Time course of recovery of different motor functions following a reproducible cortical infarction in non-human primates.

A major challenge in human stroke research is interpatient variability in the extent of sensorimotor deficits and determining the time course of recovery following stroke. Although the relationship between the extent of the lesion and the degree of sensorimotor deficits is well established, the factors determining the speed of recovery remain uncertain. To test these experimentally, we created a cortical lesion over the motor cortex using a reproducible approach in four common marmosets, and characterized the time course of recovery by systematically applying several behavioral tests before and up to 8 weeks after creation of the lesion. Evaluation of in-cage behavior and reach-to-grasp movement revealed consistent motor impairments across the animals. In particular, performance in reaching and grasping movements continued to deteriorate until 4 weeks after creation of the lesion. We also found consistent time courses of recovery across animals for in-cage and grasping movements. For example, in all animals, the score for in-cage behaviors showed full recovery at 3 weeks after creation of the lesion, and the performance of grasping movement partially recovered from 4 to 8 weeks. In addition, we observed longer time courses of recovery for reaching movement, which may rely more on cortically initiated control in this species. These results suggest that different recovery speeds for each movement could be influenced by what extent the cortical control is required to properly execute each movement.

Spectral Power in Marmoset Frontal Motor Cortex during Natural Locomotor Behavior.

During primate arboreal locomotion, substrate orientation modifies body axis orientation and biomechanical contribution of fore- and hindlimbs. To characterize the role of cortical oscillations in integrating these locomotor demands, we recorded electrocorticographic activity from left dorsal premotor, primary motor, and supplementary motor cortices of three common marmosets moving across a branch-like small-diameter pole, fixed horizontally or vertically. Animals displayed behavioral adjustments to the task, namely, the horizontal condition mainly induced quadrupedal walk with pronated/neutral forelimb postures, whereas the vertical condition induced walk and bound gaits with supinated/neutral postures. Examination of cortical activity suggests that ß (16-35 Hz) and γ (75-100 Hz) oscillations could reflect different processes in locomotor adjustments. During task, modulation of γ ERS by substrate orientation (horizontal/vertical) and epoch (preparation/execution) suggests close tuning to movement dynamics and biomechanical demands. ß ERD was essentially modulated by gait (walk/bound), which could illustrate contribution to movement sequence and coordination. At rest, modulation of ß power by substrate orientation underlines its role in sensorimotor processes for postural maintenance.

Fast Electrophysiological Mapping of Rat Cortical Motor Representation on a Time Scale of Minutes during Skin Stimulation.

The topographic map of motor cortical representation, called the motor map, is not invariant, but can be altered by motor learning, neurological injury, and functional recovery from injury. Although much attention has been paid to short-term changes of the motor map, robust measures have not been established. The existing mapping methods are time-consuming, and the obtained maps are confounded by time preference. The purpose of this study was to examine the dynamics of the motor map on a timescale of minutes during transient somatosensory input by a fast motor mapping technique. We applied 32-channel micro-electrocorticographic electrode arrays to the rat sensorimotor cortex for cortical stimulation, and the topographic profile of motor thresholds in forelimb muscle was identified by fast motor mapping. Sequential motor maps were obtained every few minutes before, during, and just after skin stimulation to the dorsal forearm using a wool buff. During skin stimulation, the motor map expanded and the center of gravity of the map was shifted caudally. The expansion of the map persisted for at least a few minutes after the end of skin stimulation. Although the motor threshold of the hotspot was not changed, the area in which it was decreased appeared caudally to the hotspot, which may be in the somatosensory cortex. The present study demonstrated rapid enlargement of the forelimb motor map in the order of a few minutes induced by skin stimulation. This helps to understand the spatial dynamism of motor cortical representation that is modulated rapidly by somatosensory input.

Accurate motor mapping in awake common marmosets using micro-electrocorticographical stimulation and stochastic threshold estimation.

OBJECTIVE: Motor map has been widely used as an indicator of motor skills and learning, cortical injury, plasticity, and functional recovery. Cortical stimulation mapping using epidural electrodes is recently adopted for animal studies. However, several technical limitations still remain. Test-retest reliability of epidural cortical stimulation (ECS) mapping has not been examined in detail. Many previous studies defined evoked movements and motor thresholds by visual inspection, and thus, lacked quantitative measurements. A reliable and quantitative motor map is important to elucidate the mechanisms of motor cortical reorganization. The objective of the current study was to perform reliable ECS mapping of motor representations based on the motor thresholds, which were stochastically estimated by motor evoked potentials and chronically implanted micro-electrocorticographical (µECoG) electrode arrays, in common marmosets. APPROACH: ECS was applied using the implanted µECoG electrode arrays in three adult common marmosets under awake conditions. Motor evoked potentials were recorded through electromyographical electrodes implanted in upper limb muscles. The motor threshold was calculated through a modified maximum likelihood threshold-hunting algorithm fitted with the recorded data from marmosets. Further, a computer simulation confirmed reliability of the algorithm. MAIN RESULTS: Computer simulation suggested that the modified maximum likelihood threshold-hunting algorithm enabled to estimate motor threshold with acceptable precision. In vivo ECS mapping showed high test-retest reliability with respect to the excitability and location of the cortical forelimb motor representations. SIGNIFICANCE: Using implanted µECoG electrode arrays and a modified motor threshold-hunting algorithm, we were able to achieve reliable motor mapping in common marmosets with the ECS system.

Cortical control of object-specific grasp relies on adjustments of both activity and effective connectivity: a common marmoset study.

KEY POINTS: The cortical mechanisms of grasping have been extensively studied in macaques and humans; here, we investigated whether common marmosets could rely on similar mechanisms despite strong differences in hand morphology and grip diversity. We recorded electrocorticographic activity over the sensorimotor cortex of two common marmosets during the execution of different grip types, which allowed us to study cortical activity (power spectrum) and physiologically inferred connectivity (phase-slope index). Analyses were performed in beta (16-35 Hz) and gamma (75-100 Hz) frequency bands and our results showed that beta power varied depending on grip type, whereas gamma power displayed clear epoch-related modulation. Strength and direction of inter-area connectivity varied depending on grip type and epoch. These findings suggest that fundamental control mechanisms are conserved across primates and, in future research, marmosets could represent an adequate model to investigate primate brain mechanisms. ABSTRACT: The cortical mechanisms of grasping have been extensively studied in macaques and humans. Here, we investigated whether common marmosets could rely on similar mechanisms despite striking differences in manual dexterity. Two common marmosets were trained to grasp-and-pull three objects eliciting different hand configurations: whole-hand, finger and scissor grips. The animals were then chronically implanted with 64-channel electrocorticogram arrays positioned over the left premotor, primary motor and somatosensory cortex. Power spectra, reflecting predominantly cortical activity, and phase-slope index, reflecting the direction of information flux, were studied in beta (16-35 Hz) and gamma (75-100 Hz) bands. Differences related to grip type, epoch (reach, grasp) and cortical area were statistically assessed. Results showed that whole-hand and scissor grips triggered stronger beta desynchronization than finger grip. Task epochs clearly modulated gamma power, especially for finger and scissor grips. Considering effective connectivity, finger and scissor grips evoked stronger outflow from primary motor to premotor cortex, whereas whole-hand grip displayed the opposite pattern. These findings suggest that fundamental control mechanisms, relying on adjustments of cortical activity and connectivity, are conserved across primates. Consistently, marmosets could represent a good model to investigate primate brain mechanisms.

Histological and electrophysiological analysis of the corticospinal pathway to forelimb motoneurons in common marmosets.

Using histological and electrophysiological methods, we identified the neuroanatomical properties of the common marmoset corticospinal tract (CST), which underlies hand/arm motor control. Biotinylated dextran amine (BDA) was injected into the primary motor cortex to anterogradely label CST axons in the cervical segments, revealing that most CST axons descend in the contralateral dorsolateral funiculus (DLF; 85.0%), and some in the ipsilateral DLF (10.7%). Terminal buttons were mainly found in the contralateral lamina VII of the gray matter, but projection to lamina IX, where forelimb motoneurons are located, was rare. Bilateral projections were more abundant than found in the rat CST, resembling the CST organization of other primates. Intracellular recordings were made from 57 forelimb motoneurons on the contralateral side to stimulation, which revealed no monosynaptic excitatory postsynaptic potentials (EPSPs), but di- or polysynaptic EPSPs and inhibitory synaptic potentials were commonly found. Local field potentials showed monosynaptic excitation mainly in laminae VII, where abundant BDA-labeled CST terminals were observed. These results suggest that direct corticomotoneuronal projection is absent in common marmosets but di- or oligosynaptic effects would be mediated by spinal interneurons.

Three-dimensional motion analysis of arm-reaching movements in healthy and hemispinalized common marmosets.

Spinal cord injury (SCI) is a devastating neurological injury. At present, pharmacological, regenerative, and rehabilitative approaches are widely studied as therapeutic interventions for motor recovery after SCI. Preclinical research has been performed on model animals with experimental SCI, and those studies often evaluate hand and arm motor function using various indices, such as the success rate of the single pellet reaching test and the grip force. However, compensatory movement strategies, involuntary muscle contraction, and the subject's motivation could affect the scores, resulting in failure to assess direct recovery from impairment. Identifying appropriate assessments of motor impairment is thus important for understanding the mechanisms of motor recovery. In this study, we developed a motion capture system capable of reconstructing three-dimensional hand positions with millimeter and millisecond accuracy and evaluated hand kinematics during food retrieval movement in both healthy and hemispinalized common marmosets. As a result, the endpoint jerk, representing the accuracy of hand motor control, was asserted to be an appropriate index of upper limb motor impairment by eliminating the influence of the subject's motivation, involuntary muscle contraction, and compensatory strategies. The result also suggested that the kinematics of the limb more consistently reflects motor restoration from deficit due to spinal cord injury than the performance in the single pellet reaching test. Because of recent attention devoted to the common marmoset as a nonhuman primate model for human diseases, the present study, which clarified arm-reaching movements in spinalized marmosets, provides fundamental knowledge for future therapeutic studies.