Marco Davare

Dissociating the role of ventral and dorsal premotor cortex in precision grasping.

Small-object manipulation is essential in numerous human activities, although its neural bases are still essentially unknown. Recent functional imaging studies have shown that precision grasping activates a large bilateral frontoparietal network, including ventral (PMv) and dorsal (PMd) premotor areas. To dissociate the role of PMv and PMd in the control of hand and finger movements, we produced, by means of transcranial magnetic stimulation (TMS), transient virtual lesions of these two areas in both hemispheres, in healthy subjects performing a grip–lift task with their right, dominant hand. We found that a virtual lesion of PMv specifically impaired the grasping component of these movements: a lesion of either the left or right PMv altered the correct positioning of fingers on the object, a prerequisite for an efficient grasping, whereas lesioning the left, contralateral PMv disturbed the sequential recruitment of intrinsic hand muscles, all other movement parameters being unaffected by PMv lesions. Conversely, we found that a virtual lesion of the left PMd impaired the proper coupling between the grasping and lifting phases, as evidenced by the TMS-induced delay in the recruitment of proximal muscles responsible for the lifting phase; lesioning the right PMd failed to affect dominant hand movements. Finally, an analysis of the time course of these effects allowed us to demonstrate the sequential involvement of PMv and PMd in movement preparation. These results provide the first compelling evidence for a neuronal dissociation between the different phases of precision grasping in human premotor cortex.

Selective modulation of interactions between ventral premotor cortex and primary motor cortex during precision grasping in humans

In humans, the rostral part of the ventral premotor cortex (PMv), the homologue of F5 in monkeys, is known to be critically involved in shaping the hand to grasp objects. How does information about hand posture, that is processed in PMv, give rise to appropriate motor commands for transmission to spinal circuits controlling the hand? Whereas PMv is crucial for skilled visuomotor control of the hand, PMv sends relatively few direct corticospinal projections to spinal segments innervating hand muscles and the most likely route for PMv to contribute to the control of hand shape is through cortico‐cortical connections with primary motor cortex (M1). If this is the case, we predicted that PMv–M1 interactions should be modulated specifically during precision grasping in humans. To address this issue, we investigated PMv–M1 connections by means of paired‐pulse transcranial magnetic stimulation (TMS) and compared whether they were differentially modulated at rest, and during precision versus power grip. To do so, TMS was applied over M1 either in isolation or after a conditioning stimulus delivered, at different delays, over the ipsilateral PMv. For the parameters of TMS tested, we found that, at rest, PMv exerted a net inhibitory influence on M1 whereas, during power grip, this inhibition disappeared and was converted into a net facilitation during precision grip. The finding that, in humans, PMv–M1 interactions are selectively modulated during specific types of grasp provides further evidence that these connections play an important role in control of the hand.

Causal Connectivity between the Human Anterior Intraparietal Area and Premotor Cortex during Grasp.

Summary The cortical visuomotor grasping circuit, comprising the anterior intraparietal area (AIP), ventral premotor (PMv), and primary motor cortex (M1) allows transformation of an objects physical properties into a suitable motor command for grasp [1–9]. However, little is known about how AIP contributes to the processing of grasp-related information conveyed through the cortical grasping circuit. We addressed this by studying the consequences of AIP “virtual lesions” on physiological interactions between PMv and M1 at rest or during preparation to grasp objects with either a precision grip or a whole-hand grasp. We used a conditioning-test transcranial magnetic stimulation (TMS) paradigm to test how PMv-M1 interactions [10–12] were modified by disrupting AIP function with theta-burst TMS (cTBS) [13]. At rest, AIP virtual lesions did not modify PMv-M1 interactions. In contrast, the usual muscle-specific PMv-M1 interactions that appeared during grasp preparation were significantly reduced following AIP cTBS without directly modifying corticospinal excitability. Behaviorally, disruption of AIP was also associated with a relative loss of the grasp-specific pattern of digit muscle activity. These findings suggest that grasp-related and muscle-specific PMv-M1 interactions are driven by information about object properties provided by AIP.

Ventral premotor to primary motor cortical interactions during object-driven grasp in humans

Interactions between the ventral premotor (PMv) and the primary motor cortex (M1) are crucial for transforming an objects geometrical properties, such as its size and shape, into a motor command suitable for grasp of the object. Recently, we showed that PMv interacts with M1 in a specific fashion, depending on the hand posture. However, the functional connectivity between PMv and M1 during the preparation of an actual grasp is still unknown. To address this issue, PMv–M1 interactions were tested while subjects were preparing to grasp different visible objects requiring either a precision grip or a whole hand grasp. A conditioning–test transcranial magnetic stimulation (TMS) paradigm was used: a test stimulus was applied over M1 either in isolation or after a conditioning stimulus delivered, at different delays, over the ipsilateral PMv. Motor evoked potentials (MEPs) were recorded in the first dorsal interosseus and abductor digiti minimi muscles, which show highly differentiated activity according to grasp. While subjects prepared to grasp, delivering a conditioning PMv pulse 6 or 8 msec before a test pulse over M1 strikingly facilitated MEPs in the specific muscles that were used in the upcoming grasp. This degree of facilitation correlated with the amount of muscle activity used later in the trial to grasp the objects. The present results demonstrate that, during grasp preparation, the PMv–M1 interactions are muscle-specific. PMv appears to process the object geometrical properties relevant for the upcoming grasp, and transmits this information to M1, which in turn generates a motor command appropriate for the grasp. We also reveal that the grasp-specific facilitation resulting from PMv–M1 interactions is differently related to the upcoming grasp muscle activity than is that from paired-pulse stimulation over M1, suggesting that these two TMS paradigms assess the excitability of cortico-cortical pathways devoted to the control of grasp at two different levels.

Temporal Dissociation between Hand Shaping and Grip Force Scaling in the Anterior Intraparietal Area

In humans, both clinical and functional imaging studies have evidenced the critical role played by the posterior parietal cortex, and particularly by the anterior intraparietal area (AIP), in skilled hand movements. However, the exact contribution of AIP to precision grasping remains debated. Here we used transcranial magnetic stimulation (TMS) to induce virtual lesions of the left and/or right AIP in subjects performing a grip-lift task with either hand. We found that, during movement preparation, a virtual lesion of AIP had distinct consequences on precision grasping of either hand depending on its time of occurrence: TMS applied 270–220 ms before the fingers contacted the manipulandum altered specifically the hand shaping, whereas lesions induced 170–120 ms before contact time only affected the grip force scaling. The lateralization of these two processes in AIP is also strikingly different: whereas a bilateral lesion of AIP was necessary to impair hand shaping, only a unilateral lesion of the left AIP altered the grip force scaling in either hand. The present study shows that, during movement preparation, AIP is responsible for processing two distinct, temporally dissociated, precision grasping parameters, regardless of the hand in use. This indicates that the contribution of AIP to hand movements is “effector- independent,” a finding that may explain the invariance of grasping movements performed with either hand.

Interactions between areas of the cortical grasping network.

Highlights ► The anterior intraparietal area (AIP) is crucial for the processing of grasp-related object properties. ► AIP receives visual information about graspable objects from both the dorsal and ventral stream. ► Reciprocal interactions between the ventral premotor (PMv) and primary motor cortex (M1) allow the motor command to be grasp-specific. ► AIP plays a causal role in influencing interactions between PMv and M1.

Precision grasping in humans: from motor control to cognition

In the past decade, functional neuroimaging has proved extremely useful in mapping the human motor circuits involved in skilled hand movements. However, one major drawback of this approach is the impossibility to determine the exact contribution of each individual cortical area to precision grasping. Because transcranial magnetic stimulation (TMS) makes it possible to induce a transient virtual lesion of discrete brain regions in healthy subjects, it has been extensively used to provide direct insight into the causal role of a given area in human motor behaviour. Recent TMS studies have allowed us to determine the specific contribution, as well as the timing and the hemispheric lateralisation, of distinct parietal and frontal areas to the control of both the kinematics and dynamics of precision grasping. Moreover, recent researches have shown that the same cortical network may contribute to language and number processing, supporting the existence of tight interactions between processes involved in cognition and actions. The aim of this paper is to offer a concise overview of recent studies that have investigated the neural correlates of precision grasping and the possible contribution of the motor system to higher cognitive functions such as language and number processing.

Information about the Weight of Grasped Objects from Vision and Internal Models Interacts within the Primary Motor Cortex

When grasping and lifting different objects, visual cues and previously acquired knowledge enable us to prepare the upcoming grasp by scaling the fingertip forces according to the actual weight of the object. However, when no visual information is available, the weight of the object has to be predicted based on information learned from previous grasps. Here, we investigated how changes in corticospinal excitability (CSE) and grip force scaling depend on the presence of visual cues and the weight of previously lifted objects. CSE was assessed by delivering transcranial magnetic stimulation (TMS) at different times before grasp of the object. In conditions in which visual information was not provided, the size of motor evoked potentials (MEP) was larger when the object lifted was preceded by a heavy relative to a light object. Interestingly, the previous lift also affected MEP amplitude when visual cues about object weight were available but only in the period immediately after object presentation (50 ms); this effect had already declined for TMS delivered 150 ms after presentation. In a second experiment, we demonstrated that these CSE changes are used by the motor system to scale grip force. This suggests that the corticospinal system stores a “sensorimotor memory” of the grasp of different objects and relies on this memory when no visual cues are present. Moreover, visual information about weight interacts with this stored representation and allows the corticospinal system to switch rapidly to a different model of predictive grasp control.

Loss of sensory attenuation in patients with functional (psychogenic) movement disorders

Functional movement disorders require attention to manifest yet patients report the abnormal movement to be out of their control. In this study we explore the phenomenon of sensory attenuation, a measure of the sense of agency for movement, in this group of patients by using a force matching task. Fourteen patients and 14 healthy control subjects were presented with forces varying from 1 to 3 N on the index finger of their left hand. Participants were required to match these forces; either by pressing directly on their own finger or by operating a robot that pressed on their finger. As expected, we found that healthy control subjects consistently overestimated the force required when pressing directly on their own finger than when operating a robot. However, patients did not, indicating a significant loss of sensory attenuation in this group of patients. These data are important because they demonstrate that a fundamental component of normal voluntary movement is impaired in patients with functional movement disorders. The loss of sensory attenuation has been correlated with the loss of sense of agency, and may help to explain why patients report that they do not experience the abnormal movement as voluntary.

Reorganisation of the Right Occipito-Parietal Stream for Auditory Spatial Processing in Early Blind Humans. A Transcranial Magnetic Stimulation Study

It is well known that, following an early visual deprivation, the neural network involved in processing auditory spatial information undergoes a profound reorganization. In particular, several studies have demonstrated an extensive activation of occipital brain areas, usually regarded as essentially “visual”, when early blind subjects (EB) performed a task that requires spatial processing of sounds. However, little is known about the possible consequences of the activation of occipitals area on the function of the large cortical network known, in sighted subjects, to be involved in the processing of auditory spatial information. To address this issue, we used event-related transcranial magnetic stimulation (TMS) to induce virtual lesions of either the right intra-parietal sulcus (rIPS) or the right dorsal extrastriate occipital cortex (rOC) at different delays in EB subjects performing a sound lateralization task. Surprisingly, TMS applied over rIPS, a region critically involved in the spatial processing of sound in sighted subjects, had no influence on the task performance in EB. In contrast, TMS applied over rOC 50xa0ms after sound onset, disrupted the spatial processing of sounds originating from the contralateral hemifield. The present study shed new lights on the reorganisation of the cortical network dedicated to the spatial processing of sounds in EB by showing an early contribution of rOC and a lesser involvement of rIPS.