Long-latency Intracortical Inhibition Research Articles

Modulations of corticospinal excitability following rapid ankle dorsiflexion in skill- and endurance-trained athletes

PurposeLong-term sports training, such as skill and endurance training, leads to specific neuroplasticity. However, it remains unclear if muscle stretch-induced proprioceptive feedback influences corticospinal facilitation/inhibition differently between skill- and endurance-trained athletes. This study investigated modulation of corticospinal excitability following rapid ankle dorsiflexion between well-trained skill and endurance athletes.MethodsTen skill- and ten endurance-trained athletes participated in the study. Corticospinal excitability was tested by single- and paired-pulse transcranial magnetic stimulations (TMS) at three different latencies following passive rapid ankle dorsiflexion. Motor evoked potential (MEP), short-latency intracortical inhibition (SICI), intracortical facilitation (ICF), and long-latency intracortical inhibition (LICI) were recorded by surface electromyography from the soleus muscle.ResultsCompared to immediately before ankle dorsiflexion (Onset), TMS induced significantly greater MEPs during the supraspinal reaction period (~ 120 ms after short-latency reflex, SLR) in the skill group only (from 1.7 ± 1.0 to 2.7 ± 1.8%M-max, P = 0.005) despite both conditions being passive. ICF was significantly greater over all latencies in skill than endurance athletes (F(3, 45) = 4.64, P = 0.007), although no between-group differences for stimulations at specific latencies (e.g., at SLR) were observed.ConclusionThe skill group showed higher corticospinal excitability during the supraspinal reaction phase, which may indicate a “priming” of corticospinal excitability following rapid ankle dorsiflexion for a supraspinal reaction post-stretch, which appears absent in endurance-trained athletes.

Transcranial magnetic stimulation induced early silent period and rebound activity re-examined.

Despite being widely studied, the underlying mechanisms of transcranial magnetic brain stimulation (TMS) induced motor evoked potential (MEP), early cortical silent period (CSP) and rebound activity are not fully understood. Our aim is to better characterize these phenomena by combining various analysis tools on firing motor units. Responses of 29 tibialis anterior (TA) and 8 abductor pollicis brevis (APB) motor units to TMS pulses were studied using discharge rate and probability-based tools to illustrate the profile of the synaptic potentials as they develop on motoneurons in 24 healthy volunteers. According to probability-based methods, TMS pulse produces a short-latency MEP which is immediately followed by CSP that terminates at rebound activity. Discharge rate analysis, however, revealed not three, but just two events with distinct time courses; a long-lasting excitatory period (71.2 ± 9.0 ms for TA and 42.1 ± 11.2 ms for APB) and a long-latency inhibitory period with duration of 57.9 ± 9.5 ms for TA and 67.3 ± 13.8 ms for APB. We propose that part of the CSP may relate to the falling phase of net excitatory postsynaptic potential induced by TMS. Rebound activity, on the other hand, may represent tendon organ inhibition induced by MEP activated soleus contraction and/or long-latency intracortical inhibition. Due to generation of field potentials when high intensity TMS is used, this study is limited to investigate the events evoked by low intensity TMS only and does not provide information about later parts of much longer CSPs induced by high intensity TMS. Adding discharge rate analysis contributes to obtain a more accurate picture about the characteristics of TMS-induced events. These results have implications for interpreting motor responses following TMS for diagnosis and overseeing recovery from various neurological conditions.

Abstract 69: The Influence of Motor Cortex Inhibition on Upper Limb Recovery: A Multimodal Study

Background: After stroke, there may be abnormalities in gamma-aminobutyric acid (GABA)-mediated inhibitory function within primary motor cortex (M1), which may have implications for residual motor impairment and the potential for functional improvements at the chronic stage. The present study examined primary motor cortex (M1) inhibition in patients over the first 12 weeks after stroke, and in a cohort of age-similar healthy controls. Methods: Excitatory/inhibitory (E/I) balance was assessed from glutamate/glutamine (Glx) and gamma aminobutyric acid (GABA) concentrations from magnetic resonance spectroscopy (MRS) at 2 and 6 weeks after stroke. Threshold tracking paired-pulse transcranial magnetic stimulation (TMS) was used to assess motor cortex inhibition at 2, 6, and 12 weeks after stroke. Upper limb impairment and function were assessed with Fugl-Meyer Upper Extremity Scale and Action Research Arm Test at 2, 6, 12 and 26 weeks after stroke. Results: By 12 weeks, patients with a functionally intact corticospinal pathway as evident by the presence of MEPs in paretic upper-limb exhibited a proportional recovery such that upper limb impairment resolved by ~70% of the maximum possible (proportional recovery), whereas patients without MEPs had relatively poorer and more variable outcomes. Spectroscopy results indicated that there was an E/I in Glx:GABA ratio in both hemispheres compared to age-similar controls. Long-latency intracortical inhibition measures from TMS indicated an elevated GABA B -receptor mediated inhibition in both hemispheres during the spontaneous recovery period after stroke compared to controls. Patients with higher tonic inhibition in ipsilesional M1 tend to have a longer recovery period. Conclusion: The ability to modulate tonic inhibition levels early after stroke may have implications for upper limb recovery during the spontaneous recovery period.

Reorganization of the primary motor cortex following lower-limb amputation for vascular disease: a pre-post-amputation comparison

Purpose: This study compared bilateral corticomotor and intracortical excitability of the primary motor cortex (M1), pre- and post-unilateral transtibial amputation.Method: Three males aged 45, 55, and 48 years respectively who were scheduled for elective amputation and thirteen (10 male, 3 female) healthy control participants aged 58.9 (SD 9.8) were recruited. Transcranial magnetic stimulation assessed corticomotor and intracortical excitability of M1 bilaterally. Neurophysiological assessments were performed 10 (SD 7) days prior to surgery and again at 10 (SD 3) days following surgery. Data were analyzed descriptively and objectively compared to 95% confidence intervals from control data.Results: Prior to amputation, all three patients demonstrated stronger short-latency intracortical inhibition evoked from M1 ipsilateral to the affected limb and reduced long-latency intracortical inhibition evoked from M1 contralateral to the affected limb compared to control subjects. Following amputation, short-latency intracortical inhibition was reduced in both M1s and long-latency intracortical inhibition was reduced for the ipsilateral M1. Single-pulse motor evoked potential amplitude and motor thresholds were similar pre-to-post amputation.Conclusions: Modulation of intracortical excitability shortly following amputation indicates that the cortical environment may be optimized for reorganization in the acute post-amputation period which might be significant for learning to support prosthetic mobility.Implications for RehabilitationAmputation of a lower-limb is associated with extensive reorganization at the level of the cortex.Reorganization occurs in the acute post-amputation period implying a favorable cortical environment for recovery.Rehabilitation or brain interventions may target the acute pre-prosthetic post-amputation period to optimize recovery.

Altered function of intracortical networks in chronic lateral epicondylalgia.

Lateral epicondylalgia (LE) is a musculotendinous condition characterized by persistent pain, sensorimotor dysfunction and motor cortex reorganization. Although there is evidence linking cortical reorganization with clinical symptoms in LE, the mechanisms underpinning these changes are unknown. Here we investigated activity in motor cortical (M1) intracortical inhibitory and facilitatory networks in individuals with chronic LE and healthy controls. Surface electromyography was recorded bilaterally from the extensor carpi radialis brevis (ECRB) muscle of 14 LE (4 men, 41.5±9.9years) and 14 control participants (4 men, 42.1±11.1years). Transcranial magnetic stimulation of M1 was used to evaluate resting and active motor threshold, corticomotor output, short- (SICI) and long-latency intracortical inhibition (LICI) and intracortical facilitation (ICF) of both hemispheres. In individuals with LE, SICI (p=0.005), ICF (p=0.026) and LICI (p=0.046) were less in the M1 contralateral to the affected ECRB muscle compared with healthy controls. Motor cortical threshold (rest: p=0.57, active: p=0.97) and corticomotor output (p=0.15) were similar between groups. No differences were observed between individuals with LE and healthy controls for the M1 contralateral to the unaffected ECRB muscle. These data provide evidence of less intracortical inhibition mediated by both GABAA and GABAB receptors, and less intracortical facilitation in the M1 contralateral to the affected ECRB in individuals with LE compared with healthy controls. Similar changes were not present in the M1 contralateral to the unaffected ECRB. These changes may provide the substrate for M1 reorganization in chronic LE and could provide a target for future therapy. Lateral epicondylalgia (LE) is a common musculoskeletal condition characterized by elbow pain and sensorimotor dysfunction. The excitability and organization of the motor cortical representation of the wrist extensor muscles is altered in LE, but the mechanisms that underpin these changes are unknown. evidence of less intracortical inhibition mediated by both GABAA and GABAB receptors, and less intracortical facilitation mediated by NMDA receptors, in the M1 contralateral to the affected extensor carpi radialis brevis muscle in chronic LE compared with healthy controls. Altered activity in intracortical networks may contribute to altered motor cortex organization in LE and could provide a potential target for future treatments.

Does Transcranial Alternating Current Stimulation Induce Cerebellum Plasticity? Feasibility, Safety and Efficacy of a Novel Electrophysiological Approach.

Cerebellum-brain functional connectivity can be shaped through different non-invasive neurostimulation approaches. In this study, we propose a novel approach to perturb the cerebellum-brain functional connectivity by means of transcranial alternating current stimulation (tACS). Twenty-five healthy individuals underwent a cerebellar tACS protocol employing different frequencies (10, 50, and 300 Hz) and a sham-tACS over the right cerebellar hemisphere. We measured their after-effects on the motor evoked potential (MEP) amplitude, the cerebellum-brain inhibition (CBI), the long-latency intracortical inhibition (LICI), from the primary motor cortex of both the hemispheres. In addition, we assessed the functional adaptation to a right hand sequential tapping motor task. None of the participants had any side-effect. Following 50 Hz-tACS, we observed a clear contralateral CBI weakening, paralleled by a MEP increase with a better adaptation to frequency variations during the sequential tapping. The 300 Hz-tACS induced a contralateral CBI strengthening, without significant MEP and kinematic after-effects. The 10 Hz-tACS conditioning was instead ineffective. We may argue that tACS protocols could have interfered with the activity of CBI-sustaining Purkinje cell, affecting motor adaptation. Our safe approach seems promising in studying the cerebellum-brain functional connectivity, with possible implications in neurorehabilitative settings.

Intracortical inhibition is modulated by phase of prosthetic rehabilitation in transtibial amputees.

Reorganization of primary motor cortex (M1) is well-described in long-term lower limb amputees. In contrast cortical reorganization during the rehabilitation period after amputation is poorly understood. Thirteen transtibial amputees and 13 gender matched control participants of similar age were recruited. Transcranial magnetic stimulation was used to assess corticomotor and intracortical excitability of M1 bilaterally. Neurophysiological assessments were conducted at admission, prosthetic casting, first walk and discharge. Gait variability at discharge was assessed as a functional measure. Compared to controls, amputees had reduced short-latency intracortical inhibition (SICI) for the ipsilateral M1 at admission (p = 0.01). Analysis across rehabilitation revealed SICI was reduced for the contralateral M1 at first walk compared to discharge (p = 0.003). For the ipsilateral M1 both short and long-latency intracortical inhibition were reduced at admission (p < 0.05) and prosthetic casting (p < 0.02). Analysis of the neurophysiology and gait function revealed several interesting relationships. For the contralateral M1, reduced inhibition at admission (p = 0.04) and first walk (p = 0.05) was associated with better gait function. For the ipsilateral M1, reduced inhibition at discharge (p = 0.05) was associated with poor gait function. This study characterized intracortical excitability in rehabilitating amputees. A dichotomous relationship between reduced intracortical inhibition for each M1 and gait function was observed at different times. Intracortical inhibition may be an appropriate cortical biomarker of gait function in lower limb amputees during rehabilitation, but requires further investigation. Understanding M1 intracortical excitability of amputees undertaking prosthetic rehabilitation provides insight into brain reorganization in the sub-acute post-amputation period and may guide future studies seeking to improve rehabilitation outcomes.

Poster #M179 REDUCED THETA BAND RESPONSE TO RELEVANCE IN SCHIZOPHRENIA

Objective: The aim of the study was to examine intracortical excitability in cerebellar patients. Methods: Short-latency intracortical inhibition (SICI), long-latency intracortical inhibition (LICI) and intracortical facilitation (ICF) to paired transcranial magnetic stimulation (TMS) were investigated in 8 patients with ‘pure’ cerebellar syndromes and in 14 age-matched normal controls. The conditioning stimulus for short-latency intracortical inhibition and intracortical facilitation was set at 70% of the resting motor threshold (RMT) and preceded the test stimulus (110–120% of the resting motor threshold) by interstimulus intervals (ISIs) of 1–30 ms. For the long-latency intracortical inhibition determinations, the conditioning stimulus was set at 120% of the resting motor threshold and preceded the test stimulus (also 120% of the resting motor threshold) by interstimulus intervals of 30–500 ms. Results: No statistically significant differences were found between patients and controls as regards either short-latency intracortical inhibition or intracortical facilitation. A significant prevalence of long-latency intracortical inhibition was present in cerebellar patients at interstimulus intervals of 200–500 ms (conditioned MEP amplitude=29–41% of test MEP) as compared to controls (71–96% of test MEP). The amplitude of conditioned MEPs was persistently less than 45% of the test MEP in six patients, who were studied at interstimulus intervals up to 1000 ms. Conclusions: Long-latency intracortical inhibition was prevalent and abnormally longer-lasting in patients. Tonic hyperactivation of a subpopulation of GABAergic interneurons in the motor cortex of patients may be the mechanism responsible for this abnormality. Our findings seem to be specific to cerebellar diseases and are the opposite of those found in movement disorders such as dystonia and Parkinson's disease. These data suggest that the cerebellum and the basal ganglia may have opposite influences in tuning the excitability of the motor cortex.

Repetitive transcranial magnetic stimulation combined with treadmill training can modulate corticomotor inhibition and improve walking performance in people with Parkinson's disease

Does adding repetitive transcranial magnetic stimulation (rTMS) to treadmill training modulate cortical excitability and improve walking in people with Parkinson's disease (PD)? Randomised controlled trial with blinded outcome assessment. A medical centre in Taiwan. Individuals with Parkinson's disease (Hoehn and Yahr Stage 2-3), and ability to walk independently were key inclusion criteria. Absence of motor evoked potential in response to rTMS, history of seizure, and use of cardiac pacemaker were key exclusion criteria. Randomisation of 22 participants allocated 11 to each of the experimental and control groups. Both groups underwent 12 treatment sessions over 4 weeks. In each session, the experimental group received rTMS (5 Hz) applied over the leg area of the motor cortex in the hemisphere contralateral to the more affected leg for 6 minutes, immediately followed by 30 minutes of treadmill training. The control group received sham rTMS in addition to the 12 sessions of treadmill training. The primary outcomes were indicators of corticomotor excitability - motor threshold, silent period, short-latency and long-latency intracortical inhibition - measured in both cerebral hemispheres. The secondary outcomes were comfortable and fast walking speeds, and the timed-up-and go test. The outcomes were measured at baseline and after the 4-week intervention period. 20 participants completed the study. At the end of the 4-week intervention period, the increase in motor threshold of 3.5% and silent period of 14.0% of the contralateral hemisphere relative to the more affected leg was significantly more in the experimental group than the control group. Significantly more reduction of short-latency intracortical inhibition in the same hemisphere was also found in the experimental group relative to the control group 10.9%. The experimental group also had significantly more improvement than the control group in fast walking speed (by 10.1cm/s) and in the timed up- and-go test (by 2.0 s). No significant differences between the groups were reported in other outcomes. Repetitive transcranial magnetic stimulation can enhance the effects on corticomotor inhibition and improvement of walking function induced by treadmill training in patients with Parkinson's disease.

Mirror Symmetric Bimanual Movement Priming Can Increase Corticomotor Excitability and Enhance Motor Learning

Repetitive mirror symmetric bilateral upper limb may be a suitable priming technique for upper limb rehabilitation after stroke. Here we demonstrate neurophysiological and behavioural after-effects in healthy participants after priming with 20 minutes of repetitive active-passive bimanual wrist flexion and extension in a mirror symmetric pattern with respect to the body midline (MIR) compared to an control priming condition with alternating flexion-extension (ALT). Transcranial magnetic stimulation (TMS) indicated that corticomotor excitability (CME) of the passive hemisphere remained elevated compared to baseline for at least 30 minutes after MIR but not ALT, evidenced by an increase in the size of motor evoked potentials in ECR and FCR. Short and long-latency intracortical inhibition (SICI, LICI), short afferent inhibition (SAI) and interhemispheric inhibition (IHI) were also examined using pairs of stimuli. LICI differed between patterns, with less LICI after MIR compared with ALT, and an effect of pattern on IHI, with reduced IHI in passive FCR 15 minutes after MIR compared with ALT and baseline. There was no effect of pattern on SAI or FCR H-reflex. Similarly, SICI remained unchanged after 20 minutes of MIR. We then had participants complete a timed manual dexterity motor learning task with the passive hand during, immediately after, and 24 hours after MIR or control priming. The rate of task completion was faster with MIR priming compared to control conditions. Finally, ECR and FCR MEPs were examined within a pre-movement facilitation paradigm of wrist extension before and after MIR. ECR, but not FCR, MEPs were consistently facilitated before and after MIR, demonstrating no degradation of selective muscle activation. In summary, mirror symmetric active-passive bimanual movement increases CME and can enhance motor learning without degradation of muscle selectivity. These findings rationalise the use of mirror symmetric bimanual movement as a priming modality in post-stroke upper limb rehabilitation.

Selective and nonselective benzodiazepine agonists have different effects on motor cortex excitability

Transcranial magnetic stimulation (TMS) is a useful method to study pharmacological effects on motor cortex excitability. Zolpidem is a selective agonist of the benzodiazepine receptor subtype BZ1 and has a distinct pharmacological profile compared to diazepam. To study the different effects of these two drugs on the cortical inhibitory system, TMS was performed before and after administration of a single oral dose of zolpidem (10 mg) and diazepam (5 mg) in six healthy volunteers. TMS tests included the determination of resting and active motor threshold (MT) and measurements of the amplitudes of motor evoked potentials, intracortical facilitation (ICF), short-latency intracortical inhibition (SICI), and long-latency intracortical inhibition (LICI), and determination of the cortical silent period (CSP). Both drugs were without effect on the active or resting MT and decreased the ICF. Prolongation of the CSP and enhancement of LICI only in the presence of zolpidem point to a specific BZ1-related mechanism underlying the long-lasting component of cortical inhibition. This selective modulation of the CSP and the LICI points to a specific role of BZ1 receptors in the control of inhibitory neuronal loops within the primary motor cortex.

Asymmetries of long-latency intracortical inhibition in motor cortex and handedness

Paired-pulse transcranial magnetic stimulation was used in three experiments to measure the properties of long-latency intracortical inhibition (LICI) acting on the relaxed first dorsal interosseus muscle of the left and right hand in right-handed volunteers. The experiments show that LICI is asymmetrical: it emerges more rapidly and is greater in the dominant than non-dominant hand shortly after activation of the LICI circuits, and is greater with low-intensity conditioning stimulus intensities in the dominant than non-dominant hand. These findings suggest that asymmetrical function of long-latency inhibitory circuits in motor cortex might contribute to the asymmetrical dexterity between the hands, possibly through their inhibitory control of the circuits responsible for short-latency inhibition.

Enhanced intracortical inhibition in cerebellar patients

Objective: The aim of the study was to examine intracortical excitability in cerebellar patients. Methods: Short-latency intracortical inhibition (SICI), long-latency intracortical inhibition (LICI) and intracortical facilitation (ICF) to paired transcranial magnetic stimulation (TMS) were investigated in 8 patients with ‘pure’ cerebellar syndromes and in 14 age-matched normal controls. The conditioning stimulus for short-latency intracortical inhibition and intracortical facilitation was set at 70% of the resting motor threshold (RMT) and preceded the test stimulus (110–120% of the resting motor threshold) by interstimulus intervals (ISIs) of 1–30 ms. For the long-latency intracortical inhibition determinations, the conditioning stimulus was set at 120% of the resting motor threshold and preceded the test stimulus (also 120% of the resting motor threshold) by interstimulus intervals of 30–500 ms. Results: No statistically significant differences were found between patients and controls as regards either short-latency intracortical inhibition or intracortical facilitation. A significant prevalence of long-latency intracortical inhibition was present in cerebellar patients at interstimulus intervals of 200–500 ms (conditioned MEP amplitude=29–41% of test MEP) as compared to controls (71–96% of test MEP). The amplitude of conditioned MEPs was persistently less than 45% of the test MEP in six patients, who were studied at interstimulus intervals up to 1000 ms. Conclusions: Long-latency intracortical inhibition was prevalent and abnormally longer-lasting in patients. Tonic hyperactivation of a subpopulation of GABAergic interneurons in the motor cortex of patients may be the mechanism responsible for this abnormality. Our findings seem to be specific to cerebellar diseases and are the opposite of those found in movement disorders such as dystonia and Parkinson's disease. These data suggest that the cerebellum and the basal ganglia may have opposite influences in tuning the excitability of the motor cortex.

Long-term changes in motor cortical organisation after recovery from subcortical stroke

The present study has investigated the long-term changes in the organisation of the corticomotor projection to the hand in a group of subjects who had sustained a subcortical hemispheric stroke up to 15 years previously and had subsequently recovered normal or near-normal motor function. Transcranial magnetic cortical stimulation (TMCS) was employed to map the topography of the primary corticomotor projection to the hand and to obtain measures of cortical motor threshold, long-latency intracortical inhibition and corticospinal conduction. Changes in motor threshold and in motor-evoked potential (MEP) amplitude and latency in keeping with persisting impairment of conduction in the corticospinal pathway were still present in the majority of subjects, whereas the duration of the post-MEP silent period, reflecting the strength of long-latency intracortical inhibition, was usually normal. Topographic shifts in the corticomotor representation relative to the unaffected side were found in the majority of subjects. In some the shifts were in the mediolateral axis suggesting reorganisation within the primary motor cortex, while in the others anteroposterior shifts were present in keeping with recruitment of premotor or postcentral cortex. The present findings indicate that changes in the physiological properties of the corticomotor projection to the hand are frequently present in subjects who have recovered motor function after a subcortical stroke and may persist indefinitely. We postulate that these changes are the result of reorganisation at cortical level and that cortical reorganisation is one of the processes which contribute to motor recovery after a subcortical lesion and which may compensate for persisting impairment of conduction in the corticospinal pathway.