Proprioceptive acuity for landmarks on the hand and digits.

Previous work using visually guided reaches to localize landmarks on a hidden hand has suggested that proprioceptive acuity for hand targets is low and representation of hand dimensions is highly distorted (e.g., hand width estimated to be 60% wider than actual hand width). We re-examined these issues using a pure proprioceptive task in which 20 blindfolded subjects reached in a single movement without terminal corrections to touch the right index-tip to landmarks of the left hand placed in various locations in 3D space. Subjects were also tested with vision allowed to estimate minimal errors. Based on previous reports of high proprioceptive acuity for some hand landmarks, we hypothesized that the proprioceptive representation of the hand was much less distorted than described previously and that errors were not correlated with target hand location. Mean distance errors in proprioceptively guided reaches to the landmarks averaged less than 3 cm and were only 0.5-1.3 cm larger than when vision was allowed. Errors were not correlated with hand location in most subjects. Distortions of hand width averaged less than 20% wider than actual width and were not correlated with hand location in most subjects. We conclude that relatively accurate proprioceptive awareness of locations of hand/digit structures and dimensions is available for use in control of hand movements, which are executed largely subconsciously. Studying acuity of proprioception using conscious perceptual tasks and involving vision may not provide accurate measures of proprioceptive acuity as used by the motor system.

Cerebellar Contributions to Motor Impairments in People with Multiple Sclerosis.

Although Charcot characterized classic cerebellar symptoms in people with multiple sclerosis (PwMS) in 1877, the impact of cerebellar dysfunction on MS symptoms has predominately been evaluated in the last two decades. Recent studies have clearly demonstrated the association between cerebellar pathology, including atrophy and reduced fractional anisotropy in the peduncles, and motor impairments, such as reduced gait velocity and time to complete walking tasks. However, future studies using novel imaging techniques are needed to elucidate all potential pathophysiology that is associated with disability in PwMS. Additionally, future studies are required to determine the most effective treatments for motor impairments in PwMS, including the specific type and duration of exercise interventions, and potential means to amplify their effects, such as transcranial direct current stimulation (tDCS). This mini-review critically discusses the distinct role of cerebellar dysfunction in motor impairments in PwMS, potential treatments, and directions for future studies.

High proprioceptive acuity in slow and fast hand movements.

We can accurately reach to touch our index fingertip to various points on the body without vision. Awareness of location/motion of the index fingertip and other body parts through proprioception is required for such movements. Proprioception involves processing sensory information, but it is also debated whether internal model estimates of body state from motor commands improve proprioception. We tested the hypothesis that proprioceptive errors increase with increases in speed of hand movement and whether an internal model contributes to more accurate proprioception, especially in higher speed movements. Ten subjects made voluntary reaching movements with their dominant arm to touch its index-tip to the index-tip of the non-dominant arm that was moved passively or actively at three speeds (slow, comfortable, fast) in various directions. Four conditions required the experimenter to passively move the subject's target arm at slow, comfortable and fast speeds and in different directions. A fifth condition required the subject to actively move both arms to perform the task. Subjects performed these tasks with high accuracy during slow and comfortable speed movements of the target arm. Errors averaged 3.7 mm larger when the target was moved faster and were equivalent to errors for slower movements (p < 0.014). Errors in the active and passive target movement conditions were also equivalent (p < 0.001). These findings show that proprioception is accurate across many different speeds of passive and active target motion and that there was no evidence than an internal model contributes to improved accuracy of proprioception during active movements.

Simultaneous Recording of Motor Evoked Potentials in Hand, Wrist and Arm Muscles to Assess Corticospinal Divergence.

The purpose of this study was to further develop methods to assess corticospinal divergence and muscle coupling using transcranial magnetic stimulation (TMS). Ten healthy right-handed adults participated (7 females, age 34.0 ± 12.9 years). Monophasic single pulses were delivered to 14 sites over the right primary motor cortex at 40, 60, 80 and 100% of maximum stimulator output (MSO), using MRI-based neuronavigation. Motor evoked potentials (MEPs) were recorded simultaneously from 9 muscles of the contralateral hand, wrist and arm. For each intensity, corticospinal divergence was quantified by the average number of muscles that responded to TMS per cortical site, coactivation across muscle pairs as reflected by overlap of cortical representations, and correlation of MEP amplitudes across muscle pairs. TMS to each muscle's most responsive site elicited submaximal MEPs in most other muscles. The number of responsive muscles per cortical site and the extent of coactivation increased with increasing intensity (ANOVA, p < 0.001). In contrast, correlations of MEP amplitudes did not differ across the 60, 80 and 100% MSO intensities (ANOVA, p = 0.34), but did differ across muscle pairs (ANOVA, p < 0.001). Post hoc analysis identified 4 sets of muscle pairs (Tukey homogenous subsets, p < 0.05). Correlations were highest for pairs involving two hand muscles and lowest for pairs that included an upper arm muscle. Correlation of MEP amplitudes may quantify varying levels of muscle coupling. In future studies, this approach may be a biomarker to reveal altered coupling induced by neural injury, neural repair and/or motor learning.

Changes in ipsilesional hand motor function differ after unilateral injury to frontal versus frontoparietal cortices in Macaca mulatta.

We tested the hypothesis that injury to frontoparietal sensorimotor areas causes greater initial impairments in performance and poorer recovery of ipsilesional dexterous hand/finger movements than lesions limited to frontal motor areas in rhesus monkeys. Reaching and grasping/manipulation of small targets with the ipsilesional hand were assessed for 6-12 months post-injury using two motor tests. Initial post-lesion motor skill and long-term recovery of motor skill were compared in two groups of monkeys: (1) F2 group-five cases with lesions of arm areas of primary motor cortex (M1) and lateral premotor cortex (LPMC) and (2) F2P2 group-five cases with F2 lesions + lesions of arm areas of primary somatosensory cortex and the anterior portion of area 5. Initial post-lesion reach and manipulation skills were similar to or better than pre-lesion skills in most F2 lesion cases in a difficult fine motor task but worse than pre-lesion skill in most F2P2 lesion cases in all tasks. Subsequently, reaching and manipulation skills improved over the post-lesion period to higher than pre-lesion skills in both groups, but improvements were greater in the F2 lesion group, perhaps due to additional task practice and greater ipsilesional limb use for daily activities. Poorer and slower post-lesion improvement of ipsilesional upper limb motor skill in the F2P2 cases may be due to impaired somatosensory processing. The persistent ipsilesional upper limb motor deficits frequently observed in humans after stroke are probably caused by greater subcortical white and gray matter damage than in the localized surgical injuries studied here.

Hand Motor Recovery Following Extensive Frontoparietal Cortical Injury Is Accompanied by Upregulated Corticoreticular Projections in Monkey.

We tested the hypothesis that arm/hand motor recovery after injury of the lateral sensorimotor cortex is associated with upregulation of the corticoreticular projection (CRP) from the supplementary motor cortex (M2) to the gigantocellular reticular nucleus of the medulla (Gi). Three groups of rhesus monkeys of both genders were studied: five controls, four cases with lesions of the arm/hand area of the primary motor cortex (M1) and the lateral premotor cortex (LPMC; F2 lesion group), and five cases with lesions of the arm/hand area of M1, LPMC, S1, and anterior parietal cortex (F2P2 lesion group). CRP strength was assessed using high-resolution anterograde tracers injected into the arm/hand area of M2 and stereology to estimate of the number of synaptic boutons in the Gi. M2 projected bilaterally to the Gi, primarily targeting the medial Gi subsector and, to a lesser extent, lateral, dorsal, and ventral subsectors. Total CRP bouton numbers were similar in controls and F2 lesion cases but F2P2 lesion cases had twice as many boutons as the other two groups (p = 0.0002). Recovery of reaching and fine hand/digit function was strongly correlated with estimated numbers of CRP boutons in the F2P2 lesion cases. Because we previously showed that F2P2 lesion cases experience decreased strength of the M2 corticospinal projection (CSP), whereas F2 lesion monkeys experienced increased strength of the M2 CSP, these results suggest one mechanism underlying arm/hand motor recovery after F2P2 injury is upregulation of the M2 CRP. This M2-CRP response may influence an important reticulospinal tract contribution to upper-limb motor recovery following frontoparietal injury.SIGNIFICANCE STATEMENT We previously showed that after brain injury affecting the lateral motor cortex controlling arm/hand motor function, recovery is variable and closely associated with increased strength of corticospinal projection (CSP) from an uninjured medial cortical motor area. Hand motor recovery also varies after brain injury affecting the lateral sensorimotor cortex, but medial motor cortex CSP strength decreases and cannot account for recovery. Here we observed that motor recovery following sensorimotor cortex injury is closely associated with increased strength of the descending projection from an uninjured medial cortical motor area to a brainstem reticular nucleus involved in control of arm/hand function, suggesting an enhanced corticoreticular projection may compensate for injury to the sensorimotor cortex to enable recovery of arm/hand motor function.

Recovery of precision grasping after motor cortex lesion does not require forced use of the impaired hand in Macaca mulatta.

We investigated recovery of precision grasping of small objects between the index finger and thumb of the impaired hand without forced use after surgically placed lesions to the hand/arm areas of M1 and M1 + lateral premotor cortex in two monkeys. The unilateral lesions were contralateral to the monkey's preferred hand, which was established in prelesion testing as the hand used most often to acquire raisins in a foraging board (FB) task in which the monkey was free to use either hand to acquire treats. The lesions initially produced a clear paresis of the contralesional hand and use of only the ipsilesional hand to acquire raisins in the FB task. However, beginning about 3 weeks after the lesion both monkeys spontaneously began using the impaired contralesional hand in the FB task and increased use of that hand over the next few tests. Moreover, the monkeys clearly used precision grasp to acquire the raisins in a similar manner to prelesion performances, although grasp durations were longer. Although the monkeys used the contralesional hand more often than the ipsilesional hand in some postlesion testing sessions, they did not recover to use the hand as often as in prelesion testing when the preferred hand was used almost exclusively. These findings suggest that recovery of fine hand/digit motor function after localized damage to the lateral frontal motor areas in rhesus monkeys does not require forced use of the impaired hand.

Pointing to oneself: active versus passive proprioception revisited and implications for internal models of motor system function.

We re-examined the issue of active versus passive proprioception to more fully characterize the accuracy afforded by proprioceptive information in natural, unconstrained, movements in 3-dimensions. Subjects made pointing movements with their non-dominant arm to various locations with eyes closed. They then proprioceptively localized the tip of its index finger with a prompt pointing movement of their dominant arm, thereby bringing the two indices in apposition. Subjects performed this task with remarkable accuracy. More remarkably, the same subjects were equally accurate at localizing the index finger when the arm was passively moved and maintained in its final position by an experimenter. Two subjects were also tested with eyes open, and they were no more accurate than with eyes closed. We also found that the magnitude of the error did not depend on movement duration, which is contrary to a key observation in support of the existence of an internal forward model-based state-reconstruction scheme. Three principal conclusions derive from this study. First, in unconstrained movements, proprioceptive information provides highly accurate estimates of limb position. Second, so-called active proprioception does not provide better estimates of limb position than passive proprioception. Lastly, in the active movement condition, an internal model-based estimation of limb position should, according to that hypothesis, have occurred throughout the movement. If so, it did not lead to a better estimate of final limb position, or lower variance of the estimate, casting doubt on the necessity to invoke this hypothetical construct.

Laterality affects spontaneous recovery of contralateral hand motor function following motor cortex injury in rhesus monkeys.

The purpose of this study was to test whether brain laterality influences spontaneous recovery of hand motor function after controlled brain injuries to arm areas of M1 and lateral premotor cortex (LPMC) of the hemisphere contralateral to the preferred hand in rhesus monkeys. We hypothesized that monkeys with stronger hand preference would exhibit poorer recovery of skilled hand use after such brain injury. Degree of handedness was assessed using a standard dexterity board task in which subjects could use either hand to retrieve small food pellets. Fine hand/digit motor function was assessed using a modified dexterity board before and after the M1 and LPMC lesions in ten monkeys. We found a strong negative relationship between the degree of handedness and the recovery of manipulation skill, demonstrating that higher hand preference was associated with poorer recovery of hand fine motor function. We also observed that monkeys with larger lesions within M1 and LPMC had greater initial impairment of manipulation and poorer recovery of reaching skill. We conclude that monkeys with a stronger hand preference are likely to show poorer recovery of contralesional hand fine motor skill after isolated brain lesions affecting the lateral frontal motor areas. These data may be extended to suggest that humans who exhibit weak hand dominance, and perhaps individuals who use both hands for fine motor tasks, may have a more favorable potential for recovery after a unilateral stroke or brain injury affecting the lateral cortical motor areas than individuals with a high degree of hand dominance.

Acuity of Proprioceptive Localization Varies with Body Region.

We accurately sense locations of objects touching various points on the body and, if they are irritants, make accurate rapid movements to remove them. Such movements require accurate proprioception of orientation and motion of the reaching limb and of the target. However, it is unknown whether acuity of these sensations is similar for different points on the body. We investigated accuracy of comfortable speed reaching movements of the right index-tip by 10 subjects (five females) to touch 12 different body locations with and without vision with the body part stationary in different locations and moving in different directions. Reaching movements to points on the face/head and trunk had mean errors averaging less than 0.2 cm greater than under vision conditions. Mean errors for reaches to touch points on the left arm and digits were less accurate (p < 0.05), but average less than 1 cm relative to vision conditions. Mean errors for reaches to touch points on the left lower limb were least accurate (p < 0.05), with mean errors averaging 1.5-3.1 cm relative to movements made with vision. We conclude that there is high proprioceptive acuity for locations of points on axial structures and the left upper limb including the digits, which contrasts with previous reports of greatly distorted proprioceptive maps of the face/head and hand. Apparently low proprioceptive acuity for points on the leg may be task sensitive as many lower limb motor tasks can be performed accurately without vision.

Terminal organization of the corticospinal projection from the arm/hand region of the rostral primary motor cortex (M1r or old M1) to the cervical enlargement (C5-T1) in rhesus monkey.

High-resolution anterograde tracers and stereology were used to study the terminal organization of the corticospinal projection (CSP) from the rostral portion of the primary motor cortex (M1r) to spinal levels C5-T1. Most of this projection (90%) terminated contralaterally within laminae V-IX, with the densest distribution in lamina VII. Moderate bouton numbers occurred in laminae VI, VIII, and IX with few in lamina V. Within lamina VII, labeling occurred over the distal-related dorsolateral subsectors and proximal-related ventromedial subsectors. Within motoneuron lamina IX, most terminations occurred in the proximal-related dorsomedial quadrant, followed by the distal-related dorsolateral quadrant. Segmentally, the contralateral lamina VII CSP gradually declined from C5-T1 but was consistently distributed at C5-C7 in lamina IX. The ipsilateral CSP ended in axial-related lamina VIII and adjacent ventromedial region of lamina VII. These findings demonstrate the M1r CSP influences distal and proximal/axial-related spinal targets. Thus, the M1r CSP represents a transitional CSP, positioned between the caudal M1 (M1c) CSP, which is 98% contralateral and optimally organized to mediate distal upper extremity movements (Morecraft et al., 2013), and dorsolateral premotor (LPMCd) CSP being 79% contralateral and optimally organized to mediate proximal/axial movements (Morecraft et al., 2019). This distal to proximal CSP gradient corresponds to the clinical deficits accompanying caudal to rostral motor cortex injury. The lamina IX CSP is considered in the light of anatomical and neurophysiological evidence which suggests M1c gives rise to the major proportion of the cortico-motoneuronal (CM) projection, while there is a limited M1r CM projection.

Diet-induced changes in functional disability are mediated by fatigue in relapsing-remitting multiple sclerosis: A secondary analysis of the WAVES randomized parallel-arm trial.

Background: People with multiple sclerosis (MS) often report dietary modifications; however, evidence on functional outcomes remains sparse. Objective: Evaluate the impact of the low-saturated fat (Swank) and modified Paleolithic elimination (Wahls) diets on functional disability among people with relapsing-remitting MS. Methods: Baseline-referenced MS functional composite (MSFC) scores were calculated from nine-hole peg-test (NHPT), timed 25-foot walk, and oral symbol digit modalities test (SDMT-O) collected at four study visits: (a) run-in, (b) baseline, (c) 12 weeks, and (d) 24 weeks. Participants were observed at run-in and then randomized at baseline to either the Swank (n = 44) or Wahls (n = 43) diets. Results: Among the Swank group, MSFC scores significantly increased from -0.13 ± 0.14 at baseline to 0.10 ± 0.11 at 12 weeks (p = 0.04) and 0.14 ± 0.11 at 24 weeks (p = 0.02). Among the Wahls group, no change in MSFC scores was observed at 12 weeks from 0.10 ± 0.11 at baseline but increased to 0.28 ± 0.13 at 24 weeks (p = 0.002). In both groups, NHPT and SDMT-O z-scores increased at 24 weeks. Changes in MSFC and NHPT were mediated by fatigue. Discussion: Both diets reduced functional disability as mediated by fatigue. Trial Registration: Clinicaltrials.gov Identifier: NCT02914964.

Functional recovery following motor cortex lesions in non-human primates: experimental implications for human stroke patients.

This review discusses selected classical works and contemporary research on recovery of contralesional fine hand motor function following lesions to motor areas of the cerebral cortex in non-human primates. Findings from both the classical literature and contemporary studies show that lesions of cortical motor areas induce paresis initially, but are followed by remarkable recovery of fine hand/digit motor function that depends on lesion size and post-lesion training. Indeed, in recent work where considerable quantification of fine digit function associated with grasping and manipulating small objects has been observed, very favorable recovery is possible with minimal forced use of the contralesional limb. Studies of the mechanisms underlying recovery have shown that following small lesions of the digit areas of primary motor cortex (M1), there is expansion of the digit motor representations into areas of M1 that did not produce digit movements prior to the lesion. However, after larger lesions involving the elbow, wrist and digit areas of M1, no such expansion of the motor representation was observed, suggesting that recovery was due to other cortical or subcortical areas taking over control of hand/digit movements. Recently, we showed that one possible mechanism of recovery after lesion to the arm areas of M1 and lateral premotor cortex is enhancement of corticospinal projections from the medially located supplementary motor area (M2) to spinal cord laminae containing neurons which have lost substantial input from the lateral motor areas and play a critical role in reaching and digit movements. Because human stroke and brain injury patients show variable, and usually poorer, recovery of hand motor function than that of nonhuman primates after motor cortex damage, we conclude with a discussion of implications of this work for further experimentation to improve recovery of hand function in human stroke patients.

Proprioceptive Acuity is Enhanced During Arm Movements Compared to When the Arm is Stationary: A Study of Young and Older Adults.

Proprioception in old age is thought to be poorer due to degeneration of the central (CNS) and peripheral nervous systems (PNS). We tested whether community-dwelling older adults (65-83 years) make larger proprioceptive errors than young adults (18-22 years) using a natural reaching task. Subjects moved the right arm to touch the index fingertip to the stationary or moving left index fingertip. The range of locations of the target index fingertip was large, sampling the natural workspace of the human arm. The target arm was moved actively by the subject or passively by the experimenter and reaching arm movements towards the target were made under visual guidance, or with vision blocked (proprioceptive guidance). Subjects did not know the direction or speed of upcoming target hand motion in the passive conditions. Mean 3D distance errors between the right and left index finger tips were small in both groups and only slightly larger when vision was blocked than when allowed, but averaged 2-5 mm larger in older than in younger adults in moving (p = 0.002) and stationary (p = 0.07) conditions, respectively. Variable errors were small and similar in the two groups (p > 0.35). Importantly, clearly larger errors were observed for reaching to the stationary than to the moving index fingertip in both groups, demonstrating that dynamic proprioceptive information during movement permits more accurate localization of the endpoint of the moving arm. This novel finding demonstrates the importance of dynamic proprioceptive information in movement guidance and bimanual coordination.

Greater Reduction in Contralesional Hand Use After Frontoparietal Than Frontal Motor Cortex Lesions in Macaca mulatta.

We previously reported that rhesus monkeys recover spontaneous use of the more impaired (contralesional) hand following neurosurgical lesions to the arm/hand representations of primary motor cortex (M1) and lateral premotor cortex (LPMC) (F2 lesion) when tested for reduced use (RU) in a fine motor task allowing use of either hand. Recovery occurred without constraint of the less impaired hand and with occasional forced use of the more impaired hand, which was the preferred hand for use in fine motor tasks before the lesion. Here, we compared recovery of five F2 lesion cases in the same RU test to recovery after unilateral lesions of M1, LPMC, S1 and anterior portion of parietal cortex (F2P2 lesion - four cases). Average and highest %use of the contralesional hand in the RU task in F2 cases were twice that in F2P2 cases (p < 0.05). Recovery in the RU task was closely associated with volume and percentage of lesion to caudal (new) M1 (M1c) in both F2 and F2P2 lesion cases. One F2P2 case, with the largest M1c lesion and a large rostral somatosensory cortex (S1r) lesion developed severe contralesional hand non-use despite exhibiting some recovery of fine motor function initially. We conclude that the degree of reduced use of the contralesional hand is primarily related to the volume of M1c injury and that severe non-use requires extensive injury to M1c and S1r. Thus, assessing peri-Rolandic injury extent in stroke patients may have prognostic value for predicting susceptibility to RU and non-use in rehabilitation.

Impact of the Swank and Wahls elimination dietary interventions on fatigue and quality of life in relapsing-remitting multiple sclerosis: The WAVES randomized parallel-arm clinical trial.

OBJECTIVE: To compare the effect of the modified Paleolithic elimination (Wahls) and low-saturated fat (Swank) diets in relapsing-remitting MS (RRMS). METHODS: Individuals (n = 87) with RRMS were randomized to the Swank or Wahls diets in a parallel group clinical trial consisting of four timepoints: 1) run-in, 2) baseline, 3) 12-weeks, and 4) 24-weeks. RESULTS: 77 participants completed 12 weeks and 72 completed 24 weeks. The 12-week change from baseline in fatigue was -0.94 ± 0.18 (FSS) and -9.87 ± 1.93 (MFIS; both p < 0.0001) for Swank, and -0.71 ± 0.24 (FSS; p = 0.004) and -14.41 ± 2.22 (MFIS; p ≤ 0.0001) for Wahls. Physical MSQoL scores improved by 6.04 ± 2.18 (p = 0.006) for Swank and by 14.5 ± 2.63 (p < 0.0001) for Wahls. Mental MSQoL scores improved by 11.3 ± at 2.79 (p < 0.0001) for Wahls while the Swank did not change (3.85 ± 2.63; p = 0.14). Neither group showed significant changes in 6-minute walking distance at 12 weeks. All outcomes were maintained or further improved at 24 weeks. CONCLUSIONS: Both diets were associated with clinically meaningful within-group reductions in fatigue and improvements in QoL.Trial Registration: Clinicaltrials.gov Identifier: NCT02914964.

Slowing of dexterous manipulation in old age: force and kinematic findings from the 'nut-and-rod' task.

The task of sliding a nut from a rod has been used to study manual slowing in old age (Smith et al. in Neurology 53:1458-1461, 1999; Neurobiol Aging 26:883-890, 2005). In this experiment, we sought to determine if the age-related slowing in this task occurs with losses of motor precision, as indicated by the forces exerted on the rod. The forces exerted by the nut on the rod were monitored along with the kinematics of the hand in old and young adults while they attempted to lift a nut from three vertically oriented rods of different shape (straight, single curve, double curve). Old adults performed the task 64% slower than young adults for the straight rod, 100% slower for the single-curve rod, and 80% slower for the double-curve rod. Old adults did not differ from the young adults in the amount of force exerted against the rods in the horizontal plane, or in the steadiness of these forces, but exerted greater force impulses in the vertical direction over the course of a trial (359% straight, 236% single curve, 214% double curve) and much more force in the vertical direction (255% straight, 267% single curve, 159% double curve). Old adults also performed the task with 35% greater average roll of the hand into pronation. We suspect that old adults tilted the nut, even for the straight rod, dragging it against the rod to create the elevated vertical forces. These observations support previous speculation that old adults do not control the external moments applied to grasped objects as well as young adults.

Minimal forced use without constraint stimulates spontaneous use of the impaired upper extremity following motor cortex injury.

The purpose of this study was to determine if recovery of neurologically impaired hand function following isolated motor cortex injury would occur without constraint of the non-impaired limb, and without daily forced use of the impaired limb. Nine monkeys (Macaca mulatta) received neurosurgical lesions of various extents to arm representations of motor cortex in the hemisphere contralateral to the preferred hand. After the lesion, no physical constraints were placed on the ipsilesional arm/hand and motor testing was carried out weekly with a maximum of 40 attempts in two fine motor tasks that required use of the contralesional hand for successful food acquisition. These motor tests were the only "forced use" of the contralesional hand. We also tested regularly for spontaneous use of the contralesional hand in a fine motor task in which either hand could be used for successful performance. This minimal intervention was sufficient to induce recovery of the contralesional hand to such a functional level that eight of the monkeys chose to use that hand on some trials when either hand could be used. Percentage use of the contralesional hand (in the task when either hand could be used) varied considerably among monkeys and was not related to lesion volume or recovery of motor skill. These data demonstrate a remarkable capacity for recovery of spontaneous use of the impaired hand following localized frontal lobe lesions. Clinically, these observations underscore the importance of therapeutic intervention to inhibit the induction of the learned nonuse phenomenon after neurological injury.

Terminal organization of the corticospinal projection from the lateral premotor cortex to the cervical enlargement (C5-T1) in rhesus monkey.

High-resolution tract tracing and stereology were used to study the terminal organization of the corticospinal projection (CSP) from the ventral (v) and dorsal (d) regions of the lateral premotor cortex (LPMC) to spinal levels C5-T1. The LPMCv CSP originated from the postarcuate sulcus region, was bilateral, sparse, and primarily targeted the dorsolateral and ventromedial sectors of contralateral lamina VII. The convexity/lateral part of LPMCv did not project below C2. Thus, very little LPMCv corticospinal output reaches the cervical enlargement. In contrast, the LPMCd CSP was 5× more prominent in terminal density. Bilateral terminal labeling occurred in the medial sectors of lamina VII and adjacent lamina VIII, where propriospinal neurons with long-range bilateral axon projections reside. Notably, lamina VIII also harbors axial motoneurons. Contralateral labeling occurred in the lateral sectors of lamina VII and the dorsomedial quadrant of lamina IX, noted for harboring proximal upper limb flexor motoneurons. Segmentally, the CSP to contralateral laminae VII and IX preferentially innervated C5-C7, which supplies shoulder, elbow, and wrist musculature. In contrast, terminations in axial-related lamina VIII were distributed bilaterally throughout all cervical enlargement levels, including C8 and T1. These findings demonstrate the LPMCd CSP is structured to influence axial and proximal upper limb movements, supporting Kuypers conceptual view of the LPMCd CSP being a major component of the medial motor control system. Thus, distal upper extremity control influenced by LPMC, including grasping and manipulation, must occur through indirect neural network connections such as corticocortical, subcortical, or intrinsic spinal circuits.

Perception of hand motion direction uses a gravitational reference.

We studied possible frames of reference for kinesthetic perception of imposed hand motion direction in the frontal plane in ten young adult subjects with no history of neuromuscular disease. In one experiment, subjects were instructed to set unseen hand motion imposed by a motorized linear slide device parallel to the trunk-fixed longitudinal axis, seven visually specified axes and vertical (gravitational axis) while in a standard erect head/trunk posture and with head/trunk orientation varied. The visually specified axes were presented on a head-mounted display that also blocked vision of the external environment. In a second experiment using the same device, subjects set unseen hand motion parallel to vertical and to subjective oblique directions of 45 degrees clockwise (cw) and counter clockwise (ccw) from vertical in erect and varied head/trunk postures. Errors for setting hand motion to vertical and to verbally specified oblique axes (45 degrees cw and ccw from vertical) were lower than to the trunk longitudinal axis and visually specified axes. There were clear oblique effects in setting hand motion to visually specified axes and to subjective oblique (45 degrees cw and ccw) axes. When head and trunk orientation were varied, variable errors were higher for all axes, but remained lowest for vertical and subjective oblique axes. Moreover, errors for setting hand motion to all axes depended on head/trunk orientation. Overall, these results show that kinesthetic perception of imposed hand motion uses a subjective gravitational frame of reference that varies somewhat with head/trunk orientation.