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I Darian-Smith

Publications and source records attributed to I Darian-Smith.

At least 19 recordsLinked to original sources

Parallel pathways mediating manual dexterity in the macaque.

Transmission of information along appropriately structured parallel pathways ensures that a great deal of information can be transferred from the source to the target very quickly, and with great security-essential features of any motor control system. Studies over the last two decades have established that the corticospinal and corticocerebellar pathways mediating manual dexterity in the primate are structurally organized to sustain the parallel transmission of sensorimotor information in multiple pathways. Serial, hierarchical control systems now seem insufficient to regulate voluntary hand movements. To achieve the required coordination, and precision and speed of execution, they must be combined with parallel control systems, which themselves incorporate elaborate feedforward and feedback controls. To illustrate these issues, two aspects of the structural organization of parallel sensorimotor pathways mediating manual dexterity in the macaque are reviewed. First, we examine the structure of the multiple corticospinal neuron subpopulations projecting from different areas of the frontoparietal cortex and how they are modified following hemisection of the cervical spinal cord. The remarkable recovery of hand function following spinal hemisection, despite the absence of any structural 'bridging' of the interrupted spinal pathways, and the fact that this is accountable in a parallel but not in a purely serial transmission system, are then reviewed. The second aspect of parallel distributed transmission examined is its occurrence within a single population of relay neurons. Our recent structural analysis of the somatic/dendritic organization of rubrospinal neurons in macaque red nucleus is used. The very large dendritic fields of individual neurons, extending over one-third or more of the nucleus, provide a framework for extracting precise somatotopic information from an input population whose axon terminal arbors overlap extensively, and, which, without effective filtering, would provide poor spatial resolution.

Animals

Corticospinal projection patterns following unilateral section of the cervical spinal cord in the newborn and juvenile macaque monkey.

Immediately following a unilateral section of the midcervical spinal cord that interrupts the dorsolateral, lateral, and ventral columns, the macaque monkey has a severe flaccid paralysis on the side of the lesion. Recovery of hand function is rapid, and, although it is incomplete, within a few months, the monkey uses the initially disabled hand and fingers with considerable skill. We examined the accompanying changes in the pattern of projection of corticospinal neurons to the cervical spinal cord that occurred following such a lesion. Spinal section was done both in newborn and juvenile macaques, and the postlesion period was followed for up to 150 weeks. Corticospinal neuron populations were visualized by using both anterogradely and retrogradely transported labels, and their origins, spinal pathways, and terminations were examined at intervals during the period of recovery of hand function. Immediately following unilateral section of the spinal cord at C3, sampled counts of soma profiles of retrogradely labeled neurons indicated that there was a profound reduction in the corticospinal projection to the hemicord caudal to the lesion. The few labeled corticospinal axons spared by the lesion bypassed the spinal lesion by descending in the contralateral cord and then crossing the midline caudal to the lesion. A few corticospinal axons may also have bypassed the lesion in the ipsilateral ventromedial column when this was not fully interrupted by the lesion. In every monkey, we observed a similar, profound reduction in the corticospinal (and rubrospinal) projections to the hemicord caudal to the lesion: This pattern did not alter significantly over an extended recovery period. An unchanging corticospinal projection to the cervical spinal cord contralateral to the lesion was also visualized in each monkey and resembled that seen in the normal macaque. Although the resolution of the labeling and counting procedures used precluded the identification of small increases in the numbers of corticospinal neurons projecting to the hemicord caudal to the lesion, we concluded that there was no substantial reconstruction of this projection over a recovery period of more than 2 years.

Age Factors

Manual dexterity and corticospinal connectivity following unilateral section of the cervical spinal cord in the macaque monkey.

The macaque recovers quite rapidly from the immediate severe flaccid hemiparesis that results from unilateral section of the cervical spinal cord (between C3 and C6) and starts to use the impaired hand to pick up objects within about 30 days following the surgery. Within another 60 days, the monkey is quite dexterous; nonetheless, there is a persisting deficit. We used video recording to study the long-term recovery of manual dexterity following unilateral section of the cervical cord in newborn and juvenile monkeys. A reach-and-retrieve manual task was examined. By using a preset oppositional force, opposition of the pads of the index finger and thumb in the vertical plane was needed to retrieve the desired target object. The corticospinal connectivity of each monkey was also examined by using retrograde or anterograde tracers at the end of the experimental period (Galea and Darian-Smith [1997] J. Comp. Neurol., this issue) and was correlated with the manual performance. Manually retrieving an object depends on the coordination of several control processes acting in parallel, including 1) visually guided components, such as directing the arm toward the object, aligning the digits with the target object by pronating the forearm, and preshaping the index/thumb separation to match with the size and shape of the target, and 2) manipulative components that depend on tactual input and that also include independent movements of the digits and the application of the appropriate oppositional forces. The impairment of manual dexterity that persisted after a cervical section, although it was small, involved these processes and was evident in 1) the less direct trajectory used in reaching, 2) the loss of preshaping of the separated index finger and thumb prior to grasping the target object, and 3) a weakening of the oppositional forces that could be developed between the pads of the index finger and thumb. Although, in the accompanying paper, we did not preclude some regeneration of severed corticospinal connections, we did show that, if any such reconstruction occurred, then it was limited. The remarkable but incomplete recovery of dexterity over a period of 6-12 months, therefore, must be achieved by 1) optimizing the transmission of information from the cortex to the spinal cord by the substantially reduced populations of corticospinal neurons and corticobulbospinal projections and/or 2) the effective use of spinal circuitry in regulating the more stereotyped elements of the manual task.

Age Factors

Thalamic projections to areas 3a, 3b, and 4 in the sensorimotor cortex of the mature and infant macaque monkey.

Area 3a in the macaque monkey, located in the fundus of the central sulcus, separates motor and somatosensory cortical areas 4 and 3b. The known connections of areas 4 and 3b differ substantially, as does the information which they receive, process, and transfer to other parts of the central nervous system. In this analysis the thalamic projections to each of these three cortical fields were examined and compared by using retrogradely transported fluorescent dyes (Fast Blue, Diamidino Yellow, Rhodamine and Green latex microspheres) as neuron labels. Coincident labeling of projections to 2-3 cortical sites in each monkey allowed the direct comparison of the soma distributions within the thalamic space of the different neuron populations projecting to areas 3a, 3b, and 4, as well as to boundary zones between these cortical fields. The soma distribution of thalamic neurons projecting to a small circumscribed zone (diameter = 0.5-1.0 mm) strictly within cortical area 3a (in region of hand representation) filled out a "territory" traversing the dorsal half of the cytoarchitectonically defined thalamic nucleus, VPLc (abbreviations as in Olszewski [1952] The Thalamus of the Macaca mulatta. Basel: Karger). This elongate, rather cylindrical, territory extended caudally into the anterior pulvinar nucleus, but not forward into VPLo. The rostrocaudal extent of the thalamic territory defining the soma distribution of neurons projecting to small zones of cortical area 3b was similar, but typically extended into the ventral part of VPLc, filling out a medially concavo-convex laminar space. Two such territories projecting to adjacent zones of areas 3a and 3b, respectively, overlapped and shared thalamic space, but not thalamic neurons. Contrasting with the 3a and 3b thalamic territories, the soma distribution of thalamic neurons projecting to a circumscribed zone in the nearby motor cortex (area 4) did not penetrate into VPLc, but instead filled out a mediolaterally flattened territory extending from rostral VLo, VLm, VPLo to caudal and dorsal VLc, LP, and Pul.o. These territories skirted around VPLc. All three cortical areas 4, 3a, and 3b) also received input from distinctive clusters of cells in the intralaminar Cn.Md. It is inferred that, in combination, the thalamic territories enveloping those neuron somas projecting to, say, the sensorimotor hand representation in areas 3a, 3b, and 4 (and also areas 1 and 2), which would be coactive during the execution of a manual task, constituted a lamellar space extending from VLo rostrally to Pul.o caudally.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging

Ipsilateral cortical projections to areas 3a, 3b, and 4 in the macaque monkey.

In the macaque monkey area 3a of the cerebral cortex separates area 4, a primary motor cortical field, from somatosensory area 3b, which has a subcortical input mainly from cutaneous mechanoreceptive neurons. That each of these cortical areas has a unique thalamic input was illustrated in the preceding paper. In the present experiments the cortical afferent projections to these 3 areas of the sensorimotor cortex monkey were visualized and compared, using 4 differentiable fluorescent dyes as axonal retrogradely transported labels. The cortical projection patterns to areas 3a, 3b, and 4 were similar in that they each consisted of (a) a "halo" of input from the immediately surrounding cortex, and (b) discrete projections from one or more remote cortical areas. However, the pattern of remote inputs from precentral, mesial, and posterior parietal cortex was different for each of the 3 cortical target areas. The cortical input configuration was least complex for area 3b, its remote input projecting mainly from insular cortex. The pattern of discrete cortical inputs to the motor area 4, however, was more complex, with projections from the cingulate motor area (24c/d), the supplementary motor area, postarcuate cortex, insular cortex, and postcentral areas 2/5. Area 3a, in addition to the proximal projections from the immediately surrounding cortex, also received input from the supplementary motor area, cingulate motor cortex, insular cortex, and areas 2/5. Thus, this pattern of cortical input to area 3a resembled more closely that of the adjacent motor rather than that of the somatosensory area 3b. Contrasting with this, however, the thalamic input to area 3a was largely from somatosensory VPLc (abbreviations from Olszewski [1952] The Thalamus of the Macaca mulatta. Basel: Karger) and not from VPLo (with input from cerebellum, and projecting to precentral motor areas).

Aging

Thalamic projections to sensorimotor cortex in the macaque monkey: use of multiple retrograde fluorescent tracers.

We used several fluorescent dyes (Fast Blue, Diamidino Yellow, Rhodamine Latex Microspheres, Evans Blue, and Fluoro-Gold) in each of eight macaques, to examine the patterns of thalamic input to the sensorimotor cortex of macaques 12 months or older. Inputs to different zones of motor, premotor, and postarcuate cortex, supplementary motor area, and areas 3b/1 and 2/5 in the postcentral cortex, were examined. Coincident labeling of thalamocortical neuron populations with different dyes (1) increased the precision with which their soma distributions could be related within thalamic space, and (2) enabled the detection by double labeling, of individual thalamic neurons that were common to the thalamic soma distributions projecting to separate, dye-injected cortical zones. Double-labeled thalamic neurons projecting to sensorimotor cortex were rarely seen in mature macaques, even when the injection sites were only 1-1.5 mm apart, implying that their terminal arborizations were quite restricted horizontally. By contrast, separate neuron populations in each thalamic nucleus with input to sensorimotor cortex projected to more than one cytoarchitecturally distinct cortical area. In ventral posterior lateral (oral) (VPLo), for example, separate populations of cells sent axons to precentral medial, and lateral area 4, medial premotor, and postarcuate cortex, as well as to supplementary motor area. Extensive convergence of thalamic input even to the smallest zones of dye uptake in the cortex (approximately 0.5 mm3) characterized the sensorimotor cortex. The complex forms of these projection territories were explored using 3-dimensional reconstructions from coronal maps. These projection territories, while highly ordered, were not contained by the cytoarchitectonic boundaries of individual thalamic nuclei. Their organization suggests that the integration of the diverse information from spinal cord, cerebellum, and basal ganglia that is needed in the execution of complex sensorimotor tasks begins in the thalamus.

Afferent Pathways

Thalamic projections to sensorimotor cortex in the newborn macaque.

In the present experiments thalamocortical projections to different functional areas of the newborn (or prematurely delivered) macaque's sensorimotor cortex were labeled using retrogradely transported fluorescent dyes. Several dyes were used in each animal to (1) enable the direct comparison of the soma distributions of different thalamocortical projections within thalamic space, and (2) identify by double labeling neurons shared between these distributions. The projection patterns in the newborn macaque were compared with those of the mature animal reported by Darian-Smith et al. (J. Comp. Neurol. 1990;298:000-000). The main observations were (1) all thalamocortical projections to the sensorimotor cortex of the mature macaque are well established by embryonic days 146-150, as was shown by labeling these pathways in infants delivered by cesarean section, (2) a significant number of thalamocortical neurons in the newborn were double-labeled following dye injections into different pre- or postcentral areas, and where the margins of the dye uptake zones were separated by 3-8 mm, and (3) extensive projections from the anterior pulvinar nucleus to the motor and premotor cortex, and to the supplementary motor cortex were labeled in the newborn macaque. Both the exuberant terminal arborizations, and the precentral pulvinar projections were diminished by the 6th postnatal month, and absent in the mature macaque. The role of epigenetic determinants of these postnatal events is briefly considered.

Afferent Pathways

Tactile discrimination of thickness.

The ability of human subjects to discriminate plane metal plates of different thickness was measured using of forced-choice paradigm. The plates, made by electroplating a thin layer of copper onto flat brass shims, were gripped between the thumb and the index finger. Subjects were presented with either 2 standard plates (0.2 mm thick), or a standard plate and a test plate that was slightly thicker, and were required in state which alternative had occurred. When the edges of the plates could not be touched, a difference in thickness of about 0.075 mm could be discriminated. Surprisingly, when the edges were included in the grip, performance did not improve. All hypotheses of strategies used by the subjects required them to sense the angles of the finger joints with a precision of about 0.1 degrees.

Adult

Skin profiles during sinusoidal vibration of the fingerpad.

Skin on the fingertips of humans and monkeys was stimulated by a probe vibrating with a sinusoidal displacement. The probe and the skin were illuminated stroboscopically and were viewed through a dissecting microscope. The stroboscope was triggered by the sinusoidal generator via a digital delay, so that the position of both the probe and the skin could be measured at regular intervals during the cycle. Six frequencies and 3 amplitudes of vibration were used. During a portion of the cycle the probe and the skin separated, so that the skin waveform was a clipped sinusoid. An increase in stimulus frequency increased the fraction of the cycle during which the probe and the skin were separated. Adding a static pre-indentation to the vibration reduced this fraction, and for this condition a decrease in vibratory amplitude also decreased the fraction. Thus the skin motion contained harmonics that were not present in the probe motion, and the harmonic content differed for different stimulus conditions.

Animals

Spatial and temporal factors determining afferent fiber responses to a grating moving sinusoidally over the monkey's fingerpad.

Gratings of alternating grooves and ridges were moved sinusoidally across the fingerpads of anesthetized monkeys, while responses were recorded from individual slowly adapting afferents (SAs), rapidly adapting afferents (RAs), and Pacinian afferents (PCs) in the median nerve. The stimulus comprised 2 spatial variables, namely, groove width (G) and ridge width (W), and 2 temporal variables, namely, the peak speed of movement (S) and the peak temporal frequency (F) at which successive spatial cycles of the grating pass over a point in the receptive field. The responses of all 3 fiber types were determined by only 1 spatial variable, G, and only 1 temporal variable, F. Changes in W or S affected responses only if there was a concomitant change in either G or F. Responses were phase-locked to the occurrence of successive spatial cycles of the grating, and we have used the number of impulses elicited by a single spatial cycle as the fundamental measure of response. An equation of the form I = cGaexp(-b square root of F) describes the responses of all 3 fiber types. For SAs, the effect of groove width was greater (a = 2.64) than for RAs and PCs (a = 0.924 and 1.05, respectively). The reduction in response with frequency was most marked for SAs (b = 0.262), and greater for PCs (b = 0.167) than for RAs (b = 0.130). From the equation, the instantaneous response during the entire sinusoidal cycle was reconstructed as well as a second measure, the mean cyclic response. These 2 measures behaved differently with changes in the stimulus parameters. The temporal properties of the fibers, as revealed by gratings, may appear to be in conflict with those established by vibratory threshold studies; in fact, they are compatible with suprathreshold responses to vibrating probes.

Animals

Perceived roughness of a grating: correlation with responses of mechanoreceptive afferents innervating the monkey's fingerpad.

Human subjects scaled gratings of alternating grooves and ridges for perceived roughness. Roughness increased with an increase in groove width and decreased with an increase in ridge width, but the effect of groove width was much greater than the effect of ridge width. In corresponding neurophysiological experiments, the gratings were moved sinusoidally across the receptive fields of single mechano-receptive afferents innervating the fingerpads of anesthetized monkeys. The measure of response used was the mean cyclic discharge rate (averaged over one cycle of the sinusoid). Slowly adapting afferents (SAs), rapidly adapting afferents (RAs), and Pacinian afferents (PCs) all showed a marked increase in response when groove width increased. An increase in ridge width had no consistent effect on the responses of SAs or RAs but resulted in a small decrease in the response of PCs. The response to a smooth surface differed significantly from the responses to the finer gratings only for the RAs. An alternative measure of response (the number of impulses elicited by each spatial cycle of the grating) increased with an increase in ridge width for all 3 fiber types. Thus, the large effect of groove width on perceived roughness can be accounted for by the mean cyclic discharge rate in the active afferent fibers. The smaller effect of ridge width can be accounted for by the number of impulses per spatial cycle of the grating.

Adult

A stimulator for moving textured surfaces sinusoidally across the skin.

The stimulator allows textured surfaces to be moved sinusoidally across the skin of the fingerpad. Sinusoidal motion is produced by a "scotch yolk" driven by a DC motor. The amplitude of movement is adjustable up to a maximum of 80 mm peak to peak and the frequency is continuously adjustable from 0.1 Hz to 2.0 Hz. Movement of the surface is monitored by an optical transducer and contact force between the finger and the surface is monitored by a strain gauge bridge. The stimulator is simple and robust and is suitable for both neurophysiological and psychophysical experiments in animals and humans.

Animals

Tactile discrimination of gratings.

Human subjects were required to differentiate grating surfaces of alternating grooves and ridges by moving a finger back and forth across the surface. Their discriminative capacities were measured, as well as the movement and force profiles that they selected. To measure discrimination, a forced choice paradigm was used in which three surfaces were presented on each trial. Two surfaces were the same (standards) and the subject was required to indicate which of the three surfaces (the comparison) differed from the other two. Two series of surfaces were used with standards whose spatial periods were 770 and 1002 mu, respectively. Subjects were able to discriminate, at the 75% correct level, two gratings which differed in spatial period by the order of 5%. When tangential movement between the surface and the finger was eliminated, and only radial contact permitted, discrimination was degraded and the 75% correct levels increased to the order of 10%. Subjects were free to choose their own patterns of finger movement and of contact force between finger and surface. Movement was measured cinematographically. For all subjects movement patterns were close to sinusoidal, with frequencies in the range of 4.0 Hz and with mean velocities of the order of 160 mm/s. Patterns of contact force were measured by a force transducer. For all subjects the force varied rhythmically in synchrony with movement, but the patterns and magnitudes varied with the subject. Gratings were scaled for perceived roughness by a magnitude estimation technique: the relationship between perceived roughness and grating period was monotonic.

Adolescent

Transcutaneous recording of single neuron activity in the cerebral cortex of the monkey.

A new method is described for recording responses of single neurons in the monkey's cerebral cortex by passing a microelectrode directly through the overlying skin and dura. Previous to this recording a window had been cut in the calvarium, and the bone deficit repaired using a full-thickness skin graft. Stable unitary recordings have been made over a period of one year following craniotomy, the only skull attachment being a small stainless steel peg, on which the microdrive was mounted when required.

Animals

Touching textured surfaces: cells in somatosensory cortex respond both to finger movement and to surface features.

Single neurons in Brodmann's areas 3b and 1 of the macaque postcentral gyrus discharge when the monkey rubs the contralateral finger pads across a textured surface. Both the finger movement and the spatial pattern of the surface determine this discharge in each cell. The spatial features of the surface are represented unambiguously only in the responses of populations of these neurons, and not in the responses of the constitutent cells.

Animals

Touch in primates.

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Afferent Pathways

Peripheral neural representation of the spatial frequency of a grating moving across the monkey's finger pad.

1. Responses in mechanoreceptive afferent fibres innervating the monkey's finger pads were examined when a ridged surface ("grating') was moved across the fibre's receptive field with a specified velocity and applied force. 2. The stimulus feature represented in single fibre responses was the temporal frequency of the moving grating (stimulus temporal frequency = velocity of moving surface/spatial period); information about the spatial period of the grating was represented equivocally. 3. Peripheral neural representation of the grating's spatial period (or spatial frequency) depended on information signalled by the responding fibre population rather than by individual fibres. 4. The three mechanoreceptive fibre populations responded differentially to a grating moving across the finger pad. Slowly adapting fibres coded best those stimulus combinations with a stimulus temporal frequency in the range 20-60 Hz, rapidly adapting fibres coded best those with frequencies of 60-200 Hz, and Pacinian fibres best defined those stimuli with a high temporal frequency (100-300 Hz). 5. Applying the moving grating to the skin with varying radial forces in the range 20-60 g wt. did not greatly modify the pattern of discharge in the responding fibre populations.

Action Potentials