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. Author manuscript; available in PMC: 2024 Apr 1.
Published in final edited form as: Clin Neurophysiol. 2023 Jan 25;148:9–16. doi: 10.1016/j.clinph.2023.01.004

Spinal cord H-reflex post-activation depression is linked with hand motor control in adults with cerebral palsy

Saihari S Dukkipati 1, Sarah J Walker 1, Michael P Trevarrow 1, Morgan T Busboom 1, Max J Kurz 1,2,*
PMCID: PMC9998348  NIHMSID: NIHMS1870124  PMID: 36773504

Abstract

Objective:

Cerebral palsy (CP) is associated with upper extremity motor impairments that are largely assumed to arise from alterations in the supraspinal networks. The objective of this study was to determine if post-activation depression of the spinal H-reflexes is altered in adults with CP and connected with altered upper extremity function.

Methods:

The post-activation depression of the flexor carpi radialis (FCR) H-reflex of adults with CP and healthy adults (HA) controls were assessed by 1) a 1 Hz continuous single-pulse stimulus train and 2) 0.11 Hz / 1 Hz paired-pulse stimuli. Secondarily, we measured the maximum key grip force and the box and blocks assessment of manual dexterity.

Results:

Our results revealed that adults with CP had reduced post-activation depression of the FCR H-reflex during the stimulus train and the paired pulse protocol. A greater reduction in H-reflex post-activation depression was connected to lower manual dexterity and weaker grip forces.

Conclusions:

Our results indicate that the post-activation depression of the upper extremity spinal H-reflex pathways is altered in adults with CP and possibly linked with their uncharacteristic upper extremity motor performance. Alterations in the spinal networks may also play a significant role in the altered motor control of adults with CP.

Significance:

Our results identify spinal H-reflex modulation as a possible locus for hand motor control in CP.

Keywords: spinal networks, manual dexterity, grip strength, upper extremity, hand motor control

INTRODUCTION

Cerebral palsy (CP) is the most prevalent pediatric neurologic impairment diagnosed in the United States (Maenner et al., 2016). The focus of the clinical research and care of individuals with CP has primarily had an emphasis on childhood with less attention placed on the transition of these children into adulthood. In fact, only four percent of all National Institutes of Health-funded research on CP between 2001 to 2013 was on adults (Wu et al., 2015). One important area of emphasis for studies on adults with CP is focused on the neurophysiological changes that are likely contributing to declines in motor function as youth with CP transition into adulthood. Although most of the neurophysiological studies have been focused on supraspinal networks (Hoffman et al., 2021, Trevarrow et al., 2021a, Trevarrow et al., 2021b), the spinal cord pathways connecting the brain and musculoskeletal systems may also significantly contribute to the impaired motor control noted in adults with CP (Achache et al., 2010, Edgerton et al., 2021, Gad et al., 2021).

The Hoffman reflex, or H-reflex, is a well-studied and highly replicated neurophysiological probe of the proprioceptive sensory pathways that activate the spinal motoneurons (Knikou, 2008). Post-activation depression is a spinal pathway mechanism that leads to a depressive effect of the size of the H-reflex (Hultborn et al., 1996). This depression results from changes in the probability of neurotransmitter release at the Ia afferent synapses and is dependent on prior Ia afferent activity (Kuno, 1964). It is a process that is thought to minimize afferent inputs during sustained or repeated muscle stretches (Floeter and Kohn, 1997). Changes in the post-activation depression have been observed in multiple neuromotor conditions including spasticity (Achache et al., 2010, Field-Fote et al., 2006, Grey et al., 2008, Lamy et al., 2009), rigidity (Raoul et al., 2012), and flaccidity (Ozyurt et al., 2020a). Importantly, this pathway has been shown to be altered in the lower limb musculature of adults with CP and linked with the severity of ankle spasticity and clonus (Achache et al., 2010). Intriguingly, the stimulus parameters normally utilized (0.33 Hz or higher) to obtain the spinal H-reflex in people with CP have largely been indicative of a loss in post-activation depression (Achache et al., 2010, Futagi and Abe, 1985, Hodapp et al., 2007, Hodapp et al., 2009, Mahmud et al., 2011), which is thought to occur at frequencies higher than 0.125 Hz (Hultborn et al., 1996).

Post-activation depression might play a role in the uncharacteristic upper extremity motor actions of adults with cerebral palsy (CP). Therefore, the purpose of this series of experiments was to determine if post-activation depression is altered in the flexor carpi radialis (FCR) muscle of adults with CP and plays a role in the reduced hand motor function noted in this population. To that end, we quantified the amount of post-activation depression of the FCR H-reflex of adults with CP under two conditions: 1) 1 Hz continuous single-pulse stimulus train and 2) 0.11 Hz / 1 Hz paired-pulse stimulus paradigm. Notably, we sought to examine the effect of repetitive stimulation on the amount of PAD generated by using the train paradigm. Secondarily, we evaluated the hand motor control by quantifying the maximum key grip force and the Box and Blocks assessment of manual dexterity. Based on the lower extremity literature, we hypothesized that the adults with CP would display a diminished post-activation depression of the FCR H-reflex relative to healthy adults (HA). We also hypothesized that the adults with CP would display lower hand key grip forces and manual dexterity relative to HA controls. Lastly, we hypothesized that the extent of the hand motor impairments seen in the adults with CP would be linked with uncharacteristic post-activation depression of the FCR H-reflex.

MATERIALS AND METHODS

Participants.

The Institutional Review Board reviewed and approved the protocol for this investigation. Furthermore, this experimental work conformed to the standards set by the Declaration of Helsinki, except for registration in a database. Participants and/or their guardians provided written informed consent to experimental procedures and all participants assented to participate in the investigation. In total, thirty-four subjects participated in this investigation. Sixteen were adults with CP (N = 16, Ages 20 to 60, average = 29.26+/−10.4 yrs.; 9 males/7 females; Manual Ability Classification System (MACS) levels I-IV) and eighteen were HA controls (N = 18, Ages 21 to 62, average = 31.22+/−10.1 yrs.; 7 males/11 females). The HA had no known neurological or musculoskeletal impairments that affected their hand movements at the time of the investigation. The exclusion criteria for the individuals with CP were excluded from the study if they had a dorsal root rhizotomy at the cervical levels or underwent upper extremity botulinum injections within the last 6 months. Healthy adult controls were excluded if presenting with an upper extremity musculoskeletal injury or neurological disorder. Further details of the participants with CP included in this investigation are shown in Table 1.

Table 1.

Demographics of the participants with cerebral palsy that were included in this investigation.

Age (yrs.) Sex MACS GMFCS Clinical Presentation Brain Insults
23 F 2 2 Spastic Diplegic Bilateral polymicrogyria most prominent in the occipital and parietal lobes, cerebellar hypoplasia/dysplasia, callosal dysgenesis
23 M 1 1 L Spastic Hemiplegia R periatrial trigone focus of remote ischemia
22 M 3 3 Spastic Diplegic Severe corpus callosal aplasia, posterior white matter atrophy, parietal cortical atrophy
34 F 2 2 Spastic Diplegic No abnormal findings noted
29 M 3 2 R Spastic Hemiplegia L frontal atrophy and polymicrogyria, corpus callous aplasia with parietal and cerebellar atrophy
38 M 4 4 Spastic Quadriplegia Bilateral posterior parietal periventricular volume loss and diffuse abnormal white matter signal, atrophy of the posterior corpus callosum
26 M 3 2 L Spastic Hemiplegia R parietal polymicrogyria, mild asymmetric enlargement of R lateral ventricle, corpus callosum enlargement
24 M 2 2 Spastic Diplegia Partial absence of the corpus callosum
20 F 1 1 R Spastic Hemiplegia Unable to complete MRI due to metal
33 F 4 4 Spastic Quadriplegia Bilateral posterior superior ventricle periventricular volume loss, empty sella
40 F 1 1 Spastic Diplegia No abnormal findings noted
60 M 3 1 Spastic Diplegia No abnormal findings noted
23 F 3 3 Spastic Diplegia* Unable to complete MRI due to metal
21 M 1 1 Spastic Hemiplegia Mild signal loss bilaterally in the periatrial trigones, periventricular leukomalacia
19 F 3 1 Spastic Diplegia No abnormal findings noted.
26 M 2 1 R Spastic Hemiplegia Unable to complete MRI due to metal
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MACS = Manual Ability Classification Scale, GMFCS= Gross Motor Function Classification Score, R= Right, L= Left.

*

participant was taking oral baclofen. The information provided on the participant’s brain insults represent the radiologist’s read of a T1 brain MRI.

Experimental Design.

All participants were comfortably seated in a custom, upright neck-supporting chair. The examined arm was positioned with the shoulder in a neutral position and elbow flexed at 90°. The forearm of the tested arm was pronated and restrained by straps to limit compensatory movements. The experimental tasks were performed with the right arm. For the individuals with left-sided hemiplegia, the tasks were performed in the left arm. Initially, a percutaneous stimulation paradigm was conducted to determine the stimulus-response curves for the FCR, from which the individualized maximum H-reflex (Hmax) was identified. The maximum H-reflex was subsequently used for the post-activation depression determination using two stimulation paradigms: 1) a 1 Hz single-pulse stimulus train protocol and 2) a 0.11 Hz/1 Hz paired-pulse stimulation protocol. The participants also completed clinical assessment of their manual dexterity and hand key grip strength. Further details on the specifics of the methodology employed in this investigation are detailed in the following sections.

Electromyographic recordings.

Electromyography (EMG) was recorded from the FCR muscle through surface electrodes taped to the skin over the muscle during the H-reflex stimulus-response curve assessment and post-activation depression stimulation paradigms (Trigno; Delsys, Natick, MA, USA). The placement of the EMG sensors (at one third of the distance between the medial epicondyle and radial styloid) was done with respect to anatomical landmarks and photographed to ensure similar electrode positions between subjects. To optimize the quality of the EMG signal, the skin over the FCR muscle was cleaned with 70% isopropyl alcohol prep pads prior to electrode placement to reduce impedance at the skin-electrode interface. The collected signals were amplified, band-pass filtered (20–500 Hz), and sampled at 1926Hz (USB 6501 multifunction I/O device, National Instruments) for online and a posteriori analysis with a custom MATLAB program.

H-reflex Stimulus-Response Curves.

Initially the participants underwent an upper extremity spinal H-reflex protocol using a constant-current stimulator. Percutaneous nerve stimulation (single rectangular pulses, 1-msec pulse duration; Digitimer DS8R, Ft. Lauderdale, FL) was performed to elicit H-reflexes in the FCR muscle. The median nerve of the tested limb was stimulated with the unipolar surface electrodes positioned medially in the antecubital fossa, cathode proximal as shown in Figure 1. Prior investigations suggested that FCR H-reflexes can be elicited at rest in 95% of cases of HA controls and adults that have incurred a stroke (Christie et al., 2005, Lamy et al., 2009, Phadke et al., 2012). Our protocol followed the technical parameters from these studies to successfully elicit the H-reflex from the FCR without an active contraction. Stimulation was used to generate stimulus recruitment curves with increasing levels of stimulus intensity. The maximum H-wave (H-max) at rest was obtained at 0.1Hz to eliminate the possibility of contamination of responses by post-activation depression. The intensity that was used to generate responses at or near the H-max was subsequently used in the assessments of the post-activation depression.

Figure 1. Experimental Setup.

Figure 1.

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This figure shows the experimental setup for the neurophysiological testing. In (A), a depiction of the neurophysiological setup including the representation of the arm and forearm showing the stimulating electrodes (placed in the antecubital fossa) and the EMG sensor (placed on the belly of the flexor carpi radialis muscle) is provided. In B, the first stimulation task is depicted: a train of 10 stimuli at 1Hz. In C, the second stimulation task is depicted: a paired-pulse paradigm of 2 stimuli with an inter-pair interval (IPI) of 1 s and an inter-stimulus interval (ISI) of 9 s.

Post-activation depression testing.

Post-activation depression at the FCR Ia afferent-motoneuron synapse was studied by exploring the depressive effect by varying the stimulus rate (Achache et al., 2010, Aymard et al., 2001, Hultborn et al., 1996). To that end, the single pulse condition consisted of a stimulus train with an inter-stimulus interval (ISI) of 1s (Figure 1B), while the paired-pulse stimulation consisted of two stimulations that were applied with an inter-pair interval (IPI) of 1 s and an ISI of 9 s (Figure 1C). Essentially, the frequency of the single pulse train was 1 Hz and the pair-pulse train was 0.11 Hz. The respective stimulation paradigms allowed for 10 pairs of H-reflexes (20 reflexes each) to be measured for each condition.

The amount of post-activation depression that occurred during the single-pulse paradigm was assessed by calculating percent change in average of the H-reflex seen across the 2–10th stimulations relative to the first H-reflex:

%HTrain=1n−1Σn2max(Hreflexn)max(Hreflex1)*100 Equation 1.

where Hreflex1 is the first H-reflex evoked, n is the number of H-reflexes applied in the stimulation train. A larger HTrain signifies less post-activation depression. This calculation was modelled after the stimulus train study previously conducted by Worthington and colleagues (Worthington et al., 2021).

The post-activation depression that occurred during the paired-pulse paradigm was calculated from the following equation:

H1:H9ratio=Hresponse1Hresponse9 Equation 2.

where Hresponse1 is the response obtained every 1 second (at 1Hz) and Hresponse9 is the response obtained every 9 seconds (at 0.11Hz). A larger H1:H9 ratio would signify less post-activation depression (i.e., H1 ≅H9). This approach was modelled after the 1:6 ratio calculation of PAD undertaken previously by Achache and colleagues (Achache et al., 2010).

The train and paired-pulse paradigms were not randomized. Hence, our experimental design consisted of performing the train protocol first, followed by the paired-pulse protocol. There was a minute or longer between the respective paradigms in order to provide the participant with a break and to provide instructions on the subsequent stimulation protocol. The interval between the respective protocols exceeds the minimal duration that has been documented in the literature (at least 10 seconds, Hultborn et al., 1996).

Motor function testing.

All participants completed the standardized Box and Blocks Test of hand dexterity (Araneda et al., 2019, Mathiowetz et al., 1985). Briefly, the participants were instructed to move as many blocks as possible from one compartment across to another within a 60-second period using the tested arm. Participants that moved a fewer number of blocks were classified as having reduced hand dexterity.

The participants also completed a hand key grip task with their tested arm. Briefly, the maximal hand key grip force was assessed with a custom-built force transducer system. The force transducer system was a button load cell (CZL204E, Phidgets Inc., Calgary CA) that was interfaced with an analogue-to-digital board (Phidgets Inc., Calgary CA) and sampled at 1kHz. A custom C++/OpenGL program displayed the subject’s force production in real-time on the computer screen and was represented as a bar that ascended vertically. The subjects were given three attempts and were instructed to provide a force that moved the bar vertically as far as possible. Rests were allowed as needed between each grip to avoid fatigue, and the attempt that produced the greatest force was used for maximal key grip performance.

Statistical Analyses.

Equality of variance was initially checked for the respective outcome measures using Levene’s equality of variance testing. The D’Agostino & Pearson test for normality indicated that the post-activation depression measure was not normally distributed. Thus, group comparisons of the amount of H-reflex post-activation depression and the respective outcome measures were evaluated using nonparametric Mann-Whitney U tests. Spearman’s correlation coefficient was performed to examine the relationship between the clinical assessments and H-reflex post-activation depression measures for the adults with CP. In all tests, statistical significance was assumed if P < 0.05.

RESULTS

H-Reflex Single-Pulse Stimulation Train.

Figure 2 illustrates the results from the 1Hz single-pulse train paradigm (Task 1). The H-reflex responses evoked at each of the respective stimuli in the trains are displayed in Figure 2A. Inspection of Figure 2A suggests that the adults with CP did not have depression of their H-reflex response with subsequent stimulations, while the amplitude of the H-reflex was lower after successive stimulations for the HA controls. Statistical analysis confirmed this observation by revealing that the adults with CP had a higher HTrain compared with the healthy adult controls (HA: 71.7+/−5.89%, CP: 89.3+/−4.77%, P = 0.036; Figure 2B). Hence, these results indicate that the adults with CP were unable to modulate or properly gate the H-reflex with repetitive stimulation applied at 1 Hz.

Figure 2. The HTrain averages are lower for the healthy adults (HA) than the HTrain averages for the adults with cerebral palsy (CP).

Figure 2.

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The data from the H-Reflex stimulation train are shown for HC controls and adults with cerebral palsy (CP). (A) shows the bar graph of the mean +/− SEM of the responses for each stimulus in the 1Hz train. (B) shows a box-and-whisker plot of the HTrain averages for HA controls and adults with CP. This is an average of the second through tenth responses in the 1Hz train. Data in A and B are plotted with values standardized to a % of Hfirst. As shown, the HTrain averages were significantly larger in the adults with CP, when compared with the HA controls. * indicates P<0.05. Hfirst – the first H-reflex response in the stimulus train, HTrain average – the average of the second through tenth H-reflex responses in the stimulus train.

H-Reflex Paired-Pulse Stimulation Paradigm.

Figure 3 illustrates examples of H-waves in the FCR muscle during the paired-pulse paradigm for two representative participants (Figure 3A and 3B). Note that the response amplitudes varied for every participant. However, the second response in this paired-pulse paradigm was typically smaller than the first response, as shown in Figure 3A, in healthy adults only. Statistical analysis revealed that the adults with CP had larger H1:H9 ratio compared with the HA controls (HA: 70.2+/−4.96, CP: 96.5+/−2.83, P < 0.0001; Figure 3C). This indicates that the adults with CP continued to be unable to depress the H-reflex during the paired-pulse stimulation paradigm. We did not observe any relationship between the H-max amplitude and the H1:H9 ratios (P > 0.05) in the cohort of individuals with CP.

Figure 3. The H1:H9 ratios for healthy adults (HA) are lower than the H1:H9 ratios for the adults with cerebral palsy (CP).

Figure 3.

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Typical H-wave responses of the flexor carpi radialis (FCR) muscle from an exemplary HA control (A) and an adult with CP (B) are shown, along with a box- and-whisker plot of the group H1:H9 ratio differences and the bar graph of the mean +/− SEM of the 10 response pairs (C). V = volt; msec = milliseconds. EMG amplitude from the FCR muscle is shown on the y-axis and time (msec) is denoted on the x-axis, with 0 msec defined as the onset of the stimulus artifact. In (A) and (B), the H9 response (response obtained at 0.11 Hz) is shown on the left and the H1 response (response obtained at 1Hz) is shown on the right. As shown in (C), the H1:H9 ratios were statistically larger in the adults with CP, when compared with the HA controls. **** indicates P<0.0001.

Relationships with functional outcomes and age.

The ages of the respective groups were not significantly different (P > 0.05). The adults with CP moved fewer blocks on the Box and Blocks test compared with the HA controls (HA: 137.1 +/− 3.17 blocks, CP: 75.8 +/− 8.25 blocks, P < 0.0001). There was a trend towards weaker hand key grip forces in the adults with CP compared with the HA controls (HA: 217.0+/−11.1 V, CP: 184.1+/−12.0 V, P = 0.058). There was a significant negative rank-order relationship between the maximal key grip forces and the H1:H9 ratios for the adults with CP (rho = −0.618, P = 0.013; Figure 4A). There was also a significant negative rank-order relationship between the number of blocks moved and the H1:H9 ratios for the adults with CP (rho = −0.571, P = 0.023; Figure 4B). Altogether these correlations imply that the adults with CP that had less post-activation depression of the FCR H-reflex tended to have weaker hand key grip forces and have less manual dexterity. No other correlations between functional outcomes and respective stimulation tasks were significant (P > 0.05).

Figure 4. Post-activation depression and motor function are related in adults with cerebral palsy (CP).

Figure 4.

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The relationship between flexor carpi radialis (FCR) H-reflex post-activation depression and functional outcomes in adults with CP are shown. In (A), the rank-order correlation between the maximal hand key grip forces and H1:H9 ratios for the adults with CP are plotted. Rank-order of the H1:H9 ratios is shown on the x-axis, while the rank-order of maximal hand key grip forces is shown on the y-axis. In (B), the rank-order correlation between the number of blocks moved for the Box and Blocks test and H1:H9 ratios for the adults with CP are plotted. Rank-order of the H1:H9 ratios is shown on the x-axis, while the rank-order of the number of blocks moved is shown on the y-axis. As shown, there were significant negative correlations between the amount of post-activation depression (the size of the H1:H9 ratio) and the participant’s maximal key grip force (rho = −0.618; P = 0.013) and manual dexterity (rho = −0.571; P = 0.023). These imply that adults with CP that had higher H1:H9 ratios (lower post-activation depression) also tended to produce smaller grip forces and move less blocks.

DISCUSSION

We investigated post-activation depression of the FCR H-reflex in adults during a 1 Hz single-pulse train and paired-pulse stimulation paradigm. When compared with HA controls, our results revealed that the adults with CP had less post-activation depression for both stimulation paradigms. Furthermore, we identified that adults with CP that had less post-activation depression tended to also display lower manual dexterity and weaker hand key grip forces. Further discussion of these results and their implications are discussed in the following sections.

H-Reflex Single-Pulse 1Hz Stimulation Train

One of our primary findings is that adults with CP had larger HTrain values during the 1Hz single-pulse train paradigm. The stimulus train allows for the examination of the time course of post-activation changes in spinal H-reflex responses. The characteristic continuous depression of the H-reflex with consecutive stimuli (Hultborn et al., 1996) was noted in the FCR muscle of HA controls, but not in adults with CP. This novel finding suggests that there may be a disinhibition of the upper extremity H-reflex spinal pathways in CP that normally serve to dampen excessive afferent inputs during repetitive stimulation. The stimulation train evokes repeated firing of the Ia afferent fibers, which should cause a subsequent depression of the transmission across the monosynaptic reflex arc due to changes in neurotransmitter release at the Ia afferent-motoneuron synapses (Hultborn et al., 1996). The decreased post-activation depression of Ia synapses that we observed may be an adaptation that develops following alterations in the corticospinal motor system (see below) and aberrant wrist flexor Ia afferent firing (Williams et al., 2017). The functional significance of this alteration in PAD remains unclear, although it may be linked to the dynamics of muscle force generation (Ozyurt et al., 2020b).

H-Reflex Paired-Pulse Stimulation Paradigm

We also found that adults with CP had a larger H1:H9 ratio, which is an indicator of a decrease in rate or frequency-dependent depression of the H-reflex (Achache et al., 2010, Aymard et al., 2001, Lamy et al., 2009). Our finding largely agrees with the results from a lower extremity investigation that found a decreased post-activation depression for the soleus muscle in adults with CP (Achache et al., 2010). In addition, our results are also strikingly similar to the post-activation depression noted for the FCR muscle of adults who have incurred a stroke (Aymard et al., 2000, Lamy et al., 2009). We found that there was limited PAD in our cohort of adults with CP such that the average H1:H9 ratio was around 1. The consistently low PAD across our subjects with CP and the strong overlap in the outcomes from related studies is suggestive of a common spinal pathway modification in the lower and upper extremity pathways in adults with corticospinal lesions (adults with CP and adults after a stroke) that decreases post-activation depression.

Pathophysiological Mechanisms for Decreased PAD in CP

The corticospinal tracts are important for acquiring and maintaining spinal reflex patterns (Clowry, 2007) and their connectivity has been shown to shape spinal cord function (Eyre, 2007). In people with CP, who are thought to have perinatal lesions affecting these tracts, diminished cortical drive may be responsible for the decreased PAD. Prior TMS results have shown that adults with spastic CP likely have an impaired ability to fully activate the corticospinal pathways (Condliffe et al., 2019). The amount of PAD is thought to be greater with higher cortical drives, which allows for less inhibited conscious motor control (Faist et al., 1996, Hultborn et al., 1987, Ozyurt et al., 2020b). Intriguingly, it has recently been shown that the decreased motor cortical activity is linked with alterations in the spinal cord white matter in adults with cerebral palsy (Trevarrow et al., 2022). Hence, we speculate that changes to the activity and integrity of corticospinal pathways are potentially linked with the alterations in the PAD observed in our cohort of adults with CP.

Relationships with Clinical Outcomes.

People with CP have been shown to have reduced hand grip force and manual dexterity (Basu et al., 2018, Dekkers K. et al., 2020, Dekkers Kjfm et al., 2020, Dellatolas et al., 2005, Rich et al., 2017, Tomhave et al., 2015). In this study, we found that the diminished FCR H-reflex post-activation depression in adults with CP was linked to reductions in manual dexterity. While the hand key grip force generation was not significantly different in the adults with CP, we found that the individuals with CP that had the lowest amount of post-activation depression also generated the smallest key grip forces. Taken together, these findings suggest that the post-activation depression of the FCR H-reflex may have an important functional significance related to force generation and regulation of motor output during upper extremity tasks in adults with CP. Prior studies of post-activation depression in adults with CP and adults who have incurred a stroke have also reported strong relationships with the severity of spasticity and clonus (Achache et al., 2010, Lamy et al., 2009).

While the FCR muscle is not directly activated during handgrip and manual dexterity tasks, it functions to stabilize the wrist during these tasks (Duque et al., 1995, Forman et al., 2019). Thus, it is probable that the strong correlations we observed are related to the maintenance of wrist stability during these motor tasks in individuals with low amounts of PAD. Alternatively, individuals with greater overall motor function may have performed better on these clinical measures and the relationships reflects this notion. Contrary to this viewpoint, we did not observe a significant relationship between the clinical measures from this study and the amount of PAD measured with the stimulus train. There were a few possible explanations for this. First, the timing of the repetitive stimulation over a short period of time (measured 9 times over 10 seconds) in the train may have had a variable effect on all adults with CP compared to the paired-pulse paradigm (measured 1 time over 1 second). Second, there were more data points averaged for the paired-pulse measure compared to the train measure (10 to 1). Thus, there may have been more variability with the responses using the train stimulus paradigm.

Limitations and future directions

The heterogeneity in the cohort of people with CP in this study should be acknowledged. Some of the PAD changes we observed in people with CP may have resulted from musculoskeletal changes linked to aging, including biomechanical properties in the wrist flexor muscle. Future studies with larger sample sizes comparing individuals with different clinical presentations may be useful, especially with enough statistical power to examine different subgroups separated by age. We excluded participants with CP that were utilizing botulinum toxin on their wrist muscles or that had a cervical-level dorsal root rhizotomy affecting the upper extremities. However, one of the subjects in this study was on oral baclofen (see Table 1). The impact of botulinum toxin, dorsal root rhizotomies and baclofen on PAD in people with CP remains to be assessed in future investigations.

As we did not examine the level of spasticity in the wrist muscles of adults with CP in this study, it would be important to examine whether the low amount of PAD we observed is linked with higher levels of spasticity in the wrist flexor muscles as observed in the lower extremity muscles (Achache et al., 2010). We also utilized a single stimulus intensity (set at the intensity generating the Hmax) for assessing PAD in this study. We did not observe any relationship between the H-max amplitude and the amount of PAD in the cohort of individuals with CP. However, it would be valuable to assess PAD in people with CP using a range of stimulation intensities (i.e., 0.5 Hmax and 1.1 Hmax).

CONCLUSION

This study shows that adults with CP have diminished post-activation depression of the FCR H-reflex. This modification in the spinal pathway was linked with the extent of hand motor impairment. At this juncture, it is unclear whether the changes in post-activation depression are linked to the processes that contribute to the reduction in hand key grip forces and manual dexterity or a component of the compensatory strategies taken to amplify motor output. It is also unclear whether these changes occurred because of the systemic processes following the original brain lesion or through the cascade of lifespan modifications leading to increased immobilization and disuse of the wrist flexor muscles in persons with CP, as disuse has been shown to cause plastic changes in the spinal interneuronal circuits that regulate post-activation depression of the H-reflex (Lundbye-Jensen and Nielsen, 2008a, 2008b). Finally, modulation of post-activation depression is thought to be involved in the encoding of motor memories in the spinal cord, with increased amounts of H-reflex post-activation depression noted in tandem with improved motor performance after skilled training relative to non-skilled training (Meunier et al., 2007). Thus, plastic changes at the spinal level that occur through long-term specific motor training could be expressed in H-reflex post-activation depression as observed in swimmers (Patikas et al., 1999) and ballet dancers (Obata et al., 2022). The possibility of utilizing post-activation depression as a marker of motor skill retention with upper limb training in adults with CP is certainly an avenue for future investigations.

HIGHLIGHTS.

  • We explored the post-activation depression of H-reflexes in the upper limbs of adults with cerebral palsy.

  • In this study, we linked changes in spinal reflex pathways to upper extremity motor function in adults with cerebral palsy.

  • While the literature focuses on supraspinal pathways, our results identify spinal modulation as a possible locus for motor control in CP.

ACKNOWLEDGEMENTS

This work was partially supported by grants from the National Institutes of Health (R01HD086245, R01HD101833, 1R01HD108205, R21HD096390, P20GM144641).

Footnotes

CONFLICT OF INTEREST

The authors have no conflicts of interest to report.

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