Analyzing the Combination Effects of Repetitive Transcranial Magnetic Stimulation and Motor Control Training on Balance Function and Gait in Patients with Stroke-Induced Hemiplegia

Objective:To analyze the effects of repetitive transcranial magnetic stimulation combined with motor control training on the treatment of stroke-induced hemiplegia,specifically focusing on the impact on patients’balance function and gait.Methods:Fifty-two cases of hemiplegic stroke patients were randomly divided into two groups,26 in the control group and 26 in the observation group,using computer-generated random grouping.All participants underwent conventional treatment and rehabilitation training.In addition to these,the control group received repetitive transcranial magnetic pseudo-stimulation therapy+motor control training,while the observation group received repetitive transcranial magnetic stimulation therapy+motor control training.The balance function and gait parameters of both groups were compared before and after the interventions and assessed the satisfaction of the interventions in both groups.Results:Before the invention,there were no significant differences in balance function scores and each gait parameter between the two groups(P>0.05).However,after the intervention,the observation group showed higher balance function scores compared to the control group(P<0.05).The observation group also exhibited higher step speed and step frequency,longer step length,and a higher overall satisfaction level with the intervention compared to the control group(P<0.05).Conclusion:The combination of repetitive transcranial magnetic stimulation and motor control training in the treatment of stroke-induced hemiplegia has demonstrated positive effects.It not only improves the patient’s balance function and gait but also contributes to overall physical rehabilitation.

Double-target neural circuit-magnetic stimulation improves motor function in spinal cord injury by attenuating astrocyte activation

Multi-target neural circuit-magnetic stimulation has been clinically shown to improve rehabilitation of lower limb motor function after spinal cord injury. However, the precise underlying mechanism remains unclear. In this study, we performed double-target neural circuit-magnetic stimulation on the left motor cortex and bilateral L5 nerve root for 3 successive weeks in a rat model of incomplete spinal cord injury caused by compression at T10. Results showed that in the injured spinal cord, the expression of the astrocyte marker glial fibrillary acidic protein and inflammatory factors interleukin 1β, interleukin-6, and tumor necrosis factor-α had decreased, whereas that of neuronal survival marker microtubule-associated protein 2 and synaptic plasticity markers postsynaptic densification protein 95 and synaptophysin protein had increased. Additionally, neural signaling of the descending corticospinal tract was markedly improved and rat locomotor function recovered significantly. These findings suggest that double-target neural circuit-magnetic stimulation improves rat motor function by attenuating astrocyte activation, thus providing a theoretical basis for application of double-target neural circuit-magnetic stimulation in the clinical treatment of spinal cord injury.

The Application of Deep Brain Stimulation for Parkinson’s Disease on the Motor Pathway:A Bibliometric Analysis across 10 Years

Background and Objective Since its initial report by James Parkinson in 1817,Parkinson’s disease(PD)has remained a central subject of research and clinical advancement.The disease is estimated to affect approximately 1%of adults aged 60 and above.Deep brain stimulation,emerging as an alternative therapy for end-stage cases,has offered a lifeline to numerous patients.This review aimed to analyze publications pertaining to the impact of deep brain stimulation on the motor pathway in patients with PD over the last decade.Methods Data were obtained from the Web of Science Core Collection through the library of Huazhong University of Science and Technology(China).The search strategy encompassed the following keywords:“deep brain stimulation”,“Parkinson’s disease”,“motor pathway”,and“human”,from January 1,2012,to December 1,2022.Additionally,this review visualized the findings using the Citespace software.Results The results indicated that the United States,the United Kingdom,Germany,and China were the primary contributors to this research field.University College London,Capital Medical University,and Maastricht University were the top 3 research institutions in the research area.Tom Foltynie ranked first with 6 publications,and the journals of Brain and Brain Stimulation published the greatest number of relevant articles.The prevailing research focal points in this domain,as determined by keywords“burst analysis”,“encompassed neuronal activity”,“nucleus”,“hyper direct pathway”,etc.Conclusion This study has provided a new perspective through bibliometric analysis of the deep brain stimulation therapy for treating patients with PD,which can shed light on future research to advance our comprehension of this particular field of study.

Effect of Transcranial Direct Current Stimulation of Motor Cortex versus Insula Cortex on Chronic Post-Mastectomy Pain: Randomized Sham-Controlled Trial

Background: Transcranial direct current stimulation (tDCS) across cortical brain areas appears to improve various forms of pain, yet evidence of tDCS efficiency and ideal stimulation target is lacking. This study aimed to compare the add-on analgesic efficacy of concentric electrode transcranial direct current stimulation (CE-tDCS) stimulation over the primary motor cortex versus the insular cortex on the management of chronic postmastectomy pain. Method: Prospective randomized double-blind sham-controlled study enrolled eighty patients with chronic postmastectomy pain that were randomly assigned to four groups: active motor (AM), sham motor (SM), active insula (AI) and sham insula (SI) group, each received 5 sessions for 20-minute duration with 2 mA tDCS over the targeted area of the contralateral side of pain. Our primary outcome was VAS score, the secondary outcomes were VDS score, LANSS score and depression symptoms by HAM-D scores, assessment was done at 4 time points (prestimulation, after 5th session, 15th day and one month after the last session). Results: Both active tDCS groups (motor and insula) showed reduction of VAS (P Conclusion: Active tDCS stimulation either targeting the primary motor cortex or the insula cortex has add-on analgesic effect for controlling neuropathic chronic post mastectomy pain and the maximum effect was at 15 days after the last session.

Electromyographic evaluation of functional electrical stimulation to injured oculomotor nerve

Functional electrical stimulation delivered early after injury to the proximal nerve stump has been proposed as a therapeutic approach for enhancing the speed and specificity of axonal regeneration following nerve injury. In this study, the injured oculomotor nerve was stimulated functionally by an implantable electrode. Electromyographic monitoring of the motor unit potential of the inferior oblique muscle was conducted for 12 weeks in two injury groups, one with and one without electric stimulation. The results revealed that, at 2, 4, 6, 8 weeks after functional electric stimulation of the injured oculomotor nerve, motor unit potentials significantly increased, such that amplitude was longer and spike duration gradually shortened. These findings indicate that the injured oculomotor nerve has the potential for regeneration and repair, but this ability is not sufficient for full functional recovery to occur. Importantly, the current results indicated that recovery and regeneration of the injured oculomotor nerve can be promoted with functional electrical stimulation.

Optimal stimulation parameters for Renzhong (DU 26) electro-acupuncture for improving motor function in a rat model of middle cerebral artery occlusion

The selection of electro-acupuncture parameters remains poorly unified between clinical studies. The present study observed the effects of electro-acupuncturing Renzhong （DU 26） with different stimulation parameters on motor function recovery following middle artery occlusion injury in rats. Results showed an optimal stimulation parameter for Renzhong electro-acupuncture that was low frequency and mild current （2 Hz, 1 mA） significantly improved cortical excitability and conductive function, and promoted recovery in a rat model of motor function in middle artery occlusion. Frequency had a greater impact than current or interaction, and played a critical role in electro-acupuncture therapy.

Nerve root magnetic stimulation improves locomotor function following spinal cord injury with electrophysiological improvements and cortical synaptic reconstruction

Following a spinal cord injury,there are usually a number of neural pathways that remain intact in the spinal cord.These residual nerve fibers are important,as they could be used to reconstruct the neural circuits that enable motor function.Our group previously designed a novel magnetic stimulation protocol,targeting the motor cortex and the spinal nerve roots,that led to significant improvements in locomotor function in patients with a chronic incomplete spinal cord injury.Here,we investigated how nerve root magnetic stimulation contributes to improved locomotor function using a rat model of spinal cord injury.Rats underwent surgery to clamp the spinal cord at T10;three days later,the rats were treated with repetitive magnetic stimulation(5 Hz,25 pulses/train,20 pulse trains)targeting the nerve roots at the L5-L6 vertebrae.The treatment was repeated five times a week over a period of three weeks.We found that the nerve root magnetic stimulation improved the locomotor function and enhanced nerve conduction in the injured spinal cord.In addition,the nerve root magnetic stimulation promoted the recovery of synaptic ultrastructure in the sensorimotor cortex.Overall,the results suggest that nerve root magnetic stimulation may be an effective,noninvasive method for mobilizing the residual spinal cord pathways to promote the recovery of locomotor function.

A flexible electrode array for determining regions of motor function activated by epidural spinal cord stimulation in rats with spinal cord injury

Epidural stimulation of the spinal cord is a promising technique for the recovery of motor function after spinal cord injury.The key challenges within the reconstruction of motor function for paralyzed limbs are the precise control of sites and parameters of stimulation.To activate lower-limb muscles precisely by epidural spinal cord stimulation,we proposed a high-density,flexible electrode array.We determined the regions of motor function that were activated upon epidural stimulation of the spinal cord in a rat model with complete spinal cord,which was established by a transection method.For evaluating the effect of stimulation,the evoked potentials were recorded from bilateral lowerlimb muscles,including the vastus lateralis,semitendinosus,tibialis anterior,and medial gastrocnemius.To determine the appropriate stimulation sites and parameters of the lower muscles,the stimulation characteristics were studied within the regions in which motor function was activated upon spinal cord stimulation.In the vastus lateralis and medial gastrocnemius,these regions were symmetrically located at the lateral site of L1 and the medial site of L2 vertebrae segment,respectively.The tibialis anterior and semitendinosus only responded to stimulation simultaneously with other muscles.The minimum and maximum stimulation threshold currents of the vastus lateralis were higher than those of the medial gastrocnemius.Our results demonstrate the ability to identify specific stimulation sites of lower muscles using a high-density and flexible array.They also provide a reference for selecting the appropriate conditions for implantable stimulation for animal models of spinal cord injury.This study was approved by the Animal Research Committee of Southeast University,China(approval No.20190720001) on July 20,2019.

Sex modulates the outcome of subthalamic nucleus deep brain stimulation in patients with Parkinson's disease

There are many documented sex differences in the clinical course,symptom expression profile,and treatment response of Parkinson’s disease,creating additional challenges for patient management.Although subthalamic nucleus deep brain stimulation is an established therapy for Parkinson’s disease,the effects of sex on treatment outcome are still unclear.The aim of this retrospective observational study,was to examine sex differences in motor symptoms,nonmotor symptoms,and quality of life after subthalamic nucleus deep brain stimulation.Outcome measures were evaluated at 1 and 12 months post-operation in 90 patients with Parkinson’s disease undergoing subthalamic nucleus deep brain stimulation aged 63.00±8.01 years(55 men and 35 women).Outcomes of clinical evaluations were compared between sexes via a Student’s t-test and within sex via a paired-sample t-test,and generalized linear models were established to identify factors associated with treatment efficacy and intensity for each sex.We found that subthalamic nucleus deep brain stimulation could improve motor symptoms in men but not women in the on-medication condition at 1 and 12 months post-operation.Restless legs syndrome was alleviated to a greater extent in men than in women.Women demonstrated poorer quality of life at baseline and achieved less improvement of quality of life than men after subthalamic nucleus deep brain stimulation.Furthermore,Hoehn-Yahr stage was positively correlated with the treatment response in men,while levodopa equivalent dose at 12 months post-operation was negatively correlated with motor improvement in women.In conclusion,women received less benefit from subthalamic nucleus deep brain stimulation than men in terms of motor symptoms,non-motor symptoms,and quality of life.We found sex-specific factors,i.e.,Hoehn-Yahr stage and levodopa equivalent dose,that were related to motor improvements.These findings may help to guide subthalamic nucleus deep brain stimulation patient selection,prognosis,and stimulation programming for optimal therapeutic efficacy in Parkinson’s disease.

Effects of different frequencies of repetitive transcranial magnetic stimulation on the recovery of upper limb motor dysfunction in patients with subacute cerebral infarction

Studies have confirmed that low-frequency repetitive transcranial magnetic stimulation can decrease the activity of cortical neurons, and high-frequency repetitive transcranial magnetic stimulation can increase the excitability of cortical neurons. However, there are few studies concerning the use of different frequencies of repetitive transcranial magnetic stimulation on the recovery of upper-limb motor function after cerebral infarction. We hypothesized that different frequencies of repetitive transcranial magnetic stimulation in patients with cerebral infarction would produce different effects on the recovery of upper-limb motor function. This study enrolled 127 patients with upper-limb dysfunction during the subacute phase of cerebral infarction. These patients were randomly assigned to three groups. The low-frequency group comprised 42 patients who were treated with 1 Hz repetitive transcranial magnetic stimulation on the contralateral hemisphere primary motor cortex （M1）. The high-frequency group comprised 43 patients who were treated with 10 Hz repetitive transcranial magnetic stimulation on ipsilateral M1. Finally, the sham group comprised 42 patients who were treated with 10 Hz of false stimulation on ipsilateral M1. A total of 135 seconds of stimulation was applied in the sham group and high-frequency group. At 2 weeks after treatment, cortical latency of motor-evoked potentials and central motor conduction time were significantly lower compared with before treatment. Moreover, motor function scores were significantly improved. The above indices for the low- and high-frequency groups were significantly different compared with the sham group. However, there was no significant difference between the low- and high-frequency groups. The results show that low- and high-frequency repetitive transcranial magnetic stimulation can similarly improve upper-limb motor function in patients with cerebral infarction.

Low frequency repetitive transcranial magnetic stimulation improves motor dysfunction after cerebral infarction

Low frequency （≤ 1 Hz） repetitive transcranial magnetic stimulation （rTMS） can affect the excitability of the cerebral cortex and synaptic plasticity. Although this is a common method for clinical treatment of cerebral infarction, whether it promotes the recovery of motor function remains controversial. Twenty patients with cerebral infarction combined with hemiparalysis were equally and randomly divided into a low frequency rTMS group and a control group. The patients in the low frequency rTMS group were given 1-Hz rTMS to the contralateral primary motor cortex with a stimulus intensity of 90% motor threshold, 30 minutes/day. The patients in the control group were given sham stimulation. After 14 days of treatment, clinical function scores （National Institute of Health Stroke Scale, Barthel Index, and Fugl-Meyer Assessment） improved significantly in the low frequency rTMS group, and the effects were better than that in the control group. We conclude that low frequency （1 Hz） rTMS for 14 days can help improve motor function after cerebral infarction.

Repetitive transcranial magnetic stimulation for lower extremity motor function in patients with stroke:a systematic review and network meta-analysis

Transcranial magnetic stimulation,a type of noninvasive brain stimulation,has become an ancillary therapy for motor function rehabilitation.Most previous studies have focused on the effects of repetitive transcranial magnetic stimulation(rTMS)on motor function in stroke patients.There have been relatively few studies on the effects of different modalities of rTMS on lower extremity motor function and corticospinal excitability in patients with stroke.The MEDLINE,Embase,Cochrane Library,ISI Science Citation Index,Physiotherapy Evidence Database,China National Knowledge Infrastructure Library,and ClinicalTrials.gov databases were searched.Parallel or crossover randomized controlled trials that addressed the effectiveness of rTMS in patients with stroke,published from inception to November 28,2019,were included.Standard pairwise meta-analysis was conducted using R version 3.6.1 with the“meta”package.Bayesian network analysis using the Markov chain Monte Carlo algorithm was conducted to investigate the effectiveness of different rTMS protocol interventions.Network meta-analysis results of 18 randomized controlled trials regarding lower extremity motor function recovery revealed that low-frequency rTMS had better efficacy in promoting lower extremity motor function recovery than sham stimulation.Network meta-analysis results of five randomized controlled trials demonstrated that highfrequency rTMS led to higher amplitudes of motor evoked potentials than low-frequency rTMS or sham stimulation.These findings suggest that rTMS can improve motor function in patients with stroke,and that low-frequency rTMS mainly affects motor function,whereas high-frequency rTMS increases the amplitudes of motor evoked potentials.More highquality randomized controlled trials are needed to validate this conclusion.The work was registered in PROSPERO(registration No.CRD42020147055)on April 28,2020.

A novel functional electrical stimulation-control system for restoring motor function of post-stroke hemiplegic patients

Hemiparesis is one of the most common consequences of stroke. Advanced rehabilitation techniques are essential for restoring motor function in hemiplegic patients. Functional electrical stimulation applied to the affected limb based on myoelectric signal from the unaffected limb is a promising therapy for hemiplegia. In this study, we developed a prototype system for evaluating this novel functional electrical stimulation-control strategy. Based on surface electromyography and a vector machine model, a self-administered, muki-movement, force-modulation functional electrical stimulation-prototype system for hemiplegia was implemented. This paper discusses the hardware design, the algorithm of the system, and key points of the self-oscillation-prone system. The experimental results demonstrate the feasibility of the prototype system for further clinical trials, which is being conducted to evaluate the efficacy of the proposed rehabilitation technique.

Effect of Paired Associative Stimulation on Motor Cortex Excitability in Rats

Paired associative stimulation (PAS),combining transcranial magnetic stimulation (TMS) with electrical peripheral nerve stimulation (PNS) in pairs with an optimal interstimulus interval (ISI)in between,has been shown to influence the excitability of the motor cortex (MC)in humans.However,the underlying mechanisms remain unclear.This study was designed to explore an optimal protocol of PAS,which can modulate the excitability of MC in rats,and to investigate the underlying mechanisms. The resting motor thresholds (RMTs) of TMS-elicited motor evoked potentials (MEPs) recorded from the gastrocnemius muscle and the latency of P1 component of somatosensory evoked potentials (SEPs) induced by electrical tibial nerve stimulation were determined in male Sprague-Dawley rats (n=10).Sixty rats were then randomly divided into 3 groups:a PAS group (further divided into 10 subgroups at various ISIs calculated by using the latency of P1,n=5,respectively),a TMS (only)group (n=5)and a PNS (only)group (n=5).Ninety repetitions of PAS,TMS and PNS were administered to the rats in the 3 groups,respectively,at the frequency of 0.05 Hz and the intensity of TMS at 120% RMT and that of PNS at 6 mA.RMTs and motor evoked potentials'amplitude (MEPamp)were recorded before and immediately after the interventions.It was found that the MEPamp significantly decreased after PAS at ISI of 5 ms (P<0.05),while the MEPamp significantly increased after PAS at ISI of 15ms,as compared with those before the intervention (P<0.05).However,the RMT did not change significantly after PAS at ISI of 5 ms or 15 ms (P>0.05).PAS at other ISis as well as the sole use of TMS and PNS induced no remarkable changes in MEPamp and RMT.In conclusion,PAS can influence motor cortex excitability in rats.Neither TMS alone nor PNS alone shows significant effect.

Transcranial pulse current stimulation improves the locomotor function in a rat model of stroke

Previous studies have shown that transcranial pulse current stimulation(tPCS) can increase cerebral neural plasticity and improve patients' locomotor function.However, the precise mechanisms underlying this effect remain unclear.In the present study, rat models of stroke established by occlusion of the right cerebral middle artery were subjected to tPCS, 20 minutes per day for 7 successive days.tPCS significantly reduced the Bederson score, increased the foot print area of the affected limbs, and reduced the standing time of affected limbs of rats with stroke compared with that before intervention.Immunofluorescence staining and western blot assay revealed that tPCS significantly increased the expression of microtubule-associated protein-2 and growth-associated protein-43 around the ischemic penumbra.This finding suggests that tPCS can improve the locomotor function of rats with stroke by regulating the expression of microtubule-associated protein-2 and growth-associated protein-43 around the ischemic penumbra.These findings may provide a new method for the clinical treatment of poststroke motor dysfunction and a theoretical basis for clinical application of tPCS.The study was approved by the Animal Use and Management Committee of Shanghai University of Traditional Chinese Medicine of China(approval No.PZSHUTCM190315003) on February 22, 2019.

Effects of cortical intermittent theta burst stimulation combined with precise root stimulation on motor function after spinal cord injury: a case series study

Activation and reconstruction of the spinal cord circuitry is important for improving motor function following spinal cord injury.We conducted a case series study to investigate motor function improvement in 14 patients with chronic spinal cord injury treated with 4 weeks of unilateral(right only)cortical intermittent theta burst stimulation combined with bilateral magnetic stimulation of L3-L4 nerve roots,five times a week.Bilateral resting motor evoked potential amplitude was increased,central motor conduction time on the side receiving cortical stimulation was significantly decreased,and lower extremity motor score,Berg balance score,spinal cord independence measure-III score,and 10 m-walking speed were all increased after treatment.Right resting motor evoked potential amplitude was positively correlated with lower extremity motor score after 4 weeks of treatment.These findings suggest that cortical intermittent theta burst stimulation combined with precise root stimulation can improve nerve conduction of the corticospinal tract and lower limb motor function recovery in patients with chronic spinal cord injury.

Rebuilding motor function of the spinal cord based on functional electrical stimulation

Rebuilding the damaged motor function caused by spinal cord injury is one of the most serious challenges in clinical neuroscience.The function of the neural pathway under the damaged sites can be rebuilt using functional electrical stimulation technology.In this study,the locations of motor function sites in the lumbosacral spinal cord were determined with functional electrical stimulation technology.A three-dimensional map of the lumbosacral spinal cord comprising the relationship between the motor function sites and the corresponding muscle was drawn.Based on the individual experimental parameters and normalized coordinates of the motor function sites,the motor function sites that control a certain muscle were calculated.Phasing pulse sequences were delivered to the determined motor function sites in the spinal cord and hip extension,hip flexion,ankle plantarflexion,and ankle dorsiflexion movements were successfully achieved.The results show that the map of the spinal cord motor function sites was valid.This map can provide guidance for the selection of electrical stimulation sites during the rebuilding of motor function after spinal cord injury.

Transcallosal motor pathway from affected motor cortex to affected hand in a patient with corona radiata infarct A diffusion tensor tractography and transcranial magnetic stimulation study

The mechanisms of motor recovery through the transcallosal pathway remain poorly understood. The present study reports on a hemiplegic patient with corona radiata infarct; it attempts to confirm motor recovery through the transcallosal motor pathway, from the affected motor cortex to the affected hand, using diffusion tensor tractography and transcranial magnetic stimulation. A 54-year-old, male patient and eight age-matched, normal subjects were enrolled in the study. The patient＇s right hand was initially completely paralyzed, but slowly recovered over 6 months. In the control subjects and the unaffected hemisphere （right） of the patient, the corticospinal tracts originated from the motor cortex and descended along the known corticospinal tract pathway. However, the corticospinal tract of the affected hemisphere was disrupted at the upper pons. Following transcranial stimulation of the affected （left） motor cortex, motor evoked potential from the affected （right） abductor pollicis brevis muscle exhibited longer latency than opposite motor evoked potential. Results from the present study suggest that motor function of the affected （right） hand recovered via the transcallosal motor pathway from the affected （left） motor cortex in this patient.

EFFECTS OF TRANSCRANIAL MAGNETIC STIMULATION ON MOTOR CORTICAL EXCITABILITY AND NEUROFUNCTION AFTER CEREBRAL ISCHEMIA-REPERFUSION INJURY IN RATS

Objective To clarify the effects of repetitive transcranial magnetic stimulation (rTMS) on rat motor cortical excitabi- lity and neurofunction after cerebral ischemia-reperfusion injury. Methods After determined awake resting motor threshold (MT) and motor evoked potentials (MEPs) of right hindlimbs, 20 Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) reperfusion injury, then rTMS were applied to rTMS group (n = 10) at different time, while control group (n = 10) received no stimulation. A week later, MT and MEPs were evaluated again, as well as neurological deficits and infarct volume. The effects of rTMS and MCAO reperfusion injury on these parameters were analyzed. Results After MCAO reperfusion, both MT level and neurological deficit scores increased, distinct focal infarction formed, and latency of MEP elongated. Compared with the control group, the increased extent of MT and neurological scores of rats receiving rTMS were significantly lower (P < 0.05), as well as the infarct volumes reduced significantly(P < 0.05). But MEP was not affected by rTMS obviously. There was a positive linear correlation between postinjury MT and infarct volume (r = 0.64, P < 0.05). Conclusion rTMS may facilitate neurofunction recovery after cerebral ischemia-reperfusion. Postinjury MT could provide prognostic information after MCAO reperfusion injury.

Right lower limb apraxia in a patient with left supplementary motor area infarction: intactness of the corticospinal tract confirmed by transcranial magnetic stimulation

We reported a 50-year-old female patient with left supplementary motor area infarction who presented right lower limb apraxia and investigated the possible causes using transcranial magnetic stimulation. The patient was able to walk and climb stairs spontaneously without any assistance at 3 weeks after onset. However, she was unable to intentionally move her right lower limb although she understood what she supposed to do. The motor evoked potential evoked by transcranial magnetic stimulation from the right lower limb was within the normal range, indicating that the corticospinal tract innervating the right lower limb was uninjured. Thus, we thought that her motor dysfunction was not induced by motor weakness, and confirmed her symptoms as aprax- ia. In addition, these results also suggest that transcranial magnetic stimulation is helpful for diagnosing apraxia.