A Donders' Like Law for Arm Movements: The Signal not the Noise.

Experiments were done to determine whether the starting position of the arm influences its final configuration (posture) when pointing to, or grasping, targets located within the common workspace of the arm. Subjects were asked to point to, or grasp, each of six targets from five, or seven, widely spaced starting positions. We found that the variability (standard deviation) of the arm's configuration, measured as the angle of inclination of the plane delimited by the arm and forearm, averaged about 4° for comfortable speed pointing movements and was only slightly higher for fast pointing movements. Comfortable speed reaches to grasp the targets were associated with slightly lower variability (3.5°) in final arm configuration. The average variability of repeated movements to a given target from a single start position (3.5°) was comparable to that of movements from different start positions to the same target (4.2°). A small difference in final arm inclination angle, averaged across all subjects and targets, of 3° was found between two pairs of starting positions. This small and possibly idiosyncratic effect is within the "noise" of final arm orientation variability for repeated movements (i.e., 3.5°). Thus, the variability of final posture is not for the most part due to different start positions, it is inherent to movement per se. Our results reconcile conflicting previous studies and are consistent with past works suggesting that a Donders' like law is indeed largely upheld for unconstrained visually guided arm movements. In summary, considering movements within a typical work space, when the hand is moved voluntarily to a given spatial location the posture of the arm is nearly the same regardless of its starting position. Importantly, variability is inherent to the rule.

Sensorimotor cortex injury effects on recovery of contralesional dexterous movements in Macaca mulatta.

The effects of primary somatosensory cortex (S1) injury on recovery of contralateral upper limb reaching and grasping were studied by comparing the consequences of isolated lesions to the arm/hand region of primary motor cortex (M1) and lateral premotor cortex (LPMC) to lesions of these same areas plus anterior parietal cortex (S1 and rostral area PE). We used multiple linear regression to assess the effects of gray and white matter lesion volumes on deficits in reaching and fine motor performance during the first month after the lesion, and during recovery of function over 3, 6 and 12months post-injury in 13 monkeys. Subjects with frontoparietal lesions exhibited larger deficits and poorer recovery as predicted, including one subject with extensive peri-Rolandic injury developing learned nonuse after showing signs of recovery. Regression analyses showed that total white matter lesion volume was strongly associated with initial post-lesion deficits in motor performance and with recovery of skill in reaching and manipulation. Multiple regression analyses using percent damage to caudal M1 (M1c), rostral S1 (S1r), LPMC and area PE as predictor variables showed that S1r lesion volumes were closely related to delayed post-lesion recovery of upper limb function, as well as lower skill level of recovery. In contrast, M1c lesion volume was related primarily to initial post-lesion deficits in hand motor performance. Overall, these findings demonstrate that frontoparietal injury impairs hand motor function more so than frontal motor injury alone, and results in slower and poorer recovery than lesions limited to frontal motor cortex.

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.

Volumetric effects of motor cortex injury on recovery of ipsilesional dexterous movements.

Damage to the motor cortex of one hemisphere has classically been associated with contralateral upper limb paresis, but recent patient studies have identified deficits in both upper limbs. In non-human primates, we tested the hypothesis that the severity of ipsilesional upper limb motor impairment in the early post-injury phase depends on the volume of gray and white matter damage of the motor areas of the frontal lobe. We also postulated that substantial recovery would accompany minimal task practice and that ipsilesional limb recovery would be correlated with recovery of the contralesional limb. Gross (reaching) and fine hand motor functions were assessed for 3-12 months post-injury using two motor tests. Volumes of white and gray matter lesions were assessed using quantitative histology. Early changes in post-lesion motor performance were inversely correlated with white matter lesion volume indicating that larger lesions produced greater decreases in ipsilesional hand movement control. All monkeys showed improvements in ipsilesional hand motor skill during the post-lesion period, with reaching skill improvements being positively correlated with total lesion volume indicating that larger lesions were associated with greater ipsilesional motor skill recovery. We suggest that reduced trans-callosal inhibition from the lesioned hemisphere may play a role in the observed skill improvements. Our findings show that significant ipsilesional hand motor recovery is likely to accompany injury limited to frontal motor areas. In humans, more pronounced ipsilesional motor deficits that invariably develop after stroke may, in part, be a consequence of more extensive subcortical white and gray matter damage.

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.

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.

Selective long-term reorganization of the corticospinal projection from the supplementary motor cortex following recovery from lateral motor cortex injury.

Brain injury affecting the frontal motor cortex or its descending axons often causes contralateral upper extremity paresis. Although recovery is variable, the underlying mechanisms supporting favorable motor recovery remain unclear. Because the medial wall of the cerebral hemisphere is often spared following brain injury and recent functional neuroimaging studies in patients indicate a potential role for this brain region in the recovery process, we investigated the long-term effects of isolated lateral frontal motor cortical injury on the corticospinal projection (CSP) from intact, ipsilesional supplementary motor cortex (M2). After injury to the arm region of the primary motor (M1) and lateral premotor (LPMC) cortices, upper extremity recovery is accompanied by terminal axon plasticity in the contralateral CSP but not the ipsilateral CSP from M2. Furthermore, significant contralateral plasticity occurs only in lamina VII and dorsally within lamina IX. Thus, selective intraspinal sprouting transpires in regions containing interneurons, flexor-related motor neurons, and motor neurons supplying intrinsic hand muscles, which all play important roles in mediating reaching and digit movements. After recovery, subsequent injury of M2 leads to reemergence of hand motor deficits. Considering the importance of the CSP in humans and the common occurrence of lateral frontal cortex injury, these findings suggest that spared supplementary motor cortex may serve as an important therapeutic target that should be considered when designing acute and long-term postinjury patient intervention strategies aimed to enhance the motor recovery process following lateral cortical trauma.

Volumetric effects of motor cortex injury on recovery of dexterous movements.

Due to the heterogeneous nature of most brain injuries, the contributions of gray and white matter involvement to motor deficits and recovery potential remain obscure. We tested the hypothesis that duration of hand motor impairment and recovery of skilled arm and hand motor function depends on the volume of gray and white matter damage of the frontal lobe. Lesions of the primary motor cortex (M1), M1 + lateral premotor cortex (LPMC), M1 + LPMC + supplementary motor cortex (M2) or multifocal lesions affecting motor areas and medial prefrontal cortex were evaluated in rhesus monkeys. Fine hand motor function was quantitatively assessed pre-lesion and for 3-12 months post-lesion using two motor tests. White and gray matter lesion volumes were determined using histological and quantitative methods. Regression analyses showed that duration of fine hand motor impairment was strongly correlated (R(2)>0.8) with the volume of gray and white matter lesions, with white matter lesion volume being the primary predictor of impairment duration. Level of recovery of fine hand motor skill was also well correlated (R(2)>0.5) with gray and white matter lesion volume. In some monkeys post-lesion skill exceeded pre-lesion skill in one or both motor tasks demonstrating that continued post-injury task practice can improve motor performance after localized loss of frontal motor cortex. These findings will assist in interpreting acute motor deficits, predicting the time course and expected level of functional recovery, and designing therapeutic strategies in patients with localized frontal lobe injury or neurosurgical resection.

Predictors of subjective cognitive difficulties in older adults with atherosclerotic vascular disease.

OBJECTIVE: The objective of this study was to describe the relationship among cognitive test performance, psychological symptoms, and subjective cognitive difficulties in older adults with atherosclerotic vascular disease. METHOD: Participants were 80 adults over the age of 55 with an unequivocal diagnosis of atherosclerotic vascular disease. Participants completed measures of neuropsychological functioning, psychological symptoms, and two measures of subjective cognitive difficulties. RESULTS: Psychological symptoms were most strongly associated with higher levels of reported cognitive difficulties. Overall neuropsychological functioning was modestly related to subjective cognitive difficulties but did not remain significant after controlling for psychological symptoms. CONCLUSIONS: In this sample of older adults with atherosclerotic vascular disease, self-reported cognitive difficulties were most strongly related to overall level of psychological distress and not to actual cognitive test scores. Therefore, psychological factors may play an important role in the phenomenon of self-perceived cognitive decline in geriatric populations.

Neuropsychological performance is associated with vascular function in patients with atherosclerotic vascular disease.

OBJECTIVE: We previously reported preliminary data (N=14) demonstrating a significant and positive relationship between forearm vascular function and neuropsychological performance in individuals with atherosclerotic vascular disease (AVD). The current study was conducted to confirm and extend those findings in a much larger, nonoverlapping sample. METHODS AND RESULTS: Participants were 82 individuals with AVD, with no history of stroke, cardiac surgery, or dementia. Forearm vascular function was measured before and after brachial artery infusion of vasoactive agents (acetylcholine, nitroprusside, verapamil). Neuropsychological functioning was assessed with the Repeatable Battery for the Assessment of Neuropsychological Status. Statistical analysis included multiple regression and partial correlations, controlling for education. Vascular function was significantly and positively associated with neuropsychological performance [R2 change = 0.116, F change (3,74) = 3.72, P = 0.015]. Follow-up analyses indicated that smooth muscle function was the aspect of vascular function most strongly associated with neuropsychological performance. Individual vascular risk factors were not significantly associated with neuropsychological performance when controlling for vascular function. CONCLUSIONS: Better vascular function is significantly associated with better neuropsychological performance in individuals with AVD. It is possible that this relationship exists in healthy elderly individuals as well, although this cannot be determined based on the existing data, because a healthy comparison group was not studied. With additional research, measures of vascular function might be useful in the early identification of individuals who are at greatest risk for developing vascular cognitive impairment.