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Influence of body segment position during in-phase and antiphase hand and foot movements: a kinematic and functional MRI study.

Behavioral studies have provided important insights into the mechanisms governing interlimb coordination. In this study, we combined kinematic and functional magnetic resonance imaging (fMRI) analysis to investigate the brain cortical and subcortical areas involved in interlimb coordination and the influence of direction of movement and of body segment position on the activity of those areas. Fifteen right-handed healthy subjects were studied while performing cyclic in-phase and antiphase hand and foot movements with the dominant, right limbs, with the upper limb positioned either prone or supine, and in front or behind with respect to the trunk. When contrasting antiphase to in-phase movements, fMRI analysis demonstrated an increased recruitment of a widespread sensorimotor network (including regions in the frontal and parietal lobes, bilaterally, the cingulated motor area, the thalami, the visual cortex, and the cerebellum) considered to function in motor, sensory, and multimodal integration processing. When contrasting the anterior to the posterior position of the upper limb with respect to the trunk, we found different recruitment patterns in the frontal and parietal regions as well as the preferential recruitment of the basal ganglia, the insula, and the cerebellum during the first condition and of regions located in the temporal lobes during the second one. Different brain areas are engaged at a different extent during interlimb coordination. In addition to the relative difficulty of the movement, the different cognitive and sensorial loads needed to control and perform the motor act might be responsible for these findings.

Adult↗

Neural network models of cortical functions based on the computational properties of the cerebral cortex.

We describe a biologically plausible modelling framework based on the architectural and processing characteristics of the cerebral cortex. Its key feature is a multicellular processing unit (cortical column) reflecting the modular nature of cortical organization and function. In this framework, we describe a neural network model organization and function. In this framework, we describe a neural network model of the neuronal circuits of the cerebral cortex that learn different functions associated with different parts of the cortex: 1) visual integration for invariant pattern recognition, performed by a cooperation between temporal and parietal areas; 2) visual-to-motor transformation for 3D arm reaching movements, performed by parietal and motor areas; and 3) temporal integration and storage of sensorimotor programs, performed by networks linking the prefrontal cortex to associative sensory and motor areas. The architecture of the network is inspired from the features of the architecture of cortical pathways involved in these functions. We propose two rules which describe neural processing and plasticity in the network. The first rule (adaptive tuning if gating) is an analog of operant conditioning and permits to learn to anticipate an action. The second rule (adaptive timing) is based on a bistable state of activity and permits to learn temporally separate events forming a behavioral sequence.

Cerebral Cortex↗

Early appearance of functional deficits after neonatal excitotoxic and hypoxic-ischemic injury: fragile recovery after development and role of the NMDA receptor.

We sought to determine whether neonatal rats that sustain unilateral cerebral hypoxic-ischemic or excitotoxic insults (1) manifest contralateral sensorimotor deficits during development or in adulthood and (2) recover from those deficits. Seven-day-old (P7) rats received a right intrastriatal injection of the glutamate analog N-methyl-D-aspartate (NMDA). Unilateral hypoxia-ischemia (HI) was induced by right carotid ligation followed by 1.5 h in 8% O2. Both procedures produce neuronal loss in the striatum and sensorimotor cortex. Nonlesioned controls were included. We scored percent forepaw placement on the edge of a horizontal surface, with lateral vibrissa stimulation, from P9 to P19, and at P33 and P50. Then, on P50, rats were treated with the NMDA antagonist MK-801 to determine whether deficits could be reinstated. NMDA- and HI-lesioned rats exhibited a deficit in contralateral vibrissa-stimulated forepaw placing that emerged during the second week of life. Yet, by P33 and P50, the lesioned groups and controls were indistinguishable. MK-801 injection on P50 resulted in transient reinstatement of the placing deficit. After unilateral neonatal excitotoxic or HI brain injury, contralateral sensorimotor deficits are detected, but in many animals, these deficits have resolved by adulthood. Thus, timing of sensorimotor tests may influence their sensitivity for detection of focal neuropathology originating in the neonatal period.

Animals↗

Influence of somatosensory input on motor function in patients with chronic stroke.

In healthy volunteers, reduction of somatosensory input from one hand leads to rapid performance improvements in the other hand. Thus, it is possible that reduction of somatosensory input from the healthy hand can influence motor function in the paretic hand of chronic stroke patients with unilateral hand weakness. To test this hypothesis, we had 13 chronic stroke patients perform motor tasks with the paretic hand and arm during cutaneous anesthesia of the healthy hand and healthy foot in separate sessions. Performance of a finger tapping task, but not a wrist flexion task, improved significantly with anesthesia of the hand, but not the foot. This effect progressed with the duration of anesthesia and correlated with baseline motor function. We conclude that cutaneous anesthesia of the healthy hand elicits transient site-specific improvements in motor performance of the moderately paretic hand in patients with chronic stroke, consistent with interhemispheric competition models of sensorimotor processing.

Adult↗

Length of resting period between stimulation cycles modulates hemodynamic response to a motor stimulus.

The influence of different lengths of the pre-stimulation resting period on the magnitude of a hemodynamic response evoked by motor stimulation was examined in 10 subjects by means of near-infrared spectroscopy (NIRS). A motor stimulus was used which has been previously established as a model for functional activation studies with NIRS. Subjects performed a 20 s finger opposition task in the hand contralateral to NIRS probe localization over left sensorimotor area (C3', according to the 10-20 system). The duration of the pre-stimulation resting period was varied from 10s to 50s and response magnitude was assessed for each of the interstimulus intervals (10 s, 20 s, 30 s, 40 s and 50 s). Data analysis showed that response magnitude in oxygenated and deoxygenated haemoglobin concentration changed with different interstimulation intervals. Interestingly the greatest NIRS response was obtained with resting period 30 s prior to stimulation; shorter and longer resting periods resulted in smaller responses. The time course and the dependence of response magnitude on interstimulus interval differed between [oxy-Hb] and [deoxy-Hb] changes. For [oxy-Hb] the previously described fast initial increase ('overshoot') and the post-stimulation undershoot was more clearly seen with long prestimulation resting periods. Cytochromeoxidase oxygenation changes did not change significantly with different interstimulus intervals. We conclude that comparisons between different functional activation studies with techniques relying on stimulus evoked changes in cerebral hemodynamics must take into account not only the quality of the experimental paradigm and the length of the stimulation period, but also that the resting period between repetitive stimulations is important for response amplitude and its time course.

Brain↗

Oscillatory cortical activity during a motor task in a deafferented patient.

Little is known about the influence of the afferent peripheral feedback on the sensorimotor cortex activation. To answer this open question we investigated the alpha and beta band task-related spectral power decreases (TRPow) in the deafferented patient G.L. and compared the results to those of six healthy subjects. The patient has been deafferented up to the nose for 24 years but her motor fibers are unaffected and she can perform complex motor tasks under visual control. We recorded EEG (58 scalp positions) as well as the exerted force during a visuomotor task. The subjects had to maintain in precision grip an isometric force at 15% of the maximal voluntary contraction. In the patient we found a significantly higher alpha band spectral power during rest and larger alpha TRPow decreases during the motor task when compared to the healthy subjects' data. In contrast, we did not observe any significant differences between patient and controls for the beta band TRPow. The results indicate an altered functional alpha band network state in the patient, probably due to the chronic deafferentation leading to a deep 'idling' state of the contralateral sensorimotor area.

Adult↗

Motor impairment and recovery in the upper limb after stroke: behavioral and neuroanatomical correlates.

BACKGROUND AND PURPOSE: Motor recovery after stroke is associated with cerebral reorganization. However, few studies have investigated the relationship directly, and findings are equivocal. We therefore aimed to characterize the relationship between motor impairment, motor recovery, and task-related changes in regional cerebral blood flow (DeltarCBF) longitudinally. METHODS: We obtained a profile of motor impairment and recovery in the upper limb and conducted positron emission tomography motor activation studies using a simple finger-tapping task in 9 stroke patients 2 to 7 weeks after stroke and 6 months later. For correlation analysis, mean images of task-related DeltarCBF for each individual were linearly regressed with motor impairment scores. Motor recovery was correlated with longitudinal DeltarCBF images. RESULTS: Patients (7 males; 72.0+/-9.8 years) demonstrated a wide range of impairment severity and variable recovery. Upper-limb motor function was linearly correlated with task-related DeltarCBF. Importantly, sites of correlated DeltarCBF differed over time. Subacutely correlated DeltarCBF was observed in supplementary motor area (SMA), bilateral cingulate, and contralesional insula with a small area in ipsilesional primary sensorimotor cortex (SM1). Conversely, at the 6-month study, correlated DeltarCBF was primarily in ipsilesional SM1, extending to the cingulate gyrus. Better motor recovery was correlated with reduction in contralesional activity and increase in ipsilesional SM1. CONCLUSIONS: Upper-limb motor function and recovery are correlated with DeltarCBF in SMA, cingulate, insula, and SM1, highlighting the role of these areas in the recovery process. The dynamic nature of the relationship suggests ongoing adaptation within motor networks.

Aged↗

Olfactory classical conditioning in newborn mice.

Determining the behavioural phenotype of genetically altered mice is a valuable approach for elucidating the function of genes and their role in cognitive disorders. Methods for phenotyping newborn mice are scarce and generally confined to sensorimotor reflexes. Here, we describe a simple method for assessing associative abilities in newborn mice. We used a two-odour-choice classical conditioning paradigm in mice from the day of birth (post-natal age 0, P0) to P6. Acquisition required 20 trials: 10 trials during which the pups were placed over the conditioned stimulus (CS+) odour (lemon or peppermint) for 30s and simultaneously stroked gently with a paintbrush and 10 trials during which the pups were placed over the other odour (CS-) for 30s, without stroking. Then, the pups were subjected to five odour-preference trials to test for conditioning. This sequence of five trials was repeated after 5 and 24h to assess retention of the conditioned odour preference. During the immediate post-acquisition sequence, the pups spent significantly more time over the CS+ than over the CS- (p<0.0001). No extinction of the conditioned preference was observed during this test. No preference was observed after 5 or 24h, indicating that the conditioned response was promptly lost. Conditioning was effective as soon as P0-P1. Thus, conditioning may emerge in newborn mice sooner than previously reported. This paradigm is well suited to phenotyping of large samples of genetically altered mice and may shed light on the role for genes in paediatric cognitive impairments.

Age Factors↗

Prenatal protein deprivation in rats induces changes in prepulse inhibition and NMDA receptor binding.

Epidemiological studies suggest that prenatal malnutrition increases the risk of developing schizophrenia. Animal models indicate that prenatal protein deprivation (PPD) affects many aspects of adult brain function. We tested the hypothesis that PPD in rats would alter prepulse inhibition (PPI), which is an operational measure of sensorimotor gating that is deficient in schizophrenia patients. Additionally, we examined dopaminergic and glutaminergic receptor binding in the striatum and hippocampus, which have been suggested to play a role in the etiology of schizophrenia. Rat dams were fed normal (25%) or low (6%) protein diets beginning 5 weeks prior to, and throughout pregnancy. The pups were tested at postnatal days (PND) 35 and 56 for PPI. Striatal and hippocampal NMDA receptor, and striatal dopamine receptor binding were quantified post-mortem in a subset of these rats. Female rats exposed to PPD had reduced levels of PPI at PND 56, but not PND 35, suggesting the emergence of a sensorimotor gating deficit in early adulthood. Striatal NMDA receptor binding was increased in PPD females. A decrease in initial startle response (SR) was also observed in all PPD rats relative to control rats. These results suggest that PPD causes age- and sex-dependent decreases in PPI and increases in NMDA receptor binding. This animal model may be useful for the investigation of neurodevelopmental changes that are associated with schizophrenia in humans.

Animals↗

Cervical spine manipulation alters sensorimotor integration: a somatosensory evoked potential study.

OBJECTIVE: To study the immediate sensorimotor neurophysiological effects of cervical spine manipulation using somatosensory evoked potentials (SEPs). METHODS: Twelve subjects with a history of reoccurring neck stiffness and/or neck pain, but no acute symptoms at the time of the study were invited to participate in the study. An additional twelve subjects participated in a passive head movement control experiment. Spinal (N11, N13) brainstem (P14) and cortical (N20, N30) SEPs to median nerve stimulation were recorded before and for 30min after a single session of cervical spine manipulation, or passive head movement. RESULTS: There was a significant decrease in the amplitude of parietal N20 and frontal N30 SEP components following the single session of cervical spine manipulation compared to pre-manipulation baseline values. These changes lasted on average 20min following the manipulation intervention. No changes were observed in the passive head movement control condition. CONCLUSIONS: Spinal manipulation of dysfunctional cervical joints can lead to transient cortical plastic changes, as demonstrated by attenuation of cortical somatosensory evoked responses. SIGNIFICANCE: This study suggests that cervical spine manipulation may alter cortical somatosensory processing and sensorimotor integration. These findings may help to elucidate the mechanisms responsible for the effective relief of pain and restoration of functional ability documented following spinal manipulation treatment.

Adult↗

Skilled-learning-induced potentiation in rat sensorimotor cortex: a transient form of behavioural long-term potentiation.

The relation between the acquisition of a skilled motor task and synaptic plasticity in the sensorimotor cortex of the awake, freely behaving rat was examined. Skilled-motor training was previously found to induce a functional reorganization of the caudal forelimb area, and to induce an increase in synaptic efficacy, measured in vitro, on the side contralateral to the reaching forelimb. Here, we repeatedly measured neocortical evoked potential recordings in awake, freely behaving rats to examine whether skilled training would induce changes in polysynaptic efficacy on the side contralateral to the reaching forelimb. We found that the increase in task proficiency, but not the acquisition of task requirements or the maintenance of task proficiency, induced an increase in synaptic efficacy on the side contralateral to the reaching forelimb. We also tested the hypothesis that skilled learning induced potentiation shares similar mechanisms to long-term potentiation (LTP) and long-term depression by artificially manipulating polysynaptic efficacy in skilled rats with high- and low-frequency stimulation. We observed that, compared with the ipsilateral side, less potentiation but more depression could be induced on the side contralateral to the reaching forelimb. We conclude that a transient, network-based LTP-like mechanism operates during the learning of a skilled motor task.

Animals↗

Prefrontal involvement in "temporal bridging" and timing movement.

Brain activity exclusively related to a temporal delay has rarely been investigated using modern brain imaging. In this study we exploited the temporal resolution of functional magnetic resonance imaging (fMRI) to characterise, by sinusoidal regression analysis, differential neuroactivation patterns induced in healthy subjects by two sensorimotor synchronization tasks different in their premovement delay of either 0.6 s or 5 s. The short event rate condition required rhythmic tapping, while the long event rate condition required timing of intermittent movements. Left rostral prefrontal cortex, medial frontal cortex, SMA and supramarginal gyrus demonstrated increased MR signal intensity during low frequency synchronization, suggesting that these brain regions form a distributed neural network for cognitive time management processes, such as time estimation and motor output timing. Medial frontal cortex showed a biphasic pattern of response during both synchronization conditions, presumably reflecting frequency-independent motor output related attention. As predicted, sensorimotor and visual association areas demonstrated increased MR signal intensity during high frequency synchronization.

Adult↗

Inhibitory control of attention declines more than working memory during normal aging.

Changes in frontostriatal systems are believed to reduce the efficiency of executive cognitive functions during normal aging, especially the inhibitory control of attentional and behavioral responses. To characterize changes during normal aging in sensorimotor, working memory and inhibitory attentional systems, we tested 20 healthy elderly subjects (age 65-80) and 28 young adults (age 18-34) using oculomotor paradigms. Visually guided saccades of elderly subjects showed decreased peak velocity and increased reaction time, but not reduced accuracy, indicating selective age-related declines in sensorimotor systems. In an oculomotor working memory task, memory for spatial location information in elderly subjects was as accurate as in young adults. In contrast, elderly subjects demonstrated a significantly reduced ability to voluntarily inhibit eye movements toward flashed targets on an antisaccade task. These findings indicate changes in frontostriatal systems during normal aging that adversely affect volitional inhibitory processes but spare encoding and retrieval components of spatial working memory.

Adolescent↗

Temporal dissociation of parallel processing in the human subcortical outputs.

Many tasks require rapid and fine-tuned adjustment of motor performance based on incoming sensory information. This process of sensorimotor adaptation engages two parallel subcorticocortical neural circuits, involving the cerebellum and basal ganglia, respectively. How these distributed circuits are functionally coordinated has not been shown in humans. The cerebellum and basal ganglia show very similar convergence of input-output organization, which presents an ideal neuroimaging model for the study of parallel processing at a systems level. Here we used functional magnetic resonance imaging to measure the temporal coherence of brain activity during a tactile discrimination task. We found that, whereas the prefrontal cortex maintained a high level of activation, output activities in the cerebellum and basal ganglia showed different phasic patterns. Moreover, cerebellar activity significantly correlated with the activity of the supplementary motor area but not with that of the primary motor cortex; in contrast, basal ganglia activity was more strongly associated with the activity of the primary motor cortex than with that of the supplementary motor area. These results demonstrate temporally partitioned activity in the cerebellum and basal ganglia, implicating functional independence in the parallel subcortical outputs. This further supports the idea of task-related dynamic reconfiguration of large-scale neural networks.

Basal Ganglia↗

Correction for partial-volume effects on brain perfusion SPECT in healthy men.

UNLABELLED: The limited spatial resolution of SPECT scanners does not allow an exact measurement of the local radiotracer concentration in brain tissue because partial-volume effects (PVEs) underestimate concentration in small structures of the brain. The aim of this study was to determine which brain structures show greater influence of PVEs in SPECT studies on healthy volunteers and to investigate aging effects on SPECT after the PVE correction. METHODS: Brain perfusion SPECT using (99m)Tc-ethylcysteinate dimer was performed in 52 healthy men, 18-86 y old. The regional cerebral blood flow (rCBF) was noninvasively measured using graphical analysis. SPECT images were corrected for PVEs using gray-matter volume, which was segmented from coregistered MR images and convoluted with spatial resolution of SPECT scanners. Absolute rCBF data were measured using a 3-dimensional (3D) stereotactic template for regions of interest on anatomically standardized SPECT. We examined correlation of advancing age with rCBF before and after the PVE correction. To validate the correction method for PVEs, a Hoffman 3D brain phantom experiment was also performed. RESULTS: The PVE correction remarkably reduced the coefficient of variation for SPECT counts in the whole phantom. The PVE correction made the rCBF distribution more homogeneous throughout the brain with less intersubject variation than the original distribution. There were significant negative correlations between age and adjusted rCBF in the bilateral perisylvian and medial frontal areas. These correlations remained significant after the PVE correction. Instead of a positive correlation in the medial temporal structures between age and adjusted rCBF before the PVE correction, the sensorimotor and parietal areas mainly showed positive correlations after the correction. CONCLUSION: SPECT data reflect both brain volume loss and functional changes. Use of the PVE correction in brain perfusion SPECT provides a more accurate determination of rCBF even in healthy volunteers.

Adolescent↗

Activity of the dihydropyridine calcium channels following cerebral ischemia.

With an in-vivo autoradiographic method the binding of 3H-nimodipine (CAS 66085-59-4) and cerebral blood flow (14C-iodoantipyrine method) were measured in rat brain after occlusion of the middle cerebral and common carotid arteries. The dependence of the binding to neuronal cellular membranes on the duration of ischemia can be interpreted as indicator of the tissue's functional state or its responsiveness to therapy with calcium entry blockers. In the two analyzed structures, dorsolateral caudate and overlying sensorimotor cortex, the appearance of infarction is preceded by an activation of the nimodipine binding sites followed by persistent decline of the binding intensity. Binding to nimodipine may therefore be a useful marker of ischemic but salvageable brain tissue.

Animals↗

Behavioral electrophysiology of the prefrontal cortex of the primate.

The prefrontal cortex (PFC) is critical for temporal organization of behavior. It mediates cross-temporal sensorimotor contingencies, integrating motor action (including speech) with recent sensory information. It performs this role through cooperation of 2 cognitive functions represented in its dorsolateral areas: short-term memory (STM) and preparatory set. Supporting data have been obtained from monkeys performing delay tasks, which epitomize the principle of cross-temporal contingency. In a given trial, the animal performs an act contingent on a sensory cue given a few seconds or minutes earlier. During the delay between cue and response, cells in dorsolateral PFC show sustained activation. Two cell categories can be identified in tasks in which cue and response are spatially separate. Cells of the first participate in STM: Their activation tends to diminish as the delay progresses; in some, the activation level depends on the particular cue received. Similar cells are found elsewhere in the cortex. Cells of the second category seem to take part in preparation of motor response: Their activation tends to increase in anticipation of it and may be attuned to the particular movement the cue calls for. This cell type is rare outside of the frontal cortex. The temporally integrative function of the PFC is probably based on local interactions between "memory" and "motor-set" cells, as well as on neural associations between PFC and posterior cortical areas.

Animals↗

Hand-use preference for reaching and object manipulation in 6- through 13-month-old infants.

Validity, reliability, and stability of separate assessment of hand-use preferences for reaching, object manipulation, and complementary bimanual action were determined for 6 through 13 month-old male and female infants. Only hand-use preferences for complementary bimanual action varied with age. Females had more distinct hand-use preference than males but only for object manipulation. Comparison of hand-use preference among these different sensorimotor skills can provide a richer evaluation of infant handedness status required for systematic study of the development of neuropsychological functions during infancy.

Child Development↗