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Biomedical subjects

P L Strick

Publications and source records attributed to P L Strick.

At least 19 recordsLinked to original sources

Effects of a primary motor cortex lesion on step-tracking movements of the wrist.

1. We lesioned the contralateral arm area of the primary motor cortex (M1) in a monkey that had been trained to make rapid step-tracking movements of the wrist in different directions. We examined movement kinematics and electromyographic (EMG) activity of forearm muscles both before and 3.5-5 mo after the lesion. 2. The lesion caused marked changes in movement kinematics and the patterns of activity in agonist, synergist, and antagonist muscles. 3. After the lesion, movements to all targets were performed more slowly. In addition, some movements were misdirected. For example, most movements to the target that required wrist flexion and radial deviation were made in two steps, instead of in a single smooth trajectory. 4. After the lesion, distinct bursts of muscle activity were no longer observed during step-tracking movements. In addition, suppression of antagonist activity at movement onset was abolished or reduced. The relative timing of agonist and synergist muscle activity was markedly altered. 5. We conclude that M1 contributes to the precise spatiotemporal patterning of muscle activity during step-tracking movements.

Animals

Topographic organization of corticospinal projections from the frontal lobe: motor areas on the medial surface of the hemisphere.

We examined the topographic organization of corticospinal neurons in the four premotor areas on the medial wall of the hemisphere of macaques. These motor areas include the supplementary motor area (SMA) and three areas buried within the cingulate sulcus: the caudal cingulate motor area on the dorsal bank (CMAd), the caudal cingulate motor area on the ventral bank (CMAv), and the rostral cingulate motor area (CMAr). In one set of animals, we injected one fluorescent tracer into lower cervical segments of the spinal cord and another fluorescent tracer into lower lumbosacral segments to define the topographic organization of arm and leg representation within each premotor area. Similarly, in another set of animals, we injected different tracers into upper cervical and lower cervical segments to provide an indication of the topographic organization of proximal and distal arm representation within the arm representation of each premotor area. We found that all four of the premotor areas on the medial wall project to cervical and lumbosacral segments of the spinal cord. Three of these areas (SMA, CMAd, and CMAv) are like the primary motor cortex in having distinct arm and leg representations. The arm representation in each of the four motor areas on the medial wall contains separate regions that project densely to upper or to lower cervical segments. This observation suggests that each motor area contains distinct proximal and distal representations of the arm. Surprisingly, the size of the distal representation is comparable to or larger than the size of the proximal representation in each motor area. Thus, contrary to some previous hypotheses, the anatomical substrate exists for the premotor areas on the medial wall to be involved in the control of distal, as well as proximal arm movements. Our results provide a new map for guiding the exploration of the motor functions of the medial wall of the hemisphere. Furthermore, the observations of the present study support our suggestion that each of the premotor areas may be an important source of descending commands for the generation and control of movement.

Animals

Anatomical evidence for cerebellar and basal ganglia involvement in higher cognitive function.

The possibility that neurons in the basal ganglia and cerebellum innervate areas of the cerebral cortex that are involved in cognitive function has been a controversial subject. Here, retrograde transneuronal transport of herpes simplex virus type 1 (HSV1) was used to identify subcortical neurons that project via the thalamus to area 46 of the primate prefrontal cortex. This cortical area is known to be involved in spatial working memory. Many neurons in restricted regions of the dentate nucleus of the cerebellum and in the internal segment of the globus pallidus were labeled by transneuronal transport of virus from area 46. The location of these neurons was different from those labeled after HSV1 transport from motor areas of the cerebral cortex. These observations define an anatomical substrate for the involvement of basal ganglia and cerebellar output in higher cognitive function.

Animals

Activation of a cerebellar output nucleus during cognitive processing.

Magnetic resonance imaging was used to examine the involvement of the dentate nucleus of the cerebellum in cognitive operations. All seven people examined displayed a large bilateral activation in the dentate during their attempts to solve a pegboard puzzle. The area activated was three to four times greater than that activated during simple movements of the pegs. These results provide support for the concept that the computational power of the cerebellum is applied not only to the control of movement but also to cognitive functions.

Adult

Interconnections between the prefrontal cortex and the premotor areas in the frontal lobe.

We examined interconnections between a portion of the prefrontal cortex and the premotor areas in the frontal lobe to provide insights into the routes by which the prefrontal cortex gains access to the primary motor cortex and the central control of movement. We placed multiple injections of one retrograde tracer in the arm area of the primary motor cortex to define the premotor areas in the frontal lobe. Then, in the same animal, we placed multiple injections of another retrograde tracer in and around the principal sulcus (Walker's area 46). This double labeling strategy enabled us to determine which premotor areas are interconnected with the prefrontal cortex. There are three major results of this study. First, we found that five of the six premotor areas in the frontal lobe are interconnected with the dorsolateral prefrontal cortex. Second, the major site for interactions between the prefrontal cortex and the premotor areas is the ventral premotor area. Third, the prefrontal cortex is interconnected with only a portion of the arm representation in three premotor areas (supplementary motor area, the caudal cingulate motor area on the ventral bank of the cingulate sulcus, and the dorsal premotor area), whereas it is interconnected with the entire arm representation in the ventral premotor area and the rostral cingulate motor area. These observations indicate that the output of the prefrontal cortex targets specific premotor areas and even subregions within individual premotor areas.

Amidines

Input to the primate frontal eye field from the substantia nigra, superior colliculus, and dentate nucleus demonstrated by transneuronal transport.

The purpose of these experiments was to study the subcortical input to the frontal eye field (FEF) and to determine which subcortical structures might project to the FEF via pathways that contain only a single intervening synapse. We used retrograde transneuronal transport of herpes simplex virus type 1 (HSV-1) to label second-order neurons that send information to the FEF of cebus monkeys. The saccade region of the FEF was identified physiologically using intracortical stimulation and then injected with a strain of HSV-1 known to be transported transneuronally in the retrograde direction. Retrograde transport of virus labeled neurons was observed in all the thalamic sites known to innervate the FEF. In addition, we found neurons labeled by transneuronal transport in three subcortical sites: the pars reticulata of the substantia nigra, the optic and intermediate gray layers of the superior colliculus, and a posterior portion of the dentate nucleus of the cerebellum. Each of these sites has been shown in prior studies to project to thalamic regions that innervate the FEF. Moreover, the neurons labeled through transneuronal transport were located in a subregion of each subcortical site that is known to be involved in oculomotor control. These observations demonstrate that signals from the substantia nigra, superior colliculus and dentate nucleus can have a significant influence on the output of the FEF.

Animals

Multiple output channels in the basal ganglia.

The neural circuits that link the basal ganglia with the cerebral cortex are critically involved in the generation and control of voluntary movement. Retrograde transneuronal transport of herpes simplex virus type 1 was used to examine the organization of connections in the cebus monkey between an output nucleus of the basal ganglia, the internal segment of the globus pallidus (GPi), and three cortical areas: the primary motor cortex, the supplementary motor ara, and the ventral premotor area. Spatially separate regions of the GPi were labeled after virus injections into each cortical area. The GPi projects to multiple cortical motor areas, and this pallidal output is organized into discrete channels. This information provides a new anatomical framework for examining the function of the basal ganglia in skeletomotor control.

Animals

Preferential activity of dentate neurons during limb movements guided by vision.

1. We recorded the activity of dentate neurons while monkeys (n = 2) performed sequential pointing movements under two task conditions: visually guided and remembered. For both conditions, a monkey faced a panel with five touch pads. The animal began a trial by placing his right hand on a hold key in front of him. In the Remembered Sequence Task, light-emitting diodes (LEDs) over three touch pads were illuminated in a sequence as an instruction to the monkey. At the end of a variable instruction period, an auditory "Go" signal told the monkey to release the hold key and press the touch pads according to the instructed sequence. In the Tracking Task, the monkey was required to press three touch pads immediately after the LED over each of them was illuminated. 2. We recorded from 172 neurons in the dentate that showed task-related changes in activity during the reaction time (RT) period (i.e., the interval between the onset of the Go signal and the release of the hold key). Approximately 40% of these neurons were considered task-dependent because they displayed exclusive or enhanced (> +/- 50%) changes in peak activity during the RT period for one of the two task conditions. Almost 80% of the task-dependent neurons displayed exclusive or enhanced activity changes during the Tracking Task. Many of these neurons were located ventral and lateral to dentate neurons, which were not task-dependent. 3. These results suggest that a portion of the dentate nucleus is preferentially involved in the generation and/or guidance of movement based on visual cues.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Corticospinal terminations in two new-world primates: further evidence that corticomotoneuronal connections provide part of the neural substrate for manual dexterity.

Anterograde transport of 2-10% WGA-HRP was used to examine the pattern of termination of efferents from the primary motor cortex to cervical segments of the spinal cord in cebus (Cebus apella) and squirrel (Saimiri sciureus) monkeys. We have compared the pattern of termination in these monkeys because of marked differences in their manipulative abilities. Both primates have pseudo-opposable thumbs; however, only cebus monkeys use independent finger movements to pick up small objects. We found that corticospinal terminations in cervical segments of the cebus monkey are located in three main zones: a dorsolateral region of the intermediate zone, a dorsomedial region of the intermediate zone, and the ventral horn. The projection to the ventral horn in these monkeys is particularly dense at C8-T1 segments, where terminations form a "ring" that encircles the lateral motoneuronal cell group. In contrast, there are only two main zones of terminations in the squirrel monkey: a dorsolateral region of the intermediate zone and a dorsomedial region of the intermediate zone. As others have noted, efferents from the primary motor cortex of squirrel monkeys have, at best, only sparse terminations within the ventral horn. Thus, there are marked differences between cebus and squirrel monkeys in the extent of corticospinal terminations within the ventral horn. These observations provide further support for the concept that monosynaptic projections from the primary motor cortex to motoneurons in the ventral horn provide part of the neural substrate for dexterous movements of the fingers.

Animals

Topographic organization of corticospinal projections from the frontal lobe: motor areas on the lateral surface of the hemisphere.

We examined the topographic organization of corticospinal neurons in the primary motor cortex and in the two premotor areas on the lateral surface of the hemisphere [i.e., the dorsal premotor area (PMd) and the ventral premotor area (PMv)]. In two macaques, we labeled corticospinal neurons that project beyond T7 or S2 by placing crystals of HRP into the dorsolateral funiculus at these segmental levels. In another seven macaques, we labeled corticospinal neurons that project to specific segmental levels of the spinal cord by injecting the fluorescent tracers fast blue and diamidino yellow into the gray matter of the cervical and lumbosacral segments. In one set of experiments (n = 2), we defined the representations of the arm and leg in each cortical motor area by injecting one of the two fluorescent tracers into lower cervical segments (C7-T1) and the other fluorescent tracer into lower lumbosacral segments (L6-S1) of the same animal. In another set of experiments (n = 5), we defined the representations of distal and proximal parts of the forelimb in each cortical motor area by injecting one of the two fluorescent tracers into lower cervical segments (C7-T1) and the other tracer into upper cervical segments (C2-C4) of the same animal. In the primary motor cortex and the PMd, cortical regions that project to lower cervical segments were largely separate from those that project to lower lumbosacral segments. In the PMv, few neurons were labeled after tracer injections into lower cervical segments or lower lumbosacral segments. However, corticospinal neurons were labeled in the PMv after tracer injections into upper cervical segments and after HRP placement in the dorsolateral funiculus at T7. The region of the PMv that projects to upper cervical segments was separate from that which projects below T7. Cortical regions that project to upper and lower cervical segments of the spinal cord overlapped considerably in the primary motor cortex and in the PMd. Despite this overlap, we found that the regions of the primary motor cortex and PMd that project most densely to upper cervical segments were largely separate from those that project most densely to lower cervical segments. Furthermore, we found two separate regions within area 4 that send corticospinal projections primarily to the lower cervical segments. One of these regions was located within the classical "hand" area of the primary motor cortex. The other was located at the medial edge of arm representation in the primary motor cortex.(ABSTRACT TRUNCATED AT 400 WORDS)

Amidines

Step-tracking movements of the wrist. III. Influence of changes in load on patterns of muscle activity.

Human subjects performed step-tracking movements of the wrist in the radial direction. Movement amplitude, external load, and accuracy instructions were varied. We used surface electrodes to record muscle activity from an agonist, extensor carpi radialis longus, and an antagonist, extensor carpi ulnaris. When subjects performed movements "as fast as possible" that were opposed by different external loads, we observed two distinct patterns of modulation of the agonist burst. In one pattern, termed pulse-height modulation, the force of the agonist muscle was graded by varying the peak amplitude of a short-duration agonist burst. This pattern occurred when subjects performed movements of different amplitudes with a lightweight manipulandum. In the other pattern, termed pulse-width modulation, the force of the agonist muscle was graded by varying the duration of an agonist burst of nearly maximal amplitude. When the agonist burst was prolonged, the onset of antagonist activity was delayed. This pattern occurred when subjects performed movements of different amplitudes that were opposed by elastic or viscoelastic loads applied to a heavy manipulandum. The strongest subject exhibited more pulse-height modulation and less pulse-width modulation of the agonist burst than other subjects. Conversely, the weakest subject displayed more pulse-width modulation of the agonist burst than other subjects. These observations indicate that the force requirements of a task, relative to the force generating capacity of a subject's agonist muscle(s), have a significant influence on the pattern of agonist modulation. In a second experiment using three nonhuman primates, we observed that agonist bursts in wrist flexor and extensor muscles exhibited strikingly different patterns of modulation. For wrist flexion, agonist bursts in wrist flexors were brief and displayed pulse-height modulation when movement amplitude was varied. For wrist extension, agonist bursts in wrist extensors were prolonged and displayed largely pulse-width modulation when movement amplitude was varied. We suggest that the distinct patterns of modulation observed in the wrist muscles of monkeys were due to differences in the strength of wrist flexors and extensors, rather than to alterations in movement strategy. In a third experiment, we instructed human subjects to be "accurate" when they made step-tracking movements. When subjects performed movements with a lightweight manipulandum, most displayed short-duration agonist bursts that were pulse-height modulated. When subjects performed "accurate" movements that were opposed by elastic loads, they displayed pulse-width modulation of a small-amplitude agonist burst.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Medial wall motor areas and skeletomotor control.

The results of recent studies in primates provide convincing evidence that the cortex on the medial wall of the hemisphere contains multiple areas concerned with the generation and control of body movement. Highlights of these findings include the demonstration that each of these motor areas has substantial direct projections to the spinal cord, somatotopically organized projections to the primary motor cortex, a 'motor' map, revealed by intracortical stimulation, and neuronal activity that precedes trained hand movements.

Animals

Direction of transneuronal transport of herpes simplex virus 1 in the primate motor system is strain-dependent.

We examined the axonal transport of two strains of herpes simplex virus 1 (HSV-1) within the central nervous system of cebus monkeys. Each strain was injected into the "arm area" of the primary motor cortex. One strain, HSV-1(McIntyre-B), was transported transneuronally in the retrograde direction. It infected neurons at sites known to project to the arm area of the primary motor cortex (e.g., ventrolateral thalamus). In addition, "second-order" neurons were labeled in the deep cerebellar nuclei (dentate and interpositus) and in the globus pallidus (internal segment). This result supports the concept that the arm area of the primary motor cortex is a target of both cerebellar and basal ganglia output. In contrast, the other strain, HSV-1(H129), was transported transneuronally in the anterograde direction. It infected neurons at sites known to receive input from the arm area of the primary motor cortex (e.g., putamen, pontine nuclei). In addition, "third-order" neurons were labeled in the cerebellar cortex (granule and Golgi cells) and in the globus pallidus (largely the external segment). Our observations suggest that strain differences have an important impact on the direction of transneuronal transport of HSV-1. Furthermore, it should be possible to examine the organization of cerebellar and basal ganglia loops with cerebral cortex by exploiting transneuronal transport of HSV-1 and virus strain differences.

Animals

The origin of corticospinal projections from the premotor areas in the frontal lobe.

We determined the origin of corticospinal neurons in the frontal lobe. These neurons were labeled by retrograde transport of tracers after injections into either the dorsolateral funiculus at the second cervical segment or the gray matter of the spinal cord throughout the cervical enlargement. Using retrograde transport of tracer from the arm area of the primary motor cortex, we defined the arm representation in each premotor area in another set of animals. We found that corticospinal projections to cervical segments of the spinal cord originate from the primary motor cortex and from the 6 premotor areas in the frontal lobe. These are the same premotor areas that project directly to the arm area of the primary motor cortex. The premotor areas are located in parts of cytoarchitectonic area 6 on the lateral surface and medial wall of the hemisphere, as well as in subfields of areas 23 and 24 in the cingulate sulcus. The total number of corticospinal neurons in the arm representations of the premotor areas equals or exceeds the total number in the arm representation of the primary motor cortex. The premotor areas collectively comprise more than 60% of the cortical area in the frontal lobe that projects to the spinal cord. Like the primary motor cortex, each of the premotor areas contains local regions that have a high density of corticospinal neurons. These observations indicate that a substantial component of the corticospinal system originates from the premotor areas in the frontal lobe. Each of the premotor areas has direct access to the spinal cord, and as a consequence, each has the potential to influence the generation and control of movement independently of the primary motor cortex. These findings raise serious questions about the utility of viewing the primary motor cortex as the "upper motoneuron" or "final common pathway" for the central control of movement.

Afferent Pathways

The origin of thalamic inputs to the "hand" representation in the primary motor cortex.

We used retrograde transport of WGA-HRP to examine the origin of thalamic inputs to the "hand" representation in the primary motor cortex of macaques (Macaca nemestrina). Injections were placed in either the crest of the precentral gyrus or the rostral bank of the central sulcus. The sites for injection in the sulcus were determined by using intracortical stimulation to map the location of hand representation. We found that the precentral gyrus and central sulcus receive their predominant input from different subdivisions of the ventrolateral thalamus. Ventralis posterior lateralis pars oralis (VPLo) provides the most substantial input to a portion of the hand representation on the gyrus. In contrast, Ventralis lateralis pars oralis (VLo) provides the most substantial input to a portion of the hand representation in the sulcus. Prior studies have shown that VPLo is a major site of termination of cerebellar efferents and that VLo is a major site of termination of pallidal efferents. Thus, our results indicate that both the basal ganglia and the cerebellum "directly" influence the "hand" representation of the primary motor cortex.

Amidines

Step-tracking movements of the wrist in humans. II. EMG analysis.

We asked human subjects to make accurate step-tracking movements of the wrist to targets that required 5 degrees-30 degrees of radial or ulnar deviation. Speed instructions were given prior to each trial. Muscle activity was recorded from extensor carpi radialis longus (ECRL) and extensor carpi ulnaris (ECU) using surface electrodes. The agonist muscle initiated each movement with a brief burst of activity which began approximately 45 msec before movement onset. Then, the antagonist muscle displayed a brief burst of activity which began approximately 10 msec after movement onset. The magnitude, but not the timing, of these bursts was modulated by changes in the task requirements. The area of the initial agonist burst varied with changes in both displacement and intended speed. This burst was most highly correlated with the initial peaks of acceleration and jerk. In contrast, the area of the initial antagonist burst varied with changes in intended speed and was less well modulated by changes in displacement. This burst was highly correlated with the reciprocal of movement duration. Some small, fast movements had the same agonist bursts as some large, slow movements. However, the antagonist bursts for these movements differed greatly. This observation provides clear evidence that the magnitudes of the agonist and antagonist bursts are independently controlled. In a prior paper (Hoffman and Strick, 1986b), we proposed that step-tracking movements of different amplitudes and intended speeds are centrally generated by adjusting 2 kinematic variables: (1) the peak value and (2) the duration of a derivative of displacement. The present results suggest that these 2 kinematic parameters are separately generated by independently modulating the magnitudes of the agonist and antagonist bursts. Thus, the peak displacement of a step-tracking movement must be determined by the appropriate adjustment of both bursts of muscle activity.

Adult

Cerebellar connections with the motor cortex and the arcuate premotor area: an analysis employing retrograde transneuronal transport of WGA-HRP.

We have employed transneuronal transport to examine the anatomical relationships between the deep cerebellar nuclei and 2 cortical motor areas: the primary motor cortex and the arcuate premotor area (APA). In the same animals, we have also examined the patterns of labeling in the thalamus and the red nucleus to provide evidence for the potential routes of transneuronal transport to the cerebellum. When the appropriate technical procedures were employed, cortical injections of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) resulted in transneuronal labeling within portions of the contralateral deep cerebellar nuclei. Injections into the primary motor cortex labeled neurons in the dentate and in the 2 subdivisions of the interpositus. Injections into the APA labeled neurons in the dentate and in only the posterior subdivision of the interpositus. In most instances, dentate neurons were more intensely labeled following the cortical injections than interpositus neurons. The transneuronal labeling observed in the dentate nucleus was topographically organized. The dentate region that was labeled following injections into the "arm area" of the APA was caudal and ventral to the dentate region that was labeled following injections into the "arm area" of the primary motor cortex. This observation provides evidence for two "arm areas" in the dentate: one anatomically related to the APA, and the other related to the primary motor cortex. More than one route of transport may be responsible for the labeling of cerebellar neurons. We propose that the labeling observed in the dentate nucleus reflects the pattern of connections in the cerebellothalamocortical pathways that link the dentate with the cerebral cortex. Thus, our observations support the concept proposed by Schell and Strick (J. Neurosci. 4:539-560, '84)--that the cortical targets of the dentate nucleus include both the primary motor cortex and the APA.

Animals

Transneuronal transfer of herpes virus from peripheral nerves to cortex and brainstem.

The transneuronal transfer of neurotropic viruses may represent an effective tool for tracing chains of connected neurons because replication of virus in the recipient neurons after transfer amplifies the "tracer signal." Herpes simplex virus type 1 was transferred transneuronally from forelimb and hindlimb nerves of rats to the cortical and brainstem neurons that project to the spinal enlargements to which the nerves receiving injections are connected. This transneuronal transfer of herpes simplex virus type 1 from peripheral nerves has the potential to be used to identify neurons in the brain that are related transsynaptically to different nerves and muscles.

Animals