Disynaptic Reciprocal Inhibition Research Articles

Relationship between spinal reflexes and leg motor function in sub-acute and chronic stroke patients

ObjectiveTo assess the relationship between spinal reflexes and motor function in sub-acute (SAS) and chronic stroke (CS) patients. MethodsTwelve SAS and 16 CS patients underwent electrophysiological assessment of heteronymous facilitation (HF), heteronymous inhibition (HI), disynaptic reciprocal inhibition (DRI), and D1 inhibition (D1). The Fugl-Meyer Assessment Lower Extremity (FMA-LE) and modified Ashworth scale (MAS) were assessed. The relationship between spinal reflexes and motor function was examined in a cross-sectional manner. SAS patients were also longitudinally evaluated before and after intensive rehabilitation for approximately 2 months. ResultsSAS patients with triceps surae muscle spasticity (MAS ≥ 1) showed higher HF values (p = 0.03) than those without spasticity. SAS patients with quadriceps muscle spasticity showed higher HF values (p < 0.01); patients with hamstring muscle spasticity showed higher DRI value (disinhibition) (p < 0.01) than those without spasticity. CS patients showed no significant correlation between spinal reflexes and motor function. The longitudinal study revealed a significant correlation between increase in D1 inhibition and FMA-LE improvement in SAS patients (r = 0.69). ConclusionsThe association between impaired spinal reflexes varies with the stage of stroke; HF and DRI may be spasticity indicators in SAS patients. SignificanceSpinal reflexes as potential biomarkers may facilitate tailor-made rehabilitation of stroke patients.

Effects of Leg Motor Imagery Combined With Electrical Stimulation on Plasticity of Corticospinal Excitability and Spinal Reciprocal Inhibition.

Motor imagery (MI) combined with electrical stimulation (ES) enhances upper-limb corticospinal excitability. However, its after-effects on both lower limb corticospinal excitability and spinal reciprocal inhibition remain unknown. We aimed to investigate the effects of MI combined with peripheral nerve ES (MI + ES) on the plasticity of lower limb corticospinal excitability and spinal reciprocal inhibition. Seventeen healthy individuals performed the following three tasks on different days, in a random order: (1) MI alone; (2) ES alone; and (3) MI + ES. The MI task consisted of repetitive right ankle dorsiflexion for 20 min. ES was percutaneously applied to the common peroneal nerve at a frequency of 100 Hz and intensity of 120% of the sensory threshold of the tibialis anterior (TA) muscle. We examined changes in motor-evoked potential (MEP) of the TA (task-related muscle) and soleus muscle (SOL; task-unrelated muscle). We also examined disynaptic reciprocal inhibition before, immediately after, and 10, 20, and 30 min after the task. MI + ES significantly increased TA MEPs immediately and 10 min after the task compared with baseline, but did not change the task-unrelated muscle (SOL) MEPs. MI + ES resulted in a significant increase in the magnitude of reciprocal inhibition immediately and 10 min after the task compared with baseline. MI and ES alone did not affect TA MEPs or reciprocal inhibition. MI combined with ES is effective in inducing plastic changes in lower limb corticospinal excitability and reciprocal Ia inhibition.

Acute whole-body vibration increases reciprocal inhibition

Based on previous evidence that whole-body vibration (WBV) affects pathways involved in disynaptic reciprocal inhibition (DRI), the present hypothesis-driven experiment aimed to assess the acute effects of WBV on DRI and co-contraction. DRI from ankle dorsiflexors to plantar flexors was investigated during submaximal dorsiflexion before and after 1 min of WBV. With electromyography, musculus soleus (SOL) H-reflex depression following a conditioning stimulation of the peroneal nerve (1.1x motor threshold for the musculus tibialis anterior, TA) was assessed and co-contraction was calculated. After WBV, DRI was significantly increased (+4%, p < 0.05). SOL (−13%, p < 0.05) and TA (−6%, p < 0.05) activities were significantly reduced; co-contraction tended to be diminished (−8%, p = 0.05). Dorsiflexion torque remained unchanged. After WBV, DRI increased during submaximal isometric contraction in healthy subjects. The simultaneous SOL relaxation and TA contraction indicate that a more economic movement execution is of functional significance for WBV application in clinical and athletic treatment.

Reciprocal inhibition between motor neurons of the tibialis anterior and triceps surae in humans.

Motor neurons innervating antagonist muscles receive reciprocal inhibitory afferent inputs to facilitate the joint movement in the two directions. The present study investigates the mutual transmission of reciprocal inhibitory afferent inputs between the tibialis anterior (TA) and triceps surae (soleus and medial gastrocnemius) motor units. We assessed this mutual mechanism in large populations of motor units for building a statistical distribution of the inhibition amplitudes during standardized input to the motor neuron pools to minimize the effect of modulatory pathways. Single motor unit activities were identified using high-density surface electromyography (HDsEMG) recorded from the TA, soleus (Sol), and medial gastrocnemius (GM) muscles during isometric dorsi- and plantarflexion. Reciprocal inhibition on the antagonist muscle was elicited by electrical stimulation of the tibial (TN) or common peroneal nerves (CPN). The probability density distributions of reflex strength for each muscle were estimated to examine the strength of mutual transmission of reciprocal inhibitory input. The results showed that the strength of reciprocal inhibition in the TA motor units was fourfold greater than for the GM and the Sol motor units. This suggests an asymmetric transmission of reciprocal inhibition between ankle extensor and flexor muscles. This asymmetry cannot be explained by differences in motor unit type composition between the investigated muscles since we sampled low-threshold motor units in all cases. Therefore, the differences observed for the strength of inhibition are presumably due to a differential reciprocal spindle afferent input and the relative contribution of nonreciprocal inhibitory pathways. NEW & NOTEWORTHY We investigated the mutual transmission of reciprocal inhibition in large samples of motor units using a standardized input (electrical stimulation) to the motor neurons. The results demonstrated that the disynaptic reciprocal inhibition exerted between ankle flexor and extensor muscles is asymmetric. The functional implication of asymmetric transmission may be associated with the neural strategies of postural control.

P208 The effects of transcutaneous spinal cord stimulation on spinal reciprocal inhibition in healthy persons

Introduction Transcutaneous spinal cord stimulation (tSCS) is a non-invasive method to stimulate afferent structures of the spinal neural circuits related with lower limb motor control. Its application is known to improve lower limb motor function in individuals with spinal cord injury. However, it remains unknown whether tSCS induces spinal plasticity, which has an essential role in functional recovery of the lower limb after spinal cord injury and stroke. Objectives The purpose of this study was to investigate the effects of tSCS on spinal reciprocal inhibition in healthy individuals. Methods Twelve healthy volunteers participated in this single-masked, sham-controlled crossover study. The following three paradigms were randomly applied to them on three different days: (1) tSCS; (2) sham tSCS; (3) transcutaneous peripheral nerve patterned electrical stimulation (tPES). tSCS and tPES consisted of a train of 10 pulses at 100 Hz every 2 s for 20 min. tSCS was delivered to the thoracic spine level (Th11/12) with the intensity of sensory threshold × 2.0 without muscle contraction. tPES was applied to common peroneal nerve using the intensity equal to the motor threshold of tibialis anterior muscle. For sham stimulation, the same procedure was used, but the current was delivered for only 30 s.We assessed disynaptic reciprocal inhibition (RI) and presynaptic inhibition (D1) using a soleus H-reflex conditioning-test paradigm. The magnitudes of inhibition was assessed before, immediately after, 15 min and 30 min after the stimulation. Results tSCS significantly increased the amount of D1 inhibition immediately after and at 15 min after when compared with the baseline, and the effects were greater than other conditions immediately after and at 15 min after the stimulation. tSCS concurrently increased the amount of RI immediately after. tPES significantly increased the amount of RI until 15 min after the stimulation, but did not affect the D1 inhibition. Conclusion The present results provide further evidence that tSCS can induce short-term plastic changes in human spinal reciprocal inhibitory interneuron.

Resistance training with instability is more effective than resistance training in improving spinal inhibitory mechanisms in Parkinson's disease.

Patients with Parkinson's disease (PD) have motor dysfunction. Spinal inhibitory mechanisms are important for modulating both supraspinal motor commands and sensory feedback at the spinal level. Resistance training with instability was more effective than resistance training in increasing the levels of presynaptic inhibition and disynaptic reciprocal inhibition of lower limb at rest of the patients with PD, reaching the average values of the healthy controls.

The effects of anodal transcranial direct current stimulation and patterned electrical stimulation on spinal inhibitory interneurons and motor function in patients with spinal cord injury.

Supraspinal excitability and sensory input may play an important role for the modulation of spinal inhibitory interneurons and functional recovery among patients with incomplete spinal cord injury (SCI). Here, we investigated the effects of anodal transcranial direct current stimulation (tDCS) combined with patterned electrical stimulation (PES) on spinal inhibitory interneurons in patients with chronic incomplete SCI and in healthy individuals. Eleven patients with incomplete SCI and ten healthy adults participated in a single-masked, sham-controlled crossover study. PES involved stimulating the common peroneal nerve with a train of ten 100 Hz pulses every 2 s for 20 min. Anodal tDCS (1 mA) was simultaneously applied to the primary motor cortex that controls the tibialis anterior muscle. We measured reciprocal inhibition and presynaptic inhibition of a soleus H-reflex by stimulating the common peroneal nerve prior to tibial nerve stimulation, which elicits the H-reflex. The inhibition was assessed before, immediately after, 10 min after and 20 min after the stimulation. Compared with baseline, simultaneous application of anodal tDCS with PES significantly increased changes in disynaptic reciprocal inhibition and long-latency presynaptic inhibition in both healthy and SCI groups for at least 20 min after the stimulation (all, p < 0.001). In patients with incomplete SCI, anodal tDCS with PES significantly increased the number of ankle movements in 10 s at 20 min after the stimulation (p = 0.004). In conclusion, anodal tDCS combined with PES could induce spinal plasticity and improve ankle movement in patients with incomplete SCI.

Cycling Regimen Induces Spinal Circuitry Plasticity and Improves Leg Muscle Coordination in Individuals With Spinocerebellar Ataxia

ObjectivesTo compare the reciprocal control of agonist and antagonist muscles in individuals with and without spinocerebellar ataxia (SCA) and to evaluate the effect of a 4-week leg cycling regimen on functional coordination and reciprocal control of agonist and antagonist muscles in patients with SCA. DesignRandomized controlled trial with repeated measures. SettingResearch laboratory in a general hospital. ParticipantsIndividuals with SCA (n=20) and without SCA (n=20). InterventionsA single 15-minute session of leg cycling and a 4-week cycling regimen. Main Outcome MeasuresIndividuals with SCA (n=20) and without SCA (n=20) underwent disynaptic reciprocal inhibition and D1 inhibition tests of the soleus muscles before and after a single 15-minute cycling session. Individuals with SCA were randomly assigned to either participate in 4 weeks of cycling training (n=10) or to receive no training (n=10). The disynaptic reciprocal inhibition and D1 inhibition and International Cooperative Ataxia Rating Scale (ICARS) scores were evaluated in both groups after 4 weeks. ResultsIndividuals with SCA showed abnormally strong resting values of disynaptic reciprocal inhibition and D1 inhibition (P<.001) and impaired inhibition modulation capacity after a single 15-minute session of cycling (P<.001). The inhibition modulation capacity was restored (P<.001), and the ICARS scores improved significantly (pre: 13.5±9.81, post: 11.3±8.74; P=.046) after 4 weeks of cycling training. ConclusionsA 4-week cycling regimen can normalize the modulation of reciprocal inhibition and functional performance in individuals with SCA. These findings are applicable to the coordination training of patients.

Comparação de inibições medulares entre indivíduos com doença de Parkinson e saudáveis

O objetivo do presente estudo foi comparar os níveis de inibição pré-sináptica (IPS) e inibição recíproca (IR) entre indivíduos com Doença de Parkinson e saudáveis e, a correlação entre essas inibições e a rigidez muscular e a severidade clínica de indivíduos com Doença de Parkinson (avaliadas através da Escala Unificada de Avaliação da Doença de Parkinson). Foram avaliados 11 indivíduos nos estágios 2 e 3 da doença e 13 indivíduos saudáveis pareados pela idade. A IPS foi menor em indivíduos com Doença de Parkinson (31,6%) do que em saudáveis (67,1%) (p = 0,02). A IR não diferiu entre indivíduos com Doença de Parkinson (26,9%) e saudáveis (27,6%) (p = 0,91). Adicionalmente, não foram detectadas correlações entre os níveis de IPS com a rigidez e a severidade clínica (p &gt; 0,05). Portanto, mecanismos inibitórios não explicam totalmente a rigidez muscular e a severidade clinica da doença. Alterações entre ativação de músculos agonistas e antagonistas parecem estar relacionadas a influências supraespinhais anormais nos mecanismos espinhais decorrentes da doença.

Lack of Neuromuscular Origins of Adaptation After a Long-Term Stretching Program

Static stretching is commonly used during the treatment and rehabilitation of orthopedic injuries to increase joint range of motion (ROM) and muscle flexibility. Understanding the physiological adaptations that occur in the neuromuscular system as a result of long-term stretching may provide insight into the mechanisms responsible for changes in flexibility. To examine possible neurological origins and adaptations in the Ia-reflex pathway that allow for increases in flexibility in ankle ROM, by evaluating the reduction in the synaptic transmission of Ia afferents to the motoneuron pool. Repeated-measures, case-controlled study. Sports medicine research laboratory. 40 healthy volunteers with no history of cognitive impairment, neurological impairment, or lower extremity surgery or injury within the previous 12 mo. Presynaptic and postsynaptic mechanisms were evaluated with a chronic stretching pro- tocol. Twenty subjects stretched 5 times a wk for 6 wk. All subjects were measured at baseline, 3 wk, and 6 wk. Ankle-dorsiflexion ROM, Hmax:Mmax, presynaptic inhibition, and disynaptic reciprocal inhibition. Only ROM had a significant interaction between group and time, whereas the other dependent variables did not show significant differences. The experimental group had significantly improved ROM from baseline to 3 wk (mean 6.2 ± 0.9, P < .001), 3 wk to 6 wk (mean 5.0 ± 0.8, P < .001), and baseline to 6 wk (mean 11.2 ±0.9, P < .001). Ankle dorsiflexion increased by 42.25% after 6 wk of static stretching, but no significant neurological changes resulted at any point of the study, contrasting current literature. Significant neuromuscular origins of adaptation do not exist in the Ia-reflex-pathway components after a long-term stretching program as currently understood. Thus, any increases in flexibility are the result of other factors, potentially mechanical changes or stretch tolerance.

Spinal inhibition of descending command to soleus motoneurons is removed prior to dorsiflexion

It has recently been demonstrated that soleus motor-evoked potentials (MEPs) are facilitated prior to the onset of dorsiflexion. The purpose of this study was to examine if this could be explained by removal of spinal inhibition of the descending command to soleus motoneurons. To test this, we investigated how afferent inputs from the tibialis anterior muscle modulate the corticospinal activation of soleus spinal motoneurons at rest, during static contraction and prior to movement. MEPs activated by transcranial magnetic stimulation (TMS) and Hoffmann reflexes (H-reflexes), activated by electrical stimulation of the posterior tibial nerve (PTN), were conditioned by prior stimulation of the common peroneal nerve (CPN) at a variety of conditioning-test (CT) intervals. MEPs in the precontracted soleus muscle were inhibited when the TMS pulse was preceded by CPN stimulation with a CT interval of 35 ms, and they were facilitated for CT intervals of 50-55 ms. A similar inhibition of the soleus H-reflex was not observed. To investigate which descending pathways might be responsible for the afferent-evoked inhibition and facilitation, we examined the effect of CPN stimulation on short-latency facilitation (SLF) and long-latency facilitation (LLF) of the soleus H-reflex induced by a subthreshold TMS pulse at different CT intervals. SLF is known to reflect the excitability of the fastest conducting, corticomotoneuronal cells whereas LLF is believed to be caused by more indirect descending pathways. At CT intervals of 40-45 ms, the LLF was significantly more inhibited compared to the SLF when taking the effect on the H-reflex into account. Finally, we investigated how the CPN-induced inhibition and facilitation of the soleus MEP were modulated prior to dorsiflexion. Whereas the late facilitation (CT interval: 55 ms) was similar prior to dorsiflexion and at rest, no inhibition could be evoked at the earlier latency (CT interval: 35 ms) prior to onset of dorsiflexion. The observation that the CPN-induced inhibition of soleus MEPs disappears prior to onset of dorsiflexion may explain why soleus MEPs are facilitated prior to onset of dorsiflexion contraction. A possible mechanism involves the removal of inhibition of the descending command to the motoneurons at a spinal interneuronal level because the inhibition was seen in LLF and not in SLF, and the MEP inhibition was not observed in the H-reflex. The data illustrate that spinal interneuronal pathways modify descending commands to human spinal motoneurons and influence the size of MEPs elicited by TMS.

Transcranial direct current stimulation modulates the spinal plasticity induced with patterned electrical stimulation

Objective Patterned sensory electrical stimulation (PES) has been shown to induce plasticity in spinal reciprocal Ia inhibition of the calf muscles. To study the cortical modulation of spinal plasticity, we examined the effects of giving transcranial direct current stimulation (tDCS) to the motor cortex before PES. Methods Seven healthy volunteers participated in this study. PES involved stimulating the left common peroneal nerve at the fibular head with a train of 10 pulses at 100 Hz every 1.5 s for 20 min using an intensity equal to the motor threshold of the tibialis anterior. tDCS was applied for 10 min before PES. For anodal stimulation, the electrode was placed over the motor cortex, and the cathodal electrode over the contralateral supraorbital area. For cathodal stimulation, the electrodes were reversed. Reciprocal inhibition was assessed using a soleus H reflex conditioning-test paradigm. Results PES increased disynaptic reciprocal inhibition from the peroneal nerve to the soleus H reflex. When cathodal tDCS was applied before PES, PES no longer increased reciprocal inhibition. Conclusions Applying tDCS before PES modulated the effects of PES on spinal reciprocal inhibition in a polarity specific manner. Significance We suggest that the motor cortex may play a role in spinal plasticity.

WS2-3 Disynaptic Ia reciprocal inhibition in stroke patients before and after therapeutic electrical stimulation

WS2-3 Disynaptic Ia reciprocal inhibition in stroke patients before and after therapeutic electrical stimulation

Spasticity Mechanisms – for the Clinician

Spasticity, a classical clinical manifestation of an upper motor neuron lesion, has been traditionally and physiologically defined as a velocity dependent increase in muscle tone caused by the increased excitability of the muscle stretch reflex. Clinically spasticity manifests as an increased resistance offered by muscles to passive stretching (lengthening) and is often associated with other commonly observed phenomenon like clasp-knife phenomenon, increased tendon reflexes, clonus, and flexor and extensor spasms. The key to the increased excitability of the muscle stretch reflex (muscle tone) is the abnormal activity of muscle spindles which have an intricate relation with the innervations of the extrafusal muscle fibers at the spinal level (feed-back and feed-forward circuits) which are under influence of the supraspinal pathways (inhibitory and facilitatory). The reflex hyperexcitability develops over variable period of time following the primary lesion (brain or spinal cord) and involves adaptation in spinal neuronal circuitries caudal to the lesion. It is highly likely that in humans, reduction of spinal inhibitory mechanisms (in particular that of disynaptic reciprocal inhibition) is involved. While simply speaking the increased muscle stretch reflex may be assumed to be due to an altered balance between the innervations of intra and extrafusal fibers in a muscle caused by loss of inhibitory supraspinal control, the delayed onset after lesion and the frequent reduction in reflex excitability over time, suggest plastic changes in the central nervous system following brain or spinal lesion. It seems highly likely that multiple mechanisms are operative in causation of human spasticity, many of which still remain to be fully elucidated. This will be apparent from the variable mechanisms of actions of anti-spasticity agents used in clinical practice.

Motor Improvement and Corticospinal Modulation Induced by Hybrid Assistive Neuromuscular Dynamic Stimulation (HANDS) Therapy in Patients With Chronic Stroke

Background and objective . We devised a therapeutic approach to facilitate the use of the hemiparetic upper extremity (UE) in daily life by combining integrated volitional control electrical stimulation with a wrist splint, called hybrid assistive neuromuscular dynamic stimulation (HANDS). Methods. Twenty patients with chronic hemiparetic stroke (median 17.5 months) had moderate to severe UE weakness. Before and immediately after completing 3 weeks of training in 40-minute sessions, 5 days per week over 3 weeks and wearing the system for 8 hours each day, clinical measures of motor impairment, spasticity, and UE functional scores, as well as neurophysiological measures including electromyography activity, reciprocal inhibition, and intracortical inhibition were assessed. A follow-up clinical assessment was performed 3 months later. Results. UE motor function, spasticity, and functional scores improved after the intervention. Neurophysiologically, the intervention induced restoration of presynaptic and long loop inhibitory connections as well as disynaptic reciprocal inhibition. Paired pulse transcranial magnetic stimulation study indicated disinhibition of the short intracortical inhibition in the affected hemisphere. The follow-up assessment showed that improved UE functions were maintained at 3 months. Conclusion. The combination of hand splint and volitional and electrically induced muscle contraction can induce corticospinal plasticity and may offer a promising option for the management of the paretic UE in patients with stroke. A larger sample size with randomized controls is needed to demonstrate effectiveness.

Immobilization induces changes in presynaptic control of group Ia afferents in healthy humans

Neural plasticity occurs throughout adult life in response to maturation, use and disuse. Recent studies have documented that H-reflex amplitudes increase following a period of immobilization. To elucidate the mechanisms contributing to the increase in H-reflex size following immobilization we immobilized the left foot and ankle joint for 2 weeks in 12 able-bodied subjects. Disynaptic reciprocal inhibition of soleus (SOL) motoneurons and presynaptic control of SOL group Ia afferents was measured before and after the immobilization as well as following 2 weeks of recovery. Following immobilization, maximal voluntary plantar- and dorsiflexion torque (MVC) was significantly reduced and the maximal SOL H-reflex amplitude increased with no changes in the maximal compound motor response (M(max)). Decreased presynaptic inhibition of the Ia afferents probably contributed to the increase of the H-reflex size, since we observed a significant decrease in the long-latency depression of the SOL H-reflex evoked by peroneal nerve stimulation (D2 inhibition) and an increase in the size of the monosynaptic Ia facilitation of the SOL H-reflex evoked by femoral nerve stimulation. These two measures provide independent evidence of changes in presynaptic inhibition of SOL Ia afferents and taken together suggest that GABAergic presynaptic inhibition of the SOL Ia afferents is decreased following 2 weeks of immobilization. The depression of the SOL H-reflex when evoked at intervals shorter than 10 s (homosynaptic post-activation depression) also decreased following immobilization, suggesting that the activity-dependent regulation of transmitter release from the afferents was also affected by immobilization. We observed no significant changes in disynaptic reciprocal Ia inhibition. Two weeks after cast removal measurements returned to pre-immobilization levels. Together, these observations suggest that disuse causes plastic changes in spinal interneuronal circuitries responsible for presynaptic control of sensory input to the spinal cord. This may be of significance for the motor disabilities seen following immobilization as well as the development of spasticity following central motor lesions.

Increased central facilitation of antagonist reciprocal inhibition at the onset of dorsiflexion following explosive strength training

At the onset of dorsiflexion disynaptic reciprocal inhibition (DRI) of soleus motoneurons is increased to prevent activation of the antagonistic plantar flexors. This is caused by descending facilitation of transmission in the DRI pathway. Because the risk of eliciting stretch reflexes in the ankle plantar flexors at the onset of dorsiflexion is larger the quicker the movement, it was hypothesized that DRI may be increased when subjects are trained to perform dorsiflexion movements as quickly as possible For this purpose, 14 healthy human subjects participated in explosive strength training of the ankle dorsiflexor muscles 3 times a week for 4 wk. Test sessions were conducted before, shortly after, and 2 wk after the training period. The rate of torque development measured at 30, 50, 100, and 200 ms after onset of voluntary explosive isometric dorsiflexion increased by 24-33% (P < 0.05). DRI was measured as the depression of the soleus H reflex following conditioning stimulation of the peroneal nerve (1.1 x motor threshold) at an interval of 2-3 ms. At the onset of dorsiflexion the amount of DRI measured relative to DRI at rest increased significantly from 6% before the training to 22% after the training (P < 0.05). We speculate that DRI at the onset of movement may be increased in healthy subjects following explosive strength training to ensure efficient suppression of the antagonist muscles as the dorsiflexion movement becomes faster.

The spinal pathophysiology of spasticity – from a basic science point of view

Spasticity is a term, which was introduced to describe the velocity-sensitive increased resistance of a limb to manipulation in subjects with lesions of descending motor pathways. This distinguishes spasticity from the changes in passive muscle properties, which are often seen in these patients, but are not velocity-sensitive. Increased excitability of the stretch reflex is thus a central component of the definition of spasticity. This review describes changes in cellular properties and transmission in a number of spinal reflex pathways, which may explain the increased stretch reflex excitability. The review focuses mainly on results derived from the use of non-invasive electrophysiological techniques, which have been developed during the past 20-30 years to investigate spinal neuronal networks in human subjects, but work from animal models is also considered. The reflex hyperexcitability develops over several months following the primary lesion and involves adaptation in the spinal neuronal circuitries caudal to the lesion. In animal models, changes in cellular properties (such as 'plateau potentials') have been reported, but the relevance of these changes to human spasticity has not been clarified. In humans, numerous studies have suggested that reduction of spinal inhibitory mechanisms (in particular that of disynaptic reciprocal inhibition) is involved. The inter-subject variability of these mechanisms and the lack of objective quantitative measures of spasticity have impeded disclosure of a clear causal relationship between the alterations in the inhibitory mechanisms and the stretch reflex hyperexcitability. Techniques which make such a quantitative measure possible as well as longitudinal studies where development of reflex excitability and changes in the inhibitory mechanisms are followed over time are in great demand.

Reciprocal inhibition and corticospinal transmission in the arm and leg in patients with autosomal dominant pure spastic paraparesis (ADPSP)

The pathophysiological mechanisms underlying the development of spasticity are not clear, but the excitability of the disynaptic reciprocal inhibitory pathway is affected in many patients with spasticity of different origin. Patients with genetically identified autosomal dominant pure spastic paraparesis (ADPSP) develop spasticity and paresis in the legs, but usually have no symptoms in the arms. Comparison of the spinal and supraspinal control of the legs and arms in these patients may therefore provide valuable information about the pathophysiology of spasticity. In the present study, we tested the hypothesis that one of the pathophysiological mechanisms of spasticity in these patients is abnormal corticospinal transmission and that this may lead to decreased reciprocal inhibition. Ten patients and 15 healthy age-matched control subjects were investigated. The patients were all spastic in the legs (with hyperactive tendon reflexes, increased muscle tone and Babinski sign), but had no neurological symptoms in the arms (except for one patient). Disynaptic reciprocal Ia inhibition of flexor carpi radialis (FCR) and soleus (SOL) motoneurons was measured (as the depression of the background FCR and SOL EMG activity and as the short latency inhibition of the FCR and SOL H-reflex evoked by radial and peroneal nerve stimulation). In addition, the latency of motor evoked potentials (MEPs) in the FCR muscle and the tibialis anterior (TA) muscle was measured. In the patients, the mean reciprocal inhibition was normal in the arms, while it was significantly decreased in the leg compared with the healthy subjects. In the patients, the average latency of MEPs in the FCR muscle was normal, while the latency to the MEP in TA muscle was significantly longer than that found in healthy subjects. Four patients, however, differed from the other patients by having significant reciprocal inhibition in the leg and a significantly shorter latency of TA MEPs than found in the other patients. The six patients without reciprocal inhibition in the leg instead had significant short latency facilitation of the SOL H-reflex and a longer TA MEP latency than seen in the healthy subjects and in the four patients with retained reciprocal inhibition. These findings support the hypothesis that disynaptic reciprocal inhibition and short latency facilitation are involved in the development of spasticity and, furthermore, they suggest a positive correlation between impairment of corticospinal transmission and decrease of reciprocal inhibition/appearance of reciprocal facilitation.

Central nervous system lesions and segmental activity.

Study of activity in segmental pathways can help in understanding the pathophysiology of clinical disorders due to basal ganglia damage. Disynaptic Ia reciprocal inhibition (DI) acts by actively inhibiting antagonistic motoneurones and reducing the inhibition of agonist ones. During movement, activity of interneurones mediating DI is significantly modulated by descending inputs. In Parkinsonian patients, this descending modulation almost completely vanished. Lack of modulation was not dependent on L-DOPA as it occurred in treated patients and was not modified when patients were off medication. A potent heteronymous group II excitation of quadriceps MNs has been recently demonstrated in normal subjects after stimulation of the common peroneal nerve. This group II excitation was significantly enhanced in the rigid lower limb of Parkinsonian patients. We propose that enhanced group II excitation could contribute to rigidity in PD and result from a change in a tonic noradrenergic descending inhibitory control from locus coeruleus.