Functional Organization of Human Prefrontal Cortical Areas in Simple and Complex Voluntary Movement

The aim is to study the functional organization of the human motor system. Voluntary movement is a major example of human purposeful, goal-directed behaviour. Recent functional imaging and electrophysiological studies on human voluntary movement suggest that there may be a network of cortical and subcortical areas associated with voluntary action. Activity of the different components of this network is considered to be modulated by different aspects of voluntary movement such as choice, preparatory demands, and attention to action. Systematic variation of these aspects should result in modulated activity of particular network components and reveal their functional relevance in relation to the modified aspect. As a follow up to our previous electrophysiological studies, we want to use functional magnetic resonance imaging (fMRI), electroencephalography (EEG) and magnetencephalography (MEG) to investigate the functional topography and the time course of activity of cortical areas involved into different types of voluntary movement. We will study the role of the dorsolateral prefrontal cortex (DLPFC), supplementary motor area (SMA), precuneus, primary motor cortex (MI), and the lateral premotor cortex (LPC). The questions are as follows: 1. Are unilateral limb movements that require a high degree of directed attention towards the side of movement associated with enhanced activation of the contralateral DLPFC? Is any lateralization of activity in the DLPFC symmetrical for both left and right side movements, or is there a salient role of the right DLPFC in exploratory- motor attention? 2. Are there differences in the topography or magnitude of SMA activity if different types of voluntary movement are compared? Is the anterior part of the SMA particularly engaged in motor inhibition? 3. Is the contralateral MI more activated if a movement makes higher demands on motor preparation? To what extent are other lateral motor areas, such as the LPC, involved into lateralized motor preparation? 4. Do ipsilateral MI or LPC play a role in motor inhibition determined by the nature of the preceding movement? What characteristics of a preceding movement do influence such inhibitory activity? A procedural approach will be to combine the spatial resolution of fMRI and the temporal resolution of electrophysiology to investigate the anatomical substrates, time course and mechanisms of voluntary human movement. The salient spatial resolution of fMRI (in the range of millimeters) will enable us to determine the precise topographic extent of regions that are activated. The excellent temporal resolution of EEG and MEG (in the range of milliseconds) will enable us to study altering levels of activation in these regions. We also plan to examine neurological patients with frontal cortical lesions to further determine how the spatio-temporal connectivity of the human motor system is altered if components of this system fail to function. Such a multidisciplinary approach and the study of both normal and abnormal function are essential to understand the mechanisms of normal and abnormal volitional control of movement. The findings will be important in clarifying the anatomical substrates and mechanisms of voluntary movement in normals and its breakdown in patients with various cortical lesions.

The aim of the project was to study the functional organization of human voluntary movement in healthy subjects and neurological patients with stroke. Human movements are usually not made in isolation. Several elementary movements can be combined to produce a complex action. In this process, the system of motor functions can break down at any stage in the behavioural sequence that makes up voluntary action. This is often the case in neurological patients who are able to perform simple repetitive movements but have difficulties to change from one type of movement to a different type - even if the simple elementary movements which constitute the intended sequence can be made with little effort. In this context, the study of both normal and abnormal function is essential to understand the mechanisms of normal and abnormal volitional control of movement. We used a variety of electrophysiological techniques (EEG, MEG), functional imaging, and neuropsychological tests to examine voluntary movements in both neurological patients with lesions of relevant parts of the motor system and healthy controls. By comparison of simple repetitive to complex movements with a varying degree of difficulty, we were able to examine those processes needed to fulfil specific tasks (e.g., initiation, selection out of a set of possible movements, attention to sensory inputs required for feedback control). Up to now we could establish the following findings: (1) A change of the side of movement is associated with a widespread increase of activation over motor areas contralateral to the currently prepared movement, irrespective of whether these movements are self-initiated or paced by an external stimulus. (2) A widespread increase of pre- movement activation over the left hemisphere after a change of the effector (finger) confirms hypotheses about left hemispheric predominance in the spatio-temporal organisation of voluntary movement. (3) The right hemisphere may predominate motor activation or attentional demands directed towards movement execution or somatosensory inputs even in very simple repetitive motor tasks. Many elderly people are neurological patients and depend on others for their most basic activities. These patients are impaired in their ability to act independently even if intellectual capacities are spared in the decline of their abilities. Better knowledge about the function of the neuronal networks subserving normal and abnormal voluntary action will enable us to compensate these impairments at a later stage.