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PubMed2006

Maturation of executive function in autism.

BACKGROUND: Executive dysfunction has been reported at different ages in autism. It is not clear however, when this impairment emerges or how its expression is affected by development. METHODS: 61 non-mentally retarded autism participants (AUT) and 61 age, gender, and IQ matched typically developing participants (CON) were assessed with two oculomotor executive function tasks, the oculomotor delayed response task (ODR) and the antisaccade task (AS), as well as a visually-guided saccade sensorimotor task (VGS). RESULTS: The AUT group demonstrated impairments in response inhibition and spatial working memory at all ages tested. Developmental improvements in speed of sensorimotor processing and voluntary response inhibition were similar in both groups indicating sparing of some attentional control of behavior. Developmental progression in the speed of initiating a cognitive plan and maintaining information on line over time, however, was impaired in the AUT group indicating abnormal development of working memory. CONCLUSIONS: These results indicate that while executive dysfunction is present throughout development, there is evidence for both typical and atypical developmental progression of executive functions in autism. The plasticity suggested by the developmental improvements may have implications regarding appropriate developmental epochs and types of interventions aimed at enhancing cognitive capacities in individuals with autism.

Adolescent↗

PubMed1993

Pancreatic polypeptide in dorsal vagal complex stimulates gastric acid secretion and motility in rats.

High concentrations of receptors for pancreatic polypeptide (PP), a pancreatic hormone, were recently discovered in the dorsomedial region of the dorsal vagal complex (DVC). We hypothesized that gastric acid secretion and motility, digestive functions strongly influenced by vagovagal reflexes organized within the DVC, would be affected by PP applied directly to this vagal sensorimotor integration area. After urethan-anesthetized rats were prepared for antral motility recording or titrometric analysis of gastric acid output, phosphate-buffered saline or various doses of PP in phosphate-buffered saline were micropressure injected into the medial DVC. Injections of PP into the DVC produced significant, long-lasting, and dose-dependent increases in gastric acid secretion and antral motility. These gastric responses were blocked by bilateral cervical vagotomy and by atropine, suggesting that intramedullary PP stimulates vagal cholinergic pathways, resulting in enhanced gastric functions. Because PP is not synthesized within the central nervous system, these results point to a new mechanism whereby the digestive tract may modulate its own autonomic control: direct humoral action on vagovagal reflex circuits within the brain stem.

Animals↗

PubMed1998

Coordinate-free sensorimotor processing: computing with population codes.

The purpose of the study is to outline a computational architecture for the intelligent processing of sensorimotor patterns. The focus is on the nature of the internal representations of the outside world which are necessary for planning and other goal-oriented functions. A model of cortical map dynamics and self-organization is proposed that integrates a number of concepts and methods partly explored in the field. The novelty and the biological plausibility is related to the global architecture which allows one to deal with sensorimotor patterns in a coordinate-free way, using population codes as distributed internal representations of external variables and the coupled dynamics of cortical maps as a general tool of trajectory formation. The basic computational features of the model are demonstrated in the case of articulatory speech synthesis and some of the metric properties are evaluated by means of simple simulation studies.

Journal Article↗

PubMed1999

Effects of NGF, b-FGF, and cerebrolysin on water maze performance and on motor activity of rats: short- and long-term study.

The effects of 14-day treatments with nerve growth factor (NGF), basic fibroblast growth factor (b-FGF), or the peptidergic drug Cerebrolysin on postlesion acquisition of a water maze task and on motor activity were evaluated. Rats were tested in the Morris water maze 14 days (early test) and 7 to 8 months (delayed test) after a bilateral lesion of the frontoparietal (sensorimotor) cortex. Only the rats treated with Cerebrolysin performed the water maze task at the level of the nonlesioned controls in the early test. No short-term effect of NGF (6.5 ng/14 days; 38 ng/ml) or b-FGF (17 ng/14 days; 100 ng/ml) treatment was found. The delayed test revealed that water maze performance was restored in rats treated with b-FGF in comparison with intact controls. The data showed that b-FGF can support or initiate processes in the CNS that lead to a delayed functional amelioration and/or compensation for a water maze performance deficit. NGF did not influence the acquisition impairment caused by a sensorimotor cortical lesion. Two-week administration of Cerebrolysin had a time-dependent influence: it attenuated the acquisition deficit and increased the motor activity of rats, both effects declined to the level of lesioned controls within 8 months.

Aging↗

PubMed2005

Residual motor control and cortical representations of function following hemispherectomy: effects of etiology.

Fifteen posthemispherectomy children were examined to assess residual motor function of the paretic side using the 74-point Fugl-Meyer Assessment of Motor Recovery scale. The degree of residual motor control differed for upper and lower extremities, with hand function being most severely impaired. Posthemispherectomy motor outcomes also differed as a function of etiology: cortical dysplasia, perinatal infarct, and Rasmussen's encephalitis. Children whose intractable seizures resulted from perinatal middle cerebral artery stroke demonstrated the most spared motor function. To detect cortical areas that represented motor control of the hemiparetic side, we focused on voluntary control of the affected lower extremity. Seven of our patients were able to carry out a foot dorsiflexion paradigm during functional magnetic resonance imaging, and these results were compared with activations found in normal controls. All children showed activations in the sensorimotor network ipsilateral to the affected side. The perinatal infarct group demonstrated greater activity in the cingulate cortex, whereas the Rasmussen's encephalitis group had significant activations in the insula, suggesting etiology-specific differences in reorganization. These findings are discussed in the framework of our understanding of mechanisms of cortical plasticity in the injured brain and its relevance to neurologic rehabilitation. We suggest that imaging techniques are important tools in identifying cortical regions underlying functional reorganization. Furthermore, detection of such areas might become a basis for specific training promoting the optimal reorganization of cortical networks to enhance motor control.

Adolescent↗

PubMed1997

Self-organized huddles of rat pups modeled by simple rules of individual behavior.

Starting at infancy and continuing throughout adult life, huddling is a major component of the behavioral repertoire of Norway rats (Rattus norvegicus). Huddling behavior maintains the cohesion of litters throughout early life, and in adulthood, it remains a consistent feature of social behavior of R. norvegicus. During infancy, rats have severely limited sensorimotor capabilities, and yet they are capable of aggregating and display a form of group regulatory behavior that conserves metabolic effort and augments body temperature regulation. The functions of huddling are generally understood as group adaptations, which are beyond the capabilities of the individual infant rat. We show, however, that huddling as aggregative or cohesive behavior can emerge as a self-organizing process from autonomous individuals following simple sensorimotor rules. In our model, two sets of sensorimotor parameters characterize the topotaxic responses and the dynamics of contact in 7-day-old rats. The first set of parameters are conditional probabilities of activity and inactivity given prior activity or inactivity and the second set are preferences for objects in the infant rat's environment. We found that the behavior of the model and of actual rat pups compare very favorably, demonstrating that the aggregative feature of huddling can emerge from the local sensorimotor interactions of individuals, and that complex group regulatory behaviors in infant rats may also emerge from self-organizing processes. We discuss the model and the underlying approach as a paradigm for investigating the dynamics of social interactions, group behavior, and developmental change.

Animals↗

PubMed1990

Chronic effects of the selective serotoninergic neurotoxin, methylenedioxyamphetamine, upon cerebral function.

The amphetamine derivative methylenedioxyamphetamine selectively destroys serotoninergic terminals in the brain. We have studied the effects of this toxin upon resting cerebral function, as reflected in rates of glucose utilization. Rats were injected subcutaneously with either 1 ml/kg saline (n = 5) or 20 mg/kg methylenedioxyamphetamine (n = 5) twice daily for four days. Local cerebral glucose utilization was measured between six and nine weeks after treatment using [14C]2-deoxyglucose quantitative autoradiography. Samples of frontal cortex taken from these animals for in vitro [3H]paroxetine binding showed a 64% reduction in 5-hydroxytryptamine uptake sites. In the majority of the 31 functionally diverse brain areas analysed, no significant changes were measured, but significant (P less than 0.05) increases in glucose use were found in neocortical regions e.g. anterior cingulate cortex (+16%) and sensorimotor cortex (+21%). However, the most profound increases were found in globus pallidus (+30%) and hippocampus molecular layer (+34%). It would appear, therefore, that treatment with methylenedioxyamphetamine results in long-lasting alterations in cerebral functional activity.

3,4-Methylenedioxyamphetamine↗

PubMed1994

Motor recovery after early brain damage. A case of brain plasticity.

BACKGROUND: Motor recovery is remarkable when the brain is damaged early in life. We describe a case of early damage to the right hemisphere with remarkable reorganization and plastic functional changes, studied by computed neuroimaging. CASE DESCRIPTION: A 31-year-old man had a left-sided hemiplegia at the age of 12, followed by good motor recovery despite a large right cortical-subcortical lesion. Single-photon emission computed tomography with motor activation study showed cerebral blood flow increase in the left premotor and sensorimotor cortices irrespective of the hand he was moving, without flow changes in the right hemisphere. CONCLUSIONS: A remarkable reorganization and plastic brain functional changes occurred in a patient after early diffuse damage of the right hemisphere. The study points to a potential role of ipsilateral cortical efferent pathways in subserving hand movements after early cerebral damage.

Adult↗

PubMed2003

Arterial spin labeling perfusion fMRI with very low task frequency.

Functional magnetic resonance imaging (fMRI) has become the most widely used modality for visualizing regional brain activation in response to sensorimotor or cognitive tasks. While the majority of fMRI studies have used blood oxygenation level-dependent (BOLD) contrast as a marker for neural activation, baseline drift effects result in poor sensitivity for detecting slow variations in neural activity. By contrast, drift effects are minimized in arterial spin labeling (ASL) perfusion contrast, primarily as a result of successive pairwise subtraction between images acquired with and without labeling. Recent data suggest that ASL contrast shows stable noise characteristics over the entire frequency spectrum, which makes it suitable for studying low-frequency events in brain function. The present study investigates the relative sensitivities of ASL and BOLD contrast in detecting changes in motor cortex activation over a spectrum of frequencies of experimental design, where the alternating period between the resting state and activation is varied from 30 s up to 24 hr. The results demonstrate that 1) ASL contrast can detect differences in motor cortex activation over periods of minutes, hours, and even days; 2) the functional sensitivity of ASL contrast becomes superior to that of BOLD contrast when the alternating period between the resting state and activation is greater than a few minutes; and 3) task activation measured by ASL tends to have less intersubject variability than BOLD contrast. The improved sensitivity of the ASL contrast for low task frequency and longitudinal studies, along with its superior power in group analysis, is expected to extend the range of experimental designs that can be studied using fMRI.

Adult↗

PubMed2005

Propagation of EEG activity in the beta and gamma band during movement imagery in humans.

OBJECTIVES: The objective of the paper was the determination of electrical brain activity propagation in sensorimotor areas during hand movement imagery. METHODS: Right-hand and left-hand movement imagination was studied in three subjects. The 10-channel Multivariate Autoregressive Model (MVAR) was fitted to EEG signals recorded from subsets of electrodes overlying central and related brain areas. By means of the Short-time Directed Transfer Function (SDTF) the propagation of brain activity as a function of frequency and time was found. RESULTS: During imagery the relation between propagations in gamma and beta bands changed significantly for electrodes overlying sensorimotor areas, namely the increase in gamma was accompanied by the decrease in the beta band. CONCLUSIONS: The hypothesis was put forward that these kinds of changes in flow of electrical brain activity are connected with the specific information processing.

Adolescent↗

PubMed2005

Sensorimotor integration to cutaneous afferents in humans: the effect of the size of the receptive field.

Transcranial magnetic stimulation (TMS) can be used to study sensorimotor integration in humans non-invasively. Motor excitability has been found to be inhibited when afferent stimuli are given to a peripheral nerve and precede TMS at interstimulus intervals (ISIs) of 20-50 ms. This phenomenon has been referred to as short-latency afferent inhibition (SAI). To better understand the functional meaning of these phenomena, we examined the effect of the size of the receptive field on SAI to cutaneous afferents in upper-limb sensorimotor areas in humans. We examined the effect of the stimulation of the isolated right first (D1), second (D2) and third finger (D3), the right second and third finger together (D23) and the right first three fingers together (D123) on the amplitude of motor evoked potentials (MEPs) to TMS in hand and forearm muscles. We examined the right abductor pollicis brevis (APB), first dorsal interosseous (FDI), extensor carpi radialis (ECR) and flexor carpi radialis (FCR) muscles. Digital stimulation preceded TMS at ISIs of 20-50 ms. The effect of D2 stimulation was MEP inhibition (SAI), which was more marked and consistent in APB and FDI muscles than in ECR and FCR muscles. Similarly, D1 and D3 stimulation caused MEP reduction, while no MEP enhancement could be found to single finger stimulation. In contrast, D123 stimulation induced less effective SAI in upper-limb muscles. MEP potentiation was recorded in some muscles to D123 stimulation. A significant difference between D2 and D123 stimulation was found in APB (ISIs = 30-50 ms) and FDI (ISIs = 40-50 ms) muscles, but not in forearm muscles. The effect to D23stimulation on MEP amplitude was intermediate between those to D2 and D123 stimulation. Our data suggest that motor excitability to cutaneous afferents may be influenced by the size of the receptive fields, this effect being the result of increasing convergence between hand afferents in the somatosensory system. These phenomena appear to be topographically arranged across the representation of upper-limb muscles. These findings may help to understand the functional significance of SAI in normal physiology and pathophysiology.

Adult↗

PubMed1990

Electrophysiological characterization of central sensory and motor pathway function in patients with moderate hemiparesis. II. Clinical results.

The central sensory and motor pathway function in patients with moderate hemiparesis and in healthy persons was selectively characterized by evaluation of latencies of short (R1) and long (R2) latency EMG responses as well as simultaneously recorded sensorimotor potentials (N19, N26) evoked by electrical stimulation of median and peroneal nerve (additionally, calculation of peripheral and central sensory/motor conduction times). This investigation procedure permits a noninvasive quantification of disturbed central sensory and motor pathway function in hemiparetic patients. The results found are in agreement to clinical, CT and other examination findings.

Adolescent↗

PubMed1991

Electrophysiological and morphological properties of embryonic neocortical grafts developing in different regions of the host rat brain.

Parallel morphological and electrophysiological studies of embryonic neocortical tissue (primordia of anterior parietal--presumptive sensorimotor--cortex) grafted into different regions of the host adult brain (sensori-motor cortex, caudate-putamen, septum or thalamus) were carried out to investigate to what extent the properties of transplanted embryonic neocortex--an advanced organizational form of neuronal tissue--are affected by homotopic or heterotopic surroundings. The results point to the importance of the host tissue environment as it influences both the size, the morphological and functional properties of the implanted embryonic cortical plate tissue. The cortical grafts were smaller in size when developed homo-topically in sensorimotor cortex and grew larger in heterotopic environment (caudate-putamen, septum, thalamus). The orientation of neuronal dendrites in the grafts tends to follow that seen in the surroundings. The homotopic grafts showed a better structural integration into the host brain. Differences were seen between intracortical and subcortical transplants in the spontaneous firing rate of neurons and in the ratio of units with various types of spontaneous discharge.

Animals↗

PubMed2002

Adaptive functional changes in the cerebral cortex of patients with nondisabling multiple sclerosis correlate with the extent of brain structural damage.

In multiple sclerosis, the mechanisms underlying the accumulation of disability are poorly understood. Recently, it has been suggested that adaptive cortical changes may limit the clinical impact of multiple sclerosis injury. In this study, functional magnetic resonance imaging and a general search method were used to assess patterns of brain activation associated with a simple motor task in 14 right-handed, nondisabled relapsing-remitting multiple sclerosis patients that were compared to those from 15 right-handed, sex- and age-matched healthy volunteers. Also investigated were the extent to which the functional magnetic resonance imaging changes correlated with T2 lesion volume and severity of multiple sclerosis pathology in lesions and normal-appearing brain tissue, measured using magnetisation transfer and diffusion tensor magnetic resonance imaging. Compared to controls, multiple sclerosis patients showed increased activation in the contralateral primary sensorimotor cortex, bilaterally in the supplementary motor area, bilaterally in the cingulate motor area, in the contralateral ascending bank of the sylvian fissure, and in the contralateral intraparietal sulcus. T2 lesion volume was correlated with relative activation in the ipsilateral supplementary motor area, and in the ipsilateral and contralateral cingulate motor area. Average lesion magnetisaiton transfer ratio and average lesion water diffusivity were correlated with relative activation in the contralateral sensorimotor cortex. Average lesion magnetisation transfer ratio was also correlated with relative activation in the ipsilateral cingulate motor area. Average water diffusivity and peak height of the normal-appearing brain tissue diffusivity histogram were both correlated with relative activation in the contralateral intraparietal sulcus. This study shows that cortical activation occurs over a rather distributed sensorimotor network in nondisabled relapsing-remitting multiple sclerosis patients. It also suggests that increased recruitment of this cortical network contributes to the limitation of the functional impact of white matter multiple sclerosis injury.

Adaptation, Physiological↗

PubMed1982

Sensorimotor disturbances in the aging rodent.

Male rats that were 6, 12, 24, and 30 months of age were examined for sensory and motor functions, using a battery of tests of neurological capacities. An age-related decline in the ability to localize stimuli was observed, particularly in visually elicited forelimb placing. In addition, the old rats had impaired hindlimb reflexes (hindlimb placing and stepping reactions). Rats older than 12 months of age also showed abnormal tone of the forelimbs. These dysfunctions may contribute to the deterioration of complex movement sequences that has been reported in aging rodent species.

Aging↗

PubMed1996

Supplementary sensorimotor area epilepsy in adults.

Based on stimulation studies, observation of seizure phenomena in patients with epilepsy, and diagnostic studies documenting SSMA anatomic and functional abnormalities, there is evidence that epileptic involvement of the SSMA results in a set of clinical phenomena that include asymmetric tonic posturing of the extremities, abduction and elevation of the contralateral upper extremity, and speech arrest with preserved consciousness. Auras and vocalization occur less frequently. These seizures tend to be brief and to have an abrupt onset and cessation. They are more common during sleep than during wakefulness, and they tend to occur multiple times per night. The abolition of seizures following a resection limited to the SSMA provides conclusive evidence that the SSMA is the epileptogenic zone in some patients with this type of seizure. On the other hand, there is variation in seizure phenomena among patients whose seizures originate in the SSMA. In addition, there are patients with seizures suggestive of SSMA involvement whose seizures originate in a broad epileptogenic zone that includes the SSMA, other patients whose seizures originate outside the SSMA and spread to the SSMA, and still other patients whose seizures originate outside the SSMA and remain outside the SSMA. To better understand the phenomena associated with SSMA seizure onset and to determine the specificity of certain phenomena to SSMA involvement, additional data are needed from structural and functional imaging studies, video and EEG monitoring studies with noninvasive and invasive electrodes, and pathologic and surgical outcome studies. Since one cannot be certain at this time of the specificity of seizure phenomena to SSMA involvement, and because localization for possible surgery is the primary rationale for detailed study of these patients, we recommend that the term SSMA seizure refer only to those seizures that originate in the SSMA and that SSMA epilepsy refer only to epilepsies in which the patient's seizures originate in the SSMA. Since the present classification of epileptic seizures is not of value in describing the major phenomena of a partial seizure or in localization of the site of onset, a descriptive classification is needed to improve communication concerning seizure phenomena and to provide clues to localization.

Adult↗

PubMed1995

Dopaminergic microtransplants into the substantia nigra of neonatal rats with bilateral 6-OHDA lesions. II. Transplant-induced behavioral recovery.

Transplants of fetal ventral mesencephalic (VM) dopamine neurons implanted into the substantia nigra in 6-hydroxy-dopamine (6-OHDA)-lesioned neonatal pups establish axonal connections with the denervated caudate putamen (Nikkhah et al., 1995). In the present study, we have explored the functional capabilities of these animals after they reached adulthood on a battery of spontaneous and drug-induced behavioral tasks. The results demonstrate that unilateral intranigral VM grafts in bilaterally lesioned neonates induce a marked bias in spontaneous- and stress-induced rotation contralateral to the implant not present in the lesion-only controls. Amphetamine and apomorphine induced vigorous contra- and ipsilateral rotation, respectively. Moreover, grafted animals achieved 75% of the performance level in contralateral skilled forelimb use when compared to normal controls, which was significantly above lesion-only animals (50% of normal). Spontaneous nocturnal locomotor activity was elevated 2.2-fold in the grafted animals. Sensorimotor orientation and disengage behavior was spared by the neonatal dopamine lesion and unaffected by the grafts. The level of functional restoration seen in the present study was more extensive than reported previously in neonatally 6-OHDA-lesioned rats where the VM grafts were implanted ectopically into the striatum. However, functional recovery remained incomplete also after intranigral graft placement compared to normal intact animals. The present approach should provide a new promising avenue for the continued exploration of the mechanisms involved in functional recovery and structural repair in the damaged nigrostriatal system.

Amphetamine↗

PubMed2004

Changes in motor system function and recovery after stroke.

Motor system impairments are common after stroke and are a major contributor to disability after stroke. Most patients show improvement in the weeks-months following a stroke. Understanding the neurobiological underpinnings of these behavioral gains may be useful for refining treatments that aim to improve outcome and reduce disability. A number of brain mapping studies have examined how stroke affects motor system function. Numerous changes have been identified in this setting and are reviewed herein, including reduced laterality, widespread changes across a distributed sensorimotor network, and a change in the site and size of key activation foci. Some of these changes have been found to correlate with features of injury, behavior, or treatment-induced behavioral gains. A current challenge is to extend these findings to improve clinical decision making.

Humans↗