Experimental Brain Research

Greenhouse, Ian

doi: 10.1007/s00221-022-06351-5pmid: 35347346

Signatures of inhibition within the cortico-spinal pathway are frequently observed during action preparation in humans. Popular theoretical and computational models highlight a critical role for inhibition as the suppressor of motor system output, e.g., to withhold undesired action tendencies or to stop ongoing movements. However, inhibition frequently serves a modulatory role in non-motor systems. For example, in vision and somatosensory systems, inhibition can adjust the relationships between input and output, a computation referred to as gain modulation. Inhibition may modulate gain within the motor system as well. Changes in cortico-spinal inhibition observed during human behavior can reflect adjustments in motor system gain and may be sensitive to latent behavioral states. This review summarizes roles for inhibition in gain modulation, drawing principally on evidence from non-motor systems, and examines the hypothesis that homologous functions operate in the animal and human motor systems to facilitate action preparation.

Sergio, Cornelio-Martínez; Rolando, Castañeda-Arellano

doi: 10.1007/s00221-022-06331-9pmid: 35234993

Erythropoietin is a cytokine that binds to the Erythropoietin receptor and regulates the formation of erythroid cells during erythropoiesis in the bone marrow. However, many other organs and tissues express Erythropoietin and its receptor, such as the Nervous System, which principally regulates tissue protection. In the Central Nervous System, Erythropoietin is principally expressed by astrocytes, while neurons mainly express Erythropoietin receptors. Moreover, Erythropoietin acts as a pleiotropic molecule with neuroprotective effects, and its mechanisms of signal transduction pathways are defined, and there is a growing interest in its therapeutic potential. This review focuses on the role of Erythropoietin and its relationship with HIF1, PI3/Akt, GSK3B, JAK/STAT, and MAPKs signaling pathways that leads to cell survival after injury in the Central Nervous System. Knowledge of these signaling systems comprehensively could better guide EPO treatment to restoring different SNC alterations mediated by different insults.

Trotman, Megan; Kennefick, Michael; Coughlin, Scott; van Donkelaar, Paul; Dalton, Brian H.

doi: 10.1007/s00221-022-06326-6pmid: 35247064

Reactive balance control following hand perturbations is important for everyday living as humans constantly encounter perturbations to the upper limb while performing functional tasks while standing. When multiple tasks are performed simultaneously, cognitive processing is increased, and performance on at least one of the tasks is often disrupted, owing to attentional resources being divided. The purpose here was to assess the effects of increased cognitive processing on whole-body balance responses to perturbations of the hand during continuous voluntary reaching. Sixteen participants (8 females; 22.9 ± 4.5 years) stood and grasped the handle of a KINARM – a robotic-controlled manipulandum paired with an augmented visual display. Participants completed 10 total trials of 100 mediolateral arm movements at a consistent speed of one reach per second, and an auditory n-back task (cognitive task). Twenty anteroposterior hand perturbations were interspersed randomly throughout the reaching trials. The arm movements with random arm perturbations were either performed simultaneously with the cognitive task (combined task) or in isolation (arm perturbation task). Peak centre of pressure (COP) displacement and velocity, time to COP displacement onset and peak, as well as hand displacement and velocity following the hand perturbation were evaluated. N-back response times were 8% slower and 11% less accurate for the combined than the cognitive task. Peak COP displacement following posterior perturbations increased by 8% during the combined compared to the arm perturbation task alone, with no other differences detected. Hand peak displacement decreased by 5% during the combined compared to the arm perturbation task. The main findings indicate that with increased cognitive processing, attentional resources were allocated from the cognitive task towards upper limb movements, while attentional resources for balance seemed unaltered.

Salvaggio, Samuel; Masson, Nicolas; Zénon, Alexandre; Andres, Michael

doi: 10.1007/s00221-022-06329-3pmid: 35243541

Behavioural studies have suggested that number manipulation involves shifting attention along a left-to-right oriented continuum. However, these studies provide little evidence about the time course of attention shifts during number processing. We used an eye-tracker with high spatio-temporal resolution to measure eye movements during the mental solving of addition (e.g., 43 + 4) and subtraction problems (e.g., 53 − 6), as a proxy for the rightward and leftward attention shifts that accompany these operations. A first difference in eye position was observed as soon as the operator was heard: the hearing of “plus” shifted the eye rightward compared to “minus”. A second difference was observed later between problem offset and response onset: addition shifted the eye rightward and upward compared to subtraction, suggesting that the space used to represent the problem is bidimensional. Further analyses confirmed the fast deployment of spatial attention and evidenced its relationship with the carrying and borrowing procedures triggered by the problem presentation. The predictive role of horizontal eye movements, in particular, is essential to understand how attention contributes to narrow down the range of plausible answers. We propose that attention illuminates significant portions of the numerical continuum anticipatively to guide the search of the answer and facilitate the implementation of solving procedures in verbal working memory.

Barrientos, Rafael; Alatorre, Alberto; Oviedo-Chávez, Aldo; Delgado, Alfonso; Nielsen, Nielsine; Querejeta, Enrique

doi: 10.1007/s00221-022-06328-4pmid: 35234992

The reticular thalamic nucleus (RTn) is a thin shell of GABAergic neurons that covers the dorsal thalamus that regulate the global activity of all thalamic nuclei. RTn controls the flow of information between thalamus and cerebral cortex since it receives glutamatergic information from collaterals of thalamo-cortical (TCs) and cortico-thalamic neurons. It also receives aminergic information from several brain stem nuclei, including serotonergic fibers originated in the dorsal raphe nucleus. RTn neurons express serotonergic receptors including the 5-HT1A subtype, however, the role of this receptor in the RTn electrical activity has been scarcely analyzed. In this work, we recorded in vivo the unitary spontaneous electrical activity of RTn neurons in anesthetized rats; our study aimed to obtain information about the effects of 5-HT1A receptors in RTn neurons. Local application of fluoxetine (a serotonin reuptake inhibitor) increases burst firing index accompanied by a decrease in the basal spiking rate. Local application of different doses of serotonin and 8-OH-DPAT (a specific 5-HT1A receptor agonist) causes a similar response to fluoxetine effects. Local 5-HT1A receptors blockade produces opposite effects and suppresses the effect by 8-OH-DPAT. Our findings indicate the presence of a serotonergic tonic discharge in the RTn that increases the burst firing index and simultaneously decreases the basal spiking frequency through 5-HT1A receptors activation.

Arras, Tine; Snapp, Hillary; Sangen, Anouk; Snels, Chantal; Kuntz, Iris; Theunen, Tinne; Kheirkhah, Kiana; Zarowski, Andrzej; Wesarg, Thomas; van Wieringen, Astrid; Agterberg, Martijn J. H.

doi: 10.1007/s00221-022-06333-7pmid: 35238954

Several studies report that sound localization performance of acute and chronic monauralized normal-hearing listeners can improve through training. Typically, training sessions are administered daily for several days or weeks. While this intensive training is effective, it may also be that monaural localization abilities improve instantly after providing explicit top-down information about the direction dependent change in timbre and level. The aim of the present study was to investigate whether cognitive feedback (i.e., top-down information) could instantly improve sound localization in naive acutely monauralized listeners. Forty-three normal-hearing listeners (experimental group), divided over five different centers, were tested. Two control groups, consisting of, respectively, nine and eleven normal-hearing listeners, were tested in one center. Broadband sounds (0.5–20 kHz) were presented from visible loudspeakers, positioned in azimuth (− 90° to 90°). Participants in the experimental group received explicit information about the noticeable difference in timbre and the poor localization in the monauralized listening condition, resulting in an instant improvement in sound localization abilities. With subsequent roving of stimulus level (20 dB), sound localization performance deteriorated immediately. The reported improvement is related to the context of the localization test. The results provide important implications for studies investigating sound localization in a clinical setting, especially during closed-set testing, and indicate the importance of top-down information.

Govender, Sendhil; Todd, Neil P. M.; Colebatch, James G.

doi: 10.1007/s00221-022-06335-5pmid: 35243540

Recordings from over the posterior fossa following impulsive acceleration stimuli have shown short latency evoked potentials of presumed cerebellar origin. In this study, we investigated the effect of posture on these cerebellar evoked potentials (CEPs) and their relationship to postural reflexes recorded from the leg muscles evoked by the same stimuli. Nine healthy subjects were tested during lying (supine and prone), sitting and standing. Impulsive accelerations were applied at the mastoid and to truncal (both C7 and sternal) stimulation sites. The effect of vision, eyes open or closed, was investigated for all three stimuli. For the truncal stimuli, the effect of differing leaning conditions during standing was also recorded. CEP amplitudes were correlated for the three stimuli. For C7 stimulation during standing, both CEPs and postural reflexes scaled as the threat to postural stability increased. However, CEPs for all stimuli were present during lying, sitting and standing with amplitude and latency parameters mainly unaffected by posture or vision. In contrast, postural reflexes from the leg muscles were attenuated when not standing, with the effect being more marked for truncal stimuli. We conclude that CEPs evoked by axial and vestibular stimuli are not systematically gated by posture, in contrast to the reflex responses evoked by the same stimuli.

Johnson, John T.; de Mari, Daniele; Doherty, Harper; Hammond, Frank L.; Wheaton, Lewis A.

doi: 10.1007/s00221-022-06340-8pmid: 35257195

Prosthesis disuse and abandonment is an ongoing issue in upper-limb amputation. In addition to lost structural and motor function, amputation also results in decreased task-specific sensory information. One proposed remedy is augmenting somatosensory information using vibrotactile feedback to provide tactile feedback of grasping objects. While the role of frontal and parietal areas in motor tasks is well established, the neural and kinematic effects of this augmented vibrotactile feedback remain in question. In this study, we sought to understand the neurobehavioral effects of providing augmented feedback during a reach-grasp-transport task. Ten persons with sound limbs performed a motor task while wearing a prosthesis simulator with and without vibrotactile feedback. We hypothesized that providing vibrotactile feedback during prosthesis use would increase activity in frontal and parietal areas and improve grasp-related behavior. Results show that anticipation of upcoming vibrotactile feedback may be encoded in motor and parietal areas during the reach-to-grasp phase of the task. While grasp aperture is unaffected by vibrotactile feedback, the availability of vibrotactile feedback does lead to a reduction in velocity during object transport. These results help shed light on how engineered feedback is utilized by prostheses users and provide methodologies for further assessment in advanced prosthetics research.

Penton, Tegan; Wang, Xingquan; Catmur, Caroline; Bird, Geoffrey

doi: 10.1007/s00221-022-06339-1pmid: 35381863

Tasks measuring the sense of agency often manipulate the predictability of action outcomes by introducing spatial deviation. However, the extent to which spatial predictability of an outcome influences the sense of agency when spatial deviation is controlled for remains untested. We used a novel task to investigate the effect of several factors (action–outcome contingency, spatial deviation, and spatial predictability when controlling for spatial deviation of action outcomes) on the sense of agency. We also investigated trait predictors of metacognition of agency—the degree to which participants’ confidence in their agency judgements corresponds to the accuracy of those judgements. Initial and replication samples completed contingency, deviation, and predictability versions of the task. Across samples, participants’ sense of agency was impacted by action–outcome contingency and spatial deviation of action outcomes. Manipulation of the spatial predictability of action outcomes did not reliably impact the sense of agency. Metacognition of agency was related to alexithymic traits—higher alexithymia scores were associated with reduced metacognition of agency.

Zhang, Lei; Straube, Andreas; Eggert, Thomas

doi: 10.1007/s00221-022-06343-5pmid: 35286422

Friedreich’s ataxia (FA) is a hereditary system degeneration, which progressively affects sensory functions such as proprioceptive feedback, which causes progressive ataxia in FA patients. While major clinical features of movement disorders in FA patients have been identified, the underlying impaired neural control is not sufficiently understood. To elucidate the underlying control mechanism, we investigated single-joint movements of the upper limb in FA patients. Small, tolerable force perturbations were induced during voluntary single-joint arm movements to examine the compensatory reaction of the FA patient’s motor system. Movement kinematics were measured, and muscle torques were quantified. We first found that as in healthy subjects, unperturbed single-joint movements in FA patients preserved similar temporal profiles of hand velocity and muscle torques, however, scaled in duration and amplitude. In addition, the small perturbations were compensated for efficiently in both groups, with the endpoint error < 0.5° (maximum displacement of 5–15°). We further quantified the differences in movement time, torque response, and displacement between patients and controls. To distinguish whether these differences were caused by a malfunction of top-down control or a malfunction of feedback control, the responses were fitted with a detailed model of the stretch reflex. The model simulations revealed that the feedback delay, but not the feedback gain was affected in FA patients. They also showed that the descending control signal was scaled in time and amplitude and co-contraction was smaller in FA patients. Thus, our study explains how the motor deficits of FA patients result from pathological alterations of both top-down and feedback control.