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Motor and sensory impairments in children with intractable epilepsy.

During a 3-year period (1988-1991), 72 children with severe intractable epilepsy were studied. A standardized protocol for assessment of motor and sensory function was designed for school age children. Function was quantified on a 4-point scale on 47 items, including gross motor function, balance, coordination, strength, range of motion (ROM), velocity, fine motor function, sensation, perception, and neurologic tests. Classification of handicaps according to World Health Organization (WHO) definitions was performed. Videotape documentation completed the assessment. Evaluation of treatment services showed that provision of rehabilitation services had been insufficient and provided only for children with additional major movement disorders, mainly cerebral palsy (CP) cases. To minimize the handicap in children with severe epilepsy, it is essential to clarify the total sensorimotor impairment pattern, including balance, coordination, and perceptual capacity. Impairments in these functions are, as shown in this study, frequent and exist independent of major disabilities such as mental retardation or cerebral palsy. When several neuroimpairments were identified, a multiplicative rather than an additive effect on the total handicap was evident.

Adolescent↗

The endocannabinoid system: a physiological perspective on its role in psychomotor control.

The discovery of cannabinoid receptors has led to the identification of two natural activators for these receptors, anandamide and 2-arachidonoylglycerol, and to the elucidation of their biochemical pathways of formation and inactivation. Although the physiological significance of the endogenous cannabinoid system is still poorly understood, important information is becoming available on the possible functional roles of this system in the basal ganglia, a forebrain region that is involved in the control of sensorimotor and motivational aspects of behavior. These discoveries - which are going to enrich the way in which we look at basal ganglia functions - are summarized in this mini-review. The role of the endocannabinoids as modulators of psychomotor behaviors and the potential therapeutic perspectives deriving from the pharmacological manipulation of the endogenous cannabinoid system are also discussed.

Animals↗

Deficits and recovery of body stabilization during acrobatic locomotion after focal lesion to the somatosensory cortex: a kinematic analysis combined with cortical mapping.

We used a kinematic analysis for assessing locomotor impairments and evaluating the time course of recovery after focal injury to the forepaw area of the primary somatosensory cortex (SI) in rats. The animals were trained to traverse a beam that was rotated at various speeds. Changes in orientation of the body and independent movement of the anterior and posterior parts of the body were reconstructed using a 3D motion analysis. In addition, we used electrophysiological cortical mapping to search for neurophysiological changes within the spared cortical zones surrounding the lesion. Neuronal recordings were performed in the same animals prior to and 3 weeks after the lesion induction. Our findings show that a focal lesion that destroyed about 60% of the forepaw representational zone was sufficient to cause conspicuous impairments in the rats' ability to produce adequate motor adjustments to compensate for the lateral shift of the beam and to avoid falling. The main deficits were reflected in a lack of appropriate coordination between the anterior and posterior parts of the body and an inability to maintain a regular gait during locomotion. Skilled locomotion was fully recovered within a 2-3 week period. Functional recovery cannot be ascribed to a restitution of the lost sensory representations. A permanent decrease of forepaw representation was recorded despite the re-emergence of restricted representational sectors in the peri-lesion zone. We suggest that alterations may have occurred in other cortical and subcortical areas interconnected with the injured area. It is also conceivable that the functional recovery involved an increased reliance on all the available sources of sensorimotor regulation as well as the use of behavioral strategies.

Adaptation, Physiological↗

An integrative approach to the biomechanical function and neuromuscular control of the fingers.

The exquisite mechanical functionality and versatility of the human hand emerges from complex neuro-musculo-skeletal interactions that are not completely understood. I have found it useful to work within a theoretical/experimental paradigm that outlines the fundamental neuro-musculo-skeletal components and their interactions. In this integrative paradigm, the laws of mechanics, the specifications of the manipulation task, and the sensorimotor signals define the interactions among hand anatomy, the nervous system, and manipulation function. Thus, our collaborative research activities emphasize a firm grounding in the mechanics of finger function, insistence on anatomical detail, and meticulous characterization of muscle activity. This overview of our work on precision pinch (i.e., the ability to produce and control fingertip forces) presents some of our findings around three Research Themes: Mechanics-based quantification of manipulation ability; Anatomically realistic musculoskeletal finger models; and Neural control of finger muscles. I conclude that (i) driving the fingers to some limit of sensorimotor performance is instrumental to elucidating motor control strategies; (ii) that the cross-over of tendons from flexors to extensors in the extensor mechanism is needed to produce force in every direction, and (iii) the anatomical routing of multiarticular muscles makes co-contraction unavoidable for many tasks. Moreover, creating realistic and clinically useful finger models still requires developing new computational means to simulate the viscoelastic tendinous networks of the extensor mechanism, and the muscle-bone-ligament interactions in complex articulations. Building upon this neuromuscular biomechanics paradigm is of immense clinical relevance: it will be instrumental to the development of clinical treatments to preserve and restore manual ability in people suffering from neurological and orthopedic conditions. This understanding will also advance the design and control of robotic hands whose performance lags far behind that of their biological counterparts.

Biomechanical Phenomena↗

Mapping functionally related regions of brain with functional connectivity MR imaging.

BACKGROUND AND PURPOSE: In subjects who are performing no prescribed cognitive task, functional connectivity mapped with MR imaging (fcMRI) shows regions with synchronous fluctuations of cerebral blood flow. When specific tasks are performed, functional MR imaging (fMRI) can map locations in which regional cerebral blood flow increases synchronously with the performance of the task. We tested the hypothesis that fcMRI maps, based on the synchrony of low-frequency blood flow fluctuations, identify brain regions that show activation on fMRI maps of sensorimotor, visual, language, and auditory tasks. METHODS: In four volunteers, task-activation fMRI and functional connectivity (resting-state) fcMRI data were acquired. A small region of interest (in an area that showed maximal task activation) was chosen, and the correlation coefficient of the corresponding resting-state signal with the signal of all other voxels in the resting data set was calculated. The correlation coefficient was decomposed into frequency components and its distribution determined for each fcMRI map. The fcMRI maps were compared with the fMRI maps. RESULTS: For each task, fcMRI maps based on one to four seed voxel(s) produced clusters of voxels in regions of eloquent cortex. For each fMRI map a closely corresponding fcMRI map was obtained. The frequencies that predominated in the cross-correlation coefficients for the functionally related regions were below 0.1 Hz. CONCLUSION: Functionally related brain regions can be identified by means of their synchronous slow fluctuations in signal intensity. Such blood flow synchrony can be detected in sensorimotor areas, expressive and receptive language regions, and the visual cortex by fcMRI. Regions identified by the slow synchronous fluctuations are similar to those activated by motor, language, or visual tasks.

Adult↗

Multiple memory systems, development and conditioning.

A century of behavioral and neurobiological research suggests that Pavlovian conditioning involves three component memory systems: sensorimotor, affective and cognitive. In classical eyeblink conditioning, there is evidence that these three memory systems involve, respectively, the cerebellum, amygdala and hippocampus. This article reviews developmental research on eyeblink conditioning in rodents that is beginning to characterize ontogenetic dissociations and interactions among these memory systems. This research shows that the functional development of the affective system (conditioned fear response) precedes that of the sensorimotor system (conditioned eyeblink reflex). Modulation of these two systems by cognitive processes also seems to emerge at different points in ontogeny. Implications for cognitive development and research on multiple memory systems are discussed.

Animals↗

Bilateral functional MRI activation of the basal ganglia and middle temporal/medial superior temporal motion-sensitive areas: optokinetic stimulation in homonymous hemianopia.

OBJECTIVE: To determine to what extent sensorimotor control is achieved for each hemisphere separately or interactively during small-field optokinetic stimulation in patients with complete homonymous hemianopia. DESIGN: Functional and structural neuroimaging using high-resolution magnetic resonance imaging. SETTING: University medical center research facility. PATIENTS: Three patients with complete homonymous hemianopia after acute infarction of the right posterior cerebral artery. MAIN OUTCOME MEASURES: Anatomical location of activated structures during horizontal optokinetic stimulation and T2-weighted anatomical magnetic resonance imaging. RESULTS: Occipitotemporal cortical areas (Brodmann areas 39 and 40) were the only activated cortical structures that showed statistically significant (P<.01) activation on the affected hemisphere. Of the subcortical areas, activation of thalamic nuclei appeared to be missing on the affected side, whereas the basal ganglia (putamen, globus pallidus, and caudate nucleus) were bilaterally activated. CONCLUSIONS: Bilateral activation of the basal ganglia confirms the concept of the basal ganglia-thalamocortical motor loop and of the efference copy of oculomotor pathways from each hemisphere. Our findings suggest 2 possible explanations for the activation of occipitotemporal areas (the human homolog of middle temporal/medial superior temporal areas) on the infarcted hemisphere: involvement of direct extrastriatal visual pathways or interhemispheric callosal connections between right and left middle temporal/medial superior temporal areas.

Aged↗

Robust localization of the contralateral precentral gyrus in hemiparetic patients using the unimpaired ipsilateral hand: a clinical functional magnetic resonance imaging protocol.

Tumor related contralateral motor deficits complicate preoperative functional magnetic resonance imaging (fMRI). In plegic patients the localization of the sensorimotor cortex is often impossible. In this context we developed a clinical fMRI protocol dedicated to patients with motor deficits using the unaffected ipsilateral hand. Based on the hypothesis that selfpaced finger movements recruit more and larger neuronal populations with rising task complexity, different motor tasks were tested regarding ipsilateral localization in ten right handed volunteers. Complex finger opposition localized the ipsilateral premotor cortex (Brodman area 6) robustly and was introduced to preoperative fMRI in hemiparetic patients as functional landmark to identify the precentral gyrus on the tumors side. Additional contralateral automated tactile stimulation localized the primary somatosensory cortex and completed the protocol.

Adult↗

Cholecystokinin hyperresponsiveness in functional dyspepsia.

Functional dyspepsia (FD) is a common disorder of yet uncertain etiology. Dyspeptic symptoms are usually meal related and suggest an association to gastrointestinal (GI) sensorimotor dysfunction. Cholecystokinin (CCK) is an established brain-gut peptide that plays an important regulatory role in gastrointestinal function. It inhibits gastric motility and emptying via a capsaicin sensitive vagal pathway. The effects on emptying are via its action on the proximal stomach and pylorus. CCK is also involved in the regulation of food intake. It is released in the gut in response to a meal and acts via vagal afferents to induce satiety. Furthermore CCK has also been shown to be involved in the pathogenesis of panic disorder, anxiety and pain. Other neurotransmitters such as serotonin and noradrenaline may be implicated with CCK in the coordination of GI activity. In addition, intravenous administration of CCK has been observed to reproduce the symptoms in FD and this effect can be blocked both by atropine and loxiglumide (CCK-A antagonist). It is possible that an altered response to CCK may be responsible for the commonly observed gastric sensorimotor dysfunction, which may then be associated with the genesis of dyspeptic symptoms.

Atropine↗

Using electroencephalography to study functional coupling between cortical activity and electromyograms during voluntary contractions in humans.

Previous studies of neuronal oscillations in sensorimotor cortex in humans and primates have observed rhythmic 15-30 Hz activity, which is correlated with motor output. In humans, this work has been limited to magnetic recordings. In the present study we investigate if similar results can be obtained using electroencephalography (EEG). EEG recordings were made from over the sensorimotor cortex of five adult subjects who performed repeated periods of maintained wrist extension and flexion. Coherence analysis between EEG and electromyogram (EMG) recordings from these muscles revealed correlation in the 15-30 Hz range, with a synchronous correlation structure which matches that previously observed in humans and in paired cortical recordings from primates. We conclude that EEG is equally efficient at investigating functional aspects of these cortical rhythms during voluntary movement in humans.

Adult↗

Input-output organization of the sensorimotor striatum in the squirrel monkey.

The basal ganglia receive massive inputs from the neocortex and send outputs that exert both inhibitory and disinhibitory control over parts of the frontal cortex and brainstem. Between these basal ganglia inputs and outputs lies the striatum, which receives most of the cortical afferents and projects to the basal ganglia output nuclei--the globus pallidus and substantia nigra. To analyze this system we conjointly labeled, in squirrel monkeys, sensorimotor cortical inputs to the striatum and striatal outputs to the globus pallidus. Anterograde tracers were injected into the motor (MI) and somatosensory (SI) cortical body maps, at sites determined by electrophysiological stimulation and recording. Retrograde tracers were stereotaxically injected into the external and internal pallidal segments (GPe and GPi). We found that multiple dispersed modules ("matrisomes") in the putamen that all received inputs from single body-part representations in sensorimotor cortex could, in turn, send convergent outputs to single sites in the pallidum. This divergence-reconvergence pattern was found for both GPe and GPi sites, and for inputs from both SI and MI cortex. Thus, information from a single functional region in the cortex can be split up at the striatal stage only to be brought back together in the pallidum. The temporary divergence may increase lateral interactions between sensorimotor matrisomes, as well as between matrisomes and striosomes. One function of striatal modularity may thus be to set up an associative network in the striatum, which might contribute to sensorimotor learning. We also found that some sets of matrisomes did not receive strong sensorimotor inputs, even though they projected to regions of GPe and GPi that are near the sensorimotor-recipient zones described above. Thus, the matrisomal system may sort MI/SI inputs and other inputs before transfer to paired regions of GPe and GPi.

Animals↗

The pallidosubthalamic projection: an anatomical substrate for nonmotor functions of the subthalamic nucleus in primates.

The subthalamic nucleus (STN) is the best target for correcting motor disability in parkinsonian patients with high-frequency stimulation. However, STN stimulation has also been reported to modify cognitive, emotional, and motivational functions. The aim of this study was to analyze the topographic organization of the STN according to its inputs coming from the sensorimotor, associative, and limbic territories of the external globus pallidus (GPe) in monkeys, with special reference to the limbic projection. Axonal tracers were injected into the different functional territories of the GPe. Injection performed in the limbic GPe resulted in labeling of cell bodies in the dorsal nucleus accumbens and in a dense labeling of axons in the anterior and medioventral portion of the STN. In comparison, injections in the associative and sensorimotor GPe led to labeling in the central and dorsolateral parts of the STN, respectively. Individual pallidosubthalamic axons ramified into numerous varicose branches, which were restricted to a given territory in the STN. These data provide a functional cartography of this structure in primates and suggest that behavioral disorders observed in stimulated parkinsonian patients could result from a dysfunction of the limbic part of the STN.

Animals↗

Somatosensorimotor function of the superior colliculus, somatosensory cortex, and lateral hypothalamus in the rat.

The role of the superior colliculus in multimodal sensory function is unsettled, in large part because a clear distinction between the somatosensory effects and the postural/motor effects of damage to the deep layers of the superior colliculus has not been obtained. Unilateral lesions of the entire superior colliculus impair orienting of the head and eyes to tactile, visual, and auditory stimuli presented on the side of the body contralateral to the lesion; however, even in the absence of sensory stimulation animals with such a lesion tend to circle ipsiversively and fail to make contralateral head movements. To determine whether or not unilateral damage to the superior colliculus produces a somatosensory asymmetry independently of head movement/circling biases, a neurological test was used in which lateral head or trunk movements were not required. Small pieces of adhesive-backed paper were attached to each forelimb and the latencies to contact and remove the stimuli were recorded. A battery of standard neurological tests was administered as well. The entire superior colliculus was removed unilaterally, and for comparison, the sensorimotor cortex or lateral hypothalamus were damaged in additional groups. Lesions of the superior colliculus produced the expected deficit in contralateral orienting and ipsilateral circling/postural biases, but failed to produce a somatosensory asymmetry in the head movement-independent sensorimotor test. In contrast, both sensorimotor cortex and lateral hypothalamus lesions produced a severe asymmetry in the head-movement-independent sensorimotor test. We conclude that the superior colliculus is involved in the control of lateral head movements and that its role in somatosensory function is fundamentally different from that of the sensorimotor cortex or lateral hypothalamus regions.

Animals↗

Cortical reorganization in patients with subcortical hemiparesis: neural mechanisms of functional recovery and prognostic implication.

OBJECT: A systematic investigation on cortical reorganization in patients with hemiparesis of a subcortical origin, with special emphasis on functional correlates, was conducted using functional magnetic resonance (fMR) imaging performed on a 3-tesla system specifically optimized for fMR imaging investigation. METHODS: The study group included 46 patients with hemiparesis (25 with right and 21 with left hemiparesis) and 30 age-matched healthy volunteers as controls. All study participants were originally right handed. The characteristics of the lesion were putaminal hemorrhage in 19 patients, thalamic hemorrhage in 10 patients, and striatocapsular bland infarction in 17 patients. Functional recovery in subcortical hemiparesis showed two distinct phases of the recovery process involving entirely different neural mechanisms. Phase I is characterized by the process of recovery and/or reorganization of the primary system. Successful recovery of this system is typically reached within 1 month after stroke onset. Its clinical correlate is a rapid recovery course and significant recovery of function within 1 month of stroke onset. Failure of recovery of the primary system shifts the recovery process to Phase II, during which reorganization involving the ipsilateral pathway takes place. The clinical correlate of Phase II is a slow recovery course with variable functional outcome. CONCLUSIONS: Effective functional organization of the ipsilateral pathway, as identified by linked activation of the ipsilateral primary sensorimotor cortex and contralateral anterior lobe of the cerebellum, is correlated with a good prognostic outcome for patients in the slow recovery group. A high degree of connectivity between supplementary motor areas, bilaterally, appears to influence functional recovery adversely.

Aged↗

Cortical reorganization induced by virtual reality therapy in a child with hemiparetic cerebral palsy.

Virtual reality (VR) therapy is a new, neurorehabilitation intervention aimed at enhancing motor performance in children with hemiparetic cerebral palsy (CP). This case report investigated the effects of VR therapy on cortical reorganization and associated motor function in an 8-year-old male with hemiparetic CP. Cortical activation and associated motor development were measured before and after VR therapy using functional magnetic resonance imaging (fMRI) and standardized motor tests. Before VR therapy, the bilateral primary sensorimotor cortices (SMCs) and ipsilateral supplementary motor area (SMA) were predominantly activated during affected elbow movement. After VR therapy, the altered activations disappeared and the contralateral SMC was activated. This neuroplastic change was associated with enhanced functional motor skills including reaching, self-feeding, and dressing. These functions were not possible before the intervention. To our knowledge, this is the first fMRI study in the literature that provides evidence for neuroplasticity after VR therapy in a child with hemiparetic CP.

Activities of Daily Living↗

Monotonicity of nerve tests in diabetes: subclinical nerve dysfunction precedes diagnosis of polyneuropathy.

OBJECTIVE: The objective of this study was to test whether monotone worsening of nerve function, attributable to diabetes, can be demonstrated before criteria for diabetic sensorimotor polyneuropathy (DSPN) have been met. Which nerve tests are best? RESEARCH DESIGN AND METHODS: From a prevalence cohort of 504 individuals in the Rochester Diabetic Neuropathy study (RDNS), we identified 238 individuals (group 1) who at first examination were without polyneuropathy (DSPN) by a sum score of the normal deviates (from percentiles) of five attributes of nerve conduction of the legs (i.e., their five nerve conduction normal deviate values were <97.5th percentile) and were followed longitudinally two or more times. Of these 238, 90 (group 2) were followed six or more times at yearly or bi-yearly intervals. We compared different nerve tests for the ones most sensitive and reliable in showing latent nerve dysfunction and monotone (the extent to which a variable measured repeatedly over time reveals a significant trend of worsening or improvement). RESULTS: In group 1 patients, the mean sum score of five attributes of nerve conduction (sigma 5 NC nds) at baseline was 1.08 and at the last examination (only patients with Sigma 5 NC nds <97.5th percentile) was 3.63, markedly higher than that in healthy subjects (only of individuals with Sigma 5 NC nds <97.5th percentile) (-0.12), indicating a subtle latent shift of nerve conduction tests toward abnormality. Serial evaluations of many individual and especially sum scores of nerve conduction tests in group 2 patients showed statistically significant worsening with time, even when nerve conduction tests were still well within normal limits. Neurologic signs also worsened but barely to significant levels; however, symptoms and quantitative sensation tests did not. Considering the composite score sigma 5 NC nds, 42 (of 90 group 2 patients) showed significant worsening, 22 were still without DSPN by nerve conduction test criteria, and some were even below the 50th percentile at the last evaluation. CONCLUSIONS: Subtle and latent functional worsening of nerve conduction can be demonstrated even before nerve conduction test criteria for DSPN have been met. For demonstrating monotone worsening, the order (from best to worst) of tests was: some composite scores of nerve conduction and individual attributes of nerve conduction. We did not show monotone worsening of symptoms or of quantitative sensation test results. In multivariate analysis of risk factors and their association with worsening sigma 5 NC nds, 24-h microalbuminuria (a marker of microvessel disease) was found to be a significant covariate, an indication that the asymptomatic alterations of nerve conduction are meaningful.

Adult↗

Anomalous sensorimotor integration in adults who stutter: a tendon vibration study.

Anomalies in oral movement control have been identified in stuttering, which suggest this speech disorder involves a sensorimotor deficit. To test whether adults who stutter (AWS) display aberrant proprioceptive function, masseter tendon vibration was used to manipulate jaw proprioception as AWS and normal speakers performed a jaw-opening task. A movement amplitude reduction in the vibration condition was observed in both groups indicating the movements of AWS and controls were influenced in a similar manner by altering masseter proprioception. However, the undershoot magnitude was reduced in AWS relative to the control participants indicating a subtle difference in proprioceptive integration among the stuttering participants. Our interpretation is that AWS use proprioceptive information less efficiently than normal speakers, which could interfere with sensorimotor integration during speech production.

Adult↗

Vasotocin innervation and modulation of vocal-acoustic circuitry in the teleost Porichthys notatus.

Arginine vasotocin (AVT) and its mammalian homologue arginine vasopressin (AVP) modulate reproduction-related and other social behaviors in a broad range of vertebrate species. These functions of AVT/AVP may be in part achieved through the modulation of sensorimotor integration, although experimental evidence supporting this hypothesis remains limited. In the present experiments, we demonstrate (1) AVT innervation of candidate vocal-acoustic brain regions, and (2) AVT modulation of vocal-motor physiology in the plainfin midshipman fish (Porichthys notatus), which uses vocalizations in both mate attraction and agonistic contexts. AVT distribution was compared with known vocally active brain regions and to central auditory and vocal pathways. AVT-immunoreactive fibers and putative terminals descend almost exclusively from the preoptic area and are found in two primary candidate sites for vocal-acoustic integration - the anterior tuberal hypothalamus and paralemniscal midbrain tegmentum. AVT immunoreactivity is also located in several other vocally active regions, including the ventral tuberal nucleus, periaqueductal gray, and paraventricular regions of the isthmus and rostral hindbrain. The parvocellular preoptic area itself is also vocally active, although thresholds are substantially higher than for other regions. The functional significance of AVT input to vocal-acoustic regions was demonstrated in the paralemniscal midbrain where local delivery of AVT modulated electrically evoked, rhythmic vocal-motor output, which precisely mimicked natural vocalizations. AVT produced dose-dependent inhibitions of parameters associated with call initiation (burst latency and number of vocal-motor bursts elicited) but not of vocal-motor patterning (fundamental frequency and burst duration). Together, these findings provide support for the proposal that AVT modulates sensorimotor processes underlying social/acoustic communication.

Animals↗