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PubMed2006

Atypically diffuse functional connectivity between caudate nuclei and cerebral cortex in autism.

BACKGROUND: Autism is a neurodevelopmental disorder affecting sociocommunicative behavior, but also sensorimotor skill learning, oculomotor control, and executive functioning. Some of these impairments may be related to abnormalities of the caudate nuclei, which have been reported for autism. METHODS: Our sample was comprised of 8 high-functioning males with autism and 8 handedness, sex, and age-matched controls. Subjects underwent functional MRI scanning during performance on simple visuomotor coordination tasks. Functional connectivity MRI (fcMRI) effects were identified as interregional blood oxygenation level dependent (BOLD) signal cross-correlation, using the caudate nuclei as seed volumes. RESULTS: In the control group, fcMRI effects were found in circuits with known participation of the caudate nuclei (associative, orbitofrontal, oculomotor, motor circuits). Although in the autism group fcMRI effects within these circuits were less pronounced or absent, autistic subjects showed diffusely increased connectivity mostly in pericentral regions, but also in brain areas outside expected anatomical circuits (such as visual cortex). CONCLUSION: These atypical connectivity patterns may be linked to developmental brain growth disturbances recently reported in autism and suggest inefficiently organized functional connectivity between caudate nuclei and cerebral cortex, potentially accounting for stereotypic behaviors and executive impairments.

Journal Article↗
PubMed1998

White matter alterations following thromboembolic stroke: a beta-amyloid precursor protein immunocytochemical study in rats.

Thromboembolic stroke in rats leads to a well-described pattern of histopathological and behavioral abnormalities. However, limited data are available in animal models concerning the response of the white matter to embolic events. The purpose of this study was to document patterns of white matter abnormalities using beta-amyloid precursor protein (betaAPP) immunocytochemistry as a marker of axonal damage. Twelve male Wistar rats underwent photochemically induced right common carotid artery thrombosis (CCAT) or sham procedures. At 3 days after CCAT, rats were perfusion-fixed and sections immunostained for the visualization of betaAPP or stained with hematoxylin and eosin for routine histopathological analysis. As previously described, CCAT produced small ipsilateral embolic infarcts and ischemic cell change within gray matter structures including the medial cerebral cortex, striatum, hippocampus and thalamus. In areas of frank infarction, numerous reactive profiles were observed within borderzones of the damaged site. However, betaAPP immunocytochemistry also revealed reactive axonal profiles within various white matter tracts including the corpus callosum, external capsule and fimbria of the hippocampus. In many cases, the presence of axonal damage could not be appreciated with routine hematoxylin and eosin staining. These data indicate that CCAT leading to platelet embolization to the brain not only produces embolic infarcts but also produces more subtle white matter abnormalities. Previously undetected white matter damage would be expected to participate in the sensorimotor and cognitive behavioral deficits following embolic stroke.

Amyloid beta-Protein Precursor↗
PubMedDate not supplied

Sensorimotor developmental delays and lower anxiety in rats prenatally exposed to cadmium.

Pregnant rats were treated with 0.3 or 0.6 mg cadmium (CdCl2) kg(-1) injected subcutaneously on a daily basis from gestational day 7 to day 15 (organogenesis period). One control group was not injected and the other received saline. Offspring were tested for ontogeny of sensorimotor development and at 45 or 90 days of age for anxiety behavior. The study of sensorimotor development showed that gestational exposure to 0.6 mg Cd kg(-1) produced a delay in the development of the righting reflex and of the cliff aversion in the pups. No differences were observed in the development of the negative geotaxis, nor in the ages of eye and ear opening. Anxiety studies using an elevated plus maze showed a lower anxiety in all the offspring prenatally exposed to 0.6 mg Cd kg(-1) as these rats spent more time and entered the open arms more times compared with those of the other groups. The results demonstrate that exposure to low levels of Cd during organogenesis may modify some central nervous system functions.

Animals↗
PubMed1992

Cortical and striatal structure and connectivity are altered by neonatal hemidecortication in rats.

The cortical cytoarchitecture, cortical thickness, corticostriatal connections, cortical dendritic arborization, and striatal patch-matrix compartmentalization were compared in rats with neonatal (1 day of age) or adult hemidecortication. Neonatal hemidecortication produced few changes in cytoarchitecture of the remaining hemisphere and did not preclude the development of a patch-matrix compartmentalization in either striatum. There was a significant modification of contralateral cortical-striatal connections, however, as there were extensive crossed connections from layer II/III of the prefrontal cortex in the neonatal hemidecorticates, which contrasts with connections from layer V in the normal brain. Adult hemidecorticates had no crossed corticostriatal connections. Neonatal hemidecortication also led to an increase in cortical thickness relative to adult operates or controls and the neonatal hemidecorticates, and led to an increase in dendritic arborization in layer II/III pyramidal cells of the somatosensory and motor cortex but not in the visual or temporal cortex. The results suggest that the behavioral sparing of sensorimotor and some prefrontal functions after neonatal hemidecortication could be supported, in part, by the anatomical changes in the prefrontal and sensorimotor connectivity and dendritic arborization.

Animals↗
PubMed2005

Imaging speech production using fMRI.

Human speech is a well-learned, sensorimotor, and ecological behavior ideal for the study of neural processes and brain-behavior relations. With the advent of modern neuroimaging techniques such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), the potential for investigating neural mechanisms of speech motor control, speech motor disorders, and speech motor development has increased. However, a practical issue has limited the application of fMRI to issues in spoken language production and other related behaviors (singing, swallowing). Producing these behaviors during volume acquisition introduces motion-induced signal changes that confound the activation signals of interest. A number of approaches, ranging from signal processing to using silent or covert speech, have attempted to remove or prevent the effects of motion-induced artefact. However, these approaches are flawed for a variety of reasons. An alternative approach, that has only recently been applied to study single-word production, uses pauses in volume acquisition during the production of natural speech motion. Here we present some representative data illustrating the problems associated with motion artefacts and some qualitative results acquired from subjects producing short sentences and orofacial nonspeech movements in the scanner. Using pauses or silent intervals in volume acquisition and block designs, results from individual subjects result in robust activation without motion-induced signal artefact. This approach is an efficient method for studying the neural basis of spoken language production and the effects of speech and language disorders using fMRI.

Adult↗
PubMed2005

Dissecting the genetic complexity of human 6p deletion syndromes by using a region-specific, phenotype-driven mouse screen.

Monosomy of the human chromosome 6p terminal region results in a variety of congenital malformations that include brain, craniofacial, and organogenesis abnormalities. To examine the genetic basis of these phenotypes, we have carried out an unbiased functional analysis of the syntenic region of the mouse genome (proximal Mmu13). A genetic screen for recessive mutations in this region recovered thirteen lines with phenotypes relevant to a variety of clinical conditions. These include two loci that cause holoprosencephaly, two that underlie anophthalmia, one of which also contributes to other craniofacial abnormalities such as microcephaly, agnathia, and palatogenesis defects, and one locus responsible for developmental heart and kidney defects. Analysis of heterozygous carriers of these mutations shows that a high proportion of these loci manifest with behavioral activity and sensorimotor deficits in the heterozygous state. This finding argues for the systematic, reciprocal phenotypic assessment of dominant and recessive mouse mutants. In addition to providing a resource of single gene mutants that model 6p-associated disorders, the work reveals unsuspected genetic complexity at this region. In particular, many of the phenotypes associated with 6p deletions can be elicited by mutation in one of a number of genes. This finding implies that phenotypes associated with contiguous gene deletion syndromes can result not only from dosage sensitivity of one gene in the region but also from the combined effect of monosomy for multiple genes that function within the same biological process.

Animals↗
PubMedDate not supplied

Measuring human functional age: a review of empirical findings.

A review of empirical functional age studies published in English was conducted. Types of biomarkers used in functional age studies included sensorimotor, cognitive, psychosocial, behavioral, anthropometric, biomedical, physiological, and dental variables. Previous criticisms of the validity and utility of functional age research were evaluated with reference to empirical studies. While some of these criticisms remain valid, areas of research currently using established biomarkers to predict functional outcomes were identified, including driving, falls, and cognitive functioning. It was concluded that the success of functional age research is dependent on the relevance of biomarkers to specific functional outcomes.

Adult↗
PubMed2004

Weaving basic and social sciences into a case-based, clinically oriented medical curriculum: one school's approach.

Southern Illinois University School of Medicine recently completed its fourth year of a resource-session-enhanced, case-based, tutor-group-oriented curriculum. As an example of a curricular unit, the authors describe the implementation of the basic and clinical sciences in one of the four units in year one, and detail that unit's organization, logistics, content, rationale, and other characteristics. The Sensorimotor Systems and Behavior (SSB) unit is preceded by a cardio-respiratory-renal unit and is followed by an endocrine-reproductive-gastrointestinal unit. A Doctoring unit temporally spans each of these three units. The SSB unit is allotted an 11.5-week period that includes an aggregate of 2.5 weeks of available clinical time, 1.5 weeks for examinations and exam study time, and approximately 8.5 weeks for tutor-group sessions, mandatory laboratory sessions, and self-directed learning. Optional resource sessions are offered during a two- to four-hour block on a single morning each week. Clinical training in the SSB unit augments self-directed, laboratory, and tutor-group learning of neuroscience, gross anatomy, cell biology, physiology, biochemistry, behavioral and social science, embryology, limited pharmacology and genetics, and basic clinical neurology for first-year students. Although it is fast-paced and places heavy responsibility for independent learning on the students, the SSB unit culminates in significant achievement in the basic and clinical sciences. The unit provides substantial clinical training and practical experience in physical and neurological examinations that directly integrate with basic science knowledge. The unit reduces lecture-based instruction, demands self-determination, and promotes experience in team effort, professionalism, peer interaction, empathy in clinical medicine, and practical use of basic science knowledge.

Curriculum↗
PubMed2003

Diverse psychotomimetics act through a common signaling pathway.

Three distinct classes of drugs: dopaminergic agonists (such as D-amphetamine), serotonergic agonists (such as LSD), and glutamatergic antagonists (such as PCP) all induce psychotomimetic states in experimental animals that closely resemble schizophrenia symptoms in humans. Here we implicate a common signaling pathway in mediating these effects. In this pathway, dopamine- and an adenosine 3',5'-monophosphate (cAMP)-regulated phospho-protein of 32 kilodaltons (DARPP-32) is phosphorylated or dephosphorylated at three sites, in a pattern predicted to cause a synergistic inhibition of protein phosphatase-1 and concomitant regulation of its downstream effector proteins glycogen synthesis kinase-3 (GSK-3), cAMP response element-binding protein (CREB), and c-Fos. In mice with a genetic deletion of DARPP-32 or with point mutations in phosphorylation sites of DARPP-32, the effects of D-amphetamine, LSD, and PCP on two behavioral parameters-sensorimotor gating and repetitive movements-were strongly attenuated.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1995

Sensorimotor encoding by synchronous neural ensemble activity at multiple levels of the somatosensory system.

Neural ensemble processing of sensorimotor information during behavior was investigated by simultaneously recording up to 48 single neurons at multiple relays of the rat trigeminal somatosensory system. Cortical, thalamic, and brainstem neurons exhibited widespread 7- to 12-hertz synchronous oscillations, which began during attentive immobility and reliably predicted the imminent onset of rhythmic whisker twitching. Each oscillatory cycle began as a traveling wave of neural activity in the cortex that then spread to the thalamus. Just before the onset of rhythmic whisker twitching, the oscillations spread to the spinal trigeminal brainstem complex. Thereafter, the oscillations at all levels were synchronous with whisker protraction. Neural structures manifesting these rhythms also exhibited distributed spatiotemporal patterns of neuronal ensemble activity in response to tactile stimulation. Thus, multilevel synchronous activity in this system may encode not only sensory information but also the onset and temporal domain of tactile exploratory movements.

Animals↗
PubMed2006

Correlation of C-start behaviors with neural activity recorded from the hindbrain in free-swimming goldfish (Carassius auratus).

Startle behaviors in teleost fishes are well suited for investigations of mechanisms of sensorimotor integration because the behavior is quantifiable and much of the underlying circuitry has been identified. The teleost C-start is triggered by an action potential in one of the two Mauthner (M) cells. To correlate C-start behavior with electrophysiology, extracellular recordings were obtained from the surface of the medulla oblongata in the hindbrain, close to the M-axons, in freely swimming goldfish monitored using high-speed video. The recordings included action potentials generated by the two M-axons, as well as neighboring axons in the dorsal medial longitudinal fasciculus. Axonal backfills indicated that the latter originate from identifiable reticulospinal somata in rhombomeres 2-8 and local interneurons. Diverse auditory and visual stimuli evoked behaviors with kinematics characteristic of the C-start, and the amplitude of the first component of the hindbrain field potential correlated with the C-start direction. The onset of the field potential preceded that of the simultaneously recorded trunk EMG and movement initiation by 1.08+/-0.04 and 8.13+/-0.17 ms, respectively. A subsequent longer latency field potential was predictive of a counterturn. These results indicate that characteristic features of the C-start can be extracted from the neural activity of the M-cell and a population of other reticulospinal neurons in free-swimming goldfish.

Animals↗
PubMed2005

Efficacy of ear-point stimulation on experimentally induced seizure.

This study was to observe the effects of ear-point stimulation on electrocorticogram of sensorimotor cortex and behaviors of rats with penicillin-induced seizure. The model of epilepsy was by injecting penicillin into the hippocampus. One hour later, the lower 1/2 auricular lobules containing ear-points Pizhixia, Shenmen_Zeng and Nao, etc. as humans, or great auricular nerve of seizure rats, were treated twice with electrical stimulation (parameters of stimulation were as follows: electrical current intensity 0.14 approximately 0.2 mA, frequency about 80Hz, 30 min on and 30 min off). The outcome showed that rats appeared epileptic-like electrocorticogram and convulsion behaviors 5 min after injected penicillin. When they were subsequently given the ear-point or great auricular nerve electrical stimulation separately, these epileptic-like electrocorticogram and seizure behaviors were definitely improved. These anti-seizure effects could be enhanced with hour extension of electrical stimulation. If the great auricular nerve of seizure rat was severed before electrical stimulating ear-points, the effects of anti-seizure disappeared. Otherwise, the seizure rats given sham ear-point electrical stimulation (the experimental conditions were same as that of ear-point stimulation other than electric current being no applied) did not show any improvement for epileptic-like electrocorticogram and seizure behaviors. Based on the results above, it was suggested that ear-point electrical stimulation could cause certainly efficacy of anti-seizure, which may be relative with the great auricular nerve.

Acupuncture, Ear↗
PubMed1999

Ephrin-A binding and EphA receptor expression delineate the matrix compartment of the striatum.

The striatum integrates limbic and neocortical inputs to regulate sensorimotor and psychomotor behaviors. This function is dependent on the segregation of striatal projection neurons into anatomical and functional components, such as the striosome and matrix compartments. In the present study the association of ephrin-A cell surface ligands and EphA receptor tyrosine kinases (RTKs) with the organization of these compartments was determined in postnatal rats. Ephrin-A1 and ephrin-A4 selectively bind to EphA receptors on neurons restricted to the matrix compartment. Binding is absent from the striosomes, which were identified by mu-opioid receptor immunostaining. In contrast, ephrin-A2, ephrin-A3, and ephrin-A5 exhibit a different mosaic binding pattern that appears to define a subset of matrix neurons. In situ hybridization for EphA RTKs reveals that the two different ligand binding patterns strictly match the mRNA expression patterns of EphA4 and EphA7. Ligand-receptor binding assays indicate that ephrin-A1 and ephrin-A4 selectively bind EphA4 but not EphA7 in the lysates of striatal tissue. Conversely, ephrin-A2, ephrin-A3, and ephrin-A5 bind EphA7 but not EphA4. These observations implicate selective interactions between ephrin-A molecules and EphA RTKs as potential mechanisms for regulating the compartmental organization of the striatum.

Animals↗
PubMed1998

Differential recovery of sensorimotor function in GM1 ganglioside-treated vs. spontaneously recovered MPTP-treated cats: partial striatal dopaminergic reinnervation vs. neurochemical compensation.

Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to cats results in a parkinsonian syndrome characterized by rigidity, akinesia, bradykinesia, decreased response to external sensory stimuli and depletion of nigrostriatal dopamine. Cats spontaneously recover gross sensorimotor functions despite little recovery of the dopaminergic innervation of the striatum. In contrast, GM1 ganglioside administration accelerates gross behavioral recovery and causes an increased dopaminergic innervation of the striatum. This study examined whether these two recovery conditions are characterized by different degrees of functional recovery. Cats were trained to perform a sensorimotor reaching task prior to MPTP exposure and were then re-tested on the task 6 weeks later after spontaneously recovering gross motor functioning or after 6 weeks of GM1 treatment. Gross motor recovery was similar in both groups. However, the spontaneously recovered cats had significant difficulty in performing the task while GM1-treated cats performed normally. GM1-treated cats also had significant increases in striatal [3H]mazindol binding compared to spontaneously recovered cats. These results suggest that while gross motor functions may improve to a similar extent with spontaneous and GM1-induced recovery from experimental parkinsonism, complex sensorimotor behavior recovers to different extents under the different recovery conditions. More complete behavioral recovery may depend upon at least a partial recovery of striatal dopaminergic terminals rather than neurochemical compensation.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1988

Recovery of sensorimotor function after frontal cortex damage in rats: evidence that the serial lesion effect is due to serial recovery.

Multiple-staged brain lesions produce fewer and smaller behavioral effects than does damage produced in a single surgery. This is called the serial lesion effect. Two hypotheses were tested, the reduced deficit hypothesis and the serial recovery hypothesis, which attempt to explain the serial lesion effect. The effects of lesions of the medial frontal cortex on sensorimotor behavior were investigated in rats that received bilateral damage in a single surgery (n = 7), in two unilateral stages separated by 3 weeks (n = 16), or unilateral damage followed 3 weeks later by a sham surgery (n = 5). Unilateral damage produced deficits on the contralateral side in responsivity to visual, tactile, and olfactory stimuli and impairments in roll-over and paw withdrawal motor responses. All behavioral impairments except visual placement recovered over the next 3 weeks. A second unilateral lesion on the contralateral side produced the same symptoms but on the opposite side of the body. There was no reinstatement of the previously recovered deficits. Bilateral damage incurred in a single stage produced these same deficits on both sides. Because the effects of the second unilateral lesion in the two-stage group produced comparable contralateral effects to those produced in the single-stage group, but no reinstatement of ipsilateral deficits occurred, the reduced deficit hypothesis was rejected. It was concluded that at least for medial frontal cortex damage, the serial lesion effect occurred as a result of serial recovery of the deficits.

Animals↗
PubMed2007

Smoking in the absence of nicotine: behavioral, subjective and physiological effects over 11 days.

AIMS: Sensorimotor stimuli associated with tobacco smoking influence smoking behavior; however, current research has focused almost exclusively on the effects of brief, laboratory-based exposure to smoking-related stimuli. The purpose of this experiment was to characterize the effects of smoking stimuli delivered in the absence of nicotine over an extended (11-day) exposure. DESIGN, SETTING AND PARTICIPANTS: Thirty adult regular smokers participated in an in-patient study. After assessing preferred brand smoking, participants were assigned randomly to one of three groups corresponding to subsequent smoking conditions: nicotine-containing cigarettes, de-nicotinized cigarettes or no smoking. MEASUREMENTS: Measures of smoking reinforcement, subjective effects, physiological effects, withdrawal/craving and puff topography were taken repeatedly during both periods of free access and controlled assessments during abstinence. FINDINGS: Daily de-nicotinized cigarette use declined immediately by 1.7 cigarettes/day compared to the preferred brand baseline and declined by another 3.5 cigarettes over time; participants smoking de-nicotinized cigarettes also demonstrated a 31% decline in the number of puffs earned on a progressive ratio, a measure of the motivation to smoke, during the study. Subjective ratings of smoking were largely negative throughout the study in the de-nicotinized group, while the nicotine-containing condition reported increasingly positive subjective effects with repeated exposure. Acute craving suppression following smoking remained evident throughout the study regardless of nicotine content. CONCLUSIONS: These effects highlight the importance of non-nicotine sensorimotor stimuli as determinants of the maintenance of smoking behavior and suggests that extinction of conditioned reinforcement in the absence of nicotine progresses slowly.

Adolescent↗
PubMed1992

5-HT1 receptors and behavior.

The activation of different subtypes of the 5-HT1 receptor can be associated with specific behavioral responses. The present review discusses different categories of behavioral studies that have examined functional distinctions among 5-HT1 receptors. These include: 1) behavioral responses elicited by selective 5-HT receptor agonists; 2) drug discrimination experiments; 3) studies of sensorimotor reactivity and motivated behavior; and 4) behavioral models of clinical psychotherapeutic effects.

Animals↗
PubMed1987

[Molecular mechanisms of the involvement of the pyramidal neurons of the sensorimotor cortex in the organization of the feeding behavior of rabbits].

Experiments performed on freely moving rabbits have shown that pyramidal neurons which had direct connections with lateral hypothalamus were activated during realization of the feeding behaviour. Pyramidal neurons which had no connection with lateral hypothalamus were inhibited. Microiontophoretic application of the protein synthesis inhibitor to pyramidal neurons caused their disability to respond to ascending activatory influences from the lateral hypothalamus. Administration of pentagastrin during inhibition of the protein synthesis restored the ability of pyramidal neurons to participate in hypothalamic feeding reactions. It is suggested that synthesis and release of the gastrin-like peptide into the perineuronal space is necessary for involvement of sensomotor cortex pyramidal neurons in organization of the feeding behaviour.

Animals↗