**4. A clinical implication**

T = 4.90

T = 6.27

116 Neuroimaging for Clinicians – Combining Research and Practice

Importantly, the monkeys knew in advance which trial type was going to be presented by means of a colour coding of the rectangle. The discharge frequency of M1 neurones for a given force level appeared to vary with the *total* force the monkeys had to produce during the trial, i.e., the discharge frequency was lower for the second force level when the monkeys also had to produce the third force level during the trial than when the second force level was the maximum force level of the trial. This clearly shows that the coding of force in M1 neuronal population depends on the context of the task, in this case the total force range. Moreover, this adaptation to context is achieved in real time (here, trial per trial), suggesting an important flexibility at the level of functioning of the neuronal network

Fig. 2. Result of the t-contrast Ref\_Force– Ref\_Mov. Height threshold of significance: corrected P<0.01 (T = 4.90). Voxel extent threshold: 20 voxels. The voxels, all seen in the glass brain representation, are superimposed on the spm single subject canonical brain on

All of the above-mentioned results concerning the neuronal activity of M1 clearly show that M1 is not a simple transmission relay between the non-primary motor areas (that anticipate, prepare) and the spinal cord, but rather a real crossroad playing an important role in cognitive motor integration. Indeed, M1 is implicated in tasks without any motor output. Moreover, the functioning of M1 depends on the cognitive context in which a motor output

It is important to remember that M1 is not the only origin of the corticospinal tract. In monkeys, the topographical distribution of these projections has been studied by isolating the corticospinal neurons projecting on the spinal cord between the cervical and thoracic level (C5-T1), using an injection of a retrograde marker in the region of the motoneurons in the spinal cord (Dum and Strick, 1991; Maier et al., 2002). Is has been shown that half of the

the anatomical slices passing through Talairach coordinates [-2 -13 47].

will be or is produced: Its functioning is modulated in real time.

**3. Secondary cortical areas** 

within M1.

An important implication of this conception of cerebral functioning is that the whole cortex should be considered when studying, for instance, the consequences of cortical plasticity following central or peripheral lesions. In this last section of the chapter, we will use as example the amputation of the hand and/or forearm.

As already mentioned in section 2.2, after amputation of the hand or forearm, the territories of the representation of the lost body part in S1 seem rapidly occupied by afferent information from adjacent body parts (e.g., Florence & Kaas, 1995; Gagné et al., 2011; Vandermeeren et al., 2003). The same reorganization is known to hold for M1, i.e., neurons originally sending motor commands to hand muscles pre-amputation send them to stump muscles post-amputation. Indeed, TMS on this reorganized part of M1 evoked MEPs in the stump muscles (Mercier et al., 2006).

This reorganization, however, is very complex and appears to be incomplete. Indeed, after amputation, patients very often report a vivid perception of presence of their lost limb. This "phantom limb" can be the object of mechanical, thermal and even painful sensations (Kooijman et al., 2000). Even more surprisingly is that the phantom limb can often be "moved" at will (Kooijman et al., 2000; Reilly et al., 2006). Although these voluntary phantom movements are slow and more effortful than movements of the intact limb, the patients feel these movements to be "executed" corresponding to their will (e.g., Reilly et al., 2006), and they are able to imitate with their intact arm the movements they execute with

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their phantom limb. Some results in the literature suggest that the sending of motor commands is necessary in order to "perform" voluntary phantom limb movements. These motor commands, as they cannot arrive on the muscles of the lost limb, arrive on the muscles of the stump instead. Indeed, during voluntary phantom limb movements, the EMG pattern found on the stump muscles correspond to neither the EMG patterns for real movements of the stump, nor to the EMG patterns found on the corresponding muscles of the intact arm during imitation of the phantom limb movements (Reilly et al., 2006; Gagné et al., 2009). This strongly suggests that specific motor commands are sent from M1 when "executing" a specific phantom limb movement. Moreover, when the hand area of M1 in an amputated patient is stimulated with TMS, a phantom limb movement is evoked (Mercier et al., 2006). So, there exists a reorganization of the primary somatosensory and motor areas, leading to new relations between body parts and neuronal populations, where motor commands to the missing limb can still be sent.

There seems to exist a relation between the degree of cortical reorganization and the degree of phantom limb pain. Lotze and colleagues (2001), in a fMRI study, reported that patients without phantom limb pain showed significantly less reorganization of the primary sensorimotor areas than patients with phantom limb pain. This raises the question whether cortical reorganization should be avoided, and, if so, how.

Currently, it is not known what exactly underlies the appearance of phantom limb sensations such as movements or pain, but it seems likely that it is, at least partly, related to the complex cortical reorganization following amputation. The search for answers to questions such as "What causes phantom limb pain and how can we avoid it?", "Why are phantom limb movements slow and effortful?", and "Can we use phantom limb movements to increase control of prostheses?", must take into account that the primary cortical areas are an integral part of a cortical network underlying cognitive (motor) functioning, and the secondary motor areas can have an executive function. With respect to this latter point, a possible reorganization of the secondary motor areas following amputation has not yet been investigated.
