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Cerebellar ataxia and muscle spindle sensitivity.

1. The cerebellum has long been known to participate in movement control. One of the enduring theories of cerebellar function is that it "tunes" and coordinates sensorimotor traffic in other parts of the CNS. In particular, it has been implicated in the control of the sensitivity of muscle spindle stretch receptors through the fusimotor system. 2. The stretch sensitivity of spindle primary endings can be varied approximately over a 10-fold range by fusimotor efferent action. For many years it has been believed that cerebellar dysfunction is associated with reduced drive to the fusimotor system and that this in turn causes hypotonia by reducing the reflex excitation of alpha-motoneurons by spindle afferents. 3. The data on which this hypothesis is based were obtained in anesthetized or decerebrate animals. Little direct information is available on animals or humans performing voluntary movements and exhibiting ataxia or other cerebellar symptoms. 4. We tested the hypothesis by recording from nine muscle spindle afferents in behaving cats before and during reversible inactivation of cerebellar interpositus and dentate nuclei. In normal cats fusimotor action varies with motor task, greatly altering spindle stretch sensitivity. We investigated whether this same range of task-related sensitivity manifested itself during ataxia. 5. We found that the full range of spindle sensitivity was still present during ataxia. We therefore conclude that the cerebellar nuclei studied are not primarily responsible for fusimotor control, nor is the ataxia primarily caused by disordered proprioceptive sensitivity.

Afferent Pathways↗

Multimodal anatomic, functional, and metabolic brain imaging for tumor resection.

OBJECTIVE: Improvement of neurosurgical techniques with a more detailed description of brain tumors and their functional environment. METHODS: We performed: (1) anatomical magnetic resonance imaging (MRI) for reference, (2) functional sequences dedicated to the adjacent cortical structures (sensorimotor, visual, language paradigms), and (3) thallium 201 cerebral tomoscintigraphy to visualize active tumor invasion. Data were transferred to a workstation for automatic registration. RESULTS: All data were combined into one synthetic image showing the foci of high proliferative activity, which have to be completely resected, and the peritumoral functional structures, which have to be spared in order to minimize postoperative sequelae. This trimodal image is entered into a surgical neuronavigation computer for preoperative planning in order to outline tumoral target and functional risk areas. All this information is displayed in the operative microscope (Zeiss MKM) optically linked to MR images. This multimodality technique diminishes operative time by reducing electrocorticography and improves the operative short-term outcome. CONCLUSION: Multimodal imaging is useful for optimization of neurosurgical tumor resection.

Adult↗

Simulating unilateral neglect in normals: myth or reality?

Hemispatial neglect is a neurological deficit of perception, attention, representation, and/or performing actions within the left-sided space. The condition also produces many functional debilitating effects on everyday life, and is associated with poor functional recovery and inability to benefit from treatment. Numerous methods of rehabilitation (sensory stimulations or active training) have been proposed to alleviate neglect condition. It has been recently shown that visuo-manual adaptation to rightward optical shift leads to profound and enduring improvements of neglect symptoms. Based on the different methods commonly used in the rehabilitation of neglect, several techniques have been employed to simulate neglect symptoms in healthy subjects with a view to better understand the physiopathology of neglect. The present paper reviews studies of neglect-like behaviour in healthy individuals and in particular the use of prism adaptation as a procedure for simulating various symptoms of clinical neglect in normals. Neglect-like symptoms following prism adaptation offer insights as to the mechanisms of spatial neglect and provide an understanding of the interaction between low level sensorimotor processes and spatial cognition. Implications for the functional mechanisms and the anatomical substrates of prism adaptation are discussed in terms of inter-sensory plasticity and sensorimotor coordination and the way these may affect higher-level representations of space.

Adaptation, Physiological↗

Functional MRI and intraoperative brain mapping to evaluate brain plasticity in patients with brain tumours and hemiparesis.

OBJECTIVE: To support the hypothesis about the potential compensatory role of ipsilateral corticofugal pathways when the contralateral pathways are impaired by brain tumours. METHODS: Retrospective analysis was carried out on the results of functional MRI (fMRI) of a selected group of five paretic patients with Rolandic brain tumours who exhibited an abnormally high ipsilateral/contralateral ratio of activation-that is, movements of the paretic hand activated predominately the ipsilateral cortex. Brain activation was achieved with a flexion extension of the fingers. Statistical parametric activation was obtained using a t test and a threshold of p<0.001. These patients, candidates for tumour resection, also underwent cortical intraoperative stimulation that was correlated to the fMRI spatial data using three dimensional reconstructions of the brain. Three patients also had postoperative control fMRI. RESULTS: The absence of fMRI activation of the primary sensorimotor cortex normally innervating the paretic hand for the threshold chosen, was correlated with completely negative cortical responses of the cortical hand area during the operation. The preoperative fMRI activation of these patients predominantly found in the ipsilateral frontal and primary sensorimotor cortices could be related to the residual ipsilateral hand function. Postoperatively, the fMRI activation returned to more classic patterns of activation, reflecting the consequences of therapy. CONCLUSION: In paretic patients with brain tumours, ipsilateral control could be implicated in the residual hand function, when the normal primary pathways are impaired. The possibility that functional tissue still remains in the peritumorous sensorimotor cortex even when the preoperative fMRI and the cortical intraoperative stimulations are negative, should be taken into account when planning the tumour resection and during the operation.

Aged↗

[Effect of early mass training in food mazes on evoked potentials of the sensomotor cortex and caudate nucleus in the rat].

The data obtained attest that not only prolonged (three months) motor training of rats in a tretbahn, but also mass alimentary-motivated training in mazes at the same period of postnatal ontogenesis and of the same duration is attended with enhanced activity of the sensorimotor cortex as manifested in the reduction of evoked potential latencies. Such enhancement was more pronounced after training in mazes than in a tretbahn. Mass alimentary-motivated training of rats in mazes resulted in shorter latencies of the caudate nucleus EP to peripheral stimulation, which testifies to a close functional connection of this striatum structure with the sensorimotor cortex in formation of plastic reorganizations in an enriched sensory medium.

Adaptation, Psychological↗

Differential sensorimotor processing of vestibulo-ocular signals during rotation and translation.

Rotational and translational vestibulo-ocular reflexes (RVOR and TrVOR) function to maintain stable binocular fixation during head movements. Despite similar functional roles, differences in behavioral, neuroanatomical, and sensory afferent properties suggest that the sensorimotor processing may be partially distinct for the RVOR and TrVOR. To investigate the currently poorly understood neural correlates for the TrVOR, the activities of eye movement-sensitive neurons in the rostral vestibular nuclei were examined during pure translation and rotation under both stable gaze and suppression conditions. Two main conclusions were made. First, the 0.5 Hz firing rates of cells that carry both sensory head movement and motor-like signals during rotation were more strongly related to the oculomotor output than to the vestibular sensory signal during translation. Second, neurons the firing rates of which increased for ipsilaterally versus contralaterally directed eye movements (eye-ipsi and eye-contra cells, respectively) exhibited distinct dynamic properties during TrVOR suppression. Eye-ipsi neurons demonstrated relatively flat dynamics that was similar to that of the majority of vestibular-only neurons. In contrast, eye-contra cells were characterized by low-pass filter dynamics relative to linear acceleration and lower sensitivities than eye-ipsi cells. In fact, the main secondary eye-contra neuron in the disynaptic RVOR pathways (position-vestibular-pause cell) that exhibits a robust modulation during RVOR suppression did not modulate during TrVOR suppression. To explain these results, a simple model is proposed that is consistent with the known neuroanatomy and postulates differential projections of sensory canal and otolith signals onto eye-contra and eye-ipsi cells, respectively, within a shared premotor circuitry that generates the VORs.

Action Potentials↗

Anatomic and functional variability: the effects of filter size in group fMRI data analysis.

In the analysis of group fMRI scans, an optimal spatial filter should be large enough to accurately blend functionally homologous anatomic regions, yet small enough not to blur the functionally distinct regions. Hanning filters varying from 0.0 to 18.0 mm were evaluated in a group analysis of six healthy controls performing a simple finger-tapping paradigm. Test-retest reliability and Talairach-based measurements of the sensorimotor region were used to explore the optimal filter size. Two distinct regions of functional activation were noted in the sensorimotor cortex in group images (n = 6) at both time 1 and time 2. These regions merge once the filter size exceeds approximately 6.0 mm. The original hypothesis that these represented a motor and sensory activation was rejected on the basis of structural and functional variability. A discussion of the inherent difficulties in choosing an appropriate filter size is presented.

Adult↗

Chronic behavioral testing after focal ischemia in the mouse: functional recovery and the effects of gender.

Several useful behavioral tests exist for measuring behavioral recovery after ischemia in higher-order animals and rats. With the increasing use of mice in focal stroke research, simple, reliable, and reproducible behavioral testing has become a priority. As neuroprotective agents are tested, long-term outcome must be assessed, especially in studies focused on neuronal plasticity and regeneration after ischemia. Our laboratory and others have previously shown that estrogen (E2) is neuroprotective in rodent stroke paradigms. We examined a battery of behavioral tests in male and female mice subjected to 90 min of middle cerebral artery occlusion (MCAO) to determine the most sensitive tests for detecting sensorimotor dysfunction after stroke, and to determine the functional significance of E2-mediated neuroprotection. Only two tests, the corner test and the cylinder test, were able to differentiate between groups (sham and stroke) after several days of repeated testing. The cylinder test was sensitive to the neuroprotective/neurorestorative effects of E2, but 2 weeks after stroke, the cylinder test was unable to distinguish between sham and stroke animals treated with E2. In contrast, the corner test was able to differentiate stroke and sham animals even 6 weeks after stroke, but did not distinguish animals treated with E2 vs. vehicle. These tests provide a simple, rapid, reliable assessment of sensorimotor dysfunction in the mouse after focal ischemia. Hormonal status influences speed of recovery on cylinder testing in animals of both genders. This suggests that a short battery of tests including the neurological score, cylinder, and corner test may be adequate to rapidly and repeatedly assess sensorimotor dysfunction in mice of both genders.

Animals↗

Medullary reticular formation activity during ingestion and rejection in the awake rat.

The consummatory components of ingestion and rejection, organized in the caudal brainstem, include licking, swallowing, and the oral phase of rejection (gaping). Studies employing electrical-stimulation induced motor activity have localized interneurons controlling these complex motor patterns to the medullary reticular formation (RF), but the characteristics of these neurons during more naturally induced behavior are unknown. The purpose of the present study was to record the activity profiles of RF neurons during licking, swallowing, and oral rejection in response to gustatory stimulation. Two-hundred and two neurons recorded from awake, freely moving rats were broadly classified as orally related (67%) or non-orally related (33%). Orally related neurons included a large number that were rhythmically active during licking (n = 76; 38%). These "lick-rhythmic" neurons were widely distributed in the RF, but were concentrated in the caudal medullary reticular formation adjacent to the hypoglossal nucleus (Probst's region) and further rostral in the intermediate zone (IRt) of the RF. An analysis of autocorrelations determined that lick-rhythmic neurons in these regions were more closely coupled to licking than to lick-rhythmic neurons more lateral in the parvocellular RF (PCRt). In addition to neurons with weak lick-rhythmic activity, the PCRt also contained a disproportionate number of neurons with orosensory or mixed oro-sensorimotor properties. These data provide evidence for functional specialization within different regions of the medullary RF. A high proportion of lick-rhythmic neurons also showed differential activity associated with swallowing (41%) and/or gaping (75%), further suggesting that the different components of ingestion and rejection share brainstem substrates instead of being produced by unique subsets of interneurons.

Action Potentials↗

Dopaminergic modulation of visual responses in toads. I. Apomorphine-induced effects on visually directed appetitive and consummatory prey-catching behavior.

This study confirms for a phylogenetically basal terrestrial vertebrate that dopaminergic modulations interfere with the visually directed appetitive and consummatory feeding behaviors orienting and snapping, respectively. (1) In common toads Bufo bufo, intralymphatic administration of the dopamine D2/D1-receptor agonist apomorphine led to a dose-dependent facilitation of prey-snapping in response to moving objects. The snapping activity reached a maximum 15-35 min after apomorphine injection. (2) To changes in configurational stimulus features, the basic pattern of discrimination was maintained; however, the acuity of discrimination was reduced due to the high snapping response level. (3) The apomorphine-induced facilitation of snapping was accompanied by a suppression of prey-oriented lunging and turning. Toads snapped only if prey occurred frontally in the visual field at a relatively short distance. The snapping behavior was fixed in its form and stereotyped regarding its immediate release. (4) About 90 min after apomorphine administration, prey-oriented turning behavior was restored and displayed a facilitatory rebound. (5) In comparative experiments with the species B. marinus, both prey-oriented turning and snapping responses were suppressed by apomorphine in a dose-dependent manner. (6) After pre-treatment with the dopamine antagonist haloperidol, apomorphine showed no measurable effect on the visual release of prey orienting or snapping. (7) The results contribute to the sensorimotor and the motivation hypothesis of dopamine function proposed for higher vertebrates and stimulate a comparative discussion of anatomic homologies and functional analogies.

Animals↗

Comparison between monopolar and bipolar electrical stimulation of the motor cortex.

Intra-operative neurophysiological techniques allow reliable identification of the sensorimotor region and make their anatomical and functional preservation feasible. Monopolar cortical stimulation has recently been described as a new mapping technique. In the present study this method was compared to the "traditional" technique of bipolar stimulation. Functional mapping of the motor cortex was performed in 35 patients during surgery in the central region. The central sulcus (CS) was identified by somatosensory evoked potential (SEP) phase reversal. Cortical motor mapping was first performed by monopolar anodal stimulation with a train of 500 Hz (7-10 pulses) followed by bipolar stimulation (pulses at 60 Hz with max. 4 sec train duration). Surgery was performed under general anaesthesia without muscle relaxants. Of 280 motor responses elicited by bipolar cortical stimulation, 54.23% [152] were located in the primary motor cortex (PMC), 37.85% 106[ outside the motor strip in the secondary motor cortex (SMC), and 8% 22[ posterior to the CS. Of 175 motor responses elicited by monopolar cortical stimulation. 68.57% 120[ were located in the SMC, 23.42% 41[ in the SMC and 8% 14[ posterior to the CS. Contrary to the general clinical view, there is considerable overlapping of primary motor units over a cortical area much broader than the "classical" narrow motor strip along the CS. Bipolar cortical stimulation is more sensitive than monopolar for mapping motor function in the premotor frontal cortex. Both methods are equally sensitive for mapping the primary motor cortex.

Adolescent↗

The emergence of architectonic field structure and areal borders in developing monkey sensorimotor cortex.

Adult monkey sensorimotor cortex consists of several structurally and functionally distinct areas. The developmental sequence through which the characteristic architectonic features and the borders of these areas become resolved was examined in a series of fetal, postnatal and adult monkeys by using Nissl staining, cytochrome oxidase and acetylcholinesterase histochemistry, and immunocytochemistry for GABA and the neuropeptides somatostatin, neuropeptide Y, substance P and cholecystokinin. At the youngest fetal age examined (E110), the pre- and postcentral gyri possess six clearly delineated cellular layers; populations of GABA- and neuropeptide-immunoreactive cells can be identified, but their somatic sensory cortex at E110 lacks areal cytoarchitectonic parcellation. Despite the apparent homogeneity in the cytoarchitecture of the somatic sensory cortex, incipient areal borders are revealed by staining for cytochrome oxidase and acetylcholinesterase activity, and by staining immunocytochemically for several neuropeptides. The motor cortex at E110 differs from that in adults by the presence of a prominent layer IV; a clear cytoarchitectonic border between areas 3a and 4 is detectable at E110, which is also revealed by chemoarchitectonic markers. With increasing age, the characteristic architectonic features gradually emerge and areal cytoarchitectonic borders appear, becoming adult-like by early postnatal ages. The gradual changes in cytoarchitecture are paralleled by redistributions of GABA- and neuropeptide-immunoreactive cells and fiber plexuses. The data demonstrate that the progressive refinement in cytoarchitectonic features and in the distributions of neurotransmitter- and peptide-containing cells occurs primarily during the latter third of gestation. The major changes are temporally coincident with the ingrowth of afferent axonal systems, suggesting that the establishment of connectivity may be capable of modulating finer details of structural or molecular phenotype, particularly intra-areal cytoarchitectonic features and neurotransmitter or peptide expression.

Acetylcholinesterase↗

Human neural stem cells improve sensorimotor deficits in the adult rat brain with experimental focal ischemia.

Ischemic stroke is caused by the interruption of cerebral blood flow that leads to brain damage with long-term sensorimotor deficits. Stem cell transplantation may recover functional deficit by replacing damaged brain. In this study, we attempted to test whether the human neural stem cells (NSCs) can improve the outcome in the rat brain with intravenous injection and also determine the migration, differentiation and the long-term viabilities of human NSCs in the rat brain. Focal cerebral ischemia was induced by intraluminal thread occlusion of middle cerebral artery (MCA). One day after surgery, the rats were randomly divided into two groups: NSCs-ischemia vs. Ischemia-only. Human NSCs infected with retroviral vector encoding beta galactosidase were intravenously injected in NSCs-ischemia group (5 x 10(6) cells) and the same amount of saline was injected in Ischemia-only group for control. The animals were evaluated for 4 weeks using turning in an alley (TIA) test, modified limb placing test (MLPT) and rotarod test. Transplanted cells were detected by X gal cytohistochemistry or beta gal immunohistochemistry with double labeling of other cell markers. The NSCs-ischemia group showed better performance on TIA test at 2 weeks, and MLPT and rotarod test from 3 weeks after ischemia compared with the Ischemia-only group. Human NSCs were detected in the lesion side and labeled with marker for neurons or astrocytes. Postischemic hemispheric atrophy was noted but reduced in NSCs-ischemia group. X gal+ cells were detected in the rat brain as long as 540 days after transplantation. Our data suggest intravenously transplanted human NSCs can migrate and differentiate in the rat brain with focal ischemia and improve functional recovery.

Animals↗

Recovery of forepaw gripping ability and reorganization of cortical motor control following cervical spinal cord injuries in mice.

Previous studies using a grip strength meter (GSM) revealed a loss of gripping ability following cervical hemisection injuries in mice, followed by partial recovery. Here, we assess whether normal gripping ability and the recovered gripping ability after cervical hemisection depend on the cerebral cortex. First, we assessed grip strength of both forepaws of 18-week-old C57Bl/6 mice before and after a left sensorimotor cortex lesion or right lateral hemisection at C5. Both lesions led to a complete loss of gripping ability by the right forepaw and caused only minor deficits in the left. After cortical lesions, gripping ability re-appeared at about 17 days post-injury, and grip strength recovered to near-normal levels by 24 days post-injury. After C5 hemisections, gripping ability re-appeared after 31 days post-injury in 50% of the mice. Follow-up experiments were then carried out in which 10-week-old mice received C4 hemisection injuries and were tested for 28 days; then mice received secondary lesions of the sensorimotor cortex ipsi- or contralateral to the hemisection. Younger mice with cervical hemisections recovered gripping ability between 12 and 28 days post-hemisection. Cortical lesions on the side contralateral to the hemisection led to a complete loss of recovered gripping ability in all mice; cortical lesions on the side ipsilateral to the hemisection also disrupted recovered gripping ability in some animals. Surprisingly, lesions of the cortex ipsilateral to the hemisection did not impair gripping ability of the contralateral (left) forepaw. Finally, we assessed the effects of a third lesion of whichever side of the sensorimotor cortex remained, so that the sensorimotor cortex was ablated bilaterally. Remarkably, gripping function by the forepaw contralateral to the original hemisection was completely unaffected, and the recovered gripping function by the forepaw ipsilateral to the hemisection was disrupted in only some of the animals. These results indicate a substantial reorganization of motor control of gripping function after cervical injuries in mice so that gripping ability by both forepaws becomes largely independent of cortical control.

Animals↗

Sensorimotor stimulation to improve locomotor recovery after spinal cord injury.

Functional recovery after CNS injury may depend, in part, upon reorganization of undamaged neural pathways. Spinal cord circuits are capable of significant reorganization, in the form of both activity-dependent and injury-induced plasticity. This plasticity is manifest behaviourally in the ability of spinal animals to learn new locomotor tasks. Recent work with spinal-injured humans demonstrates that training can improve functional locomotor abilities. New methodologies to enhance limb movement are designed to exploit further the plastic capabilities of the spinal cord by reinforcing appropriate connections in an activity-dependent manner. In the future, these methods might also prove useful in guiding and strengthening functional synaptogenesis of regenerating axons to maximize their contribution towards restoration of function.

Animals↗

Changes in vocal intensity in Parkinson's disease following pallidotomy surgery.

The present study was designed to examine changes in vocal intensity following unilateral posteroventral pallidotomy (PVP) in a large sample of speakers with Parkinson's disease (PD) that exhibited a range of hypokinetic dysarthria. Twenty-five persons with PD were recorded using a variety of speech tasks, once prior to and once following PVP. The pre-PVP vocal SPL was subtracted from the post-PVP vocal SPL to derive a relative change in vocal SPL. Mildly dysarthric participants had significantly greater relative increases in vocal SPL following PVP than either moderately or severely dysarthric participants who had reduced vocal SPL following PVP. If future results follow those observed in the present data, mildly dysarthric Parkinson's patients may benefit most from unilateral PVP perhaps due to less overall destruction of the basal ganglia sensorimotor control circuits involved in oral facial functions, thus increasing the chances to observe improvements postsurgery.

Aged↗

Graphical and statistical techniques for cardiac cycle time (phase) dependent changes in interbeat interval.

Cardiac cycle time effects refer to the relative lengthening or shortening of a single cardiac cycle as a function of when in the cycle brief sensorimotor events occur. These effects may provide short-latency measures of cardiac sensitivity to psychological events. Conventional representations have, however, failed to clearly separate changes in interbeat interval due to cycle time--i.e., phase dependent changes--from other types of change. This paper advocates a particular technique of plotting to solve these representation problems. Heartbeat timing is represented in real time and in the context of beats both preceding and following the event of interest. The plot, a phase-sensitive plot, conceptualizes phase-sensitive (cardiac cycle time) effects as a change in linear or higher order trend. Thus, an adaptation of trend analysis is proposed as an efficient statistical analysis that follows directly from the proposed representational technique.

Data Display↗

Cerebral changes during performance of overlearned arbitrary visuomotor associations.

The posterior parietal cortex (PPC) is known to be involved in the control of automatic movements that are spatially guided, such as grasping an apple. We considered whether the PPC might also contribute to the performance of visuomotor associations in which stimuli and responses are linked arbitrarily, such as producing a certain sound for a typographical character when reading aloud or pressing pedals according to the color of a traffic light when driving a motor vehicle. The PPC does not appear to be necessary for learning new arbitrary visuomotor associations, but with extensive training, the PPC can encode nonspatial sensory features of task-relevant cues. Accordingly, we have tested whether the contributions of the PPC might become apparent once arbitrary sensorimotor mappings are overlearned. We have used functional magnetic resonance imaging to measure cerebral activity while subjects were learning novel arbitrary visuomotor associations, overlearning known mappings, or attempting to learn frequently changing novel mappings. To capture the dynamic features of cerebral activity related to the learning process, we have compared time-varying modulations of activity between conditions rather than average (steady-state) responses. Frontal, striatal, and intraparietal regions showed decreasing or stable activity when subjects learned or attempted to learn novel associations, respectively. Importantly, the same frontal, striatal, and intraparietal regions showed time-dependent increases in activity over time as the mappings become overlearned, i.e., despite time-invariant behavioral responses. The automaticity of these mappings predicted the degree of intraparietal changes, indicating that the contribution of the PPC might be related to a particular stage of the overlearning process. We suggest that, as the visuomotor mappings become robust to interference, the PPC may convey relevant sensory information toward the motor cortex. More generally, our findings illustrate how rich cerebral dynamics can underlie stable behavior.

Adult↗