A Neuroanatomical Framework for Upper Limb Synergies after Stroke

Great word salad, but totally fucking useless for survivor recovery. Will you kindly create protocols that survivors can follow?

A Neuroanatomical Framework for Upper Limb Synergies after Stroke

 
 
HUMAN NEUROSCIENCE
PERSPECTIVEARTICLE
published: 16 February 2015doi: 10.3389/fnhum.2015.00082
A neuroanatomical framework for upper limb synergiesafter stroke
Angus J. C. McMorland , Keith D. Runnalls  and Winston D. Byblow *
Movement Neuroscience Laboratory, Department of Sport and Exercise Science, Centre for Brain Research,The University of Auckland, Auckland, New Zealand
Edited by:
Ana Bengoetxea, Universidad del País Vasco-Euskal Herriko Unibertsitatea,Spain
Reviewed by:
Jean-LouisThonnard, Université Catholique de Louvain, BelgiumAaron Batista, University of Pittsburgh, USA
*Correspondence:
Winston D. Byblow, Movement Neuroscience Laboratory,Department of Sport and Exercise Science, Centre for Brain Research,The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand e-mail:  w.byblow@auckland.ac.nz
Muscle synergies describe common patterns of co- or reciprocal activation that occurduring movement. After stroke, these synergies change, often in stereotypical ways.Themechanism underlying this change reflects damage to key motor pathways as a result ofthe stroke lesion, and the subsequent reorganization along the neuroaxis, which may befurther detrimental or restorative to motor function.The time course of abnormal synergyformation seems to lag spontaneous recovery that occurs in the initial weeks after stroke.In healthy individuals, motor cortical activity, descending via the corticospinal tract (CST)is the predominant driver of voluntary behavior. When the CST is damaged after stroke,other descending pathways may be up-regulated to compensate. The contribution of these pathways may emerge as new synergies take shape at the chronic stage after stroke, as a result of plasticity along the neuroaxis.The location of the stroke lesion and properties of the secondary descending pathways and their regulation are then critical for shaping the synergies in the remaining motor behavior. A consideration of the integrity of remaining descending motor pathways may aid in the design of new rehabilitation therapies.
Keywords: muscle synergy, stroke, corticospinal tract, proximal–distal patterning, upper limb
DEFINITIONS
“Muscle synergy” can mean subtly different things, creating the opportunity for confusion. As a biological phenomenon, a commonly accepted general definition of muscle synergy is simply a stable spatiotemporal pattern of activity across muscles simultaneously involved in the performance of a movement. Descending neural activity may result in a net excitation or inhibition of the alpha motor neurons innervating each muscle. If motor neurons of two muscles are excited simultaneously, the muscles are coactivated. Conversely, activity in one muscle may coincide with quiescence in another due to reciprocal inhibition. Natural motor behaviors may result from the additive effect of several synergies. In recent experiments, the term “muscle synergy” has been used to label estimates of synergies derived from quantitative matrix factorization methods applied to simultaneous electromyographic (EMG) measurements (Tresch et al., 2006). The details of the mathematical operation determine specific properties of the synergy estimates extracted. For example,non-negative matrix factorization (NNMF) does not capture inhibitory relationships, which may be a limitation of the method. Another usage of synergy arises in clinical settings, where the term “abnormal muscle synergies” may refer only to the pathological patterns of muscle co-activation that emerge after disruption of the motor
Abbreviations:
 BB,biceps brachii; cM1,contralesional M1; CRPP,cortico-reticulo-propriospinal pathway; CST, corticospinal tract; c-tDCS, cathodal tDCS; EMG,electromyography; FM, Fugl-Meyer assessment; M1, primary motor cortex; MEP,motor evoked potential; MRI, magnetic resonance imaging; NNMF, non-negativematrix factorization; PLIC, posterior limb of the internal capsule; SR, synergy ratio; tDCS, transcranial direct current stimulation; TMS, transcranial magneticstimulation.
system, such as stroke (Brunnström, 1970). This phrasing stems from the fact that pathological synergies are “lower dimensional”than in healthy individuals, hence there are more co-dependencies(synergies) present. In the present article, we adopt the general definition of the term synergy given above, although reference will also be made to clinically abnormal synergies as well as synergies identified by matrix factorization, and the caveats with regard to the definitions of each should be borne in mind.
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 uni-manual and bimanual conditions(Kelsoetal.,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
Frontiers in Human Neuroscience www.frontiersin.org
 February 2015 |Volume 9 | Article 82 |
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McMorland et al. Neuroanatomical framework for post-stroke synergies
therefore potentially more dynamic and context-dependent thanhard synergies.In healthy humans, the corticospinal tract (CST) is the princi-pal conveyor of voluntary drive to the upper limb (Lemon,2008). Consequently, it is along this neural pathway that the sourceof 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 mus-cle 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 activationgives 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 haveeffects depending on the context.
Figure 1
 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 CSTfiberstomotorneuronpoolsinthespinalcord.Such individuated cortical connectivity is typical of distal muscles. C4 is similarly
FIGURE 1 |A schematic of descending pathways involved in the formation of synergies in healthy motor behavior, and their disruption after stroke
. Direct CST connections exist from the cortex to motor neuron pools predominantly for distal muscles, green pathways from C1 to C5.Other CST connections, dark gray pathways from C2 and C3, carry low-dimensional motor commands and innervate synergy-forming spinal modules S1 and S2, which in turn have divergent connections to multiple motor neuron pools at several rostrocaudal levels. Red lines from C4represent a cortically derived synergy controlling the three proximal motorneuron pools. Connections from C4 and C5 normally inhibit the contralateral motor cortex. Among other functions, this transcallosal input regulates alternate descending pathways like the CRPP (blue lines), which innervates propriospinal neurons linking multiple proximal limb segments.Dark red and wavy horizontal lines indicate sites of damage caused by three stroke lesions. Lesion 1 disrupts low-dimensional information from C3 tothe synergy module at S1, and therefore would interfere with activation of the whole synergy mediated by S1, while leaving the synergy structure intact. Lesion 2 represents a mild event, transecting part of the cortically derived synergy from C4, which would alter its structure. Lesion 2 also damages transcallosal connections to the contralesional hemisphere,reducing interhemispheric inhibition and up-regulating the CRPP and other alternate, ipsilateral descending pathways. Since the lesion only affects a small number of CST fibers, remaining descending connections will subsume the damaged functions, and prognosis is good.The up-regulatedCRPP interferes with productive CST drive. Suppression of the contralesional hemisphere by non-invasive brain stimulation, for example,c-tDCS, may reduce CRPP activity and thus be beneficial. Lesion 3 is larger than lesion 2, resulting in a severe impairment. Here, the CRPP represents the majority of remaining drive, meaning that c-tDCS of the contralesional hemisphere could be disadvantageous [c.f., Bradnam et al. (2012)].
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 tothe S1 module is latent (dashed) in the healthy condition. Finally,interhemispheric pathways exist from C4 and C5 to the contralat-eral motor cortex.The contralateral cortex contains, among others,connections to the brainstem and alternative descending pathways