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Correlation between motor improvements and altered fMRI activity after rehabilitative therapy.

Motor rehabilitation therapy is commonly employed after strokes, but outcomes are variable and there is little specific information about the changes in brain activity that are associated with improved function. We performed serial functional MRI (fMRI) on a group of seven patients receiving a form of rehabilitation therapy after stroke in order to characterize functional changes in the brain that correlate with behavioural improvements. Patients were scanned while performing a hand flexion-extension movement twice before and twice after a two-week home-based therapy programme combining restraint of the unaffected limb with progressive exercises for the affected limb. As expected, the extent of improvement in hand function after therapy varied between patients. Therapy-related improvements in hand function correlated with increases in fMRI activity in the premotor cortex and secondary somatosensory cortex contralateral to the affected hand, and in superior posterior regions of the cerebellar hemispheres bilaterally (Crus I and lobule VI). fMRI offers a promising, objective approach for specifically identifying changes in brain activity potentially responsible for rehabilitation-mediated recovery of function after stroke. Our results suggest that activity changes in sensorimotor regions are associated with successful motor rehabilitation.

Adult↗

Neural mechanisms generating locomotion studied in mammalian brain stem-spinal cord in vitro.

The neural control system for generation of locomotion is an important system for analysis of neural mechanisms underlying complex motor acts. In these studies, a novel experimental model using neonatal rat brain stem and spinal cord in vitro was developed for investigation of the locomotor system in mammals. The in vitro brain stem and spinal cord system was shown to retain functional circuitry for locomotor command generation, motor pattern generation, and sensorimotor integration. This system was exploited to investigate neurochemical mechanisms involved in neurogenesis of locomotion. Evidence was obtained for peptidergic and gamma-amino-butyric acid-mediated mechanisms in brain-stem circuits generating locomotor commands. Cholinergic, dopaminergic, and excitatory amino acid-mediated mechanisms were shown to activate spinal cord circuits for locomotor pattern generation. Endogenous N-methyl-D-aspartic acid receptors in spinal networks were found to play a central role in the generation of locomotion. The chemically induced patterns of motor activity and rhythmic membrane potential oscillations of spinal motoneurons were characteristic of those during locomotion in other mammals in vivo. The in vitro brain stem and spinal cord model provides a versatile and powerful experimental system with potentially broad application for investigation of diverse aspects of the neurobiology of mammalian motor control systems.

Animals↗

Dynamic susceptibility contrast MRI of regional cerebral blood volume in Alzheimer's disease.

OBJECTIVE: The purpose of this study was to investigate the potential effectiveness of dynamic susceptibility contrast magnetic resonance imaging (MRI) to discriminate elderly patients with Alzheimer's disease from normal matched comparison subjects. METHOD: Images of regional cerebral blood volume (CBV) were generated from echo-planar MRI with the dynamic susceptibility contrast method in 13 Alzheimer's disease patients and 13 comparison subjects group-matched on age and gender. RESULTS: Temporoparietal cerebral blood volume, expressed as a percentage of the cerebellum value, was reduced 17% bilaterally in the patients with Alzheimer's disease. Blood volume in sensorimotor regions was reduced only 8.5% in the patients. Discriminant function analysis based on left and right temporoparietal measures correctly classified 88.5% of the subjects as patients or comparison subjects. Temporoparietal CBV was reduced even in mildly affected Alzheimer's disease patients (Mini-Mental State scores > 24). CONCLUSIONS: Dynamic susceptibility contrast MRI of regional CBV is promising as a nonradioactive, potentially lower-cost alternative to other functional neuroimaging methods for evaluating Alzheimer's disease.

Aged↗

Widespread capacity for steroid synthesis in the avian brain and song system.

Steroids exert powerful effects on the brains and behavior of many species, but measures and manipulations of endocrine physiology in songbirds often reveal unexplained connections between steroids and the brain. The zebra finch song system, a sensorimotor neural circuit sensitive to steroids throughout life, organizes and functions largely in apparent independence from gonadally derived steroids. We tested the hypothesis that the zebra finch brain has the capacity for de novo steroidogenesis and that neurally synthesized steroids, neurosteroids, may impact the song system. Using multiple techniques, we demonstrate that the steroidogenic acute regulatory protein (StAR), cytochrome P450 side-chain cleavage (CYP11A1), and 3beta-hydroxysteroid dehydrogenase/Delta5-Delta4 isomerase, the first three factors in the steroidogenic pathway, are expressed in both developing and adult zebra finch brain. Detailed expression mapping at posthatch d 20 (P20) and adult reveals widespread area-specific expression and coexpression patterns for steroidogenic acute regulatory protein, CYP11A1, and 3beta-hydroxysteroid dehydrogenase/Delta5-Delta4 isomerase, which suggest neurosteroids may modulate multiple brain functions, including sensory and motor systems. Notably, whereas expression of other steroidogenic genes such as aromatase has been essentially absent from the song system, each of the major song nuclei express at least a subset of steroidogenic genes described here, establishing the song system as a potential steroidogenic circuit.

3-Hydroxysteroid Dehydrogenases↗

Robot-aided sensorimotor arm training improves outcome in patients with chronic stroke.

Thirty patients with chronic stroke received 6 weeks of sensorimotor robotic training in a pilot study that targeted motor function of the affected shoulder and elbow. The impairment and disability scores were stable during a 2-month observation/measurement period, improved significantly by program completion, and remained robust in the 3-month follow-up. Task-specific motor training attenuated a chronic neurologic deficit well beyond the expected period for improvement after stroke.

Adult↗

Clinical manifestations of visual information processing: part I.

This paper discusses three aspects of visual information processing and their significance to clinical optometric practice. It analyzes the factors involved in central-peripheral organization, pictorial-linguistic interaction and total versus partial utilization os sensorimotor information as they relate to perceptual style and visual function. It emphasizes these factors as possibly being the commonalities behind many of the divergent yet generally successful theoretical frameworks and techniques utilized in optometric diagnosis and therapy.

Child↗

[Pitfalls in cortical localization by intraoperative recording of cortical somatosensory evoked potentials].

Cortical somatosensory evoked potential (SEP) recordings were made in 11 patients who had lesions located in or near the somatosensory or motor gyri to localize the central sulcus and sensorimotor cortex during neurosurgical operations. Cortical localization was successful in 7 of the 11 patients by recording phase reversal waveforms of N20 and P20 at electrode sites in the hand area on opposite sides of the central sulcus. There were 4 cases in which the cortical localization failed. Locations of craniotomy were far distant from the central sulcus retrospectively in 2 of the 4 patients. Cortical SEPs couldn't be recorded despite probable exposure of the hand area and apparently adequate stimulation and recording conditions in 2 patients who had showed no or low amplitude scalp SEP preoperatively. In one of these 2 patients only low amplitude negative waves were recorded at the cortex which was thought far field potentials originated from subcortical structures. In 2 patients cortical SEP was monitored during the removal of the tumors and was useful to estimate the effects of the operative procedures on the sensorimotor cortex. It is concluded that the localization of cortical functions using cortical SEP is useful for reducing risk associated with intracranial surgery. However, we must be aware that there are some pitfalls in this method.

Adolescent↗

Effect of selenium pre-treatment on evoked cortical afterdischarges in young rats.

Prenatal or perinatal hypoxia is among the most frequent pathogenic factors of encephalopaties. It can induce wide-range of morphological, biochemical, energetic and functional alterations. Accordingly we tested changes of excitability of the sensorimotor cortex in 12, 25 and 35-day-old rats exposed and not exposed to short-term (1 hour) hypobaric and normobaric hypoxia. We studied whether sodium selenate (0,26 mg/kg b.w.) can influence character and/or intensity of evoked cortical afterdischarges or if a pre-treatment by selenium changes effects of hypoxia on such seizures. According to the results we can conclude that in our experiment arrangement sodium selenate only partially alters duration of evoked cortical afterdischarges.

Animals↗

Prolonged reaction time to a verbal working memory task predicts increased power of posterior parietal cortical activation.

We used multislice functional magnetic resonance imaging (fMRI) to investigate the association between behavioral and neurophysiological measures of working memory task performance in 20 right-handed male healthy volunteers. Images were acquired over a 5-min period at 1.5 Tesla. We used a periodic design, alternating 30-s blocks of the "n-back" working memory task with 30-s blocks of a sensorimotor control task to activate verbal working memory systems. The power of functional response to the task was estimated by sinusoidal regression at each voxel. The relationship between power of fMRI response and mean reaction time over all 11 working memory trials was explored by multiple regression, with age and mean reaction time to the control task as covariates, at voxel and regional levels of analysis. All subjects were able to perform the n-back task accurately. A spatially distributed network was activated, including dorsolateral prefrontal cortex, inferior frontal gyrus, lateral premotor cortex, and supplementary motor area (SMA) in the frontal lobes. More posteriorly, there were major foci of activation in parietal and occipitoparietal cortex, precuneus, lingual, and fusiform gyri of the ventral occipital lobe, inferior temporal gyrus, and cerebellum. The power of functional response was positively correlated with reaction time in bilateral posterior parietal cortex (Talairach coordinates in x, y, z (mm) 35, -44, 37 and -32, -56, 42), indicating that subjects who found the task difficult, and responded with a slower reaction time, tended to activate these regions more powerfully. One interpretation of this regionally specific relationship between prolonged reaction time and increased power of posterior parietal activation is consistent with prior studies identifying similar areas of parietal cortex as the site of the phonological storage function in verbal working memory.

Adult↗

[Functional state of the cerebral cortex and midbrain reticular formation during traumatic shock].

Acute experiments on cats were carried out during traumatic shock to study evoked potentials in the sensorimotor cortex and reticular formation (RF) of the midbrain in response to electrodermal irritation of the contralateral paw. The cortical function was judged by thresholds of convulsant reaction while function of RF by thresholds of activation reaction in the cortex of the course of high-frequency electrical stimulation of the structures under study. It was shown that in traumatic shock, initial and pronounced depression of the cortical function paralleled long enough stability of RF functional activity.

Animals↗

Somatotopy and movement representation sites following cortical stroke.

Stroke has been associated with many changes in motor system function, but there has been limited study of changes in somatotopic organization. This was examined in a group of patients with cortical stroke affecting primary sensorimotor cortex. In 17 patients with good outcome after cortical stroke involving precentral and/or postcentral gyri, plus 14 controls, four functional MRI evaluations of brain activity were obtained: finger, shoulder, and face motor tasks plus a sensory task, passive finger motion. For each, coordinates for contralateral primary sensorimotor cortex activation site were determined, as was a measure of inter-hemispheric balance. The normal motor somatotopy measured in controls was largely preserved after stroke. The main difference found between controls and patients was that the face was lateral to finger motor activation in all controls, but face was centered medial to finger in 43% of patients. Among patients, smaller infarct volume was associated with more ventral, and larger infarct with more dorsal, contralateral primary sensorimotor cortex activation. On the other hand, better behavioral outcome was associated with a more posterior, and poorer outcome with more anterior, activation. Larger infarct and poorer behavioral outcome were each associated with a change in inter-hemispheric balance towards the non-stroke hemisphere. Shifts in contralateral movement representation site did not correlate with changes in inter-hemispheric balance. Motor somatotopy is generally preserved after injury to primary sensorimotor cortex. Greater injury and larger behavioral deficits are associated with distinct effects on movement representation sites. Changes in motor organization within and between hemispheres arise independently after stroke.

Adult↗

Altered cortical glutamate receptor function in the R6/2 model of Huntington's disease.

Alterations in pyramidal neurons from the sensorimotor cortex may be responsible for some of the cognitive and motor symptoms of Huntington's disease (HD). The present experiments used R6/2 transgenic mice that express exon 1 of the human HD gene with an expanded number of CAG repeats. We characterized alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) currents and their modulation by cyclothiazide (CTZ) as well as N-methyl-D-aspartate (NMDA) currents and their Mg2+ sensitivity in acutely dissociated cortical pyramidal neurons in R6/2 transgenic and wild-type (WT) mice at 21 days (before overt symptoms), 40 days (when symptoms begin), and 80 days (fully symptomatic). AMPA currents, alone or in the presence of CTZ, were smaller in 21- and 40-day-old R6/2 groups compared with WT mice. In R6/2 mice, more neurons displayed desensitizing AMPA currents in the presence of CTZ, indicating increased expression of "flop" splice variants, whereas the majority of WT cells expressed the "flip" variants of AMPA receptor subunits. NMDA peak currents also were smaller in R6/2 pyramidal neurons at 21 days. At 40 days, NMDA currents were similar in WT and R6/2 mice but Mg2+ sensitivity was greater in R6/2 mice, resulting in smaller NMDA currents in the presence of Mg2+. Differences in AMPA and NMDA currents between WT and R6/2 cells were no longer detected at 80 days. Our findings indicate that currents induced by glutamate receptor agonists are decreased in isolated cortical pyramidal neurons from R6/2 mice and that this decrease occurs early. Altered glutamate receptor function could contribute to changes in cortical output and may underlie some of the cognitive and motor impairments in this animal model of HD.

Animals↗

Neuromagnetic integrated methods tracking human brain mechanisms of sensorimotor areas 'plastic' reorganisation.

The potential for reorganization in the adult brain has been largely underestimated in the past and we are just beginning to understand the organisational principles involved in functional recovery. A bulk of experimental evidences have been accumulated in support of the hypothesis that neuronal aggregates adjacent to a lesion in the cortical brain areas can be progressively vicarious to the function of the damaged neurones. Such a reorganisation, if occurring in the affected hemisphere of a patient with a monohemispheric lesion, should significantly modify the interhemispheric symmetry of somatotopic organisation of the sensorimotor cortices, both in terms of absolute surfaces and number of "recruited" neurons, as well as of spatial coordinates. In fact, a roughly symmetrical organisation of sensorimotor - particularly for the hand contorl - in the right and left hemisphere has been observed in healthy humans by different methods of functional brain imaging, including fMRI, TMS, MEG, HD-EEG. Not uniform results about the functional brain activity related to sensory, motor and cognitive functions in normal and diseased subjects are often due to differences in the experimental paradigm designed as well as in the spatial and temporal resolution of the neuroimaging techniques used. The multi-modal integration of data obtained with several neuroimaging techniques allowed a coherent modelling of human brain higher functions. Functional magnetic resonance imaging (fMRI) provided fine spatial details (millimetres) of the brain responses, which were compared with the cortical maps of the motor output to different body districts obtained with transcranial magnetic stimulation (TMS). Magnetoencephalography (MEG) ability to study sensorimotor areas by analysing cortical magnetic fields, is also complementary to the motor cortex topographical mapping provided by TMS. MEG high temporal resolution allows to detect relatively restricted functional neuronal pools activated during cerebral processing of external stimuli. Moreover, these brain responses can be investigated with magnetoencephalography (MEG) and high density electroencephalography (EEG) techniques, with elevated time resolution (ms). With respect to the high resolution EEG technique, the MEG technique allowed a more precise localisation of the sites of neural activity buried into the cortical sulci, but was unable to detect the response of the crown of the cortical giri and of the frontal-mesial cortex (including the supplementary motor area), because of its poor sensitivity to radially oriented dipoles. The integration of functional and anatomical information provide cues on the relationship between brain activity and anatomic sites where this takes place, allowing the characterisation of the physiological activity of the cortical brain layers as well as to study the plastic reorganisation of the brain in different pathological conditions following stroke, limb amputation, spinal cord injury, hemisperectomy.

Animals↗

Increased synchronization of cortical oscillatory activities between human supplementary motor and primary sensorimotor areas during voluntary movements.

In human, both primary and nonprimary motor areas are involved in the control of voluntary movements. However, the dynamics of functional coupling among different motor areas has not been fully clarified yet. Because it has been proposed that the functional coupling among cortical areas might be achieved by the synchronization of oscillatory activity, we investigated the electrocorticographic coherence between the supplementary motor and primary sensorimotor areas (SMA and S1-M1) by means of event-related partial coherence analysis in 11 intractable epilepsy patients. We found premovement increase of coherence between the SMA proper and S1-M1 at the frequency of 0-33 Hz and between the pre-SMA and S1-M1 at 0-18 Hz. Coherence between the SMA proper and M1 started to increase 0.9 sec before the movement onset and peaked 0.3 sec after the movement. There was no systematic difference within the SMA (SMA proper vs pre-SMA) or within the S1-M1, in terms of the time course as well as the peak value of coherence. The phase spectra revealed near-zero phase difference in 57% (20 of 35) of region pairs analyzed, and the remaining pairs showed inconsistent results. This increase of synchronization between multiple motor areas in the preparation and execution of voluntary movements may reflect the multiregional functional interactions in human motor behavior.

Adolescent↗

Enhancement of mouse sciatic nerve regeneration by the long chain fatty alcohol, N-Hexacosanol.

The purpose of the present study was to determine the effects of n-hexacosanol (hexa) on nerve regeneration. Hexa, a long chain fatty alcohol has been shown to possess neurotrophic properties on cultured neurons and to attenuate the degeneration of cholinergic neurons after injury. The effects of daily intraperitoneal injections of hexa (1 mg/kg) on regeneration of nerve fibers were studied in mice following a sciatic nerve crush. Measurement of axonal regeneration using the pinch test 7 days postlesion showed a 40% increase of the regeneration rate of sensory fibers in hexa-treated mice compared to controls (1.67 +/- 0.15 mm/day and 1.09 +/- 0.03 mm/day, respectively). The recovery of neuromuscular function was significantly improved, as shown by quantitative electromyography and and sensorimotor tests. Clinical signs of recovery evaluation with toe spreading reflex appeared earlier in hexa group than in control animals. Electrophysiological recordings were performed each 3 days during 34 days following nerve injury. Higher values of the compound muscle action potential (CMAP) were obtained in hexa-treated animals that correspond to an improved regeneration. Moreover, hexa induced a significantly faster regeneration rate (hexa: 2.87 +/- 0.15 mV/day; control: 2.00 +/- 0.06 mV/day), as measured by the slope of CMAP increase (44% enhancement). A morphometric analysis performed 7 days following crush showed an increased number of regenerating fibers, as well as increased diameter and thickness of the myelin in hexa-treated mice. Thus, hexa increased the regeneration of both sensory and motor axons in lesioned nerve, leading to an improved functional recovery.

Animals↗

Rehabilitation after stroke. Emphasis on usefulness in restoration of function.

The physical treatment of patients with paralysis after stroke is not a casual prescription of exercise but involves an evaluation of the patient from the mental and sensorimotor standpoint to determine his disabilities and abilities. This is necessary to prescribe and direct a precise form of activity and functional exercises that will promote a return of functional patterns of movement useful to the patient for his independence.

Cerebral Hemorrhage↗

Long-term results of functional hemispherectomy for intractable seizures.

OBJECTIVE: From May 1989 to April 1997, functional hemispherectomy was performed in 8 cases of intractable seizures. We retrospectively analyzed our experience to evaluate the seizure control and complications of this surgical technique. METHODS: Following Dr. Rasmussen's model of functional hemispherectomy or performing a modification of this operation, we removed the sensorimotor cortex and temporal lobe associated with disconnection of the remaining portions of the frontal lobe and parieto-occipital lobe. RESULTS: All the patients were followed up for 3-11 years (mean 6.7 years). Satisfactory seizure control was obtained in all the cases. Life quality improved and patients worked or studied well after the operations. No cases of superficial cerebral hemosiderosis were found. CONCLUSION: Modified functional hemispherectomy may allow the patients to lead more independent lives by leading to a cessation or reduced frequency of seizures.

Adolescent↗

Subcortical damage and cortical functional changes in men and women with Fabry disease: a multifaceted MR study.

PURPOSE: To prospectively compare brain magnetic resonance (MR) imaging and hydrogen 1 (1H) MR spectroscopy findings and to use functional MR imaging to explore the patterns of brain activation in men and women with Fabry disease (FD). MATERIALS AND METHODS: Eight men and eight women with FD (mean age, 38.8 years +/- 13.9 [standard deviation]) with absent or mild neurologic deficit and 16 healthy control subjects (eight men and eight women; mean age, 42.7 years +/- 15.3) gave informed consent to participate in the study, which was approved by the local ethical committee. Patients and control subjects underwent MR imaging, 1H MR spectroscopy of the frontal cortex and subcortical white matter, and functional MR imaging during repetitive flexion-extension of the last four fingers of the right hand. Extent of cerebral white matter damage was rated on fluid-attenuated inversion recovery MR images by using a visual score. Areas of activation were identified by using statistical parametric mapping software and the adoption of a height threshold of P < .001 (uncorrected) and an extent threshold of P < .05 (corrected). RESULTS: Men and women with FD showed a similar distribution of cerebral white matter changes, lacunar and cortical infarcts, small hemorrhages, and vertebrobasilar dolichoectasia. No significant (P > .05) difference was observed between patients with FD and control subjects for concentration of N-acetylaspartate, creatine, and choline. During the motor task, patients showed recruitment of additional cortical areas in comparison with control subjects. Increased activation of the contralateral sensorimotor area correlated (P = .002) with extent of white matter damage. CONCLUSION: Subcortical ischemic changes in men and women with FD are similar and are associated with increased recruitment of the sensorimotor network during a simple motor task, which might limit the functional effect of the white matter small-vessel disease.

Adult↗