[Show abstract][Hide abstract] ABSTRACT: 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.
Experimental Brain Research 08/2014; 232(12). DOI:10.1007/s00221-014-4068-9 · 2.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Experimental Brain Research 05/2013; 228(1). DOI:10.1007/s00221-013-3533-1 · 2.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: Experimental techniques allowing longitudinal studies of vascular disease progression or treatment effects are not readily available for most animal models. Thus, most existing studies are destined to either study individual time points or use large cohorts of animals. Here we describe a noninvasive technique for studying vascular disease that is based on in vivo imaging of the long posterior ciliary artery (LPCA) in the iris of albino rats. Using a slit-lamp biomicroscope, images of the LPCA were taken weekly in conscious normotensive Wistar Kyoto rats (WKY, n = 10) and spontaneously hypertensive rats (SHR, n = 10) for 10 wk. Using imaging software, we found that lumen diameter was significantly smaller and the wall-to-lumen (W/L) ratio larger in SHR than in WKY. Wall thickness was not different. Blood pressure correlated with the W/L ratio. Histology of the abdominal aorta also revealed a smaller lumen diameter and greater W/L ratio in SHR compared with WKY. Corneal application of the muscarinic receptor agonist pilocarpine elicited a dose-dependent vasodilation of the LPCA that could be antagonized by inhibition of nitric oxide synthase, suggesting that the pilocarpine response is mainly mediated by endothelium-derived nitric oxide. Consistent with endothelial dysfunction in SHR, pilocarpine-induced vasodilation was greater in WKY rats than in SHR. These findings indicate that in vivo imaging of the LPCA allows assessment of several structural and functional vascular parameters in conscious rats and that the LPCA responds to disease insults and pharmacologic treatments in a fashion that will make it a useful model for further studies.
[Show abstract][Hide abstract] ABSTRACT: 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.
Experimental Brain Research 05/2010; 202(3):529-42. DOI:10.1007/s00221-010-2157-y · 2.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
The Journal of Comparative Neurology 03/2010; 518(5):586-621. DOI:10.1002/cne.22218 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: Cerebrovascular myogenic function, which protects the brain from hemorrhagic stroke, is impaired in stroke-prone spontaneously hypertensive rats. Furthermore, myogenic function contributes to very low frequency blood pressure variability and dynamic autoregulation of cerebral blood flow is most effective at very low frequency in rats. Therefore, we hypothesized that very low frequency blood pressure variability is reduced in stroke-prone spontaneously hypertensive rats compared with stroke-resistant spontaneously hypertensive rats. In addition, we investigated if myogenic function also contributes to very low frequency blood pressure variability in conscious dogs.
In 8-week-old normotensive Wistar-Kyoto rats, 8-week-old and 15-week-old stroke-prone spontaneously hypertensive rats and stroke-resistant spontaneously hypertensive rats, and dogs, blood pressure variability was studied during control conditions, inhibition of myogenic function (nifedipine) and hypotension induced by sodium nitroprusside. In dogs, transfer function analysis between blood pressure and total peripheral resistance was performed to study the contribution of myogenic function to blood pressure variability.
Inhibition of myogenic function, but not hypotension induced by sodium nitroprusside, significantly reduced very low frequency variability of systolic blood pressure (rats: 0.02-0.2 Hz; dogs: 0.02-0.075 Hz) in conscious rats and dogs. In dogs, the gain of the transfer function was high (0.28 +/- 0.04 min/l) in the very low frequency band and was decreased to 0.11 +/- 0.01 min/l (P < 0.05) by nifedipine but not by sodium nitroprusside (0.26 +/- 0.02 min/l). Very low frequency blood pressure variability was significantly smaller in stroke-prone spontaneously hypertensive rats than in stroke-resistant spontaneously hypertensive rats (8 weeks of age: 7.8 +/- 1.1 vs. 13.1 +/- 2.2 mmHg; P < 0.05; 15 weeks of age: 7.1 +/- 1.2 vs. 16.5 +/- 3.6 mmHg; P < 0.05).
Myogenic function affects very low frequency blood pressure variability in conscious rats and dogs. The smaller very low frequency blood pressure variability in stroke-prone spontaneously hypertensive rats compared with stroke-resistant spontaneously hypertensive rats suggests that impaired cerebrovascular myogenic function is reflected in reduced very low frequency blood pressure variability.
Journal of Hypertension 07/2008; 26(6):1127-37. DOI:10.1097/HJH.0b013e3282fb81c8 · 4.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study investigated the relationship between hand preference and motor learning in rhesus monkeys executing fine manipulation tasks. We hypothesized that the differences in skill level of the two hands before and after task practice will strongly correlate with the magnitude of the handedness index. Subjects were male and female adult rhesus monkeys (Macaca mulatta). Preferred hand and degree of hand preference were assessed using a handedness index computed based on the percentage of initial reaches and successful acquisitions for each hand using a dexterity (Klüver) board task in which the monkeys could reach for food pellets with either hand. After assessing hand preference, monkeys were trained in two tasks using each hand without the need for restraint. These tasks were: (1) a modified movement assessment panel in which the monkey grasped and lifted carrot chips (with a central punched hole) from a flat surface and over straight and curved rods and (2) a modified dexterity board (mDB) in which the monkey grasped small food pellets from different diameter wells with 3D video recordings of hand/finger movements. Training sessions occurred on approximately a weekly basis. Performance scores on each trial for each task were computed based on acquisition success in addition to duration and size of applied 3D forces for the mMAP task and number of manipulation attempts, transport and manipulation duration, grip aperture and accuracy of hand transport in the mDB task. Learning was assessed by fitting Boltzmann equation sigmoidal curves to performance scores from the initial through final training sessions. Results in 7 monkeys showed that there were no preferred vs. non-preferred hand differences in learning the mDB task, perhaps because of previous experience with this task during determination of handedness. Surprisingly, the non-preferred hand exhibited somewhat greater learning on the mMAP task. These results support previous work suggesting that there is less evidence of hand/cerebral dominance in rhesus monkeys than in humans. Support Contributed By: NIH R01 NS 04636, NIH R24 HD 39627, S. Dakota SCI-TBI grant
[Show abstract][Hide abstract] ABSTRACT: A modified "Klüver" or dexterity board was developed to assess fine control of hand and digit movements by nonhuman primates during the acquisition of small food pellets from wells of different diameter. The primary advantages of the new device over those used previously include standardized positioning of target food pellets and controlled testing of each hand without the need for restraints, thereby allowing the monkey to move freely about the cage. Three-dimensional video analysis of hand motion was used to provide measures of reaching accuracy and grip aperture, as well as temporal measures of reach duration and food-pellet manipulation. We also present a validated performance score based on these measures, which serves as an indicator of successful food-pellet retrieval. Tests in three monkeys show that the performance score is an effective measure with which to study fine motor control associated with learning and handedness. We also show that the device and performance scores are effective for differentiating the effects of localized injury to motor areas of the cerebral cortex.
Journal of Neurophysiology 09/2007; 98(2):1015-29. DOI:10.1152/jn.00354.2007 · 2.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The mechanisms generating high- frequency (HF) and low-frequency (LF) blood pressure variability (BPV) are reasonably well understood. However, little is known about the origin of very low-frequency (VLF) BPV. We tested the hypothesis that VLF BPV is generated by L-type Ca(2+) channel-dependent mechanisms. In conscious rats, arterial blood pressure was recorded during control conditions (n = 8) and ganglionic blockade (n = 7) while increasing doses (0.01-5.0 mg.100 micro l(-1).h(-1)) of the L-type Ca(2+) channel blocker nifedipine were infused intravenously. VLF (0.02-0.2 Hz), LF (0.2-0.6 Hz), and HF (0.6-3.0 Hz) BPV were assessed by spectral analysis of systolic blood pressure. During control conditions, nifedipine caused dose-dependent declines in VLF and LF BPV, whereas HF BPV was not affected. At the highest dose of nifedipine, VLF BPV was reduced by 86% compared with baseline, indicating that VLF BPV is largely mediated by L-type Ca(2+) channel-dependent mechanisms. VLF BPV appeared to be relatively more dependent on L-type Ca(2+) channels than LF BPV because lower doses of nifedipine were required to significantly reduce VLF BPV than to reduce LF BPV. Ganglionic blockade markedly reduced VLF and LF BPV and abolished the nifedipine-induced dose-dependent declines in VLF and LF BPV, suggesting that VLF and LF BPV require sympathetic activity to be evident. In conclusion, VLF BPV is largely mediated by L-type Ca(2+) channel-dependent mechanisms. We speculate that VLF BPV is generated by myogenic vascular responses to spontaneously occurring perturbations of blood pressure. Other factors, such as sympathetic nervous system activity, may elicit a permissive effect on VLF BPV by increasing vascular myogenic responsiveness.
[Show abstract][Hide abstract] ABSTRACT: Transfer function analysis of blood pressure and cerebral blood flow in humans demonstrated that cerebrovascular autoregulation operates most effectively for slow fluctuations in perfusion pressure, not exceeding a frequency of approximately 0.15 Hz. No information on the dynamic properties of cerebrovascular autoregulation is available in rats. Therefore, we tested the hypothesis that cerebrovascular autoregulation in rats is also most effective for slow fluctuations in perfusion pressure below 0.15 Hz. Normotensive Wistar-Kyoto rats (n = 10) were instrumented with catheters in the left common carotid artery and jugular vein and flow probes around the right internal carotid artery. During isoflurane anesthesia, fluctuations in cerebral perfusion pressure were elicited by periodically occluding the abdominal aorta at eight frequencies ranging from 0.008 Hz to 0.5 Hz. The protocol was repeated during inhibition of myogenic vascular function (nifedipine, 0.25 mg/kg body wt iv). Increases in cerebral perfusion pressure elicited initial increases in cerebrovascular conductance and decreases in resistance. At low occlusion frequencies (<0.1 Hz), these initial responses were followed by decreases in conductance and increases in resistance that were abolished by nifedipine. At occlusion frequencies of 0.1 Hz and above, the gains of the transfer functions between pressure and blood flow and between pressure and resistance were equally high in the control and nifedipine trial. At occlusion frequencies below 0.1 Hz, the gains of the transfer functions decreased twice as much under control conditions than during nifedipine application. We conclude that dynamic autoregulation of cerebral blood flow is restricted to very low frequencies (<0.1 Hz) in rats.
[Show abstract][Hide abstract] ABSTRACT: When repetitively lifting an object with randomly varying mechanical properties, the fingertip forces reflect the previous lift. We examined the specificity of this "sensorimotor memory" by observing the effects of an isolated pinch on the subsequent lift of a known object. In this case, the pinch force was unrelated to the fingertip forces necessary to grip the object efficiently. The peak grip force used to lift the test object (4 N weight) depended on the preceding task. Compared with repetitively lifting the 4 N test object, the peak grip force was 2 N greater when a lift of the same object was preceded by a lift in which a hidden mass was attached to the object to increase the weight to 8 N. This 2 N increase in grip force also occurred when subjects lifted the 4 N test object after pinching a force transducer with a force of 8 N. Thus, similar grip forces were stored in sensorimotor memory for both tasks, and reflected subjects' use of 7.9 +/- 1.1 N to lift the 8 N object. Similar effects occurred when the preceding pinch or lift was performed with the opposite hand. The peak lift force was unaffected by the isolated pinch, suggesting that a generalized increase in fingertip and limb forces did not occur. We conclude that the sensorimotor memory is not specific for lifting an object. It is doubtful that this particular memory stores the physical properties of objects or reflects a forward internal model for predictively controlling fingertip forces.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 04/2003; 23(5):1981-6. · 6.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Old age impairs the ability to form new associations for declarative memory, but the ability to acquire and retain procedural memories remains relatively intact. Thus, it is unclear whether old age affects the ability to learn the visuomotor associations needed to set efficient fingertip forces for handling familiar objects. We studied the ability for human subjects to use visual cues (color) about the mechanical properties (texture or weight) of a grasped object to control fingertip forces during prehension. Old and young adults (mean age 77 years and 22 years, respectively) grasped and lifted an object that varied in texture at the gripped surfaces (experiment 1: sandpaper versus acetate surface materials) or weight (experiment 2: 200 g versus 400 g). The object was color-coded according to the mechanical property in the "visual cue" condition, and the mechanical property varied unpredictably across lifts in the "no visual cue" condition. In experiment 1 (texture), the young adults' grip force (force normal to the gripped surface) when the object lifted from the support surface was 24% smaller when the surfaces were color-coded. The old adults' grip force did not vary between the visual conditions despite their accurate reports of the grip surface colors prior to each lift. Comparable findings were obtained in experiment 2, when object weight was varied and peak grip force rate prior to object lift-off was measured. Furthermore old and young subjects alike used about 2 N of grip force when lifting the 200 g object in experiment 2. Therefore, the old adults' failure to adjust grip force when the color cue was present cannot be attributed to a general inability or unwillingness to use low grip force when handling objects. We conclude that old age affects the associative learning that links visual identification of an object with the fingertip forces for efficiently handling the object. In contrast, old and young subjects' grip force was influenced by the preceding lift, regardless of visual cues, which supports existing theories that multiple internal representations govern predictive control of fingertip forces during prehension.
Experimental Brain Research 04/2002; 143(1):35-41. DOI:10.1007/s00221-001-0965-9 · 2.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We investigated the effects of old age on the fingertip force responses that occurred when a grasped handle was pulled unexpectedly to increase the tangential load at the fingertip. These automatic responses, directed normal to the handle surface, help prevent slips between the handle and finger. Old adults (average age 78 years) responded with large peak fingertip forces compared to young adults (average age 30 years), even though the two subject groups showed similar skin slipperiness. For step-shaped loads the average response latency was the same for young and old subjects (about 80 ms). Thus, these automatic responses are not susceptible to the age-related central delays known for simple reaction-time tasks. For ramp-shaped loads the average response latency was inversely related to load rate. Response latency was 25 ms longer for the Old group versus the Young group for loads of 8 N/s, and this difference increased exponentially to a 110-ms difference for 2-N/s loads. A twofold difference in the tangential force required to evoke a response was predicted from linear regressions and can account for the latency difference (0.2 N vs 0.4 N threshold for young and old, respectively, r=0.93 for both groups). This theoretical elevation in load force threshold is consistent with degraded central information processing in old age, and the deterioration of cutaneous mechanoreceptors.
Experimental Brain Research 03/2001; 136(4):535-42. DOI:10.1007/s002210000613 · 2.04 Impact Factor