Jonathan Shemmell

The Effects of Individualized Theta Burst Stimulation on the Excitability of the Human Motor System

BACKGROUND Theta burst stimulation (TBS) is a pattern of repetitive transcranial magnetic stimulation that has been demonstrated to facilitate or suppress human corticospinal excitability when applied intermittently (iTBS) or continuously (cTBS), respectively. While the fundamental pattern of TBS, consisting of bursts of 50 Hz stimulation repeated at a 5 Hz theta frequency, induces synaptic plasticity in animals and in vitro preparations, the relationship between TBS and underlying cortical firing patterns in the human cortex has not been elucidated. OBJECTIVE To compare the effects of 5 Hz iTBS and cTBS with individualized TBS paradigms on corticospinal excitability and intracortical inhibitory circuits. METHODS Participants received standard and individualized iTBS (iTBS 5; iTBS I) and cTBS (cTBS 5; cTBS I), and sham TBS, in a randomised design. For individualized paradigms, the 5 Hz theta component of the TBS pattern was replaced by the dominant cortical frequency (4-16 Hz; upper frequency restricted by technical limitations) for each individual. RESULTS We report that iTBS 5 and iTBS I both significantly facilitated motor evoked potential (MEP) amplitude to a similar extent. Unexpectedly, cTBS 5 and cTBS I failed to suppress MEP amplitude. None of the active TBS protocols had any significant effects on intracortical circuits when compared with sham TBS. CONCLUSION In summary, iTBS facilitated MEP amplitude, an effect that was not improved by individualizing the theta component of the TBS pattern, while cTBS, a reportedly inhibitory paradigm, produced no change, or facilitation of MEP amplitude in our hands.

Bilateral impairments in task-dependent modulation of the long-latency stretch reflex following stroke

OBJECTIVE Modulation of the long-latency reflex (LLR) is important for sensorimotor control during interaction with different mechanical loads. Transcortical pathways usually contribute to LLR modulation, but the integrity of pathways projecting to the paretic and non-paretic arms of stroke survivors is compromised. We hypothesize that disruption of transcortical reflex pathways reduces the capacity for stroke survivors to appropriately regulate the LLR bilaterally. METHODS Elbow perturbations were applied to the paretic and non-paretic arms of persons with stroke, and the dominant arm of age-matched controls as subjects interacted with Stiff or Compliant environments rendered by a linear actuator. Reflexes were quantified using surface electromyograms, recorded from biceps. RESULTS LLR amplitude was significantly larger during interaction with the Compliant load compared to the Stiff load in controls. However, there was no significant change in LLR amplitude for the paretic or non-paretic arm of stroke survivors. CONCLUSION Modulation of the LLR is altered in the paretic and non-paretic arms after stroke. SIGNIFICANCE Our results are indicative of bilateral sensorimotor impairments following stroke. The inability to regulate the LLR may contribute to bilateral deficits in tasks that require precise control of limb mechanics and stability.

Interactions between stretch and startle reflexes produce task-appropriate rapid postural reactions.

Neural pathways underpinning startle reflex and limb stretch reflexes evolved independently and have served vastly different purposes. In their most basic form, the pathways responsible for these reflex responses are relatively simple processing units that produce a motoric response that is proportional to the stimulus received. It is becoming clear however, that rapid responses to external stimuli produced by human and non-human primates are context-dependent in a manner similar to voluntary movements. This mini review discusses the nature of startle and stretch reflex interactions in human and non-human primates and the involvement of the primary motor cortex in their regulation.

Numerical modelling of plasticity induced by transcranial magnetic stimulation

We use neural field theory and spike-timing dependent plasticity to make a simple but biophysically reasonable model of long-term plasticity changes in the cortex due to transcranial magnetic stimulation (TMS). We show how common TMS protocols can be captured and studied within existing neural field theory. Specifically, we look at repetitive TMS protocols such as theta burst stimulation and paired-pulse protocols. Continuous repetitive protocols result mostly in depression, but intermittent repetitive protocols in potentiation. A paired pulse protocol results in depression at short ( < ∼ 10 ms) and long ( > ∼ 100 ms) interstimulus intervals, but potentiation for mid-range intervals. The model is sensitive to the choice of neural populations that are driven by the TMS pulses, and to the parameters that describe plasticity, which may aid interpretation of the high variability in existing experimental results. Driving excitatory populations results in greater plasticity changes than driving inhibitory populations. Modelling also shows the merit in optimizing a TMS protocol based on an individual’s electroencephalogram. Moreover, the model can be used to make predictions about protocols that may lead to improvements in repetitive TMS outcomes.

Calcium dependent plasticity applied to repetitive transcranial magnetic stimulation with a neural field model

The calcium dependent plasticity (CaDP) approach to the modeling of synaptic weight change is applied using a neural field approach to realistic repetitive transcranial magnetic stimulation (rTMS) protocols. A spatially-symmetric nonlinear neural field model consisting of populations of excitatory and inhibitory neurons is used. The plasticity between excitatory cell populations is then evaluated using a CaDP approach that incorporates metaplasticity. The direction and size of the plasticity (potentiation or depression) depends on both the amplitude of stimulation and duration of the protocol. The breaks in the inhibitory theta-burst stimulation protocol are crucial to ensuring that the stimulation bursts are potentiating in nature. Tuning the parameters of a spike-timing dependent plasticity (STDP) window with a Monte Carlo approach to maximize agreement between STDP predictions and the CaDP results reproduces a realistically-shaped window with two regions of depression in agreement with the existing literature. Developing understanding of how TMS interacts with cells at a network level may be important for future investigation.

Differences in Motor Evoked Potentials Induced in Rats by Transcranial Magnetic Stimulation under Two Separate Anesthetics: Implications for Plasticity Studies

Repetitive transcranial magnetic stimulation (rTMS) is primarily used in humans to change the state of corticospinal excitability. To assess the efficacy of different rTMS stimulation protocols, motor evoked potentials (MEPs) are used as a readout due to their non-invasive nature. Stimulation of the motor cortex produces a response in a targeted muscle, and the amplitude of this twitch provides an indirect measure of the current state of the cortex. When applied to the motor cortex, rTMS can alter MEP amplitude, however, results are variable between participants and across studies. In addition, the mechanisms underlying any change and its locus are poorly understood. In order to better understand these effects, MEPs have been investigated in vivo in animal models, primarily in rats. One major difference in protocols between rats and humans is the use of general anesthesia in animal experiments. Anesthetics are known to affect plasticity-like mechanisms and so may contaminate the effects of an rTMS protocol. In the present study, we explored the effect of anesthetic on MEP amplitude, recorded before and after intermittent theta burst stimulation (iTBS), a patterned rTMS protocol with reported facilitatory effects. MEPs were assessed in the brachioradialis muscle of the upper forelimb under two anesthetics: a xylazine/zoletil combination and urethane. We found MEPs could be induced under both anesthetics, with no differences in the resting motor threshold or the average baseline amplitudes. However, MEPs were highly variable between animals under both anesthetics, with the xylazine/zoletil combination showing higher variability and most prominently a rise in amplitude across the baseline recording period. Interestingly, application of iTBS did not facilitate MEP amplitude under either anesthetic condition. Although it is important to underpin human application of TMS with mechanistic examination of effects in animals, caution must be taken when selecting an anesthetic and in interpreting results during prolonged TMS recording.

Sex differences in anticipatory postural adjustments during rapid single leg lift

The aim of this study was to assess the influence of sex on the kinetic, kinematic and neuromuscular correlates of anticipatory postural adjustments (APAs) during a single leg lift task performed by healthy participants. Fifty healthy age and body mass index matched participants (25 women and 25 men) performed 20 single leg lift task (hip flexion to 90 ° as quickly as possible) with their dominant and their non-dominant lower limbs. A force plate was used to determine the medial-lateral displacement of the center of pressure (COPML), and the initiation of weight shift (T0); kinematics was used to determine leg lift (T1); and electromyography was used to determine onset times from eight muscles: bilateral external oblique, internal oblique and lumbar multifidus, and unilateral (stance limb) gluteus maximus and biceps femoris. Movement control limb dominance was included in the analysis. Statistically significant interactions between sex and limb dominance (p < .001) were observed for T1, COPML, and muscle onsets. Also, statistically significant main effect of sex on T0 was observed. Women showed increased APA time (T1) and magnitude (COPML) in their dominant limbs compared to men. Such differences between sexes did not occur in the non-dominant limb. Women recruited proximal muscles later than their man counterparts. Overall, women appear to have a stronger effect of limb dominance on their anticipatory postural control strategy which requires further investigation. The findings of the current study indicate that women and men differ in their anticipatory postural control strategy for rapid single leg lift.

The ipsilateral motor cortex does not contribute to long-latency stretch reflex amplitude at the wrist.

A capacity for modulating the amplitude of the long‐latency stretch reflex (LLSR) allows us to successfully interact with a physical world with a wide range of different mechanical properties. It has recently been demonstrated that stretch reflex modulation is impaired in both arms following monohemispheric stroke, suggesting that reflex regulation may involve structures on both sides of the motor system.

The Effect of Paired Muscle Stimulation on Preparation for Movement

ABSTRACT Paired muscle stimulation is used clinically to facilitate the performance of motor tasks for individuals with motor dysfunction. However, the optimal temporal relationship between stimuli for enhancing movement remains unknown. We hypothesized that synchronous, muscle stimulation would increase the extent to which stimulated muscles are concurrently prepared for movement. We validated a measure of muscle-specific changes in corticomotor excitability prior to movement. We used this measure to examine the preparation of the first dorsal interosseous (FDI), abductor digiti minimi (ADM), abductor pollicis brevis (APB) muscles prior to voluntary muscle contractions before and after paired muscle stimulation at four interstimulus intervals (0, 5, 10, and 75 ms). Paired muscle stimulation increased premovement excitability in the stimulated FDI, but not in the ADM muscle. Interstimulus interval was not a significant factor in determining efficacy of the protocol. Paired stimulation, therefore, did not result in a functional association being formed between the stimulated muscles. Somatosensory potentials evoked by the muscle stimuli were small compared to those commonly elicited by stimulation of peripheral nerves, suggesting that the lack of functional association formation between muscles may be due to the small magnitude of afferent volleys from the stimulated muscles, particularly the ADM, reaching the cortex.

Differences between clinician- and self-administered shoulder sustained mobilization on scapular and shoulder muscle activity during shoulder abduction: A repeated-measures study on asymptomatic individuals

BACKGROUND Sustained glenohumeral postero-lateral glide administered by a clinician is commonly used in the management of patients with shoulder pain. This technique reduced shoulder muscle activity in asymptomatic individuals, but it is unknown whether a self-administered version of the mobilization leads to similar neuromuscular response. This study compared the effect of sustained shoulder mobilizations (performed by a physiotherapist) with self-administered mobilization (with a belt) on activity levels of scapular and glenohumeral shoulder muscles. METHODS Twenty-two individuals participated in this study, which had a cross-over, repeated measures design. Seven shoulder muscles (upper and lower trapezius, supraspinatus, infraspinatus, posterior deltoid, middle deltoid, and serratus anterior) were monitored using surface electromyography (SEMG) during shoulder abduction performed with a clinician-administered sustained mobilization, and with self-administered sustained mobilization. Muscle activity levels were measured prior, during and after the sustained glide was applied to the shoulder. Mixed-effect models for repeated measures were used for within- and between-condition comparisons. RESULTS There was no carry-over effect. Within-condition comparisons suggest that both interventions lead to changes in scapular and shoulder muscle activity levels. No differences between clinician-administered and self-administered mobilizations at intervention and follow-up were found for the monitored muscles, with the exception of upper trapezius. CONCLUSIONS In young, asymptomatic individuals, self- or clinician-administered sustained mobilizations reduced activity levels of most scapular and shoulder muscles during shoulder abduction. This effect was observed only while the sustained glides were applied to the shoulder. At the immediate follow-up, muscle activity levels were similar to baseline measurements.