Spastic type Cerebral Palsy (CP) is a motor impairment syndrome resulting from a non-progressive perinatal brain lesion. It is a lifelong condition which reduces an individual's ability to control posture and bodily movements (1). Following a central nervous system lesion, changes in development of the descending pathways causes a reduction in voluntary muscle activation and increased tonic muscle activity which may include spasticity, dystonia, hypertonia, and co-contraction (2–4). Within the lower limb, distal muscles are more impaired (5), which directly impacts lower limb neuromuscular control and the capacity to perform activities of daily living requiring ambulation (6, 7).

Lower limb functional activities of daily living such as ambulation, standing from a chair and climbing stairs, all require control over limb movements to achieve the specific task. To investigate the neuromuscular control required to perform these tasks, and the potential for neuroplasticity following motor learning, both the nervous system and the movement must be considered. Common clinical measures of CP lower limb functional capacity assess gross movement, but do not directly measure neural function during these gross motor tasks. For example, the 6 min walk test measures distance traveled (8), while the selective control assessment of the lower limb rates isolated joint movements (9). Neither assessments involve concurrent measures which probe the nervous system, for example recordings of electrical muscle activity or neural re-organization. To understand underlying neural mechanisms, neurophysiological assessments of the central and peripheral nervous systems are required. Neurophysiological assessment methods including electromyography (EMG) and magnetic resonance imaging (MRI) can determine muscle activation capacity, motor unit firing patterns and firing frequency as well as the amplitude of interference EMG signals and neural tract organization (2, 10, 11). Cross-sectional studies in individuals with CP report reduced capacity to voluntarily activate the plantar flexors and quadriceps by 20–50% (2, 4), reduced electromyography amplitude and motor unit firing rates (12), and altered muscle activation patterns, particularly for distal agonists (13–16).

Active movement training will herein be defined as an intervention requiring volitional muscular effort to achieve a given movement task, exclusive of assisted or passive movements. Intervention studies which aim to improve lower limb joint function, muscular impairment, and functional activity in individuals with CP often use active training modalities including treadmill walking and resistance training which achieve clinically important improvements in strength and walking ability, but typically do not assess neurophysiological outcomes which may indicate neuroplasticity following a perinatal brain lesion (17–19).

Increases in strength achieved with resistance training indicate the trainability of lower limb musculature in CP (20, 21). As knowledge of the neural mechanisms of motor impairment in CP is limited, understanding the neural component of movement control and its adaptability in CP is of great importance for rehabilitation. Preliminary evidence of enhanced neuromuscular control following lower limb active movement training exists in healthy adults and individuals with stroke (22–25), however few studies have used neurophysiological measures to assess changes in neural function and neuromuscular control following interventions in CP. The purpose of this study was to systematically review the current literature to determine the impact of lower limb active movement training in CP on neuromuscular control.

The electronic database search yielded 6,263 potentially relevant studies. Following duplicate removal and initial screening of title and abstract against the inclusion criteria, full texts of the 71 remaining studies were scrutinized, resulting in nine eligible studies included in this review (Figure 1).

The purpose of this study was to systematically review the current literature to determine the impact of lower limb active movement training on neuromuscular control in CP. Nine studies investigating neurophysiological outcomes of active movement training in individuals with CP were included in this review. Improved cortical representation of the ankle and reduced reflex amplitudes during gait allude to a potential for active movement training interventions to elicit favorable lower limb neuromuscular changes in CP. However, the mechanism/s for improvement are unable to be established due to a limited number of studies and diversity of outcome measures used. No study reported deterioration of outcome measures following interventions.

Treadmill training was the most common intervention. Six of the nine studies incorporated variations of treadmill walking training with a training dose ranging from 1.6 h (across 10 days) to 18 h (across 8 weeks). Following body weight supported treadmill training, favorable central nervous system adaptations for motor skill learning were reported. These include fMRI data suggestive of an increase in the area of the primary motor cortex active during isolated voluntary ankle movement (33), and a more refined representation of the foot in the somatosensory cortices, as identified using magnetoencephalography (MEG) during peripheral nerve stimulation (30). One study quantified changes in corticospinal tract (CST) integrity using diffusion tensor imaging (DTI) following a combined upper and lower limb training protocol (27). There was a significant positive group x time effect of training for the whole tract analyses, and lower limb function quantified using a 6 min walk test. Correlations between focal analyses of CST integrity and hand motor function showed a trend for improvement in hand function, but had no correlation to lower limb performance on the 6 min walk test. Combined upper and lower limb intensive motor training appears to have a favorable impact on CST integrity and hand function. However, it is unclear whether or not lower limb training contributed to the improvements in CST integrity observed in this intervention. Although there was a trend toward a relationship between improved CST changes and hand, but not leg, motor function, this observation does not rule out an effect of lower limb training on CSTs. Any such relationship between CST integrity and motor function may have been biased toward the upper limb due to a larger number of upper limb CST axons in the area of measurement. There was also only one physical lower limb performance assessment measure, which may not have been representative of functions affected strongly by CST integrity. It therefore remains unclear what effect lower limb training has on CST integrity following lower limb motor skill learning.

Favorable peripheral nervous system changes were reported in four gait training studies from varied outcome measures which overall indicate a more functionally useful swing phase and foot placement during gait. Improvements in dorsiflexion prior to foot contact and reflex modulation (reduced soleus H-reflex amplitude) (29), improved tibialis anterior coordination enhancing toe lift (coherence between proximal and distal ends of tibialis anterior of the most affected leg) (35), and triceps surae and tibialis anterior activation patterns (sEMG) more similar to typically developed children were reported (28). The fourth small cohort study (n = 2) reported combined changes in the central and peripheral nervous system, with improved corticospinal tract connectivity [increased motor evoked potential (MEP) amplitude during transcranial magnetic stimulation (TMS)] and reduced inhibition of the tibial nerve (improved H-reflex latency and maximum M-wave amplitude), such that the measures approached values observed in typically developed individuals (32). The impact of training volume and progression on these outcomes is unclear as favorable changes were obtained following a range of 100–840 min of gait training (held across 10–28 sessions), and progression of difficulty was not based on categorical performance criteria being met and poorly described (Table 3). In summary, although there are reports of improved neuromuscular control of the ankle plantar flexors and dorsiflexors during gait following treadmill training, the lack of consistency in training doses and objective outcome measures makes it difficult to make recommendations for interventions and monitoring changes.

Similarly, following coordinated dynamics therapy (crawling, treadmill walking, jumping on a spring-board and use of a coordination dynamic therapy device resembling a combined arm and leg ergometer performed seated or supine), sEMG was reported (through visual inspection) to be changed in a favorable way, but this remained unquantified (34). Olsen et al. (31) demonstrated the feasibility of recording dorsi- and plantar flexion muscle activation patterns during selected GMFM items but was unable to determine whether changes in muscle activation sequencing (sEMG on-off ratio) were favorably improved following resistance training due to outcome variability in the small sample. Resistance training has been shown to increase muscle size and strength in individuals with CP (21, 38). Twelve weeks of lower limb, explosive, progressive, heavy resistance training has recently been shown to increase lower limb muscular strength and rate of force development in tibialis anterior (39). Rate of force development is a measure of torque output during a rapid maximum muscle contraction, but is considered by some as a proxy neurophysiological measure because it is strongly determined by neural drive (40). The increase in rate of force development observed by Kirk et al. (39) was accompanied by improved maximum isometric voluntary dorsiflexion, plantar flexion, knee flexion, and knee extension strength. While it appears that strength training may have provided some improvement in capacity to activate the lower limb musculature in adults with CP, the exact mechanisms (neural vs. muscle adaptation) cannot be determined or quantified by these measures alone.

There have been numerous attempts to understand neuroplasticity and neuromuscular changes following interventions targeting muscular adaptations in humans (41–43), yet there is limited information pertaining to the trainability and measurement of neuromuscular control of the lower limb in CP. Of the nine studies included in this review, no studies performed the same neuromuscular outcome measure under the same conditions. This may have been limited by access to equipment and expertise required to perform such assessments. The location of adaptation within the nervous system following intervention is also unknown. It is particularly difficult to identify site specific changes within the nervous system as the results of non-intrusive neurophysiological measurements are often subject to modulation at multiple neural sites.

Although some nervous system changes were reported following active movement training, only three studies (that incorporated treadmill training and HABIT-ILE) found concomitant functional capacity improvements (27, 29, 33). Functional improvements in self-selected overground walking speed were elicited by a short walking training intervention (100 min across 10 days) (29). A slightly longer training duration of bodyweight supported treadmill walking (720 min across 2 weeks) improved walking speed during the 10 m walk test (33). These relatively short training periods suggest there may be an early adaptation period related to the specificity of the task of walking which improves neuromuscular control. These studies did not report on participant's current physical activity levels, familiarization and confidence with treadmill walking prior to the study.

With few studies measuring both neurophysiology and gross motor function outcomes following active movement training, we are not currently able to predict the impact and relationship of all neuromuscular changes on gross motor function. Further, the sensitivity of functional outcome measures to reflect neural changes also remains unknown. For example, intervention studies have demonstrated improvements in lower limb functional capacity without concurrent neurophysiological measurements (19, 38, 44), which limits our capacity to understand whether central and/or peripheral nervous system changes occur and contribute to these observed functional outcomes.

It is premature to speculate on the recommendations for optimal prescription of active movement training to elicit neuromuscular adaptation, due to the variability of interventions among studies and lack of consistency in choice of neuromuscular outcome measures. Despite treadmill training being a popular training mode, previous systematic reviews in children with CP have not been able to determine optimal protocol parameters (45, 46). Treadmill training is a safe and feasible training intervention, but the magnitude of benefit and improvement in lower limb neuromuscular control for individuals at different GMFCS levels is not clear. Large scale trials are still required before guidelines can be considered.

Individual study results must be interpreted with caution due to low study methodological quality, varied training loads and modalities, lack of control groups and diverse use of neurophysiological and neuroimaging outcome measures. Low participant numbers in small cohort studies do not provide sufficient power or external validity to establish whether changes in neuromuscular control are genuine. The effect of age on motor learning and whether there is an optimal time for neural plasticity is unknown. The large range in age of participants makes it difficult to understand both the age dependent adaptability of the nervous system, and the impact of development. Finally, as all participants in the studies reviewed here were diagnosed with spastic CP, and due to the differential effects of lesion location, the findings of nervous system changes suggested may not be generalisable to other types of CP.

Future research should be conscious of the existing neurophysiological outcome measures used to evaluate training interventions, in order to allow for comparison of training mode and training load on the magnitude of change. Future work should also endeavor to apply greater methodological quality than the existing studies. Careful selection of outcome measures which adequately assess regions of the nervous system targeted by training (cortical, spinal cord, neuromuscular junction) is necessary to draw conclusions regarding the impact of training. No single measure will quantify the adaptability of the nervous system as a whole, but adequate and repeated attempts are required to determine mechanisms underlying motor control changes that may be important for function. Due to the complexity of the motor control system, measures that are sensitive enough to measure change over time are required. There are inherent difficulties with performing appropriate neurophysiological assessments. Equipment, expertise and funds are often not readily accessible to clinicians in clinics where these types of interventions and treatment plans are typically conducted.

The impact of active movement training on lower limb neuromuscular control in individuals with CP cannot yet be established. Due to the small number of investigations and their low scientific quality, it is not possible to determine the mechanisms by which the different active movement interventions elicit change within the nervous system. There is disparity in the choice of outcome measures used between studies, which prevents direct comparisons between interventions and the identification of central vs. peripheral nervous system adaptations. Ultimately, the question of whether modalities such as strength training or gait training can favorably alter neuromuscular control of the lower limb in CP remains unclear and requires further investigation. It also remains unclear how changes in neurophysiological measures relate to changes or improvement in gross motor function in CP.

The datasets presented in this study can be found in online repositories. The names of the repositories and references can be found in the article.

SO'B, LB, GL, and TC: conceptualization and data interpretation. SO'B and LB: search and data extraction. SO'B: writing. LB, GL, and TC: reviewing and editing. All authors listed, have made substantial, direct and intellectual contribution to the work, and approved it for publication.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.