POPULATION DYNAMICS IN PRIMARY MOTOR CORTEX DURING COORDINATED REACH TO GRASP

Parkinson's disease patients may show a tremor that appears after a variable delay while the arms are kept outstretched (re-emergent tremor). The objectives of this study were to investigate re-emergent tremor pathophysiology by studying the role of the primary motor cortex in this tremor and making a comparison with rest tremor. We enrolled 10 Parkinson's disease patients with both re-emergent and rest tremor. Tremor was assessed by spectral analysis, corticomuscular coherence and tremor-resetting produced by transcranial magnetic stimulation over the primary motor cortex. We also recorded transcranial magnetic stimulation-evoked potentials generated by motor cortex stimulation during rest tremor, tremor suppression during wrist extension, and re-emergent tremor. Spectral analysis, corticomuscular coherence, and tremor resetting were compared between re-emergent tremor and rest tremor. Re-emergent tremor showed significant corticomuscular coherence, causal relation between motor cortex activity and tremor muscle and tremor resetting. The P60 component of transcranial magnetic stimulation-evoked potentials reduced in amplitude during tremor suppression, recovered before re-emergent tremor, was facilitated at re-emergent tremor onset, and returned to values similar to those of rest tremor during re-emergent tremor. Compared with rest tremor, re-emergent tremor showed similar corticomuscular coherence and tremor resetting, but slightly higher frequency. Re-emergent tremor is causally related with the activity of the primary motor cortex, which is likely a convergence node in the network that generates re-emergent tremor. Re-emergent tremor and rest tremor share common pathophysiological mechanisms in which the motor cortex plays a crucial role. © 2020 International Parkinson and Movement Disorder Society.

Effects of seat height on muscular pattern and interlimb coordination in cycling

Intraventricular Enzyme Replacement Improves Disease Phenotypes in a Mouse Model of Late Infantile Neuronal Ceroid Lipofuscinosis

Four electric field modeling methods of Dosing Prefrontal Transcranial Magnetic Stimulation (TMS): Introducing APEX MT dosimetry

The objective of this study was to investigate interhemispheric transcallosal connections between primary motor cortices noninvasively in awake human subjects. For this purpose, focal transcranial magnetic stimulation was performed on eight healthy, right-handed subjects and one patient with congenital collosal agenesis. Using two magnetic stimulators, we investigated the effect of a conditioning magnetic stimulus applied to the motor cortex of one hemisphere on the duration of the silent period (SP) evoked in the first dorsal interosseus (FDI) muscle by a magnetic test stimulus given over the opposite motor cortex. It is well established that SP reflects activation of inhibitory interneurons within primary motor cortex. In all normal subjects, a conditioning stimulus to one hemisphere produced a significant shortening of SP evoked by the test stimulus when the conditioning-test-interval was 10-20 ms. The effect was also observed when an electrical test stimulus was used. The conditioning coil had to be placed over the hand motor area to obtain the maximal effect. The threshold for eliciting this decrease of SP duration was higher than the threshold for eliciting an early excitatory muscle response in the contralateral FDI. Increasing the intensity of the conditioning stimulus led to linear reduction of SP duration. In the patient with callosal agenesis, no such decreasing effect on SP duration was observed. These results suggest that inhibitory interneurons within primary hand motor cortex receive transcallosal inhibitory input from the opposite motor cortex. We propose that modulation of motor cortical interneurons via transcallosal pathways may provide a gain control for the motor cortical output system and subserve interhemispheric coordination in complex, nonsymmetrical bimanual movements.

Background:The supplementary motor area (SMA) makes multiple reciprocal connections to many areas of the cerebral cortices, such as the primary motor cortex (PMC), anterior cingulate cortex, and various regions in the parietal somatosensory cortex. In patients with SMA seizures, epileptic discharges from the SMA rapidly propagate to the PMC. We sought to determine whether near-infrared spectroscopy (NIRS) is able to intraoperatively display hemodynamic changes in epileptic network activities between the SMA and the PMC.Case Descriptions:In a 60-year-old male with SMA seizures, we intraoperatively delivered a 500 Hz, 5-train stimulation to the medial cortical surface and measured the resulting hemodynamic changes in the PMC by calculating the oxyhemoglobin (HbO2) and deoxyhemoglobin (HbR) concentration changes during stimulation. No hemodynamic changes in the lateral cortex were observed during stimulation of the medial surface corresponding to the foot motor areas. In contrast, both HbO2 and HbR increased in the lateral cortex corresponding to the hand motor areas when the seizure onset zone was stimulated. In the premotor cortex and the lateral cortex corresponding to the trunk motor areas, hemodynamic changes showed a pattern of increased HbO2 with decreased HbR.Conclusions:This is the first reported study using intraoperative NIRS to characterize the epileptic network activities between the SMA and PMC. Our intraoperative NIRS procedure may thus be useful in monitoring the activities of cortico-cortical neural pathways such as the language system.

Task specific training is a cornerstone of stroke motor therapy and is thought to contribute to improvement of function in activities of daily living (ADLs). Abnormal synergies after stroke often make the training of proper inter-joint coordination during functional tasks difficult, since patients are inclined to utilize abnormal compensatory movement patterns. Effective inter-joint coordination training may be important for regaining functional use of the limb. We have developed a novel robotic method for retraining inter-joint coordination based on time independent joint based control. An integral component of this method is facilitation of proper patient interaction with the robot, which is essential to maximize gains. While robots can assist completion of movement, patient control of the movement is frequently minimal, leading to little or no effort by the patient during training. To increase patient engagement, we have incorporated feed-forward friction compensation to improve backdriveability, gravity compensation for both the robot and human arms, and a visual interface to improve patient interactions with the robot.

Although most activities of daily life require simultaneous coordination of both proximal and distal joints, motor preparation during such movements has not been well studied. Previous results for motor preparation have focused on hand/finger movements. For simple hand/finger movements, results have found that such movements typically evoke activity primarily in the contralateral motor cortices. However, increasing the complexity of the finger movements, such as during a distal sequential finger-pressing task, leads to additional recruitment of ipsilateral resources. It has been suggested that this involvement of the ipsilateral hemisphere is critical for temporal coordination of distal joints. The goal of the current study was to examine whether increasing simultaneous coordination of multiple joints (both proximal and distal) leads to a similar increase in coupling with ipsilateral sensorimotor cortices during motor preparation compared to a simple distal movement such as hand opening. To test this possibility, 12 healthy individuals participated in a high-density EEG experiment in which they performed either hand opening or simultaneous hand opening while lifting at the shoulder on a robotic device. We quantified within- and cross-frequency cortical coupling across the sensorimotor cortex for the two tasks using dynamic causal modeling. Both hand opening and simultaneous hand opening while lifting at the shoulder elicited coupling from secondary motor areas to primary motor cortex within the contralateral hemisphere exclusively in the beta band, as well as from ipsilateral primary motor cortex. However, increasing the task complexity by combining hand opening while lifting at the shoulder also led to an increase in cross-frequency coupling within the ipsilateral hemisphere including theta, beta, and gamma frequencies, as well as a change in the coupling frequency of the interhemispheric coupling between the primary motor and premotor cortices. These findings demonstrate that increasing the demand of joint coordination between proximal and distal joints leads to increases in communication with the ipsilateral hemisphere as previously observed in distal sequential finger tasks.

Coordinated movement requires patterned activation of muscles. In this study, we examined differences in selective activation of primate upper limb muscles by cortical and subcortical regions. Five macaque monkeys were trained to perform a reach and grasp task, and electromyogram (EMG) was recorded from 10 to 24 muscles while weak single-pulse stimuli were delivered through microelectrodes inserted in the motor cortex (M1), reticular formation (RF), or cervical spinal cord (SC). Stimulus intensity was adjusted to a level just above threshold. Stimulus-evoked effects were assessed from averages of rectified EMG. M1, RF, and SC activated 1.5 ± 0.9, 1.9 ± 0.8, and 2.5 ± 1.6 muscles per site (means ± SD); only M1 and SC differed significantly. In between recording sessions, natural muscle activity in the home cage was recorded using a miniature data logger. A novel analysis assessed how well natural activity could be reconstructed by stimulus-evoked responses. This provided two measures: normalized vector length L, reflecting how closely aligned natural and stimulus-evoked activity were, and normalized residual R, measuring the fraction of natural activity not reachable using stimulus-evoked patterns. Average values for M1, RF, and SC were L = 119.1 ± 9.6, 105.9 ± 6.2, and 109.3 ± 8.4% and R = 50.3 ± 4.9, 56.4 ± 3.5, and 51.5 ± 4.8%, respectively. RF was significantly different from M1 and SC on both measurements. RF is thus able to generate an approximation to the motor output with less activation than required by M1 and SC, but M1 and SC are more precise in reaching the exact activation pattern required. Cortical, brainstem, and spinal centers likely play distinct roles, as they cooperate to generate voluntary movements.NEW & NOTEWORTHY Brainstem reticular formation, primary motor cortex, and cervical spinal cord intermediate zone can all activate primate upper limb muscles. However, brainstem output is more efficient but less precise in producing natural patterns of motor output than motor cortex or spinal cord. We suggest that gross muscle synergies from the reticular formation are sculpted and refined by motor cortex and spinal circuits to reach the finely fractionated output characteristic of dexterous primate upper limb movements.

1. We have recently demonstrated that reversible, cooling-induced inactivation of the face motor cortex results in a severe impairment in the ability of monkeys (Macaca fascicularis) to perform a tongue-protrusion task but produces only relatively minor effects on the performance of a biting task by the same monkeys. To establish a neuronal correlate for these different behavioral relations, the present study has detailed the afferent input and intracortical microstimulation (ICMS)-defined output features of a population of face motor cortical neurons, and in a subsequent study we have documented the activities of the same population of neurons during the performance of the tongue-protrusion and biting tasks. 2. Of the 231 single neurons recorded within the face motor cortex, 163 were located at sites from which ICMS (less than or equal to 20 microA) could evoke tongue movements (i.e., "tongue-MI" sites) at the lowest threshold for eliciting orofacial movements. The remainder were located at sites from which ICMS evoked jaw movements ("jaw-MI" sites), face movements ("face-MI" sites), or at a few sites, tongue movements and, at the same threshold intensity, either a jaw movement or a facial movement. 3. We confirmed the general organizational features of the face motor cortex that have been defined in previous studies, but we documented in detail the organizational features for tongue-MI. Thus we found that tongue movements were well represented, whereas jaw-closing movements were poorly represented; the representations for face, jaw, and tongue movements were overlapped; the same ICMS-evoked tongue movement could be multiply represented within tongue-MI; tongue-MI was characterized by a prominent input from superficial mechanosensory afferents, whereas there was little evidence for deep input; a close spatial match was found between ICMS-defined motor output and somatosensory afferent input for tongue-MI. 4. A variety of tongue movements could be evoked by ICMS at tongue-MI sites and were categorized into protrusion, retrusion, laterally directed, and other types of tongue movement. Low-threshold (i.e., less than or equal to 5 microA) ICMS-defined tongue-MI sites, which were considered to represent "efferent zones" projecting relatively directly to motoneurons, were reconstructed three dimensionally to provide insights into the spatial organization of tongue-MI. Examples of each of the four low-threshold efferent-zone categories were usually found throughout the ICMS-defined tongue-MI without any apparent preferential distribution. Furthermore, different low-threshold efferent-zone categories had close spatial relationships to each other in cortex.(ABSTRACT TRUNCATED AT 400 WORDS)

Signals derived from the rat motor cortex can be used for controlling one-dimensional movements of a robot arm. It remains unknown, however, whether real-time processing of cortical signals can be employed to reproduce, in a robotic device, the kind of complex arm movements used by primates to reach objects in space. Here we recorded the simultaneous activity of large populations of neurons, distributed in the premotor, primary motor and posterior parietal cortical areas, as non-human primates performed two distinct motor tasks. Accurate real-time predictions of one- and three-dimensional arm movement trajectories were obtained by applying both linear and nonlinear algorithms to cortical neuronal ensemble activity recorded from each animal. In addition, cortically derived signals were successfully used for real-time control of robotic devices, both locally and through the Internet. These results suggest that long-term control of complex prosthetic robot arm movements can be achieved by simple real-time transformations of neuronal population signals derived from multiple cortical areas in primates.

ABSTRACTIntroductionA pilot study provided preliminary evidence indicating that peri‐lesional adult autologous neural cell ecosystem transplantation (so‐called ANCE) can enhance the functional recovery of manual dexterity in macaque monkeys following a unilateral lesion of the hand representation in the primary motor cortex (M1). As compared to five untreated control animals subjected to M1 lesions, the improvement of functional recovery was observed in our pilot study in two ANCE‐treated monkeys (also M1 lesioned). To strengthen these promising preliminary results, the present study aimed at introducing two additional ANCE monkeys, as well as one new control monkey, all subjected to M1 lesion.MethodsManual dexterity was assessed based on the modified Brinkman board task, performed with the contralesional hand to retrieve small food pellets from slots using the precision grip (opposition of thumb and index finger).ResultsAs with the two pilot ANCE‐treated monkeys, the two new ANCE‐treated monkeys exhibited a rebound of functional recovery (a second plateau) associated to the treatment (after approximately 2–3 months delay post‐treatment), following a first plateau of spontaneous recovery. In contrast, all control monkeys (n = 6) exhibited a single plateau of functional recovery.ConclusionThe present study confirms that ANCE treatment significantly improves functional recovery from motor cortex lesions in adult macaques, with performance gains ranging from 20% to 40%. These findings support a possible future initiative to initiate clinical trials based on ANCE therapy.

We investigated the properties of the neural response to transcranial magnetic stimulation (TMS) applied over the human primary motor cortex. Consistent with our previous findings, single pulses of TMS induce a characteristic negative deflection at 45 ms (N45) and a transient oscillation in the beta frequency-range (15-30 Hz), as measured using electroencephalograpy (EEG). Here we show the relative specificity of the beta oscillation and the N45; both are stronger when elicited by stimulation applied over the primary motor cortex, as compared with stimulation over the dorsal premotor cortex. We also provide a quantitative analysis of the beta responses to single pulses of TMS and show that the responses are highly phaselocked to the TMS pulses within single subjects; this phaselocking is similar from subject to subject. A single pulse of TMS applied over the primary motor cortex thus appears to reset the ongoing oscillations of the neurons, bringing them transiently into synchrony. Finally, we examine the effect of local or distal modulation of the excitability of the primary motor cortex on the beta oscillation and the N45 in response to single-pulse TMS. We applied low-frequency subthreshold repetitive TMS either over the primary motor cortex (local modulation) or, on a separate day, over the dorsal premotor cortex (distal modulation). The modulation was evaluated with single suprathreshold test pulses of TMS applied over the primary motor cortex before and after the subthreshold low-frequency rTMS. We recorded the EEG response throughout the testing session, i.e. to both the subthreshold and the suprathreshold pulses. After repetitive TMS applied over the primary motor cortex, but not the dorsal premotor cortex, the amplitude of the N45 in response to suprathreshold pulses tended to decrease (not significant), and subsequently increased (significant); neither type of repetitive TMS affected the amplitude of the beta oscillation. We conclude that (1) the N45 depends on circuits intrinsic to the primary motor cortex; (2) the beta oscillation is specific to stimulation of the primary motor cortex, but is not affected by modulation of either cortical area and; (3) the beta oscillatory response to pulses of TMS arises from resetting of ongoing oscillations rather than their induction.

The human hand is an amazing tool, demonstrated by its incredible motor capability and remarkable sense of touch. To enable robots to work in a human-centric environment, it is desirable to endow robotic hands with human-like capabilities for grasping and object manipulation. However, due to its inherent complexity and inevitable model uncertainty, robotic grasping and manipulation remains a challenge. This thesis focuses on grasp adaptation in the face of model and sensing uncertainties: Given an object whose properties are not known with certainty (e.g., shape, weight and external perturbation), and a multifingered robotic hand, we aim at determining where to put the fingers and how the fingers should adaptively interact with the object using tactile sensing, in order to achieve either a stable grasp or a desired dynamic behaviour. A central idea in this thesis is the object-centric dynamics: namely, that we express all control constraints into an object-centric representation. This simplifies computa- tion and makes the control versatile to the type of hands. This is an essential feature that distinguishes our work from other robust grasping work in the literature, where generating a static stable grasp for a given hand is usually the primary goal. In this thesis, grasp adaptation is a dynamic process that flexibly adapts the grasp to fit some purpose from the objectâ s perspective, in the presence of a variety of uncertainties and/or perturbations. When building a grasp adaptation for a given situation, there are two key problems that must be addressed: 1) the problem of choosing an initial grasp that is suitable for future adaptation, and more importantly 2) the problem of design- ing an adaptation strategy that can react adequately to achieve desired behaviour of the grasped object. To address challenge 1 (planning a grasp under shape uncertainty), we propose an approach to parameterizing the uncertainty in object shape using Gaussian Processes (GPs) and incorporate it as a constraint into contact-level grasp planning. To realize the planned contacts using different hands interchangeably, we further develop a prob- abilistic model to predict the feasible hand configurations, including hand pose and finger joints, given the desired contact points only. The model is built using the con- cept of Virtual Frame(VF), and it is independent from the choice of hand frame and object frame. The performance of the proposed approach is validated on two differ- ent robotic hands, an industrial gripper (4 DOF Barrett hand) and a humanoid hand (16 DOF Allegro hand) to manipulate objects of daily use with complex geometry and various texture (a spray bottle, a tea caddy, a jug and a bunny toy). In the second part of this thesis, we propose an approach to the design of adapta- tion strategy to ensure grasp stability in the presence of physical uncertainties of objects(object weight, friction at contacts and external perturbation). Based on an object-level impedance controller, we first design a grasp stability estimator in the object frame using the grasp experience and tactile sensing. Once a grasp is predicted to be unstable during online execution, the grasp adaptation strategy is triggered to improve the grasp stability, by either changing the stiffness at finger level or relocating the position of one fingertip to a better area.

<bold>Objective</bold> The contractions of abdominal muscle during voluntary urination is a motor control task, Which aims to explore the central activity characteristics of this action with functional near-infrared spectroscopy (fNIRS). <bold>Methods</bold> A total of 19 healthy subjects aged 18 years or older were recruited to undergo fNIRS testing twice, performing repetitive abdominal muscle contractions in the no-urine and strong-urine states. Brain activity under the corresponding no-abdominal muscle-contraction task was used as a baseline to analyze the cortical activities specific to abdominal muscle contractions in these two different states. <bold>Results</bold> Abdominal muscle contractions during the strong desire to urinate primarily activated the bilateral pre-motor/supplementary motor area (BA6), bilateral dorsolateral prefrontal cortex (BA9/46), bilateral frontal pole area (BA10), the anterior portion of the right inferior frontal gyrus (BA47), the right middle temporal gyrus (BA21), the right primary motor cortex (BA4), and the left primary somatosensory cortex (BA1/2/3) in conjunction with the left inferior frontal of pars triangularis Broca's area (BA45) (<italic>P</italic>&lt;0.05). In contrast, abdominal muscle contractions with no desire to urinate primarily activated the bilateral pre-motor/supplementary motor area (BA6) (<italic>P</italic>&lt;0.05), the right primary motor cortex (BA4), the right primary somatosensory cortex (BA1/2/3), the right inferior frontal of pars triangularis Broca's area (BA45), and the right supramarginal gyrus part of Wernicke's area (BA40) (<italic>P</italic>&lt;0.05). Compared to the strong urination state, stronger activation of the bilateral premotor/assistive motor area (BA6) was present in the non-urination state (<italic>P</italic>&lt;0.05). Compared to the non-urination state, stronger activation of the left dorsolateral prefrontal cortex (BA46) was present in the strong urination state (<italic>P</italic>&lt;0.05). <bold>Conclusion</bold> The primary somatosensory cortex, primary motor cortex, and pre-motor/supplementary motor area are jointly involved in the regulation of voluntary urination-associated random abdominal muscle contractions. And further activation of the prefrontal cortex can be induced during abdominal muscle contractions in the strong urination state, suggesting that the prefrontal cortex plays a positive role in facilitating abdominal muscle movements and initiating urination following the perception of urinary awareness.