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The goal of this study was to quantify the inter-individual and intra-individual variability of manual (digits) skill in adult macaque monkeys, over a motor learning phase and, lateron, when motor skills were consolidated. The hypothesis is that several attributes of the stable manual dexterity performance can be predicted from learning characteristics. The behavioral data were collected from 20 adult Macaca fascicularis, derived from their dominant hand, defined as the hand exhibiting a better performance than theother. Two manual dexterity tasks were tested: (i) the modified Brinkman board task, consisting in the retrieval of food pellets placed in 50 slots ina board, using the precision grip (opposition of the thumb and index finger);(ii) the reach and grasp drawer task, in which the grip force and the load force were continuously monitored while the monkey opened a drawer against a resistance, before grasping a pellet inside the drawer. The hypothesis was verified for the performance of manual dexterity after consolidation, correlated with the initial score before learning. Motor habit, reflected by the temporal order of sequential movements executed in the modified Brinkman board task, was established very early during the learning phase. As mostly expected, motor  learning led to an optimization of manual dexterity parameters, such as score, contact time, as well as a decrease in intra-individual variability. Overall,the data demonstrate the substantial inter-individual variability of manual dexterity in non-human primates, to be considered for further pre-clinical applications based on this animal model.

Non‐invasive reversible perturbation techniques of brain output such as continuous theta burst stimulation (cTBS), commonly used to modulate cortical excitability in humans, allow investigation of possible roles in functional recovery played by distinct intact cortical areas following stroke. To evaluate the potential of cTBS, the behavioural effects of this non‐invasive transient perturbation of the hand representation of the primary motor cortex (M1) in non‐human primates (two adult macaques) were compared with an invasive focal transient inactivation based on intracortical microinfusion of GABA‐A agonist muscimol. The effects on the contralateral arm produced by cTBS or muscimol were directly compared based on a manual dexterity task performed by the monkeys, the "reach and grasp" drawer task, allowing quantitative assessment of the grip force produced between the thumb and index finger and exerted on the drawer's knob. cTBS only induced modest to moderate behavioural effects, with substantial variability on manual dexterity whereas the intracortical muscimol microinfusion completely impaired manual dexterity, producing a strong and clear cortical inhibition of the M1 hand area. In contrast, cTBS induced mixed inhibitory and facilitatory/excitatory perturbations of M1, though with predominant inhibition. Although cTBS impacted on manual dexterity, its effects appear too limited and variable in order to use it as a reliable proof of cortical vicariation mechanism (cortical area replacing another one) underlying functional recovery following a cortical lesion in the motor control domain, in contrast to potent pharmacological block generated by muscimol infusion, whose application is though limited to an animal model such as non‐human primate. [ABSTRACT FROM AUTHOR]

The corticotectal projections, together with the corticobulbar (corticoreticular) projections, work in parallel with the corticospinal tract (CST) to influence motoneurons in the spinal cord both directly and indirectly via the brainstem descending pathways. The tectospinal tract (TST) originates in the deep layers of the superior colliculus. In the present study, we analyzed the corticotectal projections from two motor cortical areas, namely the premotor cortex (PM) and the primary motor cortex (M1) in eight macaque monkeys subjected to either a cortical lesion of the hand area in M1 (n = 4) or Parkinson's disease-like symptoms PD (n = 4). A subgroup of monkeys with cortical lesion was subjected to anti-Nogo-A antibody treatment whereas all PD monkeys were transplanted with Autologous Neural Cell Ecosystems (ANCEs). The anterograde tracer BDA was used to label the axonal boutons both en passant and terminaux in the ipsilateral superior colliculus. Individual axonal boutons were charted in the different layers of the superior colliculus. In intact animals, we previously observed that corticotectal projections were denser when originating from PM than from M1. In the present M1 lesioned monkeys, as compared to intact ones the corticotectal projection originating from PM was decreased when treated with anti-Nogo-A antibody but not in untreated monkeys. In PD-like symptoms' monkeys, on the other hand, there was no consistent change affecting the corticotectal projection as compared to intact monkeys. The present pilot study overall suggests that the corticotectal projection is less affected by M1 lesion or PD symptoms than the corticoreticular projection previously reported in the same animals. [ABSTRACT FROM AUTHOR]

Abstract: Functional recovery from central nervous system injury is likely to be partly due to a rearrangement of neural circuits. In this context, the corticobulbar (corticoreticular) motor projections onto different nuclei of the ponto‐medullary reticular formation (PMRF) were investigated in 13 adult macaque monkeys after either, primary motor cortex injury (MCI) in the hand area, or spinal cord injury (SCI) or Parkinson's disease‐like lesions of the nigro‐striatal dopaminergic system (PD). A subgroup of animals in both MCI and SCI groups was treated with neurite growth promoting anti‐Nogo‐A antibodies, whereas all PD animals were treated with autologous neural cell ecosystems (ANCE). The anterograde tracer BDA was injected either in the premotor cortex (PM) or in the primary motor cortex (M1) to label and quantify corticobulbar axonal boutons terminaux and en passant in PMRF. As compared to intact animals, after MCI the density of corticobulbar projections from PM was strongly reduced but maintained their laterality dominance (ipsilateral), both in the presence or absence of anti‐Nogo‐A antibody treatment. In contrast, the density of corticobulbar projections from M1 was increased following opposite hemi‐section of the cervical cord (at C7 level) and anti‐Nogo‐A antibody treatment, with maintenance of contralateral laterality bias. In PD monkeys, the density of corticobulbar projections from PM was strongly reduced, as well as that from M1, but to a lesser extent. In conclusion, the densities of corticobulbar projections from PM or M1 were affected in a variable manner, depending on the type of lesion/pathology and the treatment aimed to enhance functional recovery. [ABSTRACT FROM AUTHOR]

Corticospinal and corticobulbar descending pathways act in parallel with brainstem systems, such as the reticulospinal tract, to ensure the control of voluntary movements via direct or indirect influences onto spinal motoneurons. The aim of this study was to investigate the corticobulbar projections from distinct motor cortical areas onto different nuclei of the reticular formation. Seven adult macaque monkeys were analysed for the location of corticobulbar axonal boutons, and one monkey for reticulospinal neurons' location. The anterograde tracer BDA was injected in the premotor cortex ( PM), in the primary motor cortex (M1) or in the supplementary motor area ( SMA), in 3, 3 and 1 monkeys respectively. BDA anterograde labelling of corticobulbar axons were analysed on brainstem histological sections and overlapped with adjacent Nissl-stained sections for cytoarchitecture. One adult monkey was analysed for retrograde CB tracer injected in C5-C8 hemispinal cord to visualise reticulospinal neurons. The corticobulbar axons formed bilateral terminal fields with boutons terminaux and en passant, which were quantified in various nuclei belonging to the Ponto-Medullary Reticular Formation ( PMRF). The corticobulbar projections from both PM and SMA tended to end mainly ipsilaterally in PMRF, but contralaterally when originating from M1. Furthermore, the corticobulbar projection was less dense when originating from M1 than from non-primary motor areas ( PM, SMA). The main nuclei of bouton terminals corresponded to the regions where reticulospinal neurons were located with CB retrograde tracing. In conclusion, the corticobulbar projection differs according to the motor cortical area of origin in density and laterality. [ABSTRACT FROM AUTHOR]