The corticospinal (CS) tract is the anatomical support of the exquisite motor ability to skillfully manipulate small objects, a prerogative mainly of primates 1 . In case of lesion affecting the CS projection system at its origin (lesion of motor cortical areas) or along its trajectory (cervical cord lesion), there is a dramatic loss of manual dexterity (hand paralysis), as seen in some tetraplegic or hemiplegic patients. Although there is some spontaneous functional recovery after such lesion, it remains very limited in the adult. Various therapeutic strategies are presently proposed (e.g. cell therapy, neutralization of inhibitory axonal growth molecules, application of growth factors, etc), which are mostly developed in rodents. However, before clinical application, it is often recommended to test the feasibility, efficacy, and security of the treatment in non-human primates. This is especially true when the goal is to restore manual dexterity after a lesion of the central nervous system, as the organization of the motor system of rodents is different from that of primates 1,2 . Macaque monkeys are illustrated here as a suitable behavioral model to quantify manual dexterity in primates, to reflect the deficits resulting from lesion of the motor cortex or cervical cord for instance, measure the extent of spontaneous functional recovery and, when a treatment is applied, evaluate how much it can enhance the functional recovery.The behavioral assessment of manual dexterity is based on four distinct, complementary, reach and grasp manual tasks (use of precision grip to grasp pellets), requiring an initial training of adult macaque monkeys. The preparation of the animals is demonstrated, as well as the positioning with respect to the behavioral set-up. The performance of a typical monkey is illustrated for each task. The collection and analysis of relevant parameters reflecting precise hand manipulation, as well as the control of force, are explained and demonstrated with representative results. These data are placed then in a broader context, showing how the behavioral data can be exploited to investigate the impact of a spinal cord lesion or of a lesion of the motor cortex and to what extent a treatment may enhance the spontaneous functional recovery, by comparing different groups of monkeys (treated versus sham treated for instance). Advantages and limitations of the behavioral tests are discussed. The present behavioral approach is in line with previous reports emphasizing the pertinence of the non-human primate model in the context of nervous system diseases 2,3 . Video LinkThe video component of this article can be found at https://www.jove.com/video/3258/ ProtocolThe overall scheme of the experiment is depicted in Figure 1. Animal preparation and transfer to the behavioral laboratory1. In the laboratory, prepare the behavioral set-up: fill the wells of the different test boards (tests 1 to 3 below) with the pellets, which serve as reward during the behavioral tests. 2. Transfer the monkey from...

Cortical activity allotted to the tactile receptors on fingertips conforms to skilful use of the hand. For instance, in string instrument players, the somatosensory cortical activity in response to touch on the little fingertip is larger than that in control subjects. Such plasticity of the fingertip sensory representation is not limited to extraordinary skills and occurs in monkeys trained to repetitively grasp and release a handle as well. Touchscreen phones also require repetitive finger movements, but whether and how the cortex conforms to this is unknown. By using electroencephalography (EEG), we measured the cortical potentials in response to mechanical touch on the thumb, index, and middle fingertips of touchscreen phone users and nonusers (owning only old-technology mobile phones). Although the thumb interacted predominantly with the screen, the potentials associated with the three fingertips were enhanced in touchscreen users compared to nonusers. Within the touchscreen users, the cortical potentials from the thumb and index fingertips were directly proportional to the intensity of use quantified with built-in battery logs. Remarkably, the thumb tip was sensitive to the day-to-day fluctuations in phone use: the shorter the time elapsed from an episode of intense phone use, the larger the cortical potential associated with it. Our results suggest that repetitive movements on the smooth touchscreen reshaped sensory processing from the hand and that the thumb representation was updated daily depending on its use. We propose that cortical sensory processing in the contemporary brain is continuously shaped by the use of personal digital technology.

A restricted lesion of the hand area in the primary motor cortex (M1) leads to a deficit of contralesional manual dexterity, followed by an incomplete functional recovery, accompanied by plastic changes in M1 itself and in other cortical areas on both hemispheres. Using the marker SMI-32 specific to pyramidal neurons in cortical layers III and V, we investigated the impact of a focal unilateral M1 lesion (hand representation) on the rostral part (F6) and caudal part (F3) of the supplementary motor area (SMA) in both hemispheres in nine adult macaque monkeys compared with four intact control monkeys. The M1 lesion induced a consistent interhemispheric asymmetry in density of SMI-32-positive neurons in F3 layer V (statistically significant in 8 of 9 lesioned monkeys), highly correlated with the lesion volume and with the duration of functional recovery, but not with the extent of functional recovery itself. Such interhemispheric asymmetry was neither present in the intact monkeys, as expected, nor in F6 in all monkeys. In addition, the M1 lesion also impacted on the basal dendritic arborization of F3 layer V neurons. Neuronal density was clearly less affected by the M1 lesion in F3 layer III compared with layer V. We interpret the remote effect of M1 lesion onto the density of SMI-32-positive neurons and dendritic arborization in the SMAs bilaterally as the consequence of multiple factors, such as changes of connectivity, diaschisis and various mechanisms involved in cortical plasticity underlying the functional recovery from the M1 lesion. SIGNIFICANCE STATEMENT The motor system of macaque monkeys, in addition to be similarly organized as in humans, is a good candidate to study the impact of a focal lesion of the main contributor to voluntary movements, the primary motor cortex (M1), on non-primary motor cortical areas also involved in manual dexterity, both at behavioral and structural levels. Our results show that a unilateral permanent lesion of M1 hand area in nine monkeys affects the interhemispheric balance of the number of SMI-32-positive pyramidal neurons in the cortical layer V of the supplementary motor area, in a way strongly correlated to the lesion volume and duration of the incomplete functional recovery.

Background The present study aimed to determine and confront hand preference (hand chosen in priority to perform a manual dexterity task) and hand dominance (hand with best motor performance) in eight macaques (Macaca fascicularis) and in 20 human subjects (10 left-handers and 10 right-handers). Methods Four manual dexterity tests have been executed by the monkeys, over several weeks during learning and stable performance phases (in controlled body position): the modified Brinkman board, the reach and grasp drawer, the tube and the bimanual board tasks. Three behavioral tests, adapted versions from the monkeys tasks (modified Brinkman board, tube and bimanual board tasks), as well as a handedness questionnaire, have been conducted in human subjects. Results In monkeys, there was a large disparity across individuals and motor tasks. For hand dominance, two monkeys were rather right lateralized, three monkeys rather left lateralized, whereas in three monkeys, the different parameters measured were not consistent. For hand preference, none of the eight monkeys exhibited a homogeneous lateralization across the four motor tasks. Macaca fascicularis do not exhibit a clear hand preference. Furthermore, hand preference often changed with task repetition, both during training and plateau phases. For human subjects, the hand preference mostly followed the self-assessment of lateralization by the subjects and the questionnaire (in the latter, right-handers were more lateralized than left-handers), except a few discrepancies based on the tube task. There was no hand dominance in seven right-handers (the other three performed better with the right hand) and in four left-handers. Five left-handers showed left-hand dominance, whereas surprisingly, one left-hander performed better with the right hand. In the modified Brinkman board task, females performed better than males, right-handers better than left-handers. Conclusions The present study argues for a distinction between hand preference and hand dominance, especially in macaque monkeys.

High-density scalp EEG recordings are widely used to study whole-brain neuronal networks in humans non-invasively. Here, we validate EEG mapping of somatosensory evoked potentials (SSEPs) in macaque monkeys (Macaca fascicularis) for the long-term investigation of large-scale neuronal networks and their reorganisation after lesions requiring a craniotomy. SSEPs were acquired from 33 scalp electrodes in five adult anaesthetized animals after electrical median or tibial nerve stimulation. SSEP scalp potential maps were identified by cluster analysis and identified in individual recordings. A distributed, linear inverse solution was used to estimate the intracortical sources of the scalp potentials. SSEPs were characterised by a sequence of components with unique scalp topographies. Source analysis confirmed that median nerve SSEP component maps were in accordance with the somatotopic organisation of the sensorimotor cortex. Most importantly, SSEP recordings were stable both intra- and interindividually. We aim to apply this method to the study of recovery and reorganisation of large-scale neuronal networks following a focal cortical lesion requiring a craniotomy. As a prerequisite, the present study demonstrated that a 300-mm2 unilateral craniotomy over the sensorimotor cortex necessary to induce a cortical lesion, followed by bone flap repositioning, suture and gap plugging with calcium phosphate cement, did not induce major distortions of the SSEPs. In conclusion, SSEPs can be successfully and reproducibly recorded from high-density EEG caps in macaque monkeys before and after a craniotomy, opening new possibilities for the long-term follow-up of the cortical reorganisation of large-scale networks in macaque monkeys after a cortical lesion.Electronic supplementary materialThe online version of this article (doi:10.1007/s00429-014-0776-y) contains supplementary material, which is available to authorized users.