Biomedical subjects

M A Maier

Publications and source records attributed to M A Maier.

31 records · Page 2Linked to original sources

PubMed1998

X-ray crystallographic analysis of the hydration of A- and B-form DNA at atomic resolution.

We have determined single crystal structures of an A-DNA decamer and a B-DNA dodecamer at 0.83 and 0.95 A, respectively. The resolution of the former is the highest reported thus far for any right-handed nucleic acid duplex and the quality of the diffraction data allowed determination of the structure with direct methods. The structures reveal unprecedented details of DNA fine structure and hydration; in particular, we have reexamined the overall hydration of A- and B-form DNA, the distribution of water around phosphate groups, and features of the water structure that may underlie the B to A transition.

Crystallography, X-Ray↗

PubMed1998

The importance of the cortico-motoneuronal system for control of grasp.

Our recent work has revealed new evidence of the importance of direct cortico-motoneuronal (CM) connections for voluntary control of the hand. Most of these connections are derived from corticospinal neurons located in the M1 hand area, although there are some much smaller contributions from other secondary motor areas, such as the supplementary motor area (SMA). Intracellular recordings show that 75% of upper limb motoneurons in the chloralose-anaesthetized macaque monkey receive a monosynaptic projection from the corticospinal tract; evidence for non-monosynaptic, propriospinal excitatory influences from the corticospinal tract was conspicuously lacking in these anaesthetized preparations. Moreover, in the conscious monkey, hand and arm muscle motor unit responses to corticospinal tract input are dominated by single, brief peaks compatible with monosynaptic excitation. CM excitatory post-synaptic potentials, recorded from a comparable sample of hand and arm motoneurons in anaesthetized macaque and squirrel monkeys, were found to be larger and faster rising in the macaque, which is by far the more dexterous of the two species. CM cells facilitating a given muscle in the conscious macaque are distributed over a wide region of M1 cortex, and each contributes a particular pattern of discharge during a skilled task. In addition to their direct effects on target muscles there may be weaker but potentially important effects that derive from the synchronous binding of assemblies of output neurons. Synchronous oscillations between these neurons are particularly prevalent during steady grip, but disappear during digit movement.

Animals↗

PubMed1998

Activity of spinal interneurons and their effects on forearm muscles during voluntary wrist movements in the monkey.

We studied the activity of 577 neurons in the C6-T1 spinal cord of three awake macaque monkeys while they generated visually guided, isometric flexion/extension torques about the wrist. Spike-triggered averaging of electromyographic activity (EMG) identified the units' correlational linkages with </=12 forearm muscles. One hundred interneurons produced changes in the level of average postspike EMG with onset latencies consistent with mono- or oligosynaptic connections to motoneurons; these were classified as premotor interneurons (PreM-INs). Most PreM-INs (82%) produced postspike facilitations in forearm muscles. Earlier spike-related features, often beginning before the trigger spike, were seen in spike-triggered averages from 72 neurons. Postspike effects were present in one muscle for 64% of the PreM-INs. Neurons with divergent linkages to larger "muscle fields" usually generated postspike effects in synergistic muscles. Fifty-eight percent of the PreM-INs had postspike effects in flexor muscles only and 29% in extensor muscles only. Postspike effects were distributed relatively evenly among the primary flexor and extensor muscles studied. The mean percent change in EMG level from baseline and the mean onset latencies for postspike facilitations and postspike suppressions were similar. PreM-INs exhibited a variety of response patterns during the generation of isometric wrist torque. The response patterns and output effects of 24% of the PreM-INs were consistent with a strict reciprocal organization of flexor and extensor muscle control. For another 60% of the PreM-INs, there was a congruent relation between activity and output effects for only one direction of torque production. These neurons were active for both flexion and extension torques, including 37 neurons that exhibited bidirectional increases in discharge rate. The relatively small number of postspike suppressions observed suggests that inhibitory interneurons were silent when their target muscles were recruited. Compared with premotor neurons in the motor cortex, the red nucleus and the C8-T1 dorsal root ganglia, spinal PreM-INs affected flexor muscles in greater proportions and had smaller muscle fields. The magnitudes of postspike facilitations were similar in all premotor populations. Bidirectional activity, common for PreM-INs, was rare for corticomotoneuronal and premotor dorsal root ganglion cells, which discharge only for torques in their preferred direction.

Action Potentials↗

PubMed1998

Response patterns and force relations of monkey spinal interneurons during active wrist movement.

The activity of C6-T1 spinal cord neurons was recorded in three macaques while they generated isometric wrist flexion and extension torques in visually guided step-tracking tasks. Electromyographic activity (EMG) was recorded in </=12 independent forearm muscles. Spike-triggered averages (STAs) of rectified and unrectified EMG were used to classify neurons into four groups. Motoneurons (MNs) had a clear postspike motor unit signature in the unrectified STA of one muscle. Premotor interneurons (PreM-INs) had postspike effects in at least one muscle, with onset latencies of >/=3.5 ms from the trigger. Synchrony interneurons (Sy-INs) were non-PreM-Ins that had spike-related features with latencies <3.5 ms in at least one muscle. Unidentified interneurons (U-INs) showed no features in any of the STAs. A total of 572 task-related spinal neurons were studied; 29 cells were MNs, 97 PreM-INs, 32 Sy-INs, and 414 U-INs. MNs were activated predominantly in a tonic fashion during the ramp-and-hold torques and were active in one direction only. The most common response pattern for interneurons, irrespective of their class, was phasic-tonic activity, followed by purely tonic and purely phasic activity. Most interneurons (77%) were bidirectionally active in both flexion and extension. For all classes of interneurons, units with phasic response components tended to be activated first, before torque onset, followed by tonic units. The onset times of PreM-INs relative to onsets of their target muscles were distributed broadly, with a mean of -25 +/- 128 (SD) ms. For most neurons with tonic response components (all MNs, 71% of PreM-INs, 67% of Sy-INs, and 84% of U-INs), activity during the hold period was correlated significantly with the magnitude of static torque exerted by the monkey. The rate-torque regressions generally had positive slopes with higher mean slopes for extension than for flexion. The phasic response components were correlated significantly with rate of change of torque for a smaller percentage of tested PreM-Ins (50%), Sy-INs (83%), and U-INs (77%). In contrast to other premotor neurons [corticomotoneuronal (CM), rubromotoneuronal (RM), and dorsal root ganglion (DRG) afferents] previously characterized under similar conditions, a larger proportion of the spinal PreM-INs were activated after onset of their target muscles, probably reflecting a larger proportion of PreM-INs driven by peripheral input. The rate-torque slopes of PreM-INs tended to be less steep than those of CM and RM cells. Unlike the CM and DRG PreM afferents, which were activated unidirectionally, most spinal PreM-INs showed bidirectional activity, like RM cells.

Action Potentials↗

PubMed1997

Direct and indirect corticospinal control of arm and hand motoneurons in the squirrel monkey (Saimiri sciureus).

Anatomic evidence suggests that direct corticomotoneuronal (CM) projections to hand motoneurons in the New World squirrel monkey (Saimiri sciureus) are weak or absent, but electrophysiological evidence is lacking. The nature of the corticospinal linkage to these motoneurons was therefore investigated first with the use of transcranial magnetic stimulation (TMS) of the motor cortex under ketamine sedation in five monkeys. TMS produced early responses in hand muscle electromyogram, but thresholds were high (compared with macaque monkey) and the onset latency was variable. Second, stimulation of the pyramidal tract (PT) was carried out with the use of chronically implanted electrodes in ketamine-sedated monkeys; this produced more robust responses that were markedly facilitated by repetitive stimulation, with little decrease in latency on the third compared with the first shock. Finally, postsynaptic potentials were recorded intracellularly from 93 arm and hand motoneurons in five monkeys under general chloralose anesthesia. After a single PT stimulus, the most common response was a small, slowly rising excitatory postsynaptic potential (EPSP), either alone (35 of 93 motoneurons) or followed by an inhibitory postsynaptic potential (39 of 93). The segmental delay of the early EPSPs was within the monosynaptic range (mean 0.85 ms); however, the rise time of these EPSPs was slow (mean 1.3 ms) and their amplitude was small (mean 0.74 mV). These values are significantly slower and smaller than EPSPs in a comparable sample of Old World macaque monkey motoneurons. The results show that CM connections do exist in the squirrel monkey but that they are weak and possibly located on the remote dendrites of the motoneurons. The findings are consistent with earlier anatomic studies. Repetitive PT stimulation produced large, late EPSPs in some motoneurons, suggesting that, in this species, there are relatively strong nonmonosynaptic pathways linking the corticospinal tract to hand motoneurons.

Animals↗

PubMed1996

Response patterns and postspike effects of premotor neurons in cervical spinal cord of behaving monkeys.

Most of our information about spinal neurons has been derived from experiments with anesthetized or surgically. reduced preparations. To investigate these neurons under normal behavioral conditions, we recorded the activity of single afferent units in cervical dorsal root ganglia and of single interneurons in the cervical spinal cord of macaque monkeys, as they generated alternating flexion and extension torques about the wrist. Spike-triggered averages of rectified electromyographic activity were used to identify "premotor" (PreM) units associated with correlated postspike effects in active muscles. In addition to postspike effects, some spike-triggered averages showed early increases in average muscle activity, which were attributed to synchronous discharges in other PreM units. In recordings of peripheral afferents, 49% of the task-related dorsal root ganglia units produced postspike facilitation (PSF) of at least one forearm muscle, with a mean PSF latency of 5.8 +/- 0.3 ms (SE). The PSF amplitude was measured as the mean percent increase (MPI): the average increase of the PSF as a percentage of the prespike baseline mean. PreM afferent units produced PSF with an average MPI of 4.6 +/- 0.3%. In a study of cervical interneurons, about 13% (72/562) of the task-related cells showed postspike effects. These PreM interneurons had a mean PSF latency of 7.2 +/- 0.3 ms and a mean MPI of 4.6 +/- 0.2%. The MPI values for spinal neurons were similar to the MPIs reported for rubromotoneuronal and corticomotoneuronal cells. PreM neurons usually facilitated a subset of the coactivated muscles called the unit's "muscle field." The PreM afferents facilitated an average of 46% of the synergistically coactivated muscles, while PreM interneurons facilitated an average of 37%. These are comparable with the percentage of muscles facilitated by corticomotoneuronal (40%) and rubromotoneuronal (50%) cells. During the step-tracking task the monkeys generated ramp-and-hold torques about the wrist. The PreM afferents typically became active during either flexion or extension of the wrist, although a few were bidirectionally active. The most common response pattern in PreM afferents was a tonic discharge, followed by phasic and phasic-tonic discharge. The most common patterns exhibited by PreM interneurons were tonic and phasic-tonic responses. PreM afferent units began to discharge on average 51 +/- 13 ms before activation of their target muscle. This early onset supports our hypothesis that these PreM afferents arose from muscle spindles, which is also consistent with their short-latency PSF and their responses to perturbations that stretched their target muscles. The results reveal some salient differences between the discharge properties of dorsal root ganglia neurons, spinal interneurons, and supraspinal PreM cells in the motor cortex and red nucleus. All four PreM populations include tonic, phasic-tonic, and phasic cells, but in significantly different proportions. Most PreM afferents resembled corticomotoneuronal cells in being active only with their target muscles, unlike rubromotoneuronal cells and spinal PreM interneurons, which tended to exhibit more bidirectional discharges.

Afferent Pathways↗

PubMed1995

EMG activation patterns during force production in precision grip. I. Contribution of 15 finger muscles to isometric force.

Electromyographic (EMG) activity was examined in six normal subjects, producing low isometric forces between thumb and index finger in a visually guided step-tracking task. Target forces ranged between 0.5 and 3.0 N. EMG activity of all 15 muscles acting on thumb or index finger was screened with simultaneous recordings of up to 8 muscles. Linear regression was applied to quantify the EMG activity as a function of force. The intrinsic muscles and the long flexors of the index finger had a tight relation to force, as indicated by the high correlation coefficient, as did the adductor and short flexor of the thumb. In contrast, the long extensors of the index finger did not show force-related activity. The other muscles, including the long flexor and extensor of the thumb, had varying, on average moderate, correlations to force. The slope of the regression lines, a measure for the amount of EMG modulation with increasing force, revealed the same trends. Thus the majority of the intrinsic muscles were as closely related to force as the long flexors, suggesting a more important role in production of low isometric forces in the grip than previously believed, perhaps even a primary role. Systematic interindividual differences were rarely observed. Analysis of the trial-by-trial variability of EMG activity revealed that for most muscles the observed scatter was produced by varying background activity and was not a random fluctuation of relative increases in activity from one force level to the next.

Adult↗

PubMed1995

EMG activation patterns during force production in precision grip. II. Muscular synergies in the spatial and temporal domain.

Electromyographic (EMG) activity was analyzed for the occurrence of synergistic patterns during the steady hold periods of force in the precision grip. To establish the presence of muscle synergies in the amplitude (spatial) domain, the EMG activation levels of pairs of simultaneously active muscles were linearly correlated. Cross-correlations of EMG activity were computed to quantify muscle synergies in the spatiotemporal domain (synchronization). A muscle pair was defined to be synergistically coupled or synchronously activated when the correlation (amplitude domain) or cross-correlation (time domain) was significant for at least two of the three steady state force levels. Muscle synergies in the amplitude domain were found in one-third of the 213 muscle pairs tested, distributed among 47 of the 82 tested muscle combinations. Coactivation was the predominant synergistic pattern, whereas trade-off comprised not more than 23% of the synergies. Cross-correlation peak size varied between 5 and 39% of the autocorrelation size, with delays in the range of +/- 8 ms and base width between 12 and 20 ms. Synchronization was found in one-fourth of the 213 muscle pairs tested and among 35 of the 82 muscle combinations, i.e., less frequently than covariation of EMG activity levels. However, the interindividual prevalence was higher for synchronization than for synergies in the amplitude domain, since, for the synergistic muscle combinations, almost twice as many muscle pairs were found to be synchronized than coupled in the amplitude domain. Synergies in the two domains occurred independently in some pairs and concurrently in other cases, and were observed between muscles moving the thumb, the index finger, or both digits. Synchronization was more frequent in pairs of muscles supplied by branches of the same peripheral nerve (46%) than in those innervated by different nerves (18%). Synergies in the amplitude domain were distributed in similar proportions across intrinsic, extrinsic, and combinations of both types of muscles, whereas synchronization mainly occurred in pairs of intrinsic muscles. When the task was repeated with slightly lower target forces, there were fewer synergies in the amplitude domain (in 52 of the 213 pairs, distributed among 35 of 82 muscle combinations) and their distribution changed, indicating a flexible, force-dependent mechanism. In conclusion, no strictly coherent interindividual pattern of synergies in the spatial domain could be established.

Adult↗

PubMed1994

Force-related neuronal activity in two regions of the primate ventral premotor cortex.

Neuronal activity was recorded in the ventral premotor cortex of one monkey (Macaca fascicularis) trained to exert finely graded forces with thumb and index finger on a force sensor in a visuomotor step-tracking paradigm. Trials with two or three consecutive ramp-and-hold force steps were presented randomly. Most neurons displayed similar discharge patterns in the two- and three-step trials and were assigned to one of the following classes: phasic, phasic-tonic, tonic, decreasing, and mixed. For more than 50% of the neurons with tonic activity, positive or negative correlations between firing rate and force were statistically significant. The indices of force sensitivity were on average higher for the two-step than for the three-step trials, indicating that the correlations yielded linearity over only a limited force range. The force-related cells were located in two regions of the ventral premotor cortex. One group was ying rostrally within the inferior limb of the arcuate sulcus, from which microstimulation elicited movements of fingers and hand. In the other more caudal region, adjacent to the finger region of primary motor cortex, microstimulation was rarely effective, but all neurons had clear peripheral receptive fields on finger and hand. The data indicate that two populations of neurons, located in the ventral premotor cortex, are related to movement execution. Effective microstimulation also suggests that one of the populations has fairly direct access to the spinal motor apparatus.

Animals↗

PubMed1993

Contribution of the monkey corticomotoneuronal system to the control of force in precision grip.

1. The contribution of 33 corticomotoneuronal (CM) cells, recorded in the primary motor cortex, to the production of precision grip force has been investigated in four monkeys (Macaca nemestrina). These CM cells were shown, by spike-triggered averaging, to facilitate electromyographic (EMG) activity of hand and forearm muscles. 2. Single-cell recordings were obtained as the monkey performed a low force precision grip task under either isometric or auxotonic conditions. The monkey had to produce independent control of the forces exerted by the thumb and index finger and maintain them for 1-1.5 s. Steady force segments of data were selected trial-by-trial from these hold periods. For each segment the following mean values were determined: 1) CM cell firing rate, 2) EMG activity of facilitated muscles, and 3) index finger, thumb, and total force. 3. Of the 33 CM cells, 18 had a phasic-tonic pattern of discharge during the task, 7 were tonic, 5 had a ramplike increase, and 3 were deactivated during the hold period. 4. Of the 33 cells analyzed, 11 showed a significant positive (P < 0.05) correlation of their mean firing rate with static force; 4 of them had high correlation coefficients (P < 0.001). There was a considerable trial-by-trial variability in the cells' activity-force relationship. Six CM cells had significant negative correlations between their activity and isometric force (5 at the P < 0.001 level), showing lower firing rates with higher forces. 5. The force sensitivity of the CM cells, calculated from the rate-force slopes, was higher for either the thumb or the index finger force. Under isometric conditions the mean rate-force slopes, calculated from the best correlated digit force, was 32.4 Hz/N for eight positively correlated cells and -21.3 Hz/N for the cells with a negative correlation. 6. Correlation between CM cell spike activity and force was more common among neurons with slowly conducting axons (4/6 correlated) than for those with fast axons (13/27). 7. Significant correlations between target muscle EMG and force were always positive. The correlations between CM cell firing rate and target muscle EMG were comparable with those found between firing rate and force. Three of the CM cells with a negative correlation to force also had a negative correlation with EMG in one of their target muscles. 8. Each CM cell facilitated the EMG activity of one to five target muscles; postspike facilitation (PSF) was most common among intrinsic hand muscles (68/82 CM cell/muscle combinations).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1991

Contrasting properties of monkey somatosensory and motor cortex neurons activated during the control of force in precision grip.

1. Single cell activity was investigated in the precentral motor (MI) and postcentral somatosensory (SI) cortex of the monkey to compare the neuronal activity related to the control of isometric force in the precision grip and to assess the participation of SI in motor control. 2. Three monkeys (Macaca fascicularis) were trained in a visual step-tracking paradigm to generate and precisely maintain force on a transducer held between thumb and index finger. Great care was taken to have the monkeys use only their fingers without moving the wrist or proximal joints. In two monkeys electromyographic (EMG) activity was checked in 23 muscles over several sessions. 3. Five similar classes of task-related firing patterns were found in both SI and MI cortical hand and finger representations, but their relative proportions differed. The majority of the SI neurons were phasically or phasic-tonically active (61%), whereas in MI the neurons that decreased their firing rate with force were most frequent (42%). 4. The timing of activity changes related to the onset of force increase from low to higher levels strongly differed in the two neuronal populations. In SI, only 14% of the task-related neurons increased or decreased their firing rate before the onset of force increase, in contrast to 56% in MI. Only 3% of the SI neurons showed changes before the earliest EMG activation. 5. In both SI and MI neurons with tonic and phasic-tonic, increasing or decreasing discharge patterns disclosed a relationship between neuronal activity and static force. Distinction was made between neurons modulating their activity in a monotonic way and those that were active only at one force level and had a kind of recruitment or deactivation threshold. The latter ones were more frequent in MI than in SI, and in the neuron population with decreasing firing patterns. For the neurons with increases in activity, statistically significant linear correlations between firing rate and force were found more frequently in MI than in SI, where the proportion of nonsignificant correlations was relatively high (35% vs. 15% in MI). In SI the indexes of force sensitivity, calculated from the slopes of the regression lines, covered a wider range than in MI; and their distribution was bimodal, with one mean of 30 Hz/N and the other of 155 Hz/N. In contrast, the mean rate-force slope in MI was 69 Hz/N.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed1989

Responses of motor cortex neurons to visual stimulation in the alert monkey.

Evidence for visually evoked activity in single neurons of area 4 is presented. These neurons modulated their activity in relation to stimuli moving across the visual field of the monkey, without showing habituation. Some of them even had direction sensitivity. Their activity was independent of eye movements and unrelated to muscle contractions. The visually activated neurons were distributed throughout the depth of motor cortex.

Animals↗

PubMed1989

Sensorimotor cortical control of isometric force in the monkey.

Recordings from single neurones in the primary somatosensory (SI) and motor (MI) cortex of monkeys trained to precisely regulate force between thumb and index finger have disclosed the following contrasting properties between neurones in these two cortical regions: (1) the existence of neurones with similar discharge patterns within MI and SI but, between these regions, significantly different distributions of the classes of discharge patterns; (2) a late onset of activity change in SI neurones in relation to force increase as compared to significantly earlier changes in MI neurones; (3) linear relations between firing rate and isometric force for SI and MI neurones, however with a larger range of rate-force slopes in SI as compared to MI; (4) infrequent motor reactions to intracortical microstimulation in SI but frequent reactions in MI; (5) a majority of SI neurones with cutaneous afferent input in contrast to predominant input from deep tissues to MI neurones; and (6) context independent visually evoked activity observed exclusively in MI neurones. These major differences suggest that SI neuronal activity most likely reflects the input from peripheral receptors rather than, as postulated for MI neurones, the participation in movement initiation and the control of muscular contractions.

Animals↗