Decoding M1 neurons during multiple finger movements.

We tested several techniques for decoding the activity of primary motor cortex (M1) neurons during movements of single fingers or pairs of fingers. We report that single finger movements can be decoded with >99% accuracy using as few as 30 neurons randomly selected from populations of task-related neurons recorded from the M1 hand representation. This number was reduced to 20 neurons or less when the neurons were not picked randomly but selected on the basis of their information content. We extended techniques for decoding single finger movements to the problem of decoding the simultaneous movement of two fingers. Movements of pairs of fingers were decoded with 90.9% accuracy from 100 neurons. The techniques we used to obtain these results can be applied, not only to movements of single fingers and pairs of fingers as reported here, but also to movements of arbitrary combinations of fingers. The remarkably small number of neurons needed to decode a relatively large repertoire of movements involving either one or two effectors is encouraging for the development of neural prosthetics that will control hand movements.

Constraints on somatotopic organization in the primary motor cortex.

Since the 1870s, the primary motor cortex (M1) has been known to have a somatotopic organization, with different regions of cortex participating in control of face, arm, and leg movements. Through the middle of the 20th century, it seemed possible that the principle of somatotopic organization extended to the detailed representation of different body parts within each of the three major representations. The arm region of M1, for example, was thought to contain a well-ordered, point-to-point representation of the movements or muscles of the thumb, index, middle, ring, and little fingers, the wrist, elbow, and shoulder, as conveyed by the iconic homunculus and simiusculus. In the last quarter of the 20th century, however, experimental evidence has accumulated indicating that within-limb somatotopy in M1 is not spatially discrete nor sequentially ordered. Rather, beneath gradual somatotopic gradients of representation, the representations of different smaller body parts or muscles each are distributed widely within the face, arm, or leg representation, such that the representations of any two smaller parts overlap extensively. Appreciation of this underlying organization will be essential to further understanding of the contribution to control of movement made by M1. Because no single experiment disproves a well-ordered within-limb somatotopic organization in M1, here I review the accumulated evidence, using a framework of six major features that constrain the somatotopic organization of M1: convergence of output, divergence of output, horizontal interconnections, distributed activation, effects of lesions, and ability to reorganize. Review of the classic experiments that led to development of the homunculus and simiusculus shows that these data too were consistent with distributed within-limb somatotopy. I conclude with speculations on what the constrained somatotopy of M1 might tell us about its contribution to control of movement.

Tension distribution to the five digits of the hand by neuromuscular compartments in the macaque flexor digitorum profundus.

The macaque flexor digitorum profundus (FDP) consists of a muscle belly with four neuromuscular regions and a complex insertion tendon that divides to serve all five digits of the hand. To determine the extent to which compartments within FDP act on single versus multiple digits, we stimulated the primary nerve branch innervating each neuromuscular region while recording the tension in all five distal insertion tendons. Stimulation of each primary nerve branch activated a distinct region of the muscle belly, so that each primary nerve branch and the muscle region innervated can be considered a neuromuscular compartment. Although each neuromuscular compartment provided a distinct distribution of tension across the five distal tendons, none acted on only one digital tendon. Most of the distribution of tension to multiple digits could be attributed to passive biomechanical interactions in the complex insertion tendon, although for the larger compartments a wider distribution resulted from the broad insertion of the muscle belly. Nerve ligations excluded contributions of spinal reflexes or distal axon reflexes to the distribution of tension to multiple digits. We conclude that the macaque FDP consists of four neuromuscular compartments, each of which provides a distinct distribution of tension to multiple digits.

Quantifying the independence of human finger movements: comparisons of digits, hands, and movement frequencies.

To determine whether other digits move when normal humans attempt to move just one digit, we asked 10 right-handed subjects to move one finger at a time while we recorded the motion of all five digits simultaneously with both a video motion analysis system and an instrumented glove. We quantified the independence of the digits to compare (1) the different digits, (2) the right versus the left hand, and (3) movements at a self-paced frequency versus externally paced movements at 3 Hz. We also quantified the degree to which motion occurred at the proximal, middle, or distal joint of each digit. Even when asked to move just one finger, normal human subjects produced motion in other digits. Movements of the thumb, index finger, and little finger typically were more highly individuated than were movements of the middle or ring fingers. Fingers of the dominant hand were not more independent than were those of the nondominant hand. Self-paced movements made at approximately 2 Hz were more highly individuated than were externally paced movements at 3 Hz. Angular motion tended to be greatest at the middle joint of each digit, with increased angular motion at the proximal and distal joints during 3 Hz movements. Simultaneous motion of noninstructed digits may result in part from passive mechanical connections between the digits, in part from the organization of multitendoned finger muscles, and in part from distributed neural control of the hand.

Inactivation of the ventral premotor cortex biases the laterality of motoric choices.

The visual, tactile, and motor properties of neurons in the ventral premotor cortex (PMv) suggest that the PMv plays an important role in the interaction of the face and upper extremities with visual objects, a function that might be disrupted by inactivation of the PMv. The behavior of three rhesus monkeys was, therefore, examined while the PMv was reversibly inactivated by intracortical injection of muscimol. Unilateral PMv inactivation produced no overt deficit in a monkey's ability to reach out and grasp a food morsel with either hand, nor did the monkey have difficulty in extracting a food morsel from a narrow well or in performing a visually cued individuated finger movement task. Unilateral PMv inactivation did bias the laterality of the monkeys' motoric choices, however. When two equivalent food morsels were presented simultaneously to the monkey's right and left, the likelihood that the monkey would make motoric responses contralateral to the inactivated PMv was reduced. After PMv muscimol injections, a monkey was less likely to initially turn its head contralaterally to inspect food morsels, less likely to reach for the food morsel with its contralateral hand, and less likely to take the morsel on its contralateral side. Catch trials in which a food morsel was present only on one side showed that the monkey was aware of the contralateral food morsels and was able to turn its head contralaterally and to use its contralateral arm and hand promptly and accurately. These observations suggest that, when equivalent visual objects for behavioral interaction are present bilaterally, the PMv plays a role in choosing the side to which motoric responses will be directed and the body part that will be deployed as the response effector.

Limited functional grouping of neurons in the motor cortex hand area during individuated finger movements: A cluster analysis.

Primary motor cortex (M1) hand area neurons show patterns of discharge across a set of individuated finger and wrist movements so diverse as to preclude classifying the neurons into functional groups on the basis of simple inspection. We therefore applied methods of cluster analysis to search M1 neuronal populations for groups of neurons with similar patterns of discharge across the set of movements. Populations from each of three monkeys showed a large group of neurons the discharge of which increased for many or all of the movements and a second small group the discharge of which decreased for many or all movements. Two to three other small groups of neurons that discharged more specifically for one or two movements also were found in each monkey, but these groups were less consistent than the groups with broad movement fields. The limited functional grouping of M1 hand area neurons suggests that M1 neurons act as a network of highly diverse elements in controlling individuated finger movements.

Somatotopic gradients in the distributed organization of the human primary motor cortex hand area: evidence from small infarcts.

Nine cases of relatively selective hand weakness produced by stroke were analyzed to examine the degree to which representations of different fingers are segregated in the human primary motor cortex (M1). In five cases, all the digits were involved uniformly; in four cases the radial versus ulnar digits of the hand were involved differentially. No patient showed discrete involvement of a single digit, nor did any patient have greatest weakness in the index, middle or ring finger. These findings provide little evidence that each digit is represented in a separate cortical territory, but rather suggest that broadly overlapping gradients - with the radial digits somewhat more heavily represented laterally and the ulnar digits somewhat more heavily represented medially - are superimposed on an underlying organization in which control of each finger is distributed widely throughout the human M1 hand area.

Neural coding of finger and wrist movements.

Previous work (Schieber and Hibbard, 1993) has shown that single motor cortical neurons do not discharge specifically for a particular flexion-extension finger movement but instead are active with movements of different fingers. In addition, neuronal populations active with movements of different fingers overlap extensively in their spatial locations in the motor cortex. These data suggested that control of any finger movement utilizes a distributed population of neurons. In this study we applied the neuronal population vector analysis (Georgopoulos et al., 1983) to these same data to determine (1) whether single cells are tuned in an abstract, three-dimensional (3D) instructed finger and wrist movement space with hand-like geometry and (2) whether the neuronal population encodes specific finger movements. We found that the activity of 132/176 (75%) motor cortical neurons related to finger movements was indeed tuned in this space. Moreover, the population vector computed in this space predicted well the instructed finger movement. Thus, although single neurons may be related to several disparate finger movements, and neurons related to different finger movements are intermingled throughout the hand area of the motor cortex, the neuronal population activity does specify particular finger movements.

Partial inactivation of the primary motor cortex hand area: effects on individuated finger movements.

After large lesions of the primary motor cortex (M1), voluntary movements of affected body parts are weak and slow. In addition, the relative independence of moving one body part without others is lost; attempts at individuated movements of a given body part are accompanied by excessive, unintended motion of contiguous body parts. The effects of partial inactivation of the M1 hand area are comparatively unknown, however. If the M1 hand area contains the somatotopically ordered finger representations implied by the classic homunculus or simiusculus, then partial inactivation might produce weakness, slowness, and loss of independence of one or two adjacent digits without affecting other digits. But if control of each finger movement is distributed in the M1 hand area as many studies suggest, then partial inactivation might produce dissociation of weakness, slowness, and relative independence of movement, and which fingers movements are impaired might be unrelated to the location of the inactivation along the central sulcus. To investigate the motoric deficits resulting from partial inactivation of the M1 hand area, we therefore made single intracortical injections of muscimol as trained monkeys performed visually cued, individuated flexion-extension movements of the fingers and wrist. We found little if any evidence that which finger movements were impaired after each injection was related to the injection location along the central sulcus. Unimpaired fingers could be flanked on both sides by impaired fingers, and the flexion movements of a given finger could be unaffected even though the extension movements were impaired, or vice versa. Partial inactivation also could produce dissociated weakness and slowness versus loss of independence in a given finger movement. These findings suggest that control of each individuated finger movement is distributed widely in the M1 hand area.

Multiple fragment statistical analysis of post-spike effects in spike-triggered averages of rectified EMG.

Spike-triggered averaging of EMG is a useful experimental technique for revealing functional connectivity from central neurons to motoneurons. Because EMG waveforms constitute time series, statistical analysis of spike-triggered averages is complicated. Empirical methods generally have been employed to detect the presence of post-spike effects (PSEs), since, as we argue in this report, it is not feasible to develop a rigorous yet sensitive statistical test that detects PSEs in a single grand average of rectified EMG. We have developed a method of multiple fragment statistical analysis (MFSA) of PSEs, based on dividing an experimental record into a large numbers of non-overlapping fragments. The calculations necessary to obtain accurate P-values using the multiple fragment method are simple and efficient, and therefore preliminary results can be obtained while recording. In this report, we present the rationale for MFSA, and give examples of its application. We found MFSA to have considerable utility in accurately testing the significance of small PSEs, and in detecting PSEs in shorter recordings. Statistical corrections that should be used when recording multiple channels simultaneously are discussed. MFSA could be implemented for statistical analysis of other waveforms averaged, such as evoked potentials, movement-related cortical potentials, or event-related desychronizations.

Tension distribution of single motor units in multitendoned muscles: comparison of a homologous digit muscle in cats and monkeys.

To determine whether single motor units (MUs) in multitendoned muscles distribute tension to multiple tendons or instead focus tension selectively on a single tendon, we examined the distribution of tension generated by single MUs in the cat extensor digitorum lateralis (EDLat), and in its macaque homolog, the extensor digiti quarti et quinti (ED45). General properties of MUs (maximal tetanic tension, axonal conduction velocity, and twitch rise time) were similar in these muscles to those reported for other limb muscles in cats and monkeys. Most cat EDLat MUs were found to exert tension rather selectively on one of the three tendons of the muscle. Fast fatigable MUs were slightly but significantly more selective than fast fatigue-resistant and slow MUs. In contrast, and contrary to expectation, the macaque ED45 contained a lower proportion of MUs that exerted tension selectively on one of the two tendons of the muscle, and a higher proportion of relatively nonselective MUs. These findings suggest that the cat EDLat may consist of three functional subdivisions, each acting preferentially on a different tendon, whereas the macaque ED45 is more likely to function as a single multitendoned muscle.

Primary motor cortex reorganization in a long-term monkey amputee.

The primary motor cortex (M1) was mapped with intracortical microstimulation (ICMS) in a 15 year-old macaque whose right upper extremity was amputated at the shoulder joint prior to 2 years of age. Movements of the right shoulder girdle and stump were evoked by ICMS throughout the left M1 upper extremity region. The size of the left M1 upper extremity region contralateral to the amputated arm was not appreciably different from the size of the right upper extremity region contralateral to the intact arm. Long stimulus trains and/or higher stimulus currents were needed to evoke detectable movements at significantly more loci in the left than in the right M1 upper extremity region. These observations would be consistent with unmasking of a high threshold representation of shoulder musculature that normally exists throughout the central core of the upper extremity region, where it underlies a lower threshold representation of the distal forelimb. Alternatively, invasion of the de-efferented distal forelimb core by surrounding shoulder representation may have occurred. Differences between the limited M1 reorganization observed in the present study and the more extensive reorganization of S1 observed in other studies may reflect fundamental differences between M1 and S1, and/or differences in the extent of de-efferentation versus deafferentation.

Postpartum cerebral vasospasm treated with hypervolemic therapy.

In a 23-year-old woman, gravida 1, para 1-0-0-1, headaches and seizures developed 1 week after an uncomplicated delivery. Cerebral angiography revealed severe, diffuse cerebral vasospasm. Her symptoms resolved with hyperosmolar, hypervolemic therapy and nimodipine. Magnetic resonance angiography on postpartum day 23 confirmed persistent, severe vasospasm, and repeat magnetic resonance angiography on postpartum day 33 demonstrated interval improvement. This report documents the time course of a case of postpartum vasospasm and its response to hypervolemic, hyperosmolar therapy and nimodipine.

Muscular production of individuated finger movements: the roles of extrinsic finger muscles.

Individuated finger movements--those in which one or more fingers are moved relatively independently of the movement or posture of other body parts--are produced in part by the action of the extrinsic finger muscles. Flexion/extension movements of the fingers are particularly dependent on these extrinsic muscles, most of which are multitendoned. How can contraction of multitendoned muscles move one digit without producing equivalent motion in other digits? This question was addressed by recording EMG activity from muscles of the forearm as trained rhesus monkeys performed flexion and extension individuated movements of each digit of the hand and of the wrist. Recordings showed that during movements of different fingers, a given muscle could act as an agonist, antagonist, or stabilizer of the digits it serves. Furthermore, during a given finger movement, several different muscles typically were active. A three-level connection model was developed that computed the relative motion of the digits during each finger movement based on the changes in EMG activity in the recorded muscles. The model showed that EMG activity changes in the extrinsic finger muscles, and the thenar muscles, could account for most of the motion of both the instructed digit and noninstructed digits. These results indicate that individuated finger movements were produced not by independent sets of muscles acting on each digit, but by the activity of several muscles, many of which act on more than one digit, combined such that the net effect was movement of one digit more than others.

Fiber type composition of morphologic regions in the macaque multitendoned finger muscles.

The extrinsic multitendoned finger muscles seem likely to contain distinct neuromuscular compartments that can act as independent functional subdivisions serving different fingers. Little evidence of such subdivisions is available, however. Regional specialization of histochemical fiber type composition has been described in a number of monotendoned muscles, and in some muscles different neuromuscular compartments have been shown to have different fiber type proportions. Therefore, we examined the fiber type composition of morphologically defined regions in the macaque multitendoned finger muscles. Although some trends were noted, none of the five multitendoned finger muscles showed significant regional differences in fiber type composition. Nor were differences found between muscles of the flexor group or between muscles of the extensor group. Comparing flexors and extensors revealed a slightly but significantly lower proportion of type I fibers in the flexors. We conclude that unlike certain monotendoned wrist muscles (such as FCU), the multitendoned muscles that flex and extend macaque fingers have minimal histochemical specialization.

How somatotopic is the motor cortex hand area?

The primary motor cortex (M1) is thought to control movements of different body parts from somatotopically organized cortical territories. Electrical stimulation suggests, however, that territories controlling different fingers overlap. Such overlap might be artifactual or else might indicate that activation of M1 to produce a finger movement occurs over a more widespread cortical area than usually assumed. These possibilities were distinguished in monkeys moving different fingers. Recordings showed that single M1 neurons were active with movements of different fingers. Neuronal populations active with movements of different fingers overlapped extensively. Control of any finger movement thus appears to utilize a population of neurons distributed throughout the M1 hand area rather than a somatotopically segregated population.

Electromyographic evidence of two functional subdivisions in the rhesus monkey's flexor digitorum profundus.

The main belly of the macaque's flexor digitorum profundus (FDP) is divided by a dissectible plane into radial and ulnar regions. The present report describes three findings which suggest that the radial and ulnar regions represent separate functional subdivisions of the FDP. First, electromyographic (EMG) recordings during individuated finger movements performed by rhesus monkeys demonstrated different patterns of activation in the radial versus the ulnar region of the FDP. Second, studies of single motor units discriminated from the parent EMG activity also suggested at least two differentially activated motoneuronal pools in the radial versus ulnar region. Third, the finger movements evoked by intramuscular stimulation, delivered through the recording electrodes, indicated that contraction of the radial versus ulnar region produces different patterns of tension on the finger tendons. Together these findings suggest that the radial and ulnar regions of the FDP provide differential tension on the finger tendons to individuate finger movements.

Morphologic regions of the multitendoned extrinsic finger muscles in the monkey forearm.

The macaque multitendoned extrinsic finger muscles--extensor digitorum communis, extensor digitorum quarti et quinti proprius, extensor digitorum secundi et tertii proprius, flexor digitorum superficialis and flexor digitorum profundus (FDP)--were studied to define their muscle fiber architecture, tendon structures, endplate bands and patterns of external and internal nerve branching. Muscle fiber architecture was then used to define regions in each muscle that might represent functional subdivisions. Only in the FDP were these regions innervated by primary nerve branches characteristic of neuromuscular compartments.