Mechanisms of Synergy Formation
To make sense of the ways in which stroke can alter muscle synergies, we need first to appreciate the relationship between the anatomical and physiological basis for synergy formation, and the deficit caused by the stroke, remembering that both acute and chronic changes occur. Abstractly, synergies represent low-dimensional movement information expressed in a higher dimensional space of possible activations. Some synergies may arise purely from functional coordination of high-dimensional structures (“functional synergies”). These functional synergies could be considered “soft” in the sense there are not dedicated anatomical structures existing to subserve them. For example, the spatiotemporal dynamics of upper limb movement change markedly in the context of bimanual tasks, even though the anatomical substrate (for a single side) is identical between unimanual and bimanual conditions (Kelso et al., 1979). Alternatively, synergies may be constructed in synergy-specific anatomical structures and then at some subsequent point in the motor pathway that information would have to diverge to the different muscles. These “anatomical synergies” would be “hard,” in the sense that the combinations of muscles involved will be relatively fixed. Soft synergies resulting purely from functional co-activation are therefore potentially more dynamic and context-dependent than hard synergies.
In healthy humans, the corticospinal tract (CST) is the principal conveyor of voluntary drive to the upper limb (Lemon, 2008). Consequently, it is along this neural pathway that the source of synergies has been proposed. The least flexible hard synergies are presumably expressed by dedicated interneuron networks within the spinal cord. Microstimulation in the spinal cord of frogs [reviewed in Bizzi et al. (2008) or rats (Tresch and Bizzi, 1999)] activates combinations of muscles that depend on the precise stimulation location, generate directed movements, and can be combined to form natural behaviors like jumping and swimming. This result has been taken as evidence of the existence in the spinal cord of anatomical modules that construct hard muscle synergies. Overduin et al. (2012) found that microstimulation of the motor cortex activated combinations of very similar synergies to those observed in natural grasping. That cortical activation gives rise to multiple different synergies suggests that their site of generation lies downstream of the cortex, either in the brainstem or spinal cord.
Mapping studies have been used to identify regions of cerebral cortex connected to a particular muscle, either by direct anatomical tract tracing (Rathelot and Strick, 2006), single cell recording (Schieber and Hibbard, 1993), or assessing functional connectivity with transcranial magnetic stimulation (TMS; Devanne et al., 2006). Instead of the neat, somatotopic arrangement of muscles implied by the motor homunculus concept [which was actually an oversimplification of the reports of Penfield; see Penfield (1954)], maps derived using these methods show that muscle representations on the cortical surface have distributed, complex shapes that overlap with areas connected to other muscles. Overlapping maps are consistent with an anatomical basis for cortical control of hard synergies, since such an architecture means that activation at a single locus on the cortex results in activation of all of the muscles represented at that point, and as the region of activation increases in area, neighboring regions can be recruited in a systematic manner (Wickens et al., 1994; Rathelot and Strick, 2006; Capaday et al., 2013). Distributed muscle representations in primary motor cortex, along with extensive horizontal projections (Huntley and Jones, 1991) may provide a flexible network substrate for soft synergies. A cortical basis for synergies is further supported by the observation that discharge of single corticomotor neurons strongly correlates with activity in a functional set of muscles (Holdefer and Miller, 2002). These different mechanisms and sites of synergy formation, functional, spinal, and cortical, are not mutually exclusive, and it seems likely that all could have effects depending on the context.
Figure Figure11 shows a schematic of motor control structures and descending pathways from the cortex to muscles. C1–5 represent functionally differentiated cortical modules, capturing the repertoire of theorized modes of descending output. These need not correspond to specific anatomical structures, while their relative spatial arrangement is suggestive of the distributed arrangement seen in the cortex, where adjoining regions can represent non-contiguous muscles. C1 and C5 are connected via direct CST fibers to motor neuron pools in the spinal cord. Such individuated cortical connectivity is typical of distal muscles. C4 is similarly connected, but represents a cortical synergy, potentially distinct anatomical regions that are modulated as a unit by common inputs and producing correlated outputs. C2 and C3 connect in a one-to-one fashion to spinal synergy modules (S1 and S2) that each have branching, overlapping connectivity to motor neuron pools. A lateral connection between the descending pathways from C2 to the S1 module is latent (dashed) in the healthy condition. Finally, interhemispheric pathways exist from C4 and C5 to the contralateral motor cortex. The contralateral cortex contains, among others, connections to the brainstem and alternative descending pathways such as the cortico-reticulo-propriospinal pathway (CRPP), which divergently innervate multiple, primarily proximal motor neuron pools.
