Thomas Brochier

The effects of muscimol inactivation of small regions of motor and somatosensory cortex on independent finger movements and force control in the precision grip

Abstract This study investigated the effects of inactivating small regions of the primary somatosensory (SI) and motor (MI) cortex on the control of finger forces in a precision grip. A monkey was trained to grasp and lift a computer-controlled object between the thumb and index finger and to hold it stationary within a narrow position window for 2 s. The grip force applied perpendicular to the object surface, the lifting or load force applied tangentially in the vertical direction, and the vertical displacement were sampled at 100 Hz. Also, the ability of the monkey to extract small pieces of food from narrow wells of a Klüver board was analyzed from video-tape. Preliminary single-unit recordings and microstimulation studies were used to map the extent of the thumb and index-finger representation within SI and MI. Two local injections of 1 µl each (5 µg/µl) of the GABAA-agonist muscimol were used to inactivate the thumb and index region of either the pre- or post-central gyrus. The precision grip was differently affected by muscimol injection into either SI or MI. MI injections produced a deficit in the monkey’s ability to perform independent finger movements and a general weakness in the finger muscles. Whole-hand grasping movements were inappropriately performed in an attempt to grasp either the instrumented object or morsels of food. Although the effect seemed strongest on intrinsic hand muscles, a clear deficit in digit extension was also noted. As a result, the monkey was unable to lift and maintain the object within the position window for the required 2 s, and, over time, the grip force decreased progressively until the animal stopped working. Following SI injections, the most obvious effect was a loss of finger coordination. In grasping, the placement of the fingers on the object was often abnormal and the monkey seemed unable to control the application of prehensile and lifting forces. However, the detailed analysis of forces revealed that a substantial increase in the grip force occurred well before any deficit in the coordination of finger movements was noted. This observation suggests that cutaneous feedback to SI is essential for the fine control of grip forces.

Selectivity for grasp in local field potential and single neuron activity recorded simultaneously from M1 and F5 in the awake macaque monkey

The selectivity for object-specific grasp in local field potentials (LFPs) was investigated in two awake macaque monkeys trained to observe, reach out, grasp and hold one of six objects presented in a pseudorandom order. Simultaneous, multiple electrode recordings were made from the hand representations of primary motor cortex (M1) and ventral premotor cortex (area F5). LFP activity was well developed during the observation and hold periods of the task, especially in the beta-frequency range (15–30 Hz). Selectivity of LFP activity for upcoming grasp was rare in the observation period, but common during stable grasp. The majority of M1 (90 of 92) and F5 (81of 97) sites showed selectivity for at least one frequency, which was maximal in the beta range but also present at higher frequencies (30–50 Hz). When the LFP power associated with grasp of a specific object was large in the beta-frequency range, it was usually of low power in the higher 30–50 Hz range, and vice-versa. Simple hook grips involving flexion of one or more fingers were associated with large beta power, whereas more complex grips involving the thumb (e.g., precision grip) were associated with small beta power. At many M1 sites, there was a highly significant inverse relationship between the tuning of spikes (including those of identified pyramidal tract neurons) and beta-range LFP for different grasps, whereas a positive correlation was found at higher frequencies (30–50 Hz). High levels of beta LFP and low pyramidal cell spike rate may reflect a common mechanism used to control motor set during different types of grasp.

Modulation of primary motor cortex outputs from ventral premotor cortex during visually guided grasp in the macaque monkey

Area F5, in the ventral premotor cortex of the macaque monkey, plays a critical role in determining the hand shape appropriate for grasp of a visible object. F5 neurones show increased firing for particular types of grasp, and inactivation of F5 produces deficits in visually guided grasp. But how is F5 activity transformed into the appropriate pattern of hand muscle activity for efficient grasp? Here we investigate the pathways that may be involved by testing the effect of single stimuli delivered through microwires chronically implanted in area F5 and in primary motor cortex (M1) of two macaque monkeys. The EMG responses from M1 test (T) stimulation were recorded from 4–11 contralateral hand, digit and arm muscles during reach‐to‐grasp of visually presented objects. Conditioning (C) stimulation of F5, at intensities subthreshold for motor effects, caused strong modulation (over twofold) of M1 test (T) responses. The pattern of facilitation was specific. First, facilitation of the T response was particularly evident at short C–T intervals of −1 to 1 ms. Second, this facilitation was only present in some muscles and during reach‐to‐grasp of a subset of objects; it did not appear to be simply related to the level of EMG activity in the muscles at the moment of cortical stimulation or indeed to the upcoming contribution of that muscle during grasp. At later C–T intervals (1–6 ms), F5 stimulation caused significant suppression of the test M1 response. The results are in keeping with the concept that during visually guided grasp, F5 modulates corticospinal outputs from M1 in a muscle‐ and grasp‐specific manner.

Pronounced Reduction of Digit Motor Responses Evoked from Macaque Ventral Premotor Cortex after Reversible Inactivation of the Primary Motor Cortex Hand Area

In common with other secondary motor areas, the macaque ventral premotor cortex (PMv) gives rise to corticospinal projections; it also makes numerous reciprocal corticocortical connections with the primary motor cortex (M1). Repetitive intracortical microstimulation (rICMS) of the PMv gives rise to movements of the hand and digits. To investigate whether these motor effects are dependent on the corticocortical interactions with M1, the effect of reversible inactivation of the M1 hand area was tested in three macaque monkeys with chronically implanted intracortical electrodes in the hand representations of M1 and PMv (rostral division, area F5). Monkeys were lightly sedated. Test EMG responses to rICMS were recorded from intrinsic hand muscles before and after microinjection of the GABA agonist muscimol in the M1 hand area. This not only greatly reduced EMG responses evoked from M1, but also reduced or abolished responses from F5, over a similar time course (20–50 min). Muscimol in M1 reduced the level of background EMG activity in the contralateral hand, which was paretic for several hours after injection. However, because EMG responses to direct activation of the corticospinal tract were significantly less affected than the responses to F5 stimulation, it is unlikely that reduced motoneuronal excitability explained the loss of the evoked responses from F5. Finally, muscimol injections in M1 greatly reduced the corticospinal volleys evoked by rICMS in F5. The results suggest that the motor effects evoked from F5 depend, at least in part, on corticocortical interactions with M1, leading to activation of M1 corticospinal outputs to hand muscles.

Modulations of EEG Beta Power during Planning and Execution of Grasping Movements

Although beta oscillations (≈ 13–35 Hz) are often considered as a sensorimotor rhythm, their functional role remains debated. In particular, the modulations of beta power during preparation and execution of complex movements in different contexts were barely investigated. Here, we analysed the beta oscillations recorded with electroencephalography (EEG) in a precued grasping task in which we manipulated two critical parameters: the grip type (precision vs. side grip) and the force (high vs. low force) required to pull an object along a horizontal axis. A cue was presented 3 s before a GO signal and provided full, partial or no information about the two movement parameters. We measured beta power over the centro-parietal areas during movement preparation and execution as well as during object hold. We explored the modulations of power in relation to the amount and type of prior information provided by the cue. We also investigated how beta power was affected by the grip and force parameters. We observed an increase in beta power around the cue onset followed by a decrease during movement preparation and execution. These modulations were followed by a transient power increase during object hold. This pattern of modulations did not differ between the 4 movement types (2 grips ×2 forces). However, the amount and type of prior information provided by the cue had a significant effect on the beta power during the preparatory delay. We discuss how these results fit with current hypotheses on the functional role of beta oscillations.

Excitability of human motor cortex inputs prior to grasp

Transcranial magnetic stimulation (TMS) was used to investigate corticospinal excitability during the preparation period preceding visually guided self‐paced grasping. Previously we have shown that while subjects prepare to grasp a visible object, paired‐pulse TMS at a specific interval facilitates motor‐evoked potentials (MEPs) in hand muscles in a manner that varies with the role of the muscle in shaping the hand for the upcoming grasp. This anticipatory modulation may reflect transmission of inputs to human primary motor cortex (M1) for visuomotor guidance of hand shape. Conversely, single‐pulse TMS is known to suppress MEPs during movement preparation. Here we investigate the time course of single‐ and paired‐pulse MEP modulation. TMS was delivered over M1, at different time intervals after visual presentation of either a handle or a disc to healthy subjects. Participants were instructed to view the object, and later to grasp it when given a cue. During grasp there was a specific pattern of hand muscle activity according to the object grasped. MEPs were evoked in these muscles by TMS delivered prior to grasp. Paired‐pulse MEPs were facilitated, whilst single‐pulse MEPs were suppressed. The pattern of facilitation matched the object‐specific pattern of muscle activity for TMS pulses delivered 150 ms or more after object presentation. However, this effect was not present when TMS was delivered immediately after object presentation, or if the delivery of TMS was given separately from the cue to perform the grasp action. These results suggest that object‐related information for preparation of appropriate hand shapes reaches M1 only immediately preceding execution of the grasp.

Cortical control of grasp in non-human primates

The skilled use of the hand for grasping and manipulation of objects is a fundamental feature of the primate motor system. Grasping movements involve transforming the visual information about an object into a motor command appropriate for the coordinated activation of hand and finger muscles. The cerebral cortex and its descending projections to the spinal cord are known to play a crucial role for the control of grasp. Recent studies in non-human primates have provided some striking new insights into the respective contribution of the parietal and frontal motor cortical areas to the control of grasp. Also, new approaches allowed investigating the coupling of grasp-related activity in different cortical areas for the control of the descending motor command.

Mapping the spatio-temporal structure of motor cortical LFP and spiking activities during reach-to-grasp movements

Grasping an object involves shaping the hand and fingers in relation to the object’s physical properties. Following object contact, it also requires a fine adjustment of grasp forces for secure manipulation. Earlier studies suggest that the control of hand shaping and grasp force involve partially segregated motor cortical networks. However, it is still unclear how information originating from these networks is processed and integrated. We addressed this issue by analyzing massively parallel signals from population measures (local field potentials, LFPs) and single neuron spiking activities recorded simultaneously during a delayed reach-to-grasp task, by using a 100-electrode array chronically implanted in monkey motor cortex. Motor cortical LFPs exhibit a large multi-component movement-related potential (MRP) around movement onset. Here, we show that the peak amplitude of each MRP component and its latency with respect to movement onset vary along the cortical surface covered by the array. Using a comparative mapping approach, we suggest that the spatio-temporal structure of the MRP reflects the complex physical properties of the reach-to-grasp movement. In addition, we explored how the spatio-temporal structure of the MRP relates to two other measures of neuronal activity: the temporal profile of single neuron spiking activity at each electrode site and the somatosensory receptive field properties of single neuron activities. We observe that the spatial representations of LFP and spiking activities overlap extensively and relate to the spatial distribution of proximal and distal representations of the upper limb. Altogether, these data show that, in motor cortex, a precise spatio-temporal pattern of activation is involved for the control of reach-to-grasp movements and provide some new insight about the functional organization of motor cortex during reaching and object manipulation.

Ventral Premotor-Motor Cortex Interactions in the Macaque Monkey during Grasp: Response of Single Neurons to Intracortical Microstimulation

Recent stimulation studies in monkeys and humans have shown strong interactions between ventral premotor cortex (area F5) and the hand area of primary motor cortex (M1). These short-latency interactions usually involve facilitation from F5 of M1 outputs to hand muscles, although suppression has also been reported. This study, performed in three awake macaque monkeys, sought evidence that these interactions could be mediated by short-latency excitatory and inhibitory responses of single M1 neurons active during grasping tasks. We recorded responses of these M1 neurons to single low-threshold (≤40 μA) intracortical microstimuli delivered to F5 sites at which grasp-related neurons were recorded. In 29 sessions, we tested 232 M1 neurons with stimuli delivered to between one and four sites in F5. Of the 415 responses recorded, 142 (34%) showed significant effects. The most common type of response was pure excitation (53% of responses), with short latency (1.8–3.0 ms) and brief duration (∼1 ms); purely inhibitory responses had slightly longer latencies (2–5 ms) and were of small amplitude and longer duration (5–7 ms). They accounted for 13% of responses, whereas mixed excitation then inhibition was seen in 34%. Remarkably, a rather similar set of findings applied to 280 responses of 138 F5 neurons to M1 stimulation; 109 (34%) responses showed significant effects. Thus, with low-intensity stimuli, the dominant interaction between these two cortical areas is one of short-latency, brief excitation, most likely mediated by reciprocal F5–M1 connections. Some neurons were tested with stimuli at both 20 and 40 μA; inhibition tended to dominate at the higher intensity.

Does the Processing of Sensory and Reward-Prediction Errors Involve Common Neural Resources? Evidence from a Frontocentral Negative Potential Modulated by Movement Execution Errors

In humans, electrophysiological correlates of error processing have been extensively investigated in relation to decision-making theories. In particular, error-related ERPs have been most often studied using response selection tasks. In these tasks, involving very simple motor responses (e.g., button press), errors concern inappropriate action-selection only. However, EEG activity in relation to inaccurate movement-execution in more complex motor tasks has been much less examined. In the present study, we recorded EEG while volunteers performed reaching movements in a force-field created by a robotic device. Hand-path deviations were induced by interspersing catch trials in which the force condition was unpredictably altered. Our goal was twofold. First, we wanted to determine whether a frontocentral ERP was elicited by sensory-prediction errors, whose amplitude reflected the size of kinematic errors. Then, we explored whether common neural processes could be involved in the generation of this ERP and the feedback-related negativity (FRN), often assumed to reflect reward-prediction errors. We identified a frontocentral negativity whose amplitude was modulated by the size of the hand-path deviations induced by the unpredictable mechanical perturbations. This kinematic error-related ERP presented great similarities in terms of time course, topography, and potential source-location with the FRN recorded in the same experiment. These findings suggest that the processing of sensory-prediction errors and the processing of reward-prediction errors could involve a shared neural network.