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Functional connectivity of cortical networks involved in bimanual motor sequence learning.

Motor skill learning requires the involvement and integration of several cortical and subcortical regions. In this study, we focus on how the functional connectivity of cortical networks changes with the acquisition of a novel motor skill. Using functional magnetic resonance imaging, we measured the localized blood oxygenation level-dependent (BOLD) signal in cortical regions while subjects performed a bimanual serial reaction time task under 2 conditions: 1) explicitly learning a novel sequence (NOVEL) and 2) playing a previously learned sequence (LEARNED). To investigate stages of learning, each condition was further divided into nonoverlapping early and late conditions. Functional connectivity was measured using a task-specific low-frequency coherence analysis of the data. We show that within the cortical motor network, the sensorimotor cortex, premotor cortex, and supplementary motor area have significantly greater inter- and intrahemispheric coupling during the early NOVEL condition compared with the late NOVEL condition. Additionally, we observed greater connectivity between frontal regions and cortical motor regions in the early versus late NOVEL contrast. No changes in functional connectivity were observed in the LEARNED condition. These results demonstrate that the functional connectivity of the cortical motor network is modulated with practice and suggest that early skill learning is mediated by enhanced interregional coupling.

Adult↗

The role of the inferior parietal cortex in linking the tactile perception and manual construction of object shapes.

We employed functional magnetic resonance imaging (fMRI) in 12 healthy subjects to measure cerebral activation related to a set of higher order manual sensorimotor tasks performed in the absence of visual guidance. Purposeless manipulation of meaningless plasticine lumps served as a reference against which we contrasted two tasks where manual manipulation served a meaningful purpose, either the perception and recognition of three-dimensional shapes or the construction of such shapes out of an amorphous plasticine lump. These tasks were compared with the corresponding mental imagery of the modelling process which evokes the constructive concept but lacks concomitant sensorimotor input and output. Neural overlap was found in a bilateral activity increase in the posterior and anterior intraparietal sulcus area (IPS and AIP). Differential activation was seen in the supplementary and cingulate motor areas, the left M1 and the superior parietal lobe for modelling and in the left angular and ventral premotor cortex for imagery. Our data thus point to a congruent neural substrate for both perceptive and constructive object-oriented sensorimotor cognition in the AIP and posterior IPS. The leftward asymmetry of the inferior parietal activations, including the angular gyrus, during imagery of modelling along with the ventral premotor activations emphasize the close vicinity of the circuitry for cognitive manipulative motor behaviour and language.

Adult↗

Evaluation of nigrostriatal dopaminergic function in adult +/+ and +/- BDNF mutant mice.

Deletion of a single copy of the BDNF gene has been shown to affect the nigrostriatal dopaminergic system of young adult BDNF mice. In the present report we evaluated various indices of nigrostriatal dopaminergic function between 9-month-old wild-type (+/+) and heterozygous (+/-) BDNF mutant mice. Performance in a sensorimotor beam walking task was significantly decreased in +/- mice as indicated by increased times required to traverse both a wide (21 mm) and narrow (6 mm) beam. No differences in spontaneous locomotor behavior were observed between the +/+ and +/- mice. Amphetamine-stimulated (5 mg/kg) locomotor behavior was increased to a greater degree in the +/- mice, with the number of movements performed by these mice being significantly greater than their +/+ controls. Corpus striatal dopamine concentrations were significantly greater in the +/- BDNF mice. The absence of any significant differences for dopamine concentrations within the hypothalamus and olfactory bulb of these mice, as well as an absence of any difference in striatal norepinephrine concentrations, suggested a relative specificity of these effects to the corpus striatum. Both the +/- and +/+ mice showed similar reductions in striatal dopamine concentrations in response to a neurotoxic regimen of methamphetamine (20 mg/kg). Collectively these data show increased levels of striatal dopamine concentrations associated with altered behavioral responses involving the nigrostriatal dopaminergic system within the heterozygous BDNF mutant mice.

Animals↗

Injection of a minuscule dose of FeCl3 within the ventrolateral striatum causes a chronic disturbance of the integrative function within the limbic part of the ventral striatum.

The present study shows that low amounts of applied iron have a potent effect on the ventrolateral striatum. This is reflected by an influence on spontaneous night activity, cognitive behaviour during the water maze navigation task, exploratory activity and in response to postsynaptic apomorphine stimulation. Such functional disturbances could be observed up to months after a single application of either 0.3 microgram or 1.5 micrograms FeCl3. The low dose of iron stimulates while 1.5 micrograms inhibits the spontaneous dopaminedependent locomotor night and explorative activity. The low concentration of ionic iron injected intrastriatally also increases lipid peroxidation in striatal and hippocampal tissues. These results suggest that the functional integrity of the ventral striatum and the regulation of the iron metabolism are critical for the sensorimotor performance.

Animals↗

Action prediction in the cerebellum and in the parietal lobe.

The ability of the central nervous system to predict motor behaviour is a central issue in experimental and computational studies of motor control. The parietal cortex and the cerebellum have been proposed to play a role in sensorimotor prediction. Here we discuss the roles of these two brain regions in various aspects of sensorimotor prediction according to results of recent empirical studies using a variety of techniques including electrophysiology, psychophysics, functional neuroimaging and the investigation of neurological patients.

Animals↗

Subdivisions of the dopamine-containing A8-A9-A10 complex identified by their differential mesostriatal innervation of striosomes and extrastriosomal matrix.

The mesostriatal projections from the dopamine-containing cells groups A8, A9 and A10 have been studied in the cat in relation to the histochemical compartments known to exist in the striatum. In order to do this, we made stereotaxic injections in the substantia nigra of either [3H]proline-[3H]leucine, [35S]methionine, wheat germ agglutinin-horseradish peroxidase, or the two last tracers combined, and compared the location of anterograde labeling in the striatum to the locations of striosomes and extrastriosomal matrix identified by their low or high content, respectively, of the enzyme acetylcholinesterase. A discrete innervation of dorsolateral striosomes by a caudal densocellular subdivision of the substantia nigra pars compacta was found. This densocellular zone of the pars compacta was readily identifiable in sections stained for tyrosine hydroxylase-like immunoreactivity and corresponded to the uniquely acetylcholinesterase-poor zone detected in the substantia nigra pars compacta in serially adjacent sections stained for this enzyme. Selective anterograde labeling of the extrastriosomal matrix occurred in cases with injection sites centered in cell group A8. Tracer deposits in cell group A10 also elicited a preferential labeling of the extrastriosomal matrix, but this innervation was sparse compared to the prominent labeling of fibers in the ventral striatum. An almost exclusive innervation of caudal and ventral striosomes of the head of the caudate nucleus occurred after a deposit of tracer in the pars lateralis of the substantia nigra. Mixed labeling of striosomes and matrix occurred with injection sites centered in the rostral, cell-sparse part of the pars compacta of the substantia nigra. Clusters of tyrosine hydroxylase-immunoreactive neurons within this zone, most likely representing finger-like extensions of the caudal densocellular zone of the pars compacta, might have accounted for part of the striosomal labeling in these cases. We conclude that different subdivisions of the A8-A9-A10 dopamine-containing cell complex of the cat's mesencephalon project preferentially to striosomes or to extrastriosomal matrix. On this basis we suggest that there may be different functional channels in the mesostriatal projection, including, from cell group A8, a channel providing dopaminergic modulation of sensorimotor processing in the striatal matrix, and, from the densocellular zone of the substantia nigra pars compacta, a channel leading to limbic-related mechanisms represented in the striosomal system.

Afferent Pathways↗

Quantitative assessment of mirror movements in children and adolescents with hemiplegic cerebral palsy.

Mirror movements in individuals with hemiplegic cerebral palsy (CP) may result from a reorganization of the central sensorimotor system. Motor performances of both hands were measured to characterize mirror activity (or mirroring) and hand functions in 22 participants (6 to 18 years) with hemiplegic CP and in 17 control participants. During a unimanual repetitive squeezing task, contractions of the active hand and fingertip forces of the opposite hand were recorded simultaneously. In the control group, slight mirror activity (or mirroring) was found that decreased with age. In participants with CP, mirror activity was 15 times stronger than in the control group, and was found at all age levels. Mirroring was more prominent in the unaffected hand of the CP group. The amount of mirror activity was not related to the degree of hemiplegia, which was assessed with measures of spasticity, strength, and dexterity. Mirror movements disturbed functional bimanual skills, although to some extent they could be suppressed by voluntary effort.

Adolescent↗

Motor timing deficits in community and clinical boys with hyperactive behavior: the effect of methylphenidate on motor timing.

In a previous paper we showed that community children with hyperactive behavior were more inconsistent than controls in the temporal organization of their motor output. In this study we investigated: (1) various aspects of motor timing processes in 13 clinically diagnosed boys with attention deficit hyperactivity disorder (ADHD) who were compared to 11 community boys with hyperactive behavior and to a control group and (2) the effect of methylphenidate on the motor timing processes in the clinical group with ADHD in a double blind, cross-over, medication-placebo design, including 4 weeks of medication. The clinical group with ADHD, like the community group with hyperactivity, showed greater variability in sensorimotor synchronization and in sensorimotor anticipation relative to controls. The clinical group was also impaired in time perception, which was spared in the community group with hyperactivity. The persistent, but not the acute dose, of methylphenidate reduced the variability of sensorimotor synchronization and anticipation, but had no effect on time perception. This study shows that motor timing functions are impaired in both clinical and community children with hyperactivity. It is the first study to show the effectiveness of persistent administration of methylphenidate on deficits in motor timing in ADHD children and extends the use of methylphenidate from the domain of attentional and inhibitory functions to the domain of executive motor timing.

Analysis of Variance↗

Norepinephrine and brain damage: alpha noradrenergic pharmacology alters functional recovery after cortical trauma.

The goal of these experiments was to evaluate the effects of some drugs affecting noradrenergic (NE) synaptic transmission, commonly prescribed following stroke or traumatic brain injury, on functional recovery. Measurement of recovery from a transient hemiplegia produced by a traumatic unilateral focal contusion in sensorimotor cortex (SMCX) of rats was used to assess the effects of chronic haloperidol (HAL) treatment begun early (1 day) or late (18 days to recovered animals) after injury. Additionally, using the same model, the effects of a single administration of drugs with selective action at NE receptors were also evaluated early or late (30 days) after injury. These drugs were: phenoxybenzamine (PBZ), an alpha 1-NE antagonist; prazosin (PRAZ), an alpha 1-NE antagonist; yohimbine (YOH), an alpha 2-NE antagonist; propranolol (PROP), a beta 1- and 2-NE receptor antagonist; methoxymine (METHOX), an alpha 1-NE agonist; and clonidine (CLON), an alpha 2-NE agonist. The data indicate that drugs with antagonistic effects at alpha 1 NE receptors, including HAL and PRAZ but not PROP, administered early after SMCX contusion retard locomotor recovery. Beneficial effects of enhancing NE transmission by METHOX or YOH were not observed. In animals recovered from beam walk (BW) deficits, a single administration of PBZ or PRAZ (alpha 1 NE antagonists) or CLON (alpha 2 NE agonist) transiently reinstated hemiplegic symptoms. The nonspecific beta NE receptor antagonist PROP had no effect in recovered animals. A single dose of HAL had no effect in recovered animals, but a BW deficit transiently developed in some animals following chronic treatment. The data are discussed with reference to drug contraindications noted in clinical studies of recovery from poststroke aphasia and cognition in demented patients with degenerative brain disease.

Animals↗

The neural consequences of conflict between intention and the senses.

Normal sensorimotor states involve integration of intention, action and sensory feedback. An example is the congruence between motor intention and sensory experience (both proprioceptive and visual) when we move a limb through space. Such goal-directed action necessitates a mechanism that monitors sensorimotor inputs to ensure that motor outputs are congruent with current intentions. Monitoring in this sense is usually implicit and automatic but becomes conscious whenever there is a mismatch between expected and realized sensorimotor states. To investigate how the latter type of monitoring is achieved we conducted three fully factorial functional neuroimaging experiments using PET measures of relative regional cerebral blood flow with healthy volunteers. In the first experiment subjects were asked to perform Luria's bimanual co-ordination task which involves either in-phase (conditions 1 and 3) or out-of-phase (conditions 2 and 4) bimanual movements (factor one), while looking towards their left hand. In half of the conditions (conditions 3 and 4) a mirror was used that altered visual feedback (factor two) by replacing their left hand with the mirror image of their right hand. Hence (in the critical condition 4) subjects saw in-phase movements despite performing out-of-phase movements. This mismatch between intention, proprioception and visual feedback engendered cognitive conflict. The main effect of out-of-phase movements was associated with increased neural activity in posterior parietal cortex (PPC) bilaterally [Brodmann area (BA) 40, extending into BA 7] and dorsolateral prefrontal cortex (DLPFC) bilaterally (BA 9/46). The main effect of the mirror showed increased neural activity in right DLPFC (BA 9/ 46) and right superior PPC (BA 7) only. Analysis of the critical interaction revealed that the mismatch condition led to a specific activation in the right DLPFC alone (BA 9/46). Study 2, using an identical experimental set-up but manipulating visual feedback from the right hand (instead of the left), subsequently demonstrated that this right DLPFC activation was independent of the hand attended. Finally, study 3 removed the motor intentional component by moving the subjects' hand passively, thus engendering a mismatch between proprioception and vision only. Activation in the right lateral prefrontal cortex was now more ventral than in studies 1 or 2 (BA 44/45). A direct comparison of studies 1 and 3 (which both manipulated visual feedback from the left hand) confirmed that a ventral right lateral prefrontal region is primarily activated by discrepancies between signals from sensory systems, while a more dorsal area in right lateral prefrontal cortex is activated when actions must be maintained in the face of a conflict between intention and sensory outcome.

Adult↗

Functional MRI evidence for subcortical participation in conceptual reasoning skills.

Lesions involving the dorsolateral prefrontal lobes may produce deficits on conceptual reasoning (CR) tasks in humans. Such deficits can also occur with subcortical lesions involving the basal ganglia, thalamus, or cerebellum, suggesting a common, yet widespread, neural network supporting this executive function. Here we report the results of a whole brain functional magnetic resonance imaging (fMRI) experiment in healthy volunteers while performing a CR task. Compared to a sensorimotor control condition, the CR task resulted in discrete subcortical activation sites primarily involving the right basal ganglia, right thalamus and left lateral cerebellum. Cortical activation was present in multiple systems, including the dorsolateral prefrontal and inferior frontal/insular areas; posterior parietal, superior extrastriate, and premotor areas; inferior extrastriate and middle temporal regions; and midline pre-supplementary motor and anterior cingulate regions. Our findings provide strong evidence that CR is mediated by interacting neural systems involving the cerebral cortex, basal ganglia, thalamus, and cerebellum.

Adult↗

Computational model of the role of sensory disorganization in focal task-specific dystonia.

We present a new computational model for the development of task-specific focal dystonia. The purpose of the model is to explain how altered sensory representations can lead to abnormal motor behavior. Dystonia is described as the result of excessive gain through a sensorimotor loop. The gain is determined in part by the sensory cortical area devoted to each motor function, and behaviors that lead to abnormal increases in sensory cortical area are predicted to lead to dystonia. Properties of dystonia including muscular co-contraction, overflow movements, and task specificity are predicted by properties of a linear approximation to the loop transformation. We provide simulations of several different mechanisms that can cause the gain to exceed 1 and the motor activity to become sustained and uncontrolled. The model predicts that normal plasticity mechanisms may contribute to worsening of symptoms over time.

Dystonic Disorders↗

The effect of carotid artery disease on the cerebrovascular response to physiologic stimulation.

Eight of 16 patients with severe carotid artery disease, but no evidence of functional or structural brain damage, had abnormal regional cerebral blood flow (rCBF) responses to physiologic stimulation of sensorimotor cortex (unilateral reduction in six, abnormal diffuse increase in two). Thus, in patients with cerebrovascular disease the rCBF responses during physiologic tasks may not be reliable indicators of local neuronal activity.

Brain↗

Awake surgery for glioma resection in eloquent areas--Zurich's experience and review--.

Awake surgery was performed in a series of 21 patients with gliomas in eloquent areas with the use of intraoperative electrical mapping. Gross total removal was performed in 18 patients. There was no operative mortality. Postoperative findings included no change in symptoms and signs in 10 patients, improvement of the preoperative deficit in 11 patients. Four patients had improved Karnofsky performance status (KPS) scores after surgery, 17 patients were stable, and no patient had lower KPS score. Extensive radical resection of gliomas prolongs the overall survival and improves the patient's quality of life. However, surgical resection of gliomas located within the sensorimotor or language areas remains a neurosurgical challenge in reducing eloquent neurological sequelae. Awake surgery with intraoperative functional mapping is a safe approach to maximize the extent of tumor removal and to minimize the resultant neurological deficits in the treatment of glioma involving the eloquent cortex.

Adult↗

Transforming growth factor beta1 alters synapsin distribution and modulates synaptic depression in Aplysia.

Transforming growth factor beta1 (TGF-beta1) induces long-term synaptic facilitation and long-term increases in excitability in Aplysia. Here we report that this growth factor has acute effects as well. Treatment of pleural-pedal ganglia with TGF-beta1 for 5 min activated mitogen-activated protein kinase (MAPK) and stimulated the phosphorylation of synapsin in a MAPK-dependent manner. This phosphorylation appeared to modulate synapsin distribution in cultured sensory neurons. Control neurons exhibited a punctate distribution of synapsin along neurites, which appeared to represent high concentration aggregates of synapsin. TGF-beta1-treated sensory neurons showed a significant reduction in the number of these puncta, an effect that was blocked by the MAP/ERK kinase inhibitor U0126. The functional consequence of TGF-beta1 was tested by examining its effects on synaptic transmission at the sensorimotor synapse. Application of TGF-beta1 reduced the magnitude of synaptic depression. This effect was dependent on MAPK, consistent with the hypothesis that TGF-1 mobilizes synaptic vesicles through the phosphorylation of synapsin.

Animals↗

[Changes in the structural and functional states of chromatin of the neurons of the cerebral hemisphere cortex in the early post-resuscitation period in rats].

Structuro-functional state of chromatin of the neurons' nuclei of the third, fourth and fifth layers of the sensorimotor cortex was investigated by Moore's method and with the help of ammonia silver colouring an hour and 24 hr post resuscitation in rats who had endured a systemic arrest of blood circulation. It was determined, that the level of labelling of nucleoli of light neurons increased in the early postresuscitation period, while that of dark neurons decreased as compared to check samples. The level of labelling of extranucleolar chromatin increased in both light and dark neurons in the cortex layers under investigation during the 1st hour post resuscitation. The transcriptional activity of extranucleolar chromatin of neurons of both types remained increased in the third and fourth cortex layers 24 hr post resuscitation, while in the fifth one it tended to normalize during the same period. Essential restructuring of the neurons's chromatin was determined with the help of ammonia silver in all cortex layers, which was indicative of a possible change in the spectrum of the synthesized proteins.

Animals↗

The influence of bufotenin on the feeding behavior and cerebral serotonin content in rats.

By researches carried out in male adult rats (Wistar), the influence of the intraperitoneally injected bufotenin (5 mg/kg b.w. active substance in saline solution) was followed on: I--feeding behavior; II--the serotonin concentration in hypothalamus, rhinencephalon, mesencephalon and sensorimotor cerebral cortex. The obtained results show that bufotenin influences the feeding behavior by reducing the motor functions. Its action depends on the physiological state of the animal: by increasing the alimentary motivation the rats can escape the bufotenin influence, showing a normal behavior; bufotenin does not influence the sensorials, the natural dispositions and the excitability level of the feeding and satiety hypothalamic centers. Bufotenin increases serotonin concentration only in the mesencephalic region, but not in the other studied regions. The results are interpreted as a primary bufotenin action on the serotoninic vasoconstrictive receptors at the mesencephalic level, thus disturbing the serotonin-releasing processes and possibly other chemical neurotransmitters.

Animals↗

Clinical application of a dysregulation model of illness and disease: a case of spasmodic torticollis.

A case of spasmodic torticollis is described to demonstrate the clinical usefulness of a new theoretical model of somatic illness and disease. Based on a conception of the living organism as a self-regulating system, the model attributes somatic disorders to a variety of regulatory disturbances including deficits in affect regulation and in the ability to maintain a stable and cohesive self. Throughout the analytical treatment, attention was given to repairing deficits in the patient's self-organisation, and to elevating chaotic impulses and inchoate emotions from a primitive sensorimotor level of experience to a mature representational level where they could be valued for their signal function and modulated through imaginal activity and communication with others. Analysis of the patient's pathologic internal object relations modified his self-organisation, and enabled him to establish regulatory interpersonal relationships that complemented his enhanced self-regulatory capacities. These changes were accompanied by a gradual resolution of the patient's torticollis.

Adult↗