Dopamine improves defective cortical and muscular connectivity during bilateral control of gait in Parkinson's disease.

Parkinson's Disease (PD)-typical declines in gait coordination are possibly explained by weakness in bilateral cortical and muscular connectivity. Here, we seek to determine whether this weakness and consequent decline in gait coordination is affected by dopamine levels. To this end, we compare cortico-cortical, cortico-muscular, and intermuscular connectivity and gait outcomes between body sides in people with PD under ON and OFF medication states, and in older adults. In our study, participants walked back and forth along a 12 m corridor. Gait events (heel strikes and toe-offs) and electrical cortical and muscular activities were measured and used to compute cortico-cortical, cortico-muscular, and intermuscular connectivity (i.e., coherences in the alpha, beta, and gamma bands), as well as features characterizing gait performance (e.g., the step-timing coordination, length, and speed). We observe that people with PD, mainly during the OFF medication, walk with reduced step-timing coordination. Additionally, our results suggest that dopamine intake in PD increases the overall cortico-muscular connectivity during the stance and swing phases of gait. We thus conclude that dopamine corrects defective feedback caused by impaired sensory-information processing and sensory-motor integration, thus increasing cortico-muscular coherences in the alpha bands and improving gait.

Human arm redundancy: a new approach for the inverse kinematics problem.

The inverse kinematics (IK) problem addresses how both humans and robotic systems coordinate movement to resolve redundancy, as in the case of arm reaching where more degrees of freedom are available at the joint versus hand level. This work focuses on which coordinate frames best represent human movements, enabling the motor system to solve the IK problem in the presence of kinematic redundancies. We used a multi-dimensional sparse source separation method to derive sets of basis (or source) functions for both the task and joint spaces, with joint space represented by either absolute or anatomical joint angles. We assessed the similarities between joint and task sources in each of these joint representations, finding that the time-dependent profiles of the absolute reference frame's sources show greater similarity to corresponding sources in the task space. This result was found to be statistically significant. Our analysis suggests that the nervous system represents multi-joint arm movements using a limited number of basis functions, allowing for simple transformations between task and joint spaces. Additionally, joint space seems to be represented in an absolute reference frame to simplify the IK transformations, given redundancies. Further studies will assess this finding's generalizability and implications for neural control of movement.

Biomechanics, motor control and dynamic models of the soft limbs of the octopus and other cephalopods.

Muscular hydrostats are organs composed entirely of packed arrays of incompressible muscles and lacking any skeletal support. Found in both vertebrates and invertebrates, they are of great interest for comparative biomechanics from engineering and evolutionary perspectives. The arms of cephalopods (e.g. octopus and squid) are particularly interesting muscular hydrostats because of their flexibility and ability to generate complex behaviors exploiting elaborate nervous systems. Several lines of evidence from octopus studies point to the use of both brain and arm-embedded motor control strategies that have evolved to simplify the complexities associated with the control of flexible and hyper-redundant limbs and bodies. Here, we review earlier and more recent experimental studies on octopus arm biomechanics and neural motor control. We review several dynamic models used to predict the kinematic characteristics of several basic motion primitives, noting the shortcomings of the current models in accounting for behavioral observations. We also discuss the significance of impedance (stiffness and viscosity) in controlling the octopus's motor behavior. These factors are considered in light of several new models of muscle biomechanics that could be used in future research to gain a better understanding of motor control in the octopus. There is also a need for updated models that encompass stiffness and viscosity for designing and controlling soft robotic arms. The field of soft robotics has boomed over the past 15 years and would benefit significantly from further progress in biomechanical and motor control studies on octopus and other muscular hydrostats.

Does the Cerebellum Implement or Select Geometries? A Speculative Note.

During evolution, living systems, actively interacting with their environment, developed the ability, through sensorimotor contingencies, to construct functional spaces shaping their perception and their movements. These geometries were modularly embedded in specific functional neuro-architectures. In particular, human movements were shown to obey several empirical laws, such as the 2/3 power law, isochrony, or jerk minimization principles, which constrain and adapt motor planning and execution. Outstandingly, such laws can be deduced from a combination of Euclidean, affine, and equi-affine geometries, whose neural correlates have been partly detected in several brain areas including the cerebellum and the basal ganglia. Reviving Pellionisz and Llinas general hypothesis regarding the cerebrum and the cerebellum as geometric machines, we speculate that the cerebellum should be involved in implementing and/or selecting task-specific geometries for motor and cognitive skills. More precisely, the cerebellum is assumed to compute forward internal models to help specific cortical and subcortical regions to select appropriate geometries among, at least, Euclidean and affine geometries. We emphasize that the geometrical role of the cerebellum deserves a renewal of interest, which may provide a better understanding of its specific contributions to motor and associative (cognitive) functions.

A Whole-Body Sensory-Motor Gradient is Revealed in the Medial Wall of the Parietal Lobe.

In 1954, Penfield and Jasper's findings based on electric stimulation of epileptic patients led them to hypothesize that a sensory representation of the body should be found in the precuneus. They termed this representation the "supplementary sensory" area and emphasized that the exact form of this homunculus could not be specified on the basis of their results. In the decades that followed, their prediction was neglected. The precuneus was found to be involved in numerous motor, cognitive and visual processes, but no work was done on its somatotopic organization. Here, we used a periodic experimental design in which 16 human subjects (eight women) moved 20 body parts to investigate the possible body part topography of the precuneus. We found an anterior-to-posterior, dorsal-to-ventral, toes-to-tongue gradient in a mirror orientation to the SMA. When inspecting body-part-specific functional connectivity, we found differential connectivity patterns for the different body parts to the primary and secondary motor areas and parietal and visual areas, and a shared connectivity to the extrastriate body area, another topographically organized area. We suggest that a whole-body gradient can be found in the precuneus and is connected to multiple brain areas with different connectivity for different body parts. Its exact role and relations to the other known functions of the precuneus such as self-processing, motor imagery, reaching, visuomotor and other body-mind functions should be investigated.SIGNIFICANCE STATEMENT Using fMRI, as well as sensitive spectral analysis, we found a new homunculus in the precuneus: an anterior-to-posterior, dorsal-to-ventral, toes-to-tongue somatotopic gradient in a mirror orientation to the SMA. When inspecting body-part-specific functional connectivity, we found differential connectivity patterns for the different body parts to the primary and secondary motor areas, parietal and visual areas, and a shared connectivity to the extrastriate body area, another topographically organized area. We suggest that a whole-body gradient can be found in the precuneus and is connected to multiple brain areas in a body-part-specific manner.

Emergence of behavior through morphology: a case study on an octopus inspired manipulator.

The complex motion abilities of the Octopus vulgaris have been an intriguing research topic for biologists and roboticists alike. Various studies have been conducted on the underlying control architectures employed by these high dimensional biological organisms. Researchers have attempted to replicate these architectures on robotic systems. Contrary to previous approaches, this study focuses on a robotic system, which is only morphologically similar to the Octopus vulgaris, and how it would behave under different control policies. This sheds light on the underlying optimality principles that these biological systems employ. Open loop control policies are obtained through a trajectory optimization method on a learned forward dynamic model. The motion patterns emerging from variations in morphology and environment were then derived to study the role of the body and environment. Results show that for the specific case of dynamic reaching with a soft appendage, the invariance in motion profile is a fundamental constraint imposed by the morphology and environment, independent from the controller. This suggests how morphological design can simplify stable control even for highly dimensional nonlinear dynamical systems and can provide insights into design of new soft robotic mechanisms.

Movement Decomposition in the Primary Motor Cortex.

A complex action can be described as the composition of a set of elementary movements. While both kinematic and dynamic elements have been proposed to compose complex actions, the structure of movement decomposition and its neural representation remain unknown. Here, we examined movement decomposition by modeling the temporal dynamics of neural populations in the primary motor cortex of macaque monkeys performing forelimb reaching movements. Using a hidden Markov model, we found that global transitions in the neural population activity are associated with a consistent segmentation of the behavioral output into acceleration and deceleration epochs with directional selectivity. Single cells exhibited modulation of firing rates between the kinematic epochs, with abrupt changes in spiking activity timed with the identified transitions. These results reveal distinct encoding of acceleration and deceleration phases at the level of M1, and point to a specific pattern of movement decomposition that arises from the underlying neural activity. A similar approach can be used to probe the structure of movement decomposition in different brain regions, possibly controlling different temporal scales, to reveal the hierarchical structure of movement composition.

Intersegmental coordination patterns are differently affected in Parkinson's disease and cerebellar ataxia.

The law of intersegmental coordination (Borghese et al. 1996) may be altered in pathological conditions. Here we investigated the contribution of the basal ganglia (BG) and the cerebellum to lower limb intersegmental coordination by inspecting the plane's orientation and other parameters pertinent to this law in patients with idiopathic Parkinson's disease (PD) or cerebellar ataxia (CA). We also applied a mathematical model that successfully accounts for the intersegmental law of coordination observed in control subjects (Barliya et al. 2009). In the present study, we compared the planarity index (PI), covariation plane (CVP) orientation, and CVP orientation predicted by the model in 11 PD patients, 8 CA patients, and two groups of healthy subjects matched for age, height, weight, and gender to each patient group (Ctrl_PD and Ctrl_CA). Controls were instructed to alter their gait speed to match those of their respective patient group. PD patients were examined after overnight withdrawal of anti-parkinsonian medications (PD-off-med) and then on medication (PD-on-med). PI was above 96% in all gait conditions in all groups suggesting that the law of intersegmental coordination is preserved in both BG and cerebellar pathology. However, the measured and predicted CVP orientations rotated in PD-on-med and PD-off-med compared with Ctrl_PD and in CA vs. Ctrl_CA. These rotations caused by PD and CA were in opposite directions suggesting differences in the roles of the BG and cerebellum in intersegmental coordination during human locomotion. NEW & NOTEWORTHY Kinematic and muscular synergies may have a role in overcoming motor redundancies, which may be reflected in intersegmental covariation. Basal ganglia and cerebellar networks were suggested to be involved in crafting and modulating synergies. We thus compared intersegmental coordination in Parkinson's disease and cerebellar disease patients and found opposite effects in some aspects. Further research integrating muscle activities as well as biomechanical and neural control modeling are needed to account for these findings.

Motion cues modulate responses to emotion in movies.

Film theorists and practitioners suggest that motion can be manipulated in movie scenes to elicit emotional responses in viewers. However, our understanding of the role of motion in emotion perception remains limited. On the one hand, movies continuously depict local motion- movements of objects and humans, which are crucial for generating emotional responses. Movie scenes also frequently portray global motion, mainly induced by large camera movements, global motion being yet another source of information used by the brain during natural vision. Here we used functional MRI to elucidate the contributions of local and global motion to emotion perception during movie viewing. Subjects observed long (1 min) movie segments depicting emotional or neutral content. Brain activity in areas that showed preferential responses to emotional content was strongly linked over time with frame-wide variations in global motion, and to a lesser extent with local motion information. Similarly, stronger responses to emotional content were recorded within regions of interest whose activity was attuned to global and local motion over time. Since global motion fields are experienced during self-motion, we suggest that camera movements may induce illusory self-motion cues in viewers that interact with the movie's narrative and with other emotional cues in generating affective responses.

The speed-curvature power law of movements: a reappraisal.

Several types of curvilinear movements obey approximately the so called 2/3 power law, according to which the angular speed varies proportionally to the 2/3 power of the curvature. The origin of the law is debated but it is generally thought to depend on physiological mechanisms. However, a recent paper (Marken and Shaffer, Exp Brain Res 88:685-690, 2017) claims that this power law is simply a statistical artifact, being a mathematical consequence of the way speed and curvature are calculated. Here we reject this hypothesis by showing that the speed-curvature power law of biological movements is non-trivial. First, we confirm that the power exponent varies with the shape of human drawing movements and with environmental factors. Second, we report experimental data from Drosophila larvae demonstrating that the power law does not depend on how curvature is calculated. Third, we prove that the law can be violated by means of several mathematical and physical examples. Finally, we discuss biological constraints that may underlie speed-curvature power laws discovered in empirical studies.

The Effects of Reducing Preparation Time on the Execution of Intentionally Curved Trajectories: Optimization and Geometrical Analysis.

When subjects are intentionally preparing a curved trajectory, they are engaged in a time-consuming trajectory planning process that is separate from target selection. To investigate the construction of such a plan, we examined the effect of artificially shortening preparation time on the performance of intentionally curved trajectories using the Timed Response task that enforces initiation of movements prematurely. Fifteen subjects performed obstacle avoidance movements toward one of four targets that were presented 25 or 350 ms before the "go" signal, imposing short and long preparation time conditions with mean values of 170 ms and 493 ms, respectively. While trajectories with short preparation times showed target specificity at their onset, they were significantly more variable and showed larger angular deviations from the lines connecting their initial position and the target, compared to the trajectories with long preparation times. Importantly, the trajectories of the short preparation time movements still reached their end-point targets accurately, with comparable movement durations. We hypothesize that success in the short preparation time condition is a result of an online control mechanism that allows further refinement of the plan during its execution and study this control mechanism with a novel trajectory analysis approach using minimum jerk optimization and geometrical modeling approaches. Results show a later agreement of the short preparation time trajectories with the optimal minimum jerk trajectory, accompanied by a later initiation of a parabolic segment. Both observations are consistent with the existence of an online trajectory planning process.Our results suggest that when preparation time is not sufficiently long, subjects execute a more variable and less optimally prepared initial trajectory and exploit online control mechanisms to refine their actions on the fly.

Cortical circuits and modules in movement generation: experiments and theories.

Here we review recent studies of the cortical circuits subserving the control of posture and movement. This topic is addressed from neurophysiological and evolutionary perspectives describing recent advancements achieved through experimental studies in humans and non-human primates. We also describe current debates and controversies concerning motor mapping within the motor cortex and the different computational approaches aimed at resolving the mystery around motor representations and computations. In recent years there is growing interest in the possibly modular organization of motor representations and dynamical processes and the potential of such studies to provide new clues into motor information processing. Hence this review focuses on motor modularity, highlighting the new research directions inspired by empirical findings and theoretical models developed within the last several years.

Micrographia, much beyond the writer's hand.

INTRODUCTION: This review on micrographia aims to draw the clinician's attention to non-Parkinsonian etiologies, provide clues to differential diagnosis, and summarize current knowledge on the phenomenology, etiology, and mechanisms underlying micrographia. METHODS: A systematic review of the existing literature was performed. RESULTS: Micrographia, namely small sized handwriting has long been attributed to Parkinson's disease. However, it has often been observed as part of the clinical picture of additional neurodegenerative disorders, sometimes antedating the motor signs, or following focal basal ganglia lesions without any accompanying parkinsonism, suggesting that bradykinesia and rigidity are not sine-qua-non for the development of this phenomenon. Therefore, micrographia in a patient with no signs of parkinsonism may prompt the clinician to perform imaging in order to exclude a focal basal ganglia lesion. Dopaminergic etiology in this and other cases is doubtful, since levodopa ameliorates letter stroke size only partially, and only in some patients. Parkinsonian handwriting is often characterized by lack of fluency, slowness, and less frequently by micrographia. Deviations from kinematic laws of motion that govern normal movement, including the lack of movement smoothness and inability to scale movement amplitude to the desired size, may reflect impairments in motion planning, possible loss of automaticity and reduced movement vigor. CONCLUSIONS: The etiology, neuroanatomy, mechanisms and models of micrographia are discussed. Dysfunction of the basal ganglia circuitry induced by neurodegeneration or disruption by focal damage give rise to micrographia.

The Default Mode Network Differentiates Biological From Non-Biological Motion.

The default mode network (DMN) has been implicated in an array of social-cognitive functions, including self-referential processing, theory of mind, and mentalizing. Yet, the properties of the external stimuli that elicit DMN activity in relation to these domains remain unknown. Previous studies suggested that motion kinematics is utilized by the brain for social-cognitive processing. Here, we used functional MRI to examine whether the DMN is sensitive to parametric manipulations of observed motion kinematics. Preferential responses within core DMN structures differentiating non-biological from biological kinematics were observed for the motion of a realistically looking, human-like avatar, but not for an abstract object devoid of human form. Differences in connectivity patterns during the observation of biological versus non-biological kinematics were additionally observed. Finally, the results additionally suggest that the DMN is coupled more strongly with key nodes in the action observation network, namely the STS and the SMA, when the observed motion depicts human rather than abstract form. These findings are the first to implicate the DMN in the perception of biological motion. They may reflect the type of information used by the DMN in social-cognitive processing.

Brain activity correlates with emotional perception induced by dynamic avatars.

An accurate judgment of the emotional state of others is a prerequisite for successful social interaction and hence survival. Thus, it is not surprising that we are highly skilled at recognizing the emotions of others. Here we aimed to examine the neuronal correlates of emotion recognition from gait. To this end we created highly controlled dynamic body-movement stimuli based on real human motion-capture data (Roether et al., 2009). These animated avatars displayed gait in four emotional (happy, angry, fearful, and sad) and speed-matched neutral styles. For each emotional gait and its equivalent neutral gait, avatars were displayed at five morphing levels between the two. Subjects underwent fMRI scanning while classifying the emotions and the emotional intensity levels expressed by the avatars. Our results revealed robust brain selectivity to emotional compared to neutral gait stimuli in brain regions which are involved in emotion and biological motion processing, such as the extrastriate body area (EBA), fusiform body area (FBA), superior temporal sulcus (STS), and the amygdala (AMG). Brain activity in the amygdala reflected emotional awareness: for visually identical stimuli it showed amplified stronger response when the stimulus was perceived as emotional. Notably, in avatars gradually morphed along an emotional expression axis there was a parametric correlation between amygdala activity and emotional intensity. This study extends the mapping of emotional decoding in the human brain to the domain of highly controlled dynamic biological motion. Our results highlight an extensive level of brain processing of emotional information related to body language, which relies mostly on body kinematics.

Stopping is not an option: the evolution of unstoppable motion elements (primitives).

Stopping performance is known to depend on low-level motion features, such as movement velocity. It is not known, however, whether it is also subject to high-level motion constraints. Here, we report results of 15 subjects instructed to connect four target points depicted on a digitizing tablet and stop "as rapidly as possible" upon hearing a "stop" cue (tone). Four subjects connected target points with straight paths, whereas 11 subjects generated movements corresponding to coarticulation between adjacent movement components. For the noncoarticulating and coarticulating subjects, stopping performance was not correlated or only weakly correlated with motion velocity, respectively. The generation of a straight, point-to-point movement or a smooth, curved trajectory was not disturbed by the occurrence of a stop cue. Overall, the results indicate that stopping performance is subject to high-level motion constraints, such as the completion of a geometrical plan, and that globally planned movements, once started, must run to completion, providing evidence for the definition of a motion primitive as an unstoppable motion element.

Arm coordination in octopus crawling involves unique motor control strategies.

To cope with the exceptional computational complexity that is involved in the control of its hyper-redundant arms [1], the octopus has adopted unique motor control strategies in which the central brain activates rather autonomous motor programs in the elaborated peripheral nervous system of the arms [2, 3]. How octopuses coordinate their eight long and flexible arms in locomotion is still unknown. Here, we present the first detailed kinematic analysis of octopus arm coordination in crawling. The results are surprising in several respects: (1) despite its bilaterally symmetrical body, the octopus can crawl in any direction relative to its body orientation; (2) body and crawling orientation are monotonically and independently controlled; and (3) contrasting known animal locomotion, octopus crawling lacks any apparent rhythmical patterns in limb coordination, suggesting a unique non-rhythmical output of the octopus central controller. We show that this uncommon maneuverability is derived from the radial symmetry of the arms around the body and the simple pushing-by-elongation mechanism by which the arms create the crawling thrust. These two together enable a mechanism whereby the central controller chooses in a moment-to-moment fashion which arms to recruit for pushing the body in an instantaneous direction. Our findings suggest that the soft molluscan body has affected in an embodied way [4, 5] the emergence of the adaptive motor behavior of the octopus.

New whole-body sensory-motor gradients revealed using phase-locked analysis and verified using multivoxel pattern analysis and functional connectivity.

Topographic organization is one of the main principles of organization in the human brain. Specifically, whole-brain topographic mapping using spectral analysis is responsible for one of the greatest advances in vision research. Thus, it is intriguing that although topography is a key feature also in the motor system, whole-body somatosensory-motor mapping using spectral analysis has not been conducted in humans outside M1/SMA. Here, using this method, we were able to map a homunculus in the globus pallidus, a key target area for deep brain stimulation, which has not been mapped noninvasively or in healthy subjects. The analysis clarifies contradictory and partial results regarding somatotopy in the caudal-cingulate zone and rostral-cingulate zone in the medial wall and in the putamen. Most of the results were confirmed at the single-subject level and were found to be compatible with results from animal studies. Using multivoxel pattern analysis, we could predict movements of individual body parts in these homunculi, thus confirming that they contain somatotopic information. Using functional connectivity, we demonstrate interhemispheric functional somatotopic connectivity of these homunculi, such that the somatotopy in one hemisphere could have been found given the connectivity pattern of the corresponding regions of interest in the other hemisphere. When inspecting the somatotopic and nonsomatotopic connectivity patterns, a similarity index indicated that the pattern of connected and nonconnected regions of interest across different homunculi is similar for different body parts and hemispheres. The results show that topographical gradients are even more widespread than previously assumed in the somatosensory-motor system. Spectral analysis can thus potentially serve as a gold standard for defining somatosensory-motor system areas for basic research and clinical applications.

Alpha and beta band event-related desynchronization reflects kinematic regularities.

The short-lasting attenuation of brain oscillations is termed event-related desynchronization (ERD). It is frequently found in the alpha and beta bands in humans during generation, observation, and imagery of movement and is considered to reflect cortical motor activity and action-perception coupling. The shared information driving ERD in all these motor-related behaviors is unknown. We investigated whether particular laws governing production and perception of curved movement may account for the attenuation of alpha and beta rhythms. Human movement appears to be governed by relatively few kinematic laws of motion. One dominant law in biological motion kinematics is the 2/3 power law (PL), which imposes a strong dependency of movement speed on curvature and is prominent in action-perception coupling. Here we directly examined whether the 2/3 PL elicits ERD during motion observation by characterizing the spatiotemporal signature of ERD. ERDs were measured while human subjects observed a cloud of dots moving along elliptical trajectories either complying with or violating the 2/3 PL. We found that ERD within both frequency bands was consistently stronger, arose faster, and was more widespread while observing motion obeying the 2/3 PL. An activity pattern showing clear 2/3 PL preference and lying within the alpha band was observed exclusively above central motor areas, whereas 2/3 PL preference in the beta band was observed in additional prefrontal-central cortical sites. Our findings reveal that compliance with the 2/3 PL is sufficient to elicit a selective ERD response in the human brain.