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PubMed2003

Should the injured and intact hemispheres be treated differently during the early phases of physical restorative therapy in experimental stroke or parkinsonism?

Over a century ago the intact cortex was proposed to contribute to recovery from unilateral brain injury, but its possible role in functional outcome has become more appreciated in recent years as a result of anatomic, metabolic and behavioral studies. Although use of the contralesional limb is naturally impaired after sensorimotor cortex injury, neural and astrocytic events in the intact hemisphere may give rise to, and may be influenced by, an enhanced ability to compensate for lost motor function. The debate is still open as to whether the neural changes are generally compensatory in nature, with activity in the homotopic cortex leading to greater capability in the nonimpaired limb, or whether they are actually a matter of reorganization in the homotopic cortex leading to connections to denervated targets in the opposite hemisphere, thus allowing the homotopic cortex to control motor programs there. Although both phenomena may occur to some degree, there is mounting evidence in support of the former view. Careful behavioral techniques have been developed that can expose compensatory tricks, and the time course of these behaviors correlates well with anatomic data. Moreover, if the intact cortex sustains a second lesion after recovery from the first, forelimb sensorimotor function specific to the first-impaired side of the body is not worsened. Partial denervation of callosal fibers coming from the injured hemisphere, plus preferential use of the good forelimb caused by a cortical injury, may increase trophic factors in the intact hemisphere. These and related events seem to provide a growth-favorable environment there that permits motor learning in the intact forelimb at a level of skill exceeding that which a normal animal can attain in the same period of time. There are anecdotal cases in human neurologic patients that are consistent with these findings. For example, a colleague of the authors who sustained a unilateral infarction that rendered his dominant right hand severely impaired noticed that soon after the stroke he was able to use his left hand for writing and computers as well as he had ever used his right hand. Cross-midline placing tests also indicate that the structural events observed in the intact cortex may potentiate projections to the damaged hemisphere. These changes may help restore the capacity of tactile information projecting to the intact hemisphere to control limb placing in the impaired forelimb. Neural events in the injured hemisphere can be affected by behavior differently than the neural events in the intact hemisphere. Different therapeutic strategies might well be used on opposing limbs at different times after unilateral sensorimotor cortex injury to optimize recovery (and, indeed, to avoid exaggerating the insult). Finally, the details of reorganization in both hemispheres differ greatly depending on the type of brain injury sustained (eg, in stroke versus Parkinson's disease), suggesting that an approach that considers the role of both hemispheres is likely to be beneficial in research on a broad variety of brain pathologies.

Animals↗
PubMed2006

A parametric fMRI investigation of context effects in sensorimotor timing and coordination.

Mounting evidence suggests that information derived from environmental and behavioral sources is represented and maintained in the brain in a context-dependent manner. Here we investigate whether activity patterns underlying movements paced according to an internal temporal representation depend on how that representation is acquired during a previous pacing phase. We further investigate the degree to which context dependence is modulated by different time delays between pacing and continuation. BOLD activity was recorded while subjects moved at a rate established during a pacing interval involving either synchronized or syncopated coordination. Either no-delay or a 3, 6 or 9s delay was introduced prior to continuation. Context-dependent regions were identified when differences in neural activity generated during pacing continued to be observed during continuation despite the intervening delay. This pattern was observed in pre-SMA, bilateral lateral premotor cortex, bilateral declive and left inferior semi lunar lobule. These regions were more active when continuation followed from syncopation than from synchronization regardless of the delay length putatively revealing a context-dependent neural representation of the temporal interval. Alternatively, task related regions in which coordination-dependent differences did not persist following the delay, included bilateral putamen and supplementary-motor-area. This network may support the differential timing demands of coordination. A classic prefrontal-parietal-temporal working memory network was active only during continuation possibly providing mnemonic support for actively maintaining temporal information during the variable delay. This work provides support for the hypothesis that some timing information is represented in a task-dependent manner across broad cortical and subcortical networks.

Adult↗
PubMed1998

Sensorimotor adaptation in speech production.

Human subjects are known to adapt their motor behavior to a shift of the visual field brought about by wearing prism glasses over their eyes. The analog of this phenomenon was studied in the speech domain. By use of a device that can feed back transformed speech signals in real time, subjects were exposed to phonetically sensible, online perturbations of their own speech patterns. It was found that speakers learn to adjust their production of a vowel to compensate for feedback alterations that change the vowel's perceived phonetic identity; moreover, the effect generalizes across phonetic contexts and to different vowels.

Adaptation, Physiological↗
PubMed2006

Mapping information flow in sensorimotor networks.

Biological organisms continuously select and sample information used by their neural structures for perception and action, and for creating coherent cognitive states guiding their autonomous behavior. Information processing, however, is not solely an internal function of the nervous system. Here we show, instead, how sensorimotor interaction and body morphology can induce statistical regularities and information structure in sensory inputs and within the neural control architecture, and how the flow of information between sensors, neural units, and effectors is actively shaped by the interaction with the environment. We analyze sensory and motor data collected from real and simulated robots and reveal the presence of information structure and directed information flow induced by dynamically coupled sensorimotor activity, including effects of motor outputs on sensory inputs. We find that information structure and information flow in sensorimotor networks (a) is spatially and temporally specific; (b) can be affected by learning, and (c) can be affected by changes in body morphology. Our results suggest a fundamental link between physical embeddedness and information, highlighting the effects of embodied interactions on internal (neural) information processing, and illuminating the role of various system components on the generation of behavior.

Biomimetics↗
PubMed1992

[Neurology of behavior as basis in neuro-rehabilitation].

Based on phylogenetic and ontogenetic aspects of sensorimotor development, human behaviour may be differentiated on three levels: (1) visceration as movements within the organism itself; (2) expression of inner states in posture, language and gesture by which only other living organisms can be influenced (socioverse activity); and (3) effectuation, which leads to changes of the living and material environment by direct contact (materioverse activity). These levels of behaviour are organized in different, cooperating structures of the central nervous system. Knowledge of them, and their practical applicability, form the basis of neurorehabilitation.

Behavior↗
PubMed2000

An associational model of birdsong sensorimotor learning I. Efference copy and the learning of song syllables.

Birdsong learning provides an ideal model system for studying temporally complex motor behavior. Guided by the well-characterized functional anatomy of the song system, we have constructed a computational model of the sensorimotor phase of song learning. Our model uses simple Hebbian and reinforcement learning rules and demonstrates the plausibility of a detailed set of hypotheses concerning sensory-motor interactions during song learning. The model focuses on the motor nuclei HVc and robust nucleus of the archistriatum (RA) of zebra finches and incorporates the long-standing hypothesis that a series of song nuclei, the Anterior Forebrain Pathway (AFP), plays an important role in comparing the bird's own vocalizations with a previously memorized song, or "template." This "AFP comparison hypothesis" is challenged by the significant delay that would be experienced by presumptive auditory feedback signals processed in the AFP. We propose that the AFP does not directly evaluate auditory feedback, but instead, receives an internally generated prediction of the feedback signal corresponding to each vocal gesture, or song "syllable." This prediction, or "efference copy," is learned in HVc by associating premotor activity in RA-projecting HVc neurons with the resulting auditory feedback registered within AFP-projecting HVc neurons. We also demonstrate how negative feedback "adaptation" can be used to separate sensory and motor signals within HVc. The model predicts that motor signals recorded in the AFP during singing carry sensory information and that the primary role for auditory feedback during song learning is to maintain an accurate efference copy. The simplicity of the model suggests that associational efference copy learning may be a common strategy for overcoming feedback delay during sensorimotor learning.

Algorithms↗
PubMed1995

An internal model for sensorimotor integration.

On the basis of computational studies it has been proposed that the central nervous system internally simulates the dynamic behavior of the motor system in planning, control, and learning; the existence and use of such an internal model is still under debate. A sensorimotor integration task was investigated in which participants estimated the location of one of their hands at the end of movements made in the dark and under externally imposed forces. The temporal propagation of errors in this task was analyzed within the theoretical framework of optimal state estimation. These results provide direct support for the existence of an internal model.

Brain↗
PubMed2000

Song selectivity and sensorimotor signals in vocal learning and production.

Bird song, like human speech, is a learned vocal behavior that requires auditory feedback. Both as juveniles, while they learn to sing, and as adults, songbirds use auditory feedback to compare their own vocalizations with an internal model of a target song. Here we describe experiments that explore a role for the songbird anterior forebrain pathway (AFP), a basal ganglia-forebrain circuit, in evaluating song feedback and modifying vocal output. First, neural recordings in anesthetized, juvenile birds show that single AFP neurons are specialized to process the song stimuli that are compared during sensorimotor learning. AFP neurons are tuned to both the bird's own song and the tutor song, even when these stimuli are manipulated to be very different from each other. Second, behavioral experiments in adult birds demonstrate that lesions to the AFP block the deterioration of song that normally follows deafening. This observation suggests that deafening results in an instructive signal, indicating a mismatch between feedback and the internal song model, and that the AFP is involved in generating or transmitting this instructive signal. Finally, neural recordings from behaving birds reveal robust singing-related activity in the AFP. This activity is likely to originate from premotor areas and could be modulated by auditory feedback of the bird's own voice. One possibility is that this activity represents an efference copy, predicting the sensory consequences of motor commands. Overall, these studies illustrate that sensory and motor processes are highly interrelated in this circuit devoted to vocal learning, as is true for brain areas involved in speech.

Animal Communication↗
PubMed2005

Behavioral correlates of activity in identified hypocretin/orexin neurons.

Micropipette recording with juxtacellular Neurobiotin ejection, linked micropipette-microwire recording, and antidromic and orthodromic activation from the ventral tegmental area and locus coeruleus were used to identify hypocretin (Hcrt) cells in anesthetized rats and develop criteria for identification of these cells in unanesthetized, unrestrained animals. We found that Hcrt cells have broad action potentials with elongated later positive deflections that distinguish them from adjacent antidromically identified cells. They are relatively inactive in quiet waking but are transiently activated during sensory stimulation. Hcrt cells are silent in slow wave sleep and tonic periods of REM sleep, with occasional burst discharge in phasic REM. Hcrt cells discharge in active waking and have moderate and approximately equal levels of activity during grooming and eating and maximal activity during exploratory behavior. Our findings suggest that these cells are activated during emotional and sensorimotor conditions similar to those that trigger cataplexy in narcoleptic animals.

Action Potentials↗
PubMed2001

Mosaic model for sensorimotor learning and control.

Humans demonstrate a remarkable ability to generate accurate and appropriate motor behavior under many different and often uncertain environmental conditions. We previously proposed a new modular architecture, the modular selection and identification for control (MOSAIC) model, for motor learning and control based on multiple pairs of forward (predictor) and inverse (controller) models. The architecture simultaneously learns the multiple inverse models necessary for control as well as how to select the set of inverse models appropriate for a given environment. It combines both feedforward and feedback sensorimotor information so that the controllers can be selected both prior to movement and subsequently during movement. This article extends and evaluates the MOSAIC architecture in the following respects. The learning in the architecture was implemented by both the original gradient-descent method and the expectation-maximization (EM) algorithm. Unlike gradient descent, the newly derived EM algorithm is robust to the initial starting conditions and learning parameters. Second, simulations of an object manipulation task prove that the architecture can learn to manipulate multiple objects and switch between them appropriately. Moreover, after learning, the model shows generalization to novel objects whose dynamics lie within the polyhedra of already learned dynamics. Finally, when each of the dynamics is associated with a particular object shape, the model is able to select the appropriate controller before movement execution. When presented with a novel shape-dynamic pairing, inappropriate activation of modules is observed followed by on-line correction.

Brain↗
PubMed1977

Aphagia, behavior sequencing and body weight set point following orbital frontal lesions in rats.

Discrete lesions were made in the orbital frontal neocortex of rats and eating, drinking, sensorimotor responsiveness, and sequencing of motor acts were studied. Duration of aphagia was related to palatability/texture of food. Rats were aphagic for a mean of two days to palatable cookie mash presented on a spatula, six days to a high fat diet mash presented in a 4 cm high dish and for seven days to dry laboratory food. Water drinking was resumed with injestion of dry food. Rats presurgically fattened to 120% of body weight appeared stuporous and akinetic for 2-3 postoperative days, and the period for acceptance of food in tall tests was protracted. Rats presurgically dieted to 80% of normal body weight did not show accelerated recovery of feeding. Preoperatively normal, fattened and dieted rats assumed a chronic postoperative body weight level 25% lower than control rats. Rats with lesions showed sensorimotor neglect when tested on an open table top, but did not show neglect when tested in their home cages. In grooming tests, rats with lesions showed all of the components of normal grooming, but failed to exhibit the long chains of grooming characteristics of control rats. They also showed attenuated tongue extension and had difficulty manipulating food with the forepaws. The experiments suggest that following orbital frontal lesions, motor impairments, motor sequencing dysfunctions, change in body weight set point, and depending upon the test situation, sensorimotor neglect, may all be contributing factors to aphagia. The orbital frontal cortex may influence feeding and other behaviors via descending neural projections to the hypothalamus and branistem.

Animals↗
PubMed2000

Effects-of fluoxetine on sensorimotor and spatial learning deficits following focal cerebral ischemia in rats.

Purpose: The present study investigated the effects of fluoxetine, a serotonin reuptake blocker, on behavioral deficits of rats subjected to transient focal cerebral ischemia. Methods: The right middle cerebral artery of rats was occluded for 120 min using the intraluminal filament method. Fluoxetine treatment (5 mg/kg, i.p.) was started 2 days after ischemia induction and treatment was continued for 10 days thereafter. Sensorimotor recovery was assessed using the limb-placing test and cognitive impairment was assessed using a water-maze test at the end of the experiment. Results: Fluoxetine treatment did not improve performance of ischemic rats in the limb-placing test. Nor was the ischemia-induced deficit in the water-maze test affected by fluoxetine. The infarct volumes in the cortex or striatum, determined after the experiment, were not different between ischemic groups. Conclusion: These results suggest that subchronic fluoxetine treatment following experimental focal cerebral ischemia is not detrimental to behavioral outcome, but it also does not enhance spontaneous sensorimotor recovery or attenuate spatial learning deficits.

Journal Article↗
PubMed1997

Reduced aggressive behaviour in mice with targeted disruption of the oxytocin gene.

Oxytocin (OT) has been reported to mediate aggressive and affiliative behaviours in several species. The behavioural role of OT has been established with physiological manipulations that potentially affected blood pressure, which may have indirectly affected the behaviours under study. To provide converging evidence of the physiological role of OT in aggressive behavior, wild type (WT), heterozygous (OT-/+), and homozygous (OT-/-) mutant mice were tested in two aggression paradigms. In general, there was no significant difference in aggressiveness between WT and OT-/+ mice. However, there were significant reductions in the duration of aggressive behaviors among OT-/- animals, especially in agonistic encounters within neutral arenas. The OT-/- mice did not exhibit any sensorimotor deficits or display any altered general anxiety levels that may have accounted for the observed reduction in aggressive behavior. These data indicate that aggression is mediated in part by OT in mice and that increased aggressiveness is not an obligatory phenotypic result of targeted genetic disruption of any gene.

Aggression↗
PubMedDate not supplied

The chemical nature of the hypothalamocortical activation underlying drinking behavior.

The injection of cholinergic substances (carbocholine, carbathin [karbatin], acetylcholine) into the lateral field of the hypothalamus of cats is accompanied by the appearance in the electrohypothalamogram of characteristic hypersynchronized activity and drinking behavior. The swallowing of water temporarily stops the hypersynchronized activity; the injection of adrenaline into the hypothalamus elicits the same effect. The injection of the same cholinergic preparations into the posterior sigmoid gyrus of the cerebral cortex is accompanied by similar, but less pronounced bioelectrical and behavioral effects. The presentation of a closed drink dispenser containing water to the animals against the background of cholinergic activation of the hypothalamus or cortex leads to desynchronization of the bioelectrical activity and suppression of the bursts of hypersynchronized activity. The drinking behavior of cats which appears on the basis of centrally created thirst motivation reflects the activity of a primary dominant focus in the hypothalamus and of a secondary dominant focus in the sensorimotor cortex. These foci are cholinergic in nature. The cessation of the drinking behavior may be related to the activation of adrenergic mechanisms of the same brain structures.

Acetylcholine↗
PubMed2005

Distinct basal ganglia territories are engaged in early and advanced motor sequence learning.

In this study, we used functional MRI (fMRI) at high field (3T) to track the time course of activation in the entire basal ganglia circuitry, as well as other motor-related structures, during the explicit learning of a sequence of finger movements over a month of training. Fourteen right-handed healthy volunteers had to practice 15 min daily a sequence of eight moves using the left hand. MRI sessions were performed on days 1, 14 and 28. In both putamen, activation decreased with practice in rostrodorsal (associative) regions. In contrast, there was a significant signal increase in more caudoventral (sensorimotor) regions of the putamen. Subsequent correlation analyses between signal variations and behavioral variables showed that the error rate (movement accuracy) was positively correlated with signal changes in areas activated during early learning, whereas reaction time (movement speed) was negatively correlated with signal changes in areas activated during advanced learning stages, including the sensorimotor putamen and globus pallidus. These results suggest the possibility that motor representations shift from the associative to the sensorimotor territories of the striato-pallidal complex during the explicit learning of motor sequences, suggesting that motor skills are stored in the sensorimotor territory of the basal ganglia that supports a speedy performance.

Adult↗
PubMed2001

Modeling functions of striatal dopamine modulation in learning and planning.

The activity of midbrain dopamine neurons is strikingly similar to the reward prediction error of temporal difference reinforcement learning models. Experimental evidence and simulation studies suggest that dopamine neuron activity serves as an effective reinforcement signal for learning of sensorimotor associations in striatal matrisomes. In the current study, we simulate dopamine neuron activity with the extended temporal difference model of Pavlovian learning and examine the influences of this signal on medium spiny neurons in striatal matrisomes. The modeled influences include transient membrane effects of dopamine D(1) receptor activation, dopamine-dependent long-term adaptations of corticostriatal transmission, and effects of dopamine on rhythmic fluctuations of the membrane potential between an elevated "up-state" and a hyperpolarized "down-state". The most dominant activity in the striatal matrisomes is assumed to elicit behaviors via projections from the basal ganglia to the thalamus and the cortex. This "standard model" performs successfully when tested for sensorimotor learning and goal-directed behavior (planning). To investigate the contributions of our model assumptions to learning and planning, we test the performance of several model variants that lack one of these mechanisms. These simulations show that the adaptation of the dopamine-like signal is necessary for sensorimotor learning and planning. Sensorimotor learning requires dopamine-dependent long-term adaptation of corticostriatal transmission. Lack of dopamine-like novelty responses decreases the number of exploratory acts, which impairs planning capabilities. The model loses its planning capabilities if the dopamine-like signal is simulated with the original temporal difference model, because the original temporal difference model does not form novel associative chains. Transient membrane effects of the dopamine-like signal on striatal firing substantially shorten the reaction time in the planning task. The capability for planning is improved by influences of dopamine on the durations of membrane potential fluctuations and by manipulations that prolong the reaction time of the model. These results suggest that responses of dopamine neurons to conditioned stimuli contribute to sensorimotor reward learning, novelty responses of dopamine neurons stimulate exploration, and transient dopamine membrane effects are important for planning.

Animals↗
PubMed1999

Brain alpha 1-adrenergic neurotransmission is necessary for behavioral activation to environmental change in mice.

Terazosin, a water-soluble alpha 1 antagonist that can be administered in high doses intraventricularly was used to study the relationship between brain alpha 1 adrenoceptor neurotransmission and behavioral activation in the mouse. The antagonist was found to produce a dose-dependent, complete inhibition of motor activity and catalepsy which were reversed preferentially by coinfusion of an alpha 1 agonist (phenylephrine) compared to a D1 (SKF38393) or a D2 agonist, (quinpirole). Blockade of central beta-1 (betaxolol), alpha-2 (RX821002) or beta-2 (ICI 118551) adrenoceptors had smaller or non-significant effects. Terazosin's selectivity for alpha 1 receptors versus dopaminergic receptors was verified under the present conditions by showing that the intraventricularly administered antagonist protected striatal and cerebral cortical alpha 1 receptors but not striatal or cortical D1 receptors from in vivo alkylation by N-ethoxycarbonyl-2-ethoxy-1, 2-dihydroxyquinoline. That its effect was due to blockade of brain rather than peripheral receptors was shown by the finding that intraperitoneal doses of terazosin three to 66 times greater than the maximal intraventricular dose produced less behavioral inhibition. Intraventricular terazosin also produced hypothermia and a reduced respiratory rate suggestive of a reduced sympathetic outflow. However, external heat did not affect the inactivity, and captopril, a hypotensive agent, did not mimic it. Terazosin did not impair performance on a horizontal wire test or the ability to make co-ordinated movements in a swim test suggesting that its activity-reducing effect was not due to sedation and may have a motivational or sensory gating component. It is concluded that central alpha 1-noradrenergic neurotransmission is required for behavioral activation to environmental change in the mouse and may operate on sensorimotor and motivational processes.

Adrenergic alpha-Agonists↗
PubMed2003

A comparison of long-term neurological symptoms after two different focal ischemic models in Mongolian gerbils.

The aim of the present study was to elucidate the relationship between specific tasks and the responsible ischemic lesions after experimentally induced cerebral hemispheric ischemia in Mongolian gerbils. We used the elevated body swing test (EBST) to evaluate asymmetry motor behavior, the bilateral asymmetry test (BAT) to evaluate sensory dysfunction, and the T-maze test to assess cognitive deficit during 4 weeks after either 10-min single unilateral carotid artery occlusion (sCCAO) or 10-min repeated unilateral occlusion (rCCAO). rCCAO produced persistent sensorimotor and severe cognitive deficits. Infarction was confined to the ipsilateral cerebral cortex, hippocampus, dorsolateral nucleus of thalamus and caudate nucleus. sCCAO did not induce sensorimotor abnormalities, but did produce mild cognitive deficits; these animals also showed increased locomotor activity during the early post-ischemic period. In sCCAO, neuronal death was confined to the ipsilateral CA1 sector of the hippocampus. Thus, unilateral CA1 neuronal death was sufficient for evolution of cognitive deficits in this model of experimental focal ischemia. Ischemic lesions extending to the ipsilateral cerebral cortex, basal ganglia, and hippocampus produced persistent and severe sensorimotor impairment accompanying severe cognitive deficits. These findings regarding region-specific behavioral tasks in cerebral ischemia will facilitate improved assessment of stroke therapy.

Animals↗