Sensory-motor integration in human motor cortex at the pre-motoneurone level: beyond the age of simple MEP measurements.

Abstract

Somatosensory information is important for motor control. Sensory input is integrated with motor commands at several levels of the motor system: spinal, subcortical and cortical. Some of this integration occurs directly at the motor output cells, i.e. the α-motoneurone in the spinal cord and the corticospinal neurone in the motor cortex. This direct linkage between sensory input and motor output has been studied extensively in humans with classical spinal and transcortical reflex testing. However, recent research has indicated that the situation can be much more complex than simple reflex loops. In the human spinal cord, sensory integration takes place also at a pre-motoneurone level. For example, part of the cortical command for arm movements is modulated by sensory feedback in cervical propriospinal pre-motoneurones interposed in the corticospinal pathways to upper limb α-motoneurones (for review see Pierrot-Deseilligny, 1996). Does similar pre-motoneurone integration of sensory information also occur in the motor cortex? It was not possible to study this until recently. Single-pulse transcranial magnetic stimulation (TMS) allows measurement of corticospinal excitability through the size of the motor-evoked potential (MEP). Numerous TMS studies showed modulation of MEP size when conditioned by sensory afferents (e.g. Bertolasi et al. 1998) or when tested during various motor tasks (e.g. Lemon et al. 1995). However, MEP size is a somewhat ‘dirty’ measurement that contains information from all stages along the motor pathways. Only the recent development of paired-pulse TMS protocols enabled neurophysiologists to study specifically interneurones in human motor cortex at the pre-motoneurone level. One particularly important paired-pulse TMS protocol employs a first stimulus sub-threshold for the MEP followed at short interstimulus intervals in the range of 1-20 ms by a supra-threshold second stimulus (for review see Ziemann, 1999). At intervals of 1-5 ms, the conditioning shock results in MEP inhibition, while MEP facilitation occurs at intervals of 7-20 ms. It was shown that this modulation of MEP size takes place at the cortical level and that separate populations of inhibitory and excitatory interneurones are responsible for this intracortical inhibition (ICI) and facilitation (ICF). In this issue of The Journal of Physiology, Aimonetti & Nielsen used ICI and ICF testing to measure sensory-motor integration in human motor cortex at these interneurones (Aimonetti & Nielsen, 2001). The main finding was that ICI decreased and ICF increased in the wrist muscles when conditioned by electrical stimulation of the antagonist nerve (for instance, stimulation of the median nerve when testing ICI and ICF in the wrist extensors). Aimonetti & Nielsen (2001) speculated that this pattern of reciprocal disinhibition/facilitation may serve to co-contract the wrist extensors and flexors, for example when stabilisation of the wrist is needed during manipulative finger movements. It is important to note that the modulation of ICI and ICF occurred in the absence of changes in single-pulse MEP size. Therefore, this form of sensory-motor integration in human motor cortex at the pre-motoneurone level would have gone unnoticed with conventional simple MEP measurements. As it appears that sensory-motor integration in human motor cortex is complex, the present work of Aimonetti & Nielsen (2001) could set the stage for a more comprehensive exploration of this interesting field in the future since many questions remain unresolved. What type of sensory afferents are involved and how specific are the present findings with respect to the target muscles? The present work provided evidence for a rather indirect, probably multisynaptic, low-threshold, fast-conducting and non-cutaneous afferent system. However, one previous study showed a similar disinhibition by cutaneous nerve stimulation when testing the first dorsal interosseous muscle (Ridding & Rothwell, 1999). Therefore, the present findings of Aimonetti & Nielsen (2001) may be specific for wrist muscles and not valid for other muscles. What is the significance of the present findings with respect to motor task? In the present study, subjects had to exert a slight isometric contraction selectively of either the wrist extensors or flexors. What happens if subjects are instructed to co-contract the wrist muscles or to perform manipulative finger movements that require co-contraction of the wrist muscles for best-level performance? If the findings in the study of Aimonetti & Nielsen (2001) bear functional relevance, one would expect to see an enhancement of reciprocal disinhibition/facilitation during such co-contraction tasks. Despite the many open questions, testing the modulation of ICI and ICF (in the absence of changes in MEP size) may allow us to look deeper into human motor cortex physiology than was possible with single-pulse MEP measurements, and the study of Aimonetti & Nielsen (2001) is an important and encouraging step in this direction.