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Preoperative regimens of magnesium facilitate recovery of function and prevent subcortical atrophy following lesions of the rat sensorimotor cortex.

Following brain injury, there is a reduction of intra- and extracellular levels of magnesium (Mg++), which may contribute to the severity of the lesion-induced behavioral impairments. Injections of magnesium prior to or after brain injury attenuate these behavioral impairments. The present study extends these findings by manipulating the number of injections and the time period between the injections and the time of injury. Rats were given either two or five daily preoperative injections of MgCl2 (1 mmol/kg, i.p.), or saline (1 ml/kg, i.p.) with the final injection given 24 h prior to electrolytic lesions of the somatic sensorimotor cortex (SMC). Following SMC lesions the rats exhibited contralateral deficits in forelimb placing and locomotor placing. Rats treated with either two or five preoperative injections of MgCl2 showed a reduction in the initial magnitude of the contralateral deficits and an accelerated rate of recovery compared to saline-treated rats. In addition, analysis of striatal atrophy revealed that MgCl2 treatment prevented atrophy in the ipsilateral posterior striatum compared to rats treated with saline. These data suggest that preoperative injections of MgCl2 produce facilitation of sensorimotor recovery and reduce subcortical atrophy. Moreover, to observe the beneficial effects of MgCl2, the timing of injections need not be tied to the period immediately around the brain injury. The present data may indicate that daily supplements of magnesium may partially protect against some of the deleterious effects of brain injury.

Animals↗

Age-related synaptic changes in sensorimotor cortex of the Brown Norway X fischer 344 rat.

Investigations of age-related changes in synapse density have yielded contradictory conclusions. The goal of the present study was to determine whether there is a significant decline in the number of cortical synapses in old age. Therefore, brains from 10-, 15-, and 32-month-old Brown Norway X Fischer 344 rats were prepared for electron microscopy and synapses were counted in a stereotaxically-identified region of sensorimotor cortex. Within this cortical area, synapses were counted in layers 2 and 4 and the data have been presented both as number of synapses per volume of neuropil and as the ratio of synapses per neuron. Results indicated that there was a decline in synapse density between 15 and 32 months in layer 2, but not in layer 4. This decline was significant not only for total synapses, but also for subcategories of synapses when classified by presynaptic features or postsynaptic element. Specifically, there was a significant decline in presumptive inhibitory synaptic terminals, i.e., those containing nonround synaptic vesicles, as well as a significant decline in synapses that contact dendritic spines.

Aging↗

Locus coeruleus activation shortens synaptic drive while decreasing spike latency and jitter in sensorimotor cortex. Implications for neuronal integration.

Chronic recording of locus coeruleus (LC) neurons in rat and monkey have pointed out that brief, phasic LC discharges, but not sustained activity, are specifically related to salient stimuli and attention. However, the sensory consequences of phasic activation of the noradrenergic system by a brief conditioning stimulation of the LC have not been fully investigated. This study examined the effect of LC activation on synaptic and neuronal responses to a tactile stimulus in the sensorimotor cortex of the anaesthetized rat, by analysing the fine temporal structure of sensory discharges and current source-density profiles recorded from the same electrodes. LC stimulation, with minimal EEG effects, consistently reduced the synaptic input in layers IV and V-VI, by decreasing the amplitude and duration of short-latency current sinks, but not the slope of their early rising phase. Simultaneously, most multiple and single unit excitatory responses were shortened by the suppression of their late component after 25-30 ms, whereas robust temporal facilitation of the early discharge was found for spike latency mean and variance, spike timing and synchronization to the stimulus, but leaving the number of spikes unaffected. These two apparently opposite effects on the synaptic drive and neuronal response are reminiscent of the noradrenergic depression of afferent synaptic potentials observed with an increased neuronal excitability in vitro. They are interpreted as a noradrenergic sharpening of thalamocortical processing consistent with a presumed role of synchronous discharges in perception that would depend on activated states, particularly when LC activity is correlated with vigilance or attention.

Animals↗

Morphology of layer III pyramidal neurons is altered following induction of LTP in sensorimotor cortex of the freely moving rat.

The organization of specific cortical connections can be altered by sensory and motor experience. These changes are believed to result from activity-dependent changes in synaptic connectivity, similar to those induced in the hippocampus by high-frequency stimulation in long-term potentiation (LTP) experiments. If similar mechanisms are involved, then neocortical LTP induction may induce some of the same morphological changes that are seen following learning. We induced LTP in the contralateral sensorimotor cortex by repeated, daily tetanization of the corpus callosum in chronically implanted, freely moving rats. Anatomical results showed that the LTP induction was associated with alterations in dendrite morphology and increased spine density. These changes are qualitatively and quantitatively similar to those commonly observed in studies in which rats are housed in complex environments. The similarity of results following exposure to complex environments and after LTP induction in the neocortex may indicate a reliance on the same cellular mechanisms in both situations.

Animals↗

Interactions between LTP- and LTD-inducing stimulation in the sensorimotor cortex of the awake freely moving rat.

Bidirectional modifications in synaptic efficacy are central components in models of cortical learning and memory. More recently, the regulation of synaptic plasticity according to the history of synaptic activation, termed "metaplasticity," has become a focus of research on the physiology of memory. Here we explore such interactions between long-term potentiation (LTP) and long-term depression (LTD) in the chronically prepared rat. The effects of successive high- and low-frequency stimulation were examined in sensorimotor cortex in the adult, freely moving rat. High-frequency (300 Hz) stimulation (HFS) applied to the white matter was used to induce LTP, and prolonged, low-frequency (1 Hz) stimulation (LFS) was used to induce either depotentiation or LTD. Combined stimulation (HFS/LFS or LFS/HFS) during the induction phase attenuated potentiation effects only if the LFS followed the HFS. LTD induced by LFS alone was expressed as a reduction in the amplitude of both short- and long-latency field potential components, whereas depotentiation was primarily expressed as a decrease in the amplitude of the potentiated long-latency component. In other experiments, LTP (or LTD) was induced to asymptotic levels before applying LFS (or HFS). LFS caused depotentiation of the late component but had no measurable effect on the early component. HFS reversed previously induced LTD, but the potentiation decayed more rapidly than usual. LTP and LTD therefore modulate each other in the awake, behaving rat.

Analysis of Variance↗

Rapid modulation of GABA in sensorimotor cortex induced by acute deafferentation.

Recovery of function after acute injury to the central nervous system may be controlled by the availability of gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the cerebral cortex. Acute lesions as well as manipulation of sensory inputs can lead to rapid reorganization of the cerebral cortex, occurring within minutes to hours. Reduction of cortical inhibitory tone through a decrease in the availability of GABA has been suggested as a possible mechanism; however, the degree and temporal course of the changes in brain GABA are not known. A novel method using two-dimensional J-resolved magnetic resonance spectroscopy showed that GABA levels in the human sensorimotor cortex are quickly reduced within minutes of deafferentation. This finding strongly supports the view that the release of latent corticocortical projections from tonic inhibition through decreased GABA availability is a mechanism of rapid cortical plasticity. Reduction of brain GABA can play a pivotal role in regulating the extent of rapid cortical reorganization after lesions or changes in sensory input.

Adult↗

L-DOPS-Accelerated recovery of locomotor function in rats subjected to sensorimotor cortex ablation injury: pharmacobehavioral studies.

Central norepinephrine (NE) has been shown to play a beneficial role in amphetamine-facilitated recovery of behavior. To give insight into understanding the mechanism, the present studies were conducted to examine (a) the effects of L-threo-3,4-dihydroxyphenylserine (L-DOPS) combined with benserazide (BSZ; a peripheral aromatic amino acid decarboxylase inhibitor) and L-3,4-dihydroxyphenylalanine (L-DOPA), precursors of NE and dopamine (DA), respectively, on the recovery from beam-walking performance deficits in rats subjected to unilateral sensorimotor cortex ablation injury, and (b) the relationships between the behavioral recovery and the frequency of postoperative training and the size of ablation injury. It was found that the combined treatments with L-DOPS and BSZ promoted the recovery of locomotor function as early as 24 hours after injury. L-DOPA alone, however, did not facilitate behavioral recovery. The results of assay for the tissue levels of NE and its major metabolite (3-methoxy-4-hydoxyphenylethylene glycol; MHPG) in the brain using high-pressure liquid chromotography showed MHPG, but not NE, significantly increased in the cerebellum and the hippocampus. The behavioral recovery was also significantly correlated with the frequency of training subsequent to injury, but inversely with the size of cortex ablation. These results suggest that NE is likely to modulate functional recovery in this rodent model.

Animals↗

Cortical and brainstem neurons containing calcium-binding proteins in a murine model of Duchenne's muscular dystrophy: selective changes in the sensorimotor cortex.

In the muscular dystrophic (mdx) mouse, which is characterized by deficient dystrophin expression and provides a model of Duchenne's muscular dystrophy, we previously demonstrated marked central nervous system alterations and in particular a quantitative reduction of corticospinal and rubrospinal neurons and pathologic changes of these cells. Prompted by these findings and in view of the relations between calcium ions and dystrophin, we analyzed with immunohistochemistry the neurons containing the calcium-binding proteins parvalbumin, calbindin D28k, and calretinin in cortical areas and brainstem nuclei of mdx mice. In the sensorimotor cortex, parvalbumin-positive and calbindin-positive neurons, which represent a subset of cortical interneurons, were significantly more numerous in mdx mice than in wild-type ones. In addition, the laminar distribution of parvalbumin-positive neurons in the motor and somatosensory cortical areas of mdx mice was altered with respect to wild-type animals. No alterations in the number and distribution were found in the parvalbumin- or calbindin-expressing cell populations of the visual and anterior cingulate cortices of mdx mice. The pattern of calretinin immunoreactivity was normal in all investigated cortical areas. The cell populations containing either calcium-binding protein were similar in brainstem nuclei of mdx and wild-type mice. The present findings demonstrated selective changes of subsets of interneurons in the motor and somatosensory cortical areas of mdx mice. Therefore, the data showed that, in the cortices of these mutant animals, the previously demonstrated pathologic changes of corticospinal cell populations are accompanied by marked alterations in the local circuitry.

Animals↗

Functional MR imaging of the human sensorimotor cortex during haptic discrimination.

This study attempted to determine whether haptic discriminations of shape (haptic task) activate the same tissue in the central cortical region of normal human subjects as do finger movements (opposition task). Opposition and haptic tasks both activated the central sulcus, as expected from previous imaging studies. The haptic task activated about 50% of the cortical territory activated by the opposition task. The results suggest that exploratory digital movements performed to collect precise somatosensory information and automatic movements performed during finger positioning activate partially overlapping parts of the sensorimotor cortex.

Brain Mapping↗

Different ipsilateral representations for distal and proximal movements in the sensorimotor cortex: activation and deactivation patterns.

Each hemisphere is known to be also involved in controlling the ipsilateral arm, but with an asymmetry favoring the dominant hemisphere. However, the relative role of primary and secondary motor areas in ipsilateral control is not well defined. We used whole brain functional magnetic resonance imaging in healthy human subjects to differentiate between contributions from primary and secondary areas during discrete unilateral distal finger and proximal shoulder movements. It was found that ipsilateral distal movements activated secondary areas only, while sparing or even significantly deactivating the primary sensorimotor cortex. Ipsilateral proximal movements substantially activated both SM1 and secondary areas. A newly defined small territory within the precentral gyrus, extending from the premotor cortex and intruding toward SM1, showed an activation pattern corresponding to secondary motor areas. Finally, the effects of hemispheric dominance were confirmed, but attributed exclusively to secondary areas. These new imaging findings agree well with functional requirements as well as established anatomical and neurophysiological data.

Adult↗

Functional mapping of the sensorimotor cortex: combined use of magnetoencephalography, functional MRI, and motor evoked potentials.

Combined use of magnetoencephalography (MEG), functional magnetic resonance imaging (f-MRI), and motor evoked potentials (MEPs) was carried out on one patient in an attempt to localise precisely a structural lesion to the central sulcus. A small cyst in the right frontoparietal region was thought to be the cause of generalised seizures in an otherwise asymptomatic woman. First the primary sensory cortex was identified with magnetic source imaging (MSI) of somatosensory evoked magnetic fields using MEG and MRI. Second, the motor area of the hand was identified using f-MRI during hand-squeezing. Then transcranial magnetic stimulation localised the hand motor area on the scalp, which was mapped onto the MRI. There was a good agreement between MSI, f-MRI and MEP as to the location of the sensorimotor cortex and its relationship to the lesion. Multimodality mapping techniques may thus prove useful in the precise localisation of cortical lesions, and in the preoperative determination of the best treatment for peri-rolandic lesions.

Adult↗

A neuromagnetic study of the functional organization of the sensorimotor cortex.

Movement-related neuromagnetic fields from eight healthy human subjects were investigated in a Bereitschaftspotential paradigm. The three conditions studied were right-sided mouth, index finger and foot movement. The neuromagnetic field patterns corresponding to the motor field and the movement-evoked field I were analysed using a moving dipole model. For both components a somatotopic organization was found: the estimated dipole locations for the mouth were more lateral and those for the foot more medial than the estimated dipole positions for the index finger movement. With regard to possible clinical applications, e.g. non-invasive mapping of the sensorimotor cortex and studies of plasticity of the motor function, the present results suggest that the investigation of movement-evoked field I for the index finger condition is most likely to yield further results.

Adult↗

Transcranial magnetic stimulation (TMS) of the sensorimotor cortex and medial frontal cortex modifies human pain perception.

OBJECTIVE: Although recent neuroimaging studies have shown that painful stimuli can produce activity in multiple cortical areas, the question remains as to the role of each area in particular aspects of human pain perception. To solve this problem we used transcranial magnetic stimulation (TMS) as an 'interference approach' tool to test the consequence on pain perception of disrupting activity in several areas of cortex known to be activated by painful input. METHODS: Weak CO(2) laser stimuli at an intensity around the threshold for pain were given to the dorsum of the left hand in 9 normal subjects. At variable delays (50, 150, 250, 350 ms) after the onset of the laser stimulus, pairs of TMS pulses (dTMS: interpulse interval of 50 ms, and stimulus intensity of 120% resting motor threshold) were applied in separate blocks of trials over either the right sensorimotor cortex (SMI), midline occipital cortex (OCC), second somatosensory cortex (SII), or medial frontal cortex (MFC). Subjects were instructed to judge whether or not the stimulus was painful and to point to the stimulated spot on a drawing of subject's hand. RESULTS: Subjects judged that the stimulus was painful on more trials than control when dTMS was delivered over SMI at 150-200 ms after the laser stimulus; the opposite occurred when dTMS was delivered over MFC at 50-100 ms. dTMS over the SII or OCC failed to alter the pain threshold. CONCLUSIONS: These results suggest that TMS to SMI can facilitate whereas stimulation over MFC suppresses central processing of pain perception. Since there was no effect of dTMS at any of the scalp sites on the localization task, the cortical locus for point localization of pain may be different from that for perception of pain intensity or may involve a more complex mechanism than the latter. SIGNIFICANCE: This is the first report that TMS of SMI facilitates while that of MFC suppresses the central processing of pain perception. This raises the possibility of using TMS as a therapeutic device to control pain.

Adult↗

Functional mapping of human sensorimotor cortex with 3D BOLD fMRI correlates highly with H2(15)O PET rCBF.

Positron emission tomography (PET) functional imaging is based on changes in regional cerebral blood flow (rCBF). Functional magnetic resonance imaging (fMRI) is based on a variety of physiological parameters as well as rCBF. This study is aimed at the cross validation of three-dimensional (3D) fMRI, which is sensitive to changes in blood oxygenation, with oxygen-15-labeled water (H2(15)O) PET. Nine normal subjects repeatedly performed a simple finger opposition task during fMRI scans and during PET scans. Within-subject statistical analysis revealed significant ("activated") signal changes (p < 0.05, Bonferroni corrected for number of voxels) in contralateral primary sensorimotor cortex (PSM) in all subjects with fMRI and with PET. With both methods, 78% of all activated voxels were located in the PSM. Overlap of activated regions occurred in all subjects (mean 43%, SD 26%). The size of the activated regions in PSM with both methods was highly correlated (rho = 0.87, p < 0.01). The mean distance between centers of mass of the activated regions in the PSM for fMRI versus PET was 6.7 mm (SD 3.0 mm). Average magnitude of signal change in activated voxels in this region, expressed as z-values adapted to timeseries, zt, was similar (fMRI 5.5, PET 5.3). Results indicate that positive blood oxygen level-dependent (BOLD) signal changes obtained with 3D principles of echo shifting with a train of observations (PRESTO) fMRI are correlated with rCBF, and that sensitivity of fMRI can equal that of H2(15)O PET.

Adult↗

Activation of the sensorimotor cortex at 1.0 T: comparison of echo-planar and gradient-echo imaging.

PURPOSE: The increasing demand for the clinical application of functional MR imaging raises the question of whether this technique can be routinely performed on 1.0-T MR scanners. To this end, we assessed the feasibility of functional MR imaging at 1.0 T. METHODS: Healthy volunteers were scanned during the performance of a motor task. Functional data were acquired with echo-planar imaging (EPI) and with gradient-echo (GRE) and dual-echo GRE sequences. The signal intensity variations of the EPI and GRE sequences were compared, and the influence of inflow and blood oxygen level-dependent (BOLD) effects on the signal variations was assessed with the dual-echo GRE sequences. RESULTS: In 11 of the 12 subjects we found activation in the primary motor cortex with both the GRE and EPI sequences. Active voxels had a significantly higher mean percentage of signal changes with the EPI sequence than with the GRE sequence (EPI: 1% to 6.1%, mean 2.4%; GRE: 1% to 4.5%, mean 1.9%). The EPI sequence was less sensitive to motion artifacts and enabled imaging of a larger brain volume in a shorter time. With a dual-echo sequence we found an increasing contribution of inflow effect with an increasing percentage of signal changes. CONCLUSION: Functional MR imaging of the sensorimotor cortex can be routinely performed at 1.0 T.

Adult↗

Recruitment of the sensorimotor cortex--a developmental FMRI study.

INTRODUCTION: The growing mastery of motor tasks is one of the most visible changes in the developing child. The cortex is known to play a central role in learning, planning, and performance of motor tasks. We investigated the age dependency of motor cortex activation using functional magnetic resonance imaging (fMRI). METHODS: Thirty-two right-handed subjects were studied: 11 children (median age 9 years, range 6 - 10 years), 10 adolescents (median age 13 years, range 11 - 15 years), and 11 adults (median age 27 years, range 23 - 42 years). The subjects performed a simple, paced unilateral motor task (repetitive squeezing of a ball with the right hand). Also, we set up a control experiment (visual stimulation using an alternating checkerboard pattern) in which no age-related differences were expected. RESULTS: Compared to children, adults showed significantly increased activation of the bilateral sensorimotor cortex, parietal areas, the supplementary motor area, and the cerebellum. In the visual stimulation experiment there were no age-related differences. CONCLUSION: Children show a significant difference in the degree of cortical activation compared to adults when performing a simple motor task. The change in fMRI activation patterns may reflect a maturation process of primary and secondary motor areas.

Adolescent↗

[Changes in the reactivity of the sensorimotor cortex resulting from the treatment of patients with depressive disorders].

Changes in the mu-rhythm power in response to sound (non-specific reactivity, NR) and related with the actual and imaginary movement with the right and left hand in response to sound (specific reactivity, SR) were studied in 38 right-handed patients with subdepressive psychogenic (PD) and endogenous (ED) disorders before and after successful complex treatment (pharmacotherapy and acupuncture) in comparison with 23 healthy subjects. The successful treatment was found to be accompanied by a certain extent of normalization of the disturbed SR which was different in PD and ED. The more complete recovery of the normal reactions in PD was mainly accounted for by the relative decrease in the NR and increase in the SR. The ED treatment predominantly modified the SR. Substantial reorganization of interhemispheric relations during movements in the PD patients resulted in disappearance of the abnormal ipsilateral reactions and transition to the contralateral reactions of the sensorimotor cortex.

Acupuncture Therapy↗

Effects of hypothalamic stimulation on unit responses recorded from neurons of sensorimotor cortex of awake cats during conditioning.

1. The activity of single units of the coronal pericruciate (CPC) cortex was studied in 11 awake cats during sessions in which a click conditioned stimulus (CS) was repeatedly paired with glabella tap unconditioned stimulus (US) and hypothalamic stimulation (HS). Effects of HS on the activity of cortical units were also studied during sessions in which HS alone was delivered repeatedly every 10 s. 2. HS evoked an increase in spike activity of less than 60 ms latency in 89 of 116 units tested. 3. Repeated presentation of HS that was effective in producing rapid behavioral conditioning resulted in a characteristic reduction in the latency of discharge evoked by HS in cortical units. 4. Short-latency activation (less than 20 ms) of units of the sensorimotor cortex appeared to be characteristic of HS that led to enhanced rates of conditioned response (CR) acquisition. One of the cells responding in this way was identified as a pyramidal cell of layer V by intracellular injection of horseradish peroxidase (HRP). 5. Further analyses of activity were performed on 16 units of the CPC cortex that were followed through conditioning (or reconditioning) and extinction of the CR. After less than 10 CS-US-HS pairings, there was a selective augmentation of unit response to the CS but not of response to an explicitly unpaired discriminative stimulus (DS). Responses to the CS were not similarly augmented when presentations of HS preceded rather than followed the presentations of the CS and US. The rapid development of CS-evoked unit activity coincided with the rapid acquisition of discriminative CRs behaviorally. 6. During conditioning, the most conspicuous increases in CS-evoked unit response occurred at latencies 100 ms or more after onset of the click CS. This corresponded with the behavioral observation that the majority of eye blink CRs occurred with onset latencies longer than 100 ms.

Animals↗