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[Morphophysiologic study of reticulo-cortical pathways in the rabbit].

The character of functional connections between the midbrain reticular formation (RF) and the neocortex was studied in rabbits. Unit activity was recorded in sensorimotor cortex by extracellular microelectrode during RF stimulation. Short-latency neuronal reactions were found presumably identified as monosynaptic responses. Results of the studies of anterograde degeneration of myelinic fibers and axonal terminals after electrocoagulation of the RF carried out with the help of electronic microscope allowed to suppose that there were few (less than 0.5 per cent) monosynaptic connections between the RF and the sensorimotor cortex. The main forms of direct connections between these structures were axo-dendritic (situated at the dendritic trunk) and axosomatic synapses at the neurones of the sensorimotor cortex.

Animals↗

[Correlation between bioelectrical processes of the cortex, thalamus, midbrain reticular formation during formation of a defensive conditioned reflex in rabbits].

EEG power spectra of the sensorimotor area of the neocortex, the dorsal hippocampus, midbrain reticular formation and anteroventral thalamic nucleus, as well as corresponding coherence functions and phase spectra, undergo changes during formation and performance of defensive conditioned reflex in rabbit. The conclusion is draen that in the process of conditioning a morphofunctional system of brain structures is established including the above mentioned formations. Their functional integration occurs on the basis of theta-rhythm. The execution of a conditioned act requires isorhythmicity of electrical processes within the theta-range in the studied structures and an adequate level of their excitability, which is manifested in the dominance of 6,0 c/s frequency.

Animals↗

Use of neuronavigation and electrophysiology in surgery of subcortically located lesions in the sensorimotor strip.

OBJECTIVES: Subcortical lesions in the sensorimotor strip are often considered to be inoperable. The purpose of this study was to evaluate the usefulness of a combined approach for surgery in this region, aided by a robotic neuronavigation system under electrophysiological control. METHODS: In a prospective study on 10 patients, space occupying lesions in the sensorimotor central area were removed using the Surgiscope robotic navigation system and the Nicolet Viking IV electrophysiological system. RESULTS: Precise tumour localisation with the neuronavigation system and the information on the patient's cortical motor distribution obtained by bipolar cortical stimulation led to postoperative improvement in motor function in all but one patient. Seven of the patients had focal, defined pathology (four metastases; two cavernoma; one aspergilloma). CONCLUSION: Due to the implementation of two recent technologies, surgery of lesions in the subcortical sensorimotor region can be performed with greater confidence.

Adult↗

Intracerebral ERD/ERS in voluntary movement and in cognitive visuomotor task.

In order to study cerebral activity related to preparation and execution of movement, evoked and induced brain electrical activities were compared to each other and to fMRI results in voluntary self-paced movements. Also, the event-related desynchronization and synchronization (ERD/ERS) were studied in complex movements with various degrees of cognitive load. The Bereitschaftspotential (BP) and alpha (8-12 Hz) and beta (16-24 Hz) ERD/ERS rhythms in self-paced simple movements were analyzed in 14 epilepsy surgery candidates. In previous studies, the cortical sources of BP were consistently displayed contralateral to the movement in the primary motor cortex and somatosensory cortex, and bilateral in the supplementary motor area (SMA) and in the cingulate cortex. There were also small and inconstant BP generators in the ipsilateral sensorimotor, premotor, and dorsolateral prefrontal cortex. Alpha and beta ERD/ERS were also observed in these cortical regions. The distribution of contacts showing ERD or ERS was larger than of those showing BP. In contrast to BP, ERD, and ERS frequently occurred in the orbitofrontal, lateral and mesial temporal cortices, and inferior parietal lobule. The spatial location of brain activation for self-paced repetitive movements, i.e., writing simple dots, was studied using event-related functional MRI (fMRI) in 10 healthy right-handed subjects. We observed significant activation in regions known to participate in motor control: contralateral to the movement in the primary sensorimotor and supramarginal cortices, the SMA and the underlying cingulate, and, to a lesser extent, the ipsilateral sensorimotor region. When the fMRI was compared with the map of the brain areas electrically active with self-paced movements (intracerebral recordings; Rektor et al., 1994, 1998, 2001b, c; Rektor, 2003), there was an evident overlap of most results. Nevertheless, the electrophysiological studies were more sensitive in uncovering small active areas, i.e., in the premotor and prefrontal cortices. The BP and the event-related hemodynamic changes were displayed in regions known to participate in motor control. The cortical occurrence of oscillatory activities in the alpha-beta range was clearly more widespread. Four epilepsy surgery candidates with implanted depth brain electrodes performed two visuomotor-cognitive tasks with cued complex movements: a simple task--copying randomly presented letters from the monitor; and a more complex task--writing a letter other than that which appears on the monitor. The second task demanded an increased cognitive load, i.e., of executive functions. Alpha and beta ERD/ERS rhythms were evaluated. Similar results for both tasks were found in the majority of the frontal contacts, i.e., in the SMA, anterior cingulate, premotor, and dorsolateral prefrontal cortices. The most frequent observed activity was ERD in the beta rhythm; alpha ERS and ERD were also present. Significant differences between the two tasks appeared in several frontal areas--in the dorsolateral and ventrolateral prefrontal and orbitofrontal cortices (BA 9, 45, 11), and in the temporal neocortex (BA 21). In several contacts localized in these areas, namely in the lateral temporal cortex, there were significant changes only with the complex task--mostly beta ERD. Although the fMRI results fit well with the map of the evoked activity (BP), several discrepant localizations were displayed when the BP was compared with the distribution of the oscillatory activity (ERD-ERS). The BP and hemodynamic changes are closely related to the motor control areas; ERD/ERS represent the broader physiological aspects of motor execution and control. The BP probably reflects regional activation, while the more widespread ERD/ERS may reflect the spread of task-relevant information across relevant areas. In the writing tasks, the spatial distribution of the alpha-beta ERD/ERS in the frontal and lateral temporal cortices was partially task dependent. The ERD/ERS occurred there predominantly in the more complex of the writing tasks. Some sites were only active in the task with the increased demand on executive functions. In the temporal neocortex only, the oscillatory, but not the evoked, activity was recorded in the self-paced movement. The temporal appearance of changes of oscillatory activities in the self-paced movement task as well as in the cued movement task with an increased load of executive functions raises the interesting question of the role of this region in cognitive-movement information processing.

Adolescent↗

Functional image-guided neurosurgical simulation system using computerized three-dimensional graphics and dipole tracing.

This report describes a preoperative simulation and intraoperative localization system for use with three-dimensional functional images in intracranial surgery. The system, which produces three-dimensional functional images by superimposition of the generators of somatosensory evoked potentials derived from dipole tracing, was applied in the preoperative localization of central sulci in 12 patients with intracranial disorders. The preoperative localization of central sulci was assessed by intraoperative cortical recording of somatosensory evoked potentials in three patients. In six patients, three-dimensional computer graphics were reconstructed from magnetic resonance images and allowed visualization of the lesions through the semitransparent views of the scalp surface and the brain. The three-dimensional functional images were created by superimposing the generators of somatosensory evoked potentials on three-dimensional computer graphics. This combined technique provided preoperative data regarding the three-dimensional relationship between the sensorimotor cortex and the lesions. We also developed a three-dimensional digitizer that incorporates a mechanical arm and a laser pointer for use in integrating information obtained in the preoperative simulation into the surgical field. Intraoperative localization can be performed in real time on the three-dimensional computer graphics in combination with the functional images created from dipole tracing. This system was applied in five patients who underwent surgical brain tumor resections with minimal damage to the normal brain tissue. The use of this system for stereotactic craniotomy increased the safety of the surgery by affording preoperative simulation and intraoperative localization with the three-dimensional functional images. Two illustrative case reports are presented.

Brain Diseases↗

Dorsal and ventral stream interaction: contributions from optic ataxia.

In monkeys and humans, two functionally specialized cortical streams of visual processing emanating from V1 have been proposed: a dorsal, action-related system and a ventral, perception-related pathway. Traditionally, a separate organization of the two streams is assumed; the extent of functional interaction is unknown. After lesions of the dorsal stream in patients with optic ataxia, it has recently been shown that the ventral perception-related system might contribute to visuomotor processing if movements rely on remembered target positions. The ventral pathway thus seemed to participate in goal-directed movements, a function that previously has been assigned exclusively to the dorsal stream. We wondered whether different types of pointing movements are controlled by switching between two separated cortical pathways or whether a variable interaction of interconnected systems should be assumed. Our study investigated two acute stroke patients with optic ataxia following lesions of the dorsal stream in a delayed pointing task. The delays ranged from 0 to 10 sec. The patients' pointing error decreased in a linear manner with the length of time. The finding suggests a gradual change between dorsal and ventral control of reaching behavior, rather than a sudden switch between two separated cortical processing streams. Although our observations with two patients require further validation, the results suggest that the ventral and dorsal systems interact closely in the sensorimotor control of reaching behavior.

Aged↗

Cerebral networks in sensorimotor disturbances.

Increasing evidence suggests that the human brain employs multiple, interconnected brain areas for information processing and control of behavior, including the performance of laboratory tasks. Brain diseases are expected to affect these networks directly by interference and indirectly as a consequence of deficit compensation. Covariance analyses applied to functional brain imaging data open the opportunity to study neural networks and their disease-related changes in the human brain. Here, we review our analytic approach based on principal component analysis (PCA) to address such questions. We will discuss its methodological foundations and applications in patients with sensorimotor disorders. We will show that PCA in combination with, both, hypothesis-driven testing and correlation statistics provides a powerful tool for elucidating disease-related abnormalities and postlesional reorganization of neural networks in the human brain.

Adult↗

Progressive sensorimotor impairment is not associated with reduced dopamine and high energy phosphate donors in a model of ataxia-telangiectasia.

Ataxia-telangiectasia (A-T) is a genetic disease, associated with progressive motor impairment and a lack of functional ATM protein. It has been reported that immunoreactive tyrosine hydroxylase and dopamine transporter are reduced in an Atm-/- mouse model of A-T. These observations led to a hypothesis that A-T is associated with loss of nigrostriatal dopamine and prompted the launch of clinical trials to evaluate a therapeutic utility of the anti-parkinsonian drug, l-DOPA. To test for dopamine depletion more directly, we measured regional levels of monoamines and their metabolites in the Atm-/- mouse brain. We also measured levels of NAD+, a cofactor for dopamine biosynthesis and substrate of the DNA damage surveillance enzyme, poly(ADP-ribose) polymerase (PARP). Constitutive activation of PARP has been posited to cause NAD+ depletion. We observed no reduction in monoamine transmitters and no depletion of NAD+, or other high energy phosphate donors in the adult Atm-/- cerebellum, striatum, or ventral mesencephalon. However, our studies did reveal a progressive sensorimotor impairment in Atm-/- mice that may serve as a relevant proxy for progressive neurological impairment in the human disease. Our results call into question the involvement of dopamine in A-T and the therapeutic strategy of enhancing dopaminergic function with l-DOPA.

Adenosine Diphosphate↗

Afferent connections of the nucleus posterior thalami in the rat, with some evolutionary and functional considerations.

The afferents to the nucleus posterior thalami were investigated in the rat using the methods of retrograde and anterograde transport of horseradish peroxidase (HRP). The main afferents arise from the following structures: sensorimotor cortex, zona incerta, thalamic ventrobasal complex, pretectum, intermediate and deep layers of the superior colliculus, nucleus suprageniculatus, nucleus ruber and perirubral area, mesencephalic reticular formation, nucleus interstitialis of Cajal, nucleus tegmenti pedunculopontinus, nucleus reticularis pontis, sensorial and spinal tract trigeminal nuclei. There is some confusion about the anatomical localization and appellation of the posterior thalamic region among mammals. In most of them, however, the pattern of afferents to this area appears to be relatively homogeneous. We conclude that the projections to the thalamic posterior nucleus of the rat are similar to those reported in other mammals. This nucleus has been suspected of playing a role in the processing of somaesthetic or visual informations. On the basis of the multimodal nature of its afferents, a specific role of this nucleus is excluded. Instead, a non-specific function of modulation or integration is suggested.

Afferent Pathways↗

The anatomical substrate for telencephalic function.

The basic thesis for this study was that the telencephalon is needed to make decisions in new situations. Subsidiary hypotheses were that the telencephalon consists of: (a) a sensorimotor system which generates motor activity from sensory input and (b) a selection system which makes choices from possible motor programs. It was postulated that the selection system should fulfil the following requirements: be accessible for past and present events, have the capacity to process this information in a nondetermined way with a possibility for ordering, and have access to motor-affecting systems (the sensorimotor system). The ability of the selection system to correlate information in a nonpredetermined way was considered most important. In short: The selection system should be able to associate any information in any combination, and have the capability for internal control of neuronal activity and external selection of motor programs (see Fig. 1A.) Xenopus laevis was chosen as a subject, since it has a relatively simple telencephalon, with characteristics that it shares with "primitive" species of different vertebrate classes, and because it is easy to maintain as a laboratory animal. The main method used was the determination of connections with HRP. The pallium was in the focus of attention, since it was considered to be the core of the selection system. Immunohistochemistry was used as an additional parameter to compare Xenopus laevis forebrain with those of other vertebrates. The results showed that the pallium can be subdivided into a rostral (third) and a caudal (two-thirds) entity. The rostral third is the main recipient for thalamic and olfactory input. The caudal two-thirds are linked up to the rostral third and have a refined microcircuitry. Efferents from the pallium remain restricted to the forebrain. The entire pallium consists of a network of intrinsic reciprocal connections and can be considered to be positioned between the medial pallium (hippocampus), septum, and amygdaloid complex (amygdala). As a whole this system targets the hypothalamus. The hypothalamus in turn projects into the striatum complex (striatum with anterior entopeduncular nucleus). The rostral dorsal pallium and the amygdaloid complex also project into the striatum complex. The striatum is positioned between the sensory input from the thalamus and olfactory bulbs, and the motor output to the medulla. It is concluded, on the basis of its straightforward input-output relations and uniform appearance, that the striatum complex fulfils the requirements for a sensorimotor system. The pallium together with the septum, amygdaloid complex, and hypothalamus fulfils the requirements for a selection system.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Withdrawal of the aldose reductase inhibitor tolrestat in patients with diabetic neuropathy: effect on nerve function. The Tolrestat Study Group.

A double-blind, placebo-controlled clinical trial was conducted to study the effects of discontinuing tolrestat, an aldose reductase inhibitor, on peripheral sensorimotor diabetic neuropathy. After an average of 4.2 years of continuous tolrestat use, 372 patients were randomly assigned to either placebo or continued tolrestat therapy and were followed for 52 weeks. After 3 months, patients who perceived worsening of symptoms of neuropathy were allowed to switch once to the alternate treatment group while maintaining the double-blind. Patients assigned to placebo had significant deterioration in motor nerve conduction velocity (MNCV) while those maintained on tolrestat did not (p < 0.05). The 28 patients who were randomly assigned to tolrestat and elected to switch to placebo had a significant deterioration in MNCV while the 36 assigned to placebo who switched to tolrestat had a significant improvement (p < 0.05). Treatment differences in favor of tolrestat were observed for sensation in the toes as well as for pain (p < 0.05). These data indicate that withdrawal from long-term treatment with tolrestat has a detrimental effect on several measures of diabetic neuropathy, whereas continuation of treatment is associated with stabilization of these measures, suggesting a continued role for polyol pathway activity in late neuropathy.

Aldehyde Reductase↗

A study of children with learning disabilities and sensorimotor problems or let's not throw the baby out with the bathwater.

The 1986 position statement by the Board of Trustees fo the Council for Learning Disabilities called for a moratorium on the measurement and training of perceptual and perceptual-motor function as a part of services for children with learning disabilities (LD). Estimates in the literature, however, indicate that approximately 13% of children with LD exhibit motor deficits. Such children with motor or perceptual-motor problems are of ten referred to occupational therapy and found to have sensory integrative (SI) dysfunction; subsequently, they are treated with techniques aimed at remediating perceptual or sensorimotor dysfunction. Because the results of research concerned with the efficacy fo sensorimotor therapy are inconclusive and incomplete at this time, the position statement may be premature. Occupational therapists, however, must be aware of the statement and respond appropriately. In order to respond, they must have a better understanding of the nature of this subgroup of children with LD who have motor problems. the purpose fo this study was to assist in the definition of this population. Eighty children with LD between 5 years and 8 years 11 months were examined. They had been referred for occupational therapy at six centres in Southern Ontario. Results indicated that these children were similar to other children with LD in terms of gender and IQ distribution, developmental history, and academic achievement. The study population, however, tended to have less generalized emotional/behavioral disorder than the general population with LD. As expected, these children also had major deficits in gross and fine motor performance. A focus of the paper is on the importance of sensorimotor deficit for learning and self-concept in the child. Implications for both the position statement and practice and research in occupational therapy are discussed.

Journal Article↗

Administration of raloxifene reduces sensorimotor and working memory deficits following traumatic brain injury.

Hormonal differences between males and females have surfaced as a crucial component in the search for effective treatments after experimental models of traumatic brain injury (TBI). Recent findings have shown that selective estrogen receptor modulators (SERMs) may have therapeutic benefit. The present study examined the effects of raloxifene, a SERM, on functional recovery after bilateral cortical contusion injury (bCCI) or sham procedure. Male rats received injections of raloxifene (3.0mg/kg, i.p.) or vehicle (1.0 ml/kg, i.p.) 15 min, 24, 48, 72, and 96 h after bCCI or sham procedure. Rats were tested on both sensorimotor (bilateral tactile removal and locomotor placing tests) and cognitive tests (reference and working memory in the Morris water maze). Raloxifene-treated animals showed a significant reduction in the initial magnitude of the deficit and facilitated the rate of recovery for the bilateral tactile removal test, compared to vehicle-treated animals. The raloxifene-treated animals also showed a significant improvement in the acquisition of working memory compared to vehicle-treated animals. However, raloxifene did not significantly improve the acquisition of reference memory or locomotor placing ability. Raloxifene treatment also did not result in a significant reduction in the size of the lesion cavity. Thus, the task-dependent improvements seen following raloxifene treatment do not appear to be the result of cortical neuroprotection. However, these results suggest that raloxifene improves functional outcome following bCCI and may present an interesting avenue for future research.

Analysis of Variance↗

The role of the supplementary motor area in externally timed movement: the influence of predictability of movement timing.

A significant role in the planning and preparation for voluntary movement has been ascribed to secondary motor areas located on the medial wall of the cerebral hemispheres, and in particular to the supplementary motor area (SMA). Within the SMA, rostral and caudal subdivisions have been described, and differential roles have been attributed to these regions in relation to movement planning, preparation and execution. We have used functional magnetic resonance imaging (fMRI) to investigate the role of the SMA in the timing of movement execution, by recording the fMRI signal from mesial pre-motor areas and primary sensorimotor cortex (SM1) during the execution of a simple motor task externally cued at predictable (regular) and unpredictable (irregular) time intervals. The mean rate of movement was matched in both experiments. There was a greater activation of caudal than rostral SMA with both predictably and unpredictably cued movements, and a doubling of the signal when the timing of the motor response was unpredictable. In contrast, there was no difference in the activation of primary sensorimotor cortex with the two tasks. The data demonstrate that the caudal SMA has an important role in the execution of externally cued movements. The results also suggest a greater role for this region in the performance of unpredictably timed compared with predictably timed movements, however a model is proposed (based on electrophysiological data) which shows how the difference in functional signal in these two situations can be explained on the basis of a difference in the time course of neuronal activation in the SMA, rather than in the overall degree of activation.

Adult↗

Increased sensitivity to the sensorimotor gating-disruptive effects of apomorphine after lesions of medial prefrontal cortex or ventral hippocampus in adult rats.

Sensorimotor gating of the startle reflex is impaired in humans with schizophrenia and in rats after mesolimbic D2 dopamine receptor activation. The loss of startle gating after D2 activation in rats has been used as an animal model of impaired sensorimotor gating in schizophrenia, because the ability of antipsychotics to restore startle gating in D2-activated rats correlates significantly with antipsychotic clinical potency. Substantial evidence indicates that the pathophysiology of schizophrenia includes structural and functional deficits in prefrontal and temporal regions, particularly the dorsolateral prefrontal cortex and the hippocampus and parahippocampal gyrus. The present study assessed startle gating in adult rats after ibotenic acid lesions of the medial prefrontal cortex or ventral hippocampus. Medial prefrontal cortex lesioned rats exhibited normal startle amplitude and normal sensorimotor gating, as reflected by prepulse inhibition (PPI) of the startle reflex. Hippocampus lesioned rats exhibited elevated startle amplitude, and similar to rats with medial prefrontal cortex lesions, did not show significant changes in basal PPI. Low doses of the mixed dopamine agonist apomorphine did not significantly reduce PPI in sham lesioned rats, but significantly disrupted PPI in both medial prefrontal cortex- and ventral hippo-campus lesioned rats. These data are consistent with the hypothesis that cell damage in frontal and temporal cortex increases the sensitivity to the sensorimotor gating-disruptive effects of dopamine receptor activation.

Animals↗

A functional MRI study of movement-associated cortical changes in patients with Devic's neuromyelitis optica.

Movement-associated cortical changes have been shown in several neurological conditions and were found to be associated to the extent of brain and cord damage. Devic's neuromyelitis optica (DNO) is characterized by a severe involvement of the cord and optic nerve, with sparing of the brain. To assess the actual role of cord pathology on the pattern of movement-associated cortical recruitment, we obtained functional magnetic resonance imaging (fMRI) from patients with DNO and investigated whether the extent of brain activation is correlated with the extent of cervical cord damage. We studied 10 right-handed DNO patients and 15 sex- and age-matched healthy controls. The MRI assessment consisted of the following: (a) fMRI during repetitive flexion extension of the last four fingers of the right and left hand, (b) brain and cervical cord conventional MRI, and (c) cervical cord magnetization transfer (MT) MRI. Compared to controls and for both tasks, DNO patients had an increased recruitment of several regions of the sensorimotor network (primary sensorimotor cortex, postcentral gyrus, middle frontal gyrus, rolandic operculum, secondary sensorimotor cortex, precuneus, and cerebellum) and of several other regions mainly in the temporal and occipital lobes, such as MT/V5, the fusiform gyrus, the cuneus, and the parahippocampal gyrus. For both tasks, strong correlations (r values ranging from -0.76 to -0.85) were found between relative activations of cortical sensorimotor areas and the severity of cervical cord damage. This study shows an abnormal pattern of movement-associated cortical activations in patients with DNO, which extends beyond the 'classical' sensorimotor network and also involves visual areas devoted to motion processing. The correlation found between fMRI changes and the extent of cord damage suggests that such functional cortical changes might have an adaptive role in limiting the clinical outcome of DNO structural pathology.

Adult↗

Motor behaviour deficits and their histopathological and functional correlates in the nigrostriatal system of dopamine transporter knockout mice.

Chronic dysregulation of dopamine homeostasis has been shown to induce behavioural impairment in dopamine transporter knockout mutant mice arising from the dysfunction of the mesolimbic and hypothalamo-infundibular system. Here, we assessed whether there are also any motor consequences of a chronic and constitutive hyperdopaminergia in the nigrostriatal system in dopamine transporter knockout mutant mice. For this, we analysed motor performances using tests assessing balance, coordinated motor skills (rotarod, pole test), stride lengths and locomotor activity. Dopamine transporter knockout mutant mice were markedly hyperactive in the open field with central compartment avoidance, as previously shown. However, sensorimotor integration was also found to be altered in dopamine transporter knockout mutant mice which displayed a reduced fore- and hind-limb mean stride length, impaired motor coordination on the pole test and reduced rearings in the open field. Moreover, dopamine transporter knockout mutant mice showed a slower task acquisition on the rotarod. Six-week-old dopamine transporter knockout wild type mice having the same femur size as adult dopamine transporter knockout mutant mice ruled out a possible size-effect bias. Whilst there was no significant difference in the striatal volume, we found a slight but significant reduction in neuronal density in the striatum but not in the nucleus accumbens of dopamine transporter knockout mutant mice. There was a reduced binding in the striatum and nucleus accumbens of dopamine(1) receptors ([(3)H]SCH 23390) and dopamine(2) receptors ([(3)H]YM-09151-2). There was no significant difference in the number of dopaminergic neurons in the substantia nigra between dopamine transporter knockout mutant mice and dopamine transporter knockout wild type mice. These results suggest an impaired functioning of the nigrostriatal system in dopamine transporter knockout mutant hyperdopaminergic mice, as illustrated by motor and sensorimotor integration deficits, despite their apparent hyperactivity. These dysfunctions may arise from combined striatal cell loss and/or functional changes of dopaminergic neurotransmission.

Animals↗