Role of primate magnocellular red nucleus neurons in controlling hand preshaping during reaching to grasp.

Reaching to grasp is of fundamental importance to primate motor behavior and requires coordinating hand preshaping with limb transport and grasping. We aimed to clarify the role of cerebellar output via the magnocellular red nucleus (RNm) to the control of reaching to grasp. Rubrospinal fibers originating from RNm constitute one pathway by which cerebellar output influences spinal circuitry directly. We recorded discharge from individual forelimb RNm neurons while monkeys performed a reach-to-grasp task and two tasks that were similar to the reach-to-grasp task in trajectory, amplitude, and direction but did not include a grasp. One of these, the device task, elicited reaches while holding a handle, and the other, the free-reach task, elicited reaches that did not require any specific hand use for task performance. The results demonstrate that coordinated whole-limb reaching movements are associated with large discharge modulations of RNm neurons predominantly when hand use is included. Therefore RNm neurons can at best only make a minor contribution to the control of reaching movements that lack hand use. We evaluated relations between the discharge of individual RNm neurons and electromyographic (EMG) activity of forelimb muscles during the reach-to-grasp task by comparing times of peak RNm discharge to times of peak EMG activity. The results are consistent with the view that RNm discharge may contribute to EMG activity of both distal and proximal muscles during reaching to grasp especially digit extensor and limb elevation muscles. Relations between the discharge of individual RNm neurons and movements of the metacarpi-phalangeal (MCP), wrist, elbow, and shoulder joints during individual trials of task performance were quantified by parametric correlation analyses on a subset of neurons studied during the reach-to-grasp and free-reach tasks. The results indicate that MCP extensions were consistently preceded by bursts of RNm discharge, and strong correlations were observed between parameters of discharge and the duration, velocity, and amplitude of corresponding MCP extensions. In contrast, relations between discharge and movements of proximal joints were poorly represented, and RNm discharge was not related to the speed of limb transport. Based on our data and those of others, we hypothesize that cerebellar output via RNm is specialized for controlling hand use and conclude that RNm may contribute to the control of hand preshaping during reaching to grasp by activating muscle synergies that produce the appropriate MCP extension at the appropriate phase of limb transport.

Construction of a reach-to-grasp.

Reaching out to grasp an object requires the coordinated action of many different areas of the brain. Each area probably makes a unique contribution to the control of limb movement. We have studied the discharge of interpositus, the output nucleus of intermediate cerebellum, and magnocellular red nucleus, which connects interpositus to the spinal cord. The neurons in these areas discharge at high rates only if a hand movement is included with the reach, and discharge pattern is similar regardless of reach direction. Therefore, interpositus and magnocellular red nucleus are involved primarily in grasp control during the reach-to-grasp; other areas must be controlling the reach. Several other areas of the brain, including the reticular formation, rostral mesencephalon, superior colliculus and motor cortex, are active during reaching. The output from these descending systems converges on interneurons at spinal level C1 and C2 which, in turn, project to level C6, where motor neurons innervating shoulder muscles are located. We hypothesize that reach control is achieved by the convergence of multiple descending pathways onto a complex spinal interneuronal system.

Reduction of rostral dorsal accessory olive responses during reaching.

1. Rostral dorsal accessory olive (rDAO) neurons are sensitive to light touch but have little or no discharge during active movement. We hypothesize that sensitivity of the rDAO is reduced during movement. To test this hypothesis, we evaluated sensitivity of rDAO neurons as cats reached out and retrieved a handle. On selected trials, mechanical or electrical perturbations to the forelimb were presented, and responses of rDAO neurons to the disturbances were recorded. 2. All rDAO units were highly sensitive to somatosensory stimuli during periods of stance. The cells responded to stimuli such as touch to hairs or light taps to the platform on which the cat was standing. 3. Discharges of rDAO neurons showed little or no synchronization to any aspect of the reaching task. rDAO neurons failed to fire to mechanical perturbations of the food handle during retrieval or hold phases of the task, even when their receptive fields included the surface of the paw in contact with the handle. 4. Electrical stimulation of the skin produced the greatest evoked response at all rDAO recording sites when the cats were at stance. Stimulation at any time during the reaching task, including periods of holding and licking, produced lower-amplitude evoked responses. The reduction in evoked response could be large and was restricted to the limb performing the task. 5. The data support the hypothesis that the cutaneous sensitivity of the rDAO is reduced during behavior. However, the inhibition does not appear to be tailored to specific times during the task or to neurons with specific receptive field locations on the actively moving limb. The reduction in sensitivity is as likely to be dependent on limb posture as on movement. We conclude that the rDAO discharge provides the cerebellum with information about vibration or contact during stance; it does not provide reliable information about undisturbed or disturbed movement. Climbing fiber input from rDAO might be useful in the preparation to make a movement, but it is probably not useful for correction of movement errors.

Activity of interpositus neurons during a visually guided reach.

Neurons in the cerebellar interpositus nucleus greatly increase their discharge rates when a monkey reaches out to grasp an object. However, when the monkey is required to track a target on a screen by moving a manipulandum, the increase in discharge rate is relatively small or nonexistent. Moving the hand directly to a target is a visuomotor task that may be fundamentally different from a remote tracking task. We hypothesize that the interpositus nucleus is specialized for direct visual guidance of the limb or, alternatively, interpositus is specialized for controlling hand movements required to grasp an object. A monkey was trained to hold a sensor and move it directly over a visual target to obtain water reward. Small drawers were mounted next to two of the targets; on some trials a drawer would open so that the monkey would reach out and retrieve a raisin that had been placed in it. Interpositus neurons discharged strongly during reach to grasp the raisin but not when the monkey was positioning the sensor over the target. For individual cells, discharge pattern and amplitude were largely independent of the size and direction of the reach to grasp, suggesting that interpositus does not control direction or amplitude of the reach. The results are consistent with the hypothesis that neurons in forelimb regions of interpositus participate in the control of hand movements used in grasping, but they are not consistent with the hypothesis that interpositus neurons participate in direct visual guidance of the limb.

The importance of hand use to discharge of interpositus neurones of the monkey.

1. Monkey interpositus neurones show large discharge modulations during reaching to grasp, however, the same neurones show little or no modulation during operation of devices that exercise individual forelimb joints. We tested the hypothesis that grasping during the reach-to-grasp is necessary for eliciting high discharge modulation. 2. Three monkeys (Macaca mulatta) moved an articulated lever between low and high target zones. While in the lower zone the monkey's hand was at its waist, in the upper zone its hand was in a position that required forelimb extension at right-angles to the body axis. Small drawers adjacent to the target zones contained raisins, and the drawers could be remotely opened. Thus, we could elicit two types of reaches having similar trajectories: one reach involved limb transport while holding the lever handle, and the other involved limb transport while forming the hand to grasp a raisin. 3. Eighty-one neurones from two monkeys, mostly from interpositus with some from adjacent regions of dentate, were tested during device use and reaching to grasp: 93% of the neurones discharged at high rates during at least one of the tasks. Of these, about half increased discharge rate solely during reaching to grasp; the other half showed some increase during device use but only discharged strongly during reaching to grasp. Overall, discharge modulations during the reach-to-grasp averaged twice as high as during the corresponding device movement (112 versus 56 impulses s-1). 4. Individual neurones consistently discharged with characteristic patterns during the reach-to-grasp with rates often exceeding 300 impulses s-1. Discharge during the reach-to-grasp was independent of reach trajectory: discharge patterns and amplitudes were similar when reaching from either the lower or upper target zone to the upper raisin drawer as when reaching from the upper target zone to the upper raisin drawer. Reach direction also made little difference: reaches from the upper target zone to the lower drawer typically elicited similar discharge modulation as those from the lower target zone to the upper drawer. 5. High discharge rates associated with grasping were independent of the item being grasped: typically, grasping the device handle elicited as high discharge rates as grasping a raisin. 6. The hypothesis was confirmed that grasping is critical for eliciting high discharge modulation in interpositus during reaching to grasp. Discharge pattern and modulation do not vary with reach direction or amplitude of the reach and, therefore, it is unlikely that intermediate cerebellum controls these features of the reach-to-grasp.(ABSTRACT TRUNCATED AT 400 WORDS)

Correlation of primate red nucleus discharge with muscle activity during free-form arm movements.

1. We recorded from 239 neurons located in the magnocellular division of the red nucleus of four alert macaque monkeys. At the same time, we recorded electromyographic (EMG) signals from as many as twenty electrodes chronically implanted on muscles of the shoulder, arm, forearm and hand. We recorded EMG signals for periods ranging from several months to a year. 2. The monkeys were trained to perform three free-form food retrieval tasks, each of which activated all of the recorded muscles and most of the neurons. The 'prehension' task required simply that the monkey grasp a piece of food from a fixed point in space. The 'barrier' task required the monkey to reach around a small barrier to obtain the food, and the 'Kluver' task required that food be removed from small holes. During the prehension task, we found approximately equal numbers of neurons that were strongly active while the hand was being moved toward the target (70% of units), and while the food was being grasped (60%). Relatively few units were active as the hand was returned to the mouth (15%). 3. Data files of 1-2 min duration were collected while the monkey performed a single behavioural task. Whenever possible, we recorded files for all three tasks from each neuron. For each file we calculated long time-span analog cross-correlations (+/- 1.28 s) between instantaneous neuronal firing rate and each of the full-wave rectified, low-pass filtered EMG signals. We used the peak correlation and the time of the peak as two summary measures of the functional relation between modulation of neuronal activity and EMG. 4. The magnitude of the strongest correlations was between 0.4 and 0.5 (normalized to a perfect correlation of +/- 1.0). Distal muscles were the most frequently correlated, and extensors were more frequently correlated than flexors. For all monkeys, the lags for well correlated muscles were distributed broadly about a uni-modal value near 0 ms. Eighty five per cent of the correlations larger than or equal to 0.25 had peaks between -150 and 200 ms. 5. The activity of each neuron was represented in a muscle co-ordinate system by an n-dimensional 'functional linkage vector', each element of which was the peak correlation with one of n muscles. The vector for any given neuron points in a particular direction in muscle space, depending on the similarity between the activity of the neuron and the activity of each muscle.(ABSTRACT TRUNCATED AT 400 WORDS)

Output organization of intermediate cerebellum of the monkey.

1. The goal of this study was to investigate the motor organization of monkey nucleus interpositus (NI) and neighboring regions of the lateral nucleus (NL) by correlating discharge of single neurons with active movements. Neurons were surveyed during free-form movements as well as during operation of six devices that required movement about specific forelimb joints. The paradigm allowed us to test the hypothesis that discharge of individual cells relates to movements about individual joints. 2. One hundred sixty-two isolated nuclear neurons from two monkeys were studied. Eighty-three percent showed large increases in discharge (an average of 3 times resting rate for forelimb neurons) during movement of one body part, either forelimb, hindlimb, mouth/face, or eyes. 3. Anterior interpositus contains neurons related to hindlimb movement in anterior regions and neurons related to forelimb movement in posterior regions. A mouth/face-related area exists in the dorsal-posterior regions and is continuous with a mouth/face area in the dorsal regions of NL. Posterior interpositus (NIP) showed no clear separation between forelimb and hindlimb neurons: forelimb neurons were encountered throughout the nucleus, and hindlimb neurons were encountered in the medial-anterior two thirds. A distinct eye movement area exists in lateral, posterior, and ventral regions of NIP. This area borders regions of NL that also contain eye movement-related neurons. 4. Forelimb interpositus neurons discharged strongly during reach and grasp; discharge rates were recorded for 41 neurons during a stereotyped reach and the average depth of modulation was 149 imp/s. Nineteen neurons that modulated during device tracking were also tested during reaching, and the depth of modulation was much greater during reaching. 5. Fifty-nine forelimb neurons were tested with device tracking. Twenty-seven (46%) produced no audible modulation, regardless of the joint being exercised. The remaining 32 neurons modulated during movement on at least one device (mean depth of modulation = 84 imp/s). Comparison of discharge during use of different devices revealed no strong evidence for device-specific discharge. 6. Discharge modulations during device tracking were phasic, preceded movement, and, for a small number of cells, showed consistent parametric relations to duration, amplitude, and velocity of movement. 7. Despite a clear somatotopy within NI and NL, there is no finer mapping based on active movements about individual joints within forelimb regions. Discharge modulation depends on movements involving the whole limb. Progress in understanding the function of intermediate cerebellum depends on determining the variables required to elicit consistent and high modulation of neural discharge.(ABSTRACT TRUNCATED AT 400 WORDS)

Movement-related inputs to intermediate cerebellum of the monkey.

1. The primary goal of this study was to characterize the information about single-joint forelimb movements supplied to intermediate cerebellar cortex by mossy fibers. Discharge of mossy fibers and Golgi cells was studied while monkeys operated six devices that required movements about specific joints. Additional control experiments in anesthetized cats and monkeys established criteria for identification of mossy fibers and Golgi cells. 2. The control experiments demonstrate that mossy fibers can be distinguished from Purkinje and Golgi cells by the waveshapes of their action potentials. Asynaptic activation from the inferior cerebellar peduncle, in combination with histological localization of recording sites in granular layer or subcortical white matter, verified that mossy fibers produce a variety of waveshapes that are characterized by brief initial phases and relatively small amplitudes. The same waveshapes were observed for the mossy fiber recordings from awake monkeys, and many identified mossy fibers had sensory properties similar to those found in the awake animals. From these combined criteria, we conclude that the recordings in the awake animals were from mossy fibers. Golgi cells, recorded exclusively in the granular layer of cerebellar cortex, were characterized by action potentials of longer duration and larger amplitude as compared with mossy fibers, and none were asynaptically activated from the inferior cerebellar peduncle. 3. Units were isolated while the monkeys made free-form and tracking movements. We studied movement-related discharge of 80 mossy fibers and 12 Golgi cells. Mossy fibers showed high modulations during use of at least one of the six manipulanda and had clear preferences for movement about a specific joint, although they often showed consistent but weaker firing during movement about a neighboring joint. Separation of movements by more than one joint produced a large reduction in discharge: shoulder units never fired well to movements of the finger, and finger units never fired well to movement of the shoulder. 4. The tracking task required maintenance of fixed limb positions (a static phase) as well as movements between these positions (a dynamic phase). Of 80 mossy fibers, 18% had purely tonic discharge patterns, 63% were phasic-tonic, and 20% were purely phasic. Discharge patterns were reciprocal (45%), bidirectional (42%), or unidirectional (13%). 5. Eighty percent of the mossy fibers exhibited tonic discharge that was significantly (P < 0.01) correlated with joint angle (r = 0.65 +/- 0.19, mean +/- SD), and about one third had phasic components that were significantly correlated with movement velocity.(ABSTRACT TRUNCATED AT 400 WORDS)

A horizontal stripe of displacement sensitivity in the human visual field.

Displacement thresholds of peripheral sites in monocular human vision were obtained. The average of 12 directional thresholds at different visual field sites was used to define isometric lines of average displacement threshold about central vision. Isometric lines extended further into the temporal visual fields along the horizontal meridian than along other meridians. At any single site in the peripheral visual field the thresholds were not the same in all directions; they were larger toward and away from central vision. These two psychophysical findings vary in a qualitatively similar manner across the retinal field, as does the average size and the collected orientation bias of dendritic fields of retinal ganglion cells.

Activity of primate magnocellular red nucleus related to hand and finger movements.

Single cells were recorded in the magnocellular red nucleus (RNm) of two cynomolgus monkeys using tungsten microelectrodes. The first monkey was trained to press finger switches and to operate a push-pull device. Comparison of responses while operating the two devices demonstrated a strong distal bias. The finger device elicited large modulations in discharge (greater than or equal to 50 impulses/s) in 75% of the sampled neurons. Most cells fired optimally during thumb switch operation, but also fired vigorously in association with other switch operations. The left motor cortex was removed from the second monkey 18 months prior to microelectrode recording. Cells in the cortically denervated RNm discharged vigorously in association with grouped finger movements that opened and closed the affected right hand. These results coupled with our previous findings suggest that the RNm is preferentially linked to distal limb muscles, and the primary role of the forelimb zone may be to control coordinated hand function including grouped movements of the fingers.

Response covariance in cat visual cortex.

The activity of pairs of neurons in the visual cortex (area 17) of anaesthetized, paralysed cats was recorded using two independently manipulated micropipettes. The number of spikes in the evoked responses of pairs of single neurons were analyzed for response covariance. Responses of the majority of cell pairs (83%) did not covary. Covariance was restricted to closeby neurons with distances of less than 150 microns and with identical orientation and ocular dominance preference.