Learning about Time: Plastic Changes and Interindividual Brain Differences

Learning the timing of rapidly changing sensory events is crucial to construct a reliable representation of the environment and to efficiently control behavior. The neurophysiological mechanisms underlying the learning of time are unknown. We used functional and structural magnetic resonance imaging to investigate neurophysiological changes and individual brain differences underlying the learning of time in the millisecond range. We found that the representation of a trained visual temporal interval was associated with functional and structural changes in a sensory-motor network including occipital, parietal, and insular cortices, plus the cerebellum. We show that both types of neurophysiological changes correlated with changes of performance accuracy and that activity and gray-matter volume of sensorimotor cortices predicted individual learning abilities. These findings represent neurophysiological evidence of functional and structural plasticity associated with the learning of time in humans and highlight the role of sensory-motor circuits in the perceptual representation of time in the millisecond range.     

Miller–Fisher syndrome associated with SARS-CoV-2: a case report

SARS-CoV-2 infections are increasingly associated with neurological complications, including immune-mediated neuropathies. Miller–Fisher syndrome is a rare variant of Guillain-Barré syndrome characterised by the triad of ataxia, ophthalmoplegia and areflexia.Here we present a case of Miller–Fisher syndrome following COVID-19 infection. The clinical presentation was a short history of a rapidly-progressive peripheral sensorimotor neuropathy with bulbar dysfunction and facial weakness following mild COVID infection. Examination revealed global areflexia and a broad-based ataxic gait. CSF analysis revealed albuminocytological dissociation and neurophysiological testing later supported the diagnosis. The patient required high flow nasal oxygen therapy for respiratory dysfunction in a level 2 care setting and received immunological treatment with intravenous immunoglobulins.We conclude that Miller–Fisher syndrome needs to be considered in patients presenting with new sensorimotor dysfunction following SARS-COV-2 infection. Early recognition is key given the propensity to cause life-threatening respiratory failure, and early administration of immunological treatment is associated with improved prognosis.     

Self-organized control of bipedal locomotion by neural oscillators in unpredictable environment

A new principle of sensorimotor control of legged locomotion in an unpredictable environment is proposed on the basis of neurophysiological knowledge and a theory of nonlinear dynamics. Stable and flexible locomotion is realized as a global limit cycle generated by a global entrainment between the rhythmic activities of a nervous system composed of coupled neural oscillators and the rhythmic movements of a musculo-skeletal system including interaction with its environment. Coordinated movements are generated not by slaving to an explicit representation of the precise trajectories of the movement of each part but by dynamic interactions among the nervous system, the musculo-skeletal system and the environment. The performance of a bipedal model based on the above principle was investigated by computer simulation. Walking movements stable to mechanical perturbations and to environmental changes were obtained. Moreover, the model generated not only the walking movement but also the running movement by changing a single parameter nonspecific to the movement. The transitions between the gait patterns occurred with hysteresis.     

Simulating Discrete and Rhythmic Multi-joint Human Arm Movements by Optimization of Nonlinear Performance Indices

An optimization approach applied to mechanical linkage models is used to simulate human arm movements. Predicted arm trajectories are the result of minimizing a nonlinear performance index that depends on kinematic or dynamic variables of the movement. A robust optimization algorithm is presented that computes trajectories which satisfy the necessary conditions with high accuracy. It is especially adapted to the analysis of discrete and rhythmic movements. The optimization problem is solved by parameterizing each generalized coordinate (e.g., joint angular displacement) in terms of Jacobi polynomials and Fourier series, depending on whether discrete or rhythmic movements are considered, combined with a multiple shooting algorithm. The parameterization of coordinates has two advantages. First, it provides an initial guess for the multiple shooting algorithm which solves the optimization problem with high accuracy. Second, it leads to a low dimensional representation of discrete and rhythmic movements in terms of expansion coefficients. The selection of a suitable feature space is an important prerequisite for comparison, recognition and classification of movements. In addition, the separate computational analysis of discrete and rhythmic movements is motivated by their distinct neurophysiological realizations in the cortex. By investigating different performance indices subject to different boundary conditions, the approach can be used to examine possible strategies that humans adopt in selecting specific arm motions for the performance of different tasks in a plane and in three-dimensional space.     

Modulation of brain activity during action observation: influence of perspective, transitivity and meaningfulness

The coupling process between observed and performed actions is thought to be performed by a fronto-parietal perception-action system including regions of the inferior frontal gyrus and the inferior parietal lobule. When investigating the influence of the movements' characteristics on this process, most research on action observation has focused on only one particular variable even though the type of movements we observe can vary on several levels. By manipulating the visual perspective, transitivity and meaningfulness of observed movements in a functional magnetic resonance imaging study we aimed at investigating how the type of movements and the visual perspective can modulate brain activity during action observation in healthy individuals. Importantly, we used an active observation task where participants had to subsequently execute or imagine the observed movements. Our results show that the fronto-parietal regions of the perception action system were mostly recruited during the observation of meaningless actions while visual perspective had little influence on the activity within the perception-action system. Simultaneous investigation of several sources of modulation during active action observation is probably an approach that could lead to a greater ecological comprehension of this important sensorimotor process.     

Modulation of Arm Reaching Movements during Processing of Arm/Hand-Related Action Verbs with and without Emotional Connotation

The theory of embodied language states that language comprehension relies on an internal reenactment of the sensorimotor experience associated with the processed word or sentence. Most evidence in support of this hypothesis had been collected using linguistic material without any emotional connotation. For instance, it had been shown that processing of arm-related verbs, but not of those leg-related verbs, affects the planning and execution of reaching movements; however, at present it is unknown whether this effect is further modulated by verbs evoking an emotional experience. Showing such a modulation might shed light on a very debated issue, i.e. the way in which the emotional meaning of a word is processed. To this end, we assessed whether processing arm/hand-related verbs describing actions with negative connotations (e.g. to stab) affects reaching movements differently from arm/hand-related verbs describing actions with neutral connotation (e.g. to comb). We exploited a go/no-go paradigm in which healthy participants were required to perform arm-reaching movements toward a target when verbs expressing emotional hand actions, neutral hand actions or foot actions were shown, and to refrain from moving when no-effector-related verbs were presented. Reaction times and percentages of errors increased when the verb involved the same effector as used to give the response. However, we also found that the size of this interference decreased when the arm/hand-related verbs had a negative emotional connotation. Crucially, we show that such modulation only occurred when the verb semantics had to be retrieved. These results suggest that the comprehension of negatively valenced verbs might require the simultaneous reenactment of the neural circuitry associated with the processing of the emotion evoked by their meaning and of the neural circuitry associated with their motor features.     

Corticosteroid actions from neuronal membrane to behavior: neurophysiological mechanisms underlying rapid behavioral effects of corticosterone.

Investigation of the rapid suppression of male courtship clasping behavior by corticosterone in roughskin newts (Taricha granulosa) has led to the identification of a specific neuronal membrane receptor for this stress steroid. This paper describes studies of the neurophysiological effects of the rapid, membrane receptor mediated action of corticosterone on neurons that are involved in the control of clasping. In freely behaving newts, medullary neurons, including reticulospinal neurons, process clasp-triggering sensory signals and participate in control of clasping movements. Corticosterone injection causes these brainstem neurons to show selective depression of clasping-related sensorimotor function. These corticosterone effects appear in 3-10 min and are closely associated with the simultaneous depression of clasping. In addition to these functionally specific effects, corticosterone simultaneously causes widespread, primarily depressive effects on neuronal activity and excitability in the medulla and elsewhere in the brain. Thus, the membrane actions of corticosterone lead to diverse neural effects, including changes in membrane excitability as well as specific, network-level actions that are apparent only during behavior. These rapid corticosterone effects strongly interact with actions of the neuropeptides vasotocin and corticotropin-releasing factor, such that the form and magnitude of the steroid's effects depend on the prevailing neuroendocrine state of the brain.     

Sensorimotor experience influences recovery of forelimb abilities but not tissue loss after focal cortical compression in adult rats

Sensorimotor activity has been shown to play a key role in functional outcome after extensive brain damage. This study was aimed at assessing the influence of sensorimotor experience through subject-environment interactions on the time course of both lesion and gliosis volumes as well as on the recovery of forelimb sensorimotor abilities following focal cortical injury. The lesion consisted of a cortical compression targeting the forepaw representational area within the primary somatosensory cortex of adult rats. After the cortical lesion, rats were randomly subjected to various postlesion conditions: unilateral C5-C6 dorsal root transection depriving the contralateral cortex from forepaw somatosensory inputs, standard housing or an enriched environment promoting sensorimotor experience and social interactions. Behavioral tests were used to assess forelimb placement during locomotion, forelimb-use asymmetry, and forepaw tactile sensitivity. For each group, the time course of tissue loss was described and the gliosis volume over the first postoperative month was evaluated using an unbiased stereological method. Consistent with previous studies, recovery of behavioral abilities was found to depend on post-injury experience. Indeed, increased sensorimotor activity initiated early in an enriched environment induced a rapid and more complete behavioral recovery compared with standard housing. In contrast, severe deprivation of peripheral sensory inputs led to a delayed and only partial sensorimotor recovery. The dorsal rhizotomy was found to increase the perilesional gliosis in comparison to standard or enriched environments. These findings provide further evidence that early sensory experience has a beneficial influence on the onset and time course of functional recovery after focal brain injury.     

Broadband Criticality of Human Brain Network Synchronization

Self-organized criticality is an attractive model for human brain dynamics, but there has been little direct evidence for its existence in large-scale systems measured by neuroimaging. In general, critical systems are associated with fractal or power law scaling, long-range correlations in space and time, and rapid reconfiguration in response to external inputs. Here, we consider two measures of phase synchronization: the phase-lock interval, or duration of coupling between a pair of (neurophysiological) processes, and the lability of global synchronization of a (brain functional) network. Using computational simulations of two mechanistically distinct systems displaying complex dynamics, the Ising model and the Kuramoto model, we show that both synchronization metrics have power law probability distributions specifically when these systems are in a critical state. We then demonstrate power law scaling of both pairwise and global synchronization metrics in functional MRI and magnetoencephalographic data recorded from normal volunteers under resting conditions. These results strongly suggest that human brain functional systems exist in an endogenous state of dynamical criticality, characterized by a greater than random probability of both prolonged periods of phase-locking and occurrence of large rapid changes in the state of global synchronization, analogous to the neuronal “avalanches” previously described in cellular systems. Moreover, evidence for critical dynamics was identified consistently in neurophysiological systems operating at frequency intervals ranging from 0.05–0.11 to 62.5–125 Hz, confirming that criticality is a property of human brain functional network organization at all frequency intervals in the brain's physiological bandwidth.     

Characterisation of whisker control in the California sea lion (Zalophus californianus) during a complex,dynamic sensorimotor task

Studies in pinniped whisker use have shown that their whiskers are extremely sensitive to tactile and hydrodynamic signals. While pinnipeds position their whiskers on to objects and have some control over their whisker protractions, it has always been thought that head movements are more responsible for whisker positioning than the movement of the whiskers themselves. This study uses ball balancing, a dynamic sensorimotor skill that is often used in human and robotic coordination studies, to promote sea lion whisker movements during the task. For the first time, using tracked video footage, we show that sea lion whisker movements respond quickly (26.70 ms) and mirror the movement of the ball, much more so than the head. We show that whisker asymmetry and spread are both altered to help sense and control the ball during balancing. We believe that by designing more dynamic sensorimotor tasks we can start to characterise the active nature of this specialised sensory system in pinnipeds.     

Conditioned Whisking in the Rat

The rat's mystacial vibrissae are active during exploratory and discriminative behaviors, with individual vibrissae serving as elements in a receptive array scanned across object surfaces. To facilitate neurobehavioral analysis of this sensorimotor system, we have developed an experimental paradigm that confines vibrissa movements to a defined physical location, makes possible on-line monitoring of “whisking” activity, and brings such activity under associative control using operant conditioning procedures. Rats were secured, and movements of an identified bilaterally homologous pair of vibrissae (right and left gamma straddlers) were detected by laser-based photodetectors. Subjects were maintained on a water deprivation schedule, and whisker movements were monitored during adaptation to the test situation and after the clipping of other vibrissae on both sides of the snout. Rats were reinforced with water delivery for emitting vibrissa movements in the presence of a conditioned stimulus (tone) whose presentation was made contingent upon a prior period of nonwhisking. The rate and temporal distribution of vibrissa movements were brought under experimental control by means of interval and ratio reinforcement schedules. Although the procedures provide minimal information about the kinematics or topography of conditioned vibrissa movements, they permit the investigator to manipulate response parameters normally under the voluntary control of the animal in a preparation amenable to neurophysiological analysis     

Deriving theoretical phase locking values of a coupled cortico-thalamic neural mass model using center manifold reduction

Cognitive functions such as sensory processing and memory processes lead to phase synchronization in the electroencephalogram or local field potential between different brain regions. There are a lot of computational researches deriving phase locking values (PLVs), which are an index of phase synchronization intensity, from neural models. However, these researches derive PLVs numerically. To the best of our knowledge, there have been no reports on the derivation of a theoretical PLV. In this study, we propose an analytical method for deriving theoretical PLVs from a cortico-thalamic neural mass model described by a delay differential equation. First, the model for generating neural signals is transformed into a normal form of the Hopf bifurcation using center manifold reduction. Second, the normal form is transformed into a phase model that is suitable for analyzing synchronization phenomena. Third, the Fokker–Planck equation of the phase model is derived and the phase difference distribution is obtained. Finally, the PLVs are calculated from the stationary distribution of the phase difference. The validity of the proposed method is confirmed via numerical simulations. Furthermore, we apply the proposed method to a working memory process, and discuss the neurophysiological basis behind the phase synchronization phenomenon. The results demonstrate the importance of decreasing the intensity of independent noise during the working memory process. The proposed method will be of great use in various experimental studies and simulations relevant to phase synchronization, because it enables the effect of neurophysiological changes on PLVs to be analyzed from a mathematical perspective.     

Just follow your nose: homing by olfactory cues in ants

How is an ant-equipped with a brain that barely exceeds the size of a pinhead-capable of achieving navigational marvels? Even though evidences suggest that navigation is a multimodal process, ants heavily depend on olfactory cues-of pheromonal and non-pheromonal nature-for foraging and orientation. Recent studies have directed their attention to the efficiency of pheromone trail networks. Advances in neurophysiological techniques make it possible to investigate trail pheromone processing in the ant's brain. In addition to relying on pheromone odours, ants also make use of volatiles emanating from the nest surroundings. Deposited in the vicinity of the nest, these home-range markings help the ants to home after a foraging run. Furthermore, olfactory landmarks associated with the nest enhance ants' homing abilities.     

Proprioceptive Feedback and Brain Computer Interface (BCI) Based Neuroprostheses

Brain computer interface (BCI) technology has been proposed for motor neurorehabilitation, motor replacement and assistive technologies. It is an open question whether proprioceptive feedback affects the regulation of brain oscillations and therefore BCI control. We developed a BCI coupled on-line with a robotic hand exoskeleton for flexing and extending the fingers. 24 healthy participants performed five different tasks of closing and opening the hand: (1) motor imagery of the hand movement without any overt movement and without feedback, (2) motor imagery with movement as online feedback (participants see and feel their hand, with the exoskeleton moving according to their brain signals, (3) passive (the orthosis passively opens and closes the hand without imagery) and (4) active (overt) movement of the hand and rest. Performance was defined as the difference in power of the sensorimotor rhythm during motor task and rest and calculated offline for different tasks. Participants were divided in three groups depending on the feedback receiving during task 2 (the other tasks were the same for all participants). Group 1 (n = 9) received contingent positive feedback (participants'' sensorimotor rhythm (SMR) desynchronization was directly linked to hand orthosis movements), group 2 (n = 8) contingent “negative” feedback (participants'' sensorimotor rhythm synchronization was directly linked to hand orthosis movements) and group 3 (n = 7) sham feedback (no link between brain oscillations and orthosis movements). We observed that proprioceptive feedback (feeling and seeing hand movements) improved BCI performance significantly. Furthermore, in the contingent positive group only a significant motor learning effect was observed enhancing SMR desynchronization during motor imagery without feedback in time. Furthermore, we observed a significantly stronger SMR desynchronization in the contingent positive group compared to the other groups during active and passive movements. To summarize, we demonstrated that the use of contingent positive proprioceptive feedback BCI enhanced SMR desynchronization during motor tasks.     

Coarse Electrocorticographic Decoding of Ipsilateral Reach in Patients with Brain Lesions

In patients with unilateral upper limb paralysis from strokes and other brain lesions, strategies for functional recovery may eventually include brain-machine interfaces (BMIs) using control signals from residual sensorimotor systems in the damaged hemisphere. When voluntary movements of the contralateral limb are not possible due to brain pathology, initial training of such a BMI may require use of the unaffected ipsilateral limb. We conducted an offline investigation of the feasibility of decoding ipsilateral upper limb movements from electrocorticographic (ECoG) recordings in three patients with different lesions of sensorimotor systems associated with upper limb control. We found that the first principal component (PC) of unconstrained, naturalistic reaching movements of the upper limb could be decoded from ipsilateral ECoG using a linear model. ECoG signal features yielding the best decoding accuracy were different across subjects. Performance saturated with very few input features. Decoding performances of 0.77, 0.73, and 0.66 (median Pearson''s r between the predicted and actual first PC of movement using nine signal features) were achieved in the three subjects. The performance achieved here with small numbers of electrodes and computationally simple decoding algorithms suggests that it may be possible to control a BMI using ECoG recorded from damaged sensorimotor brain systems.     

Murine succinate semialdehyde dehydrogenase (SSADH) deficiency, a heritable disorder of GABA metabolism with epileptic phenotype

Murine models of inborn errors of metabolism represent an established approach for investigating pathophysiological mechanisms associated with the corresponding human disorder. Our laboratory studies human inherited defects of GABA synthesis and degradation. One of these, succinate semialdehyde dehydrogenase (SSADH) deficiency (or gamma-hydroxybutyric aciduria; OMIM 271980; E.C. 1.2.1.24), has recently been modeled via gene targeting in the mouse. SSADH-/- mice succumb to early lethality in status epilepticus at postnatal (PN) days 20 - 26. Numerous metabolic, neurochemical and neurophysiological abnormalities have been documented using in vitro and in vivo approaches, substantially altering our thoughts about the complexity of the corresponding human condition. Moreover, novel preclinical treatment paradigms have been developed through drug trials in gene-ablated animals. The greatest utility of this animal, however, may reside in its transition from early absence seizures to generalized convulsions and eventual status epilepticus. Accurate neurochemical assessment during this transition may provide clues to the same transition process in patients, for which the underlying mechanisms remain undefined.     

Simultaneous Brain–Cervical Cord fMRI Reveals Intrinsic Spinal Cord Plasticity during Motor Sequence Learning

The spinal cord participates in the execution of skilled movements by translating high-level cerebral motor representations into musculotopic commands. Yet, the extent to which motor skill acquisition relies on intrinsic spinal cord processes remains unknown. To date, attempts to address this question were limited by difficulties in separating spinal local effects from supraspinal influences through traditional electrophysiological and neuroimaging methods. Here, for the first time, we provide evidence for local learning-induced plasticity in intact human spinal cord through simultaneous functional magnetic resonance imaging of the brain and spinal cord during motor sequence learning. Specifically, we show learning-related modulation of activity in the C6–C8 spinal region, which is independent from that of related supraspinal sensorimotor structures. Moreover, a brain–spinal cord functional connectivity analysis demonstrates that the initial linear relationship between the spinal cord and sensorimotor cortex gradually fades away over the course of motor sequence learning, while the connectivity between spinal activity and cerebellum gains strength. These data suggest that the spinal cord not only constitutes an active functional component of the human motor learning network but also contributes distinctively from the brain to the learning process. The present findings open new avenues for rehabilitation of patients with spinal cord injuries, as they demonstrate that this part of the central nervous system is much more plastic than assumed before. Yet, the neurophysiological mechanisms underlying this intrinsic functional plasticity in the spinal cord warrant further investigations.     

Electrophysiological correlates of action observation treatment in children with cerebral palsy: A pilot study

Action Observation Treatment (AOT) has been shown to be effective in the functional recovery of several clinical populations. However, little is known about the neural underpinnings of the clinical efficacy of AOT in children with Cerebral Palsy (CP). Using electroencephalography (EEG), we recorded µ rhythm desynchronization as an index of sensorimotor cortex modulation during a passive action observation task before and after AOT. The relationship between sensorimotor modulation and clinical outcomes was also assessed. Eight children with CP entered the present randomized controlled crossover pilot study in which the experimental AOT preceded or followed a control Videogame Observation Treatment (VOT). Results provide further evidence of the clinical efficacy of AOT for improving hand motor function in CP, as assessed with the Assisting Hand Assessment (AHA) and Melbourne Assessment of Unilateral Upper Limb Function Scale (MUUL). The novel finding is that AOT increases µ rhythm desynchronization at scalp locations corresponding to the hand representation areas. This effect is associated to functional improvement assessed with the MUUL. These preliminary findings, although referred to as a small sample, suggest that AOT may affect upper limb motor recovery in children with CP and modulate the activation of sensorimotor areas, offering a potential neurophysiological correlate to support the clinical utility of AOT.     

Visual Feedback Dominates the Sense of Agency for Brain-Machine Actions

Recent advances in neuroscience and engineering have led to the development of technologies that permit the control of external devices through real-time decoding of brain activity (brain-machine interfaces; BMI). Though the feeling of controlling bodily movements (sense of agency; SOA) has been well studied and a number of well-defined sensorimotor and cognitive mechanisms have been put forth, very little is known about the SOA for BMI-actions. Using an on-line BMI, and verifying that our subjects achieved a reasonable level of control, we sought to describe the SOA for BMI-mediated actions. Our results demonstrate that discrepancies between decoded neural activity and its resultant real-time sensory feedback are associated with a decrease in the SOA, similar to SOA mechanisms proposed for bodily actions. However, if the feedback discrepancy serves to correct a poorly controlled BMI-action, then the SOA can be high and can increase with increasing discrepancy, demonstrating the dominance of visual feedback on the SOA. Taken together, our results suggest that bodily and BMI-actions rely on common mechanisms of sensorimotor integration for agency judgments, but that visual feedback dominates the SOA in the absence of overt bodily movements or proprioceptive feedback, however erroneous the visual feedback may be.     

Reading “Sun” and Looking Up: The Influence of Language on Saccadic Eye Movements in the Vertical Dimension

Traditionally, language processing has been attributed to a separate system in the brain, which supposedly works in an abstract propositional manner. However, there is increasing evidence suggesting that language processing is strongly interrelated with sensorimotor processing. Evidence for such an interrelation is typically drawn from interactions between language and perception or action. In the current study, the effect of words that refer to entities in the world with a typical location (e.g., sun, worm) on the planning of saccadic eye movements was investigated. Participants had to perform a lexical decision task on visually presented words and non-words. They responded by moving their eyes to a target in an upper (lower) screen position for a word (non-word) or vice versa. Eye movements were faster to locations compatible with the word''s referent in the real world. These results provide evidence for the importance of linguistic stimuli in directing eye movements, even if the words do not directly transfer directional information.