Time-Specific Contribution of the Supplementary Motor Area to Intermanual Transfer of Procedural Knowledge

Discussion

Here, we investigated the timing of the contribution of the SMA to successful intermanual transfer of procedural knowledge. We found that a transient virtual lesion over the SMA applied between individual key presses (premovement group) during learning with the right hand substantially interfered with intermanual transfer to the left hand, without disrupting learning. Neither SMA disruption during key press movements (movement group) nor sham stimulation under our experimental design had any effect on intermanual transfer or learning.

Several studies have demonstrated that a motor skill learned with one hand can transfer to the opposite hand (Parlow and Kinsbourne, 1989; Howard and Howard, 1997; Grafton et al., 2002; Japikse et al., 2003; Wang and Sainburg, 2003; Obayashi, 2004; Perez et al., 2007a,b). Cortical areas such as the primary motor cortex, which has relatively sparse interhemispheric connections for the distal musculature (Rouiller et al., 1994), contribute to nonspecific performance improvements in the transfer hand, particularly optimizing the timing of visuomotor processing (Grafton et al., 2002; Perez et al., 2007a), whereas other motor regions, such as the SMA, with strong interhemispheric projections (Liu et al., 2002), play a critical role in successful intermanual transfer of motor sequence skills, both in healthy individuals (Perez et al., 2007b) and in patients with lesions of the corpus callosum (de Guise et al., 1999). Here, we investigated when the SMA makes the contribution to intermanual transfer of procedural sequence knowledge in healthy subjects.

We found that disruption of SMA activity before but not during each individual finger key press or during sham substantially diminished intermanual transfer of knowledge. Previous work showed that activity in SMA neurons encodes the order of components of a motor sequence (Tanji and Shima, 1994). Consistently, in humans, disruption of the SMA before execution affects the ability to choose the proper upcoming movements in a motor sequence (Gerloff et al., 1997). Although these studies provided crucial information on the role of the SMA in the preparation of individual movements in a sequence, the timing of SMA contribution to intermanual transfer of knowledge from a learning to a resting hand has not been investigated. Our findings show that this contribution occurs between key presses, during the time when memory of the previous movement (and current hand posture) could contribute to encoding a movement pair. As a sequence is learned, this interval is increasingly involved in preparing and selecting the next movement in the learned sequence. In agreement, studies in monkeys have shown that activity in SMA neurons encodes the order of components of a motor sequence, especially during the period between movements (Tanji and Shima, 1994; Shima and Tanji, 1998, 2000). One possible account for our result, therefore, is that rTMS applied during this preparatory phase interfered with sensorimotor processes, reflected in the preparatory neural activity, that encode the sequence in a form suitable for transfer of knowledge to the opposite hemisphere (Krakauer et al., 2006; Seidler and Noll, 2008).

There are different mechanisms by which the SMA may contribute to intermanual transfer of learning. It is possible that a memory representation stored in the SMA during learning can be accessed by either hand at the time of transfer as proposed by the “access model” of intermanual transfer by Taylor and Heilman (1980). Also, a separate memory can be stored during learning in the contralateral hemisphere, which can be accessed on-line by the transfer hand as proposed by the “cross-activation model” by Parlow and Kinsbourne (1989). Our results of a selective interference of transfer by SMA stimulation support the view that the SMA is involved in encoding a memory trace that can be accessed by both hands, and that this concept can be distinguished from an on-line transfer process that guides the opposite hand. It is important to note that the behavioral effects of rTMS over SMA on intermanual transfer could represent the consequence of focal disruption of activity in the SMA (Gerloff et al., 1997), or its interconnected areas (Lee et al., 2003), and/or disruption of other areas of the brain intending to compensate for the transient SMA deficit.

However, rTMS applied to the SMA during the movement did not disrupt intermanual transfer, suggesting that SMA movement-related activity, which encodes information on movement kinematics and dynamics (Seitz and Roland, 1992; Padoa-Schioppa et al., 2002) and contributes to monitor motor performance (Lee and Quessy, 2003), may play a less critical role in intermanual transfer.

Intermanual transfer of a sequence of events in the SRTT (Nissen and Bullemer, 1987) requires first that participants learn to respond as rapidly as possible to the location of the stimuli. The subjects in our study learned at a slower pace than in previous investigations (Perez et al., 2007a,b), consistent with previous reports we found that the SRTT task performed at slower presentation rates elicits less prominent sequence learning (Willingham et al., 1997; Soetens et al., 2004) than when the task is performed at faster presentation rates (Willingham et al., 1997; Soetens et al., 2004). Importantly, learning of the SRTT under our experimental conditions was comparable across groups, consistent with previous results (Pascual-Leone et al., 1996), although we note that higher rTMS stimulus intensities can disrupt motor learning (Gerloff et al., 1997). In our study, subjects also showed improvements in the control sequence when performing with the left (transfer) hand. Although this improvement was not significantly different from that for the random block, it appears to have resulted mainly from rapid learning of the control sequence during transfer testing. This fast learning may be related to the previous experience with the control sequence that established a baseline level of performance (Fig. 1, left part), some high frequency pairs that are common to the training and control sequence (such as 4-2 and 1-3) (see Materials and Methods), or a possible effect of rTMS during movement on later performance (Avanzino et al., 2008).

Our finding of differential effects of SMA disruption on transfer as opposed to learning is consistent with the view that intermanual transfer and motor learning, although related processes, engage partially different mechanisms (Seidler, 2007; Seidler and Noll, 2008). These findings may also be explained by the model for sequence learning proposed by Hikosaka et al. (1999). These authors suggested that sequence knowledge is acquired by parallel networks, one involved in a goal-based sequence representation (an extrinsic coordinate frame) and another involved in a movement-based sequence representation (an intrinsic coordinate frame). Because the SMA appears to be a critical node in the network guiding the movement-based representation, one possibility is that compensation by the goal-based system may account for the failure of SMA stimulation to affect sequence learning (as opposed to transfer). Furthermore, our observation that rTMS disrupted the intermanual transfer of both the mirror sequence (a movement-based representation) and the original sequence (a goal-based representation), to the same extent, supports the view that the role of the SMA in transfer involves sequence representations that draw on both intrinsic and extrinsic coordinate frames. If, as suggested by the model of Hikosaka et al. (1999), SMA primarily contributes to movement-based representations, then its disruption during learning appears to affect the formation of both goal- and movement-based representations that are available to the controllers of both hands.