State-based decoding of hand and finger kinematics using neuronal ensemble and LFP activity during dexterous reach-to-grasp movements.

The performance of brain-machine interfaces (BMIs) that continuously control upper limb neuroprostheses may benefit from distinguishing periods of posture and movement so as to prevent inappropriate movement of the prosthesis. Few studies, however, have investigated how decoding behavioral states and detecting the transitions between posture and movement could be used autonomously to trigger a kinematic decoder. We recorded simultaneous neuronal ensemble and local field potential (LFP) activity from microelectrode arrays in primary motor cortex (M1) and dorsal (PMd) and ventral (PMv) premotor areas of two male rhesus monkeys performing a center-out reach-and-grasp task, while upper limb kinematics were tracked with a motion capture system with markers on the dorsal aspect of the forearm, hand, and fingers. A state decoder was trained to distinguish four behavioral states (baseline, reaction, movement, hold), while a kinematic decoder was trained to continuously decode hand end point position and 18 joint angles of the wrist and fingers. LFP amplitude most accurately predicted transition into the reaction (62%) and movement (73%) states, while spikes most accurately decoded arm, hand, and finger kinematics during movement. Using an LFP-based state decoder to trigger a spike-based kinematic decoder [r = 0.72, root mean squared error (RMSE) = 0.15] significantly improved decoding of reach-to-grasp movements from baseline to final hold, compared with either a spike-based state decoder combined with a spike-based kinematic decoder (r = 0.70, RMSE = 0.17) or a spike-based kinematic decoder alone (r = 0.67, RMSE = 0.17). Combining LFP-based state decoding with spike-based kinematic decoding may be a valuable step toward the realization of BMI control of a multifingered neuroprosthesis performing dexterous manipulation.

Spatiotemporal variation of multiple neurophysiological signals in the primary motor cortex during dexterous reach-to-grasp movements.

To examine the spatiotemporal distribution of discriminable information about reach-to-grasp movements in the primary motor cortex upper extremity representation, we implanted four microelectrode arrays in the anterior bank and lip of the central sulcus in each of two monkeys. We used linear discriminant analysis to compare information, quantified as decoding accuracy, contained in various neurophysiological signals. For all signal types, decoding accuracy increased immediately after the movement cue, peaked around movement onset, and declined during the static hold. Spike recordings and local field potential (LFP) time domain amplitude provided more discriminable information than LFP frequency domain power. Discriminable information on movement type was distributed evenly across recording sites by LFP amplitude and 1-4 Hz power but unevenly by 100-170 Hz power and spike recordings. These latter two signal types provided higher decoding accuracies closer to the hemispheric surface than deep in the anterior bank and also provided accuracies that varied along the central sulcus. This variation in the distribution of movement-type information may be related to differences in the rostral versus caudal regions of the primary motor cortex and to its underlying somatotopic organization. The even distribution of information by LFP amplitude and 1-4 Hz power compared with the more localized distribution by 100-170 Hz power and spikes suggest that these different neurophysiological signals reflect different underlying processes that distribute information through the motor cortex during reach-to-grasp movements.

Measuring the motor output of the pontomedullary reticular formation in the monkey: do stimulus-triggered averaging and stimulus trains produce comparable results in the upper limbs?

The pontomedullary reticular formation (PMRF) of the monkey produces motor outputs to both upper limbs. EMG effects evoked from stimulus-triggered averaging (StimulusTA) were compared with effects from stimulus trains to determine whether both stimulation methods produced comparable results. Flexor and extensor muscles of scapulothoracic, shoulder, elbow, and wrist joints were studied bilaterally in two male M. fascicularis monkeys trained to perform a bilateral reaching task. The frequency of facilitation versus suppression responses evoked in the muscles was compared between methods. Stimulus trains were more efficient (94% of PMRF sites) in producing responses than StimulusTA (55%), and stimulus trains evoked responses from more muscles per site than from StimulusTA. Facilitation (72%) was more common from stimulus trains than StimulusTA (39%). In the overall results, a bilateral reciprocal activation pattern of ipsilateral flexor and contralateral extensor facilitation was evident for StimulusTA and stimulus trains. When the comparison was restricted to cases where both methods produced a response in a given muscle from the same site, agreement was very high, at 80%. For the remaining 20%, discrepancies were accounted for mainly by facilitation from stimulus trains when StimulusTA produced suppression, which was in agreement with the under-representation of suppression in the stimulus train data as a whole. To the extent that the stimulus train method may favor transmission through polysynaptic pathways, these results suggest that polysynaptic pathways from the PMRF more often produce facilitation in muscles that would typically demonstrate suppression with StimulusTA.

Bilateral spike-triggered average effects in arm and shoulder muscles from the monkey pontomedullary reticular formation.

Pontomedullary reticular formation (PMRF) neurons (309) were recorded simultaneously with electromyographic activity from arm and shoulder muscles in four monkeys performing arm-reaching tasks. Spike-triggered averages (SpikeTAs) were compiled for 292 neurons (3836 neuron-muscle pairs). Fourteen PMRF neurons located in a region ventral to the abducens nucleus produced 42 significant SpikeTA effects in arm and shoulder muscles. Of these 14 PMRF neurons, nine produced SpikeTA effects bilaterally. Overall, PMRF neurons facilitated ipsilateral flexors and contralateral extensors, while suppressing ipsilateral extensors and contralateral flexors. Spike- and stimulus-triggered averaging effects obtained from the same recording site were similar. These findings indicate that single PMRF neurons can directly influence movements of both upper limbs.

Comparing effects in spike-triggered averages of rectified EMG across different behaviors.

Effects in spike-triggered averages (SpikeTAs) of rectified electromyographic activity (EMG) compiled for the same neuron-muscle pair during various behaviors often appear different. Do these differences represent significant changes in the effect of the neuron on the muscle activity? Quantitative comparison of such differences has been limited by two methodological problems, which we address here. First, although the linear baseline trend of many SpikeTAs can be adjusted with ramp subtraction, the curvilinear baseline trend of other SpikeTAs can not. To address this problem, we estimated baseline trends using a form of moving average. Artificial triggers were created in 1 ms increments from 40 ms before to 40 ms after each spike used to compile the SpikeTA. These 81 triggers were used to compile another average of rectified EMG, which we call a single-spike increment-shifted average (single-spike ISA). Single-spike ISAs were averaged to produce an overall ISA, which captured slow trends in the baseline EMG while distributing any spike-locked features evenly throughout the 80 ms analysis window. The overall ISA then was subtracted from the initial SpikeTA, removing any slow baseline trends for more accurate measurement of SpikeTA effects. Second, the measured amplitude and temporal characteristics of SpikeTA effects produced by the same neuron-muscle pair may vary during different behaviors. But whether or not such variation is significant has been difficult to ascertain. We therefore applied a multiple fragment approach to permit statistical comparison of the measured features of SpikeTA effects for the same neuron-muscle pair during different behavioral epochs. Spike trains recorded in each task were divided into non-overlapping fragments of 100 spikes each, and a separate, ISA-corrected, SpikeTA was compiled for each fragment. Measurements made on these fragment SpikeTAs then were used as test statistics for comparison of peak percent increase, mean percent increase, peak width at half maximum, onset latency, and offset latency. The average of each test statistic measured from the fragment SpikeTAs was well correlated with the single measurement made on the overall SpikeTA. The multiple fragment approach provides a sensitive means of identifying significant changes in SpikeTA effects.

Rapid changes in throughput from single motor cortex neurons to muscle activity.

Motor cortex output is capable of considerable reorganization, which involves modulation of excitability within the cortex. Does such reorganization also involve changes beyond the cortex, at the level of throughput from single motor cortex neurons to muscle activity? We examined such throughput during a paradigm that provided incentive for enhancing functional connectivity from motor cortex neurons to muscles. Short-latency throughput from a recorded neuron to muscle activity not present during some behavioral epochs often appeared during others. Such changes in throughput could not always be attributed to a higher neuron firing rate, to more ongoing muscle activity, or to neuronal synchronization, indicating that reorganization of motor cortex output may involve rapid changes in functional connectivity from single motor cortex neurons to alpha-motoneuron pools.

Bilateral actions of the reticulospinal tract on arm and shoulder muscles in the monkey: stimulus triggered averaging.

The motor output of the pontomedullary reticular formation (PMRF) was investigated to determine the reticulospinal system's capacity for bilateral control of the upper limbs. Stimulus triggered electromyographic averages (StimulusTA) were constructed from muscles of both upper limbs while two awake monkeys (Macaca fascicularis) performed a reaching task using either arm. Extensor and flexor muscles were studied at the wrist, elbow, and shoulder; muscles acting on the scapula were also studied. Post-stimulus effects (PStEs) resulted from 435 (81%) of 535 sites tested. Of 1611 PStEs analyzed, 58% were post-stimulus suppression (PStS), and 42% were post-stimulus facilitation (PStF). Onset latency was earlier for PStF than PStS, duration was longer for PStS, and amplitude was larger for PStF. Ipsilateral and contralateral PStEs were equally prevalent; bilateral responses were typical. In the ipsilateral forelimb and shoulder, the prevalent pattern was flexor PStF and extensor PStS; the opposite pattern was prevalent contralaterally. Sites producing strong ipsilateral upper trapezius PStF were concentrated in a region caudal and ventral to abducens. The majority of muscles studied had no clear somatotopic organization. Overall, the results indicate the monkey PMRF has the capacity to support bilateral coordination of limb movements using reciprocal actions within a limb and between sides.

Motor outputs from the primate reticular formation to shoulder muscles as revealed by stimulus-triggered averaging.

The motor output of the medial pontomedullary reticular formation (mPMRF) was investigated using stimulus-triggered averaging (StimulusTA) of EMG responses from proximal arm and shoulder muscles in awake, behaving monkeys (M. fascicularis). Muscles studied on the side ipsilateral (i) to stimulation were biceps (iBic), triceps (iTri), anterior deltoid (iADlt), posterior deltoid (iPDlt), and latissimus dorsi (iLat). The upper and middle trapezius were studied on the ipsilateral and contralateral (c) side (iUTr, cUTr, iMTr, cMTr). Of 133 sites tested, 97 (73%) produced a poststimulus effect (PStE) in one or more muscles; on average, 38% of the sampled muscles responded per effective site. For responses that were observed in the arm and shoulder, poststimulus facilitation (PStF) was prevalent for the flexors, iBic (8 responses, 100% PStF) and iADlt (13 responses, 77% PStF), and poststimulus suppression (PStS) was prevalent for the extensors, iTri (22 responses, 96% PStS) and iLat (16 responses, 81% PStS). For trapezius muscles, PStS of upper trapezius (iUTr, 49 responses, 73% PStS) and PStF of middle trapezius (iMTr, 22 responses, 64% PStF) were prevalent ipsilaterally, and PStS of middle trapezius (cMTr, 6 responses, 67% PStS) and PStF of upper trapezius (cUTr, 46 responses, 83% PStS) were prevalent contralaterally. Onset latencies were significantly earlier for PStF (7.0 +/- 2.2 ms) than for PStS (8.6 +/- 2.0 ms). At several sites, extremely strong PStF was evoked in iUTr, even though PStS was most common for this muscle. The anatomical antagonists iBic/iTri were affected reciprocally when both responded. The bilateral muscle pair iUTr/cUTr demonstrated various combinations of effects, but cUTr PStF with iUTr PStS was prevalent. Overall, the results are consistent with data from the cat and show that outputs from the mPMRF can facilitate or suppress activity in muscles involved in reaching; responses that would contribute to flexion of the ipsilateral arm were prevalent.

Movement-related and preparatory activity in the reticulospinal system of the monkey.

Three monkeys ( M. fascicularis) performed a center-out, two-dimensional reaching task that included an instructed delay interval based on a color-coded visuospatial cue. Neural activity in the medial pontomedullary reticular formation (mPMRF) was recorded along with hand movement. Of 176 neurons with movement-related activity, 109 (62%) had movement-related but not preparatory activity (M cells), and 67 (38%) had both movement-related and preparatory activity (MP cells). EOG analyses indicated that the preparatory activity was not consistent with control of eye movements. There were slight changes in electromyograms (EMG) late in the instructed delay period before the Go cue, but these were small compared with the movement-related EMG activity. Preparatory activity, like the EMG activity, was also confined to the end of the instructed delay period for 14 MP cells, but the remaining 53 MP cells (30%) had preparatory activity that was not reflected in the EMG. Peri-movement neural activity varied with movement direction for 70% of the cells, but this variation rarely fit circular statistics commonly used for studies of directional tuning; directional tuning was even less common in the preparatory activity. These data show that neurons in the mPMRF are strongly modulated during small reaching movements, but this modulation was rarely correlated with the trajectory of the hand. In accord with findings in the literature from other regions of the CNS, evidence of activity related to motor preparation in these cells indicates that this function is distributed in the nervous system and is not a feature limited to the cerebral cortex.