Corticoreticular Pathway in Post-Stroke Spasticity: A Diffusion Tensor Imaging Study

One of the pathophysiologies of post-stroke spasticity (PSS) is the imbalance of the reticulospinal tract (RST) caused by injury to the corticoreticular pathway (CRP) after stroke. We investigated the relationship between injuries of the CRP and PSS using MR diffusion tensor imaging (DTI). The subjects were divided into spasticity and control groups. We measured the ipsilesional fractional anisotropy (iFA) and contralesional fractional anisotropy (cFA) values on the reticular formation (RF) of the CRP were on the DTI images. We carried out a retrospective analysis of 70 patients with ischemic stroke. The cFA values of CRP in the spasticity group were lower than those in the control group (p = 0.04). In the sub-ROI analysis of CRP, the iFA values of pontine RF were lower than the cFA values in both groups (p < 0.05). The cFA values of medullary RF in the spasticity group were lower than the iFA values within groups, and also lower than the cFA values in the control group (p < 0.05). This results showed the CRP injury and that imbalance of RST caused by CRP injury was associated with PSS. DTI analysis of CRP could provide imaging evidence for the pathophysiology of PSS.

Express arm Responses Appear Bilaterally on Upper-limb Muscles in Arm Choice Reaching Task

When required, humans can generate very short latency reaches towards a visual target, like catching a phone falling off a desk. During such rapid reaches, express arm responses are the first wave of upper limb muscle recruitment, occurring within ~80-100 ms of target appearance. There is accumulating evidence that express arm responses arise from signaling along the tecto-reticulo-spinal tract, but the involvement of the reticulo-spinal tract has not been well-studied. Since the reticulospinal tract projects bilaterally, we studied whether express arm responses would be expressed bilaterally. Human participants (n = 14; 7 female) performed visually guided reaches in a modified emerging target paradigm where either arm could be used to intercept a target once it emerged below a barrier. We recorded electromyographic activity bilaterally from the pectoralis major muscle. Our analysis focused on target locations where participants reached with the right arm on some trials, and the left arm on others. In support of the involvement of the reticulospinal tract, the express arm response persisted bilaterally regardless of which arm reached to the target. While the latency of the express arm response was the same on the reaching vs non-reaching arm, the response magnitude was slightly larger on the reaching arm, in part due to anticipatory muscle recruitment related to arm choice. Our results support the involvement of the reticulo-spinal tract in mediating the express arm response, and we surmise that the increased magnitude on the arm chosen to move arises from convergence of cortically derived signals with the largely independent express arm response.

The Strength of the Corticospinal Tract Not the Reticulospinal Tract Determines Upper-Limb Impairment Level and Capacity for Skill-Acquisition in the Sub-Acute Post-Stroke Period

Background. Upper-limb impairment in patients with chronic stroke appears to be partly attributable to an upregulated reticulospinal tract (RST). Here, we assessed whether the impact of corticospinal (CST) and RST connectivity on motor impairment and skill-acquisition differs in sub-acute stroke, using transcranial magnetic stimulation (TMS)–based proxy measures. Methods. Thirty-eight stroke survivors were randomized to either reach training 3-6 weeks post-stroke (plus usual care) or usual care only. At 3, 6 and 12 weeks post-stroke, we measured ipsilesional and contralesional cortical connectivity (surrogates for CST and RST connectivity, respectively) to weak pre-activated triceps and deltoid muscles with single pulse TMS, accuracy of planar reaching movements, muscle strength (Motricity Index) and synergies (Fugl-Meyer upper-limb score). Results. Strength and presence of synergies were associated with ipsilesional (CST) connectivity to the paretic upper-limb at 3 and 12 weeks. Training led to planar reaching skill beyond that expected from spontaneous recovery and occurred for both weak and strong ipsilesional tract integrity. Reaching ability, presence of synergies, skill-acquisition and strength were not affected by either the presence or absence of contralesional (RST) connectivity. Conclusion. The degree of ipsilesional CST connectivity is the main determinant of proximal dexterity, upper-limb strength and synergy expression in sub-acute stroke. In contrast, there is no evidence for enhanced contralesional RST connectivity contributing to any of these components of impairment. In the sub-acute post-stroke period, the balance of activity between CST and RST may matter more for the paretic phenotype than RST upregulation per se.

Measurement of stretch-evoked brainstem function using fMRI

Knowledge on the organization of motor function in the reticulospinal tract (RST) is limited by the lack of methods for measuring RST function in humans. Behavioral studies suggest the involvement of the RST in long latency responses (LLRs). LLRs, elicited by precisely controlled perturbations, can therefore act as a viable paradigm to measure motor-related RST activity using functional Magnetic Resonance Imaging (fMRI). Here we present StretchfMRI, a novel technique developed to study RST function associated with LLRs. StretchfMRI combines robotic perturbations with electromyography and fMRI to simultaneously quantify muscular and neural activity during stretch-evoked LLRs without loss of reliability. Using StretchfMRI, we established the muscle-specific organization of LLR activity in the brainstem. The observed organization is partially consistent with animal models, with activity primarily in the ipsilateral medulla for flexors and in the contralateral pons for extensors, but also includes other areas, such as the midbrain and bilateral pontomedullary contributions.

Ipsilateral Motor Evoked Potentials as a Measure of the Reticulospinal Tract in Age-Related Strength Changes

Background: The reticulospinal tract (RST) is essential for balance, posture, and strength, all functions which falter with age. We hypothesized that age-related strength reductions might relate to differential changes in corticospinal and reticulospinal connectivity.Methods: We divided 83 participants (age 20–84) into age groups &lt;50 (n = 29) and ≥50 (n = 54) years; five of which had probable sarcopenia. Transcranial Magnetic Stimulation (TMS) was applied to the left cortex, inducing motor evoked potentials (MEPs) in the biceps muscles bilaterally. Contralateral (right, cMEPs) and ipsilateral (left, iMEPs) MEPs are carried by mainly corticospinal and reticulospinal pathways respectively; the iMEP/cMEP amplitude ratio (ICAR) therefore measured the relative importance of the two descending tracts. Grip strength was measured with a dynamometer and normalized for age and sex.Results: We found valid iMEPs in 74 individuals (n = 44 aged ≥50, n = 29 &lt; 50). Younger adults had a significant negative correlation between normalized grip strength and ICAR (r = −0.37, p = 0.045); surprisingly, in older adults, the correlation was also significant, but positive (r = 0.43, p = 0.0037).Discussion: Older individuals who maintain or strengthen their RST are stronger than their peers. We speculate that reduced RST connectivity could predict those at risk of age-related muscle weakness; interventions that reinforce the RST could be a candidate for treatment or prevention of sarcopenia.

The knowns and unknowns of neural adaptations to resistance training

The initial increases in force production with resistance training are thought to be primarily underpinned by neural adaptations. This notion is firmly supported by evidence displaying motor unit adaptations following resistance training; however, the precise locus of neural adaptation remains elusive. The purpose of this review is to clarify and critically discuss the literature concerning the site(s) of putative neural adaptations to short-term resistance training. The proliferation of studies employing non-invasive stimulation techniques to investigate evoked responses have yielded variable results, but generally support the notion that resistance training alters intracortical inhibition. Nevertheless, methodological inconsistencies and the limitations of techniques, e.g. limited relation to behavioural outcomes and the inability to measure volitional muscle activity, preclude firm conclusions. Much of the literature has focused on the corticospinal tract; however, preliminary research in non-human primates suggests reticulospinal tract is a potential substrate for neural adaptations to resistance training, though human data is lacking due to methodological constraints. Recent advances in technology have provided substantial evidence of adaptations within a large motor unit population following resistance training. However, their activity represents the transformation of afferent and efferent inputs, making it challenging to establish the source of adaptation. Whilst much has been learned about the nature of neural adaptations to resistance training, the puzzle remains to be solved. Additional analyses of motoneuron firing during different training regimes or coupling with other methodologies (e.g., electroencephalography) may facilitate the estimation of the site(s) of neural adaptations to resistance training in the future.

Activation of the Supplementary Motor Areas Enhances Spinal Reciprocal Inhibition in Healthy Individuals

The supplementary motor area (SMA) may modulate spinal reciprocal inhibition (RI) because the descending input from the SMA is coupled to interneurons in the spinal cord via the reticulospinal tract. Our study aimed to verify whether the anodal transcranial direct current stimulation (anodal-tDCS) of the SMA enhances RI. Two tDCS conditions were used: the anodal stimulation (anodal-tDCS) and sham stimulation (sham-tDCS) conditions. To measure RI, there were two conditions: one with the test stimulus (alone) and the other with the conditioning-test stimulation intervals (CTIs), including 2 ms and 20 ms. RI was calculated at multiple time points: before the tDCS intervention (Pre); at 5 (Int 5) and 10 min; and immediately after (Post 0); and at 5, 10 (Post 10), 15, and 20 min after the intervention. In anodal-tDCS, the amplitude values of H-reflex were significantly reduced for a CTI of 2 ms at Int 5 to Post 0, and a CTI of 20 ms at Int 5 to Pot 10 compared with Pre. Stimulation of the SMA with anodal-tDCS for 15 min activated inhibitory interneurons in RIs by descending input from the reticulospinal tract via cortico–reticulospinal projections. The results showed that 15 min of anodal-tDCS in the SMA enhanced and sustained RI in healthy individuals.

Measurement of stretch-evoked brainstem function using fMRI

ABSTRACTKnowledge on the organization of motor function in the reticulospinal tract (RST) is limited by the lack of methods for measuring RST function in humans. Behavioral studies suggest the involvement of the RST in long latency responses (LLRs). LLRs, elicited by precisely controlled perturbations, can therefore act as a viable paradigm to measure motor-related RST activity using functional Magnetic Resonance Imaging (fMRI).Here we present StretchfMRI, a novel technique developed to study RST function associated with LLRs. StretchfMRI combines robotic perturbations with electromyography and fMRI to simultaneously quantify muscular and neural activity during stretch-evoked LLRs without loss of reliability. Using StretchfMRI, we established the muscle-specific organization of LLR activity in the brainstem. The observed organization is partially consistent with animal models, with activity primarily in the ipsilateral medulla for flexors and in the contralateral pons for extensors, but also include other areas, such as the midbrain and bilateral pontomedullary contributions.

Limited Capacity for Ipsilateral Secondary Motor Areas to Support Hand Function Post-Stroke

Recent findings have shown connections of ipsilateral cortico-reticulospinal tract (CRST), predominantly originating from secondary motor areas, to not only proximal but also distal portions of the arm. In unilateral stroke, CRST from the ipsilateral side is intact and thus has been proposed as a possible backup system for post-stroke rehabilitation even for the hand. We argue that although CRST from ipsilateral secondary motor areas can provide control for proximal joints, it is insufficient to control either hand or coordinated shoulder and hand movements due to its extensive branching compared to contralateral corticospinal tract. To address this issue, we combined MRI, high-density EEG, and robotics in 17 individuals with severe chronic hemiparetic stroke and 12 age-matched controls. We tested for changes in structural morphometry of the sensorimotor cortex and found that individuals with stroke demonstrated higher gray matter density in secondary motor areas ipsilateral to the paretic arm compared to controls. We then measured cortical activity while participants attempted to generate hand opening either supported on a table or while lifting against a shoulder abduction load. The addition of shoulder abduction during hand opening increased reliance on ipsilateral secondary motor areas in stroke, but not controls. Crucially, increased use of ipsilateral secondary motor areas was associated with decreased hand opening ability while lifting the arm due to involuntary coupling between the shoulder and wrist/finger flexors. Together, this evidence implicates a compensatory role for ipsilateral (i.e., contralesional) secondary motor areas post-stroke, but with limited capacity to support hand function.

Following Spinal Cord Injury Transected Reticulospinal Tract Axons Develop New Collateral Inputs to Spinal Interneurons in Parallel with Locomotor Recovery

The reticulospinal tract (RtST) descends from the reticular formation and terminates in the spinal cord. The RtST drives the initiation of locomotion and postural control. RtST axons form new contacts with propriospinal interneurons (PrINs) after incomplete spinal cord injury (SCI); however, it is unclear if injured or uninjured axons make these connections. We completely transected all traced RtST axons in rats using a staggered model, where a hemisection SCI at vertebra T10 is followed by a contralateral hemisection at vertebra T7. In one group of the animals, the T7 SCI was performed 2 weeks after the T10 SCI (delayed; dSTAG), and in another group, the T10 and T7 SCIs were concomitant (cSTAG). dSTAG animals had significantly more RtST-PrIN contacts in the grey matter compared to cSTAG animals (p<0.05). These results were accompanied by enhanced locomotor recovery with dSTAG animals significantly outperforming cSTAG animals (BBB test;p<0.05). This difference suggests that activity in neuronal networks below the first SCI may contribute to enhanced recovery, because dSTAG rats recovered locomotor ability before the second hemisection. In conclusion, our findings support the hypothesis that the injured RtST forms new connections and is a key player in the recovery of locomotion post-SCI.