues (Kirton A, Ciechanski P, Zewdie E, Andersen J, Nettel-Aguirre A, Carlson H, Carsolio L, Herrero M, Quigley J, Mineyko A, Hodge J, Hill M. Neurology 88: 259–267, 2017) applied noninvasive brain stimulation to children with congenital hemiparesis but found no significant effect of noninvasive brain stimulation on motor function. Here, we explore theories about cortical reorganization in both adult and children with hemiparesis and discuss how to improve the approaches of noninvasive brain stimulation to generate optimal motor improvement and development for children with congenital hemiparesis.

Emotion regulation is crucial in maintaining healthy psychological well-being, and its dysregulation is often linked to a range of neuropsychiatric disorders including depression. The neurobiological underpinnings of cognitive reappraisal, an emotion regulation strategy, have been shown to include the amygdala and regions of the prefrontal cortex. A novel study by Doré, Weber, and Ochsner (J Neurosci 37: 2580–2588, 2017) has demonstrated that neural activity in these regions during uninstructed visualization of affective stimuli can successfully predict which individuals are more likely to subsequently employ emotion regulation, and under what circumstances.

Following rostral spinal cord injury (SCI) in larval lampreys, injured descending brain neurons, particularly reticulospinal (RS) neurons, regenerate their axons, and locomotor behavior recovers in a few weeks. However, axonal regeneration of descending brain neurons is mostly limited to relatively short distances, but the mechanisms for incomplete axonal regeneration are unclear. First, lampreys with rostral SCI exhibited greater axonal regeneration of descending brain neurons, including RS neurons, as well as more rapid recovery of locomotor muscle activity right below the lesion site, compared with animals with caudal SCI. In addition, following rostral SCI, most injured RS neurons displayed the “injury phenotype,” whereas following caudal SCI, most injured neurons displayed normal electrical properties. Second, following rostral SCI, at cold temperatures (~4–5°C), axonal transport was suppressed, axonal regeneration and behavioral recovery were blocked, and injured RS neurons displayed normal electrical properties. Cold temperatures appear to prevent injured RS neurons from detecting and/or responding to SCI. It is hypothesized that following rostral SCI, injured descending brain neurons are strongly stimulated to regenerate their axons, presumably because of elimination of spinal synapses and reduced neurotrophic support. However, when these neurons regenerate their axons and make synapses right below the lesion site, restoration of neurotrophic support very likely suppress further axonal regeneration. In contrast, caudal SCI is a weak stimulus for axonal regeneration, presumably because of spared synapses above the lesion site. These results may have implications for mammalian SCI, which can spare synapses above the lesion site for supraspinal descending neurons and propriospinal neurons. NEW & NOTEWORTHY Lampreys with rostral spinal cord injury (SCI) exhibited greater axonal regeneration of descending brain neurons and more rapid recovery of locomotor muscle activity below the lesion site compared with animals with caudal SCI. In addition, following rostral SCI, most injured reticulospinal (RS) neurons displayed the “injury phenotype,” whereas following caudal SCI, most injured neurons had normal electrical properties. We hypothesize that following caudal SCI, the spared synapses of injured RS neurons might limit axonal regeneration and behavioral recovery.

Epiretinal prostheses for treating blindness activate axon bundles, causing large, arc-shaped visual percepts that limit the quality of artificial vision. Improving the function of epiretinal prostheses therefore requires understanding and avoiding axon bundle activation. This study introduces a method to detect axon bundle activation on the basis of its electrical signature and uses the method to test whether epiretinal stimulation can directly elicit spikes in individual retinal ganglion cells without activating nearby axon bundles. Combined electrical stimulation and recording from isolated primate retina were performed using a custom multielectrode system (512 electrodes, 10-μm diameter, 60-μm pitch). Axon bundle signals were identified by their bidirectional propagation, speed, and increasing amplitude as a function of stimulation current. The threshold for bundle activation varied across electrodes and retinas, and was in the same range as the threshold for activating retinal ganglion cells near their somas. In the peripheral retina, 45% of electrodes that activated individual ganglion cells (17% of all electrodes) did so without activating bundles. This permitted selective activation of 21% of recorded ganglion cells (7% of expected ganglion cells) over the array. In one recording in the central retina, 75% of electrodes that activated individual ganglion cells (16% of all electrodes) did so without activating bundles. The ability to selectively activate a subset of retinal ganglion cells without axon bundles suggests a possible novel architecture for future epiretinal prostheses. NEW & NOTEWORTHY Large-scale multielectrode recording and stimulation were used to test how selectively retinal ganglion cells can be electrically activated without activating axon bundles. A novel method was developed to identify axon activation on the basis of its unique electrical signature and was used to find that a subset of ganglion cells can be activated at single-cell, single-spike resolution without producing bundle activity in peripheral and central retina. These findings have implications for the development of advanced retinal prostheses.

Coupled oscillatory activity recorded between sensorimotor regions of the basal ganglia-thalamocortical loop is thought to reflect information transfer relevant to movement. A neuronal firing-rate model of basal ganglia-thalamocortical circuitry, however, has dominated thinking about basal ganglia function for the past three decades, without knowledge of the relationship between basal ganglia single neuron firing and cortical population activity during movement itself. We recorded activity from 34 subthalamic nucleus (STN) neurons, simultaneously with cortical local field potentials and motor output, in 11 subjects with Parkinson's disease (PD) undergoing awake deep brain stimulator lead placement. STN firing demonstrated phase synchronization to both low- and high-beta-frequency cortical oscillations, and to the amplitude envelope of gamma oscillations, in motor cortex. We found that during movement, the magnitude of this synchronization was dynamically modulated in a phase-frequency-specific manner. Importantly, we found that phase synchronization was not correlated with changes in neuronal firing rate. Furthermore, we found that these relationships were not exclusive to motor cortex, because STN firing also demonstrated phase synchronization to both premotor and sensory cortex. The data indicate that models of basal ganglia function ultimately will need to account for the activity of populations of STN neurons that are bound in distinct functional networks with both motor and sensory cortices and code for movement parameters independent of changes in firing rate. NEW & NOTEWORTHY Current models of basal ganglia-thalamocortical networks do not adequately explain simple motor functions, let alone dysfunction in movement disorders. Our findings provide data that inform models of human basal ganglia function by demonstrating how movement is encoded by networks of subthalamic nucleus (STN) neurons via dynamic phase synchronization with cortex. The data also demonstrate, for the first time in humans, a mechanism through which the premotor and sensory cortices are functionally connected to the STN.

Unilateral arm movements require trunk stabilization through bilateral contraction of axial muscles. Interhemispheric interactions between primary motor cortices (M1) could enable such coordinated contractions, but these mechanisms are largely unknown. Using transcranial magnetic stimulation (TMS), we characterized interhemispheric interactions between M1 representations of the trunk-stabilizing muscles erector spinae at the first lumbar vertebra (ES L1) during a right isometric shoulder flexion. These interactions were compared with those of the anterior deltoid (AD), the main agonist in this task, and the first dorsal interosseous (FDI). TMS over the right M1 elicited ipsilateral silent periods (iSP) in all three muscles on the right side. In ES L1, but not in AD or FDI, ipsilateral motor evoked potential (iMEP) could precede the iSP or replace it. iMEP amplitude was not significantly different whether ES L1 was used to stabilize the trunk or was voluntarily contracted. TMS at the cervicomedullary junction showed that the size of cervicomedullary evoked potential was unchanged during the iSP but increased during iMEP, suggesting that the iSP, but not the iMEP, is due to intracortical mechanisms. Using a dual-coil paradigm with two coils over the left and right M1, interhemispheric inhibition could be evoked at interstimulus intervals of 6 ms in ES L1 and 8 ms in AD and FDI. Together, these results suggest that interhemispheric inhibition is dominant when axial muscles are involved in a stabilizing task. The ipsilateral facilitation could be evoked by ipsilateral or subcortical pathways and could be used depending on the role axial muscles play in the task. NEW & NOTEWORTHY The mechanisms involved in the bilateral coordination of axial muscles during unilateral arm movement are poorly understood. We thus investigated the nature of interhemispheric interactions in axial muscles during arm motor tasks in healthy subjects. By combining different methodologies, we showed that trunk muscles receive both inhibitory and facilitatory cortical outputs during activation of arm muscles. We propose that inhibition may be conveyed mainly through interhemispheric mechanisms and facilitation by subcortical mechanisms or ipsilateral pathways.

Methylphenidate (MPD), also known as Ritalin, is a psychostimulant used to treat attention deficit hyperactivity disorder. However, it is increasingly being misused by normal adolescents for recreation and academic advantage. Therefore, it is important to elucidate the behavioral and neurophysiological effects of MPD in normal subjects. MPD inhibits the reuptake of catecholamines, mainly found in the ventral tegmental area (VTA) and locus coeruleus (LC). The VTA and LC normally mediate attention, motivation, and drug reward behaviors. Selective neuronal connections between the VTA and LC have been identified implicating regular interaction between the structures. The objective of this study was to compare the neuronal responses of the VTA and LC to MPD in normal adolescent rats. Animals were implanted with permanent electrodes in the VTA and LC, and neuronal units were recorded following acute and repetitive (chronic) saline or 0.6, 2.5, or 10.0 mg/kg MPD exposure. Animals displayed either behavioral sensitization or tolerance to all three doses of MPD. Acute MPD exposure elicited excitation in the majority of all VTA and LC units. Chronic MPD exposure elicited a further increase in VTA and LC neuronal activity in animals exhibiting behavioral sensitization and an attenuation in VTA and LC neuronal activity in animals exhibiting behavioral tolerance, demonstrating neurophysiological sensitization and tolerance, respectively. The similar pattern in VTA and LC unit activity suggests that the two structures are linked in their response to MPD. These results may help determine the exact mechanism of action of MPD, resulting in optimized treatment of patients. NEW & NOTEWORTHY The same dose of 0.6, 2.5, and 10 mg/kg methylphenidate (MPD) elicits either behavioral sensitization or tolerance in adolescent rats. There is a direct correlation between the ventral tegmental area (VTA) and locus coeruleus (LC) neuronal response to chronic MPD exposure. Both the VTA and LC are involved in the behavioral and neurophysiological effects of chronic MPD.

The continuous perception of motion-through-depth is critical for both navigation and interacting with objects in a dynamic three-dimensional (3D) world. Here we used 3D tracking to simultaneously assess the perception of motion in all directions, facilitating comparisons of responses to motion-through-depth to frontoparallel motion. Observers manually tracked a stereoscopic target as it moved in a 3D Brownian random walk. We found that continuous tracking of motion-through-depth was selectively impaired, showing different spatiotemporal properties compared with frontoparallel motion tracking. Two separate factors were found to contribute to this selective impairment. The first is the geometric constraint that motion-through-depth yields much smaller retinal projections than frontoparallel motion, given the same object speed in the 3D environment. The second factor is the sluggish nature of disparity processing, which is present even for frontoparallel motion tracking of a disparity-defined stimulus. Thus, despite the ecological importance of reacting to approaching objects, both the geometry of 3D vision and the nature of disparity processing result in considerable impairments for tracking motion-through-depth using binocular cues. NEW & NOTEWORTHY We characterize motion perception continuously in all directions using an ecologically relevant, manual target tracking paradigm we recently developed. This approach reveals a selective impairment to the perception of motion-through-depth. Geometric considerations demonstrate that this impairment is not consistent with previously observed spatial deficits (e.g., stereomotion suppression). However, results from an examination of disparity processing are consistent with the longer latencies observed in discrete, trial-based measurements of the perception of motion-through-depth.

Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine implicated in cardiovascular and autonomic regulation via actions in the central nervous system. TNF-α^−/− mice do not develop angiotensin II (ANG II)-induced hypertension, and administration of TNF-α into the bloodstream of rats increases blood pressure and sympathetic tone. Recent studies have shown that lesion of the subfornical organ (SFO) attenuates the hypertensive and autonomic effects of TNF-α, while direct administration of TNF-α into the SFO increases blood pressure, suggesting the SFO to be a key site for the actions of TNF-α. Therefore, we used patch-clamp techniques to examine both acute and long-term effects of TNF-α on the excitability of Sprague-Dawley rat SFO neurons. It was observed that acute bath application of TNF-α depolarized SFO neurons and subsequently increased action potential firing rate. Furthermore, the magnitude of depolarization and the proportion of depolarized SFO neurons were concentration dependent. Interestingly, following 24-h incubation with TNF-α, the basal firing rate of the SFO neurons was increased and the rheobase was decreased, suggesting that TNF-α elevates SFO neuron excitability. This effect was likely mediated by the transient sodium current, as TNF-α increased the magnitude of the current and lowered its threshold of activation. In contrast, TNF-α did not appear to modulate either the delayed rectifier potassium current or the transient potassium current. These data suggest that acute and long-term TNF-α exposure elevates SFO neuron activity, providing a basis for TNF-α hypertensive and sympathetic effects. NEW & NOTEWORTHY Considerable recent evidence has suggested important links between inflammation and the pathological mechanisms underlying hypertension. The present study describes cellular mechanisms through which acute and long-term exposure of tumor necrosis factor-α (TNF-α) influences the activity of subfornical organ neurons by modulating the voltage-gated transient Na⁺ current. This provides critical new information regarding the specific pathological mechanisms through which inflammation and TNF-α in particular may result in the development of hypertension.

Nonspatially selective attention is based on the notion that specific features or objects in the visual environment are effectively prioritized in cortical visual processing. Feature-based attention (FBA), in particular, is a well-studied process that dynamically and selectively addresses neurons preferentially processing the attended feature attribute (e.g., leftward motion). In everyday life, however, behavior may require high sensitivity for an entire feature dimension (e.g., motion), but experimental evidence for a feature dimension-specific attentional modulation on a cellular level is lacking. Therefore, we investigated neuronal activity in macaque motion-selective mediotemporal area (MT) in an experimental setting requiring the monkeys to detect either a motion change or a color change. We hypothesized that neural activity in MT is enhanced when the task requires perceptual sensitivity to motion. In line with this, we found that mean firing rates were higher in the motion task and that response variability and latency were lower compared with values in the color task, despite identical visual stimulation. This task-specific, dimension-based modulation of motion processing emerged already in the absence of visual input, was independent of the relation between the attended and stimulating motion direction, and was accompanied by a spatially global reduction of neuronal variability. The results provide single-cell support for the hypothesis of a feature dimension-specific top-down signal emphasizing the processing of an entire feature class. NEW & NOTEWORTHY Cortical processing serving visual perception prioritizes information according to current task requirements. We provide evidence in favor of a dimension-based attentional mechanism addressing all neurons that process visual information in the task-relevant feature domain. Behavioral tasks required monkeys to attend either color or motion, causing modulations of response strength, variability, latency, and baseline activity of motion-selective monkey area MT neurons irrespective of the attended motion direction but specific to the attended feature dimension.

To investigate mechanisms of action sequencing, we examined the relationship between timing and sequencing of syllables in Bengalese finch song. An individual’s song comprises acoustically distinct syllables organized into probabilistic sequences: a given syllable potentially can transition to several different syllables (divergence points), and several different syllables can transition to a given syllable (convergence points). In agreement with previous studies, we found that more probable transitions at divergence points occur with shorter intersyllable gaps. One intuition for this relationship is that selection between syllables reflects a competitive branching process, in which stronger links to one syllable lead to both higher probabilities and shorter latencies for transitions to that syllable vs. competing alternatives. However, we found that simulations of competitive race models result in overlapping winning-time distributions for competing outcomes and fail to replicate the strong negative correlation between probability and gap duration found in song data. Further investigation of song structure revealed strong positive correlation between gap durations for transitions that share a common convergent point. Such transitions are not related by a common competitive process, but instead reflect a common terminal syllable. In contrast to gap durations, transition probabilities were not correlated at convergence points. Together, our data suggest that syllable selection happens early during the gap, with gap timing determined chiefly by the latency to syllable initiation. This may result from a process in which probabilistic sequencing is first stabilized, followed by a shortening of the latency to syllables that are sung more often. NEW & NOTEWORTHY Bengalese finch songs consist of probabilistic sequences of syllables. Previous studies revealed a strong negative correlation between transition probability and the duration of intersyllable gaps. We show here that the negative correlation is inconsistent with previous suggestions that timing at syllable transitions is governed by a race between competing alternatives. Rather, the data suggest that syllable selection happens early during the gap, with gap timing determined chiefly by the latency to syllable initiation.

Neurons in the middle temporal area (MT) of the primate cerebral cortex respond to moving visual stimuli. The sensitivity of MT neurons to motion signals can be characterized by using random-dot stimuli, in which the strength of the motion signal is manipulated by adding different levels of noise (elements that move in random directions). In macaques, this has allowed the calculation of “neurometric” thresholds. We characterized the responses of MT neurons in sufentanil/nitrous oxide-anesthetized marmoset monkeys, a species that has attracted considerable recent interest as an animal model for vision research. We found that MT neurons show a wide range of neurometric thresholds and that the responses of the most sensitive neurons could account for the behavioral performance of macaques and humans. We also investigated factors that contributed to the wide range of observed thresholds. The difference in firing rate between responses to motion in the preferred and null directions was the most effective predictor of neurometric threshold, whereas the direction tuning bandwidth had no correlation with the threshold. We also showed that it is possible to obtain reliable estimates of neurometric thresholds using stimuli that were not highly optimized for each neuron, as is often necessary when recording from large populations of neurons with different receptive field concurrently, as was the case in this study. These results demonstrate that marmoset MT shows an essential physiological similarity to macaque MT and suggest that its neurons are capable of representing motion signals that allow for comparable motion-in-noise judgments. NEW & NOTEWORTHY We report the activity of neurons in marmoset MT in response to random-dot motion stimuli of varying coherence. The information carried by individual MT neurons was comparable to that of the macaque, and the maximum firing rates were a strong predictor of sensitivity. Our study provides key information regarding the neural basis of motion perception in the marmoset, a small primate species that is becoming increasingly popular as an experimental model.

Aging is typically accompanied by a decline in manual dexterity and handedness; the dominant hand executes tasks of manual dexterity more quickly and accurately than the nondominant hand in younger adults, but this advantage typically declines with age. Age-related changes in intracortical inhibitory processes might play a role in the age-related decline in manual dexterity. Long-interval intracortical inhibition (LICI) is asymmetric in young adults, with more sensitive and more powerful LICI circuits in the dominant hemisphere than in the nondominant hemisphere. Here we investigated whether the hemispheric asymmetry in LICI in younger adults persists in healthy older adults. Paired-pulse transcranial magnetic stimulation was used to measure LICI in the dominant and nondominant hemispheres of younger and older adults; LICI stimulus-response curves were obtained by varying conditioning stimulus intensity at two different interstimulus intervals [100 ms (LICI₁₀₀) and 150 ms]. We have replicated the finding that LICI₁₀₀ circuits are more sensitive and more powerful in the dominant than the nondominant hemisphere of young adults and extend this finding to show that the hemispheric asymmetry in LICI₁₀₀ is lost with age. In the context of behavioral observations showing that dominant hand movements in younger adults are more fluent than nondominant hand movements in younger adults and dominant hand movements in older adults, we speculate a role of LICI₁₀₀ in the age-related decline in manual dexterity. NEW & NOTEWORTHY In younger adults, more sensitive and more powerful long-interval intracortical inhibitory circuits are evident in the hemisphere controlling the more dexterous hand; this is not the case in older adults, for whom long-interval intracortical inhibitory circuits are symmetric and more variable than in younger adults. We speculate that the highly sensitive and powerful long-interval intracortical inhibition circuits in the dominant hemisphere play a role in manual dexterity.

Various studies have explored different ways to speed emergence from anesthesia. Previously, we have shown that three drugs that elevate intracellular cAMP (forskolin, theophylline, and caffeine) accelerate emergence from anesthesia in rats. However, our earlier studies left two main questions unanswered. First, were cAMP-elevating drugs effective at all anesthetic concentrations? Second, given that caffeine was the most effective of the drugs tested, why was caffeine more effective than forskolin since both drugs elevate cAMP? In our current study, emergence time from anesthesia was measured in adult rats exposed to 3% isoflurane for 60 min. Caffeine dramatically accelerated emergence from anesthesia, even at the high level of anesthetic employed. Caffeine has multiple actions including blockade of adenosine receptors. We show that the selective A_2a adenosine receptor antagonist preladenant or the intracellular cAMP ([cAMP]_i)-elevating drug forskolin, accelerated recovery from anesthesia. When preladenant and forskolin were tested together, the effect on anesthesia recovery time was additive indicating that these drugs operate via different pathways. Furthermore, the combination of preladenant and forskolin was about as effective as caffeine suggesting that both A_2A receptor blockade and [cAMP]_i elevation play a role in caffeine’s ability to accelerate emergence from anesthesia. Because anesthesia in rodents is thought to be similar to that in humans, these results suggest that caffeine might allow for rapid and uniform emergence from general anesthesia in humans at all anesthetic concentrations and that both the elevation of [cAMP]_i and adenosine receptor blockade play a role in this response. NEW & NOTEWORTHY Currently, there is no method to accelerate emergence from anesthesia. Patients “wake” when they clear the anesthetic from their systems. Previously, we have shown that caffeine can accelerate emergence from anesthesia. In this study, we show that caffeine is effective even at high levels of anesthetic. We also show that caffeine operates by both elevating intracellular cAMP levels and by blocking adenosine receptors. This complicated pharmacology makes caffeine especially effective in accelerating emergence from anesthesia.

To perform goal-oriented hand movement, humans combine multiple sensory signals (e.g., vision and proprioception) that can be encoded in various reference frames (body centered and/or exo-centered). In a previous study (Tagliabue M, McIntyre J. PLoS One 8: e68438, 2013), we showed that, when aligning a hand to a remembered target orientation, the brain encodes both target and response in visual space when the target is sensed by one hand and the response is performed by the other, even though both are sensed only through proprioception. Here we ask whether such visual encoding is due 1) to the necessity of transferring sensory information across the brain hemispheres, or 2) to the necessity, due to the arms’ anatomical mirror symmetry, of transforming the joint signals of one limb into the reference frame of the other. To answer this question, we asked subjects to perform purely proprioceptive tasks in different conditions: Intra, the same arm sensing the target and performing the movement; Inter/Parallel, one arm sensing the target and the other reproducing its orientation; and Inter/Mirror, one arm sensing the target and the other mirroring its orientation. Performance was very similar between Intra and Inter/Mirror (conditions not requiring joint-signal transformations), while both differed from Inter/Parallel. Manipulation of the visual scene in a virtual reality paradigm showed visual encoding of proprioceptive information only in the latter condition. These results suggest that the visual encoding of purely proprioceptive tasks is not due to interhemispheric transfer of the proprioceptive information per se, but to the necessity of transforming joint signals between mirror-symmetric limbs. NEW & NOTEWORTHY Why does the brain encode goal-oriented, intermanual tasks in a visual space, even in the absence of visual feedback about the target and the hand? We show that the visual encoding is not due to the transfer of proprioceptive signals between brain hemispheres per se, but to the need, due to the mirror symmetry of the two limbs, of transforming joint angle signals of one arm in different joint signals of the other.

Visual and inertial stimuli provide heading discrimination cues. Integration of these multisensory stimuli has been demonstrated to depend on their relative reliability. However, the reference frame of visual stimuli is eye centered while inertia is head centered, and it remains unclear how these are reconciled with combined stimuli. Seven human subjects completed a heading discrimination task consisting of a 2-s translation with a peak velocity of 16 cm/s. Eye position was varied between 0° and ±25° left/right. Experiments were done with inertial motion, visual motion, or a combined visual-inertial motion. Visual motion coherence varied between 35% and 100%. Subjects reported whether their perceived heading was left or right of the midline in a forced-choice task. With the inertial stimulus the eye position had an effect such that the point of subjective equality (PSE) shifted 4.6 ± 2.4° in the gaze direction. With the visual stimulus the PSE shift was 10.2 ± 2.2° opposite the gaze direction, consistent with retinotopic coordinates. Thus with eccentric eye positions the perceived inertial and visual headings were offset ~15°. During the visual-inertial conditions the PSE varied consistently with the relative reliability of these stimuli such that at low visual coherence the PSE was similar to that of the inertial stimulus and at high coherence it was closer to the visual stimulus. On average, the inertial stimulus was weighted near Bayesian ideal predictions, but there was significant deviation from ideal in individual subjects. These findings support visual and inertial cue integration occurring in independent coordinate systems. NEW & NOTEWORTHY In multiple cortical areas visual heading is represented in retinotopic coordinates while inertial heading is in body coordinates. It remains unclear whether multisensory integration occurs in a common coordinate system. The experiments address this using a multisensory integration task with eccentric gaze positions making the effect of coordinate systems clear. The results indicate that the coordinate systems remain separate to the perceptual level and that during the multisensory task the perception depends on relative stimulus reliability.

Individuals with damage to the cerebellum perform poorly in sensorimotor adaptation paradigms. This deficit has been attributed to impairment in sensory prediction error-based updating of an internal forward model, a form of implicit learning. These individuals can, however, successfully counter a perturbation when instructed with an explicit aiming strategy. This successful use of an instructed aiming strategy presents a paradox: In adaptation tasks, why do individuals with cerebellar damage not come up with an aiming solution on their own to compensate for their implicit learning deficit? To explore this question, we employed a variant of a visuomotor rotation task in which, before executing a movement on each trial, the participants verbally reported their intended aiming location. Compared with healthy control participants, participants with spinocerebellar ataxia displayed impairments in both implicit learning and aiming. This was observed when the visuomotor rotation was introduced abruptly (experiment 1) or gradually (experiment 2). This dual deficit does not appear to be related to the increased movement variance associated with ataxia: Healthy undergraduates showed little change in implicit learning or aiming when their movement feedback was artificially manipulated to produce similar levels of variability (experiment 3). Taken together the results indicate that a consequence of cerebellar dysfunction is not only impaired sensory prediction error-based learning but also a difficulty in developing and/or maintaining an aiming solution in response to a visuomotor perturbation. We suggest that this dual deficit can be explained by the cerebellum forming part of a network that learns and maintains action-outcome associations across trials. NEW & NOTEWORTHY Individuals with cerebellar pathology are impaired in sensorimotor adaptation. This deficit has been attributed to an impairment in error-based learning, specifically, from a deficit in using sensory prediction errors to update an internal model. Here we show that these individuals also have difficulty in discovering an aiming solution to overcome their adaptation deficit, suggesting a new role for the cerebellum in sensorimotor adaptation tasks.

Rats and mice are able to perform a variety of subtle tactile discriminations with their mystacial vibrissae. Increasingly, the design and interpretation of neurophysiological and behavioral studies are inspired by and linked to a more precise understanding of the detailed physical properties of the whiskers and their associated hair follicles. Here we used a piezoelectric sensor (bimorph) to examine how contact forces are influenced by the geometry of individual whisker hairs. For a given point along a whisker, bimorph signals are linearly related to whisker movement velocity. The slope of this linear function, called velocity sensitivity (VS), diminishes nonlinearly as whisker diameter decreases. Whiskers differ in overall length, thickness, and proximal-distal taper. Thus VS varies along an individual whisker and among different whiskers on the mystacial pad. Thinner, shorter whiskers, such as those located rostrally in rats and those in mice, have lower overall VSs, rendering them potentially less effective for mediating discriminations that rely on subtle velocity cues. The nonlinear effect of diameter combined with the linear effect of arc length produces radial distance tuning curves wherein small differences in the proximal-distal location of impacts yields larger differences in signal magnitude. Such position-dependent cues could contribute to the localization of objects near the face. Proximal-to-distal changes in contact location during whisking sweeps could also provide signals that aid texture discrimination. NEW & NOTEWORTHY This study describes the geometry of facial whiskers distributed across the mystacial pad with emphasis on velocity encoding of object strikes. Findings indicate how the shapes, lengths, and thicknesses of individual hairs can contribute to sophisticated vibrissa-based tactile discrimination.

In the natural world, self-motion always stimulates several different sensory modalities. Here we investigated the interplay between a visual optic flow stimulus simulating self-motion and a tactile stimulus (air flow resulting from self-motion) while human observers were engaged in a distance reproduction task. We found that adding congruent tactile information (i.e., speed of the air flow and speed of visual motion are directly proportional) to the visual information significantly improves the precision of the actively reproduced distances. This improvement, however, was smaller than predicted for an optimal integration of visual and tactile information. In contrast, incongruent tactile information (i.e., speed of the air flow and speed of visual motion are inversely proportional) did not improve subjects’ precision indicating that incongruent tactile information and visual information were not integrated. One possible interpretation of the results is a link to properties of neurons in the ventral intraparietal area that have been shown to have spatially and action-congruent receptive fields for visual and tactile stimuli. NEW & NOTEWORTHY This study shows that tactile and visual information can be integrated to improve the estimates of the parameters of self-motion. This, however, happens only if the two sources of information are congruent—as they are in a natural environment. In contrast, an incongruent tactile stimulus is still used as a source of information about self-motion but it is not integrated with visual information.

In contrast to hand movements, the existence of a neural representation of saccade kinematics is unclear. Saccade kinematics is typically thought to be specified by motor error/desired displacement and generated by brain stem circuits that are not penetrable to voluntary control. We studied the influence of instructed hand movement velocity on the kinematics of saccades executed without explicit instructions. When the hand movement was slow the saccade velocity decreased, independent of saccade amplitude. We leveraged this modulation of saccade velocity to study the optimality of saccades (in terms of velocity and endpoint accuracy) in relation to the well-known speed-accuracy tradeoff that governs voluntary movements (Fitts’ law). In contrast to hand movements that obeyed Fitts' law, normometric saccades exhibited the greatest endpoint accuracy and lower reaction times, relative to saccades accompanying slow and fast hand movements. In the slow condition, where saccade endpoint accuracy suffered, we observed that targets were more likely to be foveated by two saccades resulting in step-saccades. Interestingly, the endpoint accuracy was higher in two-saccade trials, compared with one-saccade trials in both the slow and fast conditions. This indicates that step-saccades are a part of the kinematic plan for optimal control of endpoint accuracy. Taken together, these findings suggest normometric saccades are already optimized to maximize endpoint accuracy and the modulation of saccade velocity by hand velocity is likely to reflect the sharing of kinematic plans between the two effectors. NEW & NOTEWORTHY The optimality of saccade kinematics has been suggested by modeling studies but experimental evidence is lacking. However, we observed that, when subjects voluntarily modulated their hand velocity, the velocity of saccades accompanying these hand movements was also modulated, suggesting a shared kinematic plan for eye and hand movements. We leveraged this modulation to show that saccades had less endpoint accuracy when their velocity decreased, illustrating that normometric saccades have optimal speed and accuracy.

The aims of this study were to investigate changes 1) in the coordination of activation of the triceps surae muscle group, and 2) in muscle belly length of soleus (SO) and lateral gastrocnemius (LG) during locomotion (trotting) in response to increased stiffness of intermuscular connective tissues in the rat. We measured muscle activation and muscle belly lengths, as well as hindlimb kinematics, before and after an artificial enhancement of the connectivity between SO and LG muscles obtained by implanting a tissue-integrating surgical mesh at the muscles’ interface. We found that SO muscle activation decreased to 62%, while activation of LG and medial gastrocnemius muscles increased to 134 and 125%, respectively, compared with the levels measured preintervention. Although secondary additional or amplified activation bursts were observed with enhanced connectivity, the primary pattern of activation over the stride and the burst duration were not affected by the intervention. Similar muscle length changes after manipulation were observed, suggesting that length feedback from spindle receptors within SO and LG was not affected by the connectivity enhancement. We conclude that peripheral mechanical constraints given by morphological (re)organization of connective tissues linking synergists are taken into account by the central nervous system. The observed shift in activity toward the gastrocnemius muscles after the intervention suggests that these larger muscles are preferentially recruited when the soleus has a similar mechanical disadvantage in that it produces an unwanted flexion moment around the knee. NEW & NOTEWORTHY Connective tissue linkages between muscle-tendon units may act as an additional mechanical constraint on the musculoskeletal system, thereby reducing the spectrum of solutions for performing a motor task. We found that intermuscular coordination changes following intermuscular connectivity enhancement. Besides showing that the extent of such connectivity is taken into account by the central nervous system, our results suggest that recruitment of triceps surae muscles is governed by the moments produced at the ankle-knee joints.

Evidence indicates that CO₂/H⁺-evoked ATP released from retrotrapezoid nucleus (RTN) astrocytes modulates the activity of CO₂-sensitive neurons. RTN astrocytes also sense H⁺ by inhibition of Kir4.1 channels; however, the relevance of this pH-sensitive current remains unclear since ATP release appears to involve CO₂-dependent gating of connexin 26 hemichannels. Considering that depolarization mediated by H⁺ inhibition of Kir4.1 channels is expected to increase sodium bicarbonate cotransporter (NBC) conductance and favor Ca²⁺ influx via the sodium calcium exchanger (NCX), we hypothesize that depolarization in the presence of CO₂ is sufficient to facilitate ATP release and enhance respiratory output. Here, we confirmed that acute exposure to fluorocitrate (FCt) reversibly depolarizes RTN astrocytes and increased activity of RTN neurons by a purinergic-dependent mechanism. We then made unilateral injections of FCt into the RTN or two other putative chemoreceptor regions (NTS and medullary raphe) to depolarize astrocytes under control conditions and during P2-recepetor blockade while measuring cardiorespiratory activities in urethane-anesthetized, vagotomized, artificially ventilated male Wistar rats. Unilateral injection of FCt into the RTN increased phrenic (PNA) amplitude and frequency without changes in arterial pressure. Unilateral injection of pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonate (PPADS, a P2-receptor antagonist) into the RTN dampened both PNA amplitude and frequency responses to FCt. Injection of MRS2179 (P2Y1-receptor antagonist) into the RTN did not affect the FCt-induced respiratory responses. Fluorocitrate had no effect on breathing when injected into the NTS or raphe. These results suggest that depolarization can facilitate purinergic enhancement of respiratory drive from the RTN. NEW & NOTEWORTHY Astrocytes in the retrotrapezoid nucleus (RTN) are known to function as respiratory chemoreceptors; however, it is not clear whether changes in voltage contribute to astrocyte chemoreception. We showed that depolarization of RTN astrocytes at constant CO₂ levels is sufficient to modulate RTN chemoreception by a purinergic-dependent mechanism. These results support the possibility that astrocyte depolarization can facilitate purinergic enhancement of respiratory drive from the RTN.

Sensory input can alter swallowing control in both the cortex and brainstem. Electrical stimulation of superior laryngeal nerve afferents increases reflexive swallowing in animals, with different frequencies optimally effective across species. Here we determined 1) if neck vibration overlying the larynx affected the fundamental frequency of the voice demonstrating penetration of vibration into the laryngeal tissues, and 2) if vibration, in comparison with sham, increased spontaneous swallowing and enhanced cortical hemodynamic responses to swallows in the swallowing network. A device with two motors, one over each thyroid lamina, delivered intermittent 10-s epochs of vibration. We recorded swallows and event-related changes in blood oxygenation level to swallows over the motor and sensory swallowing cortexes bilaterally using functional near infrared spectroscopy. Ten healthy participants completed eight 20-min conditions in counterbalanced order with either epochs of continuous vibration at 30, 70, 110, 150, and 70 + 110 Hz combined, 4-Hz pulsed vibration at 70 + 110 Hz, or two sham conditions without stimulation. Stimulation epochs were separated by interstimulus intervals varying between 30 and 45 s in duration. Vibration significantly reduced the fundamental frequency of the voice compared with no stimulation demonstrating that vibration penetrated laryngeal tissues. Vibration at 70 and at 150 Hz increased spontaneous swallowing compared with sham. Hemodynamic responses to swallows in the motor cortex were enhanced during conditions containing stimulation compared with sham. As vibratory stimulation on the neck increased spontaneous swallowing and enhanced cortical activation for swallows in healthy participants, it may be useful for enhancing swallowing in patients with dysphagia. NEW & NOTEWORTHY Vibratory stimulation at 70 and 150 Hz on the neck overlying the larynx increased the frequency of spontaneous swallowing. Simultaneously vibration also enhanced hemodynamic responses in the motor cortex to swallows when recorded with functional near-infrared spectroscopy (fNIRS). As vibrotactile stimulation on the neck enhanced cortical activation for swallowing in healthy participants, it may be useful for enhancing swallowing in patients with dysphagia.

In daily life, people are constantly presented with situations in which they have to learn and acquire new motor skills in complex environments, where attention is often distracted by other events. Being able to generalize and perform the acquired motor action in different environments is a crucial part of visuomotor learning. The current study examined whether attentional distraction impairs generalization of visuomotor adaptation or whether consistent distraction can operate as an internal cue to facilitate generalization. Using a dual-task paradigm combining visuomotor rotational adaptation and an attention-demanding secondary task, we showed that switching the attentional context from training (dual-task) to generalization (single-task) reduced the range of transfer of visuomotor adaptation to untrained directions. However, when consistent distraction was present throughout training and generalization, visuomotor generalization was equivalent to without distractions at all. Furthermore, this attentional context-dependent generalization was evident even when sensory modality of distractions differed between training and generalization. Therefore, the general nature of the dual tasks, rather than the specific stimuli, is associated with visuomotor memory and serves as a critical cue for generalization. Taken together, we demonstrated that attention plays a critical role during sensorimotor adaptation in selecting and associating multisensory signals with motor memory. This finding provides insight into developing learning programs that are generalizable in complex daily environments. NEW & NOTEWORTHY Learning novel motor actions in complex environments with attentional distraction is a critical function. Successful motor learning involves the ability to transfer the acquired skill from the trained to novel environments. Here, we demonstrate attentional distraction does not impair visuomotor adaptation. Rather, consistency in the attentional context from training to generalization modulates the degree of transfer to untrained locations. The role of attention and memory must, therefore, be incorporated into existing models of visuomotor learning.

During continuous bimanual coordination, in-phase (IP; 0° relative phase) and anti-phase (AP; 180° relative phase) patterns can be stably performed without practice. Paradigms in which participants are required to intentionally switch between these coordination patterns have been used to investigate the interaction between the performer’s intentions and intrinsic dynamics of the body’s preferred patterns. The current study examined the processes associated with switching preparation and execution through the use of a startling acoustic stimulus (SAS) as the switch stimulus. A SAS is known to involuntarily trigger preprogrammed responses at a shortened latency and, thus, can be used to probe advance preparation. Participants performed cyclical IP and AP bimanual elbow extension-flexion movements in which they were required to switch patterns in response to an auditory switch cue, which was either nonstartling (80 dB) or a SAS (120 dB). Results indicated that reaction time to the switch stimulus (i.e., switch onset) was significantly reduced on startle trials, indicative of advance preparation of the switch response. Similarly, switching time was reduced on startle trials, which was attributed to increased neural activation caused by the SAS. Switching time was also shorter for AP to IP trials, but only when the switching stimulus occurred at either the midpoint or reversal locations within the movement cycle, suggesting that the switch location may affect the intrinsic dynamics of the system. NEW & NOTEWORTHY The current study provides novel information regarding preparation and execution of intentional switching between in-phase and anti-phase bimanual coordination patterns. Using a startling acoustic stimulus, we provide strong evidence that the switching response is prepared before the switch stimulus, and switch execution is accelerated by the startling stimulus. In addition, the time required to switch between patterns and relative limb contribution is dependent upon where in the movement cycle the switch stimulus occurred.

Incomplete cervical spinal cord hemisection at C2 (SH) disrupts descending excitatory drive to phrenic motoneurons, paralyzing the ipsilateral diaphragm muscle. Spontaneous recovery over time is associated with increased phrenic motoneuron expression of glutamatergic N-methyl-d-aspartate (NMDA) and serotonergic 5-HT2A receptors. We hypothesized that NMDA and 5-HT2A receptor-mediated neurotransmission play a role in ipsilateral diaphragm muscle activity post-SH. Adult male Sprague-Dawley rats were implanted with bilateral diaphragm EMG electrodes for chronic EMG recordings up to 28 days post-SH (SH 28D). The extent of recovery was calculated by peak root-mean-square (RMS) EMG amplitude. In all animals, absence of ipsilateral activity was verified at 3 days post-SH. Diaphragm EMG activity was also recorded during exposure to hypoxia-hypercapnia (10% O₂-5% CO₂). In SH animals displaying recovery of ipsilateral diaphragm EMG activity at SH 28D, cervical spinal cord segments containing the phrenic motor nucleus (C3–C5) were surgically exposed and either the NMDA receptor antagonist d-2-amino-5-phosphonovalerate (d-AP5; 100 mM, 30 μl) or 5-HT2A receptor antagonist ketanserin (40 mM, 30 μl) was instilled intrathecally. Following d-AP5, diaphragm EMG amplitude was reduced ipsilaterally, during both eupnea (42% of pre-d-AP5 value; P = 0.007) and hypoxia-hypercapnia (31% of pre-d-AP5 value; P = 0.015), with no effect on contralateral EMG activity or in uninjured controls. Treatment with ketanserin did not change ipsilateral or contralateral RMS EMG amplitude in SH animals displaying recovery at SH 28D. Our results suggest that spinal glutamatergic NMDA receptor-mediated neurotransmission plays an important role in ipsilateral diaphragm muscle activity after cervical spinal cord injury. NEW & NOTEWORTHY Spontaneous recovery following C2 spinal hemisection (SH) is associated with increased phrenic motoneuron expression of glutamatergic and serotonergic receptors. In this study, we show that pharmacological inhibition of glutamatergic N-methyl-d-aspartate (NMDA) receptors blunts ipsilateral diaphragm activity post-SH. In contrast, pharmacological inhibition of serotonergic 5-HT2A receptors does not change diaphragm EMG activity post-SH. Our results suggest that NMDA receptor-mediated glutamatergic neurotransmission plays an important role in enhancing rhythmic respiratory-related diaphragm activity after spinal cord injury.

This study was aimed at verifying whether aging modifies intralimb coordination strategy during corrective responses elicited by unexpected slip-like perturbations delivered during steady walking on a treadmill. To this end, 10 young and 10 elderly subjects were asked to manage unexpected slippages of different intensities. We analyzed the planar covariation law of the lower limb segments, using the principal component analysis, to verify whether elevation angles of older subjects covaried along a plan before and after the perturbation. Results showed that segments related to the perturbed limbs of both younger and older people do not covary after all perturbations. Conversely, the planar covariation law of the unperturbed limb was systematically held for younger and older subjects. These results occurred despite differences in spatio-temporal and kinematic parameters being observed among groups and perturbation intensities. Overall, our analysis revealed that aging does not affect intralimb coordination during corrective responses induced by slip-like perturbation, suggesting that both younger and older subjects adopt this control strategy while managing sudden and unexpected postural transitions of increasing intensities. Accordingly, results corroborate the hypothesis that balance control emerges from a governing set of biomechanical invariants, that is, suitable control schemes (e.g., planar covariation law) shared across voluntary and corrective motor behaviors, and across different sensory contexts due to different perturbation intensities, in both younger and older subjects. In this respect, our findings provide further support to investigate the effects of specific task training programs to counteract the risk of fall. NEW & NOTEWORTHY This study was aimed at investigating how aging affects the intralimb coordination of lower limb segments, described by the planar covariation law, during unexpected slip-like perturbations of increasing intensity. Results revealed that neither the aging nor the perturbation intensity affects this coordination strategy. Accordingly, we proposed that the balance control emerges from an invariant set of control schemes shared across different sensory motor contexts and despite age-related neuromuscular adaptations.

We studied the changes in sensitivity to a peptide modulator, crustacean cardioactive peptide (CCAP), as a response to loss of endogenous modulation in the stomatogastric ganglion (STG) of the crab Cancer borealis. Our data demonstrate that removal of endogenous modulation for 24 h increases the response of the lateral pyloric (LP) neuron of the STG to exogenously applied CCAP. Increased responsiveness is accompanied by increases in CCAP receptor (CCAPr) mRNA levels in LP neurons, requires de novo protein synthesis, and can be prevented by coincubation for the 24-h period with exogenous CCAP. These results suggest that there is a direct feedback from loss of CCAP signaling to the production of CCAPr that increases subsequent response to the ligand. However, we also demonstrate that the modulator-evoked membrane current (I_MI) activated by CCAP is greater in magnitude after combined loss of endogenous modulation and activity compared with removal of just hormonal modulation. These results suggest that both receptor expression and an increase in the target conductance of the CCAP G protein-coupled receptor are involved in the increased response to exogenous hormone exposure following experimental loss of modulation in the STG. NEW & NOTEWORTHY The nervous system shows a tremendous amount of plasticity. More recently there has been an appreciation for compensatory actions that stabilize output in the face of perturbations to normal activity. In this study we demonstrate that neurons of the crustacean stomatogastric ganglion generate apparent compensatory responses to loss of peptide neuromodulation, adding to the repertoire of mechanisms by which the stomatogastric nervous system can regulate and stabilize its own output.

Smooth pursuit and motion perception have mainly been investigated with stimuli moving along linear trajectories. Here we studied the quality of pursuit movements to curved motion trajectories in human observers and examined whether the pursuit responses would be sensitive enough to discriminate various degrees of curvature. In a two-interval forced-choice task subjects pursued a Gaussian blob moving along a curved trajectory and then indicated in which interval the curve was flatter. We also measured discrimination thresholds for the same curvatures during fixation. Motion curvature had some specific effects on smooth pursuit properties: trajectories with larger amounts of curvature elicited lower open-loop acceleration, lower pursuit gain, and larger catch-up saccades compared with less curved trajectories. Initially, target motion curvatures were underestimated; however, ∼300 ms after pursuit onset pursuit responses closely matched the actual curved trajectory. We calculated perceptual thresholds for curvature discrimination, which were on the order of 1.5 degrees of visual angle (°) for a 7.9° curvature standard. Oculometric sensitivity to curvature discrimination based on the whole pursuit trajectory was quite similar to perceptual performance. Oculometric thresholds based on smaller time windows were higher. Thus smooth pursuit can quite accurately follow moving targets with curved trajectories, but temporal integration over longer periods is necessary to reach perceptual thresholds for curvature discrimination. NEW & NOTEWORTHY Even though motion trajectories in the real world are frequently curved, most studies of smooth pursuit and motion perception have investigated linear motion. We show that pursuit initially underestimates the curvature of target motion and is able to reproduce the target curvature ∼300 ms after pursuit onset. Temporal integration of target motion over longer periods is necessary for pursuit to reach the level of precision found in perceptual discrimination of curvature.

Coherence analysis has the ability to identify the presence of common descending drive shared by motor unit pools and reveals its spectral properties. However, the link between spectral properties of shared neural drive and functional interactions among muscles remains unclear. We assessed shared neural drive between muscles of the thumb and index finger while participants executed two mechanically distinct precision pinch tasks, each requiring distinct functional coordination among muscles. We found that shared neural drive was systematically reduced or enhanced at specific frequencies of interest (~10 and ~40 Hz). While amplitude correlations between surface EMG signals also exhibited changes across tasks, only their coherence has strong physiological underpinnings indicative of neural binding. Our results support the use of intermuscular coherence as a tool to detect when coactivated muscles are members of a functional group or synergy of neural origin. Furthermore, our results demonstrate the advantages of considering neural binding at 10, ~20, and >30 Hz, as indicators of task-dependent neural coordination strategies. NEW & NOTEWORTHY It is often unclear whether correlated activity among muscles reflects their neural binding or simply reflects the constraints defining the task. Using the fact that high-frequency coherence between EMG signals (>6 Hz) is thought to reflect shared neural drive, we demonstrate that coherence analysis can reveal the neural origin of distinct muscle coordination patterns required by different tasks.

Rodent granular retrosplenial cortex (GRS) has dense connections between the anterior thalamic nuclei (ATN) and hippocampal formation. GRS superficial pyramidal neurons exhibit distinctive late spiking (LS) firing property and form patchy clusters with prominent apical dendritic bundles. The aim of this study was to investigate spatiotemporal dynamics of signal transduction in the GRS induced by ATN afferent stimulation by using fast voltage-sensitive dye imaging in rat brain slices. In coronal slices, layer 1a stimulation, which presumably activated thalamic fibers, evoked propagation of excitatory synaptic signals from layers 2–4 to layers 5–6 in a direction perpendicular to the layer axis, followed by transverse signal propagation within each layer. In the presence of ionotropic glutamate receptor antagonists, inhibitory responses were observed in superficial layers, induced by direct activation of inhibitory interneurons in layer 1. In horizontal slices, excitatory signals in deep layers propagated transversely mainly from posterior to anterior via superficial layers. Cortical inhibitory responses upon layer 1a stimulation in horizontal slices were weaker than those in the coronal slices. Observed differences between coronal and horizontal planes suggest anisotropy of the intracortical circuitry. In conclusion, ATN inputs are processed differently in coronal and horizontal planes of the GRS and then conveyed to other cortical areas. In both planes, GRS superficial layers play an important role in signal propagation, which suggests that superficial neuronal cascade is crucial in the integration of multiple information sources. NEW & NOTEWORTHY Superficial neurons in the rat granular retrosplenial cortex (GRS) show distinctive late-spiking (LS) firing property. However, little is known about spatiotemporal dynamics of signal transduction in the GRS. We demonstrated LS neuron network relaying thalamic inputs to deep layers and anisotropic distribution of inhibition between coronal and horizontal planes. Since deep layers of the GRS receive inputs from the subiculum, GRS circuits may work as an integrator of multiple sources such as sensory and memory information.

The ability to catch objects when transiently occluded from view suggests their motion can be extrapolated. Intraparietal cortex (IPS) plays a major role in this process along with other brain structures, depending on the task. For example, interception of objects under Earth’s gravity effects may depend on time-to-contact predictions derived from integration of visual signals processed by hMT/V5+ with a priori knowledge of gravity residing in the temporoparietal junction (TPJ). To investigate this issue further, we disrupted TPJ, hMT/V5+, and IPS activities with transcranial magnetic stimulation (TMS) while subjects intercepted computer-simulated projectile trajectories perturbed randomly with either hypo- or hypergravity effects. In experiment 1, trajectories were occluded either 750 or 1,250 ms before landing. Three subject groups underwent triple-pulse TMS (tpTMS, 3 pulses at 10 Hz) on one target area (TPJ | hMT/V5+ | IPS) and on the vertex (control site), timed at either trajectory perturbation or occlusion. In experiment 2, trajectories were entirely visible and participants received tpTMS on TPJ and hMT/V5+ with same timing as experiment 1. tpTMS of TPJ, hMT/V5+, and IPS affected differently the interceptive timing. TPJ stimulation affected preferentially responses to 1-g motion, hMT/V5+ all response types, and IPS stimulation induced opposite effects on 0-g and 2-g responses, being ineffective on 1-g responses. Only IPS stimulation was effective when applied after target disappearance, implying this area might elaborate memory representations of occluded target motion. Results are compatible with the idea that IPS, TPJ, and hMT/V5+ contribute to distinct aspects of visual motion extrapolation, perhaps through parallel processing. NEW & NOTEWORTHY Visual extrapolation represents a potential neural solution to afford motor interactions with the environment in the face of missing information. We investigated relative contributions by temporoparietal junction (TPJ), hMT/V5+, and intraparietal cortex (IPS), cortical areas potentially involved in these processes. Parallel organization of visual extrapolation processes emerged with respect to the target’s motion causal nature: TPJ was primarily involved for visual motion congruent with gravity effects, IPS for arbitrary visual motion, whereas hMT/V5+ contributed at earlier processing stages.

Studies suggested that motor expertise is associated with functional and structural brain alterations, which positively affect sensorimotor performance and learning capabilities. The purpose of the present study was to unravel differences in motor skill learning and associated functional neuroplasticity between endurance athletes (EA) and nonathletes (NA). For this purpose, participants had to perform a multimodal balance task (MBT) training on 2 sessions, which were separated by 1 wk. Before and after MBT training, a static balance task (SBT) had to be performed. MBT-induced functional neuroplasticity and neuromuscular alterations were assessed by means of functional near-infrared spectroscopy (fNIRS) and electromyography (EMG) during SBT performance. We hypothesized that EA would showed superior initial SBT performance and stronger MBT-induced improvements in SBT learning rates compared with NA. On a cortical level, we hypothesized that MBT training would lead to differential learning-dependent functional changes in motor-related brain regions [such as primary motor cortex (M1)] during SBT performance. In fact, EA showed superior initial SBT performance, whereas learning rates did not differ between groups. On a cortical level, fNIRS recordings (time × group interaction) revealed a stronger MBT-induced decrease in left M1 and inferior parietal lobe (IPL) for deoxygenated hemoglobin in EA. Even more interesting, learning rates were correlated with fNIRS changes in right M1/IPL. On the basis of these findings, we provide novel evidence for superior MBT training-induced functional neuroplasticity in highly trained athletes. Future studies should investigate these effects in different sports disciplines to strengthen previous work on experience-dependent neuroplasticity. NEW & NOTEWORTHY Motor expertise is associated with functional/structural brain plasticity. How such neuroplastic reorganization translates into altered motor learning processes remains elusive. We investigated endurance athletes (EA) and nonathletes (NA) in a multimodal balance task (MBT). EA showed superior static balance performance (SBT), whereas MBT-induced SBT improvements did not differ between groups. Functional near-infrared spectroscopy recordings revealed a differential MBT training-induced decrease of deoxygenated hemoglobin in left primary motor cortex and inferior parietal lobe between groups.

Birds and mammals use the interaural time difference (ITD) for azimuthal sound localization. While barn owls can use the ITD of the stimulus carrier frequency over nearly their entire hearing range, mammals have to utilize the ITD of the stimulus envelope to extend the upper frequency limit of ITD-based sound localization. ITD is computed and processed in a dedicated neural circuit that consists of two pathways. In the barn owl, ITD representation is more complex in the forebrain than in the midbrain pathway because of the combination of two inputs that represent different ITDs. We speculated that one of the two inputs includes an envelope contribution. To estimate the envelope contribution, we recorded ITD response functions for correlated and anticorrelated noise stimuli in the barn owl’s auditory arcopallium. Our findings indicate that barn owls, like mammals, represent both carrier and envelope ITDs of overlapping frequency ranges, supporting the hypothesis that carrier and envelope ITD-based localization are complementary beyond a mere extension of the upper frequency limit. NEW & NOTEWORTHY The results presented in this study show for the first time that the barn owl is able to extract and represent the interaural time difference (ITD) information conveyed by the envelope of a broadband acoustic signal. Like mammals, the barn owl extracts the ITD of the envelope and the carrier of a signal from the same frequency range. These results are of general interest, since they reinforce a trend found in neural signal processing across different species.

Requisite for understanding cerebellar function is a complete characterization of the signals provided by complex spike (CS) discharge of Purkinje cells, the output neurons of the cerebellar cortex. Numerous studies have provided insights into CS function, with the most predominant view being that they are evoked by error events. However, several reports suggest that CSs encode other aspects of movements and do not always respond to errors or unexpected perturbations. Here, we evaluated CS firing during a pseudo-random manual tracking task in the monkey (Macaca mulatta). This task provides extensive coverage of the work space and relative independence of movement parameters, delivering a robust data set to assess the signals that activate climbing fibers. Using reverse correlation, we determined feedforward and feedback CSs firing probability maps with position, velocity, and acceleration, as well as position error, a measure of tracking performance. The direction and magnitude of the CS modulation were quantified using linear regression analysis. The major findings are that CSs significantly encode all three kinematic parameters and position error, with acceleration modulation particularly common. The modulation is not related to “events,” either for position error or kinematics. Instead, CSs are spatially tuned and provide a linear representation of each parameter evaluated. The CS modulation is largely predictive. Similar analyses show that the simple spike firing is modulated by the same parameters as the CSs. Therefore, CSs carry a broader array of signals than previously described and argue for climbing fiber input having a prominent role in online motor control. NEW & NOTEWORTHY This article demonstrates that complex spike (CS) discharge of cerebellar Purkinje cells encodes multiple parameters of movement, including motor errors and kinematics. The CS firing is not driven by error or kinematic events; instead it provides a linear representation of each parameter. In contrast with the view that CSs carry feedback signals, the CSs are predominantly predictive of upcoming position errors and kinematics. Therefore, climbing fibers carry multiple and predictive signals for online motor control.

Spatial attention improves perception of attended parts of a scene, a behavioral enhancement accompanied by modulations of neuronal firing rates. These modulations vary in size across neurons in the same brain area. Models of normalization explain much of this variance in attention modulation with differences in tuned normalization across neurons (Lee J, Maunsell JHR. PLoS One 4: e4651, 2009; Ni AM, Ray S, Maunsell JHR. Neuron 73: 803–813, 2012). However, recent studies suggest that normalization tuning varies with spatial location both across and within neurons (Ruff DA, Alberts JJ, Cohen MR. J Neurophysiol 116: 1375–1386, 2016; Verhoef BE, Maunsell JHR. eLife 5: e17256, 2016). Here we show directly that attention modulation and normalization tuning do in fact covary within individual neurons, in addition to across neurons as previously demonstrated. We recorded the activity of isolated neurons in the middle temporal area of two rhesus monkeys as they performed a change-detection task that controlled the focus of spatial attention. Using the same two drifting Gabor stimuli and the same two receptive field locations for each neuron, we found that switching which stimulus was presented at which location affected both attention modulation and normalization in a correlated way within neurons. We present an equal-maximum-suppression spatially tuned normalization model that explains this covariance both across and within neurons: each stimulus generates equally strong suppression of its own excitatory drive, but its suppression of distant stimuli is typically less. This new model specifies how the tuned normalization associated with each stimulus location varies across space both within and across neurons, changing our understanding of the normalization mechanism and how attention modulations depend on this mechanism. NEW & NOTEWORTHY Tuned normalization studies have demonstrated that the variance in attention modulation size seen across neurons from the same cortical area can be largely explained by between-neuron differences in normalization strength. Here we demonstrate that attention modulation size varies within neurons as well and that this variance is largely explained by within-neuron differences in normalization strength. We provide a new spatially tuned normalization model that explains this broad range of observed normalization and attention effects.

Temporal codes are theoretically powerful encoding schemes, but their precise form in the neocortex remains unknown in part because of the large number of possible codes and the difficulty in disambiguating informative spikes from statistical noise. A biologically plausible and computationally powerful temporal coding scheme is the Hebbian assembly phase sequence (APS), which predicts reliable propagation of spikes between functionally related assemblies of neurons. Here, we sought to measure the inherent capacity of neocortical networks to produce reliable sequences of spikes, as would be predicted by an APS code. To record microcircuit activity, the scale at which computation is implemented, we used two-photon calcium imaging to densely sample spontaneous activity in murine neocortical networks ex vivo. We show that the population spike histogram is sufficient to produce a spatiotemporal progression of activity across the population. To more comprehensively evaluate the capacity for sequential spiking that cannot be explained by the overall population spiking, we identify statistically significant spike sequences. We found a large repertoire of sequence spikes that collectively comprise the majority of spiking in the circuit. Sequences manifest probabilistically and share neuron membership, resulting in unique ensembles of interwoven sequences characterizing individual spatiotemporal progressions of activity. Distillation of population dynamics into its constituent sequences provides a way to capture trial-to-trial variability and may prove to be a powerful decoding substrate in vivo. Informed by these data, we suggest that the Hebbian APS be reformulated as interwoven sequences with flexible assembly membership due to shared overlapping neurons. NEW & NOTEWORTHY Neocortical computation occurs largely within microcircuits comprised of individual neurons and their connections within small volumes (<500 μm³). We found evidence for a long-postulated temporal code, the Hebbian assembly phase sequence, by identifying repeated and co-occurring sequences of spikes. Variance in population activity across trials was explained in part by the ensemble of active sequences. The presence of interwoven sequences suggests that neuronal assembly structure can be variable and is determined by previous activity.

Lower limb paralysis from spinal cord injury (SCI) or neurological disease carries a poor prognosis for recovery and remains a large societal burden. Neurophysiological and neuroprosthetic research have the potential to improve quality of life for these patients; however, the lack of an ethical and sustainable nonhuman primate model for paraplegia hinders their advancement. Therefore, our multidisciplinary team developed a way to induce temporary paralysis in awake behaving macaques by creating a fully implantable lumbar epidural catheter-subcutaneous port system that enables easy and reliable targeted drug delivery for sensorimotor blockade. During treadmill walking, aliquots of 1.5% lidocaine with 1:200,000 epinephrine were percutaneously injected into the ports of three rhesus macaques while surface electromyography (EMG) recorded muscle activity from their quadriceps and gastrocnemii. Diminution of EMG amplitude, loss of voluntary leg movement, and inability to bear weight were achieved for 60–90 min in each animal, followed by a complete recovery of function. The monkeys remained alert and cooperative during the paralysis trials and continued to take food rewards, and the ports remained functional after several months. This technique will enable recording from the cortex and/or spinal cord in awake behaving nonhuman primates during the onset, maintenance, and resolution of paraplegia for the first time, thus opening the door to answering basic neurophysiological questions about the acute neurological response to spinal cord injury and recovery. It will also negate the need to permanently injure otherwise high-value research animals for certain experimental paradigms aimed at developing and testing neural interface decoding algorithms for patients with lower extremity dysfunction. NEW & NOTEWORTHY A novel implantable lumbar epidural catheter-subcutaneous port system enables targeted drug delivery and induction of temporary paraplegia in awake, behaving nonhuman primates. Three macaques displayed loss of voluntary leg movement for 60–90 min after injection of lidocaine with epinephrine, followed by a full recovery. This technique for the first time will enable ethical live recording from the proximal central nervous system during the acute onset, maintenance, and resolution of paraplegia.

Primary motor cortex has been studied for more than a century, yet a consensus on its functional contribution to movement control is still out of reach. In particular, there remains controversy as to the level of control produced by motor cortex (“low-level” movement dynamics vs. “high-level” movement kinematics) and the role of sensory feedback. In this review, we present different perspectives on the two following questions: What does activity in motor cortex reflect? and How do planned motor commands interact with incoming sensory feedback during movement? The four authors each present their independent views on how they think the primary motor cortex (M1) controls movement. At the end, we present a dialogue in which the authors synthesize their views and suggest possibilities for moving the field forward. While there is not yet a consensus on the role of M1 or sensory feedback in the control of upper limb movements, such dialogues are essential to take us closer to one.

Many central pattern generator (CPG)-mediated behaviors are episodic, meaning that they are not continuously ongoing; instead, there are pauses between bouts of activity. This raises an interesting possibility, that the neural networks that mediate these behaviors are not operating under “steady-state” conditions; i.e., there could be dynamic changes in motor activity as it stops and starts. Research in the feeding system of the mollusk Aplysia californica has demonstrated that this can be the case. After a pause, initial food grasping responses are relatively weak. With repetition, however, responses strengthen. In this review we describe experiments that have characterized cellular/molecular mechanisms that produce these changes in motor activity. In particular, we focus on cumulative effects of modulatory neuropeptides. Furthermore, we relate Aplysia research to work in other systems and species, and develop a hypothesis that postulates that changes in response magnitude are a reflection of an efficient feeding strategy.