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Population computation of vectorial transformations.

Many neurons of the central nervous system are broadly tuned to some sensory or motor variables. This property allows one to assign to each neuron a preferred attribute (PA). The width of tuning curves and the distribution of PAs in a population of neurons tuned to a given variable define the collective behavior of the population. In this article, we study the relationship of the nature of the tuning curves, the distribution of PAs, and computational properties of linear neuronal populations. We show that noise-resistant distributed linear algebraic processing and learning can be implemented by a population of cosine tuned neurons assuming a nonuniform but regular distribution of PAs. We extend these results analytically to the noncosine tuning and uniform distribution case and show with a numerical simulation that the results remain valid for a nonuniform regular distribution of PAs for broad noncosine tuning curves. These observations provide a theoretical basis for modeling general nonlinear sensorimotor transformations as sets of local linearized representations.

Algorithms↗

[Adenylate cyclase and 5'-nucleotidase activities in the sensorimotor and limbic structures of the rat brain after training in a manipulative skill].

The activities of adenylate cyclase (AC) and 5'-nucleotidase (NT) were studied in the limbic (amygdala, hippocampus) and sensorimotor (cortex, striatum) brain structures of three rat groups: control (without training), not well and well learning to perform movements with pushing the operandum. It was found, that after training the activity of AC was decreased in all structures studied. Moreover, in the cortex and the striatum the decrease was more pronounced in the group of well learning rats, while in the amygdala--in not well learning ones. The activity of NT in all brain structures, excepting the striatum, was more significantly decreased in the rats with low ability to learn the movements with prolonged pushing. Only in the striatum the increase of NT activity (initially the lowest in the control animals--1.0 +/- 0.04 microgram P(i)/mg protein/min) up to 1.3 +/- 0.1 in not well and up to 2.0 +/- 0.1 in well learning animals was found. The interhemispheric [correction of intrahemispheric] asymmetry of AC activity in the cortex and of NT in the hippocampus was revealed. Thus, the changes of the activity of the enzymes, participating in the biogenesis of adenosine (NT) and c-AMP (AC) are different in the limbic and sensorimotor structures dependently on learning ability of rats. The increase of NT activity after learning only in the striatum could reflect a specific role of purinergic system of this brain structure in the regulation of sensory controlled movements.

5'-Nucleotidase↗

Functional MRI reveals the existence of modality and coordination-dependent timing networks.

Growing evidence suggests that interval timing in humans is supported by distributed brain networks. Recently, we demonstrated that the specific network recruited for the performance of rhythmic timing is not static but is influenced by the coordination pattern employed during interval acquisition. Here we expand on this previous work to investigate the role of stimulus modality and coordination pattern in determining the brain areas recruited for performance of a self-paced rhythmic timing task. Subjects were paced with either a visual or an auditory metronome in either a synchronized (on the beat) or syncopated (off the beat) coordination pattern. The pacing stimulus was then removed and subjects continued to move based on the required interval. When compared with networks recruited for auditory pacing and continuation, the visual-specific activity was observed in the classic dorsal visual stream that included bilateral MT/V5, bilateral superior parietal lobe, and right ventral premotor cortex. Activity in these regions was present not only during pacing, when visual information is used to guide motor behavior, but also during continuation, when visual information specifying the temporal interval was no longer present. These results suggest a role for modality-specific areas in processing and representing temporal information. The cognitive demands imposed by syncopated coordination resulted in increased activity in a broad network that included supplementary motor area, lateral pre-motor cortex, bilateral insula, and cerebellum. This coordination-dependent activity persisted during the subsequent continuation period, when stimuli were removed and no coordination constraints were imposed. Taken together, the present results provide additional evidence that time and timing are served by a context-dependent distributed network rooted in basic sensorimotor processes.

Acoustic Stimulation↗

Continuous delivery of neurotrophin 3 by gene therapy has a neuroprotective effect in experimental models of diabetic and acrylamide neuropathies.

Neurotrophic factors (NFs) are promising agents for the treatment of peripheral neuropathies such as diabetic neuropathy. However, the value of treatment with recombinant NF is limited by the short half-lives of these molecules, which reduces efficiency, and by their potential toxicity. We explored the use of intramuscular injection of a recombinant adenovirus encoding NT-3 (AdNT-3) to deliver sustained low doses of NT-3. We assessed its effect in two rat models: streptozotocin (STZ)-induced diabetes, a model of early diabetic neuropathy characterized by demyelination, and acrylamide experimental neuropathy, a model of diffuse axonal neuropathy which, like late-onset human diabetic neuropathy, results in a diffuse sensorimotor neuropathy with dysautonomy. Treatment of STZ-diabetic rats with AdNT-3 partially prevented the slowing of motor and sensory nerve conduction velocities (p < 0.01 and p < 0.0001, respectively). Treatment with AdNT-3 of acrylamide-intoxicated rats prevented the slowing of motor and nerve conduction velocities (p < 0.001 and p < 0.0001, respectively) and the decrease in amplitude of compound muscle potentials (p < 0.0001), an index of denervation. Acrylamide-intoxicated rats treated with NT-3 had higher than control levels of muscle choline acetyltransferase activity (p < 0.05), suggesting greater muscle innervation. In addition, treatment of acrylamide-intoxicated rats with AdNT-3 significantly improved behavioral test results. Treatment with AdNT-3 was well tolerated with minimal muscle inflammation and no detectable general side effects. Therefore, our results suggest that NT-3 delivery by adenovirus-based gene therapy is a promising strategy for the prevention of both early diabetic neuropathy and axonal neuropathies, especially late axonal diabetic neuropathy.

Acrylamides↗

Bifurcation and singularity analysis of a molecular network for the induction of long-term memory.

Withdrawal reflexes of the mollusk Aplysia exhibit sensitization, a simple form of long-term memory (LTM). Sensitization is due, in part, to long-term facilitation (LTF) of sensorimotor neuron synapses. LTF is induced by the modulatory actions of serotonin (5-HT). Pettigrew et al. developed a computational model of the nonlinear intracellular signaling and gene network that underlies the induction of 5-HT-induced LTF. The model simulated empirical observations that repeated applications of 5-HT induce persistent activation of protein kinase A (PKA) and that this persistent activation requires a suprathreshold exposure of 5-HT. This study extends the analysis of the Pettigrew model by applying bifurcation analysis, singularity theory, and numerical simulation. Using singularity theory, classification diagrams of parameter space were constructed, identifying regions with qualitatively different steady-state behaviors. The graphical representation of these regions illustrates the robustness of these regions to changes in model parameters. Because persistent protein kinase A (PKA) activity correlates with Aplysia LTM, the analysis focuses on a positive feedback loop in the model that tends to maintain PKA activity. In this loop, PKA phosphorylates a transcription factor (TF-1), thereby increasing the expression of an ubiquitin hydrolase (Ap-Uch). Ap-Uch then acts to increase PKA activity, closing the loop. This positive feedback loop manifests multiple, coexisting steady states, or multiplicity, which provides a mechanism for a bistable switch in PKA activity. After the removal of 5-HT, the PKA activity either returns to its basal level (reversible switch) or remains at a high level (irreversible switch). Such an irreversible switch might be a mechanism that contributes to the persistence of LTM. The classification diagrams also identify parameters and processes that might be manipulated, perhaps pharmacologically, to enhance the induction of memory. Rational drug design, to affect complex processes such as memory formation, can benefit from this type of analysis.

Algorithms↗

Clinical and neurochemical effects of fenfluramine in children with autism.

Fifteen children with autism were treated with 60 mg d,l-fenfluramine (FEN) or placebo in a double-blind A-B-A protocol followed immediately by double-blind placebo-controlled crossover administration of FEN (total duration 62 weeks). Both biochemical and clinical outcomes were examined. Biochemically, FEN led to an increase in dihydroxyphenylacetic acid (DOPAC) and decreases in whole-blood serotonin (5-HT), plasma norepinephrine (NE), and plasma 3-methoxy-4-hydroxyphenylglycol (MHPG). The decrease in whole-blood 5-HT was seen only during treatment with FEN. However, NE levels did not return to baseline as long as 8 weeks after the first FEN treatment period. Increases in DOPAC were greater during the second FEN treatment period than the first. Persistent changes in catecholamine regulation may be related to previously reported long-term effects on central nervous system 5-HT after FEN. Clinically, FEN led to a modest decrease in parent, but not teacher, ratings of hyperactivity and to a small reduction in sensorimotor abnormalities. Abnormal social and affectual responses also decreased, but this was not directly related to FEN treatment. Effects on cognition were equivocal. Hyperserotonemic subjects did not differ from normoserotonemic subjects in clinical response. Overall, no significant advantage for the use of FEN could be established.

3,4-Dihydroxyphenylacetic Acid↗

Electrocorticographic gamma activity during word production in spoken and sign language.

OBJECTIVE: To investigate the functional-neuroanatomic substrates of word production using signed versus spoken language. METHODS: The authors studied single-word processing with varying input and output modalities in a 38-year-old woman with normal hearing and speech who had become proficient in sign language 8 years before developing intractable epilepsy. Subdural electrocorticography (ECoG) was performed during picture naming and word reading (visual inputs) and word repetition (auditory inputs); these tasks were repeated with speech and with sign language responses. Cortical activation was indexed by event-related power augmentation in the 80- to 100-Hz gamma band, and was compared with general principles of functional anatomy and with subject-specific maps of the same or similar tasks using electrical cortical stimulation (ECS). RESULTS: Speech outputs activated tongue regions of the sensorimotor cortex, and sign outputs activated hand regions. In addition, signed word production activated parietal regions that were not activated by spoken word production. Posterior superior temporal gyrus was activated earliest and to the greatest extent during auditory word repetition, and the basal temporal-occipital cortex was activated similarly during naming and reading, reflecting the different modalities of input processing. With few exceptions, topographic patterns of ECoG gamma were consistent with ECS maps of the same or similar language tasks. CONCLUSIONS: Spoken and signed word production activated many of the same cortical regions, particularly those processing auditory and visual inputs; however, they activated different regions of sensorimotor cortex, and signing activated parietal cortex more than did speech. This study illustrates the utility of electrocorticographic gamma for studying the neuroanatomy and processing dynamics of human language.

Brain Mapping↗

Effects of intracerebroventricularly injected "nerveside" on free behaviour and EEG activity of rats. A pilot study.

"Nerveside", a phosphopeptide extracted from ox and dog brains by Toh, was injected into one lateral ventricle of four rats previously prepared for the injection as well as for recordings of the EEG of the dorsal hippocampus (field CA1) and sensorimotor cortex. "Nerveside" in doses of 150 and 300 micrograms/animal induced a transient stereotyped behaviour and longer lasting alterations of the EEG activity and vigilance pattern. Wakefulness was increased, slow wave sleep and REM-sleep were diminished. The vigilance pattern was characterized by rapid shifts between all three vigilance states. The effects of "nerveside" were visible for about three hours.

Animals↗

Neurobiology of autism.

Autism is a behaviorally defined, life-long static developmental disorder of the brain that is poised for neurobiological investigation. It affects at least 1 or 2 in 1000 persons and has a broad range of severity. It has multiple causes, with genetics playing a major role. According to the DSM-IV, defining features are impaired sociability, language and communication, and range of interests and activities. Mental deficiency is frequent but by no means universal. The cognitive profile is characteristic, occasionally with a superior but narrow talent. Perseveration, concreteness, affective blunting, and lack of insight into other persons' thinking may be conspicuous. The neurological basis of autism's many sensorimotor features, including stereotypies, is unknown. Attention and sleep are affected, and one third of individuals experience epilepsy by adulthood. Whether subclinical epilepsy plays a role in the developmental regression of the one third of the toddlers who lose their language skills and become autistic remains to be determined. Clinical neuroimaging and biochemical investigations are generally unremarkable. Fewer than 35 brains have been examined pathologically, none with modern techniques. The findings thus far suggest subtle prenatal neuronal maldevelopment in the cerebellum and certain limbic structures. Abnormalities in distributed networks involving serotonin and perhaps other neurotransmitters require further documentation.

Autistic Disorder↗

Compensatory plasticity and sensory substitution in the cerebral cortex.

Cats deprived visually from birth show few overt impairments in their natural behavior. Therefore, they seem well suited as an animal model for the study of compensatory plasticity after early vision loss. It can be demonstrated that binocularly deprived cats show improved abilities of auditory localization, and at least equal tactile behavior compared to normal controls. Within the anterior ectosylvian cortex of binocularly deprived cats, where different sensory modalities come together, the anterior ectosylvian visual area is completely taken over by auditory and somatosensory inputs. Furthermore, the auditory spatial tuning of single units in this cortical region is sharpened significantly as a result of visual deprivation. Somatosensory compensation for early loss of vision can be demonstrated by a hypertrophy of the facial vibrissae, and a corresponding expansion of their central representation in the somatosensory cortex of binocularly deprived animals. The compensatory changes in the cortex can be explained by a reorganization of sensory representations under the guidance of sensorimotor feedback rather than by instruction through an extraneous 'supervisory' signal. These processes might form the neural basis of sensory substitution in blind humans.

Animals↗

The deafferentation syndrome in genetically blind rats: a model of the painful phantom limb.

The hypothesis was tested which states that the somatic deafferentation syndrome is a visually prompted response to sensorimotor loss. The dorsal roots, C5-T2, were bilaterally cut in a strain of rats known to be genetically blind. These complete dorsal rhizotomies left the forelimbs totally anesthetic, analgesic and paretic. Contact and visual placing reactions were absent, and responses to pinprick or pinch were absent. Self-mutilation limited to the distal digits appeared on the first or second postoperative days and then progressed proximally. The forelimbs were symmetrically affected, and no other body parts were mutilated. The spatial precision of this syndrome, in the absence of visual as well as peripheral somatosensory information from the affected limb, indicates that controlled guidance of the behavior arises from an existing central representation of the limb and its relationship with the total body; a phantom limb. Consideration of other reports regarding the deafferentation syndrome leads to the view that it is motivated by disturbing abnormal sensations (pain) of central neural origin.

Afferent Pathways↗

Parkinson's disease and RLS: the dopaminergic bridge.

Dopamine is a neurotransmitter that modulates diverse waking behaviors including movement, motivation, cognition, reward, and feeding. Interest in dopamine's additional contributions to normal and pathologic sleep-wake states has experienced a recent rebirth originating from two clinical disorders: Parkinson's disease and Restless Legs Syndrome. The former, the prototypical disorder of brain dopamine cell loss, is accompanied by marked sleep disruption and impairments in daytime alertness. The latter is exquisitively responsive to pharmacologic agents that act upon dopamine receptors. The potential neurobiological substrates underlying these observations are reviewed here. Converging lines of evidence suggest that mesocorticolimbic dopamine circuits are involved in promoting wakefulness, while a less studied diencephalospinal dopamine system might underly the sensorimotor dysfunction of Restless Legs Syndrome.

Brain↗

Restless legs syndrome and periodic limb movement disorder in the elderly.

Restless legs syndrome (RLS) is a sensorimotor neurological disorder characterized by an urge to move the extremities, mostly the legs, caused or accompanied by unpleasant sensations in the affected limbs. Symptoms appear or increase in the evening or during the night and at rest. Sleep disturbances are the most frequent reason why patients seek medical aid. The diagnosis of periodic limb movement disorder (PLMD) requires polysomnographic confirmation and relies on the exclusion of other causes of sleep disturbances. The diagnosis of RLS is a clinical one and usually based on the patient's history. Diagnosis criteria should be applied in a modified form in the cognitively impaired elderly. The newly revised criteria emphasize behavioral indicators and supportive features in diagnosing RLS in this special population. Prevalence of both disorders increases strongly with age. Epidemiological studies revealed a 9% to 20% prevalence of RLS and an estimated 4% to 11% prevalence of PLMD in the elderly. Recent studies indicate RLS occurring approximately twice as often in older women than in older men. Treatment with dopaminergic drugs, opioids, anticonvulsants or hypnotics are usually well tolerated in the elderly. However, interaction with other medications and the possibility of severe sedation due to slower metabolism in the elderly should be considered.

Aged↗

Reversible blockade of rodent whisking: Botulinum toxin as a tool for developmental studies.

Studies of sensorimotor systems such as the whisking system of rodents have suggested that associations between body movements and their sensory consequences during development may make an important contribution to the functional organization of the system. In the present study we have explored the possible utility of Botulinum toxin for developmental studies of whisking. Botox selectively blocks whisking-generated afference leaving other sources of whisker afference intact. We describe appropriate modes of injection, define dosage levels, and assess the effects of prolonged whisking paralysis during development upon the basic motor competency of the adult rat. Our findings indicate that: (a) Botulinum toxin may be used to block whisking behavior in adult and developing rats, (b) that the duration of the whisking paralysis produced by Botox treatment blockade is dose dependent in both developing and adult animals, (c) that the blockade is functionally reversible and (d) that Botox treatment during development does not impair either the kinematics or the rhythmic patterning of adult whisking behavior. Botox may be a useful tool for studying the role of experiential factors in the development of "active touch" in rodents.

Afferent Pathways↗

Mauthner and reticulospinal responses to the onset of acoustic pressure and acceleration stimuli.

We determined how the Mauthner cell and other large, fast-conducting reticulospinal neurons of the goldfish responded to acoustic stimuli likely to be important in coordinating body movements underlying escape. The goal was to learn about the neurophysiological responses to these stimuli and the underlying processes of sensorimotor integration. We compared the intracellularly recorded postsynaptic responses (PSPs) of 9 Mauthner cells and a population of 12 other reticulospinal neurons to acoustic pressure and acceleration stimuli. All recorded cells received both pressure and acceleration inputs and responded to stimuli regardless of initial polarity. Thus these cells receive acoustic components necessary to determine source direction. We observed that the Mauthner cell was broadly tuned to acoustic pressure from 100 to 2,000 Hz, with a Q(10dB) of 0.5-1.1 over the best frequency range, 400-800 Hz. This broad tuning is probably due to input from S1 afferents and is similar to tuning of the behavioral audiogram. Our data suggest that cells have relatively more sustained responses to acceleration than to pressure stimuli, to which they rapidly adapted. For a given cell, PSP latencies and amplitudes varied inversely with stimulus intensity. For the entire population of cells studied, minimum onset latencies (i.e., those at the highest intensities) ranged from 0.7 to 7.6 ms for acoustic pressure and 0.7 to 9.8 ms for acceleration. This distribution in minimum onset latencies is consistent with earlier EMG and kinematic findings and supports our previous hypothesis that escape trajectory angle is controlled, in part, by varying the activation time of neurons in the escape network. While the Mauthner cell latency did not differ to both onset polarities of pressure and acceleration, this was not true of all cells. Also, the Mauthner cell responses to pressure were approximately 0.6 ms faster than to acceleration; for the other cells, this difference was 1.1 ms with some cells having differences </=3 ms. To both pressure and acceleration, the average, minimum Mauthner cell latency was approximately 1 ms faster than the average of the 12 other cells. These data are consistent with the hypothesis that the Mauthner cell fires first, followed by other reticulospinal neurons, which more finely regulate escape trajectory. Finally, analysis of our results suggests that while pressure is more important in depolarizing the cell near threshold, high levels of acceleration, perhaps from fluid flow, may be very important in activating the system in a directional manner.

Acceleration↗

Long-term follow-up study of children developmentally retarded by early environmental deprivation.

In 1972, two children representing a case of severe developmental retardation were discovered and taken into custody. The children, an older sister (referred to as F) and a younger brother (referred to as G), were found to have achieved no more than the physical and mental age level normal to children 1 year of age or less, in spite of their actual respective chronological ages of 6 and 5. Investigation revealed that the children's developmental retardation was due both to extreme social isolation and to complex deprivation. By following their sensorimotor, linguistic, cognitive, and socio-emotional development from the time of discovery to the date of this writing, we have found that their physical and motor development or recovery has proceeded smoothly, whereas their linguistic and cognitive development has continued to show such weaknesses as defective functioning of internal speech (Vygotsky, 1962) and poor ability to deal with abstract, linguistic subjects. F and G have continued to exhibit a tendency toward undersocialization, but this has at times been rather a positive factor in the process of attaining ego identity during adolescence, especially for G, serving to protect him from unreasonable social pressures to conform to group behavior. In combination with other cases of severe deprivation, the case of F and G holds some interesting implications for theories of human development, particularly the notion of critical periods.

Child↗

[Effects of knee braces on sensorimotor capabilities of patients with ACL reconstruction].

In 25 test persons with Anterior-Cruciate-Ligament (ACL)-Operation the sensomotory capabilities of the affected and the unaffected side were examined by KAT 2000 (BREG Inc., Vista, C.A., USA) with and without knee-brace (Hypex knee-brace/Fa. Aircast-Europa GmbH). The results were compared with those of a control group. In all cases of test variations (both leg-static/both leg-dynamic/one leg-static) there were significant differences between testing with and without knee brace. In the one leg-static test there was an improvement of 30% (p < 0.01), in the both leg-static test an improvement of 24% (p < 0.01). The both leg-dynamic showed a similar result (23.8%; p < 0.01). These noticed adaptations may be mediated by improvements of proprioceptive and exteroceptive capabilities and a positive impact on the anticipative control of behavior. The results of the control group differ in only a few cases from the results in the group of patients. This may be judged as indicator for the variety of sensomotory capabilities in the general population.

Adaptation, Physiological↗

Dynamic regulation of sensorimotor integration in human postural control.

Upright stance in humans is inherently unstable, requiring corrective action based on spatial-orientation information from sensory systems. One might logically predict that environments providing access to accurate orientation information from multiple sensory systems would facilitate postural stability. However, we show that, after a period in which access to accurate sensory information was reduced, the restoration of accurate information disrupted postural stability. In eyes-closed trials, proprioceptive information was altered by rotating the support surface in proportion to body sway (support surface "sway-referencing"). When the support surface returned to a level orientation, most subjects developed a transient 1-Hz body sway oscillation that differed significantly from the low-amplitude body sway typically observed during quiet stance. Additional experiments showed further enhancement of the 1-Hz oscillation when the surface transitioned from a sway-referenced to a reverse sway-referenced motion. Oscillatory behavior declined with repetition of trials, suggesting a learning effect. A simple negative feedback-control model of the postural control system predicted the occurrence of this 1-Hz oscillation in conditions where too much corrective torque is generated in proportion to body sway. Model simulations were used to distinguish between two alternative explanations for the excessive corrective torque generation. Simulation results favor an explanation based on the dynamic reweighting of sensory contributions to postural control rather than a load-compensation mechanism that scales torque in proportion to a fixed combination of sensory-orientation information.

Adaptation, Physiological↗