In addition to the modulation of TMS evoked responses by voluntary activation, there are effects due to the nature of the task performed. Work in this Thesis involved applying TMS whilst subjects performed a precision grip task. Subjects squeezed together two levers using index finger and thumb to bring them into a narrow target zone. MEP amplitudes during the hold phase of this precision grip task were measured in different hand and forearm muscles.
Task modulation of MEP sizes evoked by TMS has been confirmed in studies comparing MEPs evoked whilst IDI is activated to abduct the index finger, to responses evoked whilst subjects perform various grip tasks (Datta et al. 1989; Flament et al. 1993). Datta et al. (1989) found larger MEP amplitudes elicited in IDI muscle, when a simple index finger abduction task was carried out. This was in comparison to MEPs elicited in the same muscle whilst subjects performed a power grip, suggesting that a higher level of cortical activity was involved during the isolated finger contraction (Datta et al. 1989). In complete contrast Flament et al. (1993) found larger MEPs in IDI when subjects performed various precision grip tasks, in comparison to simple adduction o f IDI.
1.16.1 Pitfalls in measuring TMS evoked responses
Conflicting data of this kind may have been due to the pitfalls involved in experiments of this kind. As accounted for in the study by Flament et al. (1993), it is important that a constant level of background EMG activity is maintained for each of the tasks used in the experiment. The effect o f low levels of voluntary activity (in comparison to the relaxed state) in facilitating TMS responses is dramatic, and it saturates very quickly at levels of around 10 % maximum voluntary contraction (Hess et al. 1987; Turton and Lemon 1999). 45
In addition using too high levels of voluntary contraction in experiments (e.g. 30 % maximum voluntary contraction) can result in the inability to measure any changes in MEP size between tasks (Kasai and Yahagi 1999).
Similarly, it is important to use the correct intensity of TMS and to understand whether MEP amplitudes reflect spinal and/or cortical excitability. However, this is made difficult by the fact that the input/output relationship between TMS intensity and MEP amplitude is complex. For IDI muscle, the relationship has been shown to be sigmoidal, and therefore highly nonlinear (Devanne et al. 1997). This is despite the fact that the discharge probability of single motoneurones, as measured by the firing probability of single motor units, increases linearly with TMS intensity. One factor contributing to the sigmoidal nature of the input/output curve is that as the intensity increases, bigger motor units (with larger potentials) are recruited (Henneman 1957). However it is argued that an additional important factor is the number and amplitude o f multiple volleys elicited by TMS, and their nature depends on the level o f motor cortex excitability (Devanne et al.
1997).
It has been shown that whilst suprathreshold TMS intensities evoke more reproducible and measurable MEP responses in active muscle than lower intensities, there is the risk that subtle changes in motor cortex excitability go unobserved (Lemon et al. 1995; Kasai and Yahagi 1999). It was shown that high responses to suprathreshold TMS were roughly proportional to background EMG levels, implying that cortical excitability had little additional modulatory effect (Lemon et al. 1995).
1.16.2 Corticospinal drive during power and precision grip tasks
A recent study that controlled for all these different factors still found consistent differences in MEP sizes between power and precision grip tasks (Hasegawa et al. 2001b). With the same levels o f background activity, MEPs were larger in IDI muscle in the precision grip task than the power grip (cf Flament et al. 1993). A possible 46
explanation for this difference is that in the precision grip, intrinsic hand muscles such as IDI are important (Long et al. 1970) whereas in the power grip, the extrinsic hand muscles provide the major grip force (Schieber 1995).
When MEP size evoked in IDI was correlated with background EMG activity, it was found that there were different regression coefficients for each task, with a steeper relationship for the precision grip than the power grip (Hasegawa et al. 2001b). This suggested that the nature of the task modulated the influence o f background EMG levels on TMS responses. Authors were able to conclude that the differences in MEP size reflected differences in the central motor commands required for precision versus power grip tasks.
In an additional study, focussing on the precision grip, the importance o f grip aperture was addressed (Hasegawa et al. 2001a). Subjects gripped levers that were either 20 mm or 80 mm apart. For each grip aperture MEP amplitude evoked in IDI was correlated with background EMG levels, and different correlation coefficients were obtained depending on grip aperture. For the narrow grip aperture, the relationship between MEP amplitude and background EMG level was dramatically modulated by TMS intensity, whereas this was not the case for the wider aperture. This suggests that when comparing MEP sizes in different grip tasks, a similar grip aperture should be used.
With regards to dynamic phases of muscle contraction (such as the ramp phase of the task used in this Thesis), MEP amplitudes evoked in IDI were higher during a step or fast contraction, than during a slower smoother contraction (Kasai and Yahagi 1999). Authors argued that whereas the step contraction was a preprogrammed ballistic movement in which corticospinal excitability could not be altered, modulation possibly by afferent input (see below) did occur during the slower ramp. When higher force levels were used, despite the fact that background activity between tasks changed, there were no differences 47
in MEP sizes. This was explained by correlation coefficients, showing that MEP amplitudes in ramp conditions were dependent on levels of background activity, but MEPs evoked in step contractions were not (Kasai and Yahagi 1999).
1.16.3 Corticospinal drive during different phases o f the precision grip task
Other studies have measured cortico-motoneuronal activity during different phases of the same precision grip task. Clear modulation of the firing rate o f corticospinal neurones projecting to intrinsic hand muscles was observed (Muir and Lemon 1983; Bennett and Lemon 1996). When monkeys performed the ramp phase o f a precision grip task there was a higher rate o f cortico-motoneuronal cell firing, than during the hold phases of the task (Bennett and Lemon 1996). Such task modulation was similar to that in active hand muscles, so may have reflected the typical ‘muscle-like’ properties of most motor cortex neurones; in addition it was argued that since independent movements of the digits were particularly important during the ramp or movement phase of the task, this required greater fractionation o f hand muscle activity. This is known to be associated with enhanced activity amongst cortico-motoneuronal cells. Authors suggested that the production o f relatively independent digit movements, unlike those involved in co contraction, required a distributed command signal to different motoneurone pools (Bennett and Lemon 1996).
In a study involving human subjects reaching out, gripping and lifting an object, it was shown that the first contact made with the object was accompanied by important changes in corticospinal activity (Lemon et al. 1995). MEP responses in the intrinsic hand muscles, IDI and AbPB were strongest during the initial touch o f the object. It has been shown that during grip, intrinsic hand muscles come into play and in particular, cutaneous inputs o f the digits are essential for muscle coordination during the grasp (Johansson and Westling 1987). Different responses were observed in forearm muscles EDS and EDC, in 48
which highest MEP amplitudes were observed during the reach phase of the task, reflecting the importance of forearm muscles in palm orientation and finger position during this phase (Lemon et al. 1995). MEP amplitudes were lowest in the static phase of the task when the object was held in the air. Authors argued that whilst important processes involved in parametizing physical properties of the object were performed in the early phases o f the task (hence higher cortical excitability), the hold phase was a more stable and automatic task requiring less cortical input (Lemon et al. 1995).