Asymmetric and Distant Effects of a Unilateral Lesion of the Primary Motor Cortex on the Bilateral Supplementary Motor Areas in Adult Macaque Monkeys

Abstract

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.

Cortical Projection From the Premotor or Primary Motor Cortex to the Subthalamic Nucleus in Intact and Parkinsonian Adult Macaque Monkeys: A Pilot Tracing Study

“…To assess the relationship between the number of BDA-labeled boutons with the interaction between motor impairment (PD symptoms based on manual dexterity in the modified-Brinkman board task post-ANCE transplantation (see above) and dopaminergic (tyrosine hydroxylase positive (TH+) neurons) loss in the substantia nigra pars compacta (SNpc), we performed a multivariable linear regression model test (MATLAB R2017b, function ''fitlm''; Contestabile et al, 2018).…”

Variable Interhemispheric Asymmetry in Layer V of the Supplementary Motor Area following Cervical Hemisection in Adult Macaque Monkeys

“…(Morecraft et al, 2016;Savidan et al, 2017) for the non-human primate). In a recent article from this laboratory, we reported that a unilateral lesion of the M1 hand area led to a variable interhemispheric asymmetry in the detection of layer V pyramidal neurons in SMA, identified with the marker SMI-32 (Contestabile et al, 2018). This anatomical variable interhemispheric Contestabile et al SMA in SCI monkeys 5 imbalance possibly reflects an adaptive interhemispheric contribution of the bilateral SMA to recovery, depending on the lesion size as well as on the duration of functional recovery (Contestabile et al, 2018).…”

“…In a recent article from this laboratory, we reported that a unilateral lesion of the M1 hand area led to a variable interhemispheric asymmetry in the detection of layer V pyramidal neurons in SMA, identified with the marker SMI-32 (Contestabile et al, 2018). This anatomical variable interhemispheric Contestabile et al SMA in SCI monkeys 5 imbalance possibly reflects an adaptive interhemispheric contribution of the bilateral SMA to recovery, depending on the lesion size as well as on the duration of functional recovery (Contestabile et al, 2018). It was argued that these observations may represent a putative anatomical support of diaschisis, originally defined as a "loss of function and electrical activity in an area of the brain due to a lesion in a remote area that is neuronally connected with it" (Finger, Koehler andJagella, 2004 andsee von Monakow, 1914).…”

“…In the current study, the main goal was to transpose this concept of interhemispheric adaptable SMA reorganization related to functional recovery from a lesion of M1 (Contestabile et al, 2018) to a cervical spinal cord hemisection. Does a unilateral spinal cord injury (SCI) also affect differently the contralesional versus the ipsilesional SMA, because the CS projection from SMA is predominantly crossed ( Fig.…”

Assessment of the effect of continuous theta burst stimulation of the motor cortex on manual dexterity in non‐human primates in a direct comparison with invasive intracortical pharmacological inactivation

“…The exact mechanisms behind this recovery are still a matter of debate. In this context, non‐human primate (NHP) models are valuable tools to study mechanisms of cortical plasticity following localized specific lesion of the motor cortex, such as interhemispheric changes of cellular density in premotor areas (Contestabile et al., ), in rewiring of cortico‐cortical connections (Dancause et al., ) or vicariation (Hoogewoud et al., ; Liu & Rouiller, ; Murata et al., ). Theories of functional recovery distinguished redundancy from vicariation (see Finger, for review; see also Slavin, Lawrence, & Stein, ).…”