Motorcortical Excitability and Synaptic Plasticity Is Enhanced in Professional Musicians

Differences of baseline excitability in non-musicians and musicians

The slope of the IOcurve depends on the distribution of excitability in populations of motoneurons and interneurons at spinal and cortical sites and is therefore influenced by many factors (Ridding and Rothwell, 1997; Boroojerdi et al., 2001; Jensen et al., 2005). There are no detailed studies of spinal excitability in musicians, so it remains possible that their steeper IOcurves are attributable to changes in the excitability of spinal motoneurons such that a larger response is evoked by a given corticospinal volley. Although subthreshold differences in the distribution of excitability in the spinal motoneuron pool between musicians and non-musicians cannot be excluded, we tried to control for this by expressing stimulus intensities relative to the SI1mV in APB, which was similar in both groups. Therefore, it seems likely that some of the increased slope of the IOcurve in musicians relates to changes in motor cortical organization.

Effects on the cortex are consistent with animal studies showing that the late phase of motor skill learning is associated with increases in the number of synapses in the corresponding area of the motor cortex (Kleim et al., 2002, 2004). The increased gray matter density found in MR images of musicians' brains suggests that a similar process occurs in them. Indeed, changes in gray matter are larger in musicians who started earlier (Gaser and Schlaug, 2003), and they reflect the choice of instrument (Bangert and Schlaug, 2006), consistent with a causal connection between presumed synaptic growth and the duration and pattern of training. If so, then it may be that increased synaptic connectivity is one factor that leads to increased recruitment in musicians.

SICI tests the excitability of local GABA_Aergic inhibitory circuits in the motor cortex (Hanajima et al., 1998; Ilic et al., 2002). The amount of SICI that is evoked depends on the stimulus intensity of the conditioning pulse, describing a “U-shaped” curve (Kujirai et al., 1993; Ziemann et al., 1996; Ilic et al., 2002; Orth et al., 2003) of which the present experiments explored the initial increase in SICI toward its peak level. Recruitment of SICI represents a tradeoff between recruitment of inhibitory and excitatory elements as the conditioning intensity rises (Ilic et al., 2002). In our study, we expressed the intensity of the conditioning stimulus relative to aMT, which had the same absolute value in musicians and non-musicians. This yielded an SICIcurve that was steeper in musicians: lower conditioning pulse intensities evoked less SICI than in non-musicians, whereas higher intensities evoked more SICI. This difference would not have been noted if we had compared the groups at only median conditioning stimulus intensity, thus reinforcing the importance of measuring the SICI with different conditioning pulse intensities.

The difference between groups may reflect differences in the threshold and/or distribution of excitability in populations of cortical interneurons. If so, we favor the possibility that, like the IOcurves, increasing the conditioning stimulus intensity recruits more intracortical inhibitory connections because of increased synpatic density in the cortex. However, the finding that at lowest conditioning stimulus intensity the SICI in musicians is not as strong as it is in non-musicians shows that the threshold above which these intracortical inhibitory projections get activated is higher in musicians.

In summary, the combination of an increased slope for both the corticospinal (IOcurve) and intracortical (SICIcurve) input–output relationships suggests that regulation of cortical output is more sensitive, or has a higher gain, in musicians than in non-musicians: that is, small changes in TMS intensity, either as a single or conditioning pulse, have a proportionally stronger effect on cortical output in musicians. This may favor rapid recruitment of corticospinal output during recruitment of the motor cortex in volitional movement. The fact that SICI is recruited at higher thresholds, but with increased gain, might complement this quick recruitment with a powerful brake to prevent unwanted spread of activation, consistent with the fact that musicians show more focused motorcortical activation during movement (Jancke et al., 2000; Krings et al., 2000; Lotze et al., 2003; Meister et al., 2005)

Differences in the effect of PAS in musicians and non-musicians

To our knowledge, the PAS effect in humans has only been measured as amplitude change of MEPs evoked by a standard test pulse (Stefan et al., 2000, 2002, 2006; Wolters et al., 2003; Ziemann et al., 2004). However, the interpretation of any differences in PAS between groups of individuals depends on whether the slopes of the IOcurves are equal in the groups. For example, using the known effect of increasing TMS intensity on the MEP size as a model for the PAS effect, then as illustrated in Figure 6, an increase in the test pulse by 20% would increase MEP by 50% in groups with “standard” IOslope. However, if the IOslope were twice as steep, then the increase in MEP would be 100%.

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Figure 6.

Effect of the baseline slope of the IOcurve on the MEP effects of PAS25. The diagram shows hypothetical IOcurves of the two different groups of subjects (gray and black) that differ in slope. In this example, PAS25 causes an equivalent 20% increase in the effectiveness of a TMS stimulus. This leads to a 50% increase in MEP amplitude in the gray group but to a 100% increase in the black group. Thus, if the PAS25 effect was only measured by its effect on MEPs elicited at a single intensity of test stimulus (e.g., a preinterventional SI1mV), the result would suggest that PAS25 is more powerful in the black group than in the gray group. However, the difference may simply reflect a difference in initial IOcurves rather than a difference in synaptic plasticity. A more complete demonstration of increased synaptic plasticity involves showing that PAS increases the slope of the IOcurve (see text).

Because in musicians and non-musicians the slopes of the baseline IOcurve were different, it was important to test the effect of PAS over the entire range of input intensities. We found that in musicians, PAS increased the slope of the IOcurve significantly more and therefore that PAS had a greater effect than in non-musicians. If the steeper baseline IOcurve in musicians reflects an increased number of interneuronal connections caused by adaptation to long-term musical training, a proportionally stronger PAS effect suggests that these synapses also have a higher propensity to undergo changes in synaptic efficacy.

The neural circuits involved in PAS and short-term behavioral motor learning overlap. Previous short-term motor learning occludes or reverses the ability of PAS to induce LTP-like plasticity, whereas it may have no effect or even increase LTD-like plasticity (Ziemann et al., 2004; Stefan et al., 2006). The musicians tested here started their musical training at an average age of ∼6.5 years, and by the age of 20 years, Ericsson et al. (1993) estimated they will have had an average of 10,000 h of practice. If occlusion between periods of learning were to occur as in non-musicians, then one would have to conclude that many of these hours of practice failed to achieve any effective outcome. However, because the number of hours of practice is well known to relate to musical skill, this seems unlikely. It may be that increased susceptibility for synaptic potentiation/depotentiation in musicians represents an adaptation to these learning demands and prevents occlusion from occurring. This might enable them to adapt motor performance quickly while preserving a high level of proficiency (e.g., when playing on an unfamiliar instrument).

Nature versus nuture?

Our experiments do not directly assess whether increased synaptic plasticity is produced by musical training, as a complex motor task and also a multimodal-sensory and emotional experience, or whether it is a genetic trait of successful musicians. However, some parameters correlated significantly with the age at which playing commenced as well as with practice intensity over the last 5 years.

Similarly, structural and functional changes in the brain of musicians are linked to performance parameters (Elbert et al., 1995; Gaser and Schlaug, 2003; Bangert and Schlaug, 2006). Although this does not completely rule out any preselectional bias, it seems likely that some of the changes of excitability and plasticity are a consequence of long-term musical practice.

Beneficial versus maladaptive?

Increased LTP-/LTD-like effects of PAS have been described in focal hand dystonia patients, where it is proposed that they may contribute to development of symptoms (Quartarone et al., 2006; Weise et al., 2006) and has even been interpreted as endophenotypic trait for focal dystonia (Quartarone et al., 2006).

However, the present data show increased plasticity in highly skilled musicians, implying that it can be associated with either maladaptive or beneficial changes. If so, then one tentative conclusion must be that other factors determine which predominates. One factor that may influence the behavioral effectiveness of enhanced PAS is the corresponding gain of inhibitory mechanisms. The steep slope of the SICIcurve in musicians may allow more effective control of enhanced plasticity and benefit performance. This might be not the case in focal dystonia, because some studies have described reduced SICI at rest (Ridding et al., 1995; Gilio et al., 2003), although this finding is inconsistent (Stinear and Byblow, 2004a,b; Butefisch et al., 2005; Rosenkranz et al., 2005).

Alternatively, aberrant plasticity might not have an early and primary pathogenic role in focal dystonia but evolve secondarily, a consequence rather than a cause of the disease (Weise et al., 2006).