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PubMed2001

Orienting attention to instants in time.

My colleagues and I have investigated whether the temporal framework can be used to guide selective attention, and have applied non-invasive methodology to reveal the brain systems and mechanisms involved. Our findings show that we are able to orient attention selectively to different points in time, enhancing behavioral performance. These effects are mediated by a left-hemisphere dominant parietal-frontal system, which partially overlaps with the networks involved in spatial orienting. The neural system for temporal orienting also includes brain areas associated with motor preparation and anticipation, suggesting that sensorimotor areas with different specializations can contribute to attentional orienting depending on the stimulus attributes guiding selection. The optimization of behavior by temporal orienting involves enhancement of the latency and amplitude of event-related potentials that are associated with motor responses and decisions. The effects are distinct from those during visual spatial attention, indicating that behavioral advantages can be conferred by multiple types of neural mechanisms. Taken together, the findings illustrate the flexibility of attentional functions in the human brain.

Attention↗
PubMed1996

The effects of amphetamine on recovery of function after cortical damage in the rat depend on the behavioral requirements of the task.

The effects of amphetamine on the recovery of function following unilateral lesions of the rat somatic sensorimotor cortex (SMC) were examined. Rats with large SMC were tested on two measures of locomotor placing: the beam-walking test and the foot-fault test. Amphetamine produced an immediate and enduring facilitation of recovery on the beam-walking test. In contrast, the drug had no effect on the rats' ability to accurately place the forelimbs on the rungs of the elevated grid during locomotion on the foot-fault test. These data suggest that amphetamine may facilitate recovery when the requirements of the task produce a deficit in the initiation of locomotion but not when the animal is required to use somatosensory and proprioceptive cues to guide performance on the task. A second group of rats with smaller SMC lesions was evaluated with tactile-placing tests and the bilateral-tactile stimulation task. The forelimb placing reaction is elicited by unilateral tactile stimulation of the vibrissae or forelimb, whereas the ipsilateral asymmetry observed on the bilateral-tactile stimulation test has been interpreted as an impairment in processing stimuli presented on both sides of the body. On two measures of forelimb placing amphetamine produced a facilitation of recovery, but restoration of function was not observed during the period of drug intoxication. In contrast, amphetamine had no effect on recovery of function on the bilateral-tactile stimulation test. Taken together, these data suggest that the behavioral requirements of the task are an important factor in determining the facilitatory effects of amphetamine on recovery of function.

Animals↗
PubMed1998

Dissociable long-term cognitive deficits after frontal versus sensorimotor cortical contusions.

Cognitive deficits are the most enduring and disabling sequelae of human traumatic brain injury (TBI), but quantifying the magnitude, duration, and pattern of cognitive deficits produced by different types of TBI has received little emphasis in preclinical animal models. The objective of the present study was to use a battery of behavioral tests to determine if different impact sites produce different patterns of behavioral deficits and to determine how long behavioral deficits can be detected after TBI. Prior to surgery, rats were trained to criteria on delayed nonmatching to position, radial arm maze, and rotarod tasks. Rats received sham surgery (controls), midline frontal contusions (frontal TBI, 2.25 m/sec impact), or unilateral sensorimotor cortex contusions (lateral TBI, 3.22 m/sec impact) at 12 months of age and were tested throughout the next 12 months. Cognitive deficits were more robust and more enduring than sensorimotor deficits for both lateral TBI and frontal TBI groups. Lateral TBI rats exhibited transient deficits in the forelimb placing and in the rotarod test of motor/ambulatory function, but cognitive deficits were apparent throughout the 12-month postsurgery period on tests of spatial learning and memory including: (1)reacquisition of a working memory version of the radial arm maze 6-7 months post-TBI, (2) performance in water maze probe trials 8 months post-TBI, and (3) repeated acquisition of the Morris water maze 8 and 11 months post-TBI. Frontal TBI rats exhibited a different pattern of deficits, with the most robust deficits in tests of attention/orientation such as: (1) the delayed nonmatching to position task (even with no delays) 1-11 weeks post-TBI, (2) the repeated acquisition version of the water maze--especially on the first "information" trial 8 months post-TBI, (3) a test of sensorimotor neglect or inattention 8.5 months post-TBI, and (4) a DRL20 test of timing and/or sustained attention 11 months after surgery. These results suggest that long-term behavioral deficits can be detected in rodent models of TBI, that cognitive deficits seem to be more robust than sensorimotor deficits, and that different TBI impact sites produce dissociable patterns of cognitive deficits in rats.

Animals↗
PubMed2004

Optimality principles in sensorimotor control.

The sensorimotor system is a product of evolution, development, learning and adaptation-which work on different time scales to improve behavioral performance. Consequently, many theories of motor function are based on 'optimal performance': they quantify task goals as cost functions, and apply the sophisticated tools of optimal control theory to obtain detailed behavioral predictions. The resulting models, although not without limitations, have explained more empirical phenomena than any other class. Traditional emphasis has been on optimizing desired movement trajectories while ignoring sensory feedback. Recent work has redefined optimality in terms of feedback control laws, and focused on the mechanisms that generate behavior online. This approach has allowed researchers to fit previously unrelated concepts and observations into what may become a unified theoretical framework for interpreting motor function. At the heart of the framework is the relationship between high-level goals, and the real-time sensorimotor control strategies most suitable for accomplishing those goals.

Adaptation, Physiological↗
PubMed2000

Lack of effect of an early stressful life event on sensorimotor gating in adult rats.

Hypotheses of the etiology of schizophrenia emphasize the important role of perinatal insults in predisposing individuals to the development of the disease, so that an animal model in which a discrete postnatal manipulation of the infant social environment yields schizophrenia-like behavior in adulthood would be valuable in terms of the study of the neural substrate and treatment of schizophrenia. Schizophrenics demonstrate a deficit in sensorimotor gating (prepulse inhibition), and a similar phenomenon has been described in adult rats following the administration of direct and indirect dopamine agonists. Recently it has been reported that a 24 h separation of rat pups from the mother results in a disruption of prepulse inhibition at adulthood. Here we report a study which investigated the same phenomenon but which, in contrast to the previous study, utilized unrelated subjects all derived from different dams. Maternal separation was conducted for 24 h with pups aged 4, 9 or 18 days and these subjects, together with non-separated controls, were tested at age 3 months in terms of their prepulse inhibition in the acoustic startle response paradigm. Maternal separation did not disrupt prepulse inhibition. Comparison of males and females (with a maximum of one opposite-sex sibling) demonstrated that acoustic startle response and prepulse inhibition of this response was enhanced in males relative to females. This study indicates that 24 h maternal separation does not provide a robust model for studying the effects of early environmental insults on the long-term abnormal development of sensorimotor gating.

Acoustic Stimulation↗
PubMed1998

Interstitial branches develop from active regions of the axon demarcated by the primary growth cone during pausing behaviors.

Interstitial branches arise from the axon shaft, sometimes at great distances behind the primary growth cone. After a waiting period that can last for days after extension of the primary growth cone past the target, branches elongate toward their targets. Delayed interstitial branching is an important but little understood mechanism for target innervation in the developing CNS of vertebrates. One possible mechanism of collateral branch formation is that the axon shaft responds to target-derived signals independent of the primary growth cone. Another possibility is that the primary growth cone recognizes the target and demarcates specific regions of the axon for future branching. To address whether behaviors of the primary growth cone and development of interstitial branches are related, we performed high-resolution time-lapse imaging on dissociated sensorimotor cortical neurons that branch interstitially in vivo. Imaging of entire cortical neurons for periods of days revealed that the primary growth cone pauses in regions in which axon branches later develop. Pausing behaviors involve repeated cycles of collapse, retraction, and extension during which growth cones enlarge and reorganize. Remnants of reorganized growth cones are left behind on the axon shaft as active filopodial or lamellar protrusions, and axon branches subsequently emerge from these active regions of the axon shaft. In this study we propose a new model to account for target innervation in vivo by interstitial branching. Our model suggests that delayed interstitial branching results directly from target recognition by the primary growth cone.

Animals↗
PubMed2004

Freeze lesion-induced focal cortical dysplasia predisposes to atypical hyperthermic seizures in the immature rat.

PURPOSE: To determine the effects of focal cortical dysplasia on the behavioral and electrographic features of hyperthermia-induced seizures (HSs) in rats. METHODS: A right sensorimotor cortex freeze lesion was induced in postnatal day 1 (P1) rat pups, and HSs were provoked at P10 under continuous monitoring of core temperature; EEGs were recorded from the right amygdala during and after hyperthermia. Controls included both sham-operated at P1 and naïve rats. RESULTS: HSs began with jaw myoclonus, followed by hindlimb clonus and generalized convulsions (GCs), and terminated by a period of posthyperthermia depression. The threshold temperature and latency of jaw myoclonus were similar across the groups. However, both the threshold temperature and latency of GCs were significantly lower in lesioned pups than in controls (40.5 +/- 0.5 degrees C, n = 24, vs. 42.0 +/- 0.2 degrees C, n = 21; p < 0.001; 6.7 +/- 0.6 min, n = 20, vs. 8.4 +/- 0.6 min, n = 22; p < 0.05). In lesioned pups, the threshold and latencies for jaw myoclonus and hindlimb clonus were similar, whereas in controls, the progression from one to the other was marked by significant differences in both parameters. Posthyperthermia depression was longer in lesioned (13.3 +/- 1.2 min, n = 21) than in control (8.0 +/- 0.8 min, n = 20; p < 0.0001) pups. Ictal EEG activity was recorded during both behavioral seizures and posthyperthermia depression. CONCLUSIONS: An HS in rats with a localized freeze lesion results in lower threshold GC and prolonged ictal manifestations, thus supporting a pathophysiologic link between focal cortical dysplasia and atypical febrile seizures, conditions that have a high prevalence in children with mesial temporal lobe epilepsy.

Animals↗
PubMed1999

Cortical injury impairs contralateral forelimb immobility during swimming: a simple test for loss of inhibitory motor control.

Most animal models of focal injury to the sensorimotor cortex have been aimed at detecting non-use or impairment of the limbs in specific tasks or during spontaneous exploratory behaviors. However, the inability to hold a limb still can be an equally disabling movement disorder. The present study investigated the loss of control of limb immobility that occurs following damage to the forelimb region of the rat sensorimotor cortex (FL-SMC). When swimming forward in a tank of water, adult rats typically hold both forepaws mostly motionless underneath the chin, using primarily the hindlimbs for stroking movements. Following a unilateral FL-SMC lesion, rats hold only the non-impaired forelimb immobile under the chin, and make 'immature' stroking movements with the impaired forelimb. We have devised a simple means of assessing and quantifying this deficit. While the criterion for most tests of motor recovery involves appropriate movement of an impaired limb, this test depends on adequate inhibition of movement as the norm, and may be a useful way to assess the loss of inhibitory motor control and the efficacy of potential restorative interventions.

Animals↗
PubMed1994

Distributed representation in the song system of oscines: evolutionary implications and functional consequences.

This paper reviews the organizational principles and implications that have emerged from the analysis of HVc, a forebrain nucleus that is a major site of sensory, motor, and sensorimotor integration in the song control system of oscine passerine birds (songbirds). Anatomical, physiological, and behavioral data support the conclusion that HVc exists within a hierarchically organized system with parallel pathways that converge onto HVc. The organization of HVc is distributed and redundant, and its outputs exhibit broad divergence. A similar pattern of connectivity exists for neostriatum adjacent to HVc. This and other data support the hypothesis that the song system arose from an elaboration or duplication of pathways generally present in all birds. Spontaneous and auditory response activity is strongly correlated throughout HVc, with auditory responses exhibiting strong temporal modulation in a synchronized fashion throughout the nucleus. This suggests that the auditory representation of song is encoded in the synchronized temporal patterns of activation, and that the predominant selectivity for the individual's own song that is observed for HVc neurons results from interactions of auditory input with central pattern generators for song. Most, or all HVc neurons are recruited during singing. The auditory response and motor recruitment properties of individual HVc neurons have no simple relationship, and the spontaneous activity in HVc may build up in the seconds preceding a song. To the extent HVc participates in perceptual phenomena associated with song, production and perception are not tightly linked in adults but may be linked by shared developmental processes during periods of sensorimotor learning.

Animals↗
PubMed2001

Mirthful laughter induced by subthalamic nucleus stimulation.

High-frequency stimulation of the subthalamic nucleus (STN) improves the motor signs of Parkinson's disease (PD). The three main components (motor, associative, and limbic) of the cortical-basal ganglia-cortical circuits pass through the STN. It is not known whether STN stimulation can influence the limbic loop. We present two PD patients in whom acute stimulation of an electrode located in the STN using high stimulation parameters (50% higher than therapeutic) induced funny associations, leading to infectious laughter and hilarity, whereas the therapeutic parameters induced a hypomanic behavior and marked improvement of akinesia. Our report suggests that the STN, with its sensorimotor, cognitive, and limbic parts is not only involved in motor, but also in psychomotor regulation.

Affect↗
PubMed1997

Intracerebroventricular glial cell line-derived neurotrophic factor improves motor function and supports nigrostriatal dopamine neurons in bilaterally 6-hydroxydopamine lesioned rats.

In order to evaluate the efficacy of glial cell line-derived neurotrophic factor (GDNF) in a model of advanced Parkinson's disease, we studied rats with extensive bilateral lesions of the nigrostriatal pathway. Adult male F344 rats were injected bilaterally into the medial forebrain bundle with the neurotoxin 6-hydroxydopamine. Locomotor ability as measured by total distance traveled in an open field over 20 min, as well as von Frey hair testing of sensorimotor neglect, was monitored weekly. Rats demonstrating severe motor impairment and sensorimotor neglect were used for this study and were sorted to achieve similar average behavioral scores between the two treatment groups. After 2 weeks of pretesting, the rats received 250 microg GDNF or vehicle injected into the right lateral cerebral ventricle. Three weeks later, an additional 500 microg GDNF or vehicle was injected into the contralateral ventricle. The rats were monitored for another 2 weeks prior to sacrifice. Behavioral results indicated that von Frey hair scores were inconsistent between tests for each rat and were unchanged following GDNF treatment. However, GDNF recipients demonstrated significant improvement in locomotor ability compared to vehicle recipients. High-pressure liquid chromatography-electrochemical detection analysis of neurotransmitter levels revealed a significant increase in dopamine content within the substantia nigra and ventral tegmenta, but not the striata, of GDNF-treated rats. Further, immunohistochemical staining of tissues from matched pairs of rats revealed increased numbers of tyrosine hydroxylase-positive ventral mesencephalic neurons in one of the two pairs of rats examined. These results suggest that intracerebroventricular GDNF administration improves motor ability and supports nigrostriatal dopaminergic neurons in a model of severe Parkinson's disease.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1994

Input-output organization of the rat vibrissal motor cortex.

The afferent and efferent connections of the vibrissal area of the rat motor cortex (VMCx) were investigated by injecting Phaseolus vulgaris leucoagglutinin (PHA-L) or wheat germ agglutinin-horseradish peroxidase into the physiologically defined VMCx. The VMCx formed reciprocal connections with the primary and secondary somatosensory cortex, lateral and ventrolateral orbital cortex, retrosplenial cortex, and perirhinal cortex. These corticocortical afferents originated from cell bodies in layers II-III and V, and some afferents originated from cell bodies in layer VI of the primary sensory cortex. All of the VMCs efferents terminated in layers I and V or layers I-III and V. The VMCx also formed reciprocal connections with the ventrolateral, ventromedial and centrolateral nucleus, the lateral portion of the mediodorsal nucleus and the posterior complex of the thalamus. It projected bilaterally to the caudate putamen, primarily ipsilaterally to the superior colliculus, anterior pretectal nucleus, and pontine nucleus, and mainly contralaterally to the oral part of the spinotrigeminal nucleus and the reticular formation around the facial nerve nucleus. Finally, injections of PHA-L into the superior colliculus demonstrated that this structure projected contralaterally to the lateral part of the facial nerve nucleus. These data suggest that the VMCx plays a key role in sensorimotor integration, through its extensive interconnectivity with numerous brain structures, and may modulate orientation behaviors by relaying processed information to the superior colliculus.

Animals↗
PubMed1987

The primate nucleus basalis of Meynert: neuronal activity related to a visuomotor tracking task.

The activity of neurons in the nucleus basalis of Meynert (nbM), both the compact (nbMc) and interstitial (nbMi) components, has been examined in monkeys trained to perform a visuomotor step-tracking task. This study was carried out in the same animals and with the same task used to examine neuronal activity in the external and internal segments of globus pallidus (GPe and GPi) and ventral pallidum (VP). The presumed interstitial cells that are located within the laminae surrounding GPe and GPi and identified physiologically by their similarity with nbMc neurons, are referred to as border cells. A major finding of this study is that a large proportion of nbMc and border cells were active in relation to either the step-tracking movements or to load application. Moreover, a high proportion of the responses of border neurons were differential for opposite directions of load and movement. The percentages of directionally specific border and nbMc neurons were considerably less than for GP, with border neurons having more directionally specific responses than nbMc neurons. The similarity between border and GP neuronal properties in this task suggests that both may receive similar sensorimotor afferent input. In the compact portion of nbM, nonspecific neuronal responses following each behavioral event in the paradigm were common. These responses appeared to have been modified by and may have been contingent upon association with reinforcement.

Animals↗
PubMed1991

Amygdaloid kindling during wakefulness and paradoxical sleep in the cat. 1. Inhibitory influence of paradoxical sleep on kindling development.

The development of amygdaloid kindling during wakefulness (W) and paradoxical sleep (PS) was compared in chronically implanted adult male cats. The animals were divided into 2 groups. One group was kindled during W (W-K) and the second during a burst of pontogeniculo-occipital (PGO) potentials during PS (PS-K). The threshold of amygdaloid afterdischarge (AD) was determined during W in the W-K group and during PS in the PS-K group. For the development of kindling, amygdala stimulation was applied daily. Results demonstrate that kindling development was markedly retarded in the PS-K group. From the first kindling trials, mean AD duration in the PS-K group was significantly shorter than in the W-K group and this difference was sustained until generalized convulsive seizures (GCSs) were reached by the W-K animals. Also, mean AD frequency in the PS-K group was significantly lower than in the W-K group. AD propagation to the contralateral amygdala and sensorimotor cortex was significantly retarded in the PS-K animals. Time spent in behavioral stages I and II of kindling was significantly longer in the PS-K animals than in W-K animals and the number of daily electrical stimuli required to reach the first GCS was significantly higher in group PS-K than in group W-K. It is concluded that PS exhibits an inhibitory influence over amygdaloid kindling development and this influence is mainly exerted during the early stages of epileptogenesis.

Amygdala↗
PubMed2004

Motor and cognitive function evaluation following experimental traumatic brain injury.

Traumatic brain injury (TBI) in humans may cause extensive sensorimotor and cognitive dysfunction. As a result, many TBI researchers are beginning to assess behavioral correlates of histologically determined damage in animal models. Although this is an important step in TBI research, there is a need for standardization between laboratories. The ability to reliably test treatments across laboratories and multiple injury models will close the gap between treatment success in the lab and success in the clinic. The goal of this review is to describe and evaluate the tests employed to assess functional outcome after TBI and to overview aspects of cognitive, sensory, and motor function that may be suitable targets for therapeutic intervention.

Animals↗
PubMed1997

Fractionating the nonspatial pretraining effect in the water maze task.

Nonspatial pretraining (NSP) enables rats to learn the general strategies of the water maze task (WMT; e.g., learning to swim away from the wall and to climb onto the hidden platform), reduces sensorimotor disturbances, and eliminates acquisition impairments caused by scopolamine hydrobromide, a muscarinic antagonist. To evaluate the contributions of the components of NSP to these effects, NSP was fractionated so that different groups of male rats swam, were placed onto the hidden platform, climbed onto the hidden platform, or were placed into an empty maze before spatial training under scopolamine. No single component of the NSP procedure was sufficient to produce its full effects on sensorimotor disturbances and WMT acquisition. Experience with most or perhaps all of the specific behaviors required in the WMT appears to be important for NSP to produce its full effects.

Animals↗
PubMed2000

Role of the basal ganglia in the control of purposive saccadic eye movements.

In addition to their well-known role in skeletal movements, the basal ganglia control saccadic eye movements (saccades) by means of their connection to the superior colliculus (SC). The SC receives convergent inputs from cerebral cortical areas and the basal ganglia. To make a saccade to an object purposefully, appropriate signals must be selected out of the cortical inputs, in which the basal ganglia play a crucial role. This is done by the sustained inhibitory input from the substantia nigra pars reticulata (SNr) to the SC. This inhibition can be removed by another inhibition from the caudate nucleus (CD) to the SNr, which results in a disinhibition of the SC. The basal ganglia have another mechanism, involving the external segment of the globus pallidus and the subthalamic nucleus, with which the SNr-SC inhibition can further be enhanced. The sensorimotor signals carried by the basal ganglia neurons are strongly modulated depending on the behavioral context, which reflects working memory, expectation, and attention. Expectation of reward is a critical determinant in that the saccade that has been rewarded is facilitated subsequently. The interaction between cortical and dopaminergic inputs to CD neurons may underlie the behavioral adaptation toward purposeful saccades.

Animals↗
PubMed1994

Pharmacotherapy of aphasia. A critical review.

BACKGROUND: Communication problems are a common sequela of cerebrovascular disease and other central nervous system disorders. Behavioral treatment of these disorders aims to harness uninjured parts of the brain to improve the communicative life of the individual. While pharmacotherapy has held promise for the treatment of aphasia for over 50 years, it has not fulfilled this promise. This article reviews both the promise and the disappointment of aphasia pharmacotherapy. SUMMARY OF REVIEW: Diverse theories of the underlying neurological deficits in aphasia have led to different pharmacologic rationales for therapy. Animal studies have demonstrated decreased levels of brain catecholamines after cortical stroke and more rapid stroke recovery with therapy aimed at augmenting brain norepinephrine and dopamine. These studies have led to recent attempts to hasten or extend language and sensorimotor rehabilitation after human stroke by administration of catecholaminergic drugs. When used as an adjunct to behavioral therapy, such pharmacotherapy appears to have benefit. CONCLUSIONS: While drug therapy is unlikely to revolutionize the treatment of aphasia, it nonetheless holds promise as an adjunct to behavioral speech and language therapy to decrease performance variability and consequently to improve mean performance in patients with mild to moderate language dysfunction. Additional studies with carefully designed methods are necessary to assess the full potential of aphasia pharmacotherapy.

Animals↗