Karin Rosenkranz

Differential Modulation of Motor Cortical Plasticity and Excitability in Early and Late Phases of Human Motor Learning

Different phases of motor skill learning appear to involve different physiological processes, with long-term potentiation (LTP) occurring at existing synapses in early and cortical reorganization involving synaptogenesis in later phases. Here, we test the evolution of skill learning-dependent changes in motor plasticity and excitability in six subjects trained to perform rapid thumb abductions over 5 d. Plasticity was examined using paired-associative stimulation (PAS) of the median nerve and motor cortex to induce LTP-like “PAS given with an interstimulus interval of 25 ms (PAS25)” or long-term depression (LTD)-like “PAS given with an interstimulus interval of 10 ms (PAS10)” plasticity. Excitability was tested by measuring recruitment of motor-evoked-potentials “input–output (IO) curve” and of short-latency intracortical inhibition (SICI curve), and sensorimotor organization (SMO). Task performance improved continuously over 5 d. After practice on day 1, the PAS25 effect reversed from facilitation to inhibition whereas the slope of the IO curve increased and the level of SICI decreased. These effects on IO curve and SICI were still present or even enhanced before the last practice on day 5, and were not changed by it. The effect of proprioceptive input from the trained muscle on SMO was also strengthened before practice on day 5. In contrast, PAS-induced plasticity was not influenced by motor practice on day 5, and had returned to prepractice values. The interference with PAS-induced plasticity suggests that the initial performance improvement relies on increasing the efficacy of existing synaptic connections. However, the long-lasting changes in the IO curve, SICI curve, and SMO suggest that continued practice enhances performance by changing Motor cortical organization. We hypothesize that new synaptic connections might have formed that allow LTP/LTD-susceptibility to be restored without reducing synaptic strength and performance skill.

Differential effect of muscle vibration on intracortical inhibitory circuits in humans

Low amplitude muscle vibration (0.5 ms; 80 Hz; duration 1.5 s) was applied in turn to each of three different intrinsic hand muscles (first dorsal interosseus, FDI; abductor pollicis brevis, APB; and abductor digiti minimi, ADM) in order to test its effect on the EMG responses evoked by transcranial magnetic stimulation (TMS). Recordings were also taken from flexor and extensor carpi radialis (FCR and ECR, respectively). We evaluated the amplitude of motor evoked potentials (MEPs) produced by a single TMS pulse, short interval intracortical inhibition and facilitation (SICI and ICF) and long interval intracortical inhibition (LICI). TMS pulses were applied 1 s after the start of vibration with subjects relaxed throughout. Vibration increased the amplitude of MEPs evoked in the vibrated muscle (162 ± 6 % of MEP with no vibration; mean ±s.e.m.), but suppressed MEPs in the two non‐vibrated hand muscles (72 ± 9 %). Compared with no vibration (test response reduced to 51 ± 5 % of control), there was less SICI in the vibrated muscle (test response reduced to 92 ± 28 % of control) and more in the non‐vibrated hand muscles (test response reduced to 27 ± 5 % of control). The opposite occurred for LICI: compared with the no vibration condition (test response reduced to 33 ± 6 % control), there was more LICI in the vibrated muscle (test response reduced to 17 ± 3 % control) than in the non‐vibrated hand muscles (test response reduced to 80 ± 11 % control) even when the intensity of the test stimulus was adjusted to compensate for the changes in baseline MEP. There was no effect on ICF. Cutaneous stimulation of the index finger (80 Hz, 1.5 s duration, twice sensory threshold) had no consistent differential effect on any of the parameters. We conclude that vibratory input from muscle can differentially modulate excitability in motor cortical circuits.

Motorcortical Excitability and Synaptic Plasticity Is Enhanced in Professional Musicians

Musicians not only have extraordinary motor and sensory skills, but they also have an increased ability to learn new tasks compared with non-musicians. We examined how these features are expressed in neurophysiological parameters of excitability and plasticity in the motor system by comparing the results of 11 professional musicians and 8 age-matched non-musicians. Parameters of motor excitability were assessed using transcranial magnetic stimulation (TMS) to measure motor-evoked potentials (MEPs) together with recruitment of corticospinal projections [input–output curve (IOcurve)] and of short-latency intracortical inhibition (SICIcurve). Plasticity, here defined as change of synaptic effectiveness, was tested by measuring MEPs and IOcurves after paired associative stimulation (PAS), which consists of an electric median nerve stimulus repeatedly paired (200 times at 0.25Hz) with a TMS pulse over the hand motor area. Using an interstimulus interval of 25 ms (PAS25) or 10 ms (PAS10), this leads to long-term potentiation- or long-term depression-like plasticity, respectively. Musicians showed steeper recruitment of MEPs and SICI (IOcurve and SICIcurve). Additionally, PAS25 increased and PAS10 decreased the MEP amplitudes and the slope of the IOcurves significantly more in musicians than in non-musicians. This is consistent with a wider modification range of synaptic plasticity in musicians. Together with the steeper recruitment of corticospinal excitatory and intracortical inhibitory projections, this suggests that they regulate plasticity and excitability with a higher gain than normal. Because some of these changes depend on age at which instrumental playing commenced and on practice intensity, they may reflect an increase in number and modifiability of synapses within the motor area caused by long-term musical practice.

The effect of sensory input and attention on the sensorimotor organization of the hand area of the human motor cortex

Sensory input can remodel representations in the sensory cortex, and this effect is heavily influenced by attention to the stimulus. Here we ask whether pure sensory input can also influence the spatial distribution of sensory effects on motor cortical hand area (sensorimotor organization) and whether this is modulated by attention. Sensorimotor organization was tested by applying short (1.5 s) periods of low amplitude vibration to single intrinsic hand muscles and measuring motor cortex excitability with transcranial magnetic stimulation (TMS). In healthy subjects, sensorimotor organization in the hand is focal, with input from one hand muscle increasing motor‐evoked potentials (MEPs), decreasing short and increasing long‐interval intracortical inhibition (SICI and LICI) in the vibrated muscle (‘homotopic’ effects) and having opposite effects on neighbouring muscles (‘heterotopic’ effects). Here we show that a 15 min intervention of vibration applied simultaneously to two hand muscles can lead to long‐term (> 30 min) changes in the spatial pattern of sensorimotor interaction. The amount and direction of the effects depended on the subjects attention during the intervention: if subjects attended to both muscles when they were receiving simultaneous vibration, subsequent short‐term vibration applied to one of them produced ‘homotopic’ effects on both muscles. ‘Heterotopic’ effects on a muscle not vibrated during the intervention were unaffected. If subjects did not attend to simultaneous vibration, subsequent short‐term vibration of the muscles involved in the intervention no longer had any effect on them although the ‘heterotopic’ effects on a muscle not involved in the intervention were unchanged. We conclude that a 15 min period of pure sensory input can remodel the way that subsequent sensory inputs interact with motor output, that the effects are specific for the motor output to muscles involved in the intervention and that they are modulated by the subjects attention.

Differences between the effects of three plasticity inducing protocols on the organization of the human motor cortex

Several experimental protocols induce lasting changes in the excitability of motor cortex. Some involve direct cortical stimulation, others activate the somatosensory system and some combine motor and sensory stimulation. The effects usually are measured as changes in amplitude of the motor‐evoked‐potential (MEP) or short‐interval intracortical inhibition (SICI) elicited by a single or paired pulses of transcranial magnetic stimulation (TMS). Recent work has also tested sensorimotor organization within the motor cortex by recording MEPs and SICI during short periods of vibration applied to single intrinsic hand muscles. Here sensorimotor organization is focal: MEPs increase and SICI decreases in the vibrated muscle, whilst the opposite occurs in neighbouring muscles. In six volunteers we compared the after effects of three protocols that lead to lasting changes in cortical excitability: (i) paired associative stimulation (PAS) between a TMS pulse and an electrical stimulus to the median nerve; (ii) motor practice of rapid thumb abduction; and (iii) sensory input produced by semicontinuous muscle vibration, on MEPs and SICI at rest and on the sensorimotor organization. PAS increased MEP amplitudes, whereas vibration changed sensorimotor organization. Motor practice had a dual effect and increased MEPs as well as affecting sensorimotor organization. The implication is that different protocols target different sets of cortical circuits. We speculate that protocols that involve repeated activation of motor cortical output lead to lasting changes in efficacy of synaptic connections in output circuits, whereas protocols that emphasize sensory inputs affect the strength of sensory inputs to motor circuits.

Sensorimotor reorganization by proprioceptive training in musician's dystonia and writer's cramp

Objective: The sensorimotor organization (SMO) of the motor hand area is abnormal in focal hand dystonia and likely contributes to symptom manifestation. In healthy subjects SMO is changed by training with proprioceptive stimulation. Here we test whether similar interventions reverse the abnormal SMO in musicians dystonia and writers cramp. If so, they could be developed for therapeutic application. Methods: In six non-musicians, six professional musicians, six patients with musicians dystonia, and six patients with writers cramp, SMO was explored by measuring changes in short-interval-intracortical-inhibition (SICI) during short periods of hand muscle vibration before and after two training types: AttVIB, involving attention to 15 minutes vibration of the abductor pollicis brevis (APB); and AttIndex, involving attention to subtle cutaneous stimulation of the index finger. Results: In healthy non-musicians, baseline SMO is spatially differentiated: SICI is reduced in projections to the vibrated, but enhanced to the non-vibrated muscles. Here AttVIB increased and AttIndex reduced the effect of subsequent APB-vibration on SMO. In healthy musicians, baseline SMO is less differentiated. AttVIB reinstated a more differential SMO pattern while AttIndex attenuated the effect of APB vibration. In focal hand dystonia, SMO is completely dedifferentiated. AttVIB tended to restore a more differential SMO in musicians dystonia but not in writers cramp while AttIndex failed to induce any changes in both groups. Conclusion: The intervention effect depends on the pre-interventional sensorimotor organization (SMO). In focal hand dystonia, particularly in musicians dystonia, it is possible to retrain an abnormal SMO toward a more differential pattern, which has potential implications for therapy.

Alteration of sensorimotor integration in musician's cramp: impaired focusing of proprioception

OBJECTIVE The influence of muscle vibration (MV) as a strong proprioceptive input on motorcortical excitability was studied in 5 patients with musicians cramp, 5 musician controls and 5 non-musician controls. METHODS The relaxed flexor carpi radialis (FCR), involved in the dystonic movement in all patients, was vibrated using low frequency (80 Hz) and low amplitude (0.5 mm). Transcranial magnetic stimulation (TMS; intensity, 120% of motor threshold) was applied without MV, 3 and 9 s after the onset of MV. Motor-evoked potentials (MEPs) in the FCR and in the antagonistic extensor carpi radialis (ECR) were recorded. RESULTS With MV, musician and non-musician controls showed a facilitation of MEPs in the FCR and a decrease of MEPs in the ECR. In musicians cramp, both phenomena were significantly less pronounced. CONCLUSIONS The reduced facilitation of MEPs in musicians cramp indicates a reduced MV-induced activation of motorcortical areas representing the FCR. The less pronounced inhibition by MV reflects a reduced inhibitory control of the antagonistic ECR. As there were no differences between musician and non-musician controls, the observed changes in musicians cramp refer to this special form of focal dystonia. An impairment of focused motorcortical activation by proprioceptive input from a muscle involved in the dystonic movement is suggested.

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

Professional musicians are an excellent model of long-term motor learning effects on structure and function of the sensorimotor system. However, intensive motor skill training has been associated with task-specific deficiency in hand motor control, which has a higher prevalence among musicians (musicians dystonia) than in the general population. Using a transcranial magnetic stimulation paradigm, we previously found an expanded spatial integration of proprioceptive input into the hand motor cortex [sensorimotor organization (SMO)] in healthy musicians. In musicians dystonia, however, this expansion was even larger. Whereas motor skills of musicians are likely to be supported by a spatially expanded SMO, we hypothesized that in musicians dystonia this might have developed too far and now disrupts rather than assists task-specific motor control. If so, motor control should be regained by reversing the excessive reorganization in musicians dystonia. Here, we test this hypothesis and show that a 15 min intervention with proprioceptive input (proprioceptive training) restored SMO in pianists with musicians dystonia to the pattern seen in healthy pianists. Crucially, task-specific motor control improved significantly and objectively as measured with a MIDI (musical instrument digital interface) piano, and the amount of behavioral improvement was significantly correlated to the degree of sensorimotor reorganization. In healthy pianists and nonmusicians, the SMO and motor performance remained essentially unchanged. These findings suggest that the differentiation of SMO in the hand motor cortex and the degree of motor control of intensively practiced tasks are significantly linked and finely balanced. Proprioceptive training restored this balance in musicians dystonia to the behaviorally beneficial level of healthy musicians.

Modulation of Proprioceptive Integration in the Motor Cortex Shapes Human Motor Learning

Sensory and motor systems interact closely during movement performance. Furthermore, proprioceptive feedback from ongoing movements provides an important input for successful learning of a new motor skill. Here, we show in humans that attention to proprioceptive input during a purely sensory task can influence subsequent learning of a novel motor task. We applied low-amplitude vibration to the abductor pollicis brevis (APB) muscle of eight healthy volunteers for 15 min while they discriminated either a small change in vibration frequency or the presence of a simultaneous weak cutaneous stimulus. Before and after the sensory attention tasks, we evaluated the following in separate experiments: (1) sensorimotor interaction in the motor cortex by testing the efficacy of proprioceptive input to reduce GABAAergic intracortical inhibition using paired-pulse transcranial magnetic stimulation, and (2) how well the same subjects learned a ballistic thumb abduction task using the APB muscle. Performance of the vibration discrimination task increased the interaction of proprioceptive input with motor cortex excitability in the APB muscle, whereas performance in the cutaneous discrimination task had the opposite effect. There was a significant correlation between the integration of proprioceptive input in the motor cortex and the motor learning gain: increasing the integration of proprioceptive input from the APB increased the rate of motor learning and reduced performance variability, while decreasing proprioceptive integration had opposite effects. These findings suggest that the sensory attention tasks transiently change how proprioceptive input is integrated into the motor cortex and that these sensory changes drive subsequent learning behavior in the human motor cortex.

Transcallosal sensorimotor integration: effects of sensory input on cortical projections to the contralateral hand.

OBJECTIVE Low amplitude vibration of forearm or hand muscles predominantly activates proprioceptive inputs that influence corticospinal projections in a focal manner, increasing output to the stimulated muscle while reducing output to neighbouring muscles. Modulation of contralateral forearm muscles by vibration has also been reported on one occasion. The aim of the current investigation was to investigate the effects of proprioceptive input from a hand muscle on corticospinal excitability, intracortical inhibition (SICI) and interhemispheric inhibition (IHI) targeting the homologous contralateral muscle. METHODS Transcranial Magnetic Stimulation (TMS) was delivered to the left cortical hand area of 10 healthy subjects and surface electromyography (EMG) recordings taken from the right First Dorsal Interosseus (FDI) and Abductor Digiti Minimi (ADM). The effect of low amplitude vibration of the left FDI on MEP amplitudes, SICI and IHI targeting the right hand was assessed. RESULTS Vibration of the left FDI caused a significant reduction in MEP amplitudes in the homologous right FDI but not in the right ADM. SICI and IHI targeting both muscles were also significantly increased. CONCLUSIONS We conclude that proprioceptive input from a hand muscle reduces the corticospinal excitability of the contralateral homologous muscle. The increases in SICI and IHI suggest that at least some of this effect occurs in the cortex ipsilateral to the stimulus and this may be mediated via transcallosal fibres. SIGNIFICANCE These results suggest that sensory input can modulate excitability in both motor cortices simultaneously, as well as the relationship between them. Interventions which modulate this transcallosal relationship may become useful in disorders where abnormal IHI is a potential therapeutic target.