Regaining Motor Control in Musician's Dystonia by Restoring Sensorimotor Organization

Professional musicians are an excellent human model of long term effects of skilled motor training on the structure and function of the motor system. However, such effects are accompanied by an increased risk of developing motor abnormalities, in particular musician's dystonia. Previously we found that there was an expanded spatial integration of proprioceptive input into the hand area of motor cortex (sensorimotor organisation, SMO) in healthy musicians as tested with a transcranial magnetic stimulation (TMS) paradigm. In musician's dystonia, this expansion was even larger, resulting in a complete lack of somatotopic organisation. We hypothesised that the disordered motor control in musician's dystonia is a consequence of the disordered SMO. In the present paper we test this idea by giving pianists with musician's dystonia 15 min experience of a modified proprioceptive training task. This restored SMO towards that seen in healthy pianists. Crucially, motor control of the affected task improved significantly and objectively as measured with a MIDI piano, and the amount of behavioural improvement was significantly correlated to the degree of sensorimotor re-organisation. In healthy pianists and non-musicians, the SMO and motor performance remained essentially unchanged. These findings suggest a link between the differentiation of SMO in the hand motor cortex and the degree of motor control of intensively practiced tasks in highly skilled individuals

Pulse Duration as Well as Current Direction Determines the Specificity of Transcranial Magnetic Stimulation of Motor Cortex during Contraction

BACKGROUND: Previous research suggested that anterior-posterior (AP) directed currents induced by TMS in motor cortex (M1) activate different interneuron circuits than posterior-anterior currents (PA). The present experiments provide evidence that pulse duration also determines the activation of specific interneuron circuits. OBJECTIVE: To use single motor unit (SMU) recordings to confirm the difference in onset latencies of motor-evoked potentials (MEPs) evoked by different current directions and pulse durations: AP30, AP120, PA30 and PA120. To test whether the amplitude of the MEPs is differentially influenced by somatosensory inputs from the hand (short-latency afferent inhibition, SAI), and examine the sensitivity of SAI to changes in cerebellar excitability produced by direct current stimulation (tDCSCb). METHODS: Surface electromyograms and SMUs were recorded from the first dorsal interosseous muscle. SAI was tested with an electrical stimulus to median or digital nerves ~20-25ms prior to TMS delivered over the M1 hand area via a controllable pulse parameter TMS (cTMS) device. SAI was also tested during the application of anodal or sham tDCSCb. Because TMS pulse specificity is greatest at low stimulus intensities, most experiments were conducted with weak voluntary contraction to reduce stimulus threshold. RESULTS: AP30 currents recruited the longest latency SMU and surface MEP responses. During contraction SAI was greater for AP30 responses versus all other pulses. Online anodal tDCSCb reduced SAI for the AP30 currents only. CONCUSIONS: AP30 currents activate an interneuron circuit with different functional properties to those activated by other pulse types. Pulse duration and current direction determine what is activated in M1 with TMS

Membrane resistance and shunting inhibition: where biophysics meets state-dependent human neurophysiology

Activation of neurons not only changes their membrane potential and firing rate but, as a secondary action reduces membrane resistance. This loss of resistance, or increase of conductance, may be of central importance in non-invasive magnetic or electric stimulation of the human brain since electrical fields cause larger changes in transmembrane voltage in resting neurones with low membrane conductances than in active neurones with high conductance. This may explain why both the immediate and after-effects of brain stimulation are smaller or even reversed during voluntary activity compared to rest. Membrane conductance is also increased during shunting inhibition, which accompanies the classic GABAa IPSP. This short-circuits nearby EPSPs and is suggested here to contribute to the magnitude and time course of short latency intracortical inhibition (SICI) and facilitation (ICF). This article is protected by copyright. All rights reserved

Explicit motor sequence learning with the paretic arm after stroke

PURPOSE: Motor sequence learning is important for stroke recovery, but experimental tasks require dexterous movements, which are impossible for people with upper limb impairment. This makes it difficult to draw conclusions about the impact of stroke on learning motor sequences. We aimed to test a paradigm requiring gross arm movements to determine whether stroke survivors with upper limb impairment were capable of learning a movement sequence as effectively as age-matched controls. MATERIALS AND METHODS: In this case-control study, 12 stroke survivors (10-138 months post-stroke, mean age 64 years) attempted the task once using their affected arm. Ten healthy controls (mean 66 years) used their non-dominant arm. A sequence of 10 movements was repeated 25 times. The variables were: time from target illumination until the cursor left the central square (onset time; OT), accuracy (path length), and movement speed. RESULTS: OT reduced with training (p  0.1). We quantified learning as the OT difference between the end of training and a random sequence; this was smaller for stroke survivors than controls (p = 0.015). CONCLUSIONS: Stroke survivors can learn a movement sequence with their paretic arm, but demonstrate impairments in sequence specific learning. Implications for Rehabilitation Motor sequence learning is important for recovery of movement after stroke. Stroke survivors were found to be capable of learning a movement sequence with their paretic arm, supporting the concept of repetitive task training for recovery of movement. Stroke survivors showed impaired sequence specific learning in comparison with age-matched controls, indicating that they may need more repetitions of a sequence in order to re-learn movements. Further research is required into the effect of lesion location, time since stroke, hand dominance and gender on learning of motor sequences after stroke

Possible role of backpropagating action potentials in corticospinal neurons in I-wave periodicity following a TMS pulse

A single pulse of TMS or direct electric stimulation over M1 causes repetitive synchronized firing of corticospinal tract (CST) neurons. Two mechanisms for the repetitive firing have been proposed: a cascade of synaptic inputs to the pyramidal neurons and a single reverberating circuit of interneurons. Here, we propose another possibility in which bursting of CST neurons is produced by dendritic Ca2+-spikes. Backpropagation of the initial action potential (I1-wave) from the soma interacts with synaptic input in the dendrites to initiate a dendritic calcium spike. These Ca2+-spikes produce a burst of somatic action potentials that starts about 1.5 ms after the initial discharge of the neuron, which may produce the later I-waves

Cerebellar–Motor Cortex Connectivity: One or Two Different Networks?

Anterior-posterior (AP) and posterior-anterior (PA) pulses of transcranial magnetic stimulation over the primary motor cortex (M1) appear to activate distinct interneuron networks that contribute differently to two varieties of physiological plasticity and motor behaviors (Hamada et al., 2014). The AP network is thought to be more sensitive to online manipulation of cerebellar (CB) activity using transcranial direct current stimulation. Here we probed CB-M1 interactions using cerebellar-brain inhibition (CBI) on young healthy female and male individuals. Transcranial magnetic stimulation (TMS) over the cerebellum produced maximal CBI of PA-evoked EMG responses at an inter-stimulus interval of 5ms (PA-CBI), whereas the maximum effect on AP responses was at 7ms (AP-CBI), suggesting that CB-M1 pathways with different conduction times interact with AP and PA networks. In addition, paired associative stimulation using ulnar nerve stimulation and PA TMS pulses over M1, a protocol used in human studies to induce cortical plasticity, reduced PA-CBI but not AP-CBI, indicating that cortical networks process cerebellar inputs in distinct ways. Finally, PA-CBI and AP-CBI were differentially modulated after performing two different types of motor learning tasks that are known to process cerebellar input in different ways. The data presented here are compatible with the idea that applying different TMS currents to the cerebral cortex may reveal cerebellar inputs to both the premotor cortex and M1. Overall, these results suggest there are two independent CB-M1networks that contribute uniquely to different motor behaviors

Impaired intracortical inhibition demonstrated in vivo in people with Dravet syndrome

OBJECTIVE: Dravet syndrome is a rare neurodevelopmental disorder characterized by seizures and other neurologic problems. SCN1A mutations account for ∼80% of cases. Animal studies have implicated mutation-related dysregulated cortical inhibitory networks in its pathophysiology. We investigated such networks in people with the condition. METHODS: Transcranial magnetic stimulation using single and paired pulse paradigms was applied to people with Dravet syndrome and to 2 control groups to study motor cortex excitability. RESULTS: Short interval intracortical inhibition (SICI), which measures GABAergic inhibitory network behavior, was undetectable in Dravet syndrome, but detectable in all controls. Other paradigms, including those testing excitatory networks, showed no difference between Dravet and control groups. CONCLUSIONS: There were marked differences in inhibitory networks, detected using SICI paradigms, while other inhibitory and excitatory paradigms yielded normal results. These human data showing reduced GABAergic inhibition in vivo in people with Dravet syndrome support established animal models

Premovement suppression of corticospinal excitability may be a necessary part of movement preparation

In a warned reaction time (RT) task, corticospinal excitability (CSE) decreases in task-related muscles at the time of the imperative signal (preparatory inhibition). Because RT tasks emphasise speed of response, it is impossible to distinguish whether preparatory inhibition reflects a mechanism preventing premature reactions, or whether it is an inherent part of movement preparation. We used transcranial magnetic stimulation (TMS) to study CSE changes preceding RT movements and movements that were either self-paced (SP) or performed at predictable times to coincide with an external event (PT). Results show that CSE changes over a similar temporal profile in all cases, suggesting that preparatory inhibition is a necessary state in planned movements allowing the transition between rest and movement. Additionally, TMS given shortly before the times to move speeded the onset of movements in both RT and SP contexts, suggesting that their initiation depends on a form of trigger that can be conditioned by external signals. On the contrary, PT movements do not show this effect, suggesting the use of a mechanistically different triggering strategy. This relative immunity of PT tasks to be biased by external events may reflect a mechanism that ensures priority of internal predictive signals to trigger movement onset

SICI during changing brain states: Differences in methodology can lead to different conclusions

Background: Short-latency intracortical inhibition (SICI) is extensively used to probe GABAergic inhibitory mechanisms in M1. Task-related changes in SICI are presumed to reflect changes in the central excitability of GABAergic pathways. Usually, the level of SICI is evaluated using a single intensity of conditioning stimulus so that inhibition can be compared in different brain states. Objective: Here, we show that this approach may sometimes be inadequate since distinct conclusions can be drawn if a different CS intensity is used. Methods: We measured SICI using a range of CS intensities at rest and during a warned simple reaction time task. Conclusions: Our results show that SICI changes that occurred during the task could be either larger or smaller than at rest depending on the intensity of the CS. These findings indicate that careful interpretation of results are needed when a single intensity of CS is used to measure task-related physiological changes